109. Glomerulonephritis (GN)

nephritic syndrome · IgA / ANCA vasculitis / lupus · RBC casts + dysmorphic RBCs + AKI + HTN · RPGN is an emergency — biopsy + immunosuppress fast · Super Compact

Sx: nephritic picture — hematuria (tea/cola-colored), HTN, edema (periorbital/dependent), AKI (oliguria), subnephrotic proteinuria · systemic clues: hemoptysis/pulmonary hemorrhage + sinusitis (ANCA), rash/arthralgias/serositis (lupus), recent URI/synpharyngitic hematuria (IgA) (rapidly rising Cr + active sediment = RPGN until proven otherwise)

Neg: denies isolated bland hematuria w/o casts (urologic source — stones/malignancy/infection) · denies nephrotic-range proteinuria + bland sediment + hypoalbuminemia (nephrotic, not nephritic) · denies pre/post-renal AKI (volume, obstruction) · denies pigment/exposure (rhabdo, contrast)

SHx: recent infection (IgA — synpharyngitic; post-strep — latent) · hemoptysis/sinus disease (ANCA/anti-GBM) · autoimmune/lupus features, photosensitivity · hepatitis B/C, HIV · drugs (hydralazine, PTU — ANCA) · smoking (anti-GBM)

Etiology: immune-mediated glomerular inflammation · IgA nephropathy (commonest worldwide; mesangial IgA; synpharyngitic hematuria) · ANCA-associated vasculitis (pauci-immune RPGN — GPA/MPA; MPO/PR3) · lupus nephritis (immune-complex; ISN/RPS class I–VI) · others — anti-GBM (Goodpasture), post-infectious, IgA vasculitis (HSP), cryoglobulinemic, MPGN

RF: autoimmune disease/SLE · chronic infection (HBV/HCV/HIV, endocarditis) · certain drugs · smoking (anti-GBM) · family history

Data: urinalysis + microscopy (dysmorphic RBCs + RBC casts = glomerular; proteinuria) · urine protein/Cr or 24h (usually subnephrotic; can overlap) · BMP (↑Cr, K) · serologies — the GN panel: ANA, anti-dsDNA, C3/C4 (lupus — low complement), ANCA (MPO/PR3), anti-GBM, complements, ASO/anti-DNase B (post-strep), cryoglobulins, hepatitis B/C + HIV, SPEP/free light chains · CBC (anemia, MAHA?) · CXR/CT chest (pulmonary hemorrhage — ANCA/anti-GBM) · renal biopsy (definitive — pattern, class, activity/chronicity; do not delay in RPGN)

DDx: nephritic causes (IgA vs ANCA vs lupus vs anti-GBM vs post-infectious — serologies + biopsy) · TMA/HUS-TTP (MAHA, schistocytes, thrombocytopenia) · nephrotic syndrome (bland, heavy proteinuria) · urologic hematuria (no casts)

Home Meds: hold nephrotoxins/NSAIDs · hold/adjust ACEi/ARB acutely if AKI/hyperkalemia (resume for proteinuria when stable) · review culprit drugs (hydralazine, PTU, allopurinol → drug-induced ANCA) · renally dose

Plan

CONSULT: Nephrology (urgent — biopsy + immunosuppression) · Rheumatology (lupus/vasculitis) · Pulmonology/ICU (pulmonary-renal syndrome/DAH) · Apheresis (plasma exchange for anti-GBM/severe ANCA)

– Recognize RPGN as an emergency: rapidly rising Cr + active urinary sediment (RBC casts) → expedite renal biopsy and do not delay immunosuppression for confirmed/strongly suspected disease — nephrons are lost by the day
– Stabilize: treat hyperkalemia (calcium gluconate 1–2 g IV for ECG changes + insulin 10 units IV + D50 25 g + albuterol neb, then removal/dialysis), manage volume/HTN, dialyze for AEIOU indications
– Send the full GN serologic panel + biopsy before/with starting therapy (ANA/dsDNA/complements, ANCA, anti-GBM, hepatitis/HIV, cryoglobulins, light chains)
– ANCA-associated vasculitis (induction): high-dose glucocorticoids (methylprednisolone (Solu-Medrol) pulse 500–1000 mg IV daily ×3 then prednisone taper) + rituximab (preferred) or cyclophosphamide; plasma exchange for severe disease (Cr requiring dialysis, diffuse alveolar hemorrhage); PJP prophylaxis (TMP-SMX)
– Anti-GBM (Goodpasture): urgent plasma exchange + glucocorticoids + cyclophosphamide — time-critical (treat before dialysis-dependence if possible)
– Lupus nephritis (proliferative III/IV): glucocorticoids + mycophenolate mofetil or cyclophosphamide (often + belimumab or voclosporin per regimen); hydroxychloroquine for all; biopsy class guides therapy
– IgA nephropathy: optimized supportive care — maximal RAAS blockade (ACEi/ARB) + BP control + SGLT2 inhibitor; glucocorticoids/immunosuppression for high-risk progressive disease per nephrology
– Post-infectious GN: supportive (treat infection, manage volume/HTN) — usually self-limited
– Supportive throughout: BP control, proteinuria reduction (RAAS when stable), nephrotoxin avoidance, vaccination before immunosuppression, infection screening (latent TB/hepatitis)
– In suspected RPGN, send the serologies and get the biopsy fast — but if anti-GBM or severe ANCA with pulmonary hemorrhage is strongly suspected, start pulse steroids and arrange plasma exchange without waiting, because every day of delay costs irreversible renal function.
– PT/OT: as tolerated
– Trend: Cr/eGFR, urine sediment + proteinuria, K, complements/titers (disease activity), Hgb/respiratory status (DAH), immunosuppression toxicity/infection
– Escalation triggers: pulmonary hemorrhage/hypoxia → ICU + plasma exchange; rapidly rising Cr → expedite biopsy + induction; dialysis indications → RRT; infection on immunosuppression → prompt treatment
– Discharge checklist: diagnosis + biopsy class documented; induction immunosuppression started + plan; prophylaxis (PJP, bone, vaccines); BP/proteinuria management (RAAS, SGLT2i); close nephrology/rheumatology follow-up + lab monitoring; return precautions (hemoptysis, decreased urine, swelling, fever on immunosuppression)

109. Glomerulonephritis (GN)

complete reference · IgA nephropathy + ANCA vasculitis + lupus nephritis · nephritic syndrome + RPGN · biopsy-directed immunosuppression · Full Card

Symptoms / Associated Sx

• Nephritic syndrome: hematuria (tea- or cola-colored urine), hypertension, edema (periorbital and dependent), acute kidney injury with oliguria, and subnephrotic proteinuria

• Systemic clues by cause: hemoptysis/pulmonary hemorrhage and upper-airway/sinus disease (ANCA vasculitis, anti-GBM); rash, arthralgias, and serositis (lupus); a recent upper respiratory infection with synpharyngitic hematuria (IgA nephropathy)

• A rapidly rising creatinine with an active sediment defines rapidly progressive glomerulonephritis (RPGN) until proven otherwise

Neg

• Pt denies isolated bland hematuria without casts — which suggests a urologic source (stones, malignancy, infection) rather than glomerular disease

• Pt denies nephrotic-range proteinuria with a bland sediment and hypoalbuminemia — which would indicate nephrotic rather than nephritic disease

• Pt denies a pre-renal or post-renal cause (volume depletion, obstruction) and denies pigment/contrast exposure (rhabdomyolysis, contrast nephropathy)

Social History (SHx)

• Recent infection (synpharyngitic in IgA nephropathy; a latent period in post-streptococcal GN)

• Hemoptysis or sinus disease (ANCA vasculitis, anti-GBM)

• Autoimmune or lupus features and photosensitivity

• Hepatitis B/C and HIV status; culprit drugs (hydralazine, propylthiouracil — drug-induced ANCA); smoking (a trigger for anti-GBM alveolar hemorrhage)

Main Etiology

• Immune-mediated glomerular inflammation

• IgA nephropathy: the most common primary GN worldwide, with mesangial IgA deposition and synpharyngitic hematuria

• ANCA-associated vasculitis: pauci-immune RPGN (granulomatosis with polyangiitis and microscopic polyangiitis), with MPO- or PR3-ANCA

• Lupus nephritis: immune-complex disease classified by the ISN/RPS system (classes I–VI), with proliferative classes III and IV requiring aggressive therapy

• Others: anti-GBM disease (Goodpasture), post-infectious GN, IgA vasculitis (Henoch–Schönlein purpura), cryoglobulinemic GN, and membranoproliferative GN

RF

• Modifiable: control of chronic infections, smoking cessation, avoidance of culprit drugs

• Non-modifiable: autoimmune disease/SLE, chronic infection (HBV/HCV/HIV, endocarditis), and family history

Data

• Urinalysis with microscopy (dysmorphic red cells and RBC casts indicate a glomerular source; proteinuria is present)

• Urine protein-to-creatinine ratio or 24-hour collection (usually subnephrotic, though overlap with nephrotic-range proteinuria occurs)

• BMP (elevated creatinine, potassium)

• Serologic GN panel: ANA and anti-dsDNA with C3/C4 (lupus typically lowers complement), ANCA (MPO/PR3), anti-GBM antibody, ASO/anti-DNase B (post-streptococcal), cryoglobulins, hepatitis B/C and HIV serologies, and SPEP/serum free light chains

• CBC (anemia; evaluate for microangiopathic features)

• Chest imaging (pulmonary hemorrhage in ANCA vasculitis and anti-GBM)

• Renal biopsy (the definitive test — establishes the pattern, class, and activity/chronicity; should not be delayed in suspected RPGN)

DDx

Nephritic causes (IgA vs ANCA vs lupus vs anti-GBM vs post-infectious — distinguished by serologies and biopsy) · thrombotic microangiopathy/HUS-TTP (microangiopathic hemolytic anemia, schistocytes, thrombocytopenia) · nephrotic syndrome (bland sediment, heavy proteinuria) · urologic hematuria (no casts)

Home Meds

• Hold: nephrotoxins and NSAIDs

• Hold/adjust: ACE inhibitors/ARBs acutely if AKI or hyperkalemia is present, resuming them for proteinuria once stable

• Review culprit drugs (hydralazine, propylthiouracil, allopurinol → drug-induced ANCA); renally dose medications

Plan

CONSULT: Nephrology (urgent — biopsy and immunosuppression) · Rheumatology (lupus, vasculitis) · Pulmonology/ICU (pulmonary–renal syndrome with diffuse alveolar hemorrhage) · Apheresis (plasma exchange for anti-GBM or severe ANCA disease)

• Recognize RPGN as an emergency: a rapidly rising creatinine with an active sediment (RBC casts) warrants an expedited renal biopsy, and immunosuppression should not be delayed for confirmed or strongly suspected disease because nephrons are lost daily

• Stabilize: treat hyperkalemia (calcium gluconate 1–2 g IV for ECG changes, insulin 10 units IV with dextrose 25 g, and nebulized albuterol, then potassium removal or dialysis), manage volume and hypertension, and dialyze for standard indications

• Send the full serologic panel and obtain the biopsy before or alongside starting therapy

• ANCA-associated vasculitis (induction): high-dose glucocorticoids (methylprednisolone (Solu-Medrol) pulse 500–1000 mg IV daily for 3 days, then a prednisone taper) plus rituximab (preferred) or cyclophosphamide; add plasma exchange for severe disease (dialysis-requiring kidney injury or diffuse alveolar hemorrhage); provide PJP prophylaxis with TMP-SMX

• Anti-GBM disease (Goodpasture): urgent plasma exchange with glucocorticoids and cyclophosphamide — time-critical, and best initiated before dialysis dependence develops

• Lupus nephritis (proliferative class III/IV): glucocorticoids with mycophenolate mofetil or cyclophosphamide (often combined with belimumab or voclosporin), hydroxychloroquine for all patients, and biopsy class guiding the regimen

• IgA nephropathy: optimized supportive care with maximal RAAS blockade (ACEi/ARB), blood pressure control, and an SGLT2 inhibitor; glucocorticoids/immunosuppression for high-risk progressive disease per nephrology

• Post-infectious GN: supportive care (treat the infection, manage volume and hypertension); usually self-limited

• Supportive throughout: blood pressure control, proteinuria reduction with RAAS blockade once stable, nephrotoxin avoidance, vaccination before immunosuppression, and screening for latent TB and hepatitis

• PT/OT: as tolerated

• Trend: creatinine/eGFR, urine sediment and proteinuria, potassium, complement levels and antibody titers (disease activity), hemoglobin and respiratory status (alveolar hemorrhage), and immunosuppression toxicity/infection

• Escalation triggers: pulmonary hemorrhage/hypoxia → ICU and plasma exchange; a rapidly rising creatinine → expedite biopsy and induction; dialysis indications → renal replacement therapy; infection on immunosuppression → prompt treatment

• Discharge checklist: diagnosis and biopsy class documented; induction immunosuppression started with a plan; prophylaxis (PJP, bone protection, vaccinations); blood pressure and proteinuria management (RAAS, SGLT2 inhibitor); close nephrology/rheumatology follow-up with laboratory monitoring; return precautions for hemoptysis, decreased urine output, swelling, or fever while immunosuppressed

Red Flags

• Rapidly progressive GN (rising creatinine + RBC casts) → expedite biopsy and start induction immunosuppression without delay

• Pulmonary–renal syndrome with diffuse alveolar hemorrhage → ICU, plasma exchange, and high-dose steroids

• Anti-GBM disease → urgent plasma exchange; outcomes hinge on treating before dialysis dependence

• Hyperkalemia or other dialysis indications → emergent management

• Overwhelming infection on immunosuppression → a competing emergency requiring prompt treatment

Senior IM Resident Pearls

• RBC casts change everything. Dysmorphic red cells and RBC casts move the diagnosis from a urologic bleed to a glomerular emergency — look at the sediment yourself in any hematuria with AKI.

• RPGN is measured in days. Send the serologies, get the biopsy fast, and don't wait for every result before treating a strongly suspected vasculitis — irreversible nephron loss accumulates while you wait.

