-
Function (Oxford, England) 2020Dent disease (DD) is a rare kidney disorder caused by mutations in the Cl/H exchanger ClC-5. Extensive physiologic characterization of the transporter has begun to... (Review)
Review
Dent disease (DD) is a rare kidney disorder caused by mutations in the Cl/H exchanger ClC-5. Extensive physiologic characterization of the transporter has begun to illuminate its role in endosomal ion homeostasis. Nevertheless, we have yet to understand how loss of ClC-5 function in the kidney proximal tubule impairs membrane traffic of megalin and cubilin receptors to cause the low molecular weight proteinuria characteristic of DD. This review identifies open questions that remain to be answered, evaluates the current literature addressing these questions, and suggests new testable models that may link loss of ClC-5 function to tubular proteinuria in DD.
Topics: Humans; Dent Disease; Endocytosis; Chloride Channels; Kidney Tubules, Proximal; Proteinuria
PubMed: 33015630
DOI: 10.1093/function/zqaa017 -
Urolithiasis Feb 2019In the last decades, proteomics has been largely applied to the Nephrology field, with the double aim to (1) elucidate the biological processes underlying renal... (Review)
Review
In the last decades, proteomics has been largely applied to the Nephrology field, with the double aim to (1) elucidate the biological processes underlying renal diseases; (2) identify disease-specific biomarkers, predictor factors of therapeutic efficacy and prognostic factors of disease progression. Kidney stone disease, and in particular, inherited nephrolithiasis (INL) are not an exception. Given the multifactorial origin of these disorders, the combination of genomics and proteomics studies may complement each other, with the final objective to give a global and comprehensive mechanistic view. In this review, we summarize the results of recent proteomic studies which have expanded our knowledge about INL, focusing the attention on monogenic forms of nephrolithiasis (cystinuria, Dent's disease, Bartter syndrome, distal renal tubular acidosis and primary hyperoxaluria), on polygenic hypercalciuria and on medullary sponge kidney disease.
Topics: Biomarkers; Humans; Hypercalciuria; Medullary Sponge Kidney; Nephrolithiasis; Proteome; Proteomics
PubMed: 30564846
DOI: 10.1007/s00240-018-01104-y -
Nephrology, Dialysis, Transplantation :... May 2023Dent's disease type 1 (DD1) is a rare X-linked nephropathy caused by CLCN5 mutations, characterized by proximal tubule dysfunction, including low molecular weight...
BACKGROUND
Dent's disease type 1 (DD1) is a rare X-linked nephropathy caused by CLCN5 mutations, characterized by proximal tubule dysfunction, including low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis-nephrocalcinosis, progressive chronic kidney disease (CKD) and kidney failure (KF). Current management is symptomatic and does not prevent disease progression. Here we describe the contemporary DD1 picture across Europe to highlight its unmet needs.
METHODS
A physician-based anonymous international e-survey supported by several European nephrology networks/societies was conducted. Questions focused on DD1 clinical features, diagnostic procedure and mutation spectra.
RESULTS
A total of 207 DD1 male patients were reported; clinical data were available for 163 with confirmed CLCN5 mutations. Proteinuria was the most common manifestation (49.1%). During follow-up, all patients showed LMWP, 66.4% nephrocalcinosis, 44.4% hypercalciuria and 26.4% nephrolithiasis. After 5.5 years, ≈50% of patients presented with renal dysfunction, 20.7% developed CKD stage ≥3 and 11.1% developed KF. At the last visit, hypercalciuria was more frequent in paediatric patients than in adults (73.4% versus 19.0%). Conversely, nephrolithiasis, nephrocalcinosis and renal dysfunction were more prominent in adults. Furthermore, CKD progressed with age. Despite no clear phenotype/genotype correlation, decreased glomerular filtration rate was more frequent in subjects with CLCN5 mutations affecting the pore or CBS domains compared with those with early-stop mutations.
CONCLUSIONS
Results from this large DD1 cohort confirm previous findings and provide new insights regarding age and genotype impact on CKD progression. Our data strongly support that DD1 should be considered in male patients with CKD, nephrocalcinosis/hypercalciuria and non-nephrotic proteinuria and provide additional support for new research opportunities.
