Eduovisual
Renal & Urinary
Minimal change disease and FSGS: management
— Most common cause of nephrotic syndrome in children (~90% age <10)
— Accounts for ~10–15% of adult primary nephrotic syndrome
— Abrupt onset of edema; often follows URI, immunization, NSAID use, or atopy
— Secondary triggers: NSAIDs, lithium, IFN, Hodgkin lymphoma
— Most common cause of primary nephrotic syndrome in US adults, especially Black patients (APOL1 risk alleles)
— More indolent onset, often with subnephrotic proteinuria, HTN, microscopic hematuria, and renal insufficiency
— Primary (circulating permeability factor, suPAR hypothesis) vs secondary (adaptive)
— Secondary causes: HIV (collapsing variant), heroin, pamidronate, anabolic steroids, obesity, reflux nephropathy, reduced nephron mass, sickle cell
— Child with periorbital edema, frothy urine, normal BP, normal complement → MCD
— Adult (often Black) with HTN, edema, rising Cr, heavy proteinuria → FSGS
— Nephrotic-range proteinuria + recent bisphosphonate or anabolic steroid → secondary FSGS
— New nephrotic syndrome in untreated HIV → collapsing FSGS
Board pearl: MCD and FSGS share diffuse foot process effacement on EM and a podocytopathy mechanism — they may even represent a disease spectrum, but FSGS uniquely shows segmental sclerosis on LM and is far more likely to progress to ESRD.
Step 3 management: First clinical decisions for any nephrotic adult are (1) quantify proteinuria (spot UPCR or 24-hr), (2) rule out secondary causes (HBV, HCV, HIV, ANA, SPEP/UPEP, DM, lupus serologies), (3) decide on kidney biopsy — adults almost always need it; children with classic features get empiric steroids first.
— Periorbital edema worse in morning, dependent edema by evening
— Rapid weight gain (often 5–15 kg) over days to weeks
— Frothy/foamy urine from heavy proteinuria
— Tight rings, shoes; scrotal/labial edema; anasarca in severe cases
— Toddler/young child with sudden edema after viral illness → MCD
— Adolescent or young adult Black male with HTN and lower-extremity edema → FSGS
— Adult >40 with new nephrotic syndrome → biopsy is mandatory; MCD still possible but membranous and FSGS more common
— NSAIDs → MCD ± interstitial nephritis
— Lithium, IFN-α, pamidronate → FSGS (collapsing for IFN/pamidronate)
— Heroin, anabolic steroids → FSGS
— Hodgkin lymphoma → paraneoplastic MCD
— HIV without ART → collapsing FSGS (HIVAN)
— Flank/abdominal pain, gross hematuria → renal vein thrombosis (more classic for membranous but possible)
— Pleuritic chest pain, dyspnea → PE from hypercoagulable state
— Fever, abdominal pain in a child with ascites → spontaneous bacterial peritonitis (encapsulated organisms, esp. S. pneumoniae)
— Foamy urine + arthralgias/rash → think secondary glomerular disease (lupus, cryos)
— FSGS in multiple relatives → hereditary podocytopathy (NPHS1/nephrin, NPHS2/podocin, INF2, TRPC6, APOL1)
Key distinction: MCD presents with selective albuminuria, preserved GFR, normal BP, normal complement, and a brisk steroid response. FSGS shows nonselective proteinuria, HTN, microscopic hematuria, reduced GFR, and frequent steroid resistance.
Board pearl: A child with steroid-resistant nephrotic syndrome should prompt genetic testing for podocin (NPHS2) mutations before escalating immunosuppression — genetic FSGS does not respond to steroids and avoids unnecessary toxicity.
— Pale, puffy facies; periorbital edema often the earliest sign
— Weight gain documented against baseline (critical in pediatrics)
— Pitting edema: pretibial, sacral (in bedbound), scrotal/labial
— Ascites with shifting dullness and fluid wave
— Pleural effusions: dullness to percussion, decreased breath sounds at bases
— JVP variable — most nephrotic patients are intravascularly volume depleted despite total-body overload (especially MCD)
— MCD child: normal or low BP, possible orthostasis from hypovolemia
— FSGS adult: hypertension in >50%, often the presenting feature
— Tachycardia + cool extremities + oliguria in a heavily edematous child → impending nephrotic crisis/AKI from underfilling
— Xanthelasma, eruptive xanthomas (severe hyperlipidemia)
— Muehrcke lines (paired white transverse nail bands from hypoalbuminemia)
— Striae from rapid edema
— Crackles if effusions or volume overload coexists
— Friction rub uncommon unless uremic in advanced FSGS
— Tense ascites; check for rebound/guarding → SBP in nephrotic children
— Unilateral leg swelling out of proportion → DVT
— Sudden flank pain + hematuria → renal vein thrombosis
— Pleuritic pain, hypoxia → PE
Step 3 management: Resist the urge to aggressively diurese a nephrotic patient with cool extremities, low BP, and rising Cr — this is intravascular underfilling. Order 20–25% albumin infusion followed by IV furosemide to mobilize edema safely. Daily weights, strict I/Os, and orthostatic vitals guide therapy.
