Abstract: PUB229
Autosomal Dominant Tubulointerstitial Kidney Disease due to Uromodulin Mutation (ADTKD-UMOD)
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Gupta, Aarzoo, Saint Vincent Hospital, Worcester, Massachusetts, United States
- Yekula, Anuroop, Saint Vincent Hospital, Worcester, Massachusetts, United States
- Gurung, Susant O., Saint Vincent Hospital, Worcester, Massachusetts, United States
- Verma, Ashish, Saint Vincent Hospital, Worcester, Massachusetts, United States
Introduction
ADKTD-UMOD is a rare genetic disorder manifesting as a slowly progressive chronic kidney disease that usually leads to end-stage kidney disease (ESKD). Here we present a patient with a typical presentation of ADKTD-UMOD-related CKD.
Case Description
A 51-year-old white male with long-standing hypertension was evaluated a decade ago for slowly progressive CKD. He had 300-1000 mg/d proteinuria. Urine sediment was bland. Kidney imaging, hepatitis B & C titers, C3 & C4, ANA, SPEP, UPEP & IF were negative. CKD was attributed to hypertensive kidney disease and efforts were directed at suppressing proteinuria and keeping blood pressures consistently below 130/80 mmHg with ACEI/ARB.
After relative stability for about 4 years, creatinine started to worsen rapidly. Sediment showed WBC casts and the patient mentioned he was taking a kidney health herbal supplement. This was stopped and a brief trial of steroids ensued with transient improvement of creatinine only to relapse a few months later. The above workup was repeated and was negative but a kidney biopsy showed tubulointerstitial nephritis besides with secondary adaptive FSGS, over 50% globally sclerosed glomeruli, and over 60% cortical atrophy with advanced arterial and arteriolar hyalinosis. A repeat course of steroids made no difference and was rapidly tapered off. A renal genetic panel was performed, and the patient tested positive for UMOD gene variant c.317 G>T which is known to be associated with ADTKD-UMOD. The patient was provided genetic counseling for the self and at-risk family. He is currently under evaluation for home dialysis and kidney transplantation.
Discussion
Uromodulin (UMOD), also known as Tamm-Horsfall protein is exclusively produced in the kidney. It regulates salt transport and protects against urinary tract infections, stones, and immune-mediated insults. Approximately 1% of patients with CKD stages 3–5 have UMOD gene mutations. ADTKD-UMOD is considered rare and mostly remains unrecognized due to the paucity of genetic testing. The disease is often insidious without characteristic hematuria or proteinuria. As no treatment options are as yet available for halting disease progression, dialysis and transplantation are often the primary therapy modalities. Full genome analysis might be helpful in identifying the etiology of CKD, prognostication, and family counseling.