Rapidly Progressive Glomerulonephritis

RPGN is a clinical syndrome of rapidly declining glomerular filtration over days to months, typically with hematuria, red-cell casts, and clinically significant proteinuria; untreated crescentic injury can progress to kidney failure within weeks to months. ScienceDirect+1ScienceDirectRapidly Progressive Glomerulonephritis - an overview | ScienceDirect TopicsOxford AcademicWhat is new in the management of rapidly progressive ... Obtain serial serum creatinine, electrolytes, bicarbonate, complete blood count, urinalysis with sediment examination, and quantitative proteinuria at presentation to document trajectory and identify urgent complications of kidney failure.

Immediately assess for diffuse alveolar hemorrhage when hemoptysis, new hypoxemia, unexplained anemia, or pulmonary infiltrates accompany nephritic urine sediment. Anti-GBM disease affects glomerular and pulmonary capillaries and presents with pulmonary hemorrhage in approximately 50% of cases. PubMedPubMedAnti-glomerular basement membrane disease—treatment standard Concurrent pulmonary involvement increases urgency for anti-GBM and ANCA testing and supports early disease-directed treatment rather than waiting for a fully completed outpatient evaluation. Kidney International+1Kidney InternationalRapidly progressive crescentic glomerulonephritisPubMedAnti-glomerular basement membrane disease—treatment standard

Exclude reversible mimics of acute kidney injury and hematuria while pursuing RPGN. Differential diagnoses specifically include reversible acute kidney injury, proteinuria, and hematuria from non-RPGN causes; thrombotic microangiopathy and acute interstitial nephritis can also enter the clinical RPGN differential. PubMed+1PubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMCPubMedRapidly Progressive Glomerulonephritis - StatPearls - NCBI In a patient with diabetes, abrupt renal decline, increased proteinuria, hematuria, or red-cell casts should trigger consideration of kidney biopsy because superimposed primary glomerular disease, acute tubular injury, and acute interstitial nephritis are frequent biopsy findings. NatureNatureKidney

Order ANCA and anti-GBM antibody testing concurrently in all patients with suspected RPGN. ANCA and anti-GBM seropositivity are the best laboratory predictors of pauci-immune crescentic GN and anti-GBM crescentic GN, respectively. Kidney InternationalKidney InternationalRapidly progressive crescentic glomerulonephritis Also obtain antinuclear antibody, anti-double-stranded DNA antibody, complement C3 and C4, serum protein electrophoresis, cryoglobulins, and infection-directed testing when the history or examination suggests lupus nephritis, cryoglobulinemia, monoclonal immunoglobulin-associated disease, or infection-related GN. ScienceDirect+2ScienceDirectAcute glomerulonephritis - ScienceDirectWolters KluwerInfection-Related Rapidly Progressive Crescentic... : Journal of the American Society of NephrologyPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMC

Perform kidney biopsy urgently when clinically feasible, including light microscopy, immunofluorescence, and electron microscopy. RPGN is classified by deposit distribution into anti-GBM disease, immune-complex GN, and pauci-immune GN; immunofluorescence is central to inferring etiology. ScienceDirect+1ScienceDirectAcute glomerulonephritis - ScienceDirectScienceDirectRapidly Progressive Glomerulonephritis - ScienceDirect Crescents establish severe glomerular injury but do not independently define the immunologic cause, because infection-related GN, lupus nephritis, IgA nephropathy, ANCA-associated vasculitis, and anti-GBM disease can each produce crescentic GN. ScienceDirect+1ScienceDirectAcute glomerulonephritis - ScienceDirectPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMC

Interpret chronicity alongside activity. Pauci-immune crescentic GN is most often due to ANCA-associated vasculitis, although ANCA-negative pauci-immune disease occurs. Oxford Academic+1Oxford AcademicKidney biopsy chronicity grading in antineutrophil cytoplasmic ...Kidney InternationalRapidly progressive crescentic glomerulonephritis In anti-GBM GN, more than 95% of biopsies show crescents and approximately 85% show crescents in at least half of glomeruli. Kidney InternationalKidney InternationalRapidly progressive crescentic glomerulonephritis A biopsy dominated by extensive chronic scarring indicates limited probability of renal recovery and should inform the balance between aggressive immunosuppression toxicity and anticipated benefit, particularly in dialysis-dependent anti-GBM disease. PubMedPubMedAnti-glomerular basement membrane disease—treatment standard