Board pearl: A nephrotic child with abdominal pain, fever, and ascites needs diagnostic paracentesis — SBP from Strep pneumoniae is the classic complication and pneumococcal vaccination plus prompt cefotaxime are the answers.
— Spot urine protein-to-creatinine ratio (UPCR) >3–3.5 mg/mg = nephrotic-range
— 24-hour urine collection: gold standard for quantification
— Urinalysis: 3–4+ protein, oval fat bodies, fatty casts, "Maltese cross" under polarized light
— Hematuria: minimal in MCD; microscopic hematuria in ~50% of FSGS
— Serum creatinine, BUN, eGFR
— MCD: usually normal Cr; transient AKI possible
— FSGS: often elevated Cr at presentation
— Hyponatremia (dilutional), hyperkalemia if AKI, low bicarb if advanced
— Albumin typically <3.0 g/dL, often <2.0 in MCD
— Total cholesterol and LDL markedly elevated
— Hypertriglyceridemia
— HIV (collapsing FSGS), HBV/HCV (membranous/MPGN, but screen)
— ANA, anti-dsDNA, C3/C4 — normal complements in MCD and primary FSGS; low C3/C4 suggests lupus, MPGN, cryos, post-infectious
— SPEP/UPEP, serum free light chains in adults >40 (rule out myeloma, amyloid, MIDD)
— HbA1c (diabetic nephropathy)
— RPR/syphilis if membranous suspected
— ASO if recent strep
— CBC: hemoconcentration possible
— Hypercoagulable state from urinary loss of antithrombin III; consider baseline PT/INR
— Renal ultrasound: normal-sized or enlarged echogenic kidneys; rules out obstruction
— Doppler if RVT suspected
CCS pearl: Order set for new nephrotic adult — CBC, BMP, LFTs, albumin, lipid panel, UA with microscopy, spot UPCR, HIV, HBsAg/anti-HCV, ANA, C3/C4, SPEP/UPEP with immunofixation, HbA1c, renal ultrasound, and nephrology consult for biopsy.
Board pearl: Selectivity index (clearance of IgG/transferrin) is rarely tested directly, but remember MCD = selective (albumin only); FSGS = nonselective (larger proteins lost) — this correlates with steroid responsiveness.
— All adults with new nephrotic syndrome (unless clear diabetic nephropathy with classic course)
— Children: biopsy is NOT required before empiric steroids if classic features (age 1–10, normal BP, normal Cr, normal complements, no hematuria)
— Biopsy children who are steroid-resistant, frequently relapsing, or atypical (age <1 or >12, HTN, hematuria, low C3, elevated Cr)
— Light microscopy: normal glomeruli
— Immunofluorescence: negative (occasionally faint mesangial IgM)
— Electron microscopy: diffuse podocyte foot process effacement — the defining finding
— LM: segmental sclerosis in <50% of glomeruli (focal); sampling error possible
— IF: nonspecific IgM and C3 in sclerotic segments
— EM: foot process effacement (diffuse in primary; segmental in secondary/adaptive)
— Collapsing: worst prognosis; HIV, IFN, pamidronate, APOL1
— Tip lesion: best prognosis; often steroid-responsive
— Cellular, perihilar, NOS (not otherwise specified)
— Primary: diffuse foot process effacement (>80%), full nephrotic syndrome
— Secondary/adaptive: segmental effacement, subnephrotic proteinuria, preserved albumin, glomerulomegaly (obesity-related)
— APOL1 genotyping in patients of African ancestry with FSGS to inform prognosis and transplant donor counseling
— Genetic panel (NPHS1, NPHS2, WT1, INF2, TRPC6) for steroid-resistant pediatric or familial cases
Key distinction: MCD biopsy looks normal on LM and IF — the diagnosis is made by EM showing foot process effacement combined with steroid response. FSGS shows segmental sclerosis on LM, and the variant predicts treatment response and prognosis.
Step 3 management: Do NOT immunosuppress secondary/adaptive FSGS (obesity, reflux, reduced renal mass) — treat with ACEi/ARB, weight loss, BP control; steroids will not work and will cause harm.
