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:

Dents Disease; Disease, Dent; Disease, Dent's; Disease, Dents; Dent's Disease

Networked: 195 relevant articles (4 outcomes, 12 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

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

Experts

1.	Thakker, Rajesh V: 14 articles (01/2021 - 08/2000)
2.	Devuyst, Olivier: 14 articles (10/2020 - 04/2003)
3.	Igarashi, Takashi: 9 articles (11/2014 - 01/2002)
4.	Ludwig, Michael: 9 articles (03/2012 - 01/2003)
5.	Scheinman, Steven J: 8 articles (01/2020 - 01/2002)
6.	Anglani, Franca: 7 articles (07/2020 - 09/2006)
7.	Thakker, R V: 7 articles (11/2001 - 01/2000)
8.	De Camilli, Pietro: 6 articles (05/2017 - 05/2008)
9.	Sekine, Takashi: 6 articles (01/2017 - 03/2009)
10.	Norden, Anthony G W: 6 articles (02/2012 - 01/2002)

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.	Proteins (Proteins, Gene)FDA Link 12/07/2016 - "When fractional clearances are plotted versus protein radius there is a remarkable parallelism between protein (molecular weight range 30-150kDa) clearance in healthy controls, in Dent's disease, in nephrotic states and the clearance of Ficolls. " 12/07/2016 - "Dent's disease results in a 2-fold increase in the fractional clearance of proteins as compared to healthy controls whereas in nephrotic states there is a further 3-fold increase in fractional clearance. " 02/01/2012 - "Modeling studies indicate that many CLCN5 mutations are located at the interface between the monomers of ClC-5, demonstrating that this protein region plays an important role in Dent's disease. " 07/15/2020 - "From protein uptake to Dent disease: An overview of the CLCN5 gene." 01/01/2020 - "The next generation sequencing identified pathogenic variant in OCRL gene causing Dent disease type 2. We report an uncommon histologic finding of FSGS in Dent disease type 2 and highlight the importance of protein content examination and genetic analysis for the proper diagnosis in these complicated cases."
3.	Phosphates (Orthophosphate)IBA 11/01/2019 - "Dent disease: A window into calcium and phosphate transport." 11/01/2019 - "This review examines calcium and phosphate transport in the kidney through the lens of the rare X-linked genetic disorder Dent disease. " 10/01/2022 - "Finally, forms of hypophosphatemic rickets caused by Fanconi syndrome, such as nephropathic cystinosis and Dent disease require disease-specific treatment in addition to phosphate supplements and active vitamin D. " 01/01/2011 - "Recent insight into molecular characteristics of transport functions in the proximal tubules, and the recognition that proximal tubule cells possess intrinsic immune responses have contributed to an improved understanding of important areas in nephrology, such as Fanconi's syndrome, renal tubular acidosis, phosphate wasting syndromes, Dent's disease, cystinuria and other amino acid transport disorders, acute kidney injury, and the role of proximal tubules in progressive kidney disease. " 11/16/2000 - "Dent's disease is an X-linked disorder associated with the urinary loss of low-molecular-weight proteins, phosphate and calcium, which often leads to kidney stones. "
4.	Amino Acids FDA Link 10/01/2009 - "The recent discovery of a novel mediator of renal amino acid transport, collectrin (the TMEM27 gene), may provide new insight on the pathogenesis of Dent's disease. " 01/01/2011 - "Recent insight into molecular characteristics of transport functions in the proximal tubules, and the recognition that proximal tubule cells possess intrinsic immune responses have contributed to an improved understanding of important areas in nephrology, such as Fanconi's syndrome, renal tubular acidosis, phosphate wasting syndromes, Dent's disease, cystinuria and other amino acid transport disorders, acute kidney injury, and the role of proximal tubules in progressive kidney disease. "
5.	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. " 01/01/2023 - "The majority of cases of Dent's disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. " 01/01/2021 - "The gene mutations of the chloride channel gene (CLCN5) can lead to the inherited X-linked Dent disease (X-Dent). " 08/01/2016 - "Genetic analysis for Dent disease indicated a mutation (c.726 + 1G > A) in Chloride Channel, Voltage-Sensitive 5 (CLCN5). " 11/01/2014 - "Dent disease is an inherited tubulopathy caused by a mutation in the CLCN5 chloride channel gene. "
6.	ChloridesIBA 03/01/2023 - " screening for inherited renal disease was performed identifying a hemizygous pathogenic variant c.2152C>T (p.Arg718*) in the Chloride Voltage-Gated Channel 5 (CLCN5) gene, confirming the diagnosis of X-linked Dent Disease. " 01/01/2023 - "Whole-genome sequencing revealed hemizygous loss of function mutations in chloride voltage-gated channel 5 (CLCN5) consistent with Dent disease. " 04/01/2022 - "Dent disease type 1 is an X-linked tubulopathy mainly caused by inactivating mutations in the chloride voltage-gated channel 5 (CLCN5) gene. " 12/01/2019 - "A novel splice site mutation (c.416-2A > G) of the chloride voltage-gated channel 5 ( CLCN5 ) gene, responsible for Dent disease type 1 was identified. " 12/15/2018 - "We present a case of Dent disease caused by a novel intronic mutation, 1348-1G>A, of the chloride voltage-gated channel 5 (CLCN5) gene. "
7.	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 - "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." 03/01/2012 - "Our aim is to report the effects of these drugs in two novel mutations patients with Dent's disease type 1. In this report, no significant correlations between dosage of hydrochlorothiazide and calciuria and no significant correlations between proteinuria and dosage of enalapril were detected. "
8.	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. " 03/01/2023 - "To our knowledge, this is the first case in the literature describing Dent disease solely presenting with ophthalmic symptoms of nyctalopia and abnormal electroretinogram findings that later reversed with vitamin A repletion. " 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."
9.	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. " 05/01/2018 - "We developed a novel XCI analytical assay of ultra-deep targeted RNA sequencing and revealed that skewed XCI explains the mechanism of onset of female Dent disease in only half of such cases." 05/01/2018 - "Here, we report four females with Dent disease, and we clarified the correlation between XCI and female cases of Dent disease using not only HUMARA assay but also a novel analytical method by RNA sequencing. " 05/01/2018 - "Development of ultra-deep targeted RNA sequencing for analyzing X-chromosome inactivation in female Dent disease."
10.	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. "

