Clinical Profile, Treatment Outcomes, and Complement Pathway Involvement in Idiopathic ANCA-negative Renal-Limited Pauci-immune Crescentic Glomerulonephritis: A Single-Centre Prospective Study

Abstract

Background: Pauci-immune crescentic glomerulonephritis (GN) refers to a category of necrotizing GN in which there are no or only a few immune deposits by immunofluorescence. They constitute a distinct yet important cause of rapidly progressive GN. Objectives: To assess the clinical, histological, biochemical, and serological characteristics of patients diagnosed with idiopathic anti-neutrophil cytoplasmic autoantibodies (ANCAs)-negative renal-limited pauci-immune crescentic GN, the treatment outcomes, and the possible role of the alternative complement pathway in etiopathogenesis. Methods: This study included a total of 21 adult patients (≥ 18 years) with renal biopsy-proven pauci-immune crescentic GN with ANCA negativity. Patients with renal biopsy indicating more than 10% crescents were eligible for inclusion, while those with crescentic GN due to secondary causes and individuals who later tested positive for immune markers during the study period were excluded from this study. A complete remission is defined as normalization of serum creatinine, normal serum C3 levels, and 24-hour urine protein excretion of < 300 mg per day. "No remission" is defined as dialysis dependence, failure of serum creatinine, and 24-hour urine protein to decrease by > 50% from the baseline towards the end of the treatment. Anyone who showed a tendency towards remission but didn’t meet the above criteria was said to have attained partial remission. Results: A total of 11 patients (52.4%) achieved either complete or partial remission with Rituximab/plasma exchange or both. The clinical remission was more among patients with cellular and non-circumferential crescents and with crescents less than 25%. Patients who received a combined rituximab and plasma exchange therapy showed a better clinical tendency towards remission, though a statistical significance could not be attached to any of the above parameters and to the outcome, given the smaller sample size. There was involvement of the alternative complement pathway in 38% (8) of the patients. Conclusions: The ANCA-negative idiopathic pauci-immune type accounts for less than five percent of crescentic GN. Patients with cellular, non-circumferential crescents and crescents of < 25% have a better prognosis. Though being referred to as pauci-immune, the alternative complement pathway is implicated in the pathogenesis in a small percentage of this distinctive group.