Section I — AKI Diagnosis

Acute Kidney Injury

Differentiate pre-renal, intrarenal, and post-renal etiologies using lab indices, urine sediment, and clinical context. Prompt categorization drives fluid, workup, and consult decisions.

Pre-renal

Decreased renal perfusion

Reduced blood flow to structurally intact kidneys. Tubular function is preserved — rapidly reversible with prompt restoration of perfusion.

Common Causes
  • Volume depletion — hemorrhage, dehydration, GI losses, burns
  • Low cardiac output — CHF, cardiogenic shock, severe valvular disease
  • Sepsis — early vasodilatory / distributive hypotension
  • NSAIDs — afferent arteriole constriction, impaired autoregulation
  • ACEi/ARBs — efferent dilation; risk in bilateral RAS or volume depletion
  • Hepatorenal syndrome, severe hypoalbuminemia / third-spacing
Lab Profile
BUN/Cr ratio
> 20:1
FENa
< 1%
Urine Na
< 20 mEq/L
Urine Osm
> 500 mOsm/kg
Urine Sediment
Bland — few hyaline casts
Management
  • Restore perfusion — IV isotonic crystalloid for hypovolemia; transfuse for hemorrhage
  • Treat the cause — antibiotics + vasopressors for septic shock, inotropes for low-output states
  • Hold offending agents — NSAIDs, ACEi/ARB (especially in bilateral RAS or volume depletion)
  • Monitor response — urine output and SCr should improve within 24–48 h of resuscitation
  • Avoid over-resuscitation in CHF — decongest with diuretics if venous congestion develops
Rapidly improves with volume challenge / restoring perfusion

Intrarenal

Intrinsic parenchymal injury

Direct injury to glomeruli, tubules, interstitium, or vasculature. Acute tubular necrosis (ATN) is the most common subtype.

Common Causes
  • ATN — ischemic (prolonged pre-renal) or nephrotoxic (contrast, aminoglycosides, rhabdomyolysis, tumor lysis)
  • Acute interstitial nephritis — penicillins, cephalosporins, PPIs, NSAIDs, sulfonamides
  • Glomerular — acute GN, RPGN
  • Vascular — cholesterol emboli, TTP/HUS, vasculitis, malignant HTN
  • Crystal nephropathy — urate, oxalate, acyclovir, indinavir
Lab Profile
BUN/Cr ratio
< 15:1
FENa
> 2%
Urine Na
> 40 mEq/L
Urine Osm
< 350 mOsm/kg
Urine Sediment
Muddy brown granular casts (ATN); RBC casts (GN); WBC/eosinophils (AIN)
Management
  • Remove the insult — stop nephrotoxins, treat infection, relieve obstruction if contributing
  • AIN: withdraw culprit drug; steroids (prednisone 0.5–1 mg/kg/day) if AKI persists 1–2 weeks
  • GN/vasculitis: immunosuppression (steroids ± cyclophosphamide/rituximab) guided by biopsy
  • Supportive care — manage volume, electrolytes, acid–base; dose-adjust all medications
  • RRT for refractory hyperkalemia, acidosis, volume overload, or uremia
No response to volume; recovery over days–weeks after the insult is removed

Post-renal

Urinary tract obstruction

Obstruction to outflow raises back-pressure and lowers GFR. Requires blockage below both kidneys (or a solitary functioning kidney).

Common Causes
  • BPH, prostate or cervical cancer — most common in older adults
  • Nephrolithiasis — bilateral, or in a solitary kidney
  • Retroperitoneal fibrosis, pelvic malignancy
  • Neurogenic bladder; anticholinergic / opioid-induced retention
  • Urethral stricture, blood clots, blocked Foley
Lab Profile
BUN/Cr ratio
~ 10–20:1
FENa
Variable
Post-void residual
> 100 mL
Renal US
Hydronephrosis
Urine Sediment
Variable — often bland; crystals, blood, or debris by cause
Management
  • Decompress promptly — Foley catheter for bladder outlet; ureteral stent or nephrostomy for upper tract
  • Treat the cause — α-blocker/5-ARI for BPH, stone management, oncology for malignancy
  • Monitor for post-obstructive diuresis — replace ~75% of urine output for 24 h after relief
  • Watch for infection — antibiotics if pyelonephritis or urosepsis; culture before decompression
  • Follow SCr trend — expect improvement over 24–72 h after relief; residual CKD if chronic obstruction
Frequently reversible with prompt decompression (catheter, stent, nephrostomy)

