conference reporter

Case for Consideration: Glomerular Diseases at a National Kidney Disease Conference

by Carla M. Nester, MD, MSA, FASN


Researchers at the NKF 2023 Spring Clinical Meetings (SCM23) reported on several interesting cases involving complement-mediated glomerular diseases. One case in particular highlighted the importance of biopsy interpretation in patients with late-stage kidney disease.

Following these presentations, featured expert Carla M. Nester, MD, MSA, FASN, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr Nester's clinical perspectives are presented here. 

Carla M. Nester, MD, MSA, FASN

Jean Robillard Professor of Pediatric Nephrology
Division Director of Pediatric Nephrology, Dialysis, and Transplantation
University of Iowa Stead Family Children's Hospital
Iowa City, IA

"This case is interesting because of all of the confounding factors, particularly the timing of the biopsy with respect to a recent infection, and because of its educational value. It is not well known that late-stage kidney biopsies often show C3 deposition—and that the presence of C3 deposition does not necessarily mean that the patient has C3G.”

Carla M. Nester, MD, MSA, FASN

Among the cases that were presented at SCM23, poster 146 really stood out to me because it dealt with the challenges of interpreting late-stage kidney biopsies that show complement 3 (C3) deposition. In this poster, Sankar et al presented the case of a 58-year-old Latina patient with a 5-year history of end-stage renal disease and dialysis dependence, as well as a history of hypertension and hypothyroidism. And, in view of her kidney disease and her young age, a transplant was being considered, and she had therefore presented for pretransplant evaluation. 

The patient had undergone biopsy previously, at the time of intraventricular shunt placement, and, at that time, the kidney biopsy revealed proliferative sclerosing glomerulonephritis (GN) with C3 deposition, chronic tubulointerstitial nephritis, and advanced chronic injury. The presumptive diagnosis of C3GN prompted concerns about kidney disease recurrence after transplantation and the need for anticomplement therapy. However, testing was undertaken using a broad, next-generation sequencing–based genetic panel, and it identified a likely pathogenic variant in COL4A4 associated with autosomal dominant Alport syndrome. In light of the entire clinical picture, it was felt that the C3 deposition was likely secondary to infection-driven inflammation associated with Alport syndrome—and was not due to C3 glomerulopathy (C3G)—such that the concerns about recurrence following transplantation were likely unsupported.

This case is interesting because of all of the confounding factors, particularly the timing of the biopsy with respect to a recent infection, and because of its educational value. It is not well known that late-stage kidney biopsies often show C3 deposition—and that the presence of C3 deposition does not necessarily mean that the patient has C3G. I see many patients with late-stage biopsies who are referred to me because of presumptive C3G, and I end up telling a good number of these families that I do not believe that they have C3G, a rare disease that results from alternative pathway complement dysregulation.

Having some degree of C3 deposition on the kidney biopsy may simply be a representation of a late-stage kidney biopsy. The explanation that has been considered for this phenomenon is that, in late-stage kidney disease, complement factor D (a positive regulator of complement activity) begins to accumulate. This, in turn, sets the stage for increased local complement activity. Regardless of the explanation for why C3 may be deposited on a late-stage kidney biopsy, these patients invariably will be found to have normal genetic studies and normal systemic complement biomarkers such as nephritic factors (the most common driver of C3G). The latter is also true in post–infection-related C3 deposition. I would agree with the authors that a concern about the recurrence of C3-dominant GN post transplant should be low in either of these circumstances.  

Ultimately, this case from SCM23 highlights the utility of genetic testing in the context of unclear renal biopsy findings, as the genetic findings helped clarify the etiology of the patient’s kidney disease and informed clinical decision making. Of course, genetic testing may also introduce a level of complexity for some patients or situations (eg, when a variant of uncertain significance is identified); nonetheless, the opportunity to clarify future risk to kidney health often makes genetic testing an important step. 


Bose S, Pathireddy S, Baradhi KM, Reddy Aeddula N. Alport's syndrome and intracranial aneurysm: mere coincidence or undiscovered causal relationship. BMJ Case Rep. 2019;12(1):e228175. doi:10.1136/bcr-2018-228175

Heiderscheit AK, Hauer JJ, Smith RJH. C3 glomerulopathy: understanding an ultra-rare complement-mediated renal disease. Am J Med Genet C Semin Med Genet. 2022;190(3):344-357. doi:10.1002/ajmg.c.31986 

Levy Erez D, Meyers KE, Sullivan KE. C3 nephritic factors: a changing landscape. J Allergy Clin Immunol. 2017;140(1):57-59. doi:10.1016/j.jaci.2017.02.018

Lin D-W, Chang C-C, Hsu Y-C, Lin C-L. New insights into the treatment of glomerular diseases: when mechanisms become vivid. Int J Mol Sci. 2022;23(7):3525. doi:10.3390/ijms23073525

Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4):753-779. doi:10.1016/j.kint.2021.05.015

Sankar L, Sanghi P, Clark D, Chang A. Genetic testing: complementary or contradictory to kidney biopsy in evaluation of patients with chronic kidney disease–a unique case [poster 146]. Poster presented at: National Kidney Foundation 2023 Spring Clinical Meetings; April 11-15, 2023; Austin, TX.

Smith RJH, Appel GB, Blom AM, et al. C3 glomerulopathy—understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019;15(3):129-143. doi:10.1038/s41581-018-0107-2  

Uffing A, Hullekes F, Riella LV, Hogan JJ. Recurrent glomerular disease after kidney transplantation: diagnostic and management dilemmas. Clin J Am Soc Nephrol. 2021;16(11):1730-1742. doi:10.2215/CJN.00280121

This information is brought to you by Engage Health Media and is not sponsored, endorsed, or accredited by the National Kidney Foundation. 

More in IgAN & C3G


IgAN & C3G

Conference Reporter in IgAN and C3G - Complement Mediated Kidney Diseases to Cover Key Topics Being Presented at the NKF 2023 Spring Clinical Meetings

Conference Reporter

Conference Reporter delivers health care providers with insights from key thought leaders on exciting news presented at major medical conferences, ...READ MORE


IgAN & C3G

Immunoglobulin A Nephropathy: Challenges and Emerging Treatments

Conference Reporter by Andrew S. Bomback, MD, MPH

Researchers and clinicians seek to improve upon the existing approach to immunoglobulin A nephropathy (IgAN). As the understanding of the pathogene...READ MORE


IgAN & C3G

Improving Outcomes in Complement-Mediated Kidney Disease

Conference Reporter by Andrew S. Bomback, MD, MPH

Complement is clearly involved in the pathogenesis of complement 3 glomerulopathy (C3G) and aspects of immunoglobulin A nephropathy (IgAN), spurrin...READ MORE

More In Conference Reporter