Glomerular Diseases - Nephritic and Nephrotic Syndromes

Overview

Glomerulonephritis (GN)/Bright’s disease = diseases primarily involving glomeruli. Split: Primary GN (glomeruli predominant site) vs Secondary (systemic/hereditary disease affecting glomeruli secondarily) — somewhat arbitrary division. Diagnosis: renal biopsy — light+EM+immunofluorescence together.

Classification

I. Primary GN: acute GN (post-strep, non-strep), RPGN, minimal change disease, membranous GN, MPGN, focal/diffuse proliferative GN, FSGS, IgA nephropathy, chronic GN.

II. Secondary systemic: lupus nephritis, diabetic nephropathy, amyloidosis, PAN, Wegener’s, Goodpasture’s, HSP, systemic infections (endocarditis, syphilis, leprosy, HBV/HCV/HIV, falciparum malaria, filariasis), idiopathic mixed cryoglobulinaemia.

III. Hereditary: Alport’s syndrome, Fabry’s disease, nail-patella syndrome.

Clinical syndromes

4 core features (proteinuria, haematuria, hypertension, ↓excretory function) combine across 6 syndromes: nephritic, nephrotic, acute/chronic renal failure, asymptomatic proteinuria/haematuria.

Acute nephritic syndrome

Acute: microscopic haematuria+mild proteinuria+HTN+oedema+oliguria, 10-20 days post-infection.

• Haematuria — slight (smoky urine), RBC casts = classical finding
• Proteinuria — mild (<3g/24h), non-selective (“nephritic-range”)
• HTN — variable, mild
• Oedema — mild, Na+/water retention
• Oliguria — variable, tracks severity

Nephrotic syndrome

Diverse diseases, unified constellation — CAUSAL CHAIN, not 6 independent findings:

1. Heavy proteinuria (>3g/24h) = primary event. Normal: 20-150mg/day crosses barrier, tubular-reabsorbed; ↑permeability overwhelms reabsorption. Selectivity: highly selective=low-MW loss; poorly selective=high-MW too. Nephrotic = mostly ALBUMIN (MW 66,000) loss.
2. Hypoalbuminaemia ← from #1 (urinary loss) + ↑renal catabolism + inadequate hepatic synthesis. Plasma albumin 1-3g/dl (normal 3.5-5.5), reversed A:G ratio. Other proteins fall too (Ig→infection risk; clotting factors/antithrombin→thrombosis risk).
3. Oedema ← from #2 (↓oncotic pressure) + secondary Na+/water retention. Peripheral usually; facial in children.
4. Hyperlipidaemia — mechanism unclear; hypothesis: liver’s massive protein synthesis response also ↑lipoprotein synthesis. ↑total lipids/cholesterol/TG/VLDL/LDL, ↓HDL (partly urinary loss).
5. Lipiduria ← from #4, same leaky barrier.
6. Hypercoagulability — spontaneous arterial/venous thrombosis, renal vein thrombosis, PE. Factors: urinary antithrombin III loss, hepatic hyperfibrinogenaemia, ↓fibrinolysis, ↑platelet aggregation, altered protein C/S.

Age-dependent causes: CHILDREN — primary GN dominates, mostly minimal change disease/lipoid nephrosis (~65%). ADULTS — systemic disease (diabetes, amyloidosis, SLE) more frequent overall; commonest PRIMARY cause = membranous GN (~40%).

Nephritic vs nephrotic

Clinical relevance

Nephrotic syndrome’s 6 features = single causal cascade (proteinuria→hypoalbuminaemia→oedema, plus parallel lipid+coagulation effects), not a checklist — makes biochemistry internally consistent, predictable from one lesion (glomerular permeability). RBC casts in nephritic syndrome = specific high-value finding — casts form ONLY in kidney, localises bleeding definitively to glomerulus/nephron. Age-dependent nephrotic causation shift (children=minimal change, adults=systemic disease/membranous GN) = practical diagnostic anchor — same syndrome, different workup by age. Nephritic-vs-nephrotic table = highest-yield single reference in glomerular pathology — most vignettes reduce to sorting into one pattern first.

Overview

Glomerulonephritis (GN), or Bright’s disease, denotes diseases primarily involving the renal glomeruli. Glomerular disease is conventionally split into primary glomerulonephritis (glomeruli are the predominant site of disease) and secondary glomerular disease (systemic/hereditary disease secondarily affecting glomeruli) — a somewhat arbitrary division, since many “primary” forms have systemic effects and many systemic diseases present initially with glomerular involvement. Diagnosis rests on renal biopsy examined by light, electron, and immunofluorescence microscopy together.

Classification

I. Primary glomerulonephritis: acute GN (post-streptococcal, non-streptococcal), rapidly progressive GN, minimal change disease, membranous GN, membranoproliferative GN, focal/diffuse proliferative GN, focal segmental glomerulosclerosis (FSGS), IgA nephropathy, chronic GN.