— Induce complete remission (proteinuria <0.3 g/day, normal albumin) or partial remission (proteinuria <3.5 g/day with 50% reduction)
— Preserve renal function
— Prevent complications: thromboembolism, infection, AKI, dyslipidemia
— ACE inhibitor or ARB for antiproteinuric and renoprotective effect — start unless contraindicated
— Sodium restriction (<2 g/day)
— Loop diuretic (furosemide, often high-dose due to albumin binding loss) for edema; add metolazone if resistant
— Statin for nephrotic dyslipidemia if persistent
— Anticoagulation considered if albumin <2.0–2.5 g/dL (especially membranous; less aggressive in MCD/FSGS) or VTE event
— Vaccinations: pneumococcal (PCV15/20 + PPSV23), influenza, varicella if seronegative — before immunosuppression
— First episode: high-dose oral prednisone is the cornerstone
— >85% of children and ~75% of adults achieve remission, though adults respond more slowly (8–16 weeks)
— Primary FSGS (diffuse foot process effacement, full nephrotic syndrome) → immunosuppression (high-dose prednisone first-line)
— Secondary/adaptive FSGS → ACEi/ARB, weight loss, treat underlying cause; NO steroids
— Genetic FSGS → supportive only; consider transplant (low recurrence)
— HIV-associated (collapsing) → start ART, add ACEi; steroids controversial
— Steroid-sensitive: remission within 4 (children) to 16 (adults) weeks
— Steroid-dependent: relapse during taper or within 2 weeks of stopping
— Frequently relapsing: ≥2 relapses in 6 months or ≥4 in 12 months
— Steroid-resistant: no remission after adequate trial
Board pearl: Before starting steroids, screen and treat latent TB, check hepatitis serologies, update vaccinations, and check glucose. Step 3 loves the question stem where a patient is started on immunosuppression and later reactivates TB or HBV.
Step 3 management: In primary FSGS, an adequate steroid trial = prednisone 1 mg/kg/day (max 80 mg) for up to 16 weeks before declaring steroid resistance — failure to wait this long is a common board trap.
— Children: prednisone/prednisolone 60 mg/m² (max 60 mg) daily × 4–6 weeks, then 40 mg/m² every other day × 4–6 weeks, then taper over 2–5 months
— Adults: prednisone 1 mg/kg/day (max 80 mg) daily or 2 mg/kg every other day × up to 16 weeks until remission, then slow taper over 6 months total
— Expect remission in 8–16 weeks in adults (slower than children)
— Prednisone 1 mg/kg/day (max 80 mg) for minimum 4 weeks up to 16 weeks until remission, then taper over 6 months
— Alternate-day dosing 2 mg/kg (max 120 mg) acceptable
— ACEi (lisinopril) or ARB (losartan) titrated to maximum tolerated dose; reduces proteinuria 30–50%
— Monitor K+ and Cr — a rise in Cr up to 30% is acceptable
— Avoid in pregnancy
— Furosemide PO, often doubled dose vs nonnephrotic patients due to urinary loss and reduced albumin-binding delivery
— Add metolazone 30 min before furosemide for diuretic resistance
— IV albumin 25% (1 g/kg) followed by IV furosemide for severe, refractory edema with intravascular underfilling
— Target gentle diuresis: 0.5–1 kg/day in adults, less in children
— Statin (atorvastatin or rosuvastatin) if dyslipidemia persists beyond remission attempt
— Consider prophylactic anticoagulation if serum albumin <2.0–2.5 g/dL, prior VTE, or additional risk factors
— Warfarin or LMWH preferred; DOAC data limited in heavy proteinuria
— Pneumococcal vaccination before immunosuppression
— PJP prophylaxis (TMP-SMX) considered for prolonged high-dose steroids or combination immunosuppression
Board pearl: In a nephrotic child with anasarca, albumin + IV furosemide is the right answer when oral diuretics fail or the child is hypovolemic — never aggressive loop diuretics alone.
CCS pearl: Set daily weights, strict I/Os, BMP every other day, UPCR weekly, blood pressure logs, and counsel on low-sodium diet as standing orders for any nephrotic patient on steroids.
— Steroid-resistant disease
— Frequently relapsing or steroid-dependent disease
— Steroid toxicity (uncontrolled DM, osteoporosis, weight gain, psychiatric)
— Contraindication to steroids
— Cyclosporine 3–5 mg/kg/day or tacrolimus 0.05–0.1 mg/kg/day divided BID
— First-line for steroid-resistant FSGS (per KDIGO) — continue for 6–12 months if response
— Monitor trough levels, Cr, BP, glucose; nephrotoxicity is the main long-term concern
— Tacrolimus → diabetogenic; cyclosporine → gum hyperplasia, hirsutism
— Oral 2 mg/kg/day for 8–12 weeks
— Used for frequently relapsing/steroid-dependent MCD (especially adults)
— Toxicities: hemorrhagic cystitis (give mesna with IV dosing), infertility, bone marrow suppression, secondary malignancy
— 750–1000 mg BID (adults); alternative steroid-sparing agent
— Useful in patients who relapse on CNIs or cannot tolerate cyclophosphamide
— GI upset, leukopenia; teratogenic — pregnancy contraindicated
— Anti-CD20 monoclonal; increasingly used for frequently relapsing/steroid-dependent MCD and some FSGS
— Particularly favored in children to avoid cumulative steroid/cyclophosphamide toxicity
— Risks: infusion reactions, hypogammaglobulinemia, JC virus/PML (rare)
— Sparsentan (dual endothelin-A/ARB antagonist) — FDA-approved for primary FSGS proteinuria reduction
— SGLT2 inhibitors (dapagliflozin) — emerging role for proteinuric CKD including FSGS
— ART is the cornerstone; add ACEi/ARB
— Steroids reserved for selected cases
— Calcium + vitamin D, bisphosphonate if prolonged ≥3 months at ≥7.5 mg/day
— PPI if GI risk; glucose monitoring
Step 3 management: For steroid-resistant FSGS, the next-line answer on Step 3 is a calcineurin inhibitor (cyclosporine or tacrolimus) — not cyclophosphamide. For steroid-dependent/frequently relapsing MCD, cyclophosphamide, CNIs, MMF, or rituximab are all acceptable; pick based on side-effect profile.