• Pulmonary hemorrhage + AKI is a pulmonary–renal syndrome (ANCA or anti-GBM) — it demands plasma exchange and ICU-level care, not a slow outpatient workup.

• Low complement narrows the field. Lupus, post-infectious, cryoglobulinemic, and membranoproliferative GN consume complement; ANCA and anti-GBM typically don't — the C3/C4 is a fast triage tool.

• Ask about hydralazine and PTU. Drug-induced ANCA vasculitis is reversible if you stop the drug — a missable history.

• Vaccinate and screen before immunosuppression (TB, hepatitis B), and start PJP prophylaxis — the treatment's complications can be as dangerous as the disease.

• Common mistake: calling glomerular hematuria a UTI or stone and treating symptomatically while the creatinine climbs — always reconcile hematuria with the sediment and renal function.

Nephrology — Nephrotic Syndrome

110. Nephrotic Syndrome

heavy proteinuria (>3.5 g/day) + hypoalbuminemia + edema + hyperlipidemia · bland sediment · the danger is thrombosis + infection · biopsy-directed therapy · Super Compact

Sx: severe edema (periorbital → dependent → anasarca, pleural effusions/ascites), frothy urine (proteinuria), weight gain · fatigue · ± thrombotic complication (DVT/PE, renal vein thrombosis — flank pain/hematuria) · infection susceptibility (the triad: heavy proteinuria, hypoalbuminemia, edema — plus hyperlipidemia)

Neg: denies active nephritic sediment (RBC casts, dysmorphic RBCs — would be GN/nephritic) · denies heavy hematuria as primary · denies cardiac/hepatic edema as sole cause (low albumin + proteinuria point renal) · denies pre-renal/obstruction AKI

SHx: diabetes (commonest secondary cause) · NSAID/drug use (membranous, MCD) · infection (HBV/HCV/HIV, syphilis) · malignancy (membranous — solid tumors; MCD — lymphoma) · autoimmune/lupus · family history

Etiology: glomerular podocyte injury → massive protein loss · primary: minimal change disease (children; adults — NSAIDs/lymphoma), FSGS (commonest primary in adults; HIV, obesity, reflux), membranous nephropathy (anti-PLA2R; idiopathic vs secondary — malignancy/HBV/lupus/drugs) · secondary: diabetic nephropathy (most common overall), amyloidosis, lupus (class V)

RF: diabetes · chronic infection (HBV/HCV/HIV) · malignancy · autoimmune disease · NSAID/drug exposure · obesity

Data: urine protein quantification (UPCR or 24h urine >3.5 g/day = nephrotic-range) · urinalysis + microscopy (bland; oval fat bodies/"Maltese cross"; minimal blood) · serum albumin (<3 — hypoalbuminemia) · lipid panel (hyperlipidemia) · BMP (renal fxn, K) · secondary workup: HbA1c/glucose, anti-PLA2R (membranous), ANA/dsDNA/complements (lupus), HBV/HCV/HIV, SPEP/free light chains + fat pad/biopsy Congo red (amyloid), age-appropriate cancer screen · consider renal biopsy (adults — establishes type unless clearly diabetic) · Doppler/CT if renal vein thrombosis suspected

DDx: primary GN types (MCD vs FSGS vs membranous — biopsy/PLA2R) · diabetic nephropathy (diabetes, retinopathy, gradual) · amyloidosis (light chains, Congo red) · nephritic syndrome (active sediment — different) · non-renal edema (CHF/cirrhosis — no proteinuria)

Home Meds: review/stop NSAIDs (MCD/membranous, worsen renal) · continue/optimize RAAS blockade (ACEi/ARB — antiproteinuric) · statin for hyperlipidemia · diuretics for edema · renally dose

Plan

CONSULT: Nephrology (diagnosis, biopsy, immunosuppression) · Hematology (thrombosis/anticoagulation decisions) · relevant service for secondary cause (oncology, ID, rheumatology)

– Confirm + classify: quantify proteinuria (UPCR/24h), serum albumin, lipids, bland sediment; pursue secondary workup (HbA1c, anti-PLA2R, autoimmune/infection/paraprotein screen); renal biopsy in adults unless clearly diabetic
– Edema management: loop diuretics (furosemide (Lasix), often higher doses given hypoalbuminemia and gut edema impairing absorption — IV preferred; add thiazide/metolazone for resistance), dietary sodium restriction (<2 g/day) + modest fluid restriction; cautious — avoid intravascular depletion/AKI
– Antiproteinuric therapy: ACEi or ARB (reduces proteinuria, slows progression) + BP control; SGLT2 inhibitor for additional renoprotection
– Hyperlipidemia: statin therapy
– THROMBOSIS — the key danger: nephrotic syndrome is hypercoagulable (urinary antithrombin loss); high risk especially membranous + albumin <2–2.5 → consider prophylactic anticoagulation; treat any VTE/renal vein thrombosis with full anticoagulation (heparin → warfarin or DOAC per nephrology/heme); maintain high suspicion (flank pain + hematuria + worsening proteinuria = renal vein thrombosis)
– Infection prophylaxis/vigilance: urinary immunoglobulin loss → susceptibility (esp encapsulated organisms — pneumococcal; spontaneous bacterial peritonitis if ascites); pneumococcal vaccination; treat infections promptly
– Disease-specific immunosuppression (per biopsy): MCD — corticosteroids (prednisone 1 mg/kg/day), usually steroid-responsive; FSGS — corticosteroids ± calcineurin inhibitor; membranous — supportive first (many remit), immunosuppression (rituximab, calcineurin inhibitor, or cyclophosphamide-steroid) for high-risk/progressive; diabetic — glycemic + BP control, RAAS, SGLT2i (no immunosuppression); lupus (class V) — per lupus regimen
– Treat secondary causes: malignancy, infection (HBV/HCV/HIV), autoimmune disease
– Don't forget the thromboembolism risk — nephrotic patients lose antithrombin in the urine and clot; new flank pain with hematuria and rising proteinuria is renal vein thrombosis until proven otherwise, and unexplained dyspnea is PE.
– PT/OT: mobilize (also reduces VTE risk)
– Trend: proteinuria/albumin (response), weight/edema, renal function/K, lipids, thrombotic/infectious complications
– Escalation triggers: PE/renal vein thrombosis → anticoagulation ± ICU; rapid renal decline → biopsy/reassess (?superimposed process); severe infection/SBP → treat urgently; refractory anasarca → diuretic escalation/ultrafiltration
– Discharge checklist: biopsy diagnosis + therapy plan documented; proteinuria-reduction regimen (RAAS, SGLT2i) + statin; diuretic + sodium restriction education; thrombosis risk assessed (± prophylaxis); pneumococcal vaccination; nephrology follow-up + labs; return precautions (leg swelling/pain, dyspnea/chest pain, flank pain/blood in urine, fever)

110. Nephrotic Syndrome

complete reference · severe edema + proteinuria + hypoalbuminemia · thrombosis/infection risk · biopsy-directed therapy · Full Card

Symptoms / Associated Sx

• Severe edema progressing from periorbital to dependent to anasarca, with pleural effusions and ascites; frothy urine from proteinuria; weight gain

• Fatigue

• Thrombotic complications (DVT, PE, and renal vein thrombosis presenting with flank pain and hematuria)

• Increased susceptibility to infection

• The defining picture is heavy proteinuria, hypoalbuminemia, and edema, accompanied by hyperlipidemia

Neg

• Pt denies an active nephritic sediment (RBC casts, dysmorphic RBCs) — which would indicate a nephritic/glomerulonephritic process instead

• Pt denies prominent hematuria as the primary feature

• Pt denies cardiac or hepatic disease as the sole cause of edema — the combination of hypoalbuminemia and heavy proteinuria points to a renal source; and denies a pre-renal or obstructive cause of any AKI

Social History (SHx)

• Diabetes (the most common secondary cause)

• NSAID or other drug use (associated with minimal change disease and membranous nephropathy)

• Infection (HBV, HCV, HIV, syphilis) and malignancy (membranous nephropathy with solid tumors; minimal change disease with lymphoma)

• Autoimmune disease/lupus; family history

Main Etiology

• Glomerular podocyte injury leading to massive urinary protein loss

• Primary: minimal change disease (the classic childhood cause; in adults associated with NSAIDs and lymphoma), focal segmental glomerulosclerosis (the most common primary cause in adults; associated with HIV, obesity, and reflux), and membranous nephropathy (anti-PLA2R antibody; idiopathic versus secondary to malignancy, hepatitis B, lupus, or drugs)

• Secondary: diabetic nephropathy (the most common cause overall), amyloidosis, and lupus (class V membranous lupus nephritis)

RF

• Modifiable: glycemic control, treatment of chronic infections, avoidance of culprit drugs, weight

• Non-modifiable: diabetes, malignancy, autoimmune disease, genetic predisposition

Data

• Urine protein quantification (urine protein-to-creatinine ratio or 24-hour collection >3.5 g/day defines nephrotic-range proteinuria)

• Urinalysis with microscopy (bland sediment with oval fat bodies and "Maltese cross" lipiduria; minimal blood)

• Serum albumin (hypoalbuminemia, typically <3 g/dL) and a lipid panel (hyperlipidemia)

• BMP (renal function, potassium)

• Secondary workup: HbA1c/glucose, anti-PLA2R antibody (membranous), ANA/anti-dsDNA/complements (lupus), HBV/HCV/HIV serologies, SPEP/serum free light chains with fat-pad or biopsy Congo red staining (amyloidosis), and age-appropriate cancer screening

• Renal biopsy (in adults, to establish the type unless the picture is clearly diabetic)

• Doppler ultrasound or CT venography (when renal vein thrombosis is suspected)

DDx

Primary GN types (minimal change vs FSGS vs membranous — biopsy and anti-PLA2R) · diabetic nephropathy (diabetes, retinopathy, gradual onset) · amyloidosis (light chains, Congo red staining) · nephritic syndrome (active sediment — a different entity) · non-renal edema (heart failure or cirrhosis without significant proteinuria)

Home Meds

• Review/stop: NSAIDs (associated with minimal change and membranous disease and worsen renal function)

• Continue/optimize: RAAS blockade (ACEi/ARB) for its antiproteinuric effect

• Add: a statin for hyperlipidemia and diuretics for edema; renally dose medications

Plan

CONSULT: Nephrology (diagnosis, biopsy, immunosuppression) · Hematology (thrombosis and anticoagulation decisions) · the relevant service for a secondary cause (oncology, infectious disease, rheumatology)

• Confirm and classify: quantify proteinuria (UPCR or 24-hour collection), measure serum albumin and lipids, confirm a bland sediment, and pursue the secondary workup (HbA1c, anti-PLA2R, and autoimmune/infectious/paraprotein screening); obtain a renal biopsy in adults unless the disease is clearly diabetic

• Edema management: loop diuretics (furosemide (Lasix), often at higher doses because hypoalbuminemia and gut wall edema impair delivery and absorption — IV is preferred, with a thiazide or metolazone added for resistance), dietary sodium restriction (<2 g/day), and modest fluid restriction, taking care to avoid intravascular depletion and prerenal AKI

• Antiproteinuric therapy: an ACE inhibitor or ARB to reduce proteinuria and slow progression, with blood pressure control, plus an SGLT2 inhibitor for additional renoprotection

• Hyperlipidemia: statin therapy

• Thrombosis — the key danger: nephrotic syndrome is a hypercoagulable state due to urinary antithrombin loss, with the highest risk in membranous nephropathy and when albumin is <2–2.5 g/dL — consider prophylactic anticoagulation in high-risk patients, and treat any venous thromboembolism or renal vein thrombosis with full anticoagulation (heparin transitioning to warfarin or a DOAC per nephrology/hematology), maintaining a high suspicion (flank pain with hematuria and worsening proteinuria suggests renal vein thrombosis)

• Infection prophylaxis and vigilance: urinary immunoglobulin loss increases susceptibility (especially to encapsulated organisms, and spontaneous bacterial peritonitis if ascites is present) — provide pneumococcal vaccination and treat infections promptly

• Disease-specific immunosuppression guided by biopsy: minimal change disease — corticosteroids (prednisone 1 mg/kg/day), usually steroid-responsive; FSGS — corticosteroids with or without a calcineurin inhibitor; membranous nephropathy — supportive care first (many achieve spontaneous remission), with immunosuppression (rituximab, a calcineurin inhibitor, or a cyclophosphamide–steroid regimen) for high-risk or progressive disease; diabetic nephropathy — glycemic and blood pressure control, RAAS blockade, and an SGLT2 inhibitor without immunosuppression; class V lupus nephritis — per the lupus regimen

• Treat secondary causes: malignancy, infection (HBV/HCV/HIV), and autoimmune disease

• PT/OT: mobilize (which also reduces VTE risk)

• Trend: proteinuria and albumin (treatment response), weight and edema, renal function and potassium, lipids, and thrombotic/infectious complications

• Escalation triggers: PE or renal vein thrombosis → anticoagulation with ICU care if unstable; rapid renal decline → biopsy or reassessment for a superimposed process; severe infection or spontaneous bacterial peritonitis → urgent treatment; refractory anasarca → diuretic escalation or ultrafiltration

• Discharge checklist: a documented biopsy diagnosis and therapy plan; a proteinuria-reduction regimen (RAAS blockade, SGLT2 inhibitor) with a statin; diuretic and sodium-restriction education; an assessed thrombosis risk with prophylaxis if indicated; pneumococcal vaccination; nephrology follow-up with laboratory monitoring; return precautions for leg swelling or pain, dyspnea or chest pain, flank pain or blood in the urine, or fever

Red Flags

• PE or renal vein thrombosis (flank pain, hematuria, worsening proteinuria, or unexplained dyspnea) → imaging and full anticoagulation

• Spontaneous bacterial peritonitis or other serious infection → urgent antibiotics

• Rapidly worsening renal function → reassess for a superimposed process (crescentic transformation, acute interstitial nephritis, renal vein thrombosis)

• Severe hypoalbuminemia (albumin <2–2.5) → especially high thrombotic risk

• Anasarca with respiratory compromise from effusions → aggressive decongestion

Senior IM Resident Pearls

• The bland sediment separates nephrotic from nephritic. Heavy proteinuria with a quiet urine is nephrotic; add RBC casts and it becomes a nephritic emergency — the microscopy is the fork in the road.

