RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

Rapid progressive glomerulonephritis (RPGN) or crescenteric GN is a severe glomerular inflammatory disease of heterogeneous etiology, characterized by rapid deterioration in renal functions within days or weeks and extensive crescent formation on renal histology.

Etiologically, RPGN may be idiopathic or superimposed on other glomerular disorders, e.g. (a) APSGN/APIGN,

(b) connective tissue disorders, e.g. SLE or HSP, (c) infec­tions, e.g. shunt nephritis, or (d) goodpasture syndrome.

Pathologically, it is characterized by widespread crescent formation in majority of glomeruli, due to proliferation of cirumferential layer of fibroblasts, macrophages and epithelial cells within Bowman's space.

Histologically, RPGN may also be classified as:

(a) immune-complex GN, (b) pauci-immune GN, and (c) anti-GBM GN.

Clinically, these cases initially present as nephritic or nephrotic syndrome, but progress rapidly to acute renal failure and end-stage renal disease (ESRD). RPGN should be suspected in any case of hematuria, which fails to resolve within 2-3 weeks. Extra-renal manifestations of causative disease, e.g. connective tissues disorders, vasculitis syndromes and infections may be present.

Diagnosis rests on renal biopsy, which is indicated in all cases with severe nephritis which does not resolve in 1-2 weeks.

Management include:

• Supportive therapy for complications, e.g. uremia, hypertension and hyperkalemia, as well as

• Specific immunosuppressive therapy. Currently recommended schedule include:

- Induction phase with (a) IV Methylprednisolone 15-20 mg/kg/d for 6 days followed by PO Prednisolone 2 mg/kg/day (tapered to 0.5-1.0 mg/ kg/ day after 4 weeks), and (b) IV Cyclophosphamide 500-750 mg/m²/dose every 3-4 weeks or PO cyclophosphamide 2 mg/kg/day, for 8 weeks.

- Subsequent maintenance therapy with PO Pre­dnisolone 0.5-1.0 mg / kg/alternate day and PO Mycophenolate 800-1200 mg/m²/day for next 12-24 months.

• Plasmapheresis is recommended in cases with anti- GBM GN or dialysis-dependent pauci-immune GN. Rituximab is another potential option under investigation.

Prognosis depends on underlying etiology, severity of disease and timing to start treatment. While some cases recover spontaneously, overall prognosis is poor in those with extensive crescent formation in gt;80% glomeruli.

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