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Pediatric Nephrology (Berlin, Germany) Oct 2022Here, we discuss the management of different forms of rickets, including new therapeutic approaches based on recent guidelines. Management includes close monitoring of...
Here, we discuss the management of different forms of rickets, including new therapeutic approaches based on recent guidelines. Management includes close monitoring of growth, the degree of leg bowing, bone pain, serum phosphate, calcium, alkaline phosphatase as a surrogate marker of osteoblast activity and thus degree of rickets, parathyroid hormone, 25-hydroxyvitamin D, and calciuria. An adequate calcium intake and normal 25-hydroxyvitamin D levels should be assured in all patients. Children with calcipenic rickets require the supplementation or pharmacological treatment with native or active vitamin D depending on the underlying pathophysiology. Treatment of phosphopenic rickets depends on the underlying pathophysiology. Fibroblast-growth factor 23 (FGF23)-associated hypophosphatemic rickets was historically treated with frequent doses of oral phosphate salts in combination with active vitamin D, whereas tumor-induced osteomalacia (TIO) should primarily undergo tumor resection, if possible. Burosumab, a fully humanized FGF23-antibody, was recently approved for treatment of X-linked hypophosphatemia (XLH) and TIO and shown to be superior for treatment of XLH compared to conventional treatment. Forms of hypophosphatemic rickets independent of FGF23 due to genetic defects of renal tubular phosphate reabsorption are treated with oral phosphate only, since they are associated with excessive 1,25-dihydroxyvitamin D production. 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. Adjustment of medication should be done with consideration of treatment-associated side effects, including diarrhea, gastrointestinal discomfort, hypercalciuria, secondary hyperparathyroidism, and development of nephrocalcinosis or nephrolithiasis.
Topics: Calcium; Child; Familial Hypophosphatemic Rickets; Fanconi Syndrome; Fibroblast Growth Factors; Humans; Osteomalacia; Paraneoplastic Syndromes; Phosphates; Rickets; Rickets, Hypophosphatemic; Vitamin D
PubMed: 35352187
DOI: 10.1007/s00467-022-05505-5 -
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 -
Journal of Lipid Research Feb 2019Phosphoinositides (PIs) play pivotal roles in the regulation of many biological processes. The quality and quantity of PIs is regulated in time and space by the activity... (Review)
Review
Phosphoinositides (PIs) play pivotal roles in the regulation of many biological processes. The quality and quantity of PIs is regulated in time and space by the activity of PI kinases and PI phosphatases. The number of PI-metabolizing enzymes exceeds the number of PIs with, in many cases, more than one enzyme controlling the same biochemical step. This would suggest that the PI system has an intrinsic ability to buffer and compensate for the absence of a specific enzymatic activity. However, there are several examples of severe inherited human diseases caused by mutations in one of the PI enzymes, although other enzymes with the same activity are fully functional. The kidney depends strictly on PIs for physiological processes, such as cell polarization, filtration, solute reabsorption, and signal transduction. Indeed, alteration of the PI system in the kidney very often results in pathological conditions, both inherited and acquired. Most of the knowledge of the roles that PIs play in the kidney comes from the study of KO animal models for genes encoding PI enzymes and from the study of human genetic diseases, such as Lowe syndrome/Dent disease 2 and Joubert syndrome, caused by mutations in the genes encoding the PI phosphatases, OCRL and INPP5E, respectively.
Topics: Animals; Humans; Kidney; Kidney Diseases; Molecular Targeted Therapy; Phosphatidylinositols
PubMed: 30314999
DOI: 10.1194/jlr.R089946 -
Journal of Clinical and Experimental... Oct 2017A considerable number of gastrointestinal disorders (GIDs) of varied nature (inflammatory, infectious, genetic and other etiology) may produce alterations in the hard... (Review)
Review
BACKGROUND
A considerable number of gastrointestinal disorders (GIDs) of varied nature (inflammatory, infectious, genetic and other etiology) may produce alterations in the hard and soft oral tissues. Among these are Crohn's disease, ulcerative colitis, celiac and gastroesophageal reflux disease.
MATERIAL AND METHODS
Article search was done using the National library of medicine (PubMed) database using different search terms and analyzed according to their importance.
RESULTS
A large variety of GIDs can give rise to oral lesions, including: RAS like ulceration, mucosal tags, cobblestoning, mucogingivitis, labial and facial swelling, pyostomatitis vegetans, disgeusia and dental abnormalities, among others. Although in most cases the gastrointestinal signs and symptoms highlight in the clinical picture, a considerable percentage of these patients are affected by oral manifestations before the onset of gastrointestinal symptoms. This lesions can cause significant functional and aesthetics damages as well deteriorate the patient quality of life.
CONCLUSIONS
Although the frequency of oral manifestations is variable across GIDs and in most cases is non-specific, these alterations may precede the underlying disease and therefore can facilitate an opportune diagnosis. Gastrointestinal disorders, oral lesions, oral mucosal disorders.
PubMed: 29167716
DOI: 10.4317/jced.54008 -
Annual Review of Physiology Feb 2017Cells lining the proximal tubule (PT) of the kidney are highly specialized for apical endocytosis of filtered proteins and small bioactive molecules from the glomerular... (Review)
Review
Cells lining the proximal tubule (PT) of the kidney are highly specialized for apical endocytosis of filtered proteins and small bioactive molecules from the glomerular ultrafiltrate to maintain essentially protein-free urine. Compromise of this pathway results in low molecular weight (LMW) proteinuria that can progress to end-stage kidney disease. This review describes our current understanding of the endocytic pathway and the multiligand receptors that mediate LMW protein uptake in PT cells, how these are regulated in response to physiologic cues, and the molecular basis of inherited diseases characterized by LMW proteinuria.
Topics: Animals; Endocytosis; Humans; Kidney Glomerulus; Kidney Tubules, Proximal; Proteinuria; Receptors, Cell Surface
PubMed: 27813828
DOI: 10.1146/annurev-physiol-022516-034234 -
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 -
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 -
British Dental Journal Jun 2022
Topics: Disease Outbreaks; Humans; Mpox (monkeypox)
PubMed: 35689039
DOI: 10.1038/s41415-022-4358-8 -
International Journal of Clinical... 2015Despite the advancements in dentistry, dental caries still remains the most common disease of the oral cavity. A major reason for this scenario is because the dental...
Despite the advancements in dentistry, dental caries still remains the most common disease of the oral cavity. A major reason for this scenario is because the dental professionals are still clinging to the outdated surgical model of dental caries. This traditional approach of caries management forces the tooth to enter into the 'restoration cycle' which usually involves several lifetime replacement procedures, resulting in increased restoration size, even more invasive procedures and finally a prosthesis. We need to acknowledge that, by simply drilling and filling the carious lesions, this disease cannot be controlled. Like other infectious diseases of the human body, if the etiological factors are not identified and managed appropriately, the disease will continue.
PubMed: 26124589
DOI: No ID Found