Mutations in the UMOD gene coding for uromodulin cause autosomal dominant tubulointerstitial kidney disease. Uromodulin is known to regulate transport processes in the thick ascending limb, but it remains unknown whether UMOD mutations are associated with functional tubular alterations in the early phase of the disease. The responses to furosemide and to a water deprivation test were compared in a 32-year-old female patient carrying the pathogenic UMOD mutation p.C217G and her unaffected 31-year-old sister. A single dose of furosemide induced an intense headache with exaggerated decrease in blood pressure (Δsyst: 30 versus 20 mmHg; Δdiast: 18 versus 5 mmHg) and body weight (Δ2.6 kg versus Δ0.9 kg over 3 h) in the proband versus unaffected sib. The diuretic response and the fall in urine osmolality were also more important and detected earlier in the affected sib. Water deprivation led to increased plasma osmolality and urine concentration in both siblings; however, the response to desmopressin was attenuated in the affected sib. These data reveal that mutations of uromodulin cause specific transport alterations, including exaggerated response to furosemide and a failure to maximally concentrate urine, in the early phase of the disease.
Keywords: NKCC2; TAL; Tamm–Horsfall protein; autosomal dominant tubulointerstitial kidney disease; furosemide.
© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.