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Abstract: TH-PO955

Collapsing Glomerulopathy in an APOL1 Compound Heterozygous Patient with CMV Infection: The Double Hit Theory

Session Information

Category: Trainee Case Report

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Al faris, Faris, Albany Medical Center, Albany, New York, United States
  • Hongalgi, Krishnakumar D., Albany Medical Center, Albany, New York, United States
Introduction

Collapsing glomerulopathy (CG) is a rare and aggressive variant of focal segmental glomerulosclerosis (FSGS). Commonly associated with human immune deficiency virus (HIV). We present a case of CG in an HIV-negative African American (AA) patient with Cytomegalovirus (CMV) infection. The patient is compound heterozygous for APOL1 risk variants. We propose that CMV can act as a “second hit” in the pathogenesis of CG in the genetically predisposed individuals.

Case Description

A 31-year-old AA female with sickle cell disease was admitted with 2 weeks of fever, malaise, nausea, vomiting, cough and chest wall tenderness. On admission her serum creatinine was 2.39 mg/dl and peaked at 7.19mg/dl. Urine investigations revealed nephrotic range proteinuria. CMV DNA PCR was positive in plasma and urine.
Renal biopsy showed features of collapsing glomerulopathy, characterized by collapse of the capillary loops, prominence of the overlying epithelial cells and extensive effacement of foot processes. Genetic testing showed compound heterozygous mutations in the APOL1 gene.
The patient was treated with high dose steroids and anti-viral therapy with ganciclovir. With resolution of CMV infection, she made full renal recovery.

Discussion

CG as well as other nephropathies have well established racial disparity, predominantly affecting AA patients. The discovery of apolipoprotein L1 gene (APOL1) helped improve our understanding of genetic predisposition to renal disease. Increased risk can be attributed to the presence of two specific variants in the APOL1 gene (G1 and G2). These variants are present in about 30% of APOL1 alleles in the AA population. Individuals with one or two risk alleles are at greater risk for developing FSGS, hypertension-attributed ESRD, sickle cell-associated kidney disease, HIV-associated nephropathy, and shortened graft survival of kidney transplants.
CG was initially described in HIV patients but also associated with viral infections (e.g. parvovirus B19 and CMV), lymphoproliferative disorders, autoimmune diseases and sickle cell disease. CMV infection could be a second hit in the genetically susceptible patient. Identification of CMV infection in patients with CG is important as they usually improve with treatment of the viral infection.