— Always biopsy — broader differential includes membranous (paraneoplastic), amyloidosis, MGUS-related disease, diabetic nephropathy
— MCD in elderly often associated with NSAIDs or hematologic malignancy (Hodgkin, leukemia) — search aggressively
— AKI more common at presentation; recovery slower
— Same weight-based induction (1 mg/kg/day) but cap at 60–80 mg
— Higher risk of: hyperglycemia → screen and treat steroid-induced diabetes, osteoporosis → DEXA + bisphosphonate, cataracts, infection, psychiatric effects, GI bleed
— Co-prescribe calcium + vitamin D, PPI if NSAID use or PUD history
— Slower taper often needed; remission may take longer
— ACEi/ARB still indicated, but watch for hyperkalemia and Cr rise >30%
— Diuretic dose increases needed as GFR falls; switch furosemide → torsemide or bumetanide for better bioavailability
— Avoid NSAIDs absolutely
— Adjust cyclophosphamide for CrCl <30 (reduce by 25–50%)
— Adjust MMF for GFR <25 (limited data; reduce dose)
— CNIs: monitor troughs more frequently
— Steroids generally safe but monitor glucose
— Cyclophosphamide metabolized hepatically — dose reduce in severe dysfunction
— Tacrolimus and cyclosporine hepatically metabolized — reduce dose and monitor troughs
— Screen HBV/HCV before immunosuppression; HBV reactivation prophylaxis with entecavir or tenofovir if HBsAg+ or anti-HBc+
— Discuss risk/benefit of immunosuppression vs symptomatic management in patients with limited life expectancy
— Conservative kidney management with ACEi/ARB, diuretics, statin may be appropriate
Board pearl: New nephrotic syndrome in an elderly patient with weight loss, night sweats, and lymphadenopathy → think MCD as paraneoplastic from Hodgkin lymphoma — order chest/abdomen imaging and consider lymph node biopsy.
Step 3 management: Before starting any prolonged steroid course, order HbA1c, DEXA scan in those >65 or postmenopausal, HBV/HCV/HIV/TB screening, and vaccinations.
— Empiric steroids without biopsy in classic presentation (age 1–10, no HTN, no hematuria, normal Cr, normal C3/C4)
— First episode: prednisolone 60 mg/m² × 4–6 weeks, then 40 mg/m² alternate days × 4–6 weeks
— Most relapse at least once; frequent relapsers/steroid-dependent → levamisole (where available), cyclophosphamide, CNIs, MMF, or rituximab
— Growth monitoring critical; minimize cumulative steroid exposure
— Vaccinate before immunosuppression; live vaccines contraindicated during therapy
— Steroid-resistant nephrotic syndrome in children → biopsy + genetic testing (NPHS1, NPHS2, WT1, INF2)
— Genetic forms: no response to immunosuppression; manage with ACEi/ARB and prepare for ESRD/transplant — low recurrence after transplant
— Non-genetic primary FSGS in children: CNI is the next step
— Contraindicated meds: ACEi, ARB, MMF, cyclophosphamide, sparsentan
— Permitted: prednisone (safe), azathioprine, tacrolimus, cyclosporine, hydroxychloroquine
— Stop ACEi/ARB pre-conception; switch antihypertensives to labetalol, nifedipine, methyldopa
— Prepregnancy counseling: aim for remission ≥6 months before conception
— Pregnancy increases risk of relapse, preeclampsia, IUGR, preterm delivery, VTE
— Distinguish nephrotic relapse from preeclampsia — preeclampsia features new HTN + proteinuria + features after 20 weeks
— Anticoagulation: LMWH if indicated (avoid warfarin in first trimester and near delivery)
— Primary FSGS has up to 30–40% recurrence post-transplant, often within hours-days
— Treat recurrence with plasmapheresis ± rituximab
— Genetic FSGS — very low recurrence; counsel donors accordingly
— APOL1 high-risk donors confer worse graft outcomes
Board pearl: A pregnant woman on MMF or ACEi for FSGS must be switched before conception — MMF causes facial clefts and ear malformations; ACEi/ARBs cause oligohydramnios, renal dysgenesis, and skull hypoplasia.
Key distinction: Genetic FSGS does not recur after transplant because the mutation is in the native kidney podocyte; primary FSGS frequently recurs due to circulating permeability factor.
