Abstract: PUB179
Beyond Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Cysts: Uncovering Uromodulin Kidney Disease in a Young Adult with Gout and CKD
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Sharma Divyadarshini, Divya, The University of Oklahoma Health Sciences College of Medicine, Oklahoma City, Oklahoma, United States
- Tjauw, Maxmillian J, The University of Oklahoma Health Sciences College of Medicine, Oklahoma City, Oklahoma, United States
- Sharma Priamvada, Gargi, East Carolina University, Greenville, North Carolina, United States
- Karim, Muhammad Sohaib, VA Oklahoma City Healthcare System, Oklahoma City, Oklahoma, United States
- Ahmad, Zahid Bashir, The University of Oklahoma Health Sciences College of Medicine, Oklahoma City, Oklahoma, United States
Introduction
Autosomal Dominant Tubulointerstitial Kidney Disease due to UMOD mutations (ADTKD-UMOD) is a hereditary cause of progressive chronic kidney disease (CKD), accounting for 0.3–1% of advanced CKD cases worldwide. It is among the most prevalent monogenic causes of CKD in adults but remains underrecognized due to its insidious clinical course, lack of distinctive features, and limited genetic screening. This case underscores the importance of considering genetic etiologies in young patients with CKD of unclear cause and highlights the growing need for awareness and targeted genetic testing in this population.
Case Description
A 32-year-old male with gout since age 21 and longstanding NSAID use was evaluated for progressive CKD. He had no history of hypertension, diabetes or family history of CKD. Laboratory workup revealed a serum creatinine of 2.16 mg/dL (baseline 1.6 mg/dL) with a bland urinalysis and urine albumin-to-creatinine ratio of 3.1 mg/g. Renal ultrasound identified three small left-sided renal cysts. Progression of kidney dysfunction prompted a biopsy, which showed mild to moderate cortical interstitial fibrosis and tubular atrophy involving 30% of the cortex. Focal intratubular inclusions within the thick ascending limb raised suspicion for ADTKD. Subsequent genetic testing confirmed a heterozygous likely pathogenic UMOD gene variant (c.1040G>A; p.Cys347Tyr), consistent with ADTKD-UMOD. The patient was counseled on prognosis, disease progression, and the importance of family screening.
Discussion
Uromodulin (Tamm-Horsfall protein) is the most abundant protein secreted in the kidney tubules under physiologic conditions. UMOD gene mutations lead to abnormal uromodulin accumulation in tubular cells, triggering cellular stress, interstitial fibrosis, and progressive tubulointerstitial damage. Clinically, ADTKD-UMOD presents with hyperuricemia, early-onset gout, bland urinary sediment, and gradual kidney function decline, often progressing to end-stage renal disease between ages 30 and 70. Early identification is essential to guide management, monitor disease progression, and provide genetic counseling to at-risk family members. This case underscores the importance of considering genetic testing in young adults with unexplained CKD, even in the absence of a known family history.