Rapidly Progressive GlomerulonephritisEdit

Rapidly progressive glomerulonephritis (RPGN) is a medical emergency characterized by a rapid loss of kidney function over days to weeks, often accompanied by hematuria, proteinuria, and hypertension. The term refers to a clinicopathological syndrome rather than a single disease, defined by the abrupt onset of renal failure and the histological finding of crescents in a majority of glomeruli on kidney biopsy. If not treated promptly and effectively, RPGN can progress to irreversible kidney damage and dependence on renal replacement therapy. Early recognition, rapid diagnostic workup, and targeted therapy are therefore essential.

RPGN sits at the crossroads of nephrology and systemic disease. Its crescentic pathology reflects severe injury to the glomerular capillary tuft with proliferation of parietal epithelial cells and infiltration by macrophages, often accompanied by the release of fibrin. This pattern can arise from several etiologies, and distinguishing among them is critical because the treatment approach and prognosis vary substantially. Because it represents a final common pathway of diverse diseases, RPGN is best managed through a structured diagnostic pathway that couples timely clinical assessment with laboratory testing and histopathology. The emphasis in modern care is on prompt initiation of therapy when indicated, while avoiding overtreatment in cases where disease is less active or likely to respond to more conservative management. See for example discussions of glomerulonephritis and crescentic glomerulonephritis for broader context crescentic glomerulonephritis and glomerulonephritis.

Etiology and classification

RPGN is classified by the pattern of immune injury observed on kidney biopsy and by the underlying disease driving the process. The three major categories are:

Type I (anti-GBM disease): This form is driven by antibodies against the glomerular basement membrane, and may occur with or without pulmonary involvement (Goodpasture syndrome). The characteristic finding is linear deposition of immunoglobulin along the basement membrane on immunofluorescence. See anti-GBM disease and Goodpasture syndrome for related concepts.
Type II (immune complex–mediated GN): This category includes RPGN arising from immune complex deposition associated with diseases such as systemic lupus erythematosus, IgA nephropathy, membranoproliferative processes, post-infectious glomerulonephritis, cryoglobulinemia, and others. Immunofluorescence typically shows granular deposits of immunoglobulins and complement along the glomerular capillary walls.
Type III (pauci-immune GN): This includes the majority of ANCA-associated vasculitides, where little or no immune deposition is seen on immunofluorescence despite severe crescentic injury. The serologic hallmark is positivity for antineutrophil cytoplasmic antibodies (ANCA), and the diseases most commonly involved are granulomatosis with polyangiitis (granulomatosis with polyangiitis), microscopic polyangiitis (microscopic polyangiitis), and eosinophilic granulomatosis with polyangiitis (eosinophilic granulomatosis with polyangiitis). In some cases, overlap or “double positivity” can occur with anti-GBM antibodies.

These categories reflect both pathophysiology and therapeutic implications. The choice of treatment and prognosis differ markedly between anti-GBM disease, immune complex GN, and pauci-immune GN. See discussions on pauci-immune crescentic GN and granulomatosis with polyangiitis for deeper context.

Clinical presentation

Patients with RPGN typically present with a rapid decline in renal function, often over days to weeks. Key features may include: - Hematuria (sometimes visible, more often microscopic) and red blood cell casts - Proteinuria, sometimes in the nephrotic range - Hypertension and edema from reduced kidney function - Oliguria or anuria in advanced cases - Systemic manifestations that reflect the underlying disease, such as sinusitis or lung involvement in GPA or alveolar hemorrhage in ANCA-associated disease; or constitutional symptoms like fever and malaise in immune complex–mediated processes

Extrarenal features guide the clinician toward the underlying etiology. For anti-GBM disease, pulmonary involvement can present as coughing up blood or dyspnea. For ANCA-associated syndromes, upper airway, sinus, and pulmonary findings may predominate. Recognizing these patterns helps prioritize diagnostic testing and therapy.

Diagnosis

The diagnostic approach to RPGN combines clinical assessment, serology, and tissue diagnosis: - Urinalysis and quantitative measures of kidney function (creatinine, estimated glomerular filtration rate) - Serologic testing for underlying etiologies: anti-GBM antibodies, ANCA (cytoplasmic or perinuclear patterns with specific antigen targets), complement levels, and tests for immune complex–related diseases such as lupus serologies - Imaging as indicated to assess organ involvement and exclude alternative causes of rapid renal deterioration - Kidney biopsy with light microscopy, immunofluorescence, and electron microscopy to confirm the crescentic pattern and to classify the disease type. The biopsy typically shows crescents in a majority of glomeruli; the immunofluorescence pattern helps distinguish anti-GBM disease (linear IgG), immune complex GN (granular deposits), and pauci-immune GN (minimal deposition)

For a broader view of the related glomerular diseases, see glomerulonephritis and the specific entities above such as anti-GBM disease and granulomatosis with polyangiitis.

Treatment

RPGN requires urgent, disease-specific therapy aimed at halting ongoing glomerular injury and preventing irreversible renal damage. General principles include: - Immediate involvement of nephrology and, when necessary, critical care support - Immunosuppressive therapy tailored to the underlying category: - Type I (anti-GBM disease): combination of high-dose steroids with cyclophosphamide or rituximab, plus plasmapheresis to remove circulating anti-GBM antibodies, particularly when pulmonary hemorrhage is present - Type II (immune complex GN): therapies directed at the underlying disease (for example, lupus nephritis protocols in systemic lupus erythematosus, or antibiotics for post-infectious GN) with immunosuppression as indicated - Type III (pauci-immune GN): high-dose glucocorticoids with either cyclophosphamide or rituximab; plasmapheresis may be considered in cases with severe renal impairment or alveolar hemorrhage, though the evidence for routine plasmapheresis in all ANCA-associated cases has evolved - Plasmapheresis (therapeutic plasma exchange): used most clearly in anti-GBM disease and in select severe cases of ANCA-associated vasculitis with alveolar hemorrhage or rapidly progressive renal failure; large randomized trials have raised questions about routine use in all ANCA-associated cases, emphasizing selective, case-by-case indication and adherence to guidelines - Supportive care: blood pressure control, management of fluid balance, careful infection surveillance, vaccination planning, and renal replacement therapy if needed - Long-term planning: duration of immunosuppression, monitoring for relapse (especially in pauci-immune GN), and evaluation for kidney transplantation when recovery is unlikely or renal replacement therapy is needed

From a resource-management standpoint, practitioners emphasize using high-level evidence and guidelines to balance the benefits and risks of potent immunosuppressive therapies against infection risk and cost. While aggressive therapy can be lifesaving in many cases, unnecessary exposure to immunosuppression carries tangible consequences, and choices should align with the patient’s severity of disease, comorbidities, and values. See plasmapheresis, cyclophosphamide, and rituximab for related treatments, and kidney transplant for long-term planning once renal recovery is unlikely.

Prognosis and outcomes

The prognosis of RPGN varies widely and is heavily dependent on the underlying etiology, the extent of renal injury at presentation, and the speed with which appropriate therapy is started. Key prognostic factors include: - Baseline renal function; patients who present with advanced renal failure are less likely to recover renal function - The degree of crescents and the extent of irreversible scarring on histology - The specific underlying disease and its responsiveness to therapy - The occurrence of life-threatening extrarenal complications, such as pulmonary hemorrhage or severe infections related to immunosuppression

Early, targeted treatment improves the likelihood of renal recovery in many cases, but a subset of patients progress to end-stage kidney disease and require dialysis or transplantation. See end-stage kidney disease and dialysis for related concepts, and kidney transplantation for long-term management options.