Topics: Male; Humans; Nephrocalcinosis; Dent Disease; Hypercalciuria; Kidney Calculi; Mutation; Europe; Renal Insufficiency; Renal Insufficiency, Chronic; Proteinuria; Chloride Channels
PubMed: 36441012
DOI: 10.1093/ndt/gfac310 -
Current Pain and Headache Reports Feb 2021The use of cannabis for the treatment of migraine has become an area of interest with the legalization of medical cannabis in the USA. Understanding the mechanisms of... (Review)
Review
PURPOSE OF REVIEW
The use of cannabis for the treatment of migraine has become an area of interest with the legalization of medical cannabis in the USA. Understanding the mechanisms of cannabinoids, available studies, and best clinical recommendations is crucial for headache providers to best serve patients.
RECENT FINDINGS
Patients utilizing medical cannabis for migraine have reported improvement in migraine profile and common comorbidities. Reduction in prescription medication is also common, especially opioids. Side effects exist, with the majority being mild. Not enough data is available for specific dose recommendations, but THC and CBD appear to mediate these observed effects. The purpose of this article is twofold: review the limited research surrounding cannabis for migraine disease and reflect on clinical management experiences to provide recommendations that best capture the potential use of cannabis for migraine.
Topics: Analgesics; Animals; Cannabis; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Evaluation, Preclinical; Humans; Medical Marijuana; Migraine Disorders
PubMed: 33630181
DOI: 10.1007/s11916-020-00931-2 -
Nephrologie & Therapeutique Feb 2021Nephrocalcinosis is defined by calcium phosphate or calcium oxalate deposits in the kidney parenchyma, particularly in tubular epithelial cells and interstitial tissue....
Nephrocalcinosis is defined by calcium phosphate or calcium oxalate deposits in the kidney parenchyma, particularly in tubular epithelial cells and interstitial tissue. It should be differentiated from urolithiasis where calcium salts deposits are located in the kidney and urinary tract. The epidemiology of nephrocalcinosis in children is unknown but the condition is not so rare, with an increased incidence in preterm infants. Often detected as an incidental finding, nephrocalcinosis may be classified according to the radiological type: medullary, cortical or diffuse. Nephrocalcinosis in children can be caused by a variety of etiology. The most common causes concern medullary nephrocalcinosis and include hereditary tubular disorders, in particular distal renal tubular acidosis and Dent disease, metabolic disorders such as idiopathic hypercalciuria and hyperoxaluria, and iatrogenic causes such as vitamin D intoxication. In the newborn, the main cause is hypercalciuria of the premature baby, whose multifactorial origin is largely iatrogenic. Primary hyperoxaluria which can lead to early onset nephrocalcinosis and usually to chronic kidney disease should always be considered and further investigated. In order to provide a specific diagnosis, it is essential to take into account the family history, the clinical context and complete laboratory data. Early initiation of an appropriate etiological treatment is recommended and may prevent or delay the progression to chronic kidney disease in some cases.
Topics: Calcium Oxalate; Child; Humans; Hyperoxaluria; Infant, Newborn; Infant, Premature; Kidney; Nephrocalcinosis
PubMed: 33461896
DOI: 10.1016/j.nephro.2020.12.001 -
Intractable & Rare Diseases Research Feb 2023Dent disease is an X-linked recessive renal tubular disorder, which is mainly caused by mutations of the gene and gene. It is characterized by low molecular weight...
Dent disease is an X-linked recessive renal tubular disorder, which is mainly caused by mutations of the gene and gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis or nephrolithiasis, and progressive renal failure. Nephrotic syndrome is a glomerular disorder characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. In this study, we report two cases of Dent disease manifesting as nephrotic syndrome. Two patients were initially diagnosed with nephrotic syndrome due to edema, nephrotic range proteinuria, hypoalbuminemia, and hyperlipidemia, and responded to prednisone and tacrolimus therapy. Genetic testing revealed mutations in the and genes. They were eventually diagnosed with Dent disease. Nephrotic syndrome is a rare and insidious phenotype of Dent disease, and its pathogenesis is not fully understood. Patients with nephrotic syndrome are recommended to routinely undergo urinary protein classification and urinary calcium testing, especially those with frequently recurrent nephrotic syndrome and poor response to steroid and immunosuppressive therapy. To date, there is no effective drug treatment for Dent disease. About 30% to 80% of patients progress to end-stage renal disease at the age of 30-50.