• Nephrotic patients clot. They lose antithrombin in the urine — keep a low threshold for renal vein thrombosis (flank pain, hematuria, rising proteinuria) and PE, and consider prophylactic anticoagulation when the albumin is very low, especially in membranous disease.

• Diurese them, but gently. Gut edema impairs oral loop absorption (use IV) and over-diuresis can drop an already-low intravascular volume into prerenal AKI.

• Membranous? Check anti-PLA2R and hunt for a secondary cause. Malignancy, hepatitis B, lupus, and drugs all cause it — and many idiopathic cases remit with supportive care alone.

• Vaccinate against pneumococcus. Urinary immunoglobulin loss makes encapsulated infections a real and preventable threat.

• RAAS blockade and SGLT2 inhibitors are foundational — they cut proteinuria and slow progression across most causes.

• Common mistake: attributing the edema to heart failure and missing the proteinuria — always dip the urine and quantify protein in new significant edema with a low albumin.

Nephrology — Rhabdomyolysis

111. Rhabdomyolysis with AKI

muscle breakdown → myoglobin → pigment AKI · trauma / statins / immobilization · aggressive IV fluids early · watch hyperkalemia + compartment syndrome · Super Compact

Sx: muscle pain/weakness/swelling, dark "tea-colored" urine (myoglobinuria) · often after trauma/crush, prolonged immobilization (found down), seizure, exertion, or drug · ± signs of complications: oliguria (AKI), hyperkalemia (arrhythmia), compartment syndrome (tense painful limb) (classic triad — myalgia, weakness, dark urine — present in a minority; CK makes the diagnosis)

Neg: denies hematuria source (urine dip heme+ but no RBCs on micro = myoglobin, not blood) · denies primary cardiac/renal cause of hyperK alone · denies other AKI (pre-renal, obstruction, ATN from other cause) · denies pure hemoglobinuria (hemolysis)

SHx: trauma/crush/prolonged down-time (found unresponsive) · alcohol/drug use (immobilization, direct toxicity, cocaine) · statins ± fibrate/interacting drug · strenuous exertion/heat · seizures · immobility/restraint

Etiology: skeletal muscle necrosis releasing myoglobin, K, phosphate, CK, urate · traumatic/crush (crush injury, prolonged immobilization/pressure, compartment syndrome) · non-traumatic: drugs/toxins (statins esp with fibrates/CYP inhibitors, alcohol, cocaine), exertional/heat, seizures, infections, metabolic (↓K/↓PO4), inherited myopathies · myoglobin → renal tubular injury (cast obstruction, vasoconstriction, direct toxicity) → pigment AKI

RF: trauma/immobilization · statin + fibrate/interacting drug · alcohol/substance use · extreme exertion/heat · hypovolemia · CKD · genetic myopathy

Data: CK (markedly elevated — often >5× ULN; AKI risk rises notably >5,000–10,000; trend it — peaks then falls) · BMP (↑Cr; hyperkalemia — early/dangerous; hyperphosphatemia; hypocalcemia early — Ca into muscle; later rebound hyperCa) · urinalysis (heme-positive dipstick with FEW/NO RBCs on microscopy = myoglobinuria; pigmented granular casts) · uric acid (↑) · urine output · ECG (hyperK changes) · coags (severe cases — DIC) · compartment exam/pressures if tense limb

DDx: other pigment/heme-positive urine (hemoglobinuria from hemolysis; true hematuria — RBCs present) · other AKI causes (pre-renal, ATN, obstruction) · myopathy/myositis (inflammatory, infectious) · primary hyperkalemia (no CK rise)

Home Meds: STOP statin (± fibrate); review interacting drugs (CYP3A4 inhibitors) · hold nephrotoxins/NSAIDs · avoid K-containing/K-sparing agents · renally dose · hold offending drugs/toxins

Plan

CONSULT: Nephrology (AKI, dialysis need) · Surgery/Orthopedics (compartment syndrome — emergent fasciotomy) · ICU (severe metabolic derangement, instability) · Toxicology (drug/toxin cause)

– Aggressive early IV fluid resuscitation (the cornerstone): isotonic crystalloid (normal saline or balanced) at high rates — start ~1–2 L/h initially in severe cases, then titrate to a urine output target ~200–300 mL/h; monitor volume status closely (avoid overload, esp in oliguric/CKD/elderly); early/aggressive fluids prevent AKI by flushing pigment and restoring perfusion
– Treat hyperkalemia emergently (the early killer): ECG; for high K or ECG changes → calcium gluconate 1–2 g IV (membrane stabilization), insulin 10 units IV + D50 25 g, albuterol 10–20 mg neb, then removal (loop diuretic if making urine, GI binder, or dialysis); recheck frequently — ongoing muscle release re-elevates K
– Hypocalcemia: usually do NOT treat asymptomatic hypocalcemia (calcium deposits in injured muscle; rebound hypercalcemia later) — treat only if symptomatic or severe hyperkalemia needing calcium
– Bicarbonate / mannitol: evidence is weak and they are not routinely recommended over aggressive isotonic fluids; urine alkalinization (bicarbonate) is sometimes used to reduce cast formation but isn't proven — prioritize volume; avoid mannitol if oliguric/overloaded
– Treat the cause: stop statin/offending drug, treat the toxin/seizure/infection; remove crush/pressure
– COMPARTMENT SYNDROME (surgical emergency): tense, painful, swollen limb with pain out of proportion / paresthesia → measure compartment pressures → emergent fasciotomy; high index of suspicion post-crush/reperfusion
– Dialysis if needed: refractory hyperkalemia, severe acidosis, volume overload, or uremia (AEIOU) — note myoglobin itself is poorly dialyzed; dialysis is for the metabolic complications
– Phosphate: treat severe hyperphosphatemia; monitor for late rebound hypercalcemia
– A heme-positive dipstick with no red cells on microscopy is the bedside clue to myoglobinuria — don't chase it as hematuria; check a CK and start fluids.
– PT/OT: mobilize as able; monitor reperfusing limbs
– Trend: CK (peak/downtrend), K + Ca + phosphate frequently, Cr/UOP, volume status, ECG, compartment exam
– Escalation triggers: hyperkalemic ECG changes → emergent treatment + dialysis; compartment syndrome → emergent fasciotomy; refractory AKI/overload/acidosis → dialysis; rising CK despite therapy → ongoing muscle injury (recheck cause/compartment)
– Discharge checklist: CK trending down + AKI recovering; offending drug stopped (statin discontinued/avoided or re-evaluated); electrolytes normalized (watch rebound hypercalcemia); cause addressed; nephrology follow-up if AKI persists; hydration/avoidance counseling (exertion, drugs); return precautions (dark urine, muscle pain/swelling, decreased urine, weakness)

111. Rhabdomyolysis with AKI

complete reference · trauma + statins + immobilization · pigment nephropathy · aggressive fluids + electrolyte/compartment vigilance · Full Card

Symptoms / Associated Sx

• Muscle pain, weakness, and swelling, with dark "tea-colored" urine from myoglobinuria

• Frequently follows trauma/crush injury, prolonged immobilization (a "found-down" patient), seizures, extreme exertion, or a culprit drug

• Complications: oliguria (AKI), hyperkalemia with arrhythmia, and compartment syndrome (a tense, painful limb)

• The classic triad of myalgia, weakness, and dark urine is present in only a minority — the CK makes the diagnosis

Neg

• Pt denies a true hematuria source — the dipstick is heme-positive but microscopy shows few or no RBCs, indicating myoglobin rather than blood

• Pt denies a primary cardiac or renal cause of isolated hyperkalemia

• Pt denies an alternative AKI mechanism (pre-renal, obstruction, ATN from another cause) and denies pure hemoglobinuria from hemolysis

Social History (SHx)

• Trauma, crush injury, or prolonged down-time (found unresponsive)

• Alcohol and drug use (immobilization, direct myotoxicity, cocaine)

• Statin use, particularly combined with a fibrate or a CYP-inhibiting interacting drug

• Strenuous exertion or heat exposure; seizures; immobility or physical restraint

Main Etiology

• Skeletal muscle necrosis releasing myoglobin, potassium, phosphate, creatine kinase, and urate into the circulation

• Traumatic/crush: crush injury, prolonged immobilization with pressure, and compartment syndrome

• Non-traumatic: drugs and toxins (statins, especially with fibrates or CYP inhibitors; alcohol; cocaine), exertional and heat-related injury, seizures, infections, metabolic derangements (hypokalemia, hypophosphatemia), and inherited myopathies

• Myoglobin causes renal tubular injury through cast obstruction, vasoconstriction, and direct toxicity, producing pigment-induced AKI

RF

• Modifiable: drug combinations (statin plus fibrate/interacting agent), alcohol/substance use, hydration before exertion, heat exposure

• Non-modifiable: trauma/immobilization, CKD, and genetic myopathies

Data

• Creatine kinase (CK) (markedly elevated, often more than 5 times the upper limit of normal; AKI risk rises notably above ~5,000–10,000 U/L; trend it, as it peaks and then falls)

• BMP (rising creatinine; hyperkalemia, which is early and dangerous; hyperphosphatemia; early hypocalcemia as calcium moves into injured muscle, with later rebound hypercalcemia)

• Urinalysis (a heme-positive dipstick with few or no RBCs on microscopy indicates myoglobinuria; pigmented granular casts may be seen)

• Uric acid (elevated from muscle breakdown)

• Urine output (the key resuscitation target); ECG (hyperkalemic changes)

• Coagulation studies (DIC in severe cases)

• Compartment examination and pressures (when a tense limb raises concern for compartment syndrome)

DDx

Other causes of pigmenturia (hemoglobinuria from hemolysis; true hematuria with RBCs present) · other AKI causes (pre-renal, ATN, obstruction) · myopathy/myositis (inflammatory or infectious) · primary hyperkalemia (without a CK rise)

Home Meds

• Stop the statin (and any fibrate); review interacting drugs (CYP3A4 inhibitors)

• Hold: nephrotoxins and NSAIDs

• Avoid: potassium-containing or potassium-sparing agents; renally dose medications and hold offending drugs/toxins

Plan

CONSULT: Nephrology (AKI and dialysis need) · Surgery/Orthopedics (compartment syndrome requiring emergent fasciotomy) · ICU (severe metabolic derangement or instability) · Toxicology (drug or toxin cause)

• Aggressive early IV fluid resuscitation is the cornerstone: isotonic crystalloid (normal saline or a balanced solution) at high rates — starting around 1–2 L/h in severe cases — then titrated to a urine output target of roughly 200–300 mL/h, while monitoring volume status closely to avoid overload (particularly in oliguric, CKD, or elderly patients); early aggressive fluids prevent AKI by flushing pigment and restoring renal perfusion

• Treat hyperkalemia emergently (the early killer): obtain an ECG and, for an elevated potassium or ECG changes, give calcium gluconate 1–2 g IV to stabilize the membrane, insulin 10 units IV with dextrose 25 g, and nebulized albuterol, then remove potassium (a loop diuretic if making urine, a GI binder, or dialysis); recheck frequently, as ongoing muscle breakdown re-elevates potassium

• Hypocalcemia: generally do not treat asymptomatic hypocalcemia, since calcium deposits in injured muscle and rebound hypercalcemia follows; treat only for symptomatic hypocalcemia or when calcium is needed for severe hyperkalemia

• Bicarbonate and mannitol: evidence is weak and neither is routinely recommended over aggressive isotonic fluids; urine alkalinization with bicarbonate is sometimes used to reduce cast formation but is unproven — prioritize volume resuscitation, and avoid mannitol in oliguric or overloaded patients

• Treat the cause: stop the statin or offending drug, treat the toxin/seizure/infection, and relieve any crush or pressure

• Compartment syndrome (a surgical emergency): a tense, painful, swollen limb with pain out of proportion or paresthesia warrants measurement of compartment pressures and emergent fasciotomy; maintain a high index of suspicion after crush injury and reperfusion

• Dialysis when indicated: for refractory hyperkalemia, severe acidosis, volume overload, or uremia; note that myoglobin itself is poorly dialyzed, so dialysis addresses the metabolic complications rather than clearing the pigment

• Phosphate: treat severe hyperphosphatemia and watch for late rebound hypercalcemia

• PT/OT: mobilize as able, monitoring reperfusing limbs

• Trend: CK (peak and downtrend), potassium, calcium, and phosphate frequently, creatinine and urine output, volume status, the ECG, and the compartment exam

• Escalation triggers: hyperkalemic ECG changes → emergent treatment and dialysis; compartment syndrome → emergent fasciotomy; refractory AKI, overload, or acidosis → dialysis; a rising CK despite therapy → ongoing muscle injury (recheck the cause and the compartments)

• Discharge checklist: a downtrending CK with recovering AKI; the offending drug stopped (statin discontinued and avoided or re-evaluated); normalized electrolytes (watching for rebound hypercalcemia); the cause addressed; nephrology follow-up if AKI persists; hydration and avoidance counseling (exertion, drugs); return precautions for dark urine, muscle pain or swelling, decreased urine output, or weakness

Red Flags

• Hyperkalemia with ECG changes → emergent treatment; potassium re-rises as muscle continues to break down

• Compartment syndrome (tense limb, pain out of proportion, paresthesia) → emergent fasciotomy

• Anuric or refractory AKI with metabolic derangement → dialysis

• DIC in severe rhabdomyolysis → supportive management and ICU care

• Markedly rising CK despite treatment → ongoing or recurrent muscle injury

Senior IM Resident Pearls

• Fluids, fluids, fluids — early. The single intervention that prevents pigment AKI is aggressive isotonic crystalloid titrated to a brisk urine output; everything else is secondary.

