Observations of a large Dent disease cohort

Abstract

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease.

The Urological Association of Asia clinical guideline for urinary stone disease

“…42 Inherited metabolic disorders are often associated with pediatric urolithiasis cases. 43 Adenine phosphoribosyltransferase deficiency, 44 cystinuria, [45][46][47] xanthinuria, 48 Dent disease, 49,50 familial hypomagnesemia with hypercalciuria and nephrocalcinosis, 51,52 and primary hyperoxaluria [53][54][55] cause urinary hypersaturation of insoluble mineral salts, which can inevitably increase the risk of kidney stone formation (LE:4).…”

Elevated serum iron level is a predictor of prognosis in severe patients with acute kidney injury

“…Level of catalytic iron in urine increased, rather than decreased in AKI patients [28][29][30]. However, body iron stores were not low in AKI patients [19,31]. The iron-mediated mechanisms in AKI were complex and may include multiple pathway.…”

A Novel CLCN5 Splice Site Mutation in a Boy with Incomplete Phenotype of Dent Disease

“…The cardinal feature of our patient was nephrotic range tubular LMWP, that is, the most constant feature of patients with Dent disease. 13 Usually, tubular proteinuria is expected to be lower than the nephrotic range 6 ; however, several cases with Dent disease have been reported to have nephrotic range tubular or mixed proteinuria, 6,14,15 and recent reports suggest even frank glomerular proteinuria with podocyte involvement in certain CLCN5 mutations. 16 Such clinical presentation in male patients, especially in the absence of hypoalbuminemia and edema, warrants investigation for tubular proteinuria and exclusion of Dent's disease before initiation of immunosuppressive treatments.…”

“…16 Such clinical presentation in male patients, especially in the absence of hypoalbuminemia and edema, warrants investigation for tubular proteinuria and exclusion of Dent's disease before initiation of immunosuppressive treatments. 6,13 Hypercalciuria is the second most common abnormality in patients with Dent disease. 13 Our patient had only mild hypercalciuria without further consequences during the follow-up period.…”

“…6,13 Hypercalciuria is the second most common abnormality in patients with Dent disease. 13 Our patient had only mild hypercalciuria without further consequences during the follow-up period. Cases of Dent disease with atypical phenotype and absence of hypercalciuria have been reported.…”