PubMed: 36873671
DOI: 10.5582/irdr.2022.01125 -
Journal of Cellular and Molecular... Nov 2019This review examines calcium and phosphate transport in the kidney through the lens of the rare X-linked genetic disorder Dent disease. Dent disease type 1 (DD1) is... (Review)
Review
This review examines calcium and phosphate transport in the kidney through the lens of the rare X-linked genetic disorder Dent disease. Dent disease type 1 (DD1) is caused by mutations in the CLCN5 gene encoding ClC-5, a Cl /H antiporter localized to early endosomes of the proximal tubule (PT). Phenotypic features commonly include low molecular weight proteinuria (LMWP), hypercalciuria, focal global sclerosis and chronic kidney disease; calcium nephrolithiasis, nephrocalcinosis and hypophosphatemic rickets are less commonly observed. Although it is not surprising that abnormal endosomal function and recycling in the PT could result in LMWP, it is less clear how ClC-5 dysfunction disturbs calcium and phosphate metabolism. It is known that the majority of calcium and phosphate transport occurs in PT cells, and PT endocytosis is essential for calcium and phosphorus reabsorption in this nephron segment. Evidence from ClC-5 KO models suggests that ClC-5 mediates parathormone endocytosis from tubular fluid. In addition, ClC-5 dysfunction alters expression of the sodium/proton exchanger NHE3 on the PT apical surface thus altering transcellular sodium movement and hence paracellular calcium reabsorption. A potential role for NHE3 dysfunction in the DD1 phenotype has never been investigated, either in DD models or in patients with DD1, even though patients with DD1 exhibit renal sodium and potassium wasting, especially when exposed to even a low dose of thiazide diuretic. Thus, insights from the rare disease DD1 may inform possible underlying mechanisms for the phenotype of hypercalciuria and idiopathic calcium stones.
Topics: Animals; Calcium; Dent Disease; Humans; Ion Channels; Ion Transport; Phosphates
PubMed: 31472005
DOI: 10.1111/jcmm.14590 -
British Dental Journal Mar 2024
Topics: Humans; Temporomandibular Joint Disorders; Temporomandibular Joint
PubMed: 38459318
DOI: 10.1038/s41415-024-7231-0 -
Clinical Kidney Journal Aug 2014Dent-Wrong disease, an X-linked recessive disorder of the proximal tubules, presents with hypercalciuria, nephrocalcinosis, nephrolithiasis, renal insufficiency,... (Review)
Review
Dent-Wrong disease, an X-linked recessive disorder of the proximal tubules, presents with hypercalciuria, nephrocalcinosis, nephrolithiasis, renal insufficiency, low-molecular-weight proteinuria, rickets and/or osteomalacia. Dent and Friedman initially characterized the disorder in 1964 following studies of two patients with rickets who presented with hypercalciuria, hyperphosphaturia, proteinuria and aminoaciduria. Since then, extensive investigation identified two genetic mutations (CLCN5 and OCRL1) to be associated with Dent-Wrong disease. Clinical features supported by laboratory findings consistent with proximal tubule dysfunction help diagnose Dent-Wrong disease. Genetic analysis supports the diagnosis; however, these two genes can be normal in a small subset of patients. The differential diagnosis includes other forms of the Fanconi syndrome, which can be hereditary or acquired (e.g. those related to exposure to exogenous substances). Treatment is supportive with special attention to the prevention of nephrolithiasis and treatment of hypercalciuria. We review the rare forms of Fanconi syndrome with special attention to Dent-Wrong disease.
PubMed: 25852908
DOI: 10.1093/ckj/sfu070 -
Journal of the American Dental... Jan 2022
Topics: Humans; Periodontal Diseases
PubMed: 34861990
DOI: 10.1016/j.adaj.2021.08.014