• Heme-positive dipstick with no RBCs = myoglobin. This bedside discrepancy is the fastest clue — send a CK rather than working it up as hematuria.

• Don't treat the hypocalcemia. It's calcium sequestered in muscle that will rebound; correcting it risks hypercalcemia later — reserve calcium for membrane stabilization in hyperkalemia or symptomatic cases.

• Bicarbonate and mannitol are not the answer. Volume resuscitation outperforms them; don't let alkalinization distract from giving enough fluid.

• Think compartment syndrome after crush and reperfusion — a limb that's tense with pain out of proportion needs pressures and possibly an emergent fasciotomy, not just elevation.

• Recheck the potassium often. Necrotic muscle keeps leaking potassium, so a "treated" level can climb back into the danger zone.

• Common mistake: giving cautious "maintenance" fluids in a sick rhabdomyolysis patient — under-resuscitation is the path to dialysis; titrate to urine output instead.

Nephrology / Onc — Tumor Lysis Syndrome

112. Tumor Lysis Syndrome (TLS)

massive tumor cell lysis → ↑K, ↑PO4, ↑uric acid, ↓Ca + AKI · prevent it (the best treatment) · hydrate + rasburicase/allopurinol · hyperkalemia kills · Super Compact

Sx: often lab-detected before symptoms · hyperkalemia (weakness, arrhythmia — the immediate killer), hypocalcemia (tetany, cramps, seizures, QT prolongation, arrhythmia), AKI/oliguria (urate/phosphate nephropathy), nausea/lethargy · usually 12–72h after starting chemo (or spontaneously in bulky disease) (the danger is K and Ca arrhythmias + AKI — anticipate, don't wait)

Neg: denies pre-existing CKD as sole AKI cause (TLS worsens it though) · denies other hyperkalemia cause · denies other AKI (obstruction, pre-renal) · denies that this is just chemo nausea (check the labs)

SHx: hematologic malignancy — high-grade lymphoma (Burkitt), acute leukemia (ALL/AML), high tumor burden/high WBC, bulky disease · recent/imminent chemotherapy (or steroids alone can trigger) · baseline renal function · prior TLS

Etiology: rapid lysis of malignant cells (spontaneous or chemo-induced) releasing intracellular contents → hyperkalemia, hyperphosphatemia, hyperuricemia, secondary hypocalcemia (Ca-phosphate precipitation); uric acid + calcium-phosphate crystal deposition in tubules → AKI; Cairo-Bishop: laboratory TLS (≥2 metabolic abnormalities) → clinical TLS (+ AKI, arrhythmia, or seizure)

RF: high-grade/bulky hematologic malignancy (Burkitt, ALL, high-count AML) · high LDH/WBC/tumor burden · pre-existing CKD/volume depletion · chemosensitive tumor · hyperuricemia at baseline

Data: BMP + Ca/Mg/phosphate + uric acid + LDH (↑K, ↑PO4, ↑uric acid, ↓Ca, ↑Cr; LDH = tumor burden marker) · frequent labs q6–12h during risk window · ECG (hyperK changes; QT from hypoCa) · UA (urate crystals) · urine output · CBC/smear (blasts, counts) · consider renal US if AKI

DDx: other causes of these electrolyte derangements (renal failure, rhabdo — check CK) · pre-renal/obstructive AKI (volume, US) · chemo nausea without TLS (normal labs) · sepsis with multi-organ involvement

Home Meds: hold nephrotoxins/NSAIDs · avoid K- and phosphate-containing fluids/supplements · caution with allopurinol + 6-MP/azathioprine interaction (reduce thiopurine dose) · renally dose · hold thiazides (urate retention)

Plan

CONSULT: Oncology/Hematology (malignancy + chemo timing) · Nephrology (AKI, dialysis need, severe metabolic derangement) · ICU (clinical TLS, arrhythmia, instability)

– PREVENTION is the main treatment — risk-stratify before chemo and treat prophylactically:
– Aggressive IV hydration (cornerstone): isotonic fluids (normal saline) at high rates (e.g. 2.5–3 L/m²/day, ~200 mL/h) to maintain brisk urine output and flush crystals; do not routinely alkalinize urine (promotes calcium-phosphate precipitation); avoid in overload — monitor closely
– Hypouricemic therapy:
  • High risk / established TLS / high uric acid: rasburicase 0.2 mg/kg IV (recombinant urate oxidase — rapidly degrades existing uric acid; check G6PD first — contraindicated in deficiency, hemolysis risk; don't send uric acid on ice without special handling — degrades ex vivo)
  • Lower/intermediate risk / prevention: allopurinol 300 mg PO daily (xanthine oxidase inhibitor — prevents new uric acid; reduce dose in renal impairment; doesn't lower existing urate)
– Hyperkalemia (the immediate threat): ECG; for high K/ECG changes → calcium gluconate 1–2 g IV (membrane stabilization), insulin 10 units IV + D50 25 g, albuterol 10–20 mg neb, then removal (GI binder, loop diuretic if urine, or dialysis); recheck often (ongoing lysis re-elevates)
– Hyperphosphatemia: oral phosphate binders, hydration; limits indirectly help calcium
– Hypocalcemia: treat only if symptomatic (tetany, seizures, arrhythmia/QT) with calcium — giving calcium into a high-phosphate state risks calcium-phosphate precipitation, so use the minimum needed; correcting phosphate is the priority
– Dialysis (low threshold in TLS): for refractory hyperkalemia, severe hyperphosphatemia, refractory acidosis/overload, or AKI not responding — nephrology early; CRRT for unstable
– Check a G6PD level before rasburicase — it causes severe hemolysis (and methemoglobinemia) in G6PD deficiency — and don't alkalinize the urine, which trades urate crystals for calcium-phosphate crystals.
– PT/OT: per illness
– Trend: K/phosphate/uric acid/Ca/Cr frequently (q6–12h in risk window), ECG, urine output, volume status, response to therapy
– Escalation triggers: hyperkalemic ECG changes → emergent treatment + dialysis; symptomatic hypocalcemia/arrhythmia → cardiac monitoring + calcium; oliguric/refractory AKI → urgent dialysis/CRRT; clinical TLS → ICU
– Discharge checklist: metabolic derangements resolved + renal function recovering; chemotherapy plan coordinated with TLS prophylaxis; ongoing allopurinol/hydration if continued risk; nephrology follow-up if AKI persists; oncology follow-up; return precautions (palpitations/weakness, cramps/tingling, decreased urine, confusion)

112. Tumor Lysis Syndrome (TLS)

complete reference · hematologic malignancies · prevention-focused · hydration + rasburicase/allopurinol + electrolyte management · Full Card

Symptoms / Associated Sx

• Often detected on labs before symptoms appear

• Hyperkalemia (weakness, arrhythmia — the immediate life threat), hypocalcemia (tetany, cramps, seizures, QT prolongation, arrhythmia), and AKI/oliguria from urate and calcium-phosphate nephropathy; nausea and lethargy

• Typically occurs 12–72 hours after starting chemotherapy, or spontaneously in bulky, rapidly proliferating disease

Neg

• Pt denies pre-existing CKD as the sole cause of the AKI (though TLS worsens underlying CKD)

• Pt denies an alternative cause of hyperkalemia and denies another AKI mechanism (obstruction, pre-renal)

• Pt denies that the picture is simply chemotherapy-related nausea — the metabolic labs distinguish the two

Social History (SHx)

• Hematologic malignancy — high-grade lymphoma (Burkitt), acute leukemia (ALL/AML), high tumor burden or high white cell count, and bulky disease

• Recent or imminent chemotherapy (corticosteroids alone can also trigger lysis)

• Baseline renal function; any prior episode of TLS

Main Etiology

• Rapid lysis of malignant cells (spontaneous or chemotherapy-induced) releasing intracellular contents — producing hyperkalemia, hyperphosphatemia, hyperuricemia, and secondary hypocalcemia (from calcium-phosphate precipitation)

• Uric acid and calcium-phosphate crystal deposition in the renal tubules causes acute kidney injury

• The Cairo-Bishop classification distinguishes laboratory TLS (≥2 metabolic abnormalities) from clinical TLS (with AKI, arrhythmia, or seizure)

RF

• Modifiable: volume status, prophylaxis before chemotherapy, avoidance of nephrotoxins

• Non-modifiable: high-grade or bulky hematologic malignancy (Burkitt lymphoma, ALL, high-count AML), high LDH/white count/tumor burden, pre-existing CKD, chemosensitive tumors, and baseline hyperuricemia

Data

• BMP with calcium, magnesium, phosphate, uric acid, and LDH (hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and rising creatinine; LDH marks tumor burden)

• Frequent monitoring every 6–12 hours during the risk window (the derangements evolve rapidly)

• ECG (hyperkalemic changes and QT prolongation from hypocalcemia)

• Urinalysis (urate crystals); urine output

• CBC and smear (blasts and counts); renal ultrasound if AKI is present

DDx

Other causes of these electrolyte derangements (renal failure, rhabdomyolysis — check CK) · pre-renal or obstructive AKI (volume status, ultrasound) · chemotherapy nausea without TLS (normal metabolic labs) · sepsis with multi-organ involvement

Home Meds

• Hold: nephrotoxins and NSAIDs

• Avoid: potassium- and phosphate-containing fluids and supplements

• Caution: allopurinol interacts with 6-mercaptopurine and azathioprine (reduce the thiopurine dose); hold thiazides (which retain urate); renally dose medications

Plan

CONSULT: Oncology/Hematology (malignancy and chemotherapy timing) · Nephrology (AKI, dialysis need, severe metabolic derangement) · ICU (clinical TLS, arrhythmia, instability)

• Prevention is the main treatment: risk-stratify before chemotherapy and treat prophylactically

• Aggressive IV hydration (the cornerstone): isotonic fluids (normal saline) at high rates (e.g. 2.5–3 L/m²/day, roughly 200 mL/h) to maintain brisk urine output and flush crystals; do not routinely alkalinize the urine, since alkalinization promotes calcium-phosphate precipitation; monitor closely and avoid overload

• Hypouricemic therapy:

• • High risk, established TLS, or high uric acid: rasburicase 0.2 mg/kg IV (recombinant urate oxidase that rapidly degrades existing uric acid); check G6PD status first, as it is contraindicated in G6PD deficiency due to hemolysis risk, and handle the uric acid sample appropriately (it degrades ex vivo at room temperature)

• • Lower or intermediate risk and prevention: allopurinol 300 mg PO daily (a xanthine oxidase inhibitor that prevents new uric acid formation but does not lower existing urate); reduce the dose in renal impairment

• Hyperkalemia (the immediate threat): obtain an ECG and, for an elevated potassium or ECG changes, give calcium gluconate 1–2 g IV to stabilize the membrane, insulin 10 units IV with dextrose 25 g, and nebulized albuterol, then remove potassium (a GI binder, a loop diuretic if making urine, or dialysis); recheck frequently, as ongoing lysis re-elevates it

• Hyperphosphatemia: oral phosphate binders and hydration; controlling phosphate also indirectly helps the calcium

• Hypocalcemia: treat only if symptomatic (tetany, seizures, arrhythmia, QT prolongation), because giving calcium into a high-phosphate state risks calcium-phosphate precipitation — use the minimum necessary, and prioritize correcting the phosphate

• Dialysis (with a low threshold in TLS): for refractory hyperkalemia, severe hyperphosphatemia, refractory acidosis or overload, or AKI not responding to therapy — involve nephrology early and use CRRT for unstable patients

• PT/OT: guided by the underlying illness

• Trend: potassium, phosphate, uric acid, calcium, and creatinine frequently (every 6–12 hours in the risk window), the ECG, urine output, volume status, and the response to therapy

• Escalation triggers: hyperkalemic ECG changes → emergent treatment and dialysis; symptomatic hypocalcemia or arrhythmia → cardiac monitoring and calcium; oliguric or refractory AKI → urgent dialysis/CRRT; clinical TLS → ICU

• Discharge checklist: resolved metabolic derangements with recovering renal function; a chemotherapy plan coordinated with TLS prophylaxis; continued allopurinol and hydration if risk persists; nephrology follow-up if AKI persists; oncology follow-up; return precautions for palpitations or weakness, cramps or tingling, decreased urine output, or confusion

Red Flags

• Hyperkalemia with ECG changes → emergent treatment and dialysis; potassium re-rises with ongoing lysis

• Symptomatic hypocalcemia (tetany, seizures, QT prolongation) → cardiac monitoring and cautious calcium

• Oliguric or refractory AKI → urgent dialysis (low threshold in TLS)

• G6PD deficiency → rasburicase is contraindicated (severe hemolysis, methemoglobinemia)

• Clinical TLS (AKI, arrhythmia, seizure) → ICU-level care

Senior IM Resident Pearls

• The best treatment is prevention. Identify the high-risk patient before chemotherapy and start hydration and hypouricemic therapy — established TLS is far harder to manage than prevented TLS.

• Check G6PD before rasburicase. It causes severe hemolysis and methemoglobinemia in deficiency — a preventable disaster, and important in populations where deficiency is common.

• Don't alkalinize the urine. Older protocols added bicarbonate, but it trades uric acid crystals for calcium-phosphate crystals — modern practice is aggressive isotonic hydration alone.

• Allopurinol prevents, rasburicase treats. Allopurinol blocks new urate formation but won't lower an already-high level; rasburicase degrades the existing uric acid quickly.

• Leave asymptomatic hypocalcemia alone. Giving calcium into a high-phosphate milieu precipitates calcium-phosphate in tissues and kidneys — fix the phosphate instead.

• Steroids count as chemotherapy here — even a steroid pulse in a bulky lymphoma can trigger lysis, so don't reserve prophylaxis only for cytotoxic regimens.

• Common mistake: sending the uric acid level in a tube that sits at room temperature after rasburicase — it keeps degrading urate ex vivo and gives a falsely low reading; the sample needs to go on ice and be run quickly.

