Autosomal dominant tubulointerstitial kidney disease: A review

Abstract

The clinical characteristics of autosomal dominant tubulointerstitial kidney disease (ADTKD) include bland urinary sediment, slowly progressive chronic kidney disease (CKD) with many patients reaching end stage renal disease (ESRD) between age 20 and 70 years, and autosomal dominant inheritance. Due to advances in genetic diagnosis, ADTKD is becoming increasingly recognized as a cause of CKD. Pathogenic variants in UMOD, MUC1, and REN are the most common causes of ADTKD. ADTKD‐UMOD is also associated with hyperuricemia and gout. ADTKD‐REN often presents in childhood with mild hypotension, CKD, hyperkalemia, acidosis, and anemia. ADTKD‐MUC1 patients present only with CKD. This review describes the pathophysiology, genetics, clinical manifestation, and diagnosis for ADTKD, with an emphasis on genetic testing and genetic counseling suggestions for patients.

A Novel Monoallelic ALG5 Variant Causing Late-Onset ADPKD and Tubulointerstitial Fibrosis

“… 37 We showed that the ALG5 mutation affected uromodulin trafficking, with abnormal deposition of uromodulin within the ER. Abnormal deposition of uromodulin has been identified as a consistent pathologic finding in ADTKD- UMOD , 38 where the clinical phenotype of tubulointerstitial fibrosis and CKD is similar to ADPKD- ALG5 . Thus, we hypothesize a 2-fold pathophysiologic process, where aberrant glycosylation of PC1 and polycystin-2 leads to decreased PC1 and polycystin-2 surface expression, further leading to cystic disease.…”

Eight-Fold Increased COVID-19 Mortality in Autosomal Dominant Tubulointerstitial Kidney Disease due toMUC1Mutations: An Observational Study

“…Unfortunately, genotyping for the vast majority of MUC1 mutations is currently not performed in any commercial genetics laboratory, as these mutations are not identified by standard Sanger sequencing. 38 Mucin-1 plays an important role in other respiratory tract infections 14 , and we need to extend our studies in patients with ADTKD- MUC1 to other pulmonary infections.…”

Genetic Counseling in Kidney Disease: A Perspective

“…Genetic testing can provide information on clinical management, prognosis, disease mitigation, transplant decision-making and reproductive planning. 1 , 6 , 7 , 8 , 9 However, there are associated complexities which arise from testing such as diagnostic versus predictive testing (testing at-risk individuals) and variant interpretation. This can lead to a lack of confidence about incorporating genomics into clinical practice.…”