Kidney Week

Abstract: PUB126

Beyond the Kidney Biopsy: Genetic Testing Unmasks Fabry Disease in Progressive CKD in the Community Setting

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Chauhan, Mallika, Augusta University, Augusta, Georgia, United States

Mallika Chauhan, MPH

• Morris, Cuyler Thomas, Mercer University School of Medicine, Macon, Georgia, United States

Cuyler Thomas Morris

• Chauhan, Rajeev, Augusta University, Augusta, Georgia, United States

Rajeev Chauhan, MD

• Smith, Tamorie L., Augusta University, Augusta, Georgia, United States

Tamorie L. Smith, MD

Introduction

Fabry disease (FD) is a rare X-linked lysosomal storage disorder that can cause progressive nephropathy, often mimicking common causes of chronic kidney disease (CKD). Late-onset disease may lack classic extrarenal findings, delaying diagnosis and treatment.

Case Description

A 49-year-old African American man with hypertension, gout, chronic NSAID exposure, and cardiac conduction disease requiring pacemaker placement presented with progressive chronic kidney disease of unclear etiology. Initial evaluation revealed a serum creatinine of 4.46 mg/dL, estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m², and nephrotic-range proteinuria of 3.6 g/day, raising concern for underlying glomerular disease.
Due to worsening kidney function and significant proteinuria, a renal biopsy was pursued; however, the specimen contained only medullary tissue without glomeruli, rendering it nondiagnostic. The patient declined repeat renal biopsy due to procedural discomfort.

Given progressive renal decline despite controlled hypertension and the absence of a definitive diagnosis, next-generation genetic testing was pursued. Testing revealed a pathogenic GLA missense mutation, absent α-galactosidase A activity, and elevated lyso-Gb3, confirming Fabry disease. Additional findings included a COL4A5 mutation and APOL1 risk alleles, suggesting possible overlapping genetic contributors to CKD progression. By the time of diagnosis, serum creatinine had increased to 6.1 mg/dL and eGFR had declined to 11 mL/min/1.73 m². Enzyme replacement therapy with agalsidase beta was initiated.

Discussion

This case highlights that when kidney biopsy is suboptimal, unavailable, or nondiagnostic, genetic testing can provide critical diagnostic information and help establish a definitive diagnosis, particularly when rare inherited kidney disease is suspected. Fabry disease should remain an important consideration in unexplained proteinuric CKD, especially when cardiac abnormalities suggest systemic involvement despite the absence of classic manifestations. This case also underscores that the diagnostic utility of renal biopsy depends on adequate cortical tissue sampling, and when histopathology is inconclusive, genetic testing may offer a high-yield pathway that can directly alter management.