Dent Disease

X-linked recessive NEPHROLITHIASIS characterized by HYPERCALCIURIA; HYPOPHOSPHATEMIA; NEPHROCALCINOSIS; and PROTEINURIA. It is associated with mutations in the voltage-gated chloride channel, CLC-5 (Dent Disease I). Another group of mutations associated with this disease is in phosphatidylinositol 4,5-bisphosphate-5-phosphatase gene.

Also Known As:

Networked: 136 relevant articles (2 outcomes, 10 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Bartter Syndrome (Syndrome, Bartter)
2.	Hypercalciuria
3.	Nephrolithiasis
4.	Hypophosphatemia
5.	Oculocerebrorenal Syndrome (Lowe Syndrome)

Experts

1.	Devuyst, Olivier: 13 articles (09/2015 - 04/2003)
2.	Thakker, Rajesh V: 12 articles (04/2013 - 01/2002)
3.	Ludwig, Michael: 8 articles (01/2011 - 01/2003)
4.	Thakker, R V: 8 articles (11/2001 - 01/2000)
5.	Igarashi, Takashi: 7 articles (07/2014 - 01/2002)
6.	Scheinman, Steven J: 7 articles (01/2009 - 01/2002)
7.	Blanchard, Anne: 6 articles (08/2015 - 01/2006)
8.	Norden, Anthony G W: 6 articles (02/2012 - 01/2002)
9.	Guggino, William B: 6 articles (05/2008 - 04/2003)
10.	De Camilli, Pietro: 5 articles (01/2014 - 05/2008)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Dent Disease:

