Kidney Week

Abstract: TH-PO502

Hiding in Plain Sight: The Diagnostic Challenge of Autosomal Dominant Tubulointerstitial Kidney Disease

Session Information

• Genetic Kidney Diseases: Genotypes and Phenotypes in Cases
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Barr, Luke, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Luke Barr, MD

• Thach, Lonnie, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Lonnie Thach, MD

• Paparello, James J., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

James J. Paparello, MD

• Quaggin, Susan E., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Susan E. Quaggin, MD, FASN

• Kanwar, Yashpal S., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Yashpal S. Kanwar, MD, PhD

• Bleyer, Anthony J., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States

Anthony J. Bleyer, MD, MS, FASN

Introduction

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of rare inherited disorders characterized by tubular damage and interstitial fibrosis, bland urinary sediment and normal imaging. Mutations in the MUC1 gene encoding mucin-1 are one cause. A cytosine insertion within MUC1 leads to formation of MUC1 frameshift proteins. Deposition of these proteins leads to ADTKD, progressive CKD and early onset ESRD.

Case Description

A 33 year old asymptomatic man was admitted after an elevated serum creatinine of 5.1 mg/dl was found on outpatient labs. There was no history of dysuria, hematuria, NSAID exposure, tobacco use, recurrent UTI, kidney stones or prematurity. While the father's clinical history was unknown, a paternal grandmother and three uncles were on renal replacement therapy.

He was hypertensive with labs notable for mild hyperkalemia 5.3 mmol/L, serum bicarbonate 19 mmol/L, BUN 68 mg/dl, serum creatinine 5.15 mg/d and uric acid 10.2 mg/dl. Urinalysis was bland. Renal ultrasound showed a R kidney 10.7 cm, L kidney 8.9 cm, few L simple renal cysts, increased echogenicity and no hydronephrosis. Kidney biopsy showed mild to moderate arteriosclerosis, ATN and moderate tubulo-interstitial disease with 40% tubular atrophy and fibrosis. Initial genetic testing was negative. Through the Rare Inherited Kidney Disease Team at Wake Forest and the Broad Institute of Harvard-MIT, advanced genetic testing identified a MUC1 mutation, confirming a diagnosis of ADTKD. Ultimately, he progressed to ESRD and is currently being evaluated for transplant.

Discussion

Our case demonstrates a classic presentation of ADTKD-MUC1 as well as the diagnostic challenges – namely the absence of typical hallmarks of kidney disease like proteinuria, hematuria, serum serologies, diagnostic imaging or pathology. This case highlights the limitation of commercially available genetic testing and the need for improved awareness of these disorders and specialized centers which can help establish the diagnosis. Accurate diagnosis is essential for family planning and prognostication, not only with respect to native kidney disease but post-transplant as well. Only with heightened awareness and identification can our understanding of ADTKD grow and lead to the discovery of early treatment options.