Renal & Urinary

Nephritic syndrome: workup and differential

Clinical Overview and When to Suspect Nephritic Syndrome

— Distinguished from nephrotic syndrome by inflammatory glomerular injury (endocapillary or crescentic) rather than podocyte effacement

— Severity spectrum: asymptomatic glomerular hematuria → classic acute nephritic syndrome → rapidly progressive glomerulonephritis (RPGN) with doubling of creatinine over days–weeks

— New AKI + active urine sediment (dysmorphic RBCs, RBC casts) in any adult

— Cola/tea-colored urine, periorbital edema, and HTN, especially in a child 1–3 weeks post-pharyngitis or 3–6 weeks post-impetigo

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

— Palpable purpura + abdominal pain + arthralgia + hematuria → IgA vasculitis (HSP)

— Recurrent gross hematuria within 1–2 days of URI in a young adult → IgA nephropathy

— Sinus disease, otitis, saddle nose, pulmonary nodules → GPA

— Asthma + eosinophilia + mononeuritis → EGPA

— Any patient with hematuria + proteinuria + HTN + rising Cr needs same-day labs and urgent nephrology consultation; do not wait weeks

— RPGN is a renal emergency—delay risks irreversible loss of nephrons within 1–2 weeks

Board pearl: The single most specific urinary finding for glomerular bleeding is the RBC cast; dysmorphic RBCs (especially acanthocytes >5%) strongly support glomerular origin over urologic bleeding.

Definition: Nephritic syndrome = glomerular inflammation producing the pentad of hematuria (often with RBC casts/dysmorphic RBCs), proteinuria (usually sub-nephrotic <3.5 g/day), hypertension, edema, and acute kidney injury (rising creatinine, oliguria)

When to suspect on Step 3:

Initial outpatient triage:

Step 3 management: When you see RBC casts on UA, immediately order complement levels (C3/C4), ANA, ANCA, anti-GBM, ASO/anti-DNase B, hepatitis B/C, HIV, cryoglobulins, and arrange biopsy planning before empirically treating.

Presentation Patterns and Key History

— Sudden tea/cola/smoky urine, facial/periorbital edema worse in the morning, new HTN, decreased urine output

— Often preceded by an antigenic trigger (infection, drug, autoimmune flare)

— Post-streptococcal GN (PSGN): child age 4–12, latency 1–3 weeks after pharyngitis or 3–6 weeks after skin infection (impetigo); resolving by the time GN appears

— IgA nephropathy: young adult male, synpharyngitic hematuria (within 1–5 days of URI, no latency); recurrent episodes

— IgA vasculitis (HSP): child <10, palpable lower-extremity purpura, colicky abdominal pain, arthritis, hematuria; often post-URI

— Lupus nephritis: young woman, malar rash, arthralgias, oral ulcers, cytopenias, serositis; class III/IV present nephritic

— Anti-GBM disease: bimodal (young men, older women), pulmonary–renal syndrome with hemoptysis; smokers/hydrocarbon exposure

— ANCA vasculitis (GPA, MPA, EGPA): older adult with constitutional symptoms for weeks, sinusitis, hemoptysis, foot drop, palpable purpura

— Cryoglobulinemic GN: HCV infection, palpable purpura, arthralgia, neuropathy, low C4

— Endocarditis-associated GN: IVDU or prosthetic valve, fever, new murmur, embolic phenomena

— MPGN: chronic infections (HCV, HBV, endocarditis), monoclonal gammopathy, complement dysregulation

— Recent infections (throat, skin, GI, GU, dental); travel; IVDU; sexual history

— Drugs: hydralazine, propylthiouracil, levamisole-cut cocaine (drug-induced ANCA)

— Family history of hematuria/deafness → Alport syndrome; benign familial hematuria → thin basement membrane

— Hemoptysis, sinus symptoms, rashes, joint pains, neurologic deficits

Key distinction: PSGN has a latent period (urine clears before kidneys flare); IgA nephropathy is synpharyngitic (hematuria coincides with URI). Mistaking one for the other is the most-tested historical pitfall.

Classic acute nephritic syndrome:

Pattern-based history clues (high-yield mapping):

Essential history checklist:

Physical Exam Findings and Hemodynamic Assessment

— Hypertension (often moderate-severe; can be hypertensive emergency in children with PSGN)

— Volume overload: periorbital and pretibial edema, weight gain, JVD, pulmonary crackles, S3 gallop

— Document orthostatics, daily weights, strict I/Os—volume status drives diuretic and antihypertensive decisions

— Skin:

— Palpable purpura on legs/buttocks → IgA vasculitis, cryoglobulinemia, ANCA vasculitis

— Malar rash, discoid lesions, oral ulcers → SLE

— Splinter hemorrhages, Janeway lesions, Osler nodes → infective endocarditis

— Livedo reticularis → polyarteritis nodosa, cryoglobulinemia, APS

— ENT:

— Saddle-nose deformity, nasal crusting, otitis media, subglottic stenosis → GPA

— Allergic rhinitis, nasal polyps → EGPA

— Pulmonary:

— Hemoptysis + bibasilar crackles → anti-GBM or ANCA pulmonary–renal syndrome

— Wheezing, late-onset asthma → EGPA

— Musculoskeletal/Neuro:

— Symmetric small-joint arthritis → SLE

— Migratory arthritis → IgA vasculitis, endocarditis

— Mononeuritis multiplex (foot drop, wrist drop) → polyarteritis nodosa, EGPA, MPA

— Eyes/ears: scleritis, episcleritis (GPA); sensorineural hearing loss + lenticonus → Alport

— Cardiac: new regurgitant murmur → endocarditis-associated GN

CCS pearl: On the CCS interface, order vital signs, weight, I/Os, full skin/ENT/lung/cardiac/neuro exam on initial visit. Recheck BP and weight daily during admission and at every follow-up; missing escalating HTN or progressive volume overload costs points and reflects real-world deterioration of nephritic patients.

