title: Is the renal kallikrein-kinin system a factor that modulates calciuria?
abstract: Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK). Both proteins are synthesised in the distal tubule and secreted in the tubular fluid. TK stimulates active calcium reabsorption through the bradykinin receptor B2 that compromises TRPV5 activation through the protein kinase C pathway. TK-deficient mice show hypercalciuria of renal origin comparable to that seen in TRPV5 knockout mice. There is a polymorphism with loss of function of the human TK gene R53H (allele H) that causes a marked decrease in enzymatic activity. The presence of the allele H seems to be common at least in the Japanese population (24%). These individuals have a tendency to greater calcium and sodium excretion in urine that is more evident during furosemide infusion. Future studies should analyse if manipulating the renal kallikrein-kinin system can correct idiopathic hypercalciuria with drugs other than thiazide diuretics.
authors.affiliation: Cátedra de Fisiología y Biofísica, Universidad del Salvador, Buenos Aires, Argentina. Electronic address: armando.negri@gmail.com.
authors.forename: Armando Luis
authors.initials: AL
authors.lastname: Negri
mesh_terms: D000483:Alleles; D000818:Animals; D002118:Calcium / Q000652:urine*; D015220:Calcium Channels / Q000172:deficiency; D018592:Cross-Over Studies; D020022:Genetic Predisposition to Disease; D005966:Glucuronidase / Q000502:physiology; D006801:Humans; D016234:Kallikrein-Kinin System / Q000235:genetics / Q000502:physiology*; D007686:Kidney Tubules, Distal / Q000503:physiopathology; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D050916:TRPV Cation Channels / Q000172:deficiency; D020840:Tissue Kallikreins / Q000172:deficiency / Q000235:genetics
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D005966:Glucuronidase; D000090265:Klotho Proteins; D020840:Tissue Kallikreins; D002118:Calcium
keywords: Calciuria; Calicreína tisular; Regulación; Regulation; Tissue kallikrein