SURPRISINGLY GOOD RESPONSE OF A SEVERE ANCA-NEGATIVE CRESCENTIC PAUCI-IMMUNE GLOMERULONEPHRITIS SUCCESSFULLY TREATED WITH CORTICOSTEROIDS, CYCLOPHOSPHAMIDE AND RITUXIMAB

Introduction:

ANCA-negative pauci-immune glomerulonephritis (PIGN) occurs in 10-30% of patients with PIGN. Although pathogenesis remains largely unclear, neutrophils seem to play a major role as in ANCA-positive PIGN. By some, it is regarded as a distinct entity with a different clinical spectrum while others suggest a failure of contemporary methods to detect ANCA.

Due to limited data on treatment, there is no consensus about the optimum protocol that should be followed in those cases.

Methods:

A 29-years old female with a history of diabetes mellitus type I, celiac disease and autoimmune thyroiditis presented with fever, acute renal insufficiency, anaemia and active urine sediment. No extrarenal organ involvement was noted.

At presentation, serum creatinine (Cr) was 5.4 mg/dL (baseline Cr was 0.9 mg/dl four months earlier), eGFR 10 ml/min/1.73 m2, 24-hour urine protein 950 mg. Immunological work-up showed positive ANA 1/80, c-ANCA negative, p-ANCA negative, anti-myeloperoxidase (MPO) negative, anti-GBM negative, C3 and C4 normal. CRP was elevated at 134 mg/L, ESR >140, Hct 21%. White blood cells were normal, blood and urine cultures were negative, and virology tests were negative for recent infection.

A renal biopsy was performed which showed cellular crescents and/or fibrinoid necrosis in 78% of glomeruli, 11% were globally sclerosed and 11% with ischemic lesions or segmental sclerosis. None of the glomeruli was normal. The interstitium showed diffuse infiltration by inflammatory cells (lympho/plasmacytes, macrophages and neutrophils).  Mild tubular atrophy (20%) and mild to moderate (20-25%) interstitial fibrosis were depicted. Immunofluorescence was negative for IgG, IgA, IgM, C3, C1q, C4, κ and λ light chains. No deposits were identified in electron microscopy.

A pauci-immune crescentic and diffusely necrotizing glomerulonephritis was diagnosed.

Infection, malignancy and drugs were excluded as a cause of PIGN.

Results:

The patient received remission induction therapy with pulse methylprednisolone (750 mg X 3 days, then tapered starting from 48 mg and reaching 4 mg in a 6-month period), per os cyclophosphamide for 2 months (1.5 mg/kg adjusted for renal function) and rituximab (1 g every 2 weeks) as per Cortazar et al protocol.

The patient received trimethoprim/sulfamethoxazole as prophylaxis.

During a follow-up period of six months, the patient suffered an episode of neutropenia at 2 months which was successfully treated with a hemopoietic growth factor. No infection episodes were recorded. Last creatinine value at six months is 1.5 mg/dL (eGFR 47 ml/min/1.73 m2). Urine analysis shows <10 red cells per HPF and proteinuria is minimal. Inflammatory indices (CRP, ESR) have all normalised.

Conclusions:

ANCA-negative PIGN is usually a renal-limited disease. It bears a worse renal prognosis than ANCA-positive PIGN with a twofold increased risk of end-stage kidney disease regardless of the severity of fibrosis in renal biopsy.

An induction treatment consisting of a combination regimen with low cumulative dose of corticosteroids and cyclophosphamide as well as rituximab seems to be effective for the induction of remission with no serious adverse events in the short term.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.