Renal & Urinary

Intrinsic AKI: ATN, AIN, and glomerular causes

Clinical Overview and When to Suspect Intrinsic AKI

— Acute tubular necrosis (ATN): ischemic (prolonged prerenal) or nephrotoxic (contrast, aminoglycosides, cisplatin, amphotericin B, myoglobin, hemoglobin, light chains)

— Acute interstitial nephritis (AIN): drug hypersensitivity (PPIs, NSAIDs, beta-lactams, sulfas, allopurinol, 5-ASA), infections, autoimmune (TINU, sarcoid, Sjögren)

— Glomerular causes: rapidly progressive glomerulonephritis (RPGN) — anti-GBM, ANCA-associated, immune complex (lupus, IgA, post-infectious, cryo)

— FENa >2%, FEUrea >50%, urine Na >40, bland or active urine sediment instead of hyaline casts

— Failure of creatinine to improve after adequate volume resuscitation

— Active sediment: muddy brown casts (ATN), WBC casts/eosinophils (AIN), RBC casts/dysmorphic RBCs (GN)

— ↑Cr ≥0.3 mg/dL within 48 h, OR ↑Cr ≥1.5× baseline within 7 days, OR urine output <0.5 mL/kg/h for 6 h

Board pearl: A hospitalized patient whose creatinine keeps rising 48 h after appropriate fluid resuscitation almost always has ATN, not persistent prerenal AKI. Pivot the workup from "give more fluid" to "find the toxin/ischemic insult and protect the kidneys" — stop nephrotoxins, dose-adjust meds, and avoid contrast unless mandatory.

Intrinsic AKI = parenchymal injury to tubules, interstitium, glomeruli, or vasculature, distinguished from prerenal azotemia (hypoperfusion) and postrenal obstruction

Three big buckets for Step 3:

When to suspect intrinsic over prerenal:

KDIGO AKI definition (memorize):

Epidemiology pearls: ATN accounts for ~45% of hospital-acquired AKI; AIN ~10–15% but rising due to PPI use; RPGN is rare but time-critical — delayed dx → dialysis dependence

Presentation Patterns and Key History

— Recent hypotension, sepsis, major surgery (especially cardiac/AAA), hemorrhage → ischemic ATN

— IV contrast within 24–72 h, aminoglycoside course >5 days, cisplatin cycle, amphotericin

— Crush injury, prolonged immobilization, statin + fibrate, seizures, cocaine → rhabdomyolysis ATN

— Hemolysis (transfusion reaction, malaria, mechanical valve) → pigment nephropathy

— Tumor lysis syndrome after chemo initiation in high-burden hematologic malignancy

— New drug 7–10 days prior (beta-lactams, sulfas, NSAIDs), or months prior for PPIs/NSAIDs

— Arthralgias, low-grade fever, flank discomfort

— Recent infection: legionella, leptospirosis, EBV, CMV, hantavirus

— Tea/cola-colored urine, foamy urine, peripheral edema, hypertension

— Hemoptysis + AKI → think anti-GBM (Goodpasture) or ANCA vasculitis (GPA)

— Sinusitis, saddle-nose, otitis → GPA

— Asthma + eosinophilia → EGPA

— Palpable purpura, abdominal pain, arthritis in child → IgA vasculitis (HSP)

— Pharyngitis 1–2 wks prior or impetigo 3–6 wks → post-strep GN

— Hepatitis C + cryoglobulinemia; HIV-associated nephropathy (collapsing FSGS)

— Malar rash, oral ulcers, serositis → lupus nephritis

Key distinction: Onset timing helps — ATN evolves over hours to days after the insult, AIN over days to weeks after drug exposure, and RPGN over weeks to months with progressive azotemia. A patient whose Cr doubled over 6 weeks with hematuria and HTN is RPGN until proven otherwise — don't wait, get nephrology and biopsy.

ATN history clues:

AIN history clues — the classic triad (fever, rash, eosinophilia) is present in <10% of cases; do not require it

Glomerular/RPGN history clues:

Physical Exam Findings (and Hemodynamic Assessment)

— Orthostatic vitals, JVP, mucous membranes, capillary refill, skin turgor

— Lung exam for crackles (volume overload, pulmonary-renal syndrome)

— Lower extremity edema, sacral edema in bedbound patients

— POCUS: IVC collapsibility >50% suggests hypovolemia; B-lines suggest pulmonary edema

— Often euvolemic to hypervolemic by the time AKI is recognized (oliguric phase)

— Asterixis, uremic fetor, pericardial friction rub if severe uremia

— Compartment tense, swollen extremity in crush/rhabdo

— Low-grade fever, maculopapular rash (only ~15%), arthralgia

— Costovertebral angle tenderness possible (interstitial edema)

— HTN and edema are the cardinal GN signs (Na/water retention)

— Palpable purpura on lower extremities → IgA vasculitis, cryoglobulinemia, ANCA

— Saddle-nose deformity, oral/nasal ulcers, sinus tenderness → GPA

— Livedo reticularis, digital ischemia → ANCA or cryo

— Malar rash, photosensitive rash, alopecia → lupus

— Hemoptysis with hypoxia and crackles → diffuse alveolar hemorrhage (anti-GBM, ANCA)

— Mononeuritis multiplex (foot drop, wrist drop) → ANCA, especially EGPA/PAN

— Uveitis + AKI in young patient → TINU syndrome (tubulointerstitial nephritis + uveitis)

Step 3 management: A patient with AKI + hemoptysis + hypoxia is a pulmonary-renal syndrome — admit to step-down/ICU, send urgent ANCA + anti-GBM + ANA + C3/C4 + anti-dsDNA, get CXR/CT chest, and call nephrology and pulm. Start empiric pulse methylprednisolone if anti-GBM strongly suspected; plasmapheresis if confirmed.