For new-onset organ-threatening ANCA-associated vasculitis, use rituximab or cyclophosphamide in combination with glucocorticoids for remission induction. PubMedPubMedThe Use of Rituximab in Glomerulonephritis: What Is the Evidence? Rituximab is particularly favored in relapsing disease, PR3-ANCA-positive disease, and when fertility preservation is important; cyclophosphamide may be preferred when clinicians require faster disease control. PubMed+1PubMedThe Use of Rituximab in Glomerulonephritis: What Is the Evidence?PubMedGranulomatosis With Polyangiitis - StatPearls - NCBI Bookshelf For the most severe presentations, including RPGN, combined rituximab and cyclophosphamide is an accepted escalation approach. PubMedPubMedThe Use of Rituximab in Glomerulonephritis: What Is the Evidence?

Historical RPGN guidance supports glucocorticoids plus either daily oral cyclophosphamide at 25-100 mg/day or intravenous cyclophosphamide at 250-750 mg/m2 monthly, adjusted for clinical grade, age, and dialysis requirement. PubMed+1PubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMCPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 Do not use these historical dose ranges as a substitute for current patient-specific vasculitis protocols; renal impairment, age, cytopenias, infection risk, and reproductive goals determine selection and dosing.

Plasma exchange in ANCA-associated RPGN is selectively considered for diffuse alveolar hemorrhage or advanced kidney failure. A guideline threshold for advanced renal involvement is serum creatinine greater than 5.8 mg/dL. PubMedPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 This differs from anti-GBM disease, in which plasma exchange is a core component of initial treatment. PubMed+1PubMedAnti-glomerular basement membrane disease—treatment standardScienceDirectRapidly Progressive Glomerulonephritis - ScienceDirect Reassess the indication after biopsy and serologies because infection-related immune-complex GN can be ANCA positive and may be worsened by indiscriminate immunosuppression. Wolters KluwerWolters KluwerInfection-Related Rapidly Progressive Crescentic... : Journal of the American Society of Nephrology

Treat anti-GBM disease with plasma exchange plus glucocorticoids and cyclophosphamide. The combination has substantially improved outcomes compared with historical untreated disease, particularly among patients who are not dialysis dependent at presentation. PubMedPubMedAnti-glomerular basement membrane disease—treatment standard Kidney biopsy showing linear IgG deposition and/or circulating anti-GBM antibodies establishes the therapeutic pathway. PubMedPubMedAnti-glomerular basement membrane disease—treatment standard

A commonly described plasma-exchange strategy is daily 4-L exchanges for 2-4 weeks, generally using 5% albumin replacement; add fresh frozen plasma when pulmonary hemorrhage is present or invasive procedures are planned. PubMedPubMedGoodpasture Syndrome - StatPearls - NCBI Bookshelf Continue daily exchange until anti-GBM antibody levels are suppressed or for 14 days, with extension for persistent active pulmonary disease or inadequate antibody decline. PubMedPubMedGoodpasture Syndrome - StatPearls - NCBI Bookshelf Pediatric guidance similarly describes daily 60 mL/kg replacement for 14 days or until anti-GBM antibodies become undetectable. PubMedPubMedRapidly progressive glomerulonephritis in children

Dialysis dependence at presentation predicts a lower likelihood of renal recovery, so treatment decisions should integrate pulmonary involvement, biopsy chronicity, comorbidity, and contraindications to cyclophosphamide. PubMedPubMedAnti-glomerular basement membrane disease—treatment standard This prognostic limitation should not obscure potentially lifesaving treatment for active pulmonary hemorrhage. In contrast to single-positive anti-GBM disease, dual-positive ANCA/anti-GBM disease can relapse and requires longer immunosuppression and long-term follow-up. PubMed+1PubMedRapidly Progressive Glomerulonephritis - StatPearls - NCBIPubMedGoodpasture Syndrome - StatPearls - NCBI Bookshelf