1.	CalciumIBA 09/01/2006 - "We assessed renal calcium excretion in 34 male patients with proven CLCN5 mutations, who had been referred because of LMW proteinuria and at least one additional symptom of Dent disease. " 05/24/2004 - "We conclude that collecting duct cells with reduced CLC-5 expression lead to a tendency to form calcium crystal agglomeration, which may help explain the nephrocalcinosis and nephrolithiasis seen in Dent's disease." 11/01/2007 - "Studies of monogenic forms of hypercalciuric nephrolithiasis in man, for example, Bartter syndrome, Dent's disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels, and receptors that are involved in regulating the renal tubular reabsorption of calcium. " 12/01/2009 - "Bartter syndrome, Dent's disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. " 07/01/2006 - "Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. "
2.	Chloride Channels (Chloride Channel)IBA 10/01/2004 - "Genetic studies indicated that mutations of the chloride channel CLC-5 in the kidney are responsible for a group of clinical disorders, collectively called Dent's disease. " 10/10/2003 - "ClC-5 is a voltage-gated chloride channel found in the proximal tubule where it has been shown to be essential for protein uptake, based on evidence from patients with Dent's disease and studies in ClC-5 knockout mice. " 09/01/2008 - "These findings suggest that OCRL and ClC-5, the chloride channel mutated in Dent disease, are involved in similar reabsorption pathways in the proximal tubule." 03/01/2008 - "Dent disease, an X-linked recessive renal tubular disease, results from loss-of-function mutations in the CLCN5 chloride channel gene. " 01/01/2006 - "How Bartter's and Gitelman's syndromes, and Dent's disease have provided important insights into the function of three renal chloride channels: ClC-Ka/b and ClC-5."
3.	Proteins (Proteins, Gene)IBA 10/01/2009 - "ClC-5, an endosomal Cl(-)/H(+) antiporter that is mutated in Dent disease, is essential for endosomal acidification and re-uptake of small molecular weight proteins in the renal proximal tubule. " 01/01/2009 - "Eighteen probands with Dent's disease were investigated for mutations in CLC-5 and two of its interacting proteins, CLC-4 and cofilin. " 01/01/2004 - "These data demonstrated that an impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. " 12/08/2000 - "Analysis of urine from patients with Dent's disease, a renal tubular disorder that alters receptor-mediated endocytic reabsorption of proteins, identified TTR as an abundant excreted protein. " 01/01/2005 - "Cytochemical studies with the endocytic tracer, peroxidase, showed poor transfer into early endocytic vesicles, suggesting that impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. "
4.	Hydrochlorothiazide (Esidrix)FDA LinkGeneric 10/01/2009 - "The hypercalciuria associated with Dent's disease was effectively corrected using hydrochlorothiazide." 06/01/2009 - "Hydrochlorothiazide-induced tubulointerstitial nephritis in a patient with Dent disease." 12/01/2008 - "Thiazide doses equivalent to 1 to 2 mg/kg/d of hydrochlorothiazide (HCTZ) have been proposed to correct hypercalciuria and prevent kidney failure in patients with Dent disease. " 12/01/2008 - "Effect of hydrochlorothiazide on urinary calcium excretion in dent disease: an uncontrolled trial." 03/01/2012 - "The long-term use of enalapril and hydrochlorothiazide in two novel mutations patients with Dent's disease type 1."
5.	Dent disease 1IBA 11/01/2014 - "Dent disease, an X-linked recessive renal tubulopathy, is caused by mutations in either CLCN5 (Dent disease 1) or OCRL (Dent disease 2). " 01/01/2010 - "The disease is caused by mutations in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes that are located on chromosome Xp11.22 and Xq25, respectively. " 02/01/2008 - "In patients with Dent disease, the presence of the above-mentioned extrarenal manifestations indicates that it is more likely that the patient is affected by Dent disease 2 than by Dent disease 1." 02/01/2008 - "Among the 12 boys with a phenotype typical of Dent disease, nine had a mutation in CLCN5 (Dent disease 1), two had a mutation in OCRL1 (Dent disease 2), and one had no mutations in either gene. " 11/01/2014 - "In total, 23 patients with Dent disease 1 (Group A), five patients with Dent disease 2 (Group B) and 19 patients with Lowe syndrome (Group C) were enrolled in our study. "
6.	Vitamin A (Retinol)FDA LinkGeneric 07/01/2012 - "The study aim was to investigate vitamin A status and RBP in serum and urine of patients with genetically confirmed Dent's disease. " 07/01/2012 - "Eight patients were studied, three boys had clinical vitamin A deficiency, three had asymptomatic deficiency, and two young men with Dent's disease and impaired renal function had normal retinol values. " 07/01/2012 - "Three patients with Dent's disease presented with complaints of impaired night vision or xerophthalmia and were found to have severely decreased serum retinol concentrations. " 09/01/2009 - "Vitamin A responsive night blindness in Dent's disease." 09/01/2009 - "We report on three boys, of Indian origin, with Dent's disease that presented at an early age (1-4 years), with polyuria, polydipsia, salt craving, recurrent vitamin A-responsive night blindness, hypophosphataemic rickets, hypercalciuria and low molecular weight proteinuria. "
7.	Peroxidase (Myeloperoxidase)IBA 01/01/2004 - "Investigations conducted in a CLC-5 knockout (KO) mouse model harbouring all the characteristic renal tubular defects of Dent's disease showed a severe impairment of endocytosis by PT cells, such that the endocytic tracer peroxidase was poorly transferred into early endocytic vesicles. " 01/01/2005 - "Cytochemical studies with the endocytic tracer, peroxidase, showed poor transfer into early endocytic vesicles, suggesting that impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. "
8.	RNA (Ribonucleic Acid)IBA 04/01/2005 - "In this study, phenotypes were analyzed in three Korean boys with Dent's disease, and genetic diagnoses were performed using a new convenient method using peripheral blood RNA. "
9.	Genetic Markers (Genetic Marker)IBA 03/01/2000 - "X-linked polymorphic genetic markers were used in linkage studies of these families, and the genes causing Dent's disease and XRN were mapped to Xp11. "
10.	Protons (Proton)IBA 09/15/2015 - "Dedifferentiation of proximal tubule cells and dysfunction of receptor-mediated endocytosis characterize Dent's disease, a rare disorder caused by inactivating mutations in the CLCN5 gene that encodes the endosomal chloride-proton exchanger, ClC-5. " 09/15/2015 - "Loss-of-function mutations of the endosomal chloride-proton exchanger ClC-5 (Dent's disease) cause a major trafficking defect in proximal tubule cells, associated with lysosomal dysfunction, oxidative stress and dedifferentiation/proliferation. " 01/01/2015 - "Mutations associated with Dent's disease affect gating and voltage dependence of the human anion/proton exchanger ClC-5." 01/01/2014 - "Characterization of this crucial region could allow a clear genetic classification of a greater number of Dent disease patients, but also provide the basis for highlighting some as yet unexplored functions of the ClC-5 proton exchanger." 12/01/2010 - "Dent's disease: chloride-proton exchange controls proximal tubule endocytosis."

Therapies and Procedures

1.	Transplants (Transplant) 01/01/2015 - "We present a case of a polyuric adult with Dent's disease who underwent staged bilateral native nephrectomies, the first operation before transplant and the second four months after transplant. "
2.	Nephrectomy 01/01/2015 - "We present a case of a polyuric adult with Dent's disease who underwent staged bilateral native nephrectomies, the first operation before transplant and the second four months after transplant. " 01/01/2015 - "Staged Hand-Assisted Bilateral Native Nephrectomy for Management of Posttransplant Polyuria in an Adult with Dent's Disease."