4.2 Glomerulonephritis, Nephrotic Syndrome & Electrolyte Imbalances

Glomerulonephritis, Nephrotic Syndrome & Electrolyte Imbalances

Glomerular diseases and electrolyte disorders represent fundamental clinical topics frequently tested in UPSC CMS. A firm understanding of light microscopy, immunofluorescence (IF), electron microscopy (EM), complement patterns, and emergency resuscitation protocols is required.

1. Nephrotic vs. Nephritic Syndrome: Clinical Paradigm

Glomerular diseases typically present along a spectrum between pure Nephrotic Syndrome (podocyte injury resulting in breakdown of the filtration barrier to proteins) and pure Nephritic Syndrome (inflammatory glomerular capillary destruction leading to reactive hematuria and GFR decline).

2. Major Nephrotic Syndromes

A. Minimal Change Disease (MCD)

• Epidemiology: Most common cause of nephrotic syndrome in children (80% of pediatric cases; peak age 2–6 years).
• Pathophysiology: T-cell dysfunction producing cytokines that cause charge-barrier disruption of the glomerular basement membrane (GBM).
• Microscopy:
  • Light Microscopy (LM): Normal glomeruli.
  • Immunofluorescence (IF): Negative (no immune complex deposits).
  • Electron Microscopy (EM): Effacement (fusion) of podocyte foot processes.
• Clinical Features: Selective proteinuria (loss of albumin, but retention of higher molecular weight immunoglobulins).
• Treatment: Oral Prednisolone (1 mg/kg/day or 60 mg/m²/day). Excellent steroid responsiveness (>90% complete remission).

B. Focal Segmental Glomerulosclerosis (FSGS)

• Epidemiology: Most common cause of primary nephrotic syndrome in Black adults. Associated with HIV infection (HIV-associated nephropathy / collapsing variant), heroin abuse, morbid obesity, and nephron loss.
• Microscopy: Segmental sclerosis affecting some but not all glomeruli on LM; diffuse podocyte foot process effacement on EM.
• Clinical Course: Non-selective proteinuria, frequently steroid-resistant, high rate of progression to ESRD (50% in 10 years).

C. Membranous Nephropathy

• Epidemiology: Most common primary nephrotic syndrome in older White adults (ages 40–60).
• Etiology: 70% primary (idiopathic), driven by antibodies against Phospholipase A2 Receptor (anti-PLA2R). Secondary causes: Hepatitis B & C, solid tumors (lung, colon, breast), NSAIDs, and SLE (Class V).
• Microscopy:
  • LM: Diffuse thickening of the capillary wall.
  • IF: Granular IgG and C3 deposition along the GBM.
  • EM: Subepithelial immune complex deposits with "spike and dome" appearance on Jones silver stain.
• Complications: Highest risk of Renal Vein Thrombosis among nephrotic syndromes (due to urinary loss of Antithrombin III).

3. Major Nephritic Syndromes

A. Post-Streptococcal Glomerulonephritis (PSGN)

• Etiology: Immune complex-mediated disease occurring 1 to 3 weeks after Group A Beta-Hemolytic Streptococcal (GABHS) pharyngitis or impetigo (Streptococcus pyogenes, nephritogenic strains 12 and 49).
• Clinical Presentation: Triad of Hematuria ("cola-colored" or smoky urine), Periorbital Edema, and Hypertension in a child.
• Laboratory Findings: Elevated ASO titers, anti-DNase B, and persistently low serum C3 levels (which normalize by 6–8 weeks).
• Histopathology:
  • LM: Diffuse hypercellular glomeruli (neutrophilic and lymphocytic infiltrate).
  • IF: "Starry sky" or lumpy-bumpy granular deposition of IgG and C3 along GBM and mesangium.
  • EM: Subepithelial electron-dense "humps".

B. IgA Nephropathy (Berger Disease)

• Epidemiology: The most common primary glomerulonephritis worldwide.
• Clinical Presentation: Recurrent episodes of gross hematuria occurring contemporaneously (1–2 days) with or immediately following an upper respiratory or gastrointestinal infection (Synpharyngitic Hematuria).
• Key Differentiating Points vs. PSGN:
  • Timing: 1–2 days (IgA) vs 1–3 weeks (PSGN).
  • Serum Complement: Normal C3/C4 levels in IgA Nephropathy vs Low C3 in PSGN.
• Biopsy: Mesangial IgA deposition on immunofluorescence.

C. Rapidly Progressive Glomerulonephritis (RPGN)

Characterized by rapid loss of renal function over days to weeks with histologic evidence of Crescent formation (extracapillary proliferation of parietal epithelial cells and monocytes in Bowman's space) in >50% of glomeruli.

1. Type I (Anti-GBM Disease / Goodpasture Syndrome): Autoantibodies against non-collagenous domain of alpha-3 chain of Type IV collagen. Linear IgG deposition along GBM. Presents with pulmonary hemorrhage + GN.
2. Type II (Immune Complex): Granular deposition (PSGN, SLE, Henoch-Schönlein Purpura).
3. Type III (Pauci-immune): Negative IF. Associated with ANCA vasculitides (c-ANCA / PR3 in Granulomatosis with Polyangiitis; p-ANCA / MPO in Microscopic Polyangiitis).

4. Emergency Management of Electrolyte Imbalances

A. Severe Hyperkalemia (Serum K⁺ >6.5 mEq/L or ECG Changes)

• ECG Progression: Peaked T waves → PR prolongation & P wave flattening → QRS widening → Sine wave pattern → Ventricular Fibrillation / Asystole.

UPSC CMS Emergency Treatment Algorithm for Hyperkalemia:

1. Membrane Stabilization (Immediate): IV Calcium Gluconate (10 mL of 10% solution over 2–5 mins). Stabilizes cardiac myocyte membrane potential without changing serum K⁺ levels. (Use with caution in digoxin toxicity).
2. Shift K⁺ Intracellularly (Minutes):
   • IV Regular Insulin (10 Units) + 50% Dextrose (50 mL / D50) to prevent hypoglycemia.
   • Nebulized Salbutamol (10–20 mg) (beta-2 agonist).
   • IV Sodium Bicarbonate (if concomitant metabolic acidosis exists).
3. Eliminate K⁺ from Body (Hours):
   • Loop Diuretics (Furosemide IV).
   • Potassium Binders: Patiromer, Sodium Zirconium Cyclosilicate (SZC), Sodium Polystyrene Sulfonate (SPS).
   • Hemodialysis: Definitive treatment in renal failure.

B. Severe Hyponatremia (Serum Na⁺ <120 mEq/L or Symptomatic)

• Classification: Determine plasma osmolality and volume status (Hypovolemic, Euvolemic [SIADH], Hypervolemic [Heart Failure, Cirrhosis]).
• Symptomatic Management: Severe symptoms (seizures, altered mental status, coma) warrant immediate 3% Hypertonic Saline (100–150 mL IV bolus over 10–20 mins) to raise serum sodium by 4–6 mEq/L rapidly.
• Safety Speed Limit: Rate of sodium correction must NOT exceed 8–10 mEq/L in 24 hours (or 0.5 mEq/L/hour) to prevent Osmotic Demyelination Syndrome (Central Pontine Myelinolysis).