Volume status assessment is mandatory — distinguishes prerenal from intrinsic and guides therapy:

ATN-specific findings:

AIN-specific findings:

Glomerular findings — look for systemic disease:

Diagnostic Workup — Initial Labs / Imaging / Urinalysis

— BMP (Cr, BUN, K, HCO3), CBC, urinalysis with microscopy, urine sodium, urine creatinine, urine urea for FENa/FEUrea

— Renal US within 24 h to exclude obstruction (postrenal)

— Bladder scan post-void if any suspicion of retention

— <1% → prerenal or early contrast/pigment ATN, glomerulonephritis, hepatorenal

— >2% → established ATN, AIN

— On diuretics, use FEUrea: <35% prerenal, >50% intrinsic

— Muddy brown granular casts + renal tubular epithelial cells → ATN

— WBCs, WBC casts, eosinophils (Hansel/Wright stain) → AIN (eosinophiluria has poor sensitivity, ~30%)

— Dysmorphic RBCs and RBC casts → glomerulonephritis (pathognomonic)

— Broad waxy casts → CKD

— Crystals: uric acid (TLS), calcium oxalate (ethylene glycol), sulfa

— Heme-positive without RBCs → myoglobinuria or hemoglobinuria (pigment ATN); check CK

— Proteinuria >3.5 g/24h or UPCR >3 → nephrotic-range, suggests glomerular (membranous, FSGS, MCD)

— Subnephrotic proteinuria + hematuria → nephritic GN

Board pearl: A patient on vancomycin + piperacillin-tazobactam with rising Cr, sterile pyuria, WBC casts, and mild eosinophilia → AIN from beta-lactam. Don't anchor on "vanc trough nephrotoxicity" — pip-tazo is a much more common AIN culprit. Stop the offending drug first; that alone may resolve AIN.

Initial bundle for any AKI:

FENa interpretation:

Urine microscopy — the single most useful test:

Urine dipstick clues:

Pigment workup: CK (>5000 supports rhabdo, >20,000 high AKI risk), LDH, haptoglobin, peripheral smear

Diagnostic Workup — Advanced or Confirmatory Studies

— ANA, anti-dsDNA, anti-Smith → lupus nephritis

— C3, C4: low both → lupus, post-strep, MPGN, cryo, endocarditis; normal → IgA, anti-GBM, ANCA, HSP

— ANCA (c-ANCA/PR3, p-ANCA/MPO) → GPA, MPA, EGPA

— Anti-GBM antibody → Goodpasture

— ASO, anti-DNase B → post-streptococcal GN

— Hepatitis B, hepatitis C, HIV → PAN, MPGN/cryo, HIVAN

— Cryoglobulins, RF → cryoglobulinemic GN

— SPEP/UPEP, free light chains → myeloma (cast nephropathy, AL amyloid)

— Complement levels, ADAMTS13, haptoglobin, LDH, schistocytes → TMA (HUS, TTP, scleroderma renal crisis)

— Renal US: assess size (small = CKD), echogenicity, hydronephrosis, resistive indices (high in HRS)

— CT without contrast if stone/obstruction suspected

— MR angiography for renal artery stenosis if asymmetric kidneys

— Cause unclear after noninvasive workup

— Suspected RPGN (every day delayed = nephrons lost)

— AIN not improving after stopping drug

— Native kidney AKI with nephrotic-range proteinuria, active sediment, or systemic disease

— Contraindications: uncontrolled HTN, bleeding diathesis, single kidney (relative), small kidneys

Step 3 management: When RPGN is on the differential, biopsy within 24–48 h and don't wait for serologies to result before starting empiric pulse steroids — irreversible crescent formation occurs over days.

