Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1

Olinger, Eric; Hofmann, Patrick; Kidd, Kendrah; Dufour, Inès; Belge, Hendrica; Schaeffer, Céline; Kipp, Anne; Bonny, Olivier; Deltas, Constantinos; Demoulin, Nathalie; Fehr, Thomas; Fuster, Daniel; Gale, Daniel P.; Goffin, Éric; Hodaňová, Kateřina; Huynh‐Do, Uyen; Kistler, Andreas D.; Morelle, Johann; Papagregoriou, Gregory; Pirson, Yves; Sandford, Richard; Sayer, John A.; Torrá, Roser; Venzin, Christina; Venzin, Reto; Vogt, Bruno; Živná, Martina; Greka, Anna; Dahan, Karin; Rampoldi, Luca; Kmoch, Stanislav; Bleyer, Anthony J.; Devuyst, Olivier

doi:10.1016/j.kint.2020.04.038

Cited by 81 publications

(158 citation statements)

References 34 publications

(76 reference statements)

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“…Because of its large sample size, important insights on the clinical course, based on ADTKD subtype, can be obtained. Indeed, this study by Olinger et al 7 confirms that patients with ADTKD-UMOD and ADTKD-MUC1 have distinct clinical features and outcomes. Kidney disease appears to be more severe in ADTKD-MUC1 compared to ADTKD-UMOD in terms of onset of end-stage kidney disease and renal survival.…”

Section: See Clinical Investigation On Page 717supporting

confidence: 72%

“…In this issue of Kidney International, Olinger et al 7 present a welcome international effort, responding to the stated need by creating the International ADTKD Cohort, which includes 726 patients from 585 families. This cohort combines the US ADTKD and the Belgo-Swiss Registries.…”

Section: See Clinical Investigation On Page 717mentioning

confidence: 99%

“…This study also uncovers important insights into the pathobiology of ADTKD. 7 Although uromodulin and mucin-1 share pathophysiological features of toxic mutant protein accumulation and activation of UPR in TAL cells, 5,6 MUC1 mutations appear not to cause ER stress and do not alter the trafficking of uromodulin itself, as ADTKD-MUC1 patients do not have reduced levels of urine uromodulin. These observations suggest that each subtype of ADTKD activates distinct downstream pathogenic cellular and molecular pathways, which could explain the divergence in the clinical features and outcomes.…”

Section: See Clinical Investigation On Page 717mentioning

confidence: 99%

“…A key contribution of this work is providing a tool for screening and guidance for clinical and genetic testing to distinguish between major ADTKD subtypes. 7 The devised clinical UMODscore was based on discriminative clinical, biochemical, histological, and imaging characteristics (Figure 1a), which were discovered in the Belgo-Swiss ADTKD Registry and validated in the US ADTKD Registry within this international cohort. The UMOD-score has a high negative predictive value to exclude ATDKD-UMOD (score < 5), and a high positive predictive value for the presence of UMOD mutations when the score is >7.…”

Section: O M M E N T a R Ymentioning

confidence: 99%

“…Nevertheless, observational studies of living kidney donors suggest that a 30% reduction in kidney function is associated with 6 (95% confidence interval, 2-11) mm Hg higher systolic BP. 7 The study's genetic instrument for BP, in contrast, found no association with risk of lower kidney function. This is arguably consistent with the randomized trials of intensive BP lowering, which have not provided compelling evidence that lowering BP preserves kidney function 8 and have focused on subgroups where effects may be larger.…”

mentioning

confidence: 97%

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Autosomal dominant tubulointerstitial kidney disease: a new tool to guide genetic testing

LaFavers

El-Achkar

2020

Kidney International

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Section: See Clinical Investigation On Page 717supporting

confidence: 72%

Section: See Clinical Investigation On Page 717mentioning

confidence: 99%

Section: See Clinical Investigation On Page 717mentioning

confidence: 99%

Section: O M M E N T a R Ymentioning

confidence: 99%

mentioning

confidence: 97%

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Autosomal dominant tubulointerstitial kidney disease: a new tool to guide genetic testing

LaFavers

El-Achkar

2020

Kidney International

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Review of genetic testing in kidney disease patients: Diagnostic yield of single nucleotide variants and copy number variations evaluated across and within kidney phenotype groups

Claus

Snoek

Knoers

et al. 2022

American J of Med Genetics Pt C

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Genetic kidney disease comprises a diverse group of disorders. These can roughly be divided in the phenotype groups congenital anomalies of the kidney and urinary tract, ciliopathies, glomerulopathies, stone disorders, tubulointerstitial kidney disease, and tubulopathies. Many etiologies can lead to chronic kidney disease that can progress to end-stage kidney disease. Despite each individual disease being rare, together these genetic disorders account for a large proportion of kidney disease cases. With the introduction of massively parallel sequencing, genetic testing has become more accessible, but a comprehensive analysis of the diagnostic yield is lacking. This review gives an overview of the diagnostic yield of genetic testing across and within the full range of kidney disease phenotypes through a systematic literature search that resulted in 115 included articles. Patient, test, and cohort characteristics that can influence the diagnostic yield are highlighted. Detection of copy number variations and their contribution to the diagnostic yield is described for all phenotype groups. Also, the impact of a genetic diagnosis for a patient and family members, which can be diagnostic, therapeutic, and prognostic, is shown through the included articles. This review will allow clinicians to estimate an a priori probability of finding a genetic cause for the kidney disease in their patients.

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Autosomal dominant tubulointerstitial kidney disease: A review

Živná

Kidd

Barešová

et al. 2022

American J of Med Genetics Pt C

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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.

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Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1

Cited by 81 publications

References 34 publications

Autosomal dominant tubulointerstitial kidney disease: a new tool to guide genetic testing

Autosomal dominant tubulointerstitial kidney disease: a new tool to guide genetic testing

Review of genetic testing in kidney disease patients: Diagnostic yield of single nucleotide variants and copy number variations evaluated across and within kidney phenotype groups

Autosomal dominant tubulointerstitial kidney disease: A review

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