Volume and hemodynamic exam:

Systemic clues that pin the differential:

Fundoscopy: look for hypertensive retinopathy in severe HTN; Roth spots in endocarditis

Diagnostic Workup — Initial Labs, Urine, and Imaging

— Dipstick: blood 2–3+, protein 1–3+

— Microscopy: dysmorphic RBCs, acanthocytes, RBC casts, granular casts; WBC casts suggest interstitial nephritis or lupus

— Spot urine protein:creatinine ratio—nephritic typically <3.5 g/g; if >3.5 consider mixed nephritic/nephrotic (lupus class IV, MPGN, severe IgA)

— BMP: ↑ Cr, ↑ K, ↑ BUN; calculate eGFR and trend daily

— CBC: anemia (chronic disease, hemolysis in TMA/lupus), thrombocytopenia (lupus, TMA)

— Albumin, LFTs (HBV/HCV screening prep)

— Trend creatinine every 24–48 hours—doubling over days defines RPGN

— Complement: C3, C4, CH50

— ANA, anti-dsDNA, anti-Smith; ANCA (PR3, MPO); anti-GBM antibody

— ASO and anti-DNase B titers

— Hepatitis B surface Ag/Ab/core; HCV Ab with reflex RNA; HIV

— Cryoglobulins (transport warm), rheumatoid factor (often + in cryo)

— SPEP/UPEP/free light chains if older adult or MPGN pattern

— Low C3, normal C4 → PSGN, MPGN type II (C3 glomerulopathy), endocarditis-associated GN

— Low C3 AND low C4 → SLE, cryoglobulinemic GN, MPGN type I, shunt nephritis

— Normal complements → IgA nephropathy, IgA vasculitis, anti-GBM, ANCA vasculitis (pauci-immune)

— Renal ultrasound: assess kidney size, echogenicity, hydronephrosis; rule out obstruction; confirm two kidneys before biopsy

— CXR for pulmonary–renal syndrome; CT chest if hemoptysis or nodules suspected

Board pearl: Complement pattern + ANCA/anti-GBM status narrows the differential to 2–3 entities before biopsy. Memorize the C3/C4 grid—it is the highest-yield 30 seconds of nephritic syndrome studying.

Urinalysis with microscopy (the single most important test):

Blood chemistry and CBC:

Serologic panel (order all up front to avoid delay):

Complement-based differential framework:

Imaging:

Diagnostic Workup — Renal Biopsy and Confirmatory Studies

— Indications: adult with acute nephritic syndrome, suspected RPGN, lupus nephritis classification, persistent unexplained hematuria + proteinuria, transplant dysfunction

— Defer biopsy in classic pediatric PSGN with typical course (resolves spontaneously) unless atypical features

— Control BP <140/90, correct coagulopathy, hold antiplatelets/anticoagulants per protocol, confirm two kidneys, type and screen, informed consent including ~1–2% major bleeding risk

— Post-biopsy: 4–6 hours flat bed rest, serial vitals, hemoglobin check

— PSGN: diffuse proliferative GN, subepithelial "humps" on EM, granular IgG/C3 ("starry sky")

— IgA nephropathy / IgAV: mesangial proliferation, dominant mesangial IgA on IF

— Lupus nephritis: "full house" IF (IgG, IgM, IgA, C3, C4); subendothelial deposits ("wire loops") in class IV; tubuloreticular inclusions on EM

— Anti-GBM: linear IgG along GBM; crescents

— ANCA vasculitis: pauci-immune (scant/no immune deposits), necrotizing crescentic GN

— MPGN: mesangial and endocapillary proliferation, double-contour/"tram-track" GBM; type I subendothelial (Ig + complement), C3 glomerulopathy (C3 only)

— Cryoglobulinemic GN: MPGN pattern with intraluminal pseudothrombi

— Type I: anti-GBM (linear IF)

— Type II: immune-complex (granular IF; lupus, IgA, PSGN, MPGN)

— Type III: pauci-immune (ANCA)

Step 3 management: In an adult with RPGN, start empiric pulse methylprednisolone while awaiting biopsy if anti-GBM or ANCA is clinically likely—delay of even 1 week worsens dialysis-free survival. Document shared decision-making.