II. Secondary systemic glomerular disease: lupus nephritis, diabetic nephropathy, amyloidosis, polyarteritis nodosa, Wegener’s granulomatosis, Goodpasture’s syndrome, Henoch-Schönlein purpura, systemic infections (bacterial endocarditis, syphilis, leprosy, HBV/HCV/HIV, falciparum malaria, filariasis), idiopathic mixed cryoglobulinaemia.

III. Hereditary nephritis: Alport’s syndrome, Fabry’s disease, nail-patella syndrome.

Clinical Syndromes

Four core features — proteinuria, haematuria, hypertension, disturbed excretory function — combine in varying patterns across six recognised glomerular syndromes: nephritic and nephrotic syndromes, acute and chronic renal failure, asymptomatic proteinuria/haematuria.

Acute Nephritic Syndrome

Acute-onset microscopic haematuria, mild proteinuria, hypertension, oedema, oliguria, typically 10–20 days after an infective illness.

• Haematuria — usually slight (smoky urine); RBCs on microscopy/chemical testing; red cell casts are a classical, diagnostically important finding.
• Proteinuria — mild (<3 g/24h), usually non-selective (“nephritic-range”).
• Hypertension — variable, generally mild.
• Oedema — mild, from sodium/water retention.
• Oliguria — variable, tracking disease severity.

Nephrotic Syndrome

A constellation seen across diverse underlying diseases with varying pathogenesis, unified by massive proteinuria, hypoalbuminaemia, oedema, hyperlipidaemia, lipiduria, hypercoagulability — worth understanding as a genuinely causal chain, not six independent findings:

1. Heavy proteinuria (>3 g/24h, “nephrotic-range”) is the primary event. Normally 20–150 mg/day of protein crosses the filtration barrier and is tubular-reabsorbed; increased glomerular permeability overwhelms tubular reabsorption capacity. Proteinuria “selectivity” matters: highly selective = low-molecular-weight protein loss; poorly selective = high-molecular-weight loss too. Nephrotic syndrome typically loses mostly albumin (MW 66,000).
2. Hypoalbuminaemia follows directly from #1 (urinary albumin loss), compounded by increased renal catabolism and inadequate hepatic synthesis. Plasma albumin often 1–3 g/dl (normal 3.5–5.5), with a reversed albumin:globulin ratio. Other plasma proteins fall too (immunoglobulins → infection risk; clotting factors/antithrombin → thrombotic risk).
3. Oedema follows from #2 — falling colloid osmotic pressure, compounded by secondary sodium/water retention. Usually peripheral; facial oedema more prominent in children.
4. Hyperlipidaemia — mechanism not fully clear, but hypothesised that the liver’s response to massive protein synthesis demand (compensating for urinary protein loss) also drives increased lipoprotein synthesis. Raised total lipids, cholesterol, triglycerides, VLDL, LDL; HDL falls (partly from direct urinary HDL loss).
5. Lipiduria follows from #4 — the same leaky filtration barrier that lets protein through also lets lipid through.
6. Hypercoagulability — spontaneous arterial/venous thrombosis, renal vein thrombosis, pulmonary embolism, from multiple compounding factors: urinary antithrombin III loss, hepatic hyperfibrinogenaemia, decreased fibrinolysis, increased platelet aggregation, altered protein C/S.

Age-dependent causes: in children, primary glomerulonephritis dominates — most often minimal change disease/lipoid nephrosis (~65%). In adults, systemic disease (diabetes, amyloidosis, SLE) is more frequent overall, and the most common primary glomerular cause is membranous glomerulonephritis (~40%).

Nephritic vs Nephrotic — Contrasted

Clinical Relevance

• The nephrotic syndrome’s six features are best learned as a single causal cascade (proteinuria → hypoalbuminaemia → oedema, plus proteinuria’s parallel downstream effects on lipids and coagulation) rather than a checklist — this is what makes the syndrome’s biochemistry internally consistent and predictable from the one triggering lesion (glomerular permeability).
• Red cell casts in acute nephritic syndrome are a specific, high-value finding precisely because casts form only in the kidney (see Urine Examination) — their presence localises the bleeding definitively to the glomerulus/nephron rather than anywhere else in the urinary tract.
• The age-dependent shift in nephrotic syndrome causation (minimal change disease dominating in children, systemic disease and membranous GN dominating in adults) is a practical diagnostic anchor — the same syndrome should trigger a different differential workup purely based on patient age.
• The nephritic-versus-nephrotic contrast table is the highest-yield single reference in glomerular pathology, since most clinical vignettes in this area reduce to correctly sorting a given presentation into one pattern or the other before reasoning about the specific underlying disease.

• Nephrotic syndrome as a causal cascade: proteinuria branching into hypoalbuminaemia/oedema and hyperlipidaemia/hypercoagulability
• Nephritic vs nephrotic syndrome: full feature comparison side by side

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