Rapidly Progressive Glomerulonephritis

The contract between this chapter and the reader.

1. 1. Define rapidly progressive GN and the crescent.
2. 2. Explain crescent formation and why speed matters.
3. 3. Classify RPGN by the three immunofluorescence patterns.
4. 4. Map each pattern to its mechanism and diseases.
5. 5. Recognise RPGN and work it up urgently.
6. 6. Test ANCA and anti-GBM (double-positive disease).
7. 7. Treat each mechanism urgently.
8. 8. Understand the role of plasma exchange.
9. 9. Recognise the prognosis and the treatment window.

A sixty-second reading. Each bullet stands alone.

• Rapidly progressive GN is a rapid loss of kidney function over days to weeks from crescentic glomerulonephritis.
• A crescent forms when severe glomerular injury fills Bowman's space with cells and fibrin.
• Crescents fibrose if untreated, becoming irreversible — so speed matters.
• RPGN is classified by the immunofluorescence pattern into three types.
• Pauci-immune (ANCA-associated) is the commonest and has little or no deposits.
• Anti-GBM disease shows linear IgG.
• Immune-complex disease shows granular deposits (lupus, IgA, post-infectious, MPGN).
• Every patient is tested for both ANCA and anti-GBM (double-positive disease).
• RPGN is a renal emergency requiring urgent serology and an urgent biopsy.
• Treatment is often started before all results return, because crescents fibrose.
• Pauci-immune and anti-GBM disease are treated with immunosuppression, with plasma exchange central in anti-GBM.
• Immune-complex crescentic GN is treated by the underlying disease plus immunosuppression.
• Renal salvage depends on the speed of treatment and the degree of fibrosis.

The medical core. An expert should agree rapidly progressive GN is fully covered here.

Why it matters at the bedside

Rapidly progressive glomerulonephritis is the clinical alarm bell of glomerular disease — a kidney failing over days, not years, because crescents are strangling its glomeruli. It is one syndrome with three mechanisms, and the whole skill is to recognise it fast, classify it by the immunofluorescence pattern, and treat before the crescents harden into scar. Here, more than anywhere, hesitation costs nephrons.

What RPGN is and the crescent

• Rapidly progressive glomerulonephritis is a clinical syndrome: a rapid loss of kidney function over days to weeks, with a nephritic sediment, caused by crescentic glomerulonephritis. The crescent — the lesion that defines it — is the morphologic mark of severe glomerular injury, and the syndrome is the clinical face of that crescentic process. RPGN names the urgency; the crescent names the lesion.

Crescent formation and why speed matters

• A crescent forms when injury is severe enough to rupture the glomerular capillary wall: fibrin, inflammatory cells, and proliferating parietal epithelial cells pour into Bowman's space, compressing the tuft. A cellular crescent is potentially reversible, but if untreated it organises into a fibrous crescent within days to weeks — irreversible scar. This is why RPGN is a renal emergency: the window between a salvageable cellular crescent and a lost fibrous one is short.

The three immunofluorescence patterns

• The unifying framework is that RPGN is classified by the immunofluorescence pattern into three types, each a mechanism from the first chapter. Pauci-immune (Type III) — little or no deposits, ANCA-associated — is the commonest. Anti-GBM (Type II) shows linear IgG. Immune-complex (Type I) shows granular deposits. The pattern is the pivot on which diagnosis and treatment turn.

Mapping patterns to mechanisms and diseases

• Each pattern maps to a mechanism and its diseases: pauci-immune to ANCA vasculitis (the vasculitis chapter); linear to anti-GBM disease/Goodpasture (the anti-GBM chapter); and granular to the immune-complex crescentic diseases — lupus, IgA, post-infectious GN, and MPGN/cryoglobulinemia (their respective chapters). Reading the pattern off the biopsy assigns the disease and the treatment.

Recognising and working up RPGN urgently

• The approach is to recognise and act fast. A rapid fall in GFR with a nephritic sediment is RPGN until proven otherwise, prompting urgent serology (ANCA, anti-GBM, complement, ANA/anti-dsDNA) and an urgent renal biopsy (for crescents and the immunofluorescence pattern). The workup is expedited precisely because the crescents are fibrosing while it proceeds.

Testing ANCA and anti-GBM

• A specific, mandatory step: every RPGN patient is tested for both ANCA and anti-GBM. About a third of anti-GBM patients are also ANCA-positive (double-positive disease, with features of both — the severity of anti-GBM and the relapsing course of ANCA), so testing only one antibody risks missing the other and misjudging the course.