Serologic workup for suspected glomerular disease (the "renal panel"):

Imaging:

Renal biopsy — the definitive test for intrinsic AKI when:

Pre-biopsy: control BP <140/90, hold anticoagulants, check platelets/INR, type & screen

Risk Stratification and First-Line Management Logic

— Stage 1: Cr 1.5–1.9× baseline or ↑0.3 mg/dL; UOP <0.5 mL/kg/h × 6–12 h

— Stage 2: Cr 2.0–2.9× baseline; UOP <0.5 × ≥12 h

— Stage 3: Cr ≥3× baseline OR Cr ≥4.0 mg/dL OR initiation of RRT OR UOP <0.3 × ≥24 h or anuria ≥12 h

— Stop nephrotoxins: NSAIDs, ACEi/ARB, aminoglycosides, IV contrast, diuretics if hypovolemic

— Dose-adjust renally cleared drugs (vancomycin, LMWH, gabapentin, metformin — hold if eGFR <30)

— Optimize hemodynamics: MAP ≥65, treat sepsis, avoid hyperchloremic fluids in large volumes

— Monitor: daily weights, strict I/Os, BMP q12–24h, urine output hourly if oliguric

— Avoid hyperglycemia and hypoglycemia

— Supportive care — no drug accelerates recovery (no dopamine, no mannitol, no loop diuretics for renal protection)

— Loop diuretics ONLY for volume management, not to "convert oliguric to non-oliguric"

— Stop the offending drug — single most important intervention

— Consider steroids (prednisone 1 mg/kg) if no improvement in 5–7 days after drug stopped, or biopsy-proven severe AIN

CCS pearl: On a CCS case with AKI, order renal US, urinalysis with micro, urine electrolytes, and review the med list in the first set of orders. Then reassess in 6–12 h with repeat BMP. Stopping nephrotoxins shows up as a scored action — explicitly discontinue NSAIDs, ACEi, and adjust antibiotic doses.

KDIGO AKI staging (drives management intensity):

Universal AKI bundle (all stages):

ATN-specific:

AIN-specific:

Glomerular-specific: immunosuppression based on pathology

Pharmacotherapy — First-Line Regimens by Etiology

— No proven pharmacotherapy accelerates recovery

— Manage hyperkalemia (calcium gluconate, insulin/D50, albuterol, kayexalate or patiromer, loop diuretic if making urine), metabolic acidosis (bicarb if pH <7.2 or HCO3 <15), volume status

— Phosphate binders if hyperphosphatemia in prolonged AKI

— Discontinue offending drug — recovery in 1–2 weeks typical

— Prednisone 1 mg/kg/day (max 60 mg) × 2–4 weeks then taper over 2–3 months if:

— Cr does not improve within 5–7 days of drug withdrawal

— Biopsy shows severe interstitial inflammation/fibrosis

— Dialysis-requiring AIN

— Mycophenolate as steroid-sparing for refractory cases

— ANCA vasculitis (GPA/MPA): pulse methylprednisolone 500–1000 mg × 3 days → prednisone 1 mg/kg + rituximab (preferred) or cyclophosphamide; plasmapheresis for severe (Cr >4, dialysis, DAH)

— Anti-GBM: pulse steroids + cyclophosphamide + plasmapheresis daily × 14 days (urgent)

— Lupus nephritis class III/IV: pulse steroids → prednisone + mycophenolate or cyclophosphamide; add belimumab or voclosporin for class III–V

— IgA nephropathy with crescents: steroids + RAAS blockade once stable

— Post-strep GN: supportive — usually self-limited; treat residual strep infection

— Cryoglobulinemic GN (HCV): direct-acting antivirals + rituximab if severe

Board pearl: Plasmapheresis is definitive for anti-GBM and adjunctive for severe ANCA vasculitis (Cr >5.7, dialysis-dependent, or pulmonary hemorrhage per PEXIVAS). Memorize these two indications.

ATN: supportive only

AIN:

Glomerular disease — induction therapy:

Adjuncts (post-recovery): ACEi/ARB for proteinuria reduction once Cr stabilized, BP <130/80, SGLT2i in proteinuric CKD

Renal Replacement Therapy and Procedural Considerations

— Acidosis: refractory metabolic acidosis, pH <7.1

— Electrolytes: refractory hyperkalemia (K >6.5 with ECG changes despite medical therapy)

— Intoxications: dialyzable toxins — methanol, ethylene glycol, salicylates, lithium, valproate, metformin (mnemonic: I STUMBLE)

— Overload: diuretic-refractory volume overload causing pulmonary edema

— Uremia: pericarditis, encephalopathy, bleeding, seizures

— STARRT-AKI and AKIKI trials: no benefit to early/preemptive RRT in absence of urgent indication

— Step 3 takeaway: don't dialyze on Cr or BUN number alone — dialyze for symptoms/indications

— Intermittent hemodialysis (IHD): hemodynamically stable patients, faster solute clearance, preferred for hyperkalemia/intoxication

— CRRT (CVVH/CVVHDF): hemodynamically unstable (shock, pressors), cerebral edema, severe hepatic failure

— SLED: hybrid option for marginally unstable patients

— Peritoneal dialysis: rarely used acutely in adults; option in pediatrics, resource-limited settings

— Acute: temporary non-tunneled internal jugular catheter (right IJ preferred); avoid subclavian (stenosis risk for future AV fistula)

— Longer term (≥1–2 weeks): tunneled cuffed catheter

— If CKD trajectory: refer to vascular surgery for AV fistula (preferred over graft) 6 months before anticipated need

CCS pearl: When ordering dialysis, include the modality, access, frequency, ultrafiltration goal, and anticoagulation plan (heparin vs. citrate vs. none). Order vascular surgery consult for fistula in patients trending toward dialysis dependence.