Nephrology / Acid-Base — Renal Tubular Acidosis

113. Renal Tubular Acidosis (RTA)

persistent NON-gap (hyperchloremic) metabolic acidosis · normal-ish GFR · type 1 (distal) / type 2 (proximal) / type 4 (hypoaldo) · urine pH + urine anion gap + K direction sort it · Super Compact

Sx: often the underlying disorder/lab finding dominates · type 1: nephrolithiasis/nephrocalcinosis, bone disease, hypokalemic weakness · type 2: features of Fanconi (glucosuria, phosphaturia, aminoaciduria), bone disease, hypokalemia · type 4: usually asymptomatic hyperkalemia + mild acidosis in diabetes/CKD (suspect RTA in a persistent normal-gap acidosis without diarrhea)

Neg: denies diarrhea/GI bicarbonate loss (the main NAGMA mimic — urine anion gap distinguishes) · denies high anion gap (this is a NON-gap acidosis) · denies low GFR as sole cause (uremic acidosis differs) · denies acetazolamide/other drug cause unexamined

SHx: autoimmune disease — Sjögren, lupus (type 1) · meds — amphotericin, ifosfamide, tenofovir, topiramate, acetazolamide (type 2), TMP, NSAIDs, ACEi/ARB, K-sparing diuretics, calcineurin inhibitors (type 4) · diabetes/CKD (type 4) · multiple myeloma (type 2 Fanconi)

Etiology: impaired renal acid handling with preserved/near-preserved GFR → non-gap acidosis · type 1 (distal): failure of distal H⁺ secretion → can't acidify urine (urine pH >5.5), hypokalemia, stones/nephrocalcinosis · type 2 (proximal): impaired HCO3 reabsorption → bicarbonate wasting (urine pH variable, can acidify when serum HCO3 low), hypokalemia, often Fanconi · type 4 (hypoaldosteronism): aldosterone deficiency/resistance → HYPERkalemia + mild acidosis (most common; diabetic CKD)

RF: autoimmune disease (type 1) · causative drugs · diabetes/CKD (type 4) · myeloma/Fanconi triggers (type 2) · genetic forms

Data: BMP (low HCO3, hyperchloremia, normal anion gap; K — low in 1&2, HIGH in 4 — the key splitter) · ABG/VBG (confirm metabolic acidosis + compensation) · urine pH (>5.5 inappropriately alkaline in type 1; can acidify in 2&4) · urine anion gap (UAG = UNa + UK − UCl) (positive in RTA — impaired NH4⁺ excretion; negative in diarrhea — appropriate NH4⁺; the key test to separate RTA from GI loss) · serum/urine electrolytes · consider serum aldosterone/renin (type 4), urine glucose/protein (Fanconi/type 2), autoimmune serologies (type 1), renal US (nephrocalcinosis)

DDx: diarrhea/GI bicarbonate loss (negative urine anion gap — the main mimic) · RTA subtypes (K direction + urine pH + UAG) · uremic acidosis of advanced CKD (low GFR) · other NAGMA (acetazolamide, ureteral diversion)

Home Meds: review/stop culprit drugs (amphotericin, tenofovir, topiramate, ifosfamide for type 2; TMP, NSAIDs, ACEi/ARB, K-sparing diuretics, calcineurin inhibitors for type 4) · renally dose · adjust per type (K supplements vs avoid)

Plan

CONSULT: Nephrology (diagnosis, classification, refractory cases) · relevant service for the cause (rheumatology for Sjögren/lupus, endocrine, oncology for myeloma)

– Step 1 — confirm it's a non-gap acidosis: BMP (calc anion gap — normal), ABG/VBG; rule out a HAGMA
– Step 2 — separate RTA from diarrhea: urine anion gap (positive → renal/RTA; negative → GI loss) ± urine pH
– Step 3 — classify by the potassium (the fast splitter) + urine pH: hypokalemia + urine pH >5.5 + stones = type 1; hypokalemia + bicarbonate wasting ± Fanconi = type 2; hyperkalemia + mild acidosis in diabetic CKD = type 4
– Treat the cause: stop/replace the offending drug, treat the underlying autoimmune disease or myeloma
– Type 1 (distal): oral alkali — sodium bicarbonate or potassium citrate (citrate corrects acidosis AND replaces K AND reduces stones); typically modest doses; treat/prevent nephrocalcinosis and bone disease
– Type 2 (proximal): often needs large alkali doses (bicarbonate wasting makes it hard to correct) plus potassium replacement (alkali worsens K wasting); thiazide can help (induces mild volume contraction → ↑proximal reabsorption); address Fanconi (phosphate, vitamin D)
– Type 4 (hypoaldosteronism): treat the hyperkalemia — dietary K restriction, loop or thiazide diuretic (kaliuretic), GI K binder if needed; fludrocortisone 0.1 mg PO daily if true mineralocorticoid deficiency (caution in volume-overloaded/HTN); review and stop contributing drugs (TMP, NSAIDs, ACEi/ARB, K-sparing diuretics, calcineurin inhibitors); modest alkali if needed
– The potassium tells you the type at a glance: low K = type 1 or 2, high K = type 4. And the urine anion gap is what separates any RTA from simple diarrhea — a positive UAG in a non-gap acidosis means the kidney isn't excreting ammonium.
– PT/OT: per underlying disease
– Trend: bicarbonate/acid-base, K (direction depends on type), urine pH, stone burden (type 1), renal function, response to alkali
– Escalation triggers: severe hypokalemia (type 1/2) with weakness/arrhythmia → urgent K repletion + cardiac monitoring; severe hyperkalemia (type 4) → emergent treatment; refractory acidosis → nephrology; nephrocalcinosis/stones → urology
– Discharge checklist: RTA type classified + cause addressed; maintenance alkali/K regimen defined (potassium citrate for type 1; high-dose alkali + K for type 2; K-lowering for type 4); offending drugs stopped; nephrology follow-up + lab monitoring (K, bicarbonate); stone prevention if type 1; return precautions (weakness, palpitations, stone symptoms)

113. Renal Tubular Acidosis (RTA)

complete reference · persistent non-gap metabolic acidosis · types 1, 2, 4 · urine anion gap + potassium direction · Full Card

Symptoms / Associated Sx

• Often the underlying disorder or an incidental lab finding dominates the presentation

• Type 1 (distal): nephrolithiasis and nephrocalcinosis, metabolic bone disease, and hypokalemic muscle weakness

• Type 2 (proximal): features of Fanconi syndrome (glucosuria, phosphaturia, aminoaciduria), bone disease, and hypokalemia

• Type 4 (hypoaldosteronism): usually asymptomatic hyperkalemia with a mild acidosis, typically in diabetes and CKD

Neg

• Pt denies diarrhea or another GI bicarbonate loss — the principal mimic of a non-gap acidosis, distinguished by the urine anion gap

• Pt denies a high anion gap — RTA produces a non-gap (hyperchloremic) acidosis

• Pt denies a low GFR as the sole explanation (uremic acidosis differs) and denies an unexamined drug cause (e.g. acetazolamide)

Social History (SHx)

• Autoimmune disease — Sjögren syndrome and lupus (type 1)

• Medications — amphotericin, ifosfamide, tenofovir, topiramate, and acetazolamide (type 2); TMP, NSAIDs, ACEi/ARB, potassium-sparing diuretics, and calcineurin inhibitors (type 4)

• Diabetes and CKD (type 4); multiple myeloma (type 2 Fanconi syndrome)

Main Etiology

• Impaired renal acid handling with a preserved or near-preserved GFR, producing a non-gap acidosis

• Type 1 (distal): failure of distal hydrogen ion secretion so the urine cannot be acidified (urine pH >5.5), with hypokalemia and stones/nephrocalcinosis

• Type 2 (proximal): impaired bicarbonate reabsorption causing bicarbonate wasting (urine pH is variable and can acidify once the serum bicarbonate is low), with hypokalemia and often Fanconi syndrome

• Type 4 (hypoaldosteronism): aldosterone deficiency or resistance causing hyperkalemia with a mild acidosis — the most common type, typically in diabetic CKD

RF

• Modifiable: culprit drugs, treatment of the underlying disease

• Non-modifiable: autoimmune disease (type 1), diabetes/CKD (type 4), myeloma and other Fanconi triggers (type 2), and genetic forms

Data

• BMP (low bicarbonate, hyperchloremia, and a normal anion gap; the potassium is the key splitter — low in types 1 and 2, high in type 4)

• ABG/VBG (confirm the metabolic acidosis and assess compensation)

• Urine pH (inappropriately alkaline, >5.5, in type 1; the urine can acidify in types 2 and 4)

• Urine anion gap (urine Na + urine K − urine Cl) (positive in RTA, reflecting impaired ammonium excretion; negative in diarrhea, reflecting appropriate ammonium excretion — the key test to separate RTA from GI bicarbonate loss)

• Serum and urine electrolytes

• Serum aldosterone and renin (type 4), urine glucose/protein (Fanconi/type 2), autoimmune serologies (type 1), and renal ultrasound for nephrocalcinosis (as indicated by the suspected type)

DDx

Diarrhea/GI bicarbonate loss (negative urine anion gap — the main mimic) · RTA subtypes (potassium direction, urine pH, urine anion gap) · uremic acidosis of advanced CKD (low GFR) · other non-gap acidoses (acetazolamide, ureteral diversion)

Home Meds

• Review/stop culprit drugs: amphotericin, tenofovir, topiramate, and ifosfamide (type 2); TMP, NSAIDs, ACEi/ARB, potassium-sparing diuretics, and calcineurin inhibitors (type 4)

• Adjust by type: potassium supplementation in types 1 and 2 versus potassium-lowering measures in type 4; renally dose medications

Plan

CONSULT: Nephrology (diagnosis, classification, refractory cases) · the relevant service for the cause (rheumatology for Sjögren/lupus, endocrinology, oncology for myeloma)

• Step 1 — confirm a non-gap acidosis: a BMP with a calculated (normal) anion gap and an ABG/VBG, excluding a high-anion-gap process

• Step 2 — separate RTA from diarrhea: the urine anion gap (positive indicates a renal/RTA cause; negative indicates GI loss), with the urine pH

• Step 3 — classify by the potassium (the fast splitter) and urine pH: hypokalemia with a urine pH >5.5 and stones suggests type 1; hypokalemia with bicarbonate wasting and possible Fanconi features suggests type 2; hyperkalemia with a mild acidosis in diabetic CKD suggests type 4

• Treat the cause: stop or replace the offending drug and treat the underlying autoimmune disease or myeloma

• Type 1 (distal): oral alkali — sodium bicarbonate or potassium citrate (citrate corrects the acidosis, replaces potassium, and reduces stone formation), typically at modest doses, while treating and preventing nephrocalcinosis and bone disease

• Type 2 (proximal): often requires large alkali doses (bicarbonate wasting makes correction difficult) plus potassium replacement (alkali worsens potassium wasting); a thiazide can help by inducing mild volume contraction that increases proximal reabsorption, and Fanconi features (phosphate, vitamin D) are addressed

• Type 4 (hypoaldosteronism): treat the hyperkalemia with dietary potassium restriction, a kaliuretic loop or thiazide diuretic, and a GI potassium binder if needed; add fludrocortisone 0.1 mg PO daily for true mineralocorticoid deficiency (with caution in volume-overloaded or hypertensive patients); review and stop contributing drugs (TMP, NSAIDs, ACEi/ARB, potassium-sparing diuretics, calcineurin inhibitors); give modest alkali if needed

• PT/OT: guided by the underlying disease

• Trend: bicarbonate and acid-base status, potassium (the direction depends on the type), urine pH, stone burden (type 1), renal function, and the response to alkali

• Escalation triggers: severe hypokalemia (types 1/2) with weakness or arrhythmia → urgent repletion and cardiac monitoring; severe hyperkalemia (type 4) → emergent treatment; refractory acidosis → nephrology; nephrocalcinosis or stones → urology

• Discharge checklist: the RTA type classified and the cause addressed; a defined maintenance regimen (potassium citrate for type 1; high-dose alkali plus potassium for type 2; potassium-lowering measures for type 4); offending drugs stopped; nephrology follow-up with laboratory monitoring (potassium, bicarbonate); stone prevention for type 1; return precautions for weakness, palpitations, or stone symptoms

Red Flags

• Severe hypokalemia in type 1 or 2 → muscle weakness, paralysis, and arrhythmia → urgent repletion

• Severe hyperkalemia in type 4 → emergent treatment, especially with contributing drugs

• Nephrocalcinosis or recurrent stones in type 1 → progressive renal damage

• Profound acidosis in proximal RTA refractory to standard alkali → nephrology and large-dose repletion

• An underlying serious cause (myeloma, autoimmune disease) → dedicated workup and treatment

Senior IM Resident Pearls

• The potassium classifies the RTA at a glance. Low potassium points to type 1 or 2; high potassium points to type 4 — start there before the finer testing.

• The urine anion gap separates kidney from gut. In a non-gap acidosis, a positive UAG means the kidney isn't excreting ammonium (RTA), while a negative UAG means appropriate excretion and GI loss (diarrhea).

• Type 4 is the common one — a mildly acidotic, hyperkalemic diabetic with CKD on an ACEi — and it's often as simple as adjusting the offending drugs and adding a kaliuretic.

• Potassium citrate is elegant in type 1 — it corrects the acidosis, replaces potassium, and reduces stone formation all at once.

• Proximal (type 2) RTA is hard to correct — bicarbonate is wasted as fast as you give it, so it needs large doses and aggressive potassium replacement.

• Giving alkali drops the potassium further in types 1 and 2 — anticipate and co-supplement potassium rather than chasing a falling level.

• Common mistake: labeling a chronic non-gap acidosis as "chronic diarrhea" without checking a urine anion gap — and missing a treatable RTA with an underlying cause like Sjögren or a drug.

