Rapidly Progressive Glomerulonephritis (RPGN)

Manifestations are usually insidious, with weakness, fatigue, fever, nausea, vomiting, anorexia, arthralgia, and abdominal pain. Some patients present similarly to those with postinfectious glomerulonephritis Postinfectious Glomerulonephritis (PIGN) Postinfectious glomerulonephritis occurs after infection, usually with a nephritogenic strain of group A beta-hemolytic streptococcus. Diagnosis is suggested by history and urinalysis and confirmed... read more , with abrupt-onset hematuria. About 50% of patients have edema and a history of an acute influenza-like illness within 4 weeks of onset of renal failure, usually followed by severe oliguria. Nephrotic syndrome is present in 10 to 30%. Hypertension is uncommon and rarely severe. Patients with anti-GBM antibody disease may have pulmonary hemorrhage, which can manifest with hemoptysis or be detectable only by findings suggestive of diffuse alveolar infiltrates on lung imaging (pulmonary-renal syndrome Pulmonary-Renal Syndrome Pulmonary-renal syndrome is diffuse alveolar hemorrhage plus glomerulonephritis, often occurring simultaneously. Cause is almost always an autoimmune disorder. Diagnosis is by serologic tests... read more or diffuse alveolar hemorrhage syndrome Diffuse Alveolar Hemorrhage Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage that originates from the lung parenchyma (ie, the alveoli) as opposed to the airways. There are numerous causes, but... read more ).

Diagnosis is suggested by acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more in patients with hematuria and dysmorphic red blood cells (RBCs) or RBC casts. Testing includes serum creatinine, urinalysis, complete blood count (CBC), serologic tests, and renal biopsy. Diagnosis is usually by serologic tests and renal biopsy.

Serum creatinine is almost always elevated.

Urinalysis shows hematuria is always present, and RBC casts are usually present. Telescopic sediment (ie, sediment with multiple elements, including white blood cells [WBCs]; dysmorphic RBCs; and WBC, RBC, granular, waxy, and broad casts) is common.

On CBC, anemia is usually present, and leukocytosis is common.

Serologic testing should include anti-GBM antibodies (anti-GBM antibody disease); antistreptolysin O antibodies, anti-DNA antibodies, or cryoglobulins (immune complex RPGN); and antineutrophil cytoplasmic antibodies (ANCA) titers (pauci-immune RPGN).

Complement measurement (serum C3 and C4) may be useful in suspected immune complex RPGN because hypocomplementemia is common.

Early renal biopsy is essential. The feature common to all types of RPGN is focal proliferation of glomerular epithelial cells, sometimes interspersed with numerous neutrophils, that forms a crescentic cellular mass (crescents) and that fills Bowman space in > 50% of glomeruli. The glomerular tuft usually appears hypocellular and collapses. Necrosis within the tuft or involving the crescent may occur and may be the most prominent abnormality. In such patients, histologic evidence of vasculitis should be sought.

Immunofluorescence microscopy findings differ for each type:

Treatment varies by disease type, although no regimens have been rigorously studied. Therapy should be instituted early, ideally when serum creatinine is < 5 mg/dL (442 micromol/L) and before the biopsy shows crescentic involvement of all glomeruli or organizing crescents as well as fibrotic interstitium and atrophic tubules. Even patients with kidney involvement and higher creatinine levels should be aggressively treated if they do not require immediate renal replacement therapy Overview of Renal Replacement Therapy Renal replacement therapy (RRT) replaces nonendocrine kidney function in patients with renal failure and is occasionally used for some forms of poisoning. Techniques include continuous hemofiltration... read more . Treatment becomes less effective as these features become more prominent and may be harmful in some patients (eg, older patients, patients with infection).

