Rapidly Progressive Glomerulonephritis (RPGN)

What is Rapidly Progressive Glomerulonephritis?

Rapidly progressive glomerulonephritis (RPGN) is a rare but life-threatening kidney disease. It is characterized by severe inflammation of the glomeruli -- the tiny filtering units within the kidneys -- leading to a rapid decline in kidney function over days to weeks. Without prompt medical treatment, RPGN can result in complete kidney failure requiring dialysis or kidney transplantation.

Causes and Classification

RPGN is classified into three main types based on the underlying cause and immune mechanism:

• Type I (Anti-GBM disease): Antibodies target the glomerular basement membrane (GBM). The most recognized example is Goodpasture syndrome, which can also involve lung hemorrhage alongside kidney damage.
• Type II (Immune complex-mediated): Deposits of antigen-antibody complexes accumulate in the glomeruli and trigger inflammation. Associated conditions include systemic lupus erythematosus (SLE), IgA nephropathy, post-infectious glomerulonephritis, and Henoch-Schonlein purpura.
• Type III (Pauci-immune, ANCA-associated): Little or no immune complex deposition is found. Instead, ANCA (antineutrophil cytoplasmic antibodies) drive the inflammation. Related conditions include granulomatosis with polyangiitis (formerly Wegener granulomatosis) and microscopic polyangiitis.

Symptoms

Symptoms of RPGN typically develop rapidly and may include:

• Reduced urine output (oliguria) or absence of urine (anuria)
• Blood in the urine (hematuria) -- urine may appear red or brown
• Foamy urine due to excess protein (proteinuria)
• Swelling (edema), particularly in the legs, ankles, and around the eyes
• High blood pressure (hypertension)
• General fatigue, nausea, and malaise
• In Type I RPGN (Goodpasture syndrome): cough and coughing up blood due to lung involvement

Diagnosis

Prompt and targeted diagnostic evaluation is essential:

• Blood tests: Measurement of creatinine and urea (kidney function markers), antibody testing (anti-GBM, ANCA, ANA, complement levels)
• Urinalysis: Detection of red blood cell casts, proteinuria, and hematuria
• Kidney biopsy: The most important diagnostic tool. Histological examination reveals the hallmark finding of crescentic proliferations (crescent formation) in more than 50% of glomeruli.
• Imaging: Renal ultrasound to assess kidney size and structure

Treatment

Treatment must be initiated immediately, as any delay significantly increases the risk of permanent kidney damage. The approach depends on the RPGN subtype:

General Measures

• High-dose corticosteroids (e.g., methylprednisolone pulse therapy) to rapidly suppress inflammation
• Immunosuppressive agents such as cyclophosphamide or rituximab, particularly for ANCA-associated and immune complex RPGN

Type-Specific Therapy

• Type I (Anti-GBM): In addition to immunosuppression, plasmapheresis (plasma exchange) is used to remove harmful antibodies from the blood
• Type II: Treatment of the underlying disease (e.g., lupus therapy) combined with immunosuppression
• Type III (ANCA-associated): Combination of corticosteroids with cyclophosphamide or rituximab; plasmapheresis may also be used in severe cases

Renal Replacement Therapy

When kidney failure has already occurred, dialysis may be required. Kidney transplantation can be a long-term option once the underlying disease is in remission.

Prognosis

The prognosis of RPGN depends on the subtype, the extent of kidney damage at diagnosis, and the response to treatment. Early and aggressive therapy can preserve or partially restore kidney function in some patients. However, in advanced disease or when diagnosis is delayed, a significant risk of permanent kidney insufficiency remains.

References

1. Jennette JC, Falk RJ. - Rapidly progressive crescentic glomerulonephritis. - Kidney International, 2022.
2. KDIGO Clinical Practice Guideline for Glomerulonephritis. - Kidney Disease: Improving Global Outcomes (KDIGO), 2021. Available at: https://kdigo.org
3. Kasper DL et al. - Harrison's Principles of Internal Medicine, 21st Edition. McGraw-Hill, 2022.