Nephrology — Polycystic Kidney Disease

114. Polycystic Kidney Disease (PKD) Complications

ADPKD · AKI / infected cyst / hematuria · the cyst infection is the tricky one (lipophilic antibiotics) · screen for intracranial aneurysms · Super Compact

Sx: flank/abdominal pain (cyst hemorrhage, infection, stone, mass effect), gross hematuria (cyst hemorrhage — common, usually self-limited), fever + flank pain + dysuria (cyst infection/pyelonephritis), palpable enlarged kidneys, HTN (early, common) · ± headache (consider intracranial aneurysm) (known ADPKD with new flank pain — distinguish hemorrhage vs infection vs stone)

Neg: denies simple UTI without cyst involvement (cyst infection needs lipophilic abx + longer course) · denies obstructing stone missed (CT) · denies ruptured aneurysm (thunderclap headache — emergency) · denies non-PKD AKI cause (obstruction, pre-renal)

SHx: family history of ADPKD (autosomal dominant), known cysts/imaging · HTN onset age · prior cyst events (hemorrhage/infection/stones) · family/personal history of brain aneurysm or SAH · liver cysts

Etiology: ADPKD (PKD1/PKD2) — progressive cyst growth replacing parenchyma → enlarging kidneys, HTN, declining GFR; complications — cyst hemorrhage (hematuria/pain), cyst infection (lipophilic-antibiotic challenge — poor cyst penetration by many agents), nephrolithiasis (uric acid/calcium oxalate — common), AKI (obstruction, infection, hemorrhage), extrarenal — intracranial (berry) aneurysms, hepatic cysts, mitral valve prolapse, diverticulosis

RF: PKD1 genotype (more severe) · HTN · larger kidney/cyst volume · prior complications · family history of aneurysm

Data: BMP (renal function vs baseline, K) · CBC (leukocytosis — infection; anemia/Hgb drop — hemorrhage) · UA + urine culture (pyuria/bacteriuria; hematuria — note cyst infections may have negative urine cx if cyst doesn't communicate) · blood cultures (if febrile) · CT abdomen/pelvis (stones, hemorrhage, complicated cyst; assess for infected cyst — wall thickening/gas) · consider MRI (better for infected/hemorrhagic cyst characterization) · ESR/CRP · inflammatory markers · MRA brain (aneurysm screening if family history/symptoms)

DDx: cyst hemorrhage vs cyst infection vs stone (fever/cultures/imaging) · pyelonephritis vs infected cyst (response to standard abx, imaging) · renal cell carcinoma (complex enhancing mass — exclude) · ruptured intracranial aneurysm (thunderclap headache — neuro emergency)

Home Meds: BP control — RAAS preferred (ACEi/ARB first-line in ADPKD HTN) · tolvaptan if on it (vasopressin antagonist slowing progression — monitor LFTs/volume) · hold nephrotoxins/NSAIDs · renally dose · anticoagulants (weigh vs hemorrhage)

Plan

CONSULT: Nephrology (PKD management, AKI, complicated cysts) · Urology/IR (refractory hemorrhage, obstructing stone, cyst drainage) · ID (complex cyst infection) · Neurosurgery (intracranial aneurysm)

– Identify which complication (hemorrhage vs infection vs stone vs aneurysm) — they look similar (flank pain) but diverge sharply in management
– Cyst hemorrhage / gross hematuria: usually self-limited — supportive: bed rest, hydration, analgesia, BP control; hold anticoagulants/antiplatelets; transfuse if significant Hgb drop; rarely IR embolization or surgery for refractory bleeding; reassure (common, typically resolves in days)
– Cyst INFECTION (the tricky one): fever + localized flank pain ± positive cultures → antibiotics with good cyst penetration (lipophilic): fluoroquinolones (ciprofloxacin 400 mg IV/500–750 mg PO q12h) or TMP-SMX are preferred because many beta-lactams penetrate cysts poorly; prolonged course (often 4–6 weeks); if no response in 1–2 weeks → cyst drainage (percutaneous/IR) and reimage; blood + urine cultures to guide
– Nephrolithiasis: CT to define; analgesia, hydration; urology for obstructing/infected stones (decompress if infected obstruction — emergency); metabolic stone workup
– AKI: identify cause (obstruction from stone/clot, infection, hemorrhage, pre-renal); relieve obstruction, treat infection, support; treat hyperkalemia emergently if present (calcium gluconate 1–2 g IV for ECG changes + insulin 10 units IV + D50 25 g + albuterol neb, then removal/dialysis)
– Hypertension: tight BP control with ACEi/ARB first-line (renoprotective in ADPKD)
– Disease-modifying: tolvaptan in selected rapidly-progressing patients (slows cyst growth/GFR decline; monitor liver function and aquaresis/volume); maintain hydration
– Intracranial aneurysm: screen with MRA if family history of aneurysm/SAH or new concerning headache; thunderclap headache = possible rupture = emergency (neuroimaging, neurosurgery); elective management of unruptured aneurysms per size/neurosurgery
– A febrile ADPKD patient with flank pain and a "negative" urine culture can still have an infected cyst that doesn't communicate with the collecting system — image it, use a cyst-penetrating antibiotic (fluoroquinolone/TMP-SMX), and treat for weeks, not days.
– PT/OT: as tolerated
– Trend: Hgb (hemorrhage), fever/WBC + cultures (infection), renal function/K, pain, response to antibiotics (reimage if no improvement)
– Escalation triggers: hemodynamically significant hemorrhage → transfusion/IR embolization; infected cyst not responding → drainage; infected obstructing stone → emergent decompression; thunderclap headache → emergent neuro workup; refractory AKI → dialysis
– Discharge checklist: complication treated (infection course defined — duration, cyst-penetrating agent; hemorrhage resolved; stone plan); BP optimized (ACEi/ARB); tolvaptan/hydration plan if applicable; aneurysm screening arranged if indicated; nephrology follow-up; genetic counseling/family screening discussion; return precautions (fever, worsening flank pain, heavy bleeding, severe headache)

114. Polycystic Kidney Disease (PKD) Complications

complete reference · ADPKD · AKI + infected cyst + hematuria · cyst-penetrating antibiotics + aneurysm awareness · Full Card

Symptoms / Associated Sx

• Flank or abdominal pain (cyst hemorrhage, infection, stone, or mass effect from enlarging kidneys)

• Gross hematuria (cyst hemorrhage — common and usually self-limited)

• Fever with flank pain and dysuria (cyst infection or pyelonephritis)

• Palpable enlarged kidneys and hypertension (early and common); headache should prompt consideration of an intracranial aneurysm

Neg

• Pt denies a simple UTI without cyst involvement — a cyst infection requires a lipophilic antibiotic and a longer course

• Pt denies a missed obstructing stone (obtain a CT)

• Pt denies a ruptured aneurysm (a thunderclap headache is a neurologic emergency) and denies a non-PKD cause of AKI (obstruction, pre-renal)

Social History (SHx)

• Family history of ADPKD (autosomal dominant inheritance) and known cysts on prior imaging

• Age at onset of hypertension; prior cyst events (hemorrhage, infection, stones)

• Personal or family history of brain aneurysm or subarachnoid hemorrhage

• Hepatic cysts

Main Etiology

• Autosomal dominant polycystic kidney disease (PKD1/PKD2 mutations) with progressive cyst growth replacing parenchyma, causing enlarging kidneys, hypertension, and a declining GFR

• Complications: cyst hemorrhage (hematuria and pain), cyst infection (a therapeutic challenge given poor cyst penetration by many antibiotics), nephrolithiasis (uric acid and calcium oxalate stones are common), and AKI (from obstruction, infection, or hemorrhage)

• Extrarenal manifestations: intracranial (berry) aneurysms, hepatic cysts, mitral valve prolapse, and colonic diverticulosis

RF

• Modifiable: blood pressure control, hydration, stone prevention

• Non-modifiable: PKD1 genotype (more severe), larger kidney/cyst volume, prior complications, and a family history of aneurysm

Data

• BMP (renal function versus baseline, potassium)

• CBC (leukocytosis with infection; a hemoglobin drop with hemorrhage)

• Urinalysis and urine culture (pyuria and bacteriuria; hematuria — note that a non-communicating infected cyst can yield a negative urine culture)

• Blood cultures (if febrile)

• CT abdomen/pelvis (stones, hemorrhage, and complicated cysts; assess for an infected cyst — wall thickening or gas)

• MRI (superior characterization of infected or hemorrhagic cysts)

• ESR/CRP and inflammatory markers

• MRA of the brain (aneurysm screening when there is a family history or concerning symptoms)

DDx

Cyst hemorrhage vs cyst infection vs stone (fever, cultures, imaging) · pyelonephritis vs infected cyst (response to standard antibiotics, imaging) · renal cell carcinoma (a complex enhancing mass — must be excluded) · ruptured intracranial aneurysm (thunderclap headache — a neurologic emergency)

Home Meds

• Blood pressure control with RAAS blockade preferred (ACE inhibitors/ARBs are first-line for hypertension in ADPKD)

• Tolvaptan if already prescribed (a vasopressin antagonist that slows progression — monitor liver function and volume status)

• Hold: nephrotoxins and NSAIDs; renally dose; weigh anticoagulants against the hemorrhage risk

Plan

CONSULT: Nephrology (PKD management, AKI, complicated cysts) · Urology/IR (refractory hemorrhage, obstructing stone, cyst drainage) · Infectious Disease (complex cyst infection) · Neurosurgery (intracranial aneurysm)

• Identify which complication is present (hemorrhage, infection, stone, or aneurysm), since they present similarly with flank pain but diverge sharply in management

• Cyst hemorrhage/gross hematuria: usually self-limited — provide supportive care with bed rest, hydration, analgesia, and blood pressure control; hold anticoagulants and antiplatelets; transfuse for a significant hemoglobin drop; rarely IR embolization or surgery for refractory bleeding; reassure the patient, as it typically resolves within days

• Cyst infection (the difficult complication): fever with localized flank pain (with or without positive cultures) calls for antibiotics with good cyst penetration — fluoroquinolones (ciprofloxacin 400 mg IV or 500–750 mg PO q12h) or TMP-SMX are preferred because many beta-lactams penetrate cysts poorly — given as a prolonged course (often 4–6 weeks); if there is no response within 1–2 weeks, pursue percutaneous cyst drainage (IR) and re-image, guided by blood and urine cultures

• Nephrolithiasis: CT to define the stone; analgesia and hydration; urology for obstructing or infected stones (an infected obstruction is an emergency requiring decompression); a metabolic stone workup

• AKI: identify the cause (obstruction from a stone or clot, infection, hemorrhage, or pre-renal), relieve obstruction, treat infection, and provide support; treat hyperkalemia emergently if present (calcium gluconate 1–2 g IV for ECG changes, insulin 10 units IV with dextrose 25 g, and nebulized albuterol, then removal or dialysis)

• Hypertension: tight blood pressure control with an ACE inhibitor or ARB as first-line therapy (renoprotective in ADPKD)

• Disease-modifying therapy: tolvaptan for selected rapidly progressing patients (slows cyst growth and GFR decline — monitor liver function and the aquaretic effect on volume), maintaining good hydration

• Intracranial aneurysm: screen with MRA for a family history of aneurysm/SAH or a new concerning headache; a thunderclap headache suggests possible rupture and is an emergency (neuroimaging and neurosurgery); manage unruptured aneurysms electively by size with neurosurgery

• PT/OT: as tolerated

• Trend: hemoglobin (hemorrhage), fever/white count and cultures (infection), renal function and potassium, pain, and the response to antibiotics (re-image if there is no improvement)

• Escalation triggers: hemodynamically significant hemorrhage → transfusion and IR embolization; an infected cyst not responding → drainage; an infected obstructing stone → emergent decompression; a thunderclap headache → emergent neurologic workup; refractory AKI → dialysis

• Discharge checklist: the complication treated (a defined infection course with duration and a cyst-penetrating agent; resolved hemorrhage; a stone plan); optimized blood pressure (ACEi/ARB); a tolvaptan/hydration plan if applicable; aneurysm screening arranged if indicated; nephrology follow-up; a discussion of genetic counseling and family screening; return precautions for fever, worsening flank pain, heavy bleeding, or severe headache

Red Flags

• Thunderclap headache → possible ruptured intracranial aneurysm → emergent neuroimaging and neurosurgery

• Infected obstructing stone or an infected cyst not responding to antibiotics → urgent decompression or drainage

• Hemodynamically significant cyst hemorrhage → transfusion and IR embolization

• Complex enhancing renal mass → exclude renal cell carcinoma

• Sepsis from a cyst infection → broad resuscitation with source control

Senior IM Resident Pearls

• Infected cysts need lipophilic antibiotics and weeks of therapy. Many beta-lactams don't penetrate cysts — reach for a fluoroquinolone or TMP-SMX, and treat for 4–6 weeks, draining if there's no response.

• A negative urine culture doesn't exclude an infected cyst. If the cyst doesn't communicate with the collecting system the urine can be sterile — image it and treat clinically.

• Cyst hemorrhage is common and usually benign. Gross hematuria with flank pain in known ADPKD typically settles with supportive care — reassure, hold anticoagulants, and reserve intervention for refractory bleeding.

• Screen the brain when the family history fits. A family history of aneurysm or SAH (or a new concerning headache) warrants MRA — and a thunderclap headache is a rupture until proven otherwise.

• ACEi/ARB is the antihypertensive of choice in ADPKD, and tolvaptan can slow progression in rapidly declining patients.

• Don't miss a malignancy. A complex, enhancing cyst is not automatically a benign PKD cyst — characterize it to exclude renal cell carcinoma.

• Common mistake: treating a cyst infection like a simple UTI with a short course of a poorly penetrating antibiotic — it relapses; the cure is a cyst-penetrating agent for weeks, with drainage if needed.