Indications for urgent RRT — "AEIOU":

Timing — early vs. late RRT:

Modality choice:

Access:

Plasmapheresis access: large-bore double-lumen catheter; runs 60–90 min per session

Special Populations — Elderly and Renal/Hepatic Impairment

— Baseline CKD is common — even small Cr changes reflect large GFR drops

— Use CKD-EPI 2021 equation (race-free); avoid Cockcroft-Gault overestimation in low muscle mass

— Sarcopenia masks AKI: a frail 80-year-old with Cr 1.4 may have eGFR <30

— Polypharmacy review: NSAIDs (chronic OA), ACEi/ARB + diuretic combos, metformin, SGLT2i (hold during AKI), bactrim, vancomycin

— Bladder outlet obstruction common — always image to exclude postrenal

— Atheroembolic disease after vascular procedures → AKI + livedo + eosinophilia + low complement (mimics AIN/vasculitis)

— Higher risk of progression to dialysis dependence after AKI episode

— Aggressively avoid contrast; if essential, use iso-/low-osmolar contrast, minimum volume, pre/post IV isotonic saline (1 mL/kg/h × 6–12 h)

— No benefit to N-acetylcysteine or sodium bicarbonate over saline (PRESERVE trial)

— Distinguish prerenal, ATN, and hepatorenal syndrome (HRS-AKI)

— HRS-AKI dx: cirrhosis + ascites + ↑Cr ≥0.3 mg/dL or ≥50% rise, no improvement after 48 h of albumin (1 g/kg/day, max 100 g) + diuretic withdrawal, absent shock, no nephrotoxins, no structural disease

— Treatment: terlipressin + albumin (FDA-approved 2022) or norepinephrine + albumin in ICU; definitive = liver transplant

— Avoid NSAIDs, aminoglycosides, large-volume paracentesis without albumin replacement (8 g albumin per L removed >5 L)

Key distinction: HRS-AKI has a bland urine sediment and FENa <0.1% — looks "prerenal" but doesn't respond to fluids. ATN in cirrhosis has muddy brown casts and FENa >2%. Getting this wrong leads to harm: pushing fluids into HRS worsens ascites; giving vasoconstrictors to ATN doesn't help.

Elderly patients (>65):

Underlying CKD ("acute-on-chronic"):

Hepatic impairment / cirrhosis:

Special Populations — Pregnancy, Pediatrics, Oncology

— Preeclampsia/HELLP: HTN + proteinuria + AKI ± hemolysis, ↑LFTs, thrombocytopenia; delivery is curative

— Acute fatty liver of pregnancy: 3rd trimester, hypoglycemia + coagulopathy + AKI; deliver

— TTP/HUS: pregnancy/postpartum trigger; ADAMTS13 <10% → TTP, plasmapheresis; aHUS → eculizumab

— Postpartum aHUS (complement-mediated): rising Cr days–weeks after delivery, schistocytes, low haptoglobin

— Avoid ACEi/ARB (teratogenic), most immunosuppressants except steroids, azathioprine, tacrolimus; mycophenolate and cyclophosphamide contraindicated — use rituximab cautiously

— HUS (Shiga toxin E. coli O157:H7): bloody diarrhea → MAHA + thrombocytopenia + AKI in child; supportive care, NO antibiotics (worsens toxin release), avoid antimotility agents; dialysis if needed

— IgA vasculitis (HSP): palpable purpura on legs/buttocks, abdominal pain, arthritis, IgA nephritis; usually self-limited, steroids for severe

— Post-strep GN: 1–3 weeks after GAS pharyngitis/impetigo; low C3 normalizes by 8 weeks

— Congenital obstruction: posterior urethral valves in male infants

— Tumor lysis syndrome: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, AKI from urate/calcium-phosphate crystals; prevent with hydration + allopurinol (low risk) or rasburicase (high risk, contraindicated in G6PD deficiency)

— Cast nephropathy (myeloma): light chain precipitation; treat myeloma + hydration

— Cisplatin, methotrexate, ifosfamide nephrotoxicity: hydrate, leucovorin rescue, glucarpidase for MTX

— Checkpoint inhibitor AIN (pembro, nivo): increasingly common; stop drug, steroids

Board pearl: Bloody diarrhea + AKI + thrombocytopenia in a child = STEC-HUS. Do not give antibiotics or loperamide.