Renal biopsy is the gold standard in adult nephritic syndrome with AKI, RPGN, or unclear etiology

Pre-biopsy checklist:

Biopsy pattern recognition (light + IF + EM):

Crescents (>50% of glomeruli) = RPGN, classified:

Risk Stratification and Initial Management Logic

— Indolent hematuria/proteinuria, stable Cr → outpatient nephrology within 1–2 weeks

— Acute nephritic syndrome with rising Cr → admit, daily labs, expedite biopsy

— RPGN (Cr doubling in days, oliguria, hemoptysis) → ICU-level monitoring, urgent biopsy + empiric immunosuppression

— Pulmonary hemorrhage, neurologic deficits, mesenteric ischemia → ICU + plasmapheresis consideration

— Skin/joint only → ward-level care

— Volume: loop diuretic (furosemide IV 40–80 mg) for edema/HTN; salt restriction <2 g/day; fluid restriction if hyponatremic

— Blood pressure: target <140/90 (lower in proteinuria); ACEi/ARB once Cr stable and K acceptable (avoid acutely if rising Cr or hyperkalemia)

— Hyperkalemia: dietary K restriction, loop diuretic, patiromer/SZC if persistent; emergent treatment if K >6.5 or ECG changes

— Acidosis: sodium bicarb if HCO3 <22

— Anemia/uremia management as KDIGO

— Hold nephrotoxins: NSAIDs, contrast, aminoglycosides; renally dose all meds

— Acidosis refractory, Electrolytes (K >6.5 refractory), Intoxication, Overload refractory to diuresis, Uremia (pericarditis, encephalopathy, bleeding)

— Suspected anti-GBM or ANCA with pulmonary hemorrhage → plasmapheresis + pulse steroids + cyclophosphamide or rituximab

— Lupus class III/IV → induction with mycophenolate or cyclophosphamide + steroids

— PSGN → supportive (BP, diuretics, treat residual infection)

CCS pearl: Document a clear management problem list ("AKI 2/2 RPGN, HTN urgency, hyperkalemia, volume overload") and re-evaluate every 24 hours; advance to dialysis or biopsy on the day criteria are met.

Triage axis 1 — tempo of injury:

Triage axis 2 — extrarenal involvement:

Initial bundle for all nephritic patients (CCS order set):

Indications for urgent dialysis (AEIOU):

Etiology-driven escalation:

Pharmacotherapy — First-Line Regimens by Etiology

— Supportive only: loop diuretics, antihypertensives (CCB or loop initially; ACEi after Cr stable)

— Penicillin/amoxicillin to eradicate residual streptococcal carriage

— No role for steroids in typical PSGN

— ACEi or ARB first-line for any proteinuria >0.5–1 g/day, titrate to max tolerated dose

— SGLT2 inhibitor (dapagliflozin, empagliflozin) added if proteinuria persists and eGFR ≥20

— If proteinuria >0.75–1 g/day after 3 months of optimized supportive care and high risk → targeted-release budesonide (Nefecon) or systemic glucocorticoids per KDIGO 2024

— IgAV with crescentic disease → steroids ± cyclophosphamide

— Induction: high-dose glucocorticoids + mycophenolate mofetil (2–3 g/day) OR low-dose IV cyclophosphamide (Euro-Lupus)

— Add belimumab or voclosporin for refractory or high-activity disease

— Maintenance: MMF 1–2 g/day or azathioprine; hydroxychloroquine in all SLE patients

— Induction: pulse methylprednisolone 500–1000 mg × 3 days → oral prednisone taper PLUS rituximab (preferred, especially relapsing/young/fertility concerns) OR cyclophosphamide

— Add avacopan (C5a receptor antagonist) to reduce steroid exposure

— Plasmapheresis considered for severe pulmonary hemorrhage or Cr >5.7/dialysis-dependent (PEXIVAS individualization)

— Maintenance: rituximab every 6 months × 18–24 months or azathioprine

— Daily plasmapheresis × 14 days + pulse steroids → oral prednisone + cyclophosphamide

— Do NOT start immunosuppression if dialysis-dependent AND no pulmonary hemorrhage AND 100% crescents (futile)—but treat lung disease regardless

Board pearl: Hydroxychloroquine is mandatory in all lupus nephritis unless contraindicated—it reduces flares, thrombosis, and renal progression. Forgetting it is a classic miss.

Post-streptococcal GN:

IgA nephropathy / IgA vasculitis:

Lupus nephritis (class III/IV ± V):

ANCA-associated vasculitis (GPA, MPA, EGPA):

Anti-GBM (Goodpasture) disease:

Procedures, Plasmapheresis, and Advanced Therapeutics

— Strong indication: anti-GBM disease (daily until anti-GBM negative, ~14 sessions)

— Selective indication in ANCA: severe alveolar hemorrhage or Cr >5.7/dialysis-requiring (PEXIVAS showed no mortality benefit but may aid renal recovery in selected patients)

— Cryoglobulinemic vasculitis with severe organ involvement

— Replacement: fresh frozen plasma if active bleeding/pre-biopsy; otherwise 5% albumin

— Monitor for citrate-induced hypocalcemia, hypotension, coagulopathy, line infection

— Real-time ultrasound–guided percutaneous, lower pole of left kidney typical

— Adequate sample: ≥10 glomeruli for light, with IF and EM

— Bleeding complications: 1–2% major (transfusion, embolization, nephrectomy); hold antiplatelets, correct INR <1.5, platelets >50–75k, BP <140/90

— Acute: IHD, CRRT for hemodynamically unstable

— If progression likely → place tunneled catheter early, refer for AV fistula creation 6 months before anticipated need