Lab Index Comparison

Side-by-side differentiators

Understanding the Indices

What each value measures & why it differentiates
BUN / Creatinine Ratio
BUN ÷ Serum Creatinine (mg/dL)
Measures
Relative handling of urea vs. creatinine — urea is passively reabsorbed; creatinine is purely filtered.
Why it differentiates
Hypoperfusion triggers ADH-mediated reabsorption of water and urea, so BUN rises faster than creatinine.
Read as
Pre-renal: > 20:1
Intrarenal: < 15:1
Post-renal: 10–20:1
Altered by GI bleeding, high-protein intake, catabolism, or liver disease (↓ urea production).
FENa (Fractional Excretion of Sodium)
(Urine Na × Plasma Cr) ÷ (Plasma Na × Urine Cr) × 100
Measures
Percentage of filtered sodium that escapes reabsorption and is excreted.
Why it differentiates
An intact, perfused kidney retains sodium (RAAS/ADH) → low FENa. Necrotic tubules lose sodium → high FENa.
Read as
Pre-renal: < 1%
Intrarenal: > 2%
Post-renal: Variable
Unreliable with diuretics, CKD, sepsis, or contrast — substitute FEUrea (< 35% suggests pre-renal).
FEUrea (Fractional Excretion of Urea)
(Urine Urea × Plasma Cr) ÷ (Plasma Urea × Urine Cr) × 100
Measures
Percentage of filtered urea that is excreted — a diuretic-resistant alternative to FENa.
Why it differentiates
Urea reabsorption parallels water; hypoperfusion conserves urea → low FEUrea. Tubular injury loses urea → high FEUrea.
Read as
Pre-renal: < 35%
Intrarenal: > 35%
Post-renal: Variable
Preferred over FENa when diuretics are on board. Less reliable in CKD, sepsis, or with ACEi/ARB.
Urine Sodium
Spot urine sodium (mEq/L)
Measures
Tubular capacity to conserve sodium.
Why it differentiates
Pre-renal physiology activates sodium retention → low urine Na. Tubular necrosis loses sodium → high urine Na.
Read as
Pre-renal: < 20 mEq/L
Intrarenal: > 40 mEq/L
Post-renal: Variable
Diuretics falsely elevate urine Na; early obstruction may still read low.
Urine Osmolality
Spot urine osmolality (mOsm/kg)
Measures
Renal concentrating ability.
Why it differentiates
Intact tubules with ADH concentrate urine (pre-renal). Damaged tubules lose the medullary gradient → isosthenuria.
Read as
Pre-renal: > 500 mOsm/kg
Intrarenal: < 350 mOsm/kg
Post-renal: Variable
Confounded by diuretics, mannitol, or baseline isosthenuria from chronic kidney disease.
Urine Specific Gravity
Refractometer or dipstick (1.000–1.030)
Measures
Bedside estimate of urine concentrating ability.
Why it differentiates
Intact tubules with ADH concentrate urine (pre-renal). Damaged tubules lose the medullary gradient → fixed near 1.010 (isosthenuria).
Read as
Pre-renal: > 1.020
Intrarenal: ~ 1.010
Post-renal: Variable
Falsely elevated by glucose, contrast, mannitol, and proteins — confirm with osmolality when confounders are present.
Urine / Plasma Creatinine Ratio
Urine Cr ÷ Plasma Cr (mg/dL)
Measures
Concentration of creatinine across the nephron — a surrogate for water reabsorption.
Why it differentiates
Intact tubules reabsorb water and concentrate creatinine → high ratio. Tubular injury loses concentrating ability → low ratio.
Read as
Pre-renal: > 40
Intrarenal: < 20
Post-renal: Variable
Less confounded by diuretics than FENa — useful alongside FEUrea in the diuretic-treated patient.
Renal Failure Index (RFI)
Urine Na ÷ (Urine Cr ÷ Plasma Cr)
Measures
Sodium excretion relative to creatinine — a FENa analog that is not multiplied by 100.
Why it differentiates
Intact tubules retain sodium → low RFI. Necrotic tubules waste sodium → high RFI.
Read as
Pre-renal: < 1
Intrarenal: > 2
Post-renal: Variable
Tracks closely with FENa and shares the same limitations with diuretics, CKD, and sepsis.
Albumin / Creatinine Ratio (ACR)
Urine albumin (mg) ÷ Urine creatinine (g)
Measures
Spot estimate of 24-hour albumin excretion — marker of glomerular permeability.
Why it differentiates
An intact filtration barrier excludes albumin. Glomerular or tubulointerstitial injury leaks albumin → elevated ACR.
Read as
Pre-renal: < 30 mg/g (normal)
Intrarenal: Elevated — high in GN
Post-renal: Variable
Confounded by vigorous exercise, fever, UTI, heart failure, or menstruation — confirm on a morning sample.
Urine Sediment
Microscopy of centrifuged urine
Measures
Direct visualization of casts, cells, and crystals — localizes the site of injury.
Why it differentiates
Bland sediment implies intact tubules (pre-renal); specific casts and cells reveal the injured compartment.
Read as
Pre-renal: Bland — hyaline casts
Intrarenal: Muddy brown (ATN), RBC casts (GN), WBC/eos (AIN)
Post-renal: Variable — crystals, blood, debris
The single most useful differentiator — obtain before fluids or diuretics confound the picture.