— DVT, PE, renal vein thrombosis, cerebral sinus thrombosis (especially pediatric)
— Mechanism: urinary loss of antithrombin III, protein S; increased platelet activation; hemoconcentration
— Risk highest when serum albumin <2.0–2.5 g/dL
— Consider prophylactic anticoagulation in selected patients
— Spontaneous bacterial peritonitis — encapsulated organisms, particularly Streptococcus pneumoniae; classic in nephrotic children with ascites
— Cellulitis from edematous tissue
— Urinary loss of IgG and complement → functional immunodeficiency
— Immunosuppression compounds risk: opportunistic infections, reactivation TB/HBV
— Prerenal from over-diuresis or intravascular underfilling
— Interstitial nephritis from NSAIDs or diuretics
— Bilateral renal vein thrombosis
— Direct tubular injury from heavy proteinuria
— Chronic nephrotic syndrome → accelerated CV disease; statin warranted if persistent
— Cushingoid features, weight gain, hyperglycemia/new DM, osteoporosis, avascular necrosis (femoral head), cataracts, glaucoma, growth suppression in children, mood/psychiatric effects, infection
— Cyclophosphamide: cystitis, infertility, malignancy
— CNIs: nephrotoxicity, HTN, diabetogenicity, neurotoxicity, gingival hyperplasia
— Rituximab: hypogammaglobulinemia, PML
— MCD: rare; usually steroid-responsive with preserved renal function
— FSGS: ~50% progress to ESRD over 5–10 years if untreated or steroid-resistant
— Collapsing variant: ESRD often within months
— Hyponatremia (dilutional)
— Vitamin D deficiency (urinary loss of vitamin D-binding protein)
— Hypothyroidism (loss of thyroxine-binding globulin) — usually subclinical
— Iron deficiency from transferrin loss
Board pearl: A child with nephrotic syndrome who develops sudden flank pain, gross hematuria, and unilateral kidney enlargement needs CT or MR venography for renal vein thrombosis and anticoagulation.
Step 3 management: Treat suspected SBP in nephrotic child with paracentesis and IV cefotaxime or ceftriaxone empirically pending cultures.
— Stable vitals, manageable edema, normal or near-normal Cr, tolerating PO
— No signs of infection or thromboembolism
— Family/patient able to monitor weights, BP, and symptoms
— Severe anasarca with respiratory compromise (large pleural effusions) or scrotal/labial edema causing pain
— AKI (Cr rise >30% or oliguria)
— Signs of intravascular volume depletion (orthostasis, prerenal azotemia)
— Thromboembolic event — DVT, PE, RVT
— Infection — SBP, pneumonia, cellulitis with bacteremia
— Failure to respond to outpatient diuretics
— Need for IV albumin + furosemide therapy
— Severe electrolyte disturbance
— Need for kidney biopsy with anticoagulation reversal or comorbidities
— Massive PE with hemodynamic compromise
— Respiratory failure from large effusions or pulmonary edema
— Septic shock from SBP or bacteremia
— Severe AKI requiring urgent dialysis
— Nephrology: every adult nephrotic patient; pediatric nephrology for all children
— Hematology: for thrombotic complications, anticoagulation planning, or workup of paraneoplastic MCD (Hodgkin lymphoma)
— Infectious disease: HIV-associated FSGS, reactivation TB/HBV, opportunistic infections during immunosuppression
— Interventional radiology: kidney biopsy, IVC filter if anticoagulation contraindicated and PE present
— Transplant nephrology: progressive FSGS approaching ESRD; counsel re: recurrence
— Genetics: pediatric steroid-resistant FSGS, familial cases
— Endocrinology: steroid-induced diabetes or osteoporosis management
— Discharge plan: clear taper schedule, follow-up labs in 1–2 weeks, sick-day rules (stress-dose steroids), weight and BP diary, dietary counseling, vaccination plan, contact for relapse symptoms
CCS pearl: Don't forget to schedule nephrology follow-up within 1–2 weeks of discharge, recheck UPCR and BMP, and document medication reconciliation — Step 3 transitions-of-care vignettes punish missed follow-up.
Board pearl: A nephrotic patient with sudden dyspnea and hypoxia → CT pulmonary angiogram, NOT just D-dimer (D-dimer always elevated); anticoagulate empirically while imaging.
