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 Aim: Active vitamin D (1,25-dihydroxyvitamin D3), PTH, fibroblast growth factor-23 (FGF-23) and Klotho protein are key regulators of phosphate metabolism. Hyperphosphatemia and increased FGF-23 level in patients with end-stage renal disease are associated with increased morbidity and mortality. The relationships among key regulators of phosphate metabolism are still being investigated. FGF-23, the humoral factor involved in phosphate metabolism, is strongly associated with serum phosphorus level. Klotho, a transmembrane protein expressed primarily in renal tubules, functions as an obligatory co-receptor for FGF-23. The soluble form of Klotho, produced by the shedding of the transmembrane protein, is detectable in body fluids. The purpose of the study was to assess if serum soluble alpha-Klotho level was related to phosphate metabolism parameters and residual renal function (RRF) in incident peritoneal dialysis (PD) patients. Methods: Thirty-five clinically stable patients 4 to 6 weeks after the onset of PD were included in the study. For each patient, clinical and laboratory data were reviewed. Serum phosphorus concentration, urinary and peritoneal phosphate clearance, serum FGF-23 and soluble Klotho protein concentrations were determined. Results: Serum soluble alpha-Klotho was strongly negatively correlated with 24-hour diuresis (Rs = -0.55, p = 0.004) and renal phosphate clearance (Rs = -0.40, p = 0.049), but not with RRF. Conclusions: Serum soluble Klotho protein concentration is inversely related to residual diuresis and renal phosphate clearance in incident PD patients.
Background: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited renal disorders with genetic heterogeneity. Mutations of two known genes are responsible for this disease: PKD1 at 16p 13.3 and PKD2 at 4q21-23. A majority of cases (85%) are caused by mutations in PKD1. Because direct mutation screening remains complex, we describe here the application of an efficient approach to studies based on highly informative dinucleotide and tetranucleotide repeats flanking genes PKD1 and PKD2. Methods: For this study a series of microsatellites closely linked to locus PKD1 (D16S291, D16S663, D16S665, D16S283, Dl6S407, D16S475) and to locus PKD2 (D4S1563, D4S2929, D4S414, D4S1534, D4S423) were selected. Short (81-242 bp) DNA fragments containing the tandem repeats were amplified by polymerase chain reaction (PCR). The number of repeat units of microsatelite markers was determined by fluorescent capillary electrophoresis. Results: DNA microsatellite analysis was performed in 25 Polish ADPKD families and established the type of disease (21 families PKDl-type, 1 family PKD2-type). Conclusions: While a disease-causing mutation in the PKD1 and PKD2 genes cannot be identified, DNA microsatellite analysis provided an early diagnosis and may be considered in ADPKD families.
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