Kidney Week

Abstract: PUB302

PAX2 Mutation Associated with Focal Segmental Glomerulosclerosis

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Santos Carrasquillo, Manuel Antonio, Cleveland Clinic Florida, Weston, Florida, United States

Manuel Antonio Santos Carrasquillo, MD

• Herlitz, Leal C., Cleveland Clinic, Cleveland, Ohio, United States

Leal C. Herlitz, MD

• Gebreselassie, Surafel K., Cleveland Clinic Florida, Weston, Florida, United States

Surafel K. Gebreselassie, MD

• Cohen, Scott D., Cleveland Clinic Florida, Weston, Florida, United States

Scott D. Cohen, MD, FASN, MPH

Introduction

FSGS is a heterogenous disorder with a variety of causes including immunologic factors, genetics, medications, and infections. Recognizing the potential pathogenic etiology is essential in the appropriate management of patients. Knowledge of genetic etiologies will avoid unnecessary patient exposure to the toxic effects of immunosuppression.

Case Description

A 19-year-old male presented with abnormal kidney function, eGFR 42 ml/min/1.73m2, serum creatinine of 2.2 mg/dl along with a nephrotic range proteinuria of 4.1 g/g on a random urine sample. Serum albumin was 4.5 g/dl. On physical examination, the patient had a blood pressure of 125/78, examination was remarkable for 1+ peripheral edema. A kidney biopsy was performed which showed FSGS with mild to moderate tubular atrophy and interstitial fibrosis. 6 out of 28 glomeruli were globally sclerotic with 7 FSGS lesions, some of which were perihilar in location, there was also moderate foot process effacement. Genetic testing was ordered and returned with a PAX2 gene mutation. The patient was referred for genetic counseling as well as ophthalmology and audiology evaluations. He was started on Losartan 25 mg once daily; on 3 month follow up the proteinuria decreased to 1.4 g/g with a serum creatinine of 2.4 mg/dl, eGFR 40 ml/min/1.73m2.

Discussion

Mutations in PAX2 are associated with autosomal dominant adult-onset FSGS. PAX2 is a transcription factor that plays an essential role in kidney development and was previously found to be associated with congenital abnormalities of the kidney and urinary tract (CAKUT) including reduced nephron mass. The reduction in nephron mass can lead to glomerular hyperfiltration and adaptive FSGS. PAX2 may also have a direct effect on the podocyte as it suppresses the expression of WT1, a nuclear protein expressed in these cells. Genetic testing can play an integral role in the diagnostic evaluation and treatment of patients with FSGS.