Pregnancy-associated AKI:

Pediatric AKI:

Oncology:

Complications and Adverse Outcomes

— Hyperkalemia → arrhythmia, cardiac arrest; peaked T waves → widened QRS → sine wave

— Metabolic acidosis (AG and non-AG) → hyperventilation, decreased contractility, hyperkalemia

— Volume overload → pulmonary edema, hypoxia, right heart strain

— Uremia → encephalopathy, pericarditis (friction rub, tamponade risk), platelet dysfunction → bleeding (treat with DDAVP, cryoprecipitate, dialysis)

— Hyperphosphatemia + hypocalcemia → tetany, QT prolongation

— Drug accumulation toxicity: digoxin, gabapentin (myoclonus), opioids (morphine metabolites cause sedation/seizures — prefer hydromorphone or fentanyl), LMWH bleeding

— CKD progression: AKI doubles long-term CKD risk; severe AKI → 30% develop CKD within 1 year

— ESRD: 5–25% after stage 3 AKI requiring RRT

— Recurrent AKI: up to 30% within 1 year

— Increased cardiovascular mortality independent of CKD

— AIN can leave residual interstitial fibrosis even after drug withdrawal

— GN can progress to ESRD even after treatment of acute phase

— Stage 3 AKI requiring RRT: 40–60% mortality in ICU patients

— Independent predictor of mortality even after adjustment

— Contrast re-exposure during workup

— Failure to dose-adjust antibiotics → supratherapeutic levels, further nephrotoxicity

— Aggressive diuresis in non-volume-overloaded ATN → prerenal hit on top of intrinsic injury

Step 3 management: All AKI survivors need outpatient nephrology follow-up within 3 months, BP control to <130/80, repeat creatinine and UPCR at 3, 6, and 12 months, and lifelong NSAID avoidance counseling. AKI is a CKD risk-equivalent event.

Acute complications of AKI:

Subacute/long-term complications:

In-hospital mortality:

Iatrogenic harms to avoid:

When to Escalate Care — ICU, Consult, Inpatient Triage

— Any KDIGO stage 2 or 3 AKI

— Suspected RPGN (active sediment, rising Cr, systemic features)

— Need for RRT or vascular access placement

— Diagnostic uncertainty requiring biopsy

— Hepatorenal syndrome

— Refractory hyperkalemia or acidosis

— Hemodynamic instability requiring vasopressors

— Need for CRRT

— Pulmonary-renal syndrome with hypoxia or DAH

— Severe hyperkalemia with arrhythmia

— Tumor lysis syndrome with rapid metabolic derangement

— Plasmapheresis for fulminant anti-GBM

— Massive rhabdomyolysis with compartment syndrome

— Urology: postrenal obstruction needing stenting/nephrostomy, neurogenic bladder, recurrent stones

— Rheumatology: ANCA vasculitis, lupus nephritis, cryoglobulinemia co-management

— Hematology: TTP/HUS, multiple myeloma cast nephropathy, plasmapheresis coordination

— Vascular surgery: AV fistula creation for impending ESRD

— Transplant nephrology: dialysis-dependent patients without contraindications → referral for transplant evaluation (can list at eGFR <20)

— Interventional radiology: nephrostomy, biopsy if percutaneous contraindicated, dialysis catheter

— Floor: stable stage 1, slowly resolving, no electrolyte crises

— Step-down: stage 2–3 needing close monitoring, fluid management, early dialysis planning

— ICU: as above

CCS pearl: A 60-year-old with new AKI, hemoptysis, and SaO2 88% must be moved to ICU, ordered ANCA/anti-GBM/CXR/CT chest, and given methylprednisolone 1 g IV with nephrology and pulmonology consults — all within the first set of orders. Plasmapheresis follows once dx confirmed.

Immediate nephrology consult:

ICU triage:

Other consults:

Floor vs. step-down vs. ICU thresholds:

Key Differentials — Same-Category (Intrinsic AKI) Causes

— Setting of hypotension, sepsis, surgery, nephrotoxin

— Muddy brown granular casts + RTE cells

— FENa >2%, FEUrea >50%

— Bland urine: no significant proteinuria, no hematuria

— Recovery in 1–3 weeks (oliguric phase → polyuric phase → recovery)

— New drug or recent infection

— Sterile pyuria, WBC casts, ± eosinophiluria

— Mild-to-moderate proteinuria (<1 g/day, except NSAID-AIN which can cause nephrotic-range)

— ± rash, fever, eosinophilia, arthralgia

— Improves within 1–2 weeks of stopping drug

— Nephritic: HTN, edema, dysmorphic RBCs, RBC casts, subnephrotic proteinuria, low GFR

— Nephrotic: proteinuria >3.5 g/24h, hypoalbuminemia, edema, hyperlipidemia

— Mixed nephritic/nephrotic: MPGN, lupus class IV, diabetic nephropathy

— Serology-driven: ANA, ANCA, anti-GBM, C3/C4, hep panel, SPEP

— Renal artery thromboembolism: sudden flank pain, ↑LDH, AKI; A-fib or recent vascular procedure

— Renal vein thrombosis: nephrotic syndrome (especially membranous), flank pain, hematuria

— Atheroembolic disease: post-cath, livedo reticularis, blue toes, eosinophilia, low complement, slowly progressive AKI over days–weeks

— TMA (HUS, TTP, malignant HTN, scleroderma renal crisis, drug-induced — calcineurin inhibitors, gemcitabine, quinine): schistocytes, ↓platelets, ↑LDH, ↓haptoglobin

— Scleroderma renal crisis: rapid HTN + AKI in diffuse scleroderma; treat with ACEi (captopril) — only time you give ACEi in AKI

Key distinction: Atheroembolic disease mimics both AIN (eosinophilia) and vasculitis (low complement, livedo). The clue is recent vascular catheterization or aortic manipulation, and biopsy shows cholesterol clefts.

