How should I manage an adult with rapidly progressive renal failure (rising serum creatinine, oliguria, red‑cell casts) including initial high‑dose corticosteroids, timely renal biopsy, disease‑specific therapy for antineutrophil cytoplasmic antibody (ANCA)‑associated vasculitis, anti‑glomerular basement membrane disease, lupus nephritis, cryoglobulinemic vasculitis, thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic uremic syndrome (aHUS), acute interstitial nephritis, and multiple myeloma‑related cast nephropathy, and appropriate renal replacement therapy?

Management of Rapidly Progressive Renal Failure

Immediate Recognition and Initial Actions

When an adult presents with rising serum creatinine, oliguria, and red-cell casts, immediately initiate high-dose corticosteroids and obtain autoimmune serologies before waiting for kidney biopsy if clinical presentation is compatible with ANCA-associated vasculitis, anti-GBM disease, or lupus nephritis. 1

First-Line Exclusions (Complete Within Hours)

• Rule out prerenal azotemia from volume depletion or hypotension with fluid challenge 2
• Exclude urinary obstruction via renal ultrasound 2
• Screen for nephrotoxic drug exposure: NSAIDs, aminoglycosides, acyclovir, contrast agents, ACE-inhibitors, ARBs 2
• The only absolute requirement before starting immunosuppression is excluding infection with as much certainty as possible 1

Diagnostic Urinalysis (Perform Immediately)

• Dysmorphic red blood cells and red-cell casts confirm glomerular hematuria and indicate glomerulonephritis 2
• Pyuria without bacteriuria suggests inflammatory glomerular disease 2
• Quantify proteinuria with spot protein-to-creatinine ratio 2

Autoimmune Serologies (Draw Before Any Immunosuppression)

• MPO-ANCA and PR3-ANCA are positive in ~90% of pauci-immune RPGN, which accounts for 50–60% of all RPGN cases 2, 3
• Anti-GBM antibodies confirm Goodpasture's syndrome (~20% of RPGN) 2, 3
• ANA and anti-dsDNA for suspected lupus nephritis 2
• Complement C3/C4 levels for immune-complex disease 2
• Hepatitis B and C serologies before immunosuppression 2, 3

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Kidney Biopsy Strategy

Do not delay treatment while awaiting biopsy if MPO- or PR3-ANCA is positive with compatible small-vessel vasculitis presentation, or if anti-GBM disease or lupus nephritis is suspected in a rapidly deteriorating patient. 1, 4

When to Proceed With Biopsy

• Biopsy is required when active urinary sediment with falling GFR has uncertain etiology 2
• Biopsy differentiates active disease from chronic scarring when eGFR < 30 mL/min/1.73 m² 2
• Biopsy provides prognostic information and should be done when feasible, but after treatment initiation 1

When Biopsy Is Unnecessary

• Multiple myeloma-related renal failure (high bleeding risk) 2
• Positive ANCA serology with compatible clinical picture already warrants treatment 1

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Disease-Specific Treatment Protocols

ANCA-Associated Vasculitis (Most Common Cause)

Initiate intravenous methylprednisolone 500–1000 mg daily for 3 consecutive days, then transition to oral prednisone 1 mg/kg/day with gradual taper over at least 6 months. 2, 4

Induction Immunosuppression Choice

• Cyclophosphamide is preferred when serum creatinine >4 mg/dL (>354 μmol/L) 1
• Rituximab is preferred when kidney dysfunction is less severe or cyclophosphamide toxicity is a concern 1, 4
• Combination of two intravenous cyclophosphamide pulses with rituximab can be considered for severe GN 1
• Limit cumulative cyclophosphamide exposure to ≤25 g to reduce malignancy risk 2

Plasma Exchange Controversy

• Plasma exchange is NOT routinely recommended for ANCA vasculitis based on the PEXIVAS trial 1, 4
• Exception: Use plasma exchange if ANCA vasculitis overlaps with anti-GBM antibody disease 1, 4

Maintenance Therapy

• Rituximab or azathioprine plus low-dose glucocorticoids for at least 18 months 1
• Rituximab is preferred over azathioprine for maintenance 1

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Anti-GBM Antibody Disease (Goodpasture's Syndrome)

Apply the same high-dose glucocorticoid plus cyclophosphamide or rituximab regimen as ANCA vasculitis, but add therapeutic plasma exchange to rapidly remove pathogenic anti-GBM antibodies. 2, 4

Plasma Exchange Protocol

• Plasma exchange is essential for all anti-GBM patients except those with 100% crescents, >50% global glomerulosclerosis, or dialysis-dependent without pulmonary hemorrhage 4
• Continue plasma exchange until anti-GBM antibodies become undetectable 5
• Typical course requires 7–14 sessions 5

Prognostic Considerations

• Patients presenting on dialysis have >90% chance of remaining dialysis-dependent 4
• Reserve treatment for those with pulmonary hemorrhage or recent dialysis initiation 4

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Lupus Nephritis With Rapid Progression