Diagnostic Workup

Stepwise approach to localize the cause
1
History & volume exam
Mucous membranes, JVP, skin turgor, edema, BP, orthostatics — assess volume status
2
Urinalysis + sediment
The single most useful differentiator — casts and cells localize the site of injury
3
Serum & urine indices
BUN, Cr, electrolytes; FENa, urine Na, urine Osm, urine Cr (spot sample)
4
Bladder catheterization
Post-void residual > 100 mL suggests obstruction — rule out post-renal first
5
Renal ultrasound
Hydronephrosis confirms obstruction; obtain if diagnosis unclear or no improvement
6
Nephrology consult
Persistent AKI, unclear etiology, or need for biopsy / dialysis — escalate early

Diagnosing Intrinsic AKI & Glomerulonephritis

Tubulointerstitial, vascular & glomerular syndromes

When intrinsic AKI is suspected (nephritic urine, rapid decline, systemic features), these syndromes account for most tubulointerstitial, vascular, and glomerular causes. Recognize the pattern, confirm with targeted serologies and biopsy, and escalate quickly.

Tubulointerstitial & Vascular
Hepatorenal Syndrome
HRS-AKI
Recognize
  • Cirrhosis with ascites and new AKI
  • Very low urine Na (< 10 mEq/L) and low FENa — intact tubules
  • Bland sediment; no significant proteinuria or hematuria
Diagnose
  1. 1Confirm cirrhosis with ascites
  2. 2Meet ICA-AKI criteria (SCr ↑ ≥ 0.3 mg/dL in 48h, ≥ 1.5× baseline, or oliguria)
  3. 3Albumin 1 g/kg/day (max 100 g) + diuretic withdrawal × 2 days — no improvement
  4. 4Rule out shock, nephrotoxic drugs, and structural kidney injury
  5. 5Normal renal US; proteinuria < 500 mg/day, < 50 RBC/hpf
Manage
  • Vasoconstrictor + albumin: terlipressin 1–2 mg IV q4h + albumin 20–40 g/day (preferred); norepinephrine if ICU
  • Treat the precipitant — SBP, GI bleed, infection; stop nephrotoxins and diuretics
  • Albumin challenge 1 g/kg/day × 2 days before confirming HRS-AKI
  • Early transplant referral; TIPS generally not recommended in HRS-AKI
  • RRT bridge to transplant if refractory or severe
Diagnosis of exclusion — Type 1 (HRS-AKI) is rapid and severe; Type 2 presents with refractory ascites.
Lymphoma-Associated AKI
Renal lymphoma / TLS
Recognize
  • Known or suspected lymphoma/leukemia with B symptoms (fever, weight loss, night sweats)
  • Rapidly rising SCr with bilateral nephromegaly and no hydronephrosis on US
  • Tumor lysis: hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia after cytotoxic therapy
  • Leukocytosis with high LDH; urate nephropathy or parenchymal infiltration
Diagnose
  1. 1Renal US — enlarged kidneys without obstruction suggests infiltration; hydronephrosis suggests obstruction
  2. 2Tumor lysis labs: uric acid, phosphate, potassium, calcium, LDH — risk-stratify before chemo
  3. 3Urinalysis — bland sediment in infiltration/TLS; nephritic if GN overlap
  4. 4Renal biopsy if etiology unclear — distinguish infiltration vs. paraneoplastic GN vs. TLS
  5. 5Hematology workup: peripheral smear, flow cytometry, LDH, β2-microglobulin, bone marrow biopsy
Manage
  • TLS prophylaxis: aggressive IV hydration, allopurinol (low risk) or rasburicase (high risk/burden)
  • Correct hyperkalemia, hyperphosphatemia, hypocalcemia; alkalinize urine cautiously
  • Hematology/oncology — treat the underlying malignancy (chemotherapy, rituximab for B-cell)
  • RRT for refractory hyperkalemia, acidosis, volume overload, or severe uremia
  • Relieve obstruction if present (nephrostomy/stent); manage infiltration with systemic therapy
Bilateral nephromegaly without obstruction in a hematologic malignancy points to renal infiltration; abrupt hyperuricemia + hyperphosphatemia after therapy is tumor lysis — hydrate and rasburicase/allopurinol prophylaxis.