Distinguishing ATN, AIN, and GN at the bedside:

ATN clues:

AIN clues:

Glomerulonephritis clues:

Vascular intrinsic causes (don't forget):

Key Differentials — Prerenal and Postrenal

— Volume depletion: vomiting, diarrhea, hemorrhage, diuretics, burns, third-spacing

— Decreased effective circulating volume: HF, cirrhosis, nephrotic syndrome, sepsis (early)

— Renal hypoperfusion: NSAIDs (afferent constriction), ACEi/ARB (efferent dilation), calcineurin inhibitors, contrast

— Renal artery stenosis (especially bilateral) + ACEi → AKI

— Labs: BUN:Cr >20:1, FENa <1%, FEUrea <35%, urine osm >500, urine Na <20, hyaline casts

— Reverses with volume restoration within 24–72 h — if not, suspect transition to ATN

— BPH, prostate cancer (most common in older men)

— Pelvic/retroperitoneal malignancy (cervical, colorectal), retroperitoneal fibrosis

— Bilateral ureteral stones (or single stone in solitary kidney)

— Neurogenic bladder

— Blocked Foley catheter — always check this first in inpatient AKI

— Eval: bladder scan, Foley placement, renal US for hydronephrosis (may be absent early or in retroperitoneal fibrosis)

— Treatment: relieve obstruction → Foley, ureteral stent, percutaneous nephrostomy

— Post-obstructive diuresis: massive UOP after relief; replace ~75% of losses with 0.45% NS, monitor electrolytes

— Sepsis: combines prerenal (hypoperfusion) + intrinsic (ATN from inflammation/cytokines)

— Cirrhosis: prerenal physiology → HRS → ATN spectrum

— Cardiorenal syndrome: HF-induced AKI; treat HF (diuresis often improves Cr despite "prerenal" labs)

— Contrast: prerenal hemodynamics + tubular toxicity

Board pearl: A patient with bilateral hydronephrosis on US + AKI + history of cervical cancer or RP nodes → bilateral ureteral obstruction. Drain immediately (stents or nephrostomies), then anticipate post-obstructive diuresis: replace fluid carefully to avoid both volume depletion and overcorrection.

Prerenal azotemia — must exclude first:

Postrenal (obstructive) AKI:

Mixed/overlap presentations:

Secondary Prevention, Discharge Medications, Long-Term Plan

— Hold or stop: NSAIDs (lifelong avoidance in AKI survivors), the offending AIN drug (document allergy/intolerance in chart)

— Hold and reassess: ACEi/ARB, SGLT2i, diuretics — restart after eGFR stabilizes and consider lower dose; document plan for outpatient titration

— Metformin: hold if eGFR <30; can resume if eGFR ≥45 and stable

— Dose-adjust: gabapentin/pregabalin, DOACs, LMWH, antibiotics, allopurinol

— Document lifelong nephrotoxin list in problem list and counsel patient

— Target BP <130/80 for CKD/proteinuria

— ACEi or ARB as first-line antihypertensive once Cr stable (especially proteinuria >300 mg/g)

— Add SGLT2 inhibitor (empagliflozin, dapagliflozin) if eGFR ≥20 and UACR >200 mg/g — DAPA-CKD/EMPA-KIDNEY evidence; reduces CKD progression and CV death

— Finerenone for diabetic CKD with albuminuria

— Pneumococcal (PCV20 or PCV15+PPSV23), influenza annually, hepatitis B (higher-dose series in dialysis), COVID-19, RSV ≥60

— Low-sodium diet (<2 g/day), DASH-style

— Avoid NSAIDs, herbal nephrotoxins (aristolochic acid, ephedra)

— Smoking cessation

— Weight, glycemic, and lipid optimization

— ANCA: rituximab every 6 months × 2 years for maintenance

— Lupus nephritis: MMF or azathioprine maintenance × 3+ years

— IgA: ACEi/ARB, SGLT2i, sparsentan, budesonide-MMX

Step 3 management: Document a "do not give" medication list (NSAIDs, the specific AIN culprit, IV contrast cautions) at discharge — this is a transitions-of-care safety item Step 3 loves.

Discharge medication reconciliation — critical hand-off point:

Blood pressure and proteinuria control:

Vaccinations for CKD/dialysis-bound patients:

Lifestyle:

Disease-specific maintenance:

Follow-Up, Monitoring, and Counseling

— Within 7–14 days post-discharge: PCP visit — BMP, BP, volume status, med reconciliation

— Within 3 months: nephrology if not already established; required for stage 2–3 AKI per KDIGO

— 3, 6, 12 months: BMP, UPCR or UACR, BP

— Annual thereafter if stable; more often if CKD progression

— Serum creatinine and eGFR trend

— Urine protein quantification (UPCR or UACR) — proteinuria is the strongest predictor of progression