— Discuss transplant evaluation early in anti-GBM (wait until anti-GBM undetectable ≥6 months) and ANCA (wait until remission ≥6 months)

— PJP prophylaxis (TMP-SMX) for patients on cyclophosphamide or high-dose steroids

— Osteoporosis prophylaxis (Ca, vitamin D, bisphosphonate per FRAX) for sustained steroid use

— Vaccinations before immunosuppression: influenza, pneumococcal, HBV, shingles (recombinant), COVID-19; avoid live vaccines once immunosuppressed

— Gonadal protection with cyclophosphamide: leuprolide in women, sperm banking in men; track cumulative dose to limit malignancy/infertility

Step 3 management: Before initiating cyclophosphamide or rituximab, screen and treat latent TB, hepatitis B, hepatitis C, and HIV; check pregnancy test; counsel contraception; update vaccines. Omitting HBV screening risks fulminant reactivation—classic safety vignette.

Plasmapheresis (therapeutic plasma exchange, TPE):

Renal biopsy procedure pearls:

Renal replacement therapy planning:

Adjunct pharmacotherapy:

Special Populations — Elderly and Renal/Hepatic Impairment

— ANCA-associated vasculitis is the #1 cause of RPGN in older adults—low threshold to send MPO/PR3

— Presentations are atypical: fatigue, weight loss, low-grade fever mistaken for malignancy or chronic infection

— Higher baseline CKD, polypharmacy, frailty—biopsy still indicated but weigh bleeding risk

— Drug-induced ANCA: hydralazine (older HTN patients), propylthiouracil, minocycline—discontinue offending agent, often only partial reversal

— Reduce cyclophosphamide dose by 25–50% in age >60 or eGFR <30; prefer rituximab to minimize bone marrow/bladder toxicity

— Lower target steroid dose; faster taper per PEXIVAS (reduced-dose glucocorticoid arm noninferior, fewer infections)

— Aggressive infection prophylaxis (PJP, antifungal in some) because infection mortality exceeds disease mortality in elderly induction

— MMF: no renal adjustment but watch GI toxicity and cytopenias

— Cyclophosphamide: reduce dose if eGFR <30; ensure mesna and hydration to prevent hemorrhagic cystitis

— Avacopan: hepatotoxicity—monitor LFTs at baseline, q4 weeks × 6 months

— ACEi/ARB: acceptable if Cr rise <30% and K manageable; hold if AKI worsening

— HBV reactivation with rituximab or cyclophosphamide can be fatal—screen HBsAg, anti-HBc; entecavir or tenofovir prophylaxis for any positive marker

— HCV-associated cryoglobulinemic GN: treat HCV with direct-acting antivirals first; add rituximab ± plasmapheresis for severe vasculitis

Key distinction: In elderly RPGN, think ANCA first, anti-GBM second; in young adults with pulmonary–renal syndrome, anti-GBM and lupus rise on the differential.

Elderly nephritic patients (>65):

Immunosuppression dosing in elderly:

Renal impairment dosing pearls:

Hepatic impairment / hepatitis:

Special Populations — Pregnancy, Pediatrics, and Demographic Subgroups

— Distinguish preeclampsia (HTN + proteinuria after 20 weeks, no hematuria/RBC casts, normal complements) from lupus nephritis flare (active sediment, hypocomplementemia, ↑ dsDNA, extrarenal lupus features)

— Continue hydroxychloroquine throughout pregnancy in SLE—reduces flare and neonatal lupus

— Safe immunosuppression: azathioprine, tacrolimus, low-dose prednisone, hydroxychloroquine

— Contraindicated: mycophenolate (teratogenic—stop ≥6 weeks before conception), cyclophosphamide (first trimester), methotrexate, ACEi/ARB (all trimesters)

— Plan pregnancy during ≥6 months of remission with stable renal function

— PSGN is the prototype: child 4–12 with cola urine, periorbital edema, HTN 1–3 weeks post-pharyngitis; supportive management, full recovery >95%, no biopsy unless atypical (persistent low C3 >8 weeks, nephrotic-range proteinuria, RPGN)

— IgA vasculitis (HSP): most common childhood vasculitis; renal involvement in 30–50%; biopsy if nephrotic-range proteinuria or impaired GFR; treat with steroids ± immunosuppression for crescentic disease

— Alport syndrome: X-linked, persistent hematuria + sensorineural hearing loss + lenticonus; family history; ACEi delays progression

— Childhood lupus nephritis tends to be more severe and class IV-predominant

— APOL1 high-risk variants (African ancestry): faster progression in lupus nephritis, HIV-associated nephropathy, FSGS

— Asian/Pacific Islander patients: higher IgA nephropathy prevalence and progression

— Pregnant women with prior lupus nephritis have ↑ risk of preeclampsia—aspirin 81 mg from 12 weeks

Board pearl: A pregnant woman at 30 weeks with HTN, proteinuria, active sediment with RBC casts, and low C3/C4 is a lupus nephritis flare, not preeclampsia—give pulse steroids and azathioprine, not magnesium and delivery alone.