Glomerular Syndromes
IgA Nephropathy
Berger disease
Recognize
  • Most common primary GN — young adults, often within 1–3 days of an upper-respiratory or GI infection
  • Episodic gross (cola-colored) hematuria or persistent asymptomatic microscopic hematuria
  • Mild proteinuria; rarely nephrotic; normal complement levels
Diagnose
  1. 1Urinalysis + sediment: dysmorphic RBCs, ± RBC casts; sub-nephrotic proteinuria
  2. 2Serologies: normal C3/C4; ANA, ANCA, anti-GBM, and hepatitis panel to exclude mimics
  3. 3Renal biopsy — mesangial IgA-dominant deposition on immunofluorescence; variable mesangial hypercellularity on light
  4. 4Risk stratify with the Oxford (MEST-C) classification and proteinuria, eGFR, and BP
Manage
  • First-line: ACEi or ARB titrated to max tolerated dose for proteinuria and hypertension
  • 6-month supportive course of glucocorticoids for high-risk disease (proteinuria > 1 g/day despite optimal supportive care)
  • Immunosuppression (cyclophosphamide + steroids) only for rapidly progressive / crescentic IgA nephropathy
  • Tonsillectomy is controversial; not routine. Omega-3 / fish oil lacks consistent benefit
  • Monitor proteinuria, BP, and eGFR; refer for transplant if progression to ESRD
Episodic synpharyngitic hematuria with normal complements points to IgA nephropathy — the timing (1–3 days post-infection) distinguishes it from PSGN (1–4 weeks).
Post-Streptococcal GN
PSGN
Recognize
  • Children 1–4 weeks after pharyngitis or impetigo (nephritogenic strains)
  • Acute nephritic syndrome — tea-colored urine, edema, hypertension, oliguria
  • Low C3 that normalizes within 6–8 weeks; elevated ASO / anti-DNase B
Diagnose
  1. 1Urinalysis + sediment: dysmorphic RBCs, RBC casts, sub-nephrotic proteinuria
  2. 2Complements: low C3 with normal C4; recheck at 6–8 weeks to confirm normalization
  3. 3Serologies: rising ASO titer (pharyngeal) or anti-DNase B (skin); throat / skin cultures
  4. 4Renal biopsy generally unnecessary — reserve for atypical course (no improvement, persistent low C3, nephrotic-range proteinuria)
Manage
  • Supportive care: salt and fluid restriction, loop diuretics for edema, antihypertensives for BP
  • Treat active infection — antibiotics for group A strep (does not alter GN course but prevents spread)
  • Manage complications: hyperkalemia, volume overload, hypertensive emergency
  • Dialysis rarely needed (uremia, refractory hyperkalemia / volume overload)
  • Most cases are self-limited in children; monitor for complete recovery and rare progression
PSGN is usually self-limited — a low C3 that fails to normalize by 6–8 weeks should prompt biopsy and a search for an alternative glomerulopathy.
Rapidly Progressive GN
RPGN
Recognize
  • Rapid SCr rise over days–weeks with a nephritic urine
  • Crescents on biopsy (> 50% of glomeruli)
  • Pulmonary hemorrhage in anti-GBM or ANCA disease
Diagnose
  1. 1Type I (anti-GBM): linear IgG on IF, anti-GBM antibody positive; assess lungs (DLCO, CT chest)
  2. 2Type II (immune-complex): granular IF — lupus, post-infectious, IgA, cryoglobulin
  3. 3Type III (pauci-immune): minimal deposition — ANCA (PR3/MPO) positive
  4. 4Serology panel: anti-GBM, ANCA, ANA/dsDNA, complements, cryoglobulins
  5. 5Renal biopsy — crescentic GN; IF pattern defines the type
Manage
  • High-dose IV methylprednisolone pulse (500–1000 mg × 3 days) then oral prednisone 1 mg/kg/day
  • Cyclophosphamide IV or oral, OR rituximab for ANCA-associated vasculitis induction
