Clinicopathological correlation of kidney diseases with monoclonal immunoglobulin deposition associated with hematopoietic disorders

ZEHRANUR KİKİ

Clinicopathological correlation of kidney diseases with monoclonal immunoglobulin deposition associated with hematopoietic disorders

Thesis Type: Expertise In Medicine

Institution Of The Thesis: Hacettepe University, Turkey

Approval Date: 2026

Thesis Language: Turkish

Student: ZEHRANUR KİKİ

Supervisor: MERAL ÜNER

Open Archive Collection: AVESIS Open Access Collection

Abstract:

Renal diseases associated with monoclonal immunoglobulin/paraprotein deposition are heterogeneous, and diagnostic classification and treatment decisions—particularly within the MGRS spectrum—can be challenging. This study aimed to characterize the morphologic spectrum of monoclonal gammopathy–associated renal lesions, evaluate the relationship between complement deposition on immunofluorescence (especially C3) and diagnostic patterns/clinical course, and explore its potential contribution to treatment strategy. A total of 104 kidney needle biopsies from 102 patients (2014–2024) were retrospectively reviewed; histology/histochemistry and immunofluorescence (IgG/IgA/IgM, C3, C1q, kappa/lambda) were re-evaluated, clinical data were retrieved, and appropriate statistical tests were used. The most frequent diagnostic pattern was PGNMIg (n=35, 33.7%). Complement deposition was identified in 46 of 104 biopsies (44.2%) and was most frequent in PGNMIg (71.4%) and MIDD (53.3%), while less common in light chain amyloidosis (16%). The association between treatment and renal course differed by C3 status: among C3-negative cases (n=26), progressive course was observed in 83.3% of patients treated with classical immunosuppressive/immunomodulatory agents versus 20.0% of patients treated with clone-directed therapy, with a significant difference (Mann–Whitney U p=0.018). In contrast, no significant difference was found in the C3-positive group (n=29; p=0.582). Overall, C3 deposition appears enriched in specific patterns (PGNMIg, MIDD) and, in this cohort, the benefit of clone-directed therapy on renal functional decline was mainly evident in C3-negative cases, suggesting C3 status may help individualize treatment strategies.