— Most common cause of primary nephrotic syndrome in older White adults
— Anti-PLA2R antibody (~70% of primary cases) — diagnostic and prognostic
— LM: thickened GBM with "spike and dome" on silver stain
— IF: granular subepithelial IgG and C3
— Highest risk of thromboembolism (renal vein thrombosis classic)
— Often secondary to hepatitis B, lupus, solid tumors (colon, lung), NSAIDs, gold, penicillamine
— Management: ACEi/ARB; immunosuppression (rituximab first-line per KDIGO) if high-risk
— Mixed nephritic/nephrotic picture
— Low C3 (and often C4)
— Secondary causes: HCV + cryoglobulinemia, lupus, monoclonal gammopathies, chronic infections
— Tram-track GBM on LM; subendothelial deposits
— Typically nephritic (hematuria, mild proteinuria), but heavy proteinuria possible
— Synpharyngitic gross hematuria within 1–2 days of URI
— IF: dominant mesangial IgA
— Most common cause of nephrotic-range proteinuria overall in US adults
— Long-standing DM, retinopathy, gradual proteinuria progression
— Biopsy not always required; Kimmelstiel-Wilson nodules if obtained
— Treat with ACEi/ARB, SGLT2 inhibitors, glycemic control, BP control
— Older adults; nephrotic syndrome + organ involvement (cardiac, neuropathy, macroglossia in AL)
— Congo red apple-green birefringence
— AL: clonal plasma cell — order SPEP/UPEP, free light chains
— AA: chronic inflammatory disease
— Multisystem features, positive ANA/dsDNA, low complements
Key distinction: Normal complements + nephrotic syndrome → MCD, primary FSGS, membranous, diabetic nephropathy, amyloid. Low complements + nephrotic features → lupus, MPGN, post-infectious GN, cryoglobulinemia, endocarditis. This single dichotomy unlocks half of Step 3 nephrology vignettes.
Board pearl: Anti-PLA2R positivity in an adult nephrotic patient is essentially diagnostic of primary membranous nephropathy and can sometimes preclude biopsy if low-risk for malignancy.
— Microalbuminuria → macroalbuminuria over years
— Concurrent retinopathy supports diagnosis
— Atypical features (sudden onset, hematuria, no retinopathy) → biopsy to rule out alternative
— Untreated HIV; APOL1 high-risk genotype
— Collapsing FSGS with tubular microcysts on biopsy
— Heavy proteinuria, rapid decline to ESRD
— Treat with ART, ACEi
— HBV: membranous nephropathy (children), MPGN
— HCV: MPGN with mixed cryoglobulinemia
— Treat underlying viral disease first
— NSAIDs: MCD ± AIN
— Pamidronate, IFN-α: collapsing FSGS
— Lithium: FSGS, nephrogenic DI, chronic interstitial nephritis
— Heroin, anabolic steroids: FSGS
— Gold, penicillamine, captopril: membranous (historical)
— Anti-VEGF agents (bevacizumab): TMA, proteinuria
— Hodgkin lymphoma → MCD (classic association)
— Solid tumors (lung, colon, prostate) → membranous
— CLL → membranous or MPGN
— Multiple myeloma → cast nephropathy, AL amyloid, MIDD
— BMI typically >35
— Adaptive FSGS variant; subnephrotic proteinuria; preserved albumin
— Treat with weight loss, ACEi/ARB, SGLT2i — not steroids
— History of recurrent childhood UTIs, single kidney, or remote nephrectomy
— Secondary FSGS — supportive care only
— Secondary FSGS; hyperfiltration injury
— Hydroxyurea, ACEi/ARB
— New HTN + proteinuria after 20 weeks
— Distinguish from underlying glomerular relapse
Step 3 management: A man with BMI 42, subnephrotic proteinuria (2 g/day), preserved albumin (3.8 g/dL), and segmental sclerosis on biopsy has obesity-related FSGS — answer is weight loss, ACEi/ARB, SGLT2 inhibitor, NOT prednisone.
Board pearl: Always pair the FSGS variant with the cause — collapsing = HIV, IFN, pamidronate, APOL1; tip lesion = best prognosis, steroid-responsive; perihilar = adaptive (obesity, reflux).
— Slow prednisone taper over total 5–6 months (longer for FSGS than MCD)
— Continue ACEi/ARB indefinitely if any residual proteinuria or HTN
— Maintain BP <130/80 (KDIGO target for proteinuric CKD)
— Continue statin if persistent hyperlipidemia
— Stop prophylactic anticoagulation once albumin >2.5–3.0 g/dL and remission achieved
— Single relapse: repeat prednisone induction
— Frequently relapsing or steroid-dependent: add steroid-sparing agent (cyclophosphamide, CNI, MMF, or rituximab)
— Long-term goal: cumulative steroid minimization
— If complete remission: taper steroids, continue ACEi/ARB
— If partial remission or relapse: maintain CNI for 12–24 months then attempt taper
— If steroid-resistant: CNI ± MMF, sparsentan, SGLT2i
— Monitor for progression to CKD/ESRD; refer to transplant evaluation at eGFR <30
— Prednisone with written taper
— ACEi or ARB
— Loop diuretic with sodium-restriction counseling
— Statin if indicated
— Calcium 1200 mg + vitamin D 800 IU; bisphosphonate if prolonged steroids
— PPI if GI risk
— Anticoagulation if indicated
— PJP prophylaxis (TMP-SMX) if combination immunosuppression or high-dose steroids prolonged
— Vaccinations completed: pneumococcal (PCV15/20 + PPSV23 8 weeks later), annual influenza, COVID, HBV if seronegative
— Sodium <2 g/day, fluid restriction if hyponatremic
— Weight loss if BMI elevated (especially adaptive FSGS)
— Smoking cessation
— Avoid nephrotoxins: NSAIDs, IV contrast when avoidable, herbal supplements
— Limit live vaccines during immunosuppression; family members can receive most live vaccines except oral polio
— Patients on chronic steroids: stress-dose steroids during major illness, surgery, trauma
— Withhold ACEi/ARB and diuretics if vomiting/diarrhea/dehydrated
Board pearl: A patient stopping chronic steroids abruptly may develop adrenal insufficiency — always taper, and educate on stress dosing and medical alert identification.