Immune-complex RPGN includes infection-related GN, IgA nephropathy, lupus nephritis, cryoglobulinemic GN, and related complement- or monoclonal immunoglobulin-associated disorders. ScienceDirect+1ScienceDirectAcute glomerulonephritis - ScienceDirectScienceDirectRapidly Progressive Glomerulonephritis - ScienceDirect Use the clinical setting and targeted serologies to assign the cause: active infection favors infection-related GN; antinuclear antibody and anti-double-stranded DNA testing support lupus; cryoglobulin testing and hepatitis C assessment address cryoglobulinemic disease; and serum protein electrophoresis helps evaluate a monoclonal immunoglobulin-associated process. ScienceDirect+2ScienceDirectAcute glomerulonephritis - ScienceDirectWolters KluwerInfection-Related Rapidly Progressive Crescentic... : Journal of the American Society of NephrologyPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMC

When diffuse proliferative lupus nephritis presents as RPGN, initial treatment is corticosteroids plus cyclophosphamide or mycophenolate mofetil. PubMed+1PubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMCPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 Plasma exchange is not routine for lupus nephritis but may be added when standard corticosteroid-immunosuppressive therapy is insufficient. PubMedPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 Biopsy remains necessary to establish the relevant proliferative lesion and distinguish lupus-associated immune-complex injury from coincident ANCA, anti-GBM, infection-related, or thrombotic processes. ScienceDirect+1ScienceDirectAcute glomerulonephritis - ScienceDirectPubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMC

In suspected infection-related RPGN, actively search for and treat the source rather than reflexively classifying a positive ANCA result as primary AAV. In one infection-related case with MRSA bacteremia, hepatitis C, low C3/C4, and atypical p-ANCA, biopsy showed necrotizing crescentic GN with mesangial immunoglobulin and strong C3 staining; management prioritized infection treatment, with glucocorticoids added because renal injury and proteinuria progressed. Wolters KluwerWolters KluwerInfection-Related Rapidly Progressive Crescentic... : Journal of the American Society of Nephrology This illustrates why biopsy and infection assessment should precede broad immunosuppression whenever the patient is stable enough for that sequence.

Track serum creatinine, urine sediment, quantitative proteinuria, blood pressure, and dialysis requirement through induction because persistent decline may reflect ongoing active necrotizing injury, delayed response, or irreversible chronicity. Repeat kidney biopsy can be useful when the clinical course and suspected disease activity diverge, although its utility is context dependent. BMJBMJ585.full.txt In anti-GBM disease, follow circulating antibody decline during plasma exchange to determine whether to continue beyond the usual treatment course. PubMed+1PubMedGoodpasture Syndrome - StatPearls - NCBI BookshelfPubMedRapidly progressive glomerulonephritis in children

Monitor for infection throughout high-dose glucocorticoid and cyclophosphamide- or rituximab-based treatment. Infection remains a leading cause of death in RPGN cohorts, and ANCA-associated vasculitis carries approximately 15% mortality at 1 year in reports of cyclophosphamide plus high-dose glucocorticoid treatment. PubMed+1PubMedEvidence-based clinical practice guidelines for rapidly progressive glomerulonephritis 2014 - PMCPubMedGranulomatosis With Polyangiitis - StatPearls - NCBI Bookshelf New fever, pulmonary findings, cytopenias, or hemodynamic instability require reassessment for infection before escalating immunosuppression.

Long-term strategy differs by cause. Single-positive anti-GBM disease is usually monophasic and generally does not require routine long-term maintenance immunosuppression after successful initial treatment, whereas dual-positive disease requires prolonged immunosuppression and relapse surveillance because recurrence is not uncommon. PubMed+1PubMedRapidly progressive glomerulonephritis in childrenPubMedGoodpasture Syndrome - StatPearls - NCBI Bookshelf In AAV, rituximab is an effective maintenance option and reduced major relapse compared with azathioprine in MAINRITSAN. PubMedPubMedThe Use of Rituximab in Glomerulonephritis: What Is the Evidence?