Pregnancy:

Pediatric nephritic syndrome:

Demographic associations:

Complications and Adverse Outcomes

— Hypertensive emergency: PRES, encephalopathy, seizures, retinopathy—especially in pediatric PSGN; treat with IV labetalol or nicardipine, target gradual reduction (~25% in first hour)

— Pulmonary edema from volume overload: IV loop diuretics, NIV, ultrafiltration if refractory

— Hyperkalemia with arrhythmia: calcium gluconate, insulin/dextrose, β-agonist, loop diuretic, dialysis

— Uremic complications: pericarditis (friction rub, effusion, tamponade risk), encephalopathy, platelet dysfunction → dialysis indication

— Anti-GBM: diffuse alveolar hemorrhage—mortality 10–20%; ARDS-level care

— ANCA vasculitis: subglottic stenosis, sensorineural deafness, mononeuritis multiplex, bowel infarction

— Lupus nephritis: thrombotic microangiopathy, antiphospholipid syndrome thromboses, infection from immunosuppression

— PSGN: rarely RPGN in adults; adult PSGN has worse prognosis than pediatric, with 25–60% CKD long-term

— IgA nephropathy: 20–40% reach ESKD over 20 years; risk stratify with MEST-C score and International IgAN Prediction Tool

— Cyclophosphamide: hemorrhagic cystitis (mesna + hydration), bladder cancer (lifetime cystoscopy surveillance), infertility, myelosuppression, MDS/leukemia

— Rituximab: infusion reactions, hypogammaglobulinemia, PML (rare), HBV reactivation

— MMF: GI intolerance, leukopenia, teratogenicity (REMS program)

— Glucocorticoids: infection, hyperglycemia, osteoporosis, AVN of hip, cataracts, weight gain, mood changes

— Plasmapheresis: citrate toxicity (paresthesias, tetany), line infection, hypogammaglobulinemia, coagulopathy

Key distinction: Adult PSGN ≠ benign pediatric PSGN. Adults frequently develop chronic glomerular scarring, especially with comorbid diabetes, alcoholism, or obesity. Counsel on long-term nephrology follow-up.

Acute complications:

Disease-specific complications:

Treatment-related adverse events:

Long-term: progression to CKD, ESKD, cardiovascular disease (the leading cause of death in CKD), increased infection and malignancy risk

When to Escalate — ICU, Consult, and Inpatient Triage

— Diffuse alveolar hemorrhage (hemoptysis, dropping Hb, infiltrates, hypoxemia)—intubate early

— Hypertensive emergency with end-organ damage (encephalopathy, PRES, ACS, pulmonary edema)

— Refractory hyperkalemia or acidosis pending emergent dialysis

— Anuria with rapidly rising Cr requiring CRRT

— Severe sepsis from immunosuppression

— Nephrology: every nephritic syndrome patient—same day if AKI, RPGN features, or biopsy needed

— Rheumatology: lupus, ANCA vasculitis, IgA vasculitis with systemic features

— Pulmonology: pulmonary–renal syndromes

— ENT: GPA with sinonasal disease, subglottic stenosis

— Ophthalmology: scleritis (GPA), uveitis, retinopathy

— ID: prior to immunosuppression if any chronic infection suspected

— Apheresis service for plasmapheresis logistics

— Admit if: AKI (Cr ↑ >0.3 mg/dL), uncontrolled HTN, volume overload, electrolyte derangement, RPGN suspicion, systemic vasculitis with active organ involvement, need for biopsy

— Outpatient if: stable Cr, isolated microscopic hematuria/mild proteinuria, controlled BP, no systemic symptoms—still arrange nephrology within 1–2 weeks

— Vitals q4h, daily weight, strict I/Os, BMP daily (BID if K/Cr labile), UA each morning, BP log

— Reassess volume status and adjust diuretic; titrate antihypertensives

— Review serology results, schedule biopsy, plan immunosuppression timing

— Update goals of care, discharge planning, immunosuppression teaching

CCS pearl: When the case is pulmonary–renal syndrome, simultaneously order anti-GBM, ANCA, biopsy, plasmapheresis consult, methylprednisolone 1 g IV, and ICU bed in parallel—not sequentially. Step 3 rewards parallel processing of emergent workups.

Immediate ICU admission criteria:

Mandatory consultations:

Inpatient vs outpatient triage:

Daily inpatient checklist (CCS rhythm):

Key Differentials — Glomerular (Same-Category) Causes

— PSGN: child, latent period after strep, transient low C3 normalizing in 6–8 weeks, granular IF, subepithelial humps; supportive care

— Infective endocarditis–associated GN: fever, murmur, blood cultures, IVDU history; treat infection, complements normalize

— Shunt nephritis: infected VP shunt or AV graft

— MPGN type I (immune-complex): HCV + cryoglobulins, HBV, SLE, monoclonal gammopathy; tram-track GBM, subendothelial deposits

— C3 glomerulopathy / dense deposit disease: complement alternative pathway dysregulation (C3 nephritic factor, factor H deficiency); isolated low C3, persistent

— IgA nephropathy: synpharyngitic hematuria, mesangial IgA; KDIGO risk stratification, RAAS + SGLT2i + targeted-release budesonide

— IgA vasculitis (HSP): systemic IgA with purpura, arthritis, abdominal pain

— Anti-GBM disease: linear IgG, pulmonary–renal syndrome, plasmapheresis + immunosuppression

— ANCA-associated GN: pauci-immune crescentic GN; GPA (PR3), MPA (MPO), EGPA (MPO, eosinophilia, asthma)