Step 3 management: Vaccinate before starting immunosuppression whenever possible; if already immunosuppressed, give inactivated vaccines but defer live vaccines (MMR, varicella, zoster live, yellow fever) until off therapy for ≥1 month.
— Initial: every 1–2 weeks after diagnosis until remission
— Post-remission: monthly × 3–6 months, then every 3 months × 1 year, then every 6 months
— More frequent during steroid taper or relapse
— BP (target <130/80)
— Weight (home log daily during edema)
— UPCR or first-morning urine dipstick for proteinuria
— BMP (creatinine, electrolytes, especially K+ on ACEi/ARB)
— Serum albumin
— Lipid panel every 6–12 months
— HbA1c in patients on steroids — at least every 3 months
— Bone density every 1–2 years if chronic steroids
— Teach patients/parents to dipstick first-morning urine at home
— 3+ or 4+ protein on 3 consecutive days = relapse, prompt call
— Daily weight log during flares
— Adherence to taper schedule — premature taper drives relapse
— Recognize and report: increasing edema, weight gain >2 kg, decreased urine output, fever, abdominal pain, leg swelling/redness, chest pain/dyspnea
— Medication safety: avoid NSAIDs, limit OTC decongestants (HTN), report all new prescriptions
— Contraception counseling on teratogenic immunosuppressants (MMF, cyclophosphamide)
— Mental health support — chronic disease, body image with cushingoid changes (especially adolescents)
— Annual eye exam (cataract, glaucoma) on chronic steroids
— Skin cancer screening on long-term immunosuppression
— Cardiovascular risk assessment annually
— Annual UPCR and BMP even in long remission
— Reproductive counseling before pregnancy
— Children: return to school once stable; avoid contact sports during ascites or anticoagulation; live vaccines as above
CCS pearl: A 1-week post-discharge visit with weight, BP, UPCR, BMP, albumin, and medication review captures most of the early Step 3 follow-up logic; advance the clock and you'll be rewarded for ordering it.
Board pearl: Frequently relapsing MCD in a child is often driven by noncompliance with steroid taper — assess adherence before escalating immunosuppression.
— Long-term steroids and steroid-sparing agents carry meaningful risk profiles (infection, malignancy, infertility, metabolic complications)
— Document discussion of risks/benefits, alternatives, and natural history
— For pediatric patients: assent from the child (age-appropriate) plus parental consent; consider impact on growth, school, and psychosocial development
— Cyclophosphamide is gonadotoxic — discuss before initiation
— Offer sperm banking for postpubertal males
— Discuss oocyte/embryo cryopreservation for females of reproductive age
— This counseling is required and frequently tested
— Document contraception plan in all reproductive-age patients on MMF, cyclophosphamide, ACEi/ARB, sparsentan
— MMF requires 2 forms of contraception per FDA REMS
— Discharge handoff must include: clear taper schedule, follow-up appointment scheduled (not just recommended), labs ordered for follow-up, contact info for relapse symptoms
— Pediatric-to-adult transition: structured transfer at age 18–21 with summary of disease course, biopsy, cumulative immunosuppression, and current regimen
— Medication reconciliation at every transition reduces error
— Live vaccine timing relative to immunosuppression is a safety issue — coordinate proactively
— Household contacts can receive most live vaccines safely (avoid oral polio, smallpox)
— HIV diagnosis (during workup of collapsing FSGS) requires reporting and partner notification per state law
— HBV/HCV reportable; counsel and link to care
— APOL1 testing and hereditary FSGS panels raise questions about insurance, family implications — discuss before testing; GINA protects against health insurance/employment discrimination but NOT life or disability insurance
— Family members with APOL1 high-risk genotype face increased risk of kidney disease after donation — must be disclosed
Step 3 management: Before initiating cyclophosphamide in a 22-year-old man with steroid-dependent MCD, offer sperm banking and document the discussion — failure to do so is both an ethics and a safety issue tested on Step 3.
Board pearl: A pediatric patient transitioning to adult care should receive a written portable medical summary including biopsy results, immunosuppression history, cumulative steroid dose, vaccination status, and current regimen — discontinuity in care is a leading cause of relapse and ESRD progression.