Nephrology — Acute Interstitial Nephritis

115. Acute Interstitial Nephritis (AIN)

drug-induced AKI · classic triad (rash + fever + eosinophilia) is rare · WBC casts + sterile pyuria + eosinophiluria · stop the drug = the treatment · Super Compact

Sx: often just an AKI found on labs after a new drug · classic triad — rash + fever + eosinophilia (present in a minority, <10–30%) · arthralgias, malaise · usually non-oliguric · onset days–weeks after exposure (immediate with re-exposure) (suspect AIN in unexplained AKI with a recent culprit drug + active urinary sediment but no obvious ATN/pre-renal cause)

Neg: denies ATN pattern (muddy brown casts, ischemic/nephrotoxic context) · denies pre-renal (volume, FENa low) · denies obstruction (US/bladder scan) · denies glomerular pattern (RBC casts, heavy proteinuria, hypertension — GN)

SHx: new/recent medications — the history is everything: antibiotics (beta-lactams, fluoroquinolones, sulfas, vancomycin), NSAIDs, PPIs, diuretics, allopurinol, 5-ASA, immune checkpoint inhibitors · infections (Legionella, leptospirosis, etc.) · autoimmune disease (sarcoid, Sjögren, lupus, TINU)

Etiology: immune-mediated inflammation of the renal interstitium (hypersensitivity) · drug-induced (most common, >70%): antibiotics, NSAIDs, PPIs, diuretics, allopurinol, 5-ASA, checkpoint inhibitors (increasingly common) · infections · autoimmune/systemic (sarcoidosis, Sjögren, TINU syndrome — tubulointerstitial nephritis + uveitis)

RF: polypharmacy/new drug exposure · prior drug reaction · autoimmune disease · checkpoint-inhibitor therapy · older age

Data: BMP (↑Cr, K) · urinalysis + microscopy (sterile pyuria, WBC casts, mild proteinuria, hematuria; eosinophiluria — Hansel/Wright stain, low sensitivity & specificity — supportive not definitive) · CBC w/ diff (peripheral eosinophilia — supportive) · urine protein/Cr (usually subnephrotic — except NSAID-AIN can cause nephrotic-range with MCD) · renal US (exclude obstruction; may show enlarged echogenic kidneys) · renal biopsy (definitive — interstitial inflammatory infiltrate ± eosinophils, tubulitis; pursue if dx unclear or steroids considered/no improvement off drug) · consider serologies for systemic causes

DDx: ATN (muddy brown casts, ischemic/toxic) · pre-renal (FENa low, volume) · glomerulonephritis (RBC casts, proteinuria, HTN) · obstruction (US) · pyelonephritis (positive urine culture vs sterile pyuria)

Home Meds: IDENTIFY + STOP the culprit drug (the core treatment) — review ALL recent meds (esp NSAIDs, PPIs, antibiotics, checkpoint inhibitors); hold all nephrotoxins; renally dose remaining meds · avoid re-challenge

Plan

CONSULT: Nephrology (diagnosis, biopsy decision, steroid use, refractory cases) · Oncology (if checkpoint-inhibitor AIN — immune-related adverse event management) · relevant service for systemic cause

– Identify and STOP the offending drug — this is the cornerstone and is often sufficient for recovery; carefully review every medication started in the preceding days–weeks (NSAIDs, PPIs, antibiotics, allopurinol, 5-ASA, checkpoint inhibitors)
– Supportive AKI care: maintain euvolemia and perfusion, treat hyperkalemia emergently if present (calcium gluconate 1–2 g IV for ECG changes + insulin 10 units IV + D50 25 g + albuterol neb, then removal/dialysis), manage acid-base/volume, avoid further nephrotoxins, renally dose meds; dialysis for AEIOU indications
– Confirm the diagnosis: urinalysis/microscopy (sterile pyuria, WBC casts), eosinophilia/eosinophiluria (supportive), exclude other AKI causes; renal biopsy when the diagnosis is uncertain, when the cause isn't drug-evident, or when steroids are being considered
– Corticosteroids (for non-resolving or significant AIN): if creatinine fails to improve within ~3–7 days of stopping the drug, or for severe AKI, consider prednisone ~1 mg/kg/day (or pulse methylprednisolone) with a taper over weeks — earlier initiation may improve renal recovery; biopsy confirmation preferred before committing; weigh risks
– Checkpoint-inhibitor AIN: manage as an immune-related adverse event with oncology — hold the agent and treat with corticosteroids per irAE protocols
– Treat systemic/infectious causes if identified (sarcoidosis, infection, TINU — ophthalmology for uveitis)
– The treatment is in the medication list — the single highest-yield action is a meticulous review of every recent drug and stopping the culprit. The classic triad is mostly absent, so don't wait for rash/fever/eosinophilia to suspect AIN.
– PT/OT: as tolerated
– Trend: Cr recovery (after stopping drug), K + electrolytes, urine sediment, steroid response if used, eosinophil count
– Escalation triggers: hyperkalemia/dialysis indications → emergent treatment + nephrology; failure to recover after stopping drug → biopsy + steroids; checkpoint-inhibitor case → oncology + irAE steroids; progression despite therapy → reassess diagnosis
– Discharge checklist: culprit drug identified + discontinued + documented as an allergy/adverse reaction (avoid re-challenge); renal recovery trajectory documented; steroid taper plan if started; nephrology follow-up + Cr monitoring; medication-reconciliation note for future prescribers; return precautions (decreased urine, swelling, rash, fever)

115. Acute Interstitial Nephritis (AIN)

complete reference · drug-induced AKI · sterile pyuria + WBC casts · stop-the-drug ± corticosteroids · Full Card

Symptoms / Associated Sx

• Frequently just an AKI found on labs after starting a new drug

• The classic triad of rash, fever, and eosinophilia is present in only a minority of patients (well under a third)

• Arthralgias and malaise; the AKI is usually non-oliguric

• Onset is typically days to weeks after exposure, and immediate with re-exposure

Neg

• Pt denies an ATN pattern (muddy brown granular casts in an ischemic or nephrotoxic context)

• Pt denies a pre-renal picture (volume depletion, low FENa) and denies obstruction (ultrasound, bladder scan)

• Pt denies a glomerular pattern (RBC casts, heavy proteinuria, hypertension), which would indicate glomerulonephritis

Social History (SHx)

• New or recent medications — the history is decisive: antibiotics (beta-lactams, fluoroquinolones, sulfonamides, vancomycin), NSAIDs, proton pump inhibitors, diuretics, allopurinol, 5-aminosalicylates, and immune checkpoint inhibitors

• Infections (Legionella, leptospirosis, and others)

• Autoimmune/systemic disease (sarcoidosis, Sjögren syndrome, lupus, and TINU syndrome)

Main Etiology

• Immune-mediated (hypersensitivity) inflammation of the renal interstitium

• Drug-induced (the most common cause, >70%): antibiotics, NSAIDs, PPIs, diuretics, allopurinol, 5-aminosalicylates, and increasingly immune checkpoint inhibitors

• Infectious causes and autoimmune/systemic causes (sarcoidosis, Sjögren syndrome, and TINU syndrome — tubulointerstitial nephritis with uveitis)

RF

• Modifiable: polypharmacy and new drug exposures, avoidance of re-challenge

• Non-modifiable: prior drug reactions, autoimmune disease, checkpoint-inhibitor therapy, and older age

Data

• BMP (rising creatinine, potassium)

• Urinalysis with microscopy (sterile pyuria and white-cell casts, mild proteinuria, and hematuria; eosinophiluria on Hansel/Wright staining is supportive but has poor sensitivity and specificity)

• CBC with differential (peripheral eosinophilia is supportive)

• Urine protein-to-creatinine ratio (usually subnephrotic, although NSAID-induced AIN can produce nephrotic-range proteinuria with minimal change disease)

• Renal ultrasound (exclude obstruction; may show enlarged echogenic kidneys)

• Renal biopsy (the definitive test — an interstitial inflammatory infiltrate with tubulitis, sometimes with eosinophils; pursue it when the diagnosis is unclear, when no drug cause is evident, or when corticosteroids are being considered or there is no improvement after stopping the drug)

• Serologies for systemic causes (when sarcoidosis, Sjögren, or TINU is suspected)

DDx

ATN (muddy brown casts, ischemic or toxic context) · pre-renal AKI (low FENa, volume depletion) · glomerulonephritis (RBC casts, proteinuria, hypertension) · obstruction (ultrasound) · pyelonephritis (a positive urine culture versus the sterile pyuria of AIN)

Home Meds

• Identify and stop the culprit drug — the core treatment — reviewing all recently started medications (especially NSAIDs, PPIs, antibiotics, and checkpoint inhibitors)

• Hold all nephrotoxins and renally dose the remaining medications

• Avoid re-challenge with the offending agent

Plan

CONSULT: Nephrology (diagnosis, biopsy decision, corticosteroid use, refractory cases) · Oncology (checkpoint-inhibitor AIN as an immune-related adverse event) · the relevant service for a systemic cause

• Identify and stop the offending drug — the cornerstone of management, often sufficient for recovery; meticulously review every medication started in the preceding days to weeks (NSAIDs, PPIs, antibiotics, allopurinol, 5-aminosalicylates, checkpoint inhibitors)

• Supportive AKI care: maintain euvolemia and perfusion; treat hyperkalemia emergently if present (calcium gluconate 1–2 g IV for ECG changes, insulin 10 units IV with dextrose 25 g, and nebulized albuterol, then removal or dialysis); manage acid-base and volume; avoid further nephrotoxins; renally dose medications; and dialyze for standard indications

• Confirm the diagnosis: urinalysis and microscopy (sterile pyuria, white-cell casts), eosinophilia/eosinophiluria as supportive findings, and exclusion of other AKI causes; obtain a renal biopsy when the diagnosis is uncertain, when no drug cause is evident, or when corticosteroids are being considered

• Corticosteroids for non-resolving or significant AIN: if the creatinine fails to improve within roughly 3–7 days of stopping the drug, or for severe AKI, consider prednisone about 1 mg/kg/day (or pulse methylprednisolone) with a taper over several weeks — earlier initiation may improve renal recovery; biopsy confirmation is preferred before committing, and the risks are weighed individually

• Checkpoint-inhibitor AIN: manage as an immune-related adverse event with oncology — hold the agent and treat with corticosteroids per irAE protocols

• Treat systemic or infectious causes when identified (sarcoidosis, infection, or TINU syndrome with ophthalmology involvement for uveitis)

• PT/OT: as tolerated

• Trend: creatinine recovery after stopping the drug, potassium and electrolytes, the urine sediment, the steroid response if used, and the eosinophil count

• Escalation triggers: hyperkalemia or dialysis indications → emergent treatment and nephrology; failure to recover after stopping the drug → biopsy and corticosteroids; a checkpoint-inhibitor case → oncology and irAE steroids; progression despite therapy → reconsider the diagnosis

• Discharge checklist: the culprit drug identified, discontinued, and documented as an allergy/adverse reaction to prevent re-challenge; the renal recovery trajectory documented; a steroid taper plan if started; nephrology follow-up with creatinine monitoring; a medication-reconciliation note for future prescribers; return precautions for decreased urine output, swelling, rash, or fever

Red Flags

• Hyperkalemia or other dialysis indications → emergent management

• Failure to recover after stopping the drug → biopsy and consideration of corticosteroids before fibrosis sets in

• Checkpoint-inhibitor AIN → a serious immune-related adverse event requiring prompt steroids and oncology input

• Granulomatous interstitial nephritis on biopsy → evaluate for sarcoidosis or TB

• Associated uveitis → consider TINU syndrome and involve ophthalmology

Senior IM Resident Pearls

• The treatment is in the medication list. The single highest-yield action is a meticulous review of every recent drug — stopping the culprit is usually curative.

• Don't wait for the classic triad. Rash, fever, and eosinophilia together are the exception, not the rule — suspect AIN in any unexplained AKI with sterile pyuria and a recent new drug.

• Sterile pyuria with white-cell casts is the urinary signature — a positive culture points to pyelonephritis instead, and eosinophiluria is only supportive.

• PPIs and checkpoint inhibitors are the modern culprits people forget — both are easy to overlook on a long medication list.

• Earlier steroids may help when the drug-stop alone doesn't. If the creatinine isn't improving in a few days, biopsy and consider corticosteroids before interstitial fibrosis becomes irreversible.

• Document the reaction as an allergy. Re-exposure causes faster, more severe recurrence — the chart needs to protect the patient from the next prescriber.

• Common mistake: attributing the AKI to ATN or pre-renal causes and missing the new PPI or NSAID — the recovery hinges on identifying and stopping the drug, not on fluids alone.