— Alport syndrome: hereditary, basement membrane "basket-weave"

— Thin basement membrane disease: benign familial hematuria, isolated hematuria

— Lupus nephritis: classified ISN/RPS I–VI; class III/IV nephritic; full-house IF, dsDNA, low C3/C4

— Cryoglobulinemic GN: HCV most common; palpable purpura, neuropathy, low C4 disproportionate to C3

— Low C3 that normalizes within 8 weeks → PSGN; persistently low → MPGN/C3 glomerulopathy/lupus

— Both crescentic and nephrotic features in young woman → think class IV lupus

— Recurrent gross hematuria with infections → IgA nephropathy

Board pearl: Anti-GBM titer can be transiently negative early; if clinical picture fits and biopsy shows linear IgG, treat. Don't wait for serology to start plasmapheresis in pulmonary hemorrhage.

Low-C3 nephritic syndromes:

Normal-complement nephritic syndromes:

Mixed / both-low-complement:

Differentiating pearls:

Key Differentials — Non-Glomerular Causes of Hematuria/AKI

— Bladder/renal/upper-tract urothelial cancer—smokers, age >35, painless gross hematuria → CT urography + cystoscopy

— Nephrolithiasis—flank pain, NCCT

— UTI/cystitis—pyuria, dysuria, positive culture

— BPH, trauma, schistosomiasis

— Acute interstitial nephritis (AIN): drug-induced (PPIs, NSAIDs, β-lactams, sulfa, allopurinol, ICIs), fever/rash/eosinophilia, WBC casts, eosinophiluria (low sensitivity), mild proteinuria, no RBC casts; stop drug ± steroids

— Pyelonephritis: WBC casts, fevers, flank pain

— Renal artery thrombosis/embolism, renal vein thrombosis (especially in nephrotic syndrome)

— Atheroembolic disease: after vascular procedure, livedo reticularis, blue toes, eosinophilia, low complement transiently

— Malignant hypertension: schistocytes, AKI, retinopathy

— Thrombotic microangiopathy (TMA): HUS, TTP, scleroderma renal crisis, APS, drug-induced—thrombocytopenia + MAHA + AKI; no RBC casts typically, but schistocytes; ADAMTS13, complement panel

— Volume depletion, hepatorenal, cardiorenal

— Acute tubular necrosis—muddy brown casts, FENa >2%

— Rhabdomyolysis—dipstick blood positive but no RBCs, CK markedly elevated, myoglobinuria

— Multiple myeloma (cast nephropathy)—older patient, anemia, hypercalcemia, bone pain; SPEP/UPEP, free light chains

— Amyloidosis—nephrotic predominantly

Key distinction: TMA and nephritic syndrome can both present with AKI and hematuria, but TMA has thrombocytopenia + schistocytes + LDH elevation without RBC casts. Always check a smear and platelet count before reflexively starting steroids.

Mimics of nephritic syndrome to exclude on Step 3:

Urologic hematuria (no RBC casts, no proteinuria, isodense RBCs):

Tubulointerstitial disease:

Vascular:

Prerenal and intrinsic mimics:

Systemic mimics:

Secondary Prevention, Discharge Medications, and Long-Term Plan

— ACEi or ARB titrated to maximum tolerated dose for proteinuria and BP control; recheck BMP 1–2 weeks after each dose change

— SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg) for proteinuric CKD with eGFR ≥20

— Statin for CKD-associated cardiovascular risk (most CKD G3–G5 not on dialysis qualify)

— Diuretic if volume overload; antihypertensives to BP target <130/80 per KDIGO 2021

— Disease-specific immunosuppression with clear taper plan

— PJP prophylaxis (TMP-SMX SS daily) while on cyclophosphamide or high-dose steroids

— Vitamin D, calcium, bisphosphonate if sustained steroid use ≥3 months at ≥7.5 mg/day

— HBV antiviral prophylaxis for any HBV serology positivity with B-cell depletion or cytotoxic therapy

— Aspirin 81 mg if established ASCVD or high cardiovascular risk

— Sodium <2 g/day; protein moderate (0.6–0.8 g/kg/day in CKD without dialysis)

— Tobacco cessation (accelerates renal progression in anti-GBM and others)

— Weight management; aerobic exercise as tolerated

— Hydration without overload

— NSAID avoidance

— Annual influenza, pneumococcal (PCV20 or PCV15+PPSV23), recombinant zoster (>50), COVID-19 updated, hepatitis B series; meningococcal if eculizumab/avacopan considerations

— Avoid live vaccines (MMR, varicella, yellow fever, live zoster, intranasal flu) while immunosuppressed

— Lupus nephritis: continue hydroxychloroquine indefinitely + maintenance MMF/azathioprine 3–5 years

— ANCA: rituximab 500 mg every 6 months × 18–24 months

— Anti-GBM: limited duration immunosuppression (6–9 months), low recurrence

— IgA: continue RAAS + SGLT2i lifelong; reassess proteinuria

Step 3 management: Always discharge with a clear plan for who follows up, when, and what labs to check—this is heavily tested under "transitions of care."

