Abstract
The aim of the present study was to evaluate the variations of some major bone metabolism markers with reference to klotho gene polymorphism (KGP) and bone mineral density (BMD) values in patients on chronic peritoneal dialysis (CPD). In 51 CPD patients and 40 healthy persons, assays for intact parathormone (iPTH), fibroblast growth factor 23 (FGF-23), osteoprotegerin (OPG), osteocalcin (OC), procollagen type-1 N terminal propeptide (PINP), beta- crosslaps (beta CTx), tartrate resistant acid phosphatase (TRAP5b), bone alkaline phosphatase (BAP), 1,25(OH)D3, and 25(OH)D3 and α-klotho gene mutations were performed. In CPD patients, 1,25(OH)D3 and 25(OH)D3 deficiency rates were 96% and 94% respectively. iPTH (249 pg/mL vs 39 pg/mL) and FGF-23 (1089 RU/mL vs 153 RU/mL), OPG, OC, PINP, beta CTx, TRAP5b levels were significantly higher in patients. iPTH levels and whole-body BMD values were negatively correlated in patients. The rate of KGP was similar in all groups. In CPD patients, besides vitamin D deficiency, high levels of OPG, OC, PINP, beta CTx, TRAP5b were evident. Positive correlation between iPTH levels and BAP and PINP levels suggested a diagnostic value for those markers during the management of CKD MBD. On the other hand, high serum TRAP5b concentrations did not seem to be affected by neither calcitriol treatment nor the severity of hyperparathyroidism. iPTH and FGF-23 levels and whole-body BMD values showed a significant negative correlation. We were unable to show any correlation between KGP and any of the CKD-MBD parameters measured in this study.
Highlights
Chronic kidney disease mineral and bone disorder (CKDMBD) is a complex and multifactorial entity
Along with klotho gene polymorphism and bone mineral density, we have evaluated the levels of some other major important parameters of bone turnover and metabolism namely intact parathormone (iPTH), fibroblast growth factor-23 (FGF-23), osteoprotegerin, osteocalcin (OC), procollagen type-1 N terminal propeptide (PINP), beta crosslaps, tartrate resistant acid phosphatase (TRAP5b), bone alkaline phosphatase (BAP), 1-25(OH)D3, and 25(OH)D3, in chronic peritoneal dialysis patients
OPG, OC, procollagen type1 N terminal propeptide (PINP), beta CTx, TRAP5b, BAP, Pi levels and CaXPi were found to be higher in patient group compared to the healthy control subjects
Summary
Chronic kidney disease mineral and bone disorder (CKDMBD) is a complex and multifactorial entity. One of the major physiologic contributors, fibroblast growth factor-23 (FGF-23) which is a hormone produced by osteocytes in response to hypophosphatemia, increases the urinary excretion of inorganic phosphate (Pi) and inhibits the renal production of 1,25(OH)D3, helping to mitigate hypophosphatemia in patients with chronic kidney disease and in normal persons [1]. It has been shown that in patients with chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality [2]. Klotho gene polymorphism has been shown to be associated with the severity of renal failure and aging parameters such as common carotid artery intima media thickness, low density lipoprotein and uric acid levels in CKD patients [6,7,8]. Klotho gene polymorphism may potentially affect all FGF-23 related CKD-MBD parameters as well as mortality and morbidity in CKD
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