— BP log — home monitoring encouraged

— Electrolytes, especially K and HCO3 if on ACEi/ARB or SGLT2i

— Hemoglobin — anemia of CKD develops as eGFR <60; iron studies, EPO if Hgb <10

— PTH, calcium, phosphate, vitamin D for CKD-MBD as eGFR <45

— Sick day rules: hold ACEi/ARB, diuretics, SGLT2i, metformin, NSAIDs during acute illness with vomiting/diarrhea/fever — "DAMN" mnemonic (Diuretics, ACEi/ARB/aldosterone, Metformin, NSAIDs); some add SGLT2i

— Stay hydrated but not overhydrated

— Avoid OTC NSAIDs, herbal supplements

— Report decreased urine output, swelling, dyspnea, weight gain >2 kg in 3 days

— Post-ICU/dialysis deconditioning: PT/OT referral

— Nutritional counseling: protein 0.8 g/kg/day in CKD (not severely restricted), low Na/K/phosphate as needed

— Smoking cessation, alcohol reduction

— Mental health: depression common post-AKI/ICU

Board pearl: "Sick day rules" — teaching patients to hold ACEi/ARB, diuretics, metformin, NSAIDs, SGLT2i during acute illness is a high-yield Step 3 outpatient counseling point that prevents recurrent AKI.

Outpatient follow-up cadence:

Monitoring parameters:

Counseling and patient education:

Rehabilitation considerations:

Ethical, Legal, and Patient Safety Considerations

— Must discuss risks (catheter infection, bleeding, hypotension, mortality), benefits (electrolyte/volume management, symptom relief), alternatives (conservative kidney management, palliative care), and prognosis

— Conservative (non-dialytic) management is a valid choice for frail elderly or those with poor prognosis — survival benefit of dialysis in patients >80 with multiple comorbidities is marginal and may worsen QOL

— Time-limited trials of dialysis are ethically appropriate

— Uremic encephalopathy can impair capacity — may need dialysis first, then revisit goals of care when mentation clears

— Use surrogate decision-makers (advance directive, MOLST/POLST, healthcare proxy) when patient lacks capacity

— Document the four capacity elements: understanding, appreciation, reasoning, expression of a choice

— Patient (or surrogate) may withdraw dialysis; median survival 7–10 days after withdrawal

— Refer to palliative care/hospice

— Renal Physicians Association guideline supports withdrawal in appropriate situations

— Med rec at discharge is the highest-risk handoff — failure to remove nephrotoxic drug or to communicate dose adjustments is a sentinel-event-class error

— Use teach-back: ask patient to repeat their med list and sick day rules

— Direct communication (not just chart) with PCP and outpatient nephrologist within 48 h

— Drug-induced AIN should be reported to FDA MedWatch when severe or with new agent

— Document drug allergy/intolerance prominently in EHR

— Contrast-induced AKI: ensure shared decision-making documented when contrast required despite CKD

— Race-free CKD-EPI 2021 equation — older equations under-diagnosed CKD in Black patients, delaying transplant referral

— Refer for transplant evaluation at eGFR ≤20, regardless of race

Step 3 management: When a frail 88-year-old with metastatic cancer develops dialysis-requiring AKI, a goals-of-care conversation with palliative care consult is the most appropriate next step — not automatic initiation of dialysis.

Informed consent for dialysis:

Capacity assessment:

Withdrawal of dialysis:

Transition-of-care safety:

Reporting and legal:

Equity:

High-Yield Associations and Rapid-Fire Clinical Facts

— NSAIDs → prerenal (afferent constriction) + AIN + MCD/membranous (nephrotic) + papillary necrosis

— ACEi/ARB → efferent dilation, AKI in bilateral RAS or volume depletion

— Aminoglycosides → non-oliguric ATN (proximal tubule), days 5–10

— Vancomycin → ATN at troughs >20, additive with pip-tazo

— Contrast → ATN within 24–72 h, peaks 3–5 days

— Cisplatin → ATN + hypomagnesemia

— Cyclosporine/tacrolimus → afferent vasoconstriction + chronic interstitial fibrosis + TMA

— PPIs → AIN (insidious, months later)

— Allopurinol → AIN + DRESS

— Lithium → nephrogenic DI + chronic TIN

— Acyclovir (IV bolus) → crystal nephropathy

— Sulfonamides, methotrexate, indinavir, atazanavir → crystal nephropathy

— Ethylene glycol → calcium oxalate crystals, AKI, AG acidosis

— Muddy brown casts → ATN

— WBC casts + eosinophiluria → AIN

— RBC casts → GN

— Fatty casts/oval fat bodies "Maltese cross" → nephrotic syndrome

— Schistocytes + thrombocytopenia + AKI → TMA

— Pulmonary-renal + linear IgG on biopsy → anti-GBM

— Crescents + pauci-immune → ANCA vasculitis

— Subepithelial humps on EM, low C3 → post-strep GN

— Tram-track on light microscopy, low C3 → MPGN

— Mesangial IgA deposits → IgA nephropathy

— Wire-loop lesions, full-house IF (IgG, IgM, IgA, C3, C1q) → lupus nephritis

— Spike-and-dome, subepithelial deposits → membranous (PLA2R antibody)

— Effacement of foot processes, normal LM → minimal change disease

— Low C3: post-strep, MPGN, lupus (also low C4), cryo, endocarditis-related GN, atheroembolic

— Normal C3: IgA, HSP, anti-GBM, ANCA

Board pearl: Pip-tazo + vancomycin is a notorious combo for AKI — both nephrotoxin and AIN risk are elevated. Consider cefepime substitution where appropriate.

