A Novel Subtype of Minimal Change Disease

Document Type

Conference Proceeding

Publication Date

10-2024

Publication Title

Journal of the American Society of Nephrology

Abstract

Introduction: Minimal change disease (MCD) is a podocytopathy which causes failure of the glomerular filtration barrier by loss of slit diaphragm architecture. Etiology is unclear. It is characterized by normal light microscopy and negative immunofluorescence(IF) with diffuse foot process effacements noted on electron microscopy(EM) however punctate IgG staining on biopsy may indicate a novel autoimmune mechanism. Case Description: A 59 yo Caucasian male with history of CKD 3b(baseline S.Cr 1.8-2), cerebral palsy complicated by chronic urinary retention with supra-pubic catheter, HTN presented with worsening B/L lower extremity edema and weight gain. The physical exam showed anasarca. Labs showed S.Cr 2.77, serum albumin 1.5 g/dl, urine albumin creatinine ratio 11,905 mg/g, dyslipidemia. UA showed 4+ proteinuria, >20 RBCs, >20 hyaline casts. Further workup for nephrotic syndrome including PLA2R antibody, HIV, hepatitis, syphilis, SPEP/UPEP, free light chains, complement levels, ANA, ANCA, cryoglobulins was negative. Kidney biopsy was consistent with MCD, mild acute tubular injury and interstitial fibrosis, moderate thickening of arteries and tubular atrophy. IF showed positive granular staining for IgG in Bowman’s space and GBM. EM showed diffuse effacement of foot processes and was unremarkable for immune complex deposits or fibrillary materials. Oral prednisone was started with plan for slow taper. Edema improved with diuretic therapy. Discussion: MCD is characterized by diffuse effacement of podocyte foot processes on EM, absence of dense deposits or immune complexes and unremarkable LM. This case is unique with positive findings on IF showing positive granular staining for IgG in Bowman’s space and GBM. Underlying molecular mechanisms are debatable, however efficacy of B-cell targeted therapies in steroid dependent and relapsing cases suggests autoantibody etiology. Anti-nephrin autoantibodies have been associated with massive proteinuria in animal models and as alloantibodies in post transplant children with congenital nephrin deficiency. A recent study (Watts et al.) hypothesized punctate IgG staining may represent in situ binding of nephrin autoantibodies resulting in redistribution of nephrin and disruption of intercellular junctions between podocytes. Further research is needed to establish prognostic significance of this subclassification of MCD and the role for targeted treatment.

Volume

35

Issue

10S

First Page

700

Comments

Kidney Week, American Society of Nephrology, October 24-27, 2024, San Diego, CA

Last Page

701

DOI

10.1681/ASN.2024mmk3cbsc

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