  • Plasmapheresis for anti-GBM disease, severe pulmonary hemorrhage, or ANCA with creatinine > 5.7 mg/dL
  • PJP prophylaxis (Bactrim) and bone protection while on steroids
  • Maintenance therapy after induction (rituximab, azathioprine, or MMF); RRT if needed
Treat as a renal emergency — early biopsy + serologies; pulmo-renal overlap in anti-GBM and ANCA disease.
ANCA-Associated Vasculitis
Renal vasculitis
Recognize
  • Systemic symptoms — fever, weight loss, arthralgia, purpura, sinusitis
  • Pulmonary hemorrhage or sinus/lung involvement
  • Nephritic urine with rapidly declining GFR
Diagnose
  1. 1ANCA: PR3 (GPA), MPO (MPA, EGPA) — pauci-immune crescentic GN
  2. 2Immune-complex overlap: ANA/dsDNA + low complements (lupus nephritis); IgA (IgA vasculitis)
  3. 3Cryoglobulins + HCV + low C4 (cryoglobulinemic vasculitis)
  4. 4Biopsy: crescentic GN; IF distinguishes pauci-immune vs immune-complex
  5. 5CT chest/sinus for extra-renal disease; evaluate for pulmonary hemorrhage
Manage
  • Induction: high-dose glucocorticoids + cyclophosphamide or rituximab (Ritux vas — non-life-threatening GPA/MPA)
  • Plasmapheresis for severe pulmonary hemorrhage or SCr > 5.7 mg/dL (MEPEX)
  • Maintenance: rituximab, azathioprine, or MMF for 18–24 months after remission
  • Treat relapses; PJP, osteoporosis, and infection prophylaxis throughout
  • Adjunctive ACEi/ARB for proteinuria; RRT for advanced renal failure
ANCA-associated vasculitis is the most common cause of RPGN in older adults.
Lupus Nephritis
SLE nephritis
Recognize
  • SLE with new hematuria, proteinuria, or rising creatinine — nephritis develops in up to 60% of lupus patients
  • Low C3 and C4; positive ANA and anti-dsDNA; nephritic or nephrotic overlap
  • Extra-renal lupus: malar rash, arthralgia, photosensitivity, cytopenias, serositis
Diagnose
  1. 1Urinalysis + sediment: dysmorphic RBCs, RBC casts, proteinuria (sub-nephrotic to nephrotic)
  2. 2Serologies: ANA, anti-dsDNA, anti-Smith; low C3 and C4; anti-Ro/La, antiphospholipid antibodies
  3. 3Renal biopsy — ISN/RPS class (I–VI) defines proliferative (III/IV), membranous (V), and guides therapy; activity vs chronicity indices
  4. 4Quantify proteinuria and renal function for prognosis and treatment monitoring
Manage
  • Induction (class III/IV): mycophenolate mofetil or cyclophosphamide + high-dose steroids; add belimumab or voclosporin
  • Membranous (class V): mycophenolate + steroids; calcineurin inhibitor if nephrotic-range proteinuria
  • Maintenance: mycophenolate or azathioprine + low-dose steroids; hydroxychloroquine for all lupus nephritis
  • ACEi/ARB for proteinuria; control BP; anticoagulation for antiphospholipid syndrome
  • Monitor proteinuria, C3/C4, dsDNA, and renal function; relapse risk and long-term immunosuppression
Class III/IV proliferative lupus nephritis needs urgent induction — the ISN/RPS class on biopsy, not the clinical picture alone, drives the intensity of immunosuppression.
Cryoglobulinemic Vasculitis
HCV · mixed cryo
Recognize
  • Meltzer triad — palpable purpura, arthralgia, and weakness
  • Hepatitis C infection (or, less often, B-cell lymphoproliferative disorder)
  • Nephritic urine with MPGN pattern; low C4 with relatively preserved C3
  • Cold-triggered symptoms: Raynaud, acrocyanosis, livedo
Diagnose
  1. 1Cryoglobulins — draw and keep sample WARM (37°C) to prevent precipitation; repeat if low suspicion
  2. 2HCV serology + RNA; consider HBV and HIV screening
  3. 3Complements — characteristically low C4, often low-normal C3; rheumatoid factor positive
  4. 4Renal biopsy — MPGN pattern with intracapillary immune deposits ("wire-loop" / hyaline thrombi)