Discharge medication bundle (most nephritic patients):

Lifestyle and dietary counseling:

Vaccination plan:

Disease-specific maintenance:

Follow-Up, Monitoring, and Patient Counseling

— Nephrology visit within 1–2 weeks post-discharge with BMP, UA, UPCR, CBC

— Monthly visits during active immunosuppression induction; every 2–3 months during maintenance

— Rheumatology in parallel for SLE/vasculitis

— MMF: CBC and LFTs every 2 weeks × 1 month, then monthly × 3 months, then every 3 months

— Cyclophosphamide: CBC weekly during induction; UA each cycle for microhematuria (bladder toxicity); cumulative dose tracking

— Rituximab: CD19/CD20 B-cell counts, IgG levels, HBV markers

— Avacopan: LFTs baseline, monthly × 6 months

— Voclosporin: BP, eGFR, K every 2 weeks initially

— Steroids: glucose, BP, weight, DEXA at 6–12 months, eye exam annually

— UPCR or 24-hour urine protein every 1–3 months

— Spot urine sediment for ongoing hematuria/RBC casts

— Lupus: dsDNA, C3/C4 every 1–3 months

— ANCA titers every 3 months (rising titer predicts but does not mandate treatment of relapse)

— Anti-GBM titer to confirm undetectable before transplant

— Home BP monitoring with diary; target <130/80

— Daily weight, report >2 kg gain in 3 days

— Sick-day rules: hold ACEi/ARB, diuretics, SGLT2i, metformin during severe illness with poor PO intake

— Infection precautions: report fever >38°C promptly; PJP/CMV awareness

— Contraception counseling on teratogens (MMF, cyclophosphamide); pre-pregnancy planning

— Mental health screening—chronic illness depression rate is high

Board pearl: A rising ANCA titer or recurrent hematuria/proteinuria after remission warrants intensified surveillance but not automatic re-treatment—decisions are based on clinical relapse evidence, not serology alone.

Post-discharge cadence:

Monitoring parameters per drug:

Disease activity tracking:

Patient counseling and self-management:

Ethical, Legal, and Patient Safety Considerations

— Disclose 1–2% major bleeding risk, transfusion, embolization, nephrectomy, very rare death

— Confirm capacity; use teach-back; provide interpreter for limited English proficiency

— Document refusal carefully if patient declines, including alternatives (empiric treatment) and risks of delay

— Discuss infertility risk with cyclophosphamide; offer sperm banking (men) or leuprolide ovarian protection (women) before initiation—failure to offer is a malpractice exposure

— Discuss malignancy risk (bladder cancer, MDS, lymphoma)

— Document teratogenicity for MMF (REMS-required counseling) and cyclophosphamide; document contraception plan for reproductive-age patients

— Discharge summary must include: active diagnoses, immunosuppression regimen with taper schedule, prophylactic medications, follow-up appointments with specific dates, pending labs/biopsy results, medication reconciliation, and explicit instructions for whom to call

— High-risk handoff: rituximab-treated patient with positive HBcAb missing tenofovir/entecavir → fatal hepatitis reactivation; this is a sentinel-event scenario

— Confirm patient has access and ability to obtain expensive biologics (avacopan, voclosporin, belimumab); prior authorization failure is a major adherence pitfall

— Streptococcal outbreaks (cluster PSGN) → notify public health

— Suspected occupational hydrocarbon exposure in anti-GBM → OSHA reporting per state

— Newly diagnosed hepatitis B or C, HIV → state reporting

— Dialysis-dependent elderly anti-GBM with no pulmonary disease: discuss futility of immunosuppression, focus on dialysis/comfort

— Advance directives in dialysis initiation, withdrawal of dialysis—palliative care consult

— APOL1 testing and disparities; ensure access to biologics across insurance tiers; document social determinants

Step 3 management: Before initiating rituximab, document HBV screening, vaccination review, contraception counseling, and TB screening—omission is the single most common safety failure in vasculitis cases.

Informed consent for renal biopsy:

Informed consent for immunosuppression:

Transitions of care (Step 3 favorite):

Mandatory reporting and public health:

Shared decision-making in advanced disease:

Equity considerations:

High-Yield Associations and Rapid-Fire Facts

— PSGN after pharyngitis: 1–3 weeks

— PSGN after impetigo: 3–6 weeks

— IgA nephropathy after URI: 1–5 days (synpharyngitic)

— Low C3 only → PSGN, MPGN II/C3GP, endocarditis

— Low C3 + Low C4 → SLE, cryoglobulinemia, MPGN I, shunt nephritis

— Normal complements → IgA, IgAV, anti-GBM, ANCA, Alport

— Linear IgG on IF → anti-GBM

— Pauci-immune crescentic GN → ANCA vasculitis

— Full-house IF, wire loops → lupus nephritis

— Subepithelial humps → PSGN

— Mesangial IgA → IgA nephropathy

— Tram-track GBM → MPGN

— Basket-weave GBM, hearing loss → Alport

— Palpable purpura + abdominal pain + arthritis + nephritis in child → IgA vasculitis

— Saddle nose + cavitary lung lesions + GN → GPA (PR3-ANCA)

— Asthma + eosinophilia + neuropathy + GN → EGPA

— HCV + palpable purpura + low C4 + GN → cryoglobulinemic MPGN

— Smoker + hemoptysis + AKI → anti-GBM (Goodpasture)

