By:

[1] Mignano SE, Pascal V, Odioemene NE, Forehand W, Javaugue V, Said SM, Sethi S, Sirac C, Nasr SH: Monoclonal Immunoglobulin Crystalline Membranous Nephropathy. Am J Kidney Dis 2024, 84:120-5. https://doi.org/10.1053/j.ajkd.2023.11.011

[2] Nasr SH, Sirac C, Leung N, Bridoux F: Monoclonal immunoglobulin crystalline nephropathies. Kidney Int 2024. https://doi.org/10.1016/j.kint.2024.02.027

Blogged by Nicolas Kozakowski, January 6th, 2025

The manifold of histological presentations of MGRS has been recently expanded with the case report by Mignano et al., describing a monoclonal immunoglobulin crystalline membranous

nephropathy (MN)¹. The fact that both monoclonal immunoglobulin-induced MN (alone or in association with other lesions) and crystalline variants of MGRS are rare events renders the association of these presentations quite exciting. The subepithelial electron-dense deposits reported in monoclonal MN cases are usually comparable to those of non-monoclonal MNs, however, this particular case displayed electron-dense rhomboid to needle-shaped crystals. Interestingly, the authors completed their analysis with an immunoglobulin repertoire sequencing assay, providing insights in the physicochemical properties of the pathogenic immunoglobulin and potential explanations on its crystallization.

Worth mentioning, some of the same authors provided an overview of monoclonal immunoglobulin crystalline nephropathies in a mini review shortly after, including this new phenotype².

Denic, Aleksandar; Bogojevic, Marija; Mullan, Aidan F.; Sabov, Moldovan; Asghar, Muhammad S.; Sethi, Sanjeev; Smith, Maxwell L.; Fervenza, Fernando C.; Glassock, Richard J.; Hommos, Musab S.; Rule, Andrew D.

JASN October 2022, 33 (10) 1927-1941; DOI: https://doi.org/10.1681/ASN.2022030234

Chronic damage as assessed in the kidney biopsy is an independent predictor of renal function decline (doi: 10.1681/ASN.2017121260, doi: 10.1681/ASN.2021010044). Different grading systems for chronicity have been published: some are diagnosis-specific, others can be used regardless of disease etiology.

The success of histologic grading schemes partly depends on ease-of-use; too detailed or time-intensive systems generally do not make it to diagnostic practice. In a recent study published in JASN, the authors examine a morphometry-based approach (with quantification of chronicity parameters assisted by software) to a standard, commonly used ‘eyeballing’ or visual estimation approach based on glomerulosclerosis, interstitial fibrosis/ tubular atrophy (IFTA) and arteriosclerosis (DOI: 10.1016/j.kint.2017.01.002). The study population consisted of a historical cohort of 353 biopsies with follow-up data, making evaluation on hard end points possible (namely, evolution to end-stage kidney disease or progressive chronic kidney disease, respectively emerging in 21% and 44% of patients, over a median follow-up of 7.5 years). Interestingly, morphometry for the above-described features did not substantially differ in predicting outcomes compared to eyeballing.

Additionally, the authors took the opportunity to examine less ‘classical’ measures of chronicity such as IFTA foci density and arteriolar hyalinosis by morphometry. A ten-point score using percentage of glomerulosclerosis, percentage of IFTA, IFTA foci density and arteriolar hyalinosis showed a superior performance. In the discussion, the authors hypothesize that this actually reflects pathogenesis of chronic damage better. The authors also claim they will work on translating this into a new visual estimation approach and as such, close the circle.

Blogged by Amélie Dendooven

Andrew J.B. Watts, Keith H. Keller, Gabriel Lerner, Ivy Rosales, A. Bernard Collins, Miroslav Sekulic, Sushrut S. Waikar, Anil Chandraker, Leonardo V. Riella, Mariam P. Alexander, Jonathan P. Troost, Junbo Chen, Damian Fermin, Jennifer L. Yee, Matthew G. Sampson, Laurence H. Beck, Joel M. Henderson, Anna Greka, Helmut G. Rennke and Astrid Weins. 

JASN January 2022, 33 (1) 238-252; DOI: https://doi.org/10.1681/ASN.2021060794

Blogged by Amélie Dendooven

Minimal change disease (MCD) is a common diagnosis in children and adults, and can be sparked by triggers such as infections or vaccination.  While a B-cell etiology was already suspected, a recent paper goes a step further. The authors show that nephrin autoantibodies are present in a subset of patients with active MCD, correlate with disease activity and associate with the presence of punctate IgG in the biopsy (colocalizing with nephrin) as evaluated by IF studies. Moreover, a case report of a 27-year old patient known with MCD is presented where pretransplant nephrin antibodies associate with massive proteinuria recurrence after transplantation. Although many questions remain, this is an exciting paper on disease mechanism in one of the most common proteinuric diseases and it invites us all to look more closely at IF in MCD.