Therapies and Procedures

1.	Therapeutics 01/01/2019 - "This article describes the clinical presentation, laboratory evaluation, genetics, pathophysiology, management, and future therapies of Dent disease." 01/06/2020 - "In cases such as Dent disease, supportive therapies are limited, and early renal replacement therapies are necessitated. " 01/01/2021 - "4PBA is a FDA-approved drug for the treatment of urea cycle disorders and offers a potential therapy for Dent disease." 02/01/2006 - "[Dent disease (idiopathic tubular proteinuria): Pathogenesis, pathophysiology, and therapy]." 01/01/2018 - "In the absence of therapy targeting for the molecular defect, the current care of patients with Dent's disease is supportive, focusing on the prevention of nephrolithiasis and nephrocalcinosis. "
2.	Renal Replacement Therapy (Therapies, Renal Replacement) 01/06/2020 - "In cases such as Dent disease, supportive therapies are limited, and early renal replacement therapies are necessitated. "
3.	Kidney Transplantation 01/01/2019 - "We describe the first successful kidney transplantation involving a patient with type 1 Dent's disease and ESRD given a kidney by an obligate carrier of the gene mutation, his mother. "
4.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 01/01/2017 - "Here we test the effects of bone marrow transplantation in Clcn5Y/- mice, a faithful model for Dent disease. " 01/01/2017 - "Bone marrow transplantation improves proximal tubule dysfunction in a mouse model of Dent disease."
5.	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."