Nephrology / Heme — Thrombotic Microangiopathy

116. Thrombotic Microangiopathy (TMA)

MAHA + thrombocytopenia + organ injury · TTP / HUS / malignant HTN · schistocytes are the clue · TTP = plasma exchange NOW (don't wait for ADAMTS13) · Super Compact

Sx: microangiopathic hemolytic anemia (fatigue, pallor, jaundice) + thrombocytopenia (petechiae, bleeding) + end-organ ischemia · TTP: neuro changes (confusion, focal deficits, seizure), fever (pentad often incomplete) · HUS: AKI prominent, often bloody diarrhea prodrome (Shiga toxin) · malignant HTN: severe BP + headache, visual changes, encephalopathy, AKI (MAHA + thrombocytopenia + organ injury = TMA until proven otherwise — a hematologic emergency)

Neg: denies DIC pattern (normal/near-normal PT/PTT/fibrinogen in TMA vs abnormal in DIC) · denies immune thrombocytopenia alone (no hemolysis/schistocytes) · denies other hemolysis (Coombs-positive — immune; here Coombs-negative) · denies sepsis as sole driver (overlaps — assess)

SHx: diarrheal prodrome/E. coli O157:H7 exposure (STEC-HUS) · drugs (quinine, calcineurin inhibitors, chemo, VEGF inhibitors, clopidogrel) · pregnancy (HELLP, aHUS, preeclampsia) · autoimmune/HIV/malignancy · HTN history (malignant HTN) · prior TMA/aHUS/complement disorder

Etiology: endothelial injury → platelet microthrombi in small vessels → mechanical RBC shearing (schistocytes) + platelet consumption + ischemic organ injury · TTP (severe ADAMTS13 deficiency <10% — autoantibody or congenital → ultralarge vWF multimers) · HUS (STEC/Shiga-toxin, or complement-mediated atypical HUS) · secondary: malignant HTN, drugs, pregnancy (HELLP), autoimmune, malignancy, transplant

RF: Shiga-toxin exposure (HUS) · complement gene variants (aHUS) · causative drugs · pregnancy · autoimmune disease · severe/uncontrolled HTN

Data: CBC + smear (anemia + thrombocytopenia + SCHISTOCYTES on smear — the key finding) · hemolysis labs (↑LDH, ↑indirect bili, ↓haptoglobin, ↑retic) · Coombs (DAT) — negative (distinguishes from immune hemolysis) · coags (PT/PTT/fibrinogen) — normal/near-normal (distinguishes TMA from DIC) · BMP (↑Cr — AKI, esp HUS; K) · ADAMTS13 activity + inhibitor (<10% = TTP; send BEFORE plasma exchange but DON'T wait for result to treat) · stool Shiga toxin/E. coli O157 (HUS) · pregnancy test, complement studies (aHUS), HIV/autoimmune workup · PLASMIC score (risk-stratify probability of severe ADAMTS13 deficiency/TTP) · BP + fundoscopy (malignant HTN)

DDx: TTP vs HUS vs aHUS vs secondary TMA (ADAMTS13, Shiga toxin, complement, clinical context) · DIC (abnormal coags, ↓fibrinogen) · malignant hypertension (severe BP, fundoscopy) · HELLP/preeclampsia (pregnancy) · autoimmune hemolysis (Coombs-positive)

Home Meds: hold antiplatelets/anticoagulants if bleeding/severe thrombocytopenia · review/stop drug triggers (quinine, calcineurin inhibitors, VEGF inhibitors) · avoid platelet transfusion in TTP unless life-threatening bleeding (can worsen microthrombosis) · renally dose

Plan

CONSULT: Hematology (emergent — TTP/TMA) · Nephrology (AKI, HUS, dialysis) · Apheresis (plasma exchange) · ICU (neuro changes, instability) · OB (if pregnant)

– TTP is a medical emergency — treat empirically, don't wait for ADAMTS13: if MAHA + thrombocytopenia without another cause (high PLASMIC score) → initiate PLASMA EXCHANGE (plasmapheresis) urgently (replaces ADAMTS13, removes autoantibody + ultralarge vWF) + high-dose corticosteroids (e.g. methylprednisolone/prednisone 1 mg/kg) + rituximab; caplacizumab (anti-vWF) in confirmed acquired TTP per hematology; send ADAMTS13 before starting but never delay treatment for the result — untreated TTP is often fatal
– STEC-HUS (Shiga-toxin, often children/diarrheal): primarily supportive — fluids/volume management, manage AKI (dialysis if needed), treat hyperkalemia emergently if present (calcium gluconate 1–2 g IV for ECG changes + insulin 10 units IV + D50 25 g + albuterol neb, then removal/dialysis); avoid antibiotics and antimotility agents in STEC (may increase toxin release/HUS risk); plasma exchange not routinely beneficial
– Atypical HUS (complement-mediated): eculizumab (anti-C5 complement inhibitor) — vaccinate against meningococcus (or give prophylactic antibiotics) before/with starting; hematology/nephrology; plasma exchange while diagnosis clarified
– Malignant hypertension TMA: the TMA is driven by the BP → controlled BP reduction (IV agent — e.g. nicardipine or labetalol infusion; lower MAP by ~10–20% in the first hour, then gradually — avoid precipitous drops/ischemia); the hematologic picture improves with BP control; ICU monitoring
– Secondary TMA: treat/remove the trigger (stop offending drug, treat malignancy/autoimmune disease, deliver for HELLP/severe preeclampsia per OB)
– Transfusion: RBCs for symptomatic anemia; AVOID prophylactic platelet transfusion in TTP (fuels microthrombosis) unless life-threatening hemorrhage
– The smear is the emergency test — schistocytes + thrombocytopenia + normal coags screams TMA, and if TTP is plausible you start plasma exchange the same day, before the ADAMTS13 result returns. Platelet transfusions in TTP can kill — withhold them unless there's catastrophic bleeding.
– PT/OT: per illness; neuro precautions if CNS involvement
– Trend: platelets + LDH (response to therapy), Hgb/hemolysis, schistocytes, Cr/UOP, neuro status, BP (malignant HTN), ADAMTS13 result
– Escalation triggers: neuro deterioration/seizure → ICU; refractory TTP → intensify (rituximab, caplacizumab, more frequent exchange); AKI/dialysis indications → RRT; malignant HTN end-organ damage → ICU BP control; aHUS → eculizumab
– Discharge checklist: diagnosis clarified (ADAMTS13, Shiga toxin, complement) + cause-directed therapy in place; platelet/LDH recovery documented; relapse plan + monitoring (TTP can relapse — hematology follow-up); offending drug avoided; eculizumab + meningococcal vaccination if aHUS; BP regimen if malignant HTN; return precautions (bruising/bleeding, confusion, decreased urine, severe headache/visual change)

116. Thrombotic Microangiopathy (TMA)

complete reference · TTP/HUS + malignant hypertension · MAHA + thrombocytopenia + organ injury · plasma exchange / eculizumab / BP control · Full Card

Symptoms / Associated Sx

• Microangiopathic hemolytic anemia (fatigue, pallor, jaundice) with thrombocytopenia (petechiae, bleeding) and end-organ ischemia

• TTP: neurologic changes (confusion, focal deficits, seizure) and fever, though the classic pentad is often incomplete

• HUS: prominent acute kidney injury, often preceded by a bloody diarrheal prodrome (Shiga toxin)

• Malignant hypertension: severe blood pressure elevation with headache, visual changes, encephalopathy, and AKI

• The combination of MAHA, thrombocytopenia, and organ injury is a thrombotic microangiopathy until proven otherwise — a hematologic emergency

Neg

• Pt denies a DIC pattern — the coagulation studies (PT, PTT, fibrinogen) are normal or near-normal in TMA, unlike DIC

• Pt denies isolated immune thrombocytopenia (no hemolysis or schistocytes)

• Pt denies a Coombs-positive (immune) hemolysis — the direct antiglobulin test is negative in TMA; and denies sepsis as the sole driver, though it can overlap

Social History (SHx)

• A diarrheal prodrome or E. coli O157:H7 exposure (Shiga toxin–producing HUS)

• Drugs (quinine, calcineurin inhibitors, chemotherapy, VEGF inhibitors, clopidogrel)

• Pregnancy (HELLP syndrome, atypical HUS, preeclampsia)

• Autoimmune disease, HIV, or malignancy; a history of hypertension (malignant hypertension); and any prior TMA, atypical HUS, or complement disorder

Main Etiology

• Endothelial injury causing platelet microthrombi in small vessels, with mechanical shearing of red cells (schistocytes), platelet consumption, and ischemic organ injury

• TTP: severe ADAMTS13 deficiency (<10%, from an autoantibody or congenital deficiency) leading to ultralarge von Willebrand factor multimers

• HUS: Shiga toxin–mediated (STEC) or complement-mediated atypical HUS

• Secondary TMA: malignant hypertension, drugs, pregnancy (HELLP), autoimmune disease, malignancy, and transplantation

RF

• Modifiable: drug triggers, blood pressure control, treatment of the underlying disease

• Non-modifiable: Shiga-toxin exposure, complement gene variants (atypical HUS), pregnancy, and autoimmune disease

Data

• CBC with peripheral smear (anemia and thrombocytopenia with schistocytes on the smear — the key finding)

• Hemolysis labs (elevated LDH and indirect bilirubin, low haptoglobin, elevated reticulocyte count)

• Direct antiglobulin (Coombs) test — negative (distinguishes from immune hemolytic anemia)

• Coagulation studies (PT, PTT, fibrinogen) — normal or near-normal (distinguishes TMA from DIC)

• BMP (rising creatinine — AKI, especially in HUS; potassium)

• ADAMTS13 activity and inhibitor (activity <10% confirms TTP; send before plasma exchange but do not wait for the result to begin treatment)

• Stool Shiga toxin and E. coli O157 testing (HUS); pregnancy test; complement studies (atypical HUS); HIV and autoimmune workup

• PLASMIC score (risk-stratifies the probability of severe ADAMTS13 deficiency/TTP to guide empiric treatment)

• Blood pressure and fundoscopic exam (malignant hypertension)

DDx

TTP vs STEC-HUS vs atypical HUS vs secondary TMA (ADAMTS13, Shiga toxin, complement studies, clinical context) · DIC (abnormal coagulation studies, low fibrinogen) · malignant hypertension (severe blood pressure, fundoscopy) · HELLP/preeclampsia (pregnancy) · autoimmune hemolysis (Coombs-positive)

Home Meds

• Hold: antiplatelets and anticoagulants with bleeding or severe thrombocytopenia

• Review/stop drug triggers (quinine, calcineurin inhibitors, VEGF inhibitors)

• Avoid platelet transfusion in TTP unless there is life-threatening bleeding (it can worsen microthrombosis); renally dose medications

Plan

CONSULT: Hematology (emergent — TTP/TMA) · Nephrology (AKI, HUS, dialysis) · Apheresis (plasma exchange) · ICU (neurologic changes, instability) · Obstetrics (if pregnant)

• TTP is a medical emergency — treat empirically rather than waiting for ADAMTS13: for MAHA with thrombocytopenia and no alternative cause (a high PLASMIC score), urgently initiate plasma exchange (plasmapheresis, which replaces ADAMTS13 and removes the autoantibody and ultralarge vWF multimers) plus high-dose corticosteroids (e.g. methylprednisolone or prednisone 1 mg/kg) and rituximab, adding caplacizumab (an anti-vWF agent) in confirmed acquired TTP per hematology; send the ADAMTS13 level before starting but never delay treatment for the result, as untreated TTP is frequently fatal

• STEC-HUS (Shiga toxin, often in children with a diarrheal prodrome): primarily supportive — fluid and volume management and treatment of AKI (dialysis if needed), with emergent treatment of hyperkalemia if present (calcium gluconate 1–2 g IV for ECG changes, insulin 10 units IV with dextrose 25 g, and nebulized albuterol, then removal or dialysis); avoid antibiotics and antimotility agents in STEC infection, which may increase toxin release and HUS risk; plasma exchange is not routinely beneficial

• Atypical (complement-mediated) HUS: eculizumab (an anti-C5 complement inhibitor), with meningococcal vaccination (or prophylactic antibiotics) before or alongside starting it, managed with hematology and nephrology; plasma exchange may be used while the diagnosis is clarified

• Malignant hypertension TMA: the microangiopathy is driven by the blood pressure, so achieve controlled blood pressure reduction with an IV agent (e.g. a nicardipine or labetalol infusion), lowering the MAP by about 10–20% in the first hour and then gradually to avoid precipitous drops and ischemia; the hematologic picture improves as the pressure is controlled, with ICU monitoring

• Secondary TMA: treat or remove the trigger (stop the offending drug, treat the malignancy or autoimmune disease, and deliver for HELLP/severe preeclampsia per obstetrics)

• Transfusion: red cells for symptomatic anemia; avoid prophylactic platelet transfusion in TTP (it fuels microthrombosis) unless there is life-threatening hemorrhage

• PT/OT: guided by the illness, with neurologic precautions if there is CNS involvement

• Trend: platelets and LDH (the response to therapy), hemoglobin and hemolysis markers, schistocytes, creatinine and urine output, neurologic status, blood pressure (malignant hypertension), and the ADAMTS13 result

• Escalation triggers: neurologic deterioration or seizure → ICU; refractory TTP → intensification (rituximab, caplacizumab, more frequent exchange); AKI with dialysis indications → renal replacement therapy; malignant hypertension with end-organ damage → ICU blood pressure control; atypical HUS → eculizumab

• Discharge checklist: the diagnosis clarified (ADAMTS13, Shiga toxin, complement) with cause-directed therapy in place; documented platelet and LDH recovery; a relapse plan and monitoring (TTP can relapse — hematology follow-up); the offending drug avoided; eculizumab with meningococcal vaccination for atypical HUS; a blood pressure regimen for malignant hypertension; return precautions for bruising or bleeding, confusion, decreased urine output, or severe headache/visual change

Red Flags

• MAHA + thrombocytopenia with normal coagulation studies → presume TTP and start plasma exchange the same day; untreated TTP is often fatal

• Neurologic deterioration or seizure → ICU and intensified therapy

• Platelet transfusion in suspected TTP → can precipitate fatal microthrombosis; withhold unless catastrophic bleeding

• STEC-HUS → avoid antibiotics and antimotility agents, which may worsen the syndrome

• Atypical HUS without eculizumab → progressive renal failure; meningococcal protection is required before starting it

Senior IM Resident Pearls

• The smear is the emergency test. Schistocytes with thrombocytopenia and normal coagulation studies scream TMA — and if TTP is plausible, plasma exchange starts the same day, before the ADAMTS13 result returns.

• Normal coags separate TMA from DIC. In DIC the PT/PTT are prolonged and fibrinogen falls; in TMA the consumption is platelet-driven with intact coagulation — a fast bedside discriminator.

• Don't transfuse platelets in TTP. Prophylactic platelets pour fuel on the microthrombosis and can be fatal — reserve them for life-threatening hemorrhage only.

• The PLASMIC score guides empiric treatment while ADAMTS13 is pending — a high score justifies starting plasma exchange without delay.

• Don't give antibiotics in STEC-HUS. They (and antimotility agents) can increase Shiga toxin release and worsen the HUS — management is supportive.

• Vaccinate before eculizumab. Complement blockade dramatically raises meningococcal risk — meningococcal vaccination or prophylaxis is mandatory before or with the first dose.

• Common mistake: labeling a TMA as "ITP plus anemia" and transfusing platelets, or waiting for the ADAMTS13 result before acting — both delays and the transfusion can cost the patient their life.