Drug → kidney lesion lightning round:

Buzzword → diagnosis:

Complement quick-reference:

Board Question Stem Patterns

— 70-year-old with DM and CKD undergoes cardiac cath; Cr rises from 1.6 to 2.8 over 48 h, muddy brown casts on UA, FENa 3%

— Answer: supportive care, hold metformin, no NAC, hydration

— Patient on pip-tazo × 10 days develops Cr rise, sterile pyuria, low-grade fever, eosinophilia

— Answer: stop pip-tazo (switch to cefepime), consider steroids if no improvement in 5–7 days

— Young smoker with hemoptysis, dyspnea, AKI, RBC casts; CXR with bilateral infiltrates

— Answer: anti-GBM antibody, urgent biopsy, pulse steroids + cyclophosphamide + plasmapheresis

— 60-year-old with sinusitis, saddle nose, hemoptysis, AKI, c-ANCA/PR3 positive

— Answer: GPA; rituximab + steroids; plasmapheresis if severe

— Child with cola-colored urine 2 weeks after pharyngitis, HTN, low C3, normal C4

— Answer: supportive, BP control, expect C3 normalization at 8 weeks

— Young woman with malar rash, arthritis, proteinuria, hematuria, low C3 and C4, ANA+, anti-dsDNA+

— Answer: biopsy → class IV → steroids + MMF (or cyclophosphamide)

— Found-down patient, CK 45,000, dark urine dipstick heme+ without RBCs, AKI

— Answer: aggressive isotonic fluid resuscitation, monitor for compartment syndrome and hyperkalemia

— Patient with new ALL, post-chemo, hyper-K/phos/uric, hypocalcemia, AKI

— Answer: rasburicase, IV fluids, dialysis if refractory; don't alkalinize urine (calcium phosphate precipitation)

— Post-cath patient with livedo reticularis, blue toes, eosinophilia, low complement, gradual Cr rise

— Answer: supportive, statin, avoid anticoagulation if possible

— Cirrhosis with ascites, Cr rises, FENa <0.1%, no improvement with albumin/diuretic hold

— Answer: terlipressin + albumin; transplant evaluation

Key distinction: Step 3 stems emphasize the next best management step, not just diagnosis — know the specific drug, dose adjustment, or follow-up interval.

Stem pattern 1 — ATN after contrast:

Stem pattern 2 — AIN from pip-tazo or PPI:

Stem pattern 3 — RPGN/anti-GBM:

Stem pattern 4 — ANCA vasculitis:

Stem pattern 5 — Post-strep GN:

Stem pattern 6 — Lupus nephritis:

Stem pattern 7 — Rhabdomyolysis:

Stem pattern 8 — Tumor lysis:

Stem pattern 9 — Cholesterol emboli:

Stem pattern 10 — HRS:

One-Line Recap

Intrinsic AKI = ATN (muddy brown casts, supportive care), AIN (drug-induced, stop the agent ± steroids), or glomerular disease (RBC casts, serologies, urgent biopsy and immunosuppression for RPGN) — and your job is to distinguish them with urinalysis microscopy, stop nephrotoxins, dose-adjust everything, and escalate within hours when pulmonary-renal syndrome or refractory metabolic derangement appears.

Board pearl: When in doubt on a Step 3 AKI vignette, the answer is usually "stop the offending drug and check the urine sediment" before you reach for any escalation.

Diagnostic anchor: Urine microscopy is the single most useful test — muddy brown casts (ATN), WBC casts/eosinophiluria (AIN), RBC casts/dysmorphic RBCs (GN). Order it on every AKI.

Universal AKI bundle: stop NSAIDs/ACEi/ARB/aminoglycosides/contrast, dose-adjust renally cleared meds, optimize hemodynamics (MAP ≥65), monitor strict I/Os and daily BMP, image to exclude obstruction. Loop diuretics only for volume — they do not "convert" or shorten ATN.

Time-critical syndromes: RPGN (anti-GBM, ANCA, severe lupus) and pulmonary-renal syndrome demand urgent biopsy, pulse methylprednisolone, and plasmapheresis (anti-GBM definitely; severe ANCA selectively). TMA needs schistocyte recognition and disease-specific therapy (plasmapheresis for TTP, eculizumab for aHUS).

Transitions-of-care: AKI survivors need nephrology follow-up within 3 months, BP <130/80, ACEi/ARB + SGLT2i once stable, lifelong NSAID avoidance, sick-day rules (hold DAMN drugs), and explicit discharge documentation of the offending drug — this is the Step 3-flavored safety closure that prevents recurrent AKI and slows CKD progression.