Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Dent disease: A window into calcium and phosphate transport. 3147 5

The proximal tubule (PT) reabsorbs filtered proteins via receptor-mediated endocytosis to prevent energetically inefficient wasting in the urine. Recent intravital imaging studies have suggested that protein reabsorption occurs in early (S1) segments, which have a very high capacity. In contrast, uptake of fluid phase substrates also occurs in distal (S2) segments. In this article, we will review these findings and their implications for understanding integrated proximal tubular function, patterns of damage caused by endocytosed toxins, and the origins of proteinuria. We will also discuss whether compensatory downstream increases in protein uptake might occur in disease states, and the environmental factors that could drive these changes.
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PMID:Axial differences in endocytosis along the kidney proximal tubule. 3165 46


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