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Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis

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Abstract

Background

Data on therapy and outcome of dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and immune-complex MPGN (IC-MPGN) in children are limited.

Methods

In this retrospective single-center study from 2007 to 2019, kidney biopsies were reviewed to include patients aged <18-years with C3 glomerulopathy and IC-MPGN. Initial immunosuppression comprised prednisolone, mycophenolate mofetil (n = 51), tacrolimus (n = 11), and/or IV cyclophosphamide (n = 20). Clinicopathological features, response to therapy, and adverse outcome (eGFRcr < 15 mL/min/1.73 m2 or death) were evaluated.

Results

A total of 92 patients were classified as DDD (n = 48, 52.2%), C3GN (n = 26, 28.3%), and IC-MPGN (n = 18, 19.6%) by immunohistochemistry and electron microscopy; 8 patients with DDD were misclassified as IC-MPGN on immunofluorescence. At last follow-up (median 4.3 years), complete or partial remission occurred in 28.5, 36.1, and 16.7% patients with DDD, C3GN, and IC-MPGN, respectively. Serum albumin at onset < 2.5 g/dL (HR = 0.29, P = 0.005) and persistently low serum C3 (HR = 0.34, P = 0.02) were associated with lack of remission. The 5-year kidney survival was 62.6, 85.5, and 88.5% in patients with DDD, C3GN, and IC-MPGN, respectively (log-rank, P = 0.006). Presentation as rapidly progressive GN (HR = 11.2, P < 0.001), age > 10 years at onset (HR = 4.0, P = 0.004), and DDD (HR = 4.2, P = 0.02) were independently associated with adverse outcome; achieving remission was protective (HR = 0.04; P < 0.001).

Conclusion

Outcome in patients with C3 glomerulopathy and IC-MPGN was unsatisfactory, and only a small proportion of patients achieved complete or partial remission. Patients with DDD were more likely to present with rapidly progressive GN and were at higher risk of adverse outcomes, including kidney failure.

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Acknowledgments

The study received funding support from the Department of Biotechnology, Government of India [BT/PR11030/MED/30/1644/2016].

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Authors and Affiliations

  1. Division of Nephrology, ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Priyanka Khandelwal, Swati Bhardwaj, Aditi Sinha, Pankaj Hari & Arvind Bagga

  2. Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Geetika Singh

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  1. Priyanka Khandelwal
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Correspondence to Pankaj Hari.

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The study was conducted following the Institute ethical clearance (IEC/NP-353/08-10-2014).

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Supplementary Fig. 1

Representative image of immune-complex membranoproliferative glomerulonephritis showing (a) membranoproliferative pattern of glomerular injury (hematoxylin eosin 20× magnification); (b–h) direct immunofluorescence panel showing negative staining for IgA, capillary wall granular staining for IgG (2+), C3c (3+), C1q (1+), kappa (3+), and lambda (2+) and peripheral entrapment of IgM (fluorescein isothiocyanate 20× magnification); and (i) transmission electron microscopy demonstrating subendothelial (white arrow) and mesangial (starred) immune-type electron dense deposits which lack organization (uranyl acetate lead citrate 1550× magnification) (JPG 98 kb)

Supplementary Fig. 2

Representative image of C3 glomerulopathy showing (a) membranoproliferative pattern of glomerular injury (hematoxylin–eosin 20× magnification); (b) direct immunofluorescence showing strong staining for C3c (3+) (fluorescein isothiocyanate 20× magnification) and transmission electron microscopy demonstrating (c) intensely osmiophilic electron dense deposits in an intramembranous location in dense deposit disease and (d) subendothelial and mesangial unorganized immune type deposits in C3 glomerulonephritis (uranyl acetate lead citrate 1250× magnification) (JPG 183 kb)

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Khandelwal, P., Bhardwaj, S., Singh, G. et al. Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis. Pediatr Nephrol 36, 591–600 (2021). https://doi.org/10.1007/s00467-020-04736-8

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