Treating each mechanism

• Treatment is mechanism-specific but shares an urgent backbone. Pauci-immune (ANCA) disease is treated with corticosteroids plus rituximab or cyclophosphamide, with plasma exchange used selectively. Anti-GBM disease is treated with the urgent triple — plasma exchange (central here), corticosteroids, and cyclophosphamide. Immune-complex crescentic GN is treated by the underlying disease (lupus induction, IgA escalation, and so on) plus immunosuppression for the crescents. High-dose steroids are usually started initially across all three.

The role of plasma exchange

• Plasma exchange's role differs by mechanism, and this is a common point of confusion. In anti-GBM disease it is central — the archetypal indication — because it removes the pathogenic antibody. In ANCA vasculitis it is selective, considered for severe renal (dialysis-requiring) or pulmonary disease rather than routine. In immune-complex disease it is generally not the mainstay. Knowing where plasma exchange belongs is part of classifying the RPGN correctly.

Prognosis and the window

• Salvage hinges on two things: the speed of treatment and the degree of fibrosis. Cellular crescents treated early can recover; extensive fibrous crescents and sclerosis cannot, and a kidney dialysis-dependent with widespread damage at presentation (especially in anti-GBM disease) rarely recovers. But the systemic and pulmonary disease is treated regardless of renal salvageability, because RPGN's extra-renal manifestations — pulmonary haemorrhage above all — are themselves life-threatening.

The unifying message

• The chapter resolves to one algorithm: RPGN is a syndrome → biopsy and immunofluorescence pattern → mechanism (pauci-immune, linear, or granular) → urgent, mechanism-specific treatment. Recognise it, work it up fast, test both antibodies, and treat before the crescents fibrose. The three disease chapters supply the detail; this chapter supplies the speed and the framework that hold them together.

Five fully-built tables.

Table A — RPGN at a glance

Table B — The three patterns

Table C — The urgent workup

Table D — Treatment by mechanism

Table E — Prognosis and the window

Visualise & Map

Causal chains, each ending in a named action.

Chain 1 — The crescent

Severe glomerular injury ruptures the capillary wall → cells and fibrin fill Bowman's space → a crescent compresses the tuft → rapidly progressive GN → ACTION: treat fast.

Chain 2 — The closing window

A cellular crescent organises over days to weeks → it becomes a fibrous, irreversible crescent → the salvage window closes → ACTION: do not wait — treat early.

Chain 3 — The pauci-immune route

Scant deposits with ANCA → pauci-immune crescentic GN → ANCA vasculitis → ACTION: steroids plus rituximab or cyclophosphamide.

Chain 4 — The linear route

Smooth linear IgG → anti-GBM crescentic GN → anti-GBM disease → ACTION: the urgent triple, plasma exchange central.

Chain 5 — The granular route

Granular deposits → immune-complex crescentic GN → lupus / IgA / post-infectious / MPGN → ACTION: treat the underlying disease and immunosuppress.

Numbered rules. These numbers are the cross-reference handle for the cases and flowcharts.

Clinical Reasoning

Five cases. Each stops you at a decision before it answers it.

Every mechanism from Level 3 earns a bedside consequence and an action.

Exhaustive. Every rule in the chapter is here.

Safety & Evidence

Panel A — Red flags

Panel B — NEVER DO

Anti-patterns clinicians fall into. Each becomes a Level 22 distractor.

The grade reflects strength of evidence, not importance.

Patient Decisions

Outcomes as natural frequencies. Figures are representative; the direction of effect is given where precise numbers are uncertain.

Apply & Test

Copy-paste chart notes that map to the real decisions in this chapter.

Template 1 — RPGN urgent workup note

• Presentation: rate of GFR loss; nephritic sediment; pulmonary/systemic features ___.
• Urgent serology: ANCA; anti-GBM (both sent); complement; ANA/anti-dsDNA ___.
• Urgent biopsy: crescents (cellular vs fibrous); immunofluorescence pattern ___.
• Pattern: pauci-immune / linear / granular; double-positive? ___.
• Empirical treatment started (steroids) pending results? ___.

Template 2 — Mechanism-specific treatment note

• Mechanism: pauci-immune (ANCA) / anti-GBM / immune-complex ___.
• ANCA: steroids + rituximab/cyclophosphamide; selective plasma exchange ___.
• Anti-GBM: urgent triple (plasma exchange central) ___.
• Immune-complex: underlying disease + immunosuppression ___.
• Salvageability (speed, fibrosis); systemic/pulmonary treatment regardless ___.

Pre-rounds compression. Rules only.

Active recall. At least one card per objective.

Micro-teaching for rounds. Two scenarios, five steps each.

Nine items, each anchored in this chapter. At least one per objective.