Corticosteroids and either cyclophosphamide or rituximab are usually given. For immune complex and pauci-immune disease, corticosteroids (methylprednisolone 1 g IV once a day over 30 minutes for 3 to 5 days followed by prednisone 1 mg/kg orally once a day) may reduce serum creatinine levels or delay dialysis for > 3 years in 50% of patients (1, 2 Treatment references Rapidly progressive glomerulonephritis is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. Diagnosis... read more ).

Cyclophosphamide is usually given and may particularly benefit antineutrophil cytoplasmic antibody (ANCA)–positive patients; IV monthly pulse regimens may cause fewer adverse effects (eg, leukopenia, infection) than oral therapy because of reduced cumulative dosing. Prednisone and cyclophosphamide are typically started concurrent with plasma exchange for anti-GBM (glomerular basement membrane) antibody disease and continued to minimize new antibody formation. Patients with idiopathic disease are usually treated with corticosteroids and cyclophosphamide, but data regarding efficacy are scarce.

Rituximab may be dosed at 375 mg/m² IV per week for 4 weeks as used in the RAVE trial (formal title: Rituximab in ANCA-Associated Vasculitis; [ 2 Treatment references Rapidly progressive glomerulonephritis is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. Diagnosis... read more ]). An alternative regimen is an initial dose of 1g followed by another 1-g dose 2 weeks later. Rituximab has not been used in the treatment of anti-GBM disease.

Plasma exchange Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more (daily 3- to 4-L exchanges for 14 days) is recommended for anti-GBM antibody disease. Plasma exchange may also be considered for immune complex and pauci-immune ANCA-associated RPGN with pulmonary hemorrhage or severe renal dysfunction on presentation (serum creatinine > 5 to 7 mg/dL [442 to 618.8 micromol/L] or dialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more dependency), but its use remains controversial. Plasma exchange is thought to rapidly remove free antibody, intact immune complexes, and mediators of inflammation (eg, fibrinogen, complement). While some evidence suggested that plasma exchange improved short-term kidney outcomes, a subsequent randomized trial did not show that it reduced the incidence of death or end-stage kidney disease (3 Treatment references Rapidly progressive glomerulonephritis is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. Diagnosis... read more ).

Aggressive immunosuppressive therapy may also be beneficial in patients who present with higher creatinine levels. Plasmapheresis combined with prednisone and cyclophosphamide benefited patients with renal involvement who did not require immediate renal replacement therapy Overview of Renal Replacement Therapy Renal replacement therapy (RRT) replaces nonendocrine kidney function in patients with renal failure and is occasionally used for some forms of poisoning. Techniques include continuous hemofiltration... read more , even if creatinine levels were elevated above 5 to 7 mg/dL (442 to 618.8 micromol/L; [ 4 Treatment references Rapidly progressive glomerulonephritis is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. Diagnosis... read more ]).

Kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more is effective for all types, but disease may recur in the graft; risk diminishes with time. In anti-GBM antibody disease, the anti-GBM titers should be undetectable for at least 12 months before transplantation. For patients with pauci-immune RPGN, disease activity should be quiescent for at least 6 months before transplantation; ANCA titers do not need to be suppressed.

Spontaneous remission is rare, and 80 to 90% of untreated patients progress to end-stage kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more within 6 months. Prognosis improves with early treatment.

Favorable prognostic factors include RPGN caused by the following:

Unfavorable prognostic factors include the following:

About 30% of patients with pauci-immune RPGN do not respond to treatment; among nonresponders, about 40% require dialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more , and 33% die within 4 years. In contrast, among patients who respond to treatment, < 20% of patients require dialysis, and about 3% die.

Patients with double-antibody disease appear to have a renal prognosis somewhat better than patients with only anti-GBM antibody disease and worse than patients with pauci-immune disease.

Patients who recover normal renal function after RPGN demonstrate residual histologic changes principally in glomeruli, consisting chiefly of hypercellularity, with little or no sclerosis within the glomerular tuft or the epithelial cells and minimal fibrosis of the interstitium.

Death is usually due to infectious or cardiac causes, providing that a uremic death is prevented by dialysis.