Hypocomplementemia at Diagnosis of Pauci-immune Glomerulonephritis Is Associated With Advanced Histopathological Activity Index and High Probability of Treatment Resistance

Sophia Lionaki; Smaragdi Marinaki; George Liapis; Emmanuel Kalaitzakis; Sophia Fragkioudaki; Petros Kalogeropoulos; Ioannis Michelakis; Andreas Goules; Athanasios G Tzioufas; John N Boletis

doi:10.1016/j.ekir.2021.05.043

Hypocomplementemia at Diagnosis of Pauci-immune Glomerulonephritis Is Associated With Advanced Histopathological Activity Index and High Probability of Treatment Resistance

Kidney Int Rep. 2021 Jun 12;6(9):2425-2435. doi: 10.1016/j.ekir.2021.05.043. eCollection 2021 Sep.

Affiliations

¹ Department of Nephrology and Transplantation Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece.
² 1 Department of Pathology, Medical School, National and Kapodistrian University of Athens, Laiko Hospital, Athens, Greece.
³ Department of Pathophysiology, School of Medicine and Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

Introduction: Recent evidence suggests that complement activation is important in the pathogenesis of pauci-immune (PI) vasculitis. This is a retrospective investigation of the frequency of hypocomplementemia at pauci-immune glomerulonephritis (PIGN) diagnosis, in relation to vasculitic manifestations, renal histopathology, and treatment outcomes.

Methods: A total of 115 patients with biopsy-proven PIGN were categorized based on their serum complement C3 (sC3). Histopathology evaluation included activity and chronicity indexes. The primary outcome of interest was treatment resistance, defined as a progressive decline in kidney function, with persistently active urine sediment, leading to dialysis dependency or vasculitis-related death.

Results: In all, 20.9% of patients had low sC3 levels associated with more advanced renal impairment (P < 0.01), requiring acute dialysis (P < 0.01) more frequently compared to patients with normal sC3. Within 1 year, 85.7% of patients with normal sC3 responded to therapy, versus 58.3% of those with low sC3 (P = 0.001). The probability of treatment resistance was strongly associated with low sC3 (P = 0.004), high serum creatinine (P < 0.001), acute dialysis requirement (P < 0.001), and high histopathological score of chronicity (P < 0.01). Advanced histopathological activity was related to more intense interstitial leukocyte infiltration (P = 0.005) and higher likelihood of fibrinoid necrosis documentation in a vessel wall (P = 0.02). The probability of treatment resistance was higher in patients with low sC3 (odds ratio [OR] = 6.47, 95% confidence interval [CI] 1.47-28.35, P = 0.013), oliguria (OR = 29.57, 95% CI = 4.74-184, P < 0.0001), and high chronicity score (OR = 1.77, 95% CI = 1.23-2.54, P = 0.002).

Conclusion: Low sC3 is emerging as an independent predictor of treatment resistance in patients with PIGN associated with higher index of histopathological activity at diagnosis compared to normal sC3.

Keywords: complement; glomerulonephritis; histopathology; outcome; pauci-immune.