  5. 5Assess for B-cell clonality (serum free light chains, SPEP/IFE) given lymphoma overlap
Manage
  • Antiviral therapy for HCV (DAAs) — first-line for HCV-driven cryoglobulinemia
  • Immunosuppression for severe organ involvement: steroids + rituximab (± cyclophosphamide)
  • Plasmapheresis for life-threatening vasculitis, RPGN, or severe neuropathy
  • Treat B-cell lymphoproliferative overlap; monitor renal function and cryocrit
  • Supportive care: analgesia for neuropathy, skin care, and avoidance of cold exposure
Type II mixed cryoglobulinemia is usually HCV-driven — palpable purpura + low C4 + MPGN pattern; keep the blood sample warm and treat the underlying infection.
MPGN / C3 Glomerulopathy
MPGN · C3G
Recognize
  • Mixed nephritic–nephrotic picture — hematuria + edema + sub-nephrotic to nephrotic proteinuria
  • Persistent low complement (C3 and/or C4) that fails to normalize after infection
  • Association with HCV, HBV, cryoglobulinemia, SLE, or monoclonal gammopathy
Diagnose
  1. 1Complements: low C3+C4 → immune-complex MPGN (HCV, cryo, lupus); low C3 with normal C4 → C3 glomerulopathy (C3G)
  2. 2Serologies: HCV RNA, HBV, cryoglobulins, ANA/dsDNA, SPEP/IFE + serum free light chains
  3. 3Renal biopsy — "tram-track" double-contour GBM on light; IF/EM separates immune-complex vs complement-mediated
  4. 4C3 nephritic factor / anti-FH antibodies if C3G suspected; genetic complement panel in recurrent or familial disease
Manage
  • Treat the underlying cause — HCV antivirals, HBV therapy, lupus immunosuppression, or monoclonal gammopathy management
  • Immune-complex MPGN: mycophenolate + steroids for idiopathic/progressive disease; rituximab for monoclonal
  • C3 glomerulopathy: eculizumab or investigational complement inhibitors; ACEi/ARB for proteinuria
  • ACEi/ARB for proteinuria and hypertension; statin for nephrotic hyperlipidemia
  • Monitor for progression to ESRD; consider transplant (recurrence risk, especially C3G)
MPGN is now reclassified by etiology — immune-complex (low C3+C4, infection/autoimmune) vs complement-mediated C3 glomerulopathy (low C3, normal C4); biopsy IF/EM and the complement pattern drive the workup.
Membranous Nephropathy
MGN / PLA2R
Recognize
  • Most common cause of nephrotic syndrome in adults (peak 40–60 years)
  • Insidious edema, nephrotic-range proteinuria, hypoalbuminemia, hyperlipidemia
  • Risk of venous thromboembolism (renal vein thrombosis); often primary (PLA2R) or secondary (malignancy, drugs, lupus, HBV)
Diagnose
  1. 1Urinalysis: nephrotic proteinuria, bland sediment; quantify proteinuria (uPCR or 24-h)
  2. 2Anti-PLA2R antibody — highly specific for primary membranous; monitor titer for disease activity
  3. 3Serologies: HBV, HCV, ANA/dsDNA, complements (usually normal); age-appropriate cancer screening for secondary causes
  4. 4Renal biopsy — subepithelial immune deposits with "spike-and-dome" on silver stain; IgG4-dominant granular IF
Manage
  • Conservative: ACEi/ARB for proteinuria, statin for hyperlipidemia, anticoagulation for high thrombotic risk (albumin < 2.5 g/dL)
  • Immunosuppression for high risk: cyclophosphamide + steroids (Ponticelli) or calcineurin inhibitor + steroids
  • Rituximab for primary membranous with persistent nephrotic proteinuria or relapse
  • Treat secondary cause — malignancy workup, stop offending drug, antivirals for HBV, lupus therapy
  • Monitor anti-PLA2R titers, proteinuria, and renal function; ~one-third achieve spontaneous remission
Anti-PLA2R antibody is both diagnostic and a biomarker of activity — a persistently positive titer predicts relapse and guides immunosuppressive decisions.
