This is Minimal Change Disease (MCD) — the most common cause of nephrotic syndrome in children, and one of the most predictably testable diagnoses on Step 1.

The diagnostic triad on biopsy: (1) Normal on light microscopy; (2) Diffuse podocyte foot process effacement on electron microscopy — the hallmark; (3) No immune deposits on immunofluorescence — “nil disease.”

Why complement is normal: MCD is NOT immune complex-mediated. It involves a circulating T-cell–derived permeability factor that disrupts podocyte architecture — no complement activation → C3 and C4 remain normal.

Treatment and prognosis: MCD is exquisitely steroid-sensitive — over 90% of children achieve complete remission with prednisone within 4–8 weeks. Relapses are common (~70%) but usually respond to repeat steroids. For steroid-resistant disease: cyclosporine, tacrolimus, mycophenolate, or rituximab.

This is Post-Streptococcal Glomerulonephritis (PSGN) — the prototype nephritic syndrome.

Pharyngitis 2–3 weeks prior + elevated ASO titer → immune complex GN → low C3, normal C4 (alternative complement pathway activated, consuming C3 but sparing C4). “Humps” = large subepithelial immune complexes = classic PSGN.

Prognosis in children: Excellent — >95% have complete recovery. C3 normalizes within 8–12 weeks. If C3 remains low beyond 8 weeks, consider MPGN or SLE.

This is Goodpasture Syndrome (anti-GBM disease) — one of the most dramatic renal emergencies on USMLE.

The Triad: Hemoptysis + hematuria + rapidly progressive renal failure = pulmonary-renal syndrome. Anti-GBM antibodies target the alpha-3 chain of type IV collagen in both glomerular and alveolar basement membranes.

Why plasmapheresis is essential: Physically removes circulating anti-GBM antibodies — the most direct way to reduce pathogenic antibody load. Immunosuppression prevents new antibody production. Without rapid intervention, permanent renal failure occurs within weeks.

This is Type 1 (Distal) RTA. In Sjögren syndrome, autoimmune damage to alpha-intercalated cells impairs distal H+ secretion → H+ accumulates in blood → urine cannot be acidified below pH 5.5 despite systemic acidosis.

Why Type 1 causes kidney stones: Alkaline urine + hypercalciuria (bone buffers H+ by releasing calcium) + low urinary citrate = calcium phosphate stones + nephrocalcinosis.

Loop diuretic–induced metabolic alkalosis is caused by multiple simultaneous mechanisms. (1) Contraction alkalosis: Furosemide blocks Na-K-2Cl in the thick ascending limb → massive Na+/K+/Cl- loss. Lost fluid is HCO3–poor → plasma HCO3- concentrates in a smaller volume. Volume contraction → RAAS → aldosterone → more H+ secreted, more HCO3- generated. (2) Hypokalemia: K+ depletion → cells release H+ to maintain electrical neutrality → extracellular H+ falls → alkalosis.

FENa <1% = kidneys are avidly retaining sodium because they “sense” low perfusion → prerenal AKI. ACE inhibitors block angiotensin II–mediated efferent arteriolar constriction → GFR falls. This is hemodynamically mediated AKI, not nephrotoxicity.

Caveat: FENa is unreliable in patients on diuretics. Use FEUrea <35% = prerenal in those patients instead.

The CKD-MBD Cascade: ↓GFR → ↑phosphate retention → ↓1-alpha hydroxylase activity → ↓calcitriol (active Vitamin D) → ↓GI calcium absorption → hypocalcemia → hyperphosphatemia chelates calcium → secondary hyperparathyroidism → PTH mobilizes calcium and phosphate from bone → renal osteodystrophy.

A normal pH NEVER rules out a mixed disorder. Always calculate the anion gap regardless of pH.

Step 1 — pH 7.44: Normal (slightly alkalemic). Misleading — does not mean no disorder.

Step 2 — HCO3- 32 (elevated): Primary metabolic alkalosis. Expected PaCO2 for compensation = 40 + (0.7 × 8) = 45.6 mmHg. Actual = 48 → within range → appropriate compensation from vomiting.

Step 3 — Anion gap 22 (elevated): An elevated AG is ALWAYS abnormal — even with normal pH. This signals a concurrent high anion gap metabolic acidosis (lactic acidosis from metformin accumulation in a dehydrated patient with poor renal clearance).

Step 4 — Delta-delta: (22−12)/(24−32) = 10/−8 = −1.25. Delta-delta <1 confirms underlying metabolic alkalosis coexists with HAGMA.

Thiazide-induced hyponatremia is the most common cause of severe symptomatic hyponatremia in elderly outpatient women — a classic USMLE scenario.

Mechanism: Thiazides block Na-Cl reabsorption in the DCT → impair maximal urine dilution → any water intake is retained → hyponatremia. Volume contraction from Na loss → ADH release → further free water retention.

Why NOT loop diuretics: Loop diuretics impair the medullary concentration gradient → actually impair ADH’s ability to concentrate urine → loops rarely cause severe hyponatremia.

Treatment: Mild/asymptomatic → fluid restrict + stop thiazide. Severe (Na <120 with symptoms) → 3% NaCl. Rate: ≤10 mEq/L per 24 hours — faster correction risks osmotic demyelination syndrome (central pontine myelinolysis).

SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) are now the most important advance in diabetic nephropathy treatment. Landmark trials: CREDENCE (canagliflozin), DAPA-CKD (dapagliflozin), EMPA-KIDNEY (empagliflozin) all demonstrated reduced progression to ESRD, reduced HF hospitalization, and reduced CV mortality.

Renal mechanism: Block glucose reabsorption in the proximal tubule → more Na+ delivered to macula densa → tubuloglomerular feedback → afferent arteriolar constriction → reduced GFR and glomerular pressure → reduced hyperfiltration (the hallmark mechanism of diabetic nephropathy).

Metformin in CKD: Safe if GFR ≥ 30 mL/min (reduce dose at GFR 30–45). Contraindicated if GFR <30. This patient’s GFR 48 → metformin is acceptable.

This is ADPKD (Autosomal Dominant PKD) — the most common inherited kidney disease. Caused by PKD1 (chromosome 16, ~85%) or PKD2 (chromosome 4, ~15%) mutations. PKD1 = earlier, more severe disease.

Treatment: Tolvaptan (V2 receptor antagonist) slows cyst growth. BP control with ACEi/ARB. Dialysis/transplant for ESRD.

Cystinuria: AR mutation in SLC3A1/SLC7A9 → defective cystine-dibasic amino acid transporter in proximal tubule and intestine → COLA amino acids spill into urine (Cystine, Ornithine, Lysine, Arginine). Only cystine is insoluble enough to precipitate into stones.

Hexagonal crystals on urine microscopy = pathognomonic for cystinuria.