Give intravenous methylprednisolone pulses followed by oral prednisone, combined with cyclophosphamide or rituximab for induction. 2, 4

Monitoring Disease Activity

• Serial anti-dsDNA titers correlate with disease activity and should be monitored 2
• Track complement C3/C4 levels as adjunctive markers 2

Overlap Syndromes

• In lupus patients with RPRF, always obtain ANCA serology and perform renal biopsy with immunofluorescence, as pauci-immune crescentic GN can occur in SLE patients 6
• Double-positive anti-GBM and ANCA in lupus requires combined treatment with corticosteroids, cyclophosphamide/rituximab, and plasma exchange 5

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Cryoglobulinemic Vasculitis (HCV-Related)

For severe/rapidly progressive cryoglobulinemic nephritis, immunosuppression is the first-line intervention because antiviral therapy alone is insufficient to rapidly control renal disease. 1

Immunosuppressive Regimen

• High-dose glucocorticoids: 3 pulses of 10–15 mg/kg methylprednisolone, then oral prednisone 0.5–1 mg/kg/day for 1 month with tapering 1
• Cyclophosphamide 1.5–2 mg/kg/day orally for 3 months, or 0.5–1 g IV every 2–4 weeks 1
• Mycophenolate mofetil for 6 months is an alternative to cyclophosphamide 1
• Plasma exchange (especially double-filtration plasmapheresis) for rapidly progressive glomerulonephritis 1

Rituximab Protocol

• Rituximab has 70–90% renal response rate (complete plus partial) 1
• Use classical schedule (375 mg/m² per infusion) rather than high-dose (1000 mg) in patients with high cryoglobulin levels to avoid flares 1
• Start with plasmapheresis before rituximab if cryoglobulin levels are very high 1
• Glomerulonephritis improves within 3 months; complete healing takes longer 1

Antiviral Therapy

• Add direct-acting antivirals to immunosuppression for HCV eradication 1, 3
• IFN-free antivirals have good tolerance even in severe renal failure 1
• Sustained virologic response correlates with improvement in serum creatinine and reduction in proteinuria 1

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Multiple Myeloma-Related Cast Nephropathy

Combine plasma exchange with corticosteroids to improve renal recovery, and maintain aggressive saline hydration to achieve urine output >3 L/day. 2

Specific Interventions

• Early plasma exchange markedly reduces the need for dialysis 2
• Aggressive IV saline hydration is especially critical with Bence-Jones proteinuria or hypercalcemia 2
• Avoid nephrotoxic drugs and iodinated contrast unless adequate hydration is ensured 2
• Contrast-induced nephropathy accounts for <1% of acute renal failure in myeloma when dehydration is avoided 2

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Acute Interstitial Nephritis

• High-dose corticosteroids are the mainstay of treatment 7
• Remove offending drug immediately 2
• Kidney biopsy confirms diagnosis when etiology is uncertain 7

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Thrombotic Microangiopathy (TTP/aHUS)

• TTP requires urgent plasma exchange with fresh frozen plasma replacement 7
• aHUS may require complement inhibition with eculizumab (not detailed in provided guidelines)
• Distinguish from immune-complex RPGN, as calcineurin inhibitors cause thrombotic microangiopathy and should be avoided 4

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Critical Contraindications to Immunosuppression

Withhold aggressive immunosuppression when eGFR <30 mL/min/1.73 m² is accompanied by extensive interstitial fibrosis, tubular atrophy, or glomerular sclerosis on biopsy, UNLESS there is clear active necrotizing or crescentic disease. 2, 4, 3

When to Treat Despite Low eGFR

• Preserved renal parenchyma with acute tubular necrosis warrants treatment 4
• Active crescentic disease justifies treatment regardless of eGFR 4
• The decision is based on biopsy findings showing renal viability, not eGFR alone 4

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Monitoring Response and Refractory Disease

Regular Assessment Parameters

• Serum creatinine, proteinuria, and urinary sediment to gauge response 2
• Serum albumin and complement levels as adjunctive markers 2
• Anti-dsDNA antibodies in lupus nephritis for activity trends 2

Management of Inadequate Response

• If no adequate response after 3–4 months, switch between mycophenolate and cyclophosphamide, add rituximab, or consider clinical trial enrollment 2

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Common Pitfalls and How to Avoid Them

• Delaying therapy while awaiting biopsy in ANCA-positive patients leads to irreversible kidney injury 2, 4
• Initiating immunosuppression without excluding active infection can precipitate life-threatening sepsis 1, 2
• Excessive glucocorticoid dosing should be avoided; use evidence-based tapering protocols from the PEXIVAS trial to minimize toxicity 1, 2
• Aggressive immunosuppression in kidneys with predominantly chronic histologic changes provides no benefit and increases adverse-event risk 2, 4
• Assuming all patients with low eGFR should not be treated is incorrect—active crescentic disease warrants treatment regardless of eGFR 4
• Using calcineurin inhibitors (tacrolimus, cyclosporine) for immune-complex RPGN causes thrombotic microangiopathy and should be avoided 4