Minimal Change Disease
MCD
Recognize
  • Most common cause of nephrotic syndrome in children (peak 2–6 years); adults ~10–15%
  • Sudden-onset severe edema, nephrotic-range proteinuria, hypoalbuminemia
  • Selective proteinuria; normal renal function (or AKI in older adults); normal complements
Diagnose
  1. 1Urinalysis: nephrotic-range proteinuria, oval fat bodies / lipiduria; bland sediment
  2. 2In children, presumptive diagnosis — biopsy reserved for atypical features (hematuria, hypertension, low C3, non-response)
  3. 3Serologies: normal C3/C4; rule out secondary causes (Hodgkin lymphoma, NSAIDs, allergy)
  4. 4Renal biopsy — normal light microscopy; diffuse foot-process effacement on electron microscopy
Manage
  • First-line: high-dose oral prednisone 1 mg/kg/day (60 mg adult cap) for 4–16 weeks until remission, then taper
  • Calcineurin inhibitor (cyclosporine/tacrolimus) or mycophenolate for frequently relapsing / steroid-dependent disease
  • Rituximab for steroid-dependent / frequently relapsing disease refractory to CNI
  • ACEi/ARB for proteinuria; salt restriction, diuretics for edema; statin for hyperlipidemia
  • Monitor for relapse (~80% of children relapse), steroid toxicity, and infection risk (encapsulated organisms)
MCD is exquisitely steroid-responsive — a child with classic nephrotic syndrome is treated empirically; lack of response within 4 weeks should trigger biopsy and a search for an alternative diagnosis.
Focal Segmental Glomerulosclerosis
FSGS
Recognize
  • Nephrotic-range proteinuria in adolescents or young adults; often steroid-resistant
  • Associations: HIV (collapsing variant), heroin use, sickle cell, obesity, reduced nephron mass, genetic/familial
  • Hypertension, microscopic hematuria, and progressive decline in GFR
Diagnose
  1. 1Urinalysis: nephrotic-range proteinuria ± microscopic hematuria; bland sediment
  2. 2Serologies: HIV, HBV/HCV; complements normal; consider genetic testing (APOL1 in at-risk populations)
  3. 3Renal biopsy — segmental sclerosis and hyalinosis in a subset of glomeruli; Columbia variant (collapsing, tip, cellular, perihilar, NOS) informs prognosis
  4. 4Distinguish primary (circulating permeability factor) from secondary / genetic / adaptive FSGS — drives therapy
Manage
  • Primary FSGS: high-dose steroids for ≥4 months; calcineurin inhibitor or mycophenolate for steroid-resistant disease
  • Secondary FSGS: treat the underlying cause (HIV, obesity, reduced nephron mass) — immunosuppression generally not indicated
  • ACEi/ARB for proteinuria and hypertension; statin; salt restriction and diuretics for edema
  • Rituximab or plasmapheresis for recurrent FSGS after transplant
  • Monitor proteinuria, BP, and GFR; high recurrence risk post-transplant (especially primary FSGS)
Distinguishing primary from secondary FSGS is critical — primary disease needs immunosuppression, while secondary FSGS responds to treating the underlying cause and optimizing RAAS blockade.
References & Further Reading
  1. 01KDIGO Clinical Practice Guideline for Acute Kidney Injury — Kidney International Supplements (2012)
  2. 02KDIGO Acute Kidney Injury Guideline — Update Public Review Draft — KDIGO (2024)
  3. 03Acute Disease Quality Initiative (ADQI) consensus on AKI — Mehta RL et al., Nephron (2016)
  4. 04Acute kidney injury — definition and classification (RIFLE) — Ronco C, Bellomo R, Kellum JA, Crit Care (2002)
  5. 05Hepatorenal syndrome in cirrhosis — ADQI & critical care consensus — Nadim MK et al., Hepatology (2024)
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