— Hydralazine, propylthiouracil, minocycline, levamisole-cocaine → drug-induced ANCA

— Procainamide, hydralazine → drug-induced lupus (rarely nephritic)

— Plasmapheresis: always for anti-GBM, selective for severe ANCA, for cryoglobulinemic vasculitis

— Hydroxychloroquine: always in lupus

— Rituximab: preferred ANCA induction in young/fertility/relapsing

— Avacopan: steroid-sparing in ANCA

— Voclosporin or belimumab: refractory lupus nephritis

— PSGN in kids: >95% full recovery

— Adult PSGN: 25–60% develop CKD

— IgA nephropathy: 20–40% ESKD by 20 years

— Anti-GBM dialysis-dependent at presentation: poor renal recovery

Board pearl: The most common cause of glomerulonephritis worldwide is IgA nephropathy; the most common cause of nephritic syndrome in children remains PSGN; the most common cause of RPGN in adults >60 is ANCA-associated vasculitis.

Latency periods (memorize):

Complement-based 30-second algorithm:

Buzzword → disease:

Drug triggers:

Treatment-defining facts:

Prognosis:

Board Question Stem Patterns

— 7-year-old with cola-colored urine, periorbital edema, HTN 165/100, 2 weeks after sore throat; low C3, normal C4, ASO elevated

— Best next step: supportive care (loop diuretic, BP control); do not biopsy; expect C3 normalization in 6–8 weeks

— Trap: choosing steroids or antibiotics for active GN; trap: missing the latency (synpharyngitic = IgA, not PSGN)

— 22-year-old man, gross hematuria 1 day after URI, recurrent episodes, normal C3/C4, mild proteinuria

— Best next step: ACEi + BP control; biopsy if proteinuria persists; SGLT2i; budesonide if high-risk

— 28-year-old smoker, hemoptysis, AKI, linear IgG on biopsy

— Diagnosis: anti-GBM (Goodpasture); treatment: plasmapheresis + steroids + cyclophosphamide

— 72-year-old with weight loss, sinusitis, foot drop, hematuria, Cr rising 0.8 → 4.2 over 3 weeks; PR3-ANCA positive; pauci-immune crescentic GN

— Treatment: pulse methylprednisolone + rituximab + avacopan; consider plasmapheresis if severe pulmonary hemorrhage

— 24-year-old, malar rash, arthritis, hematuria, 4 g/day proteinuria, low C3/C4, anti-dsDNA, full-house IF with wire loops → class IV lupus nephritis

— Treatment: steroids + MMF + hydroxychloroquine; add belimumab or voclosporin if high activity

— Palpable purpura, neuropathy, low C4 disproportionate to C3, HCV positive, MPGN on biopsy → treat HCV with DAAs first, add rituximab if severe

— 30 weeks pregnant with HTN, proteinuria, RBC casts, low complements → lupus nephritis flare, not preeclampsia

— Patient discharged on rituximab without HBV screening → fulminant HBV reactivation; tested as patient safety question

Key distinction: Read the timing, latency, and complement pattern first—they pre-diagnose the case before you reach the biopsy line.

Stem 1 — Pediatric PSGN:

Stem 2 — Young adult IgA nephropathy:

Stem 3 — Pulmonary–renal syndrome:

Stem 4 — Elderly RPGN:

Stem 5 — Young woman with lupus nephritis:

Stem 6 — HCV cryoglobulinemia:

Stem 7 — Pregnancy distinction:

Stem 8 — Safety/transitions:

One-Line Recap

Nephritic syndrome is glomerular inflammation presenting with hematuria, RBC casts, sub-nephrotic proteinuria, hypertension, edema, and AKI—diagnosed through a complement-anchored serologic algorithm (C3/C4, ANA, ANCA, anti-GBM, hepatitis, cryoglobulins) plus renal biopsy, with management tailored to etiology and tempo (supportive for PSGN; RAAS+SGLT2i±budesonide for IgA; steroids+MMF/cyclophosphamide+hydroxychloroquine for lupus; rituximab+steroids±avacopan±plasmapheresis for ANCA; plasmapheresis+steroids+cyclophosphamide for anti-GBM), with RPGN treated as a renal emergency.

Board pearl: When you see hematuria + RBC casts + AKI, your first three orders are complement levels, ANCA/anti-GBM, and nephrology consult—everything else flows from there.

Diagnostic anchor: RBC casts + dysmorphic RBCs + sub-nephrotic proteinuria + AKI define the syndrome; complement pattern narrows the differential to 2–3 diseases in seconds

Tempo drives urgency: Stable chronic findings → outpatient nephrology; rising Cr over days–weeks = RPGN → admit, biopsy, and start empiric immunosuppression for likely anti-GBM or ANCA without waiting for full serologies

Treatment is etiology-specific, not generic: PSGN supportive; IgA RAAS + SGLT2i + targeted budesonide; lupus needs MMF + lifelong hydroxychloroquine; ANCA needs rituximab + avacopan; anti-GBM needs plasmapheresis

Safety nets that win Step 3 points: HBV/TB screening before immunosuppression, contraception and fertility counseling with cyclophosphamide/MMF, vaccinations before B-cell depletion, BP <130/80, ACEi + SGLT2i for proteinuria, structured 1–2 week post-discharge nephrology follow-up