— Hodgkin lymphoma — paraneoplastic MCD
— NSAIDs — MCD ± AIN
— Atopy/allergies, recent immunization, URI
— Lithium, IFN-α (also FSGS)
— HIV → collapsing FSGS (HIVAN)
— APOL1 high-risk alleles (G1/G2) in African ancestry
— Heroin, anabolic steroids, pamidronate, IFN, lithium, anti-VEGF
— Obesity, sleep apnea, reflux nephropathy, single kidney, sickle cell — adaptive FSGS
— Genetic: NPHS1 (nephrin), NPHS2 (podocin), WT1, INF2, TRPC6, ACTN4
— MCD: normal LM, negative IF, diffuse foot process effacement on EM
— FSGS: segmental sclerosis, IgM/C3 nonspecific, foot process effacement
— Collapsing FSGS: glomerular tuft collapse with podocyte hyperplasia
— Furosemide dosing doubled in nephrotic syndrome
— IV albumin + IV furosemide for refractory edema with underfilling
— Tacrolimus diabetogenic; cyclosporine causes gingival hyperplasia, hirsutism
— MMF and cyclophosphamide teratogenic
— Sparsentan now FDA-approved for primary FSGS proteinuria
— Hypercoagulable: VTE, renal vein thrombosis (especially membranous; less common but real in MCD/FSGS)
— SBP in children with ascites — Strep pneumoniae
— Steroid AVN of femoral head — hip pain on prolonged steroids
— MCD: selective proteinuria, steroid-responsive, excellent prognosis
— FSGS: nonselective, 50% ESRD at 5–10 years if untreated
— Tip lesion FSGS — best prognosis
— Collapsing FSGS — worst prognosis
— Primary FSGS: 30–40% recurrence, often within hours
— Genetic FSGS: minimal recurrence
— Treat recurrence: plasmapheresis + rituximab
— Empiric steroids in classic MCD presentation — no biopsy
— Biopsy if atypical, steroid-resistant, or relapsing
— Pneumococcal vaccination critical before immunosuppression
Board pearl: When a vignette mentions bisphosphonate (pamidronate) infusion for malignancy followed by new nephrotic syndrome, the answer is collapsing FSGS — discontinue the drug and refer for biopsy.
Key distinction: Diffuse foot process effacement = primary podocytopathy (MCD or primary FSGS — immunosuppression indicated). Segmental foot process effacement with preserved albumin = adaptive/secondary FSGS — treat the cause, no steroids.
— 4-year-old with periorbital edema after URI, normal BP, normal Cr, 4+ proteinuria, albumin 1.8
— Answer: empiric prednisolone, no biopsy needed
— Distractor: ordering biopsy first → wrong
— 32-year-old Black man with leg edema, BP 152/94, Cr 1.6, UPCR 8, microscopic hematuria
— Answer: kidney biopsy before treatment; expect FSGS
— Start ACEi, diuretic while awaiting biopsy
— 28-year-old with night sweats, cervical lymphadenopathy, and nephrotic syndrome
— Answer: lymph node biopsy / chest CT — Hodgkin lymphoma
— Untreated HIV patient with rapidly progressive proteinuria and rising Cr
— Biopsy: collapsing FSGS, tubular microcysts
— Answer: initiate ART
— Adult on prednisone 1 mg/kg × 16 weeks without remission
— Answer: add tacrolimus (or cyclosporine) — a CNI
— Child with 4 relapses in 12 months
— Answer: steroid-sparing agent — cyclophosphamide, MMF, CNI, or rituximab
— Nephrotic patient with sudden flank pain, hematuria, unilateral kidney swelling → renal vein thrombosis → CT/MR venogram, anticoagulate
— Nephrotic child with fever, ascites, abdominal pain → SBP → paracentesis + cefotaxime
— BMI 44, subnephrotic proteinuria, preserved albumin, biopsy shows perihilar FSGS
— Answer: weight loss + ACEi/ARB, NOT steroids
— Anasarca despite oral furosemide
— Answer: IV albumin + IV furosemide, add metolazone
— Patient on MMF/ACEi planning pregnancy
— Answer: switch to azathioprine, stop ACEi/ARB, target remission ≥6 months before conception
— Day-1 post-transplant proteinuria 12 g
— Answer: plasmapheresis ± rituximab for primary FSGS recurrence
— Hip pain on chronic steroids → AVN of femoral head — MRI
Step 3 management: Pay attention to time on steroids — "16 weeks" before declaring resistance in adult FSGS is the trap. Don't switch agents at 6 weeks just because remission hasn't occurred.
Board pearl: When the stem provides biopsy with foot process effacement but normal LM, the diagnosis is MCD regardless of patient age — treat with steroids.
Minimal change disease and FSGS are podocytopathies presenting with nephrotic syndrome, both treated initially with high-dose prednisone plus ACEi/ARB and supportive care — but MCD is overwhelmingly steroid-responsive with an excellent prognosis, while FSGS frequently progresses to ESRD and often requires calcineurin inhibitors or newer agents like sparsentan, with the critical preliminary step of distinguishing primary FSGS (immunosuppress) from secondary/adaptive FSGS (treat underlying cause, no steroids).
Board pearl: The single most testable distinction across this topic is primary vs secondary FSGS by foot process effacement extent — diffuse = immunosuppress; segmental with preserved albumin = treat cause, ACEi/ARB only.