RESUMO
Background Progressive loss of kidney function in chronic kidney disease (CKD) leads to altered mineral homeostasis, reflected by the imbalance in calcium and phosphorus, and has been associated with progression of renal failure. Aims The aim of this study was to investigate CKD-mineral bone disorder (CKD-MBD)-associated candidate variables and its relationship with parathyroid hormone (PTH), as well as to quantify the prevalence of CKD-associated mineral disturbances in nondialyzed CKD patients. Materials and Methods This cross-sectional analytical study included 124 CKD patients and 157 control participants. Blood samples were analyzed for serum total calcium, phosphorus, PTH, electrolytes, and other hematological/hemodynamic parameters by standard methods. Suitable descriptive statistics was used for different variables. Results The 124 patients had a mean age of 50.2 ± 7.8 years with male to female ratio of 1.58; majority of patients had stage 3 CKD (40.32%), and the most common comorbid conditions were diabetes mellitus ( n = 78 [62.9%]) and hypertension ( n = 63 [50.8%]). A high prevalence of mineral metabolite abnormalities was observed in a patient cohort; overall prevalence of hyperparathyroidism was found in 57.25% patients, hypocalcemia in 61.29%, and hyperphosphatemia in 82.25% patients. Prevalence of abnormal homeostasis (with regard to total calcium, phosphate, and PTH) increased progressively with the severity of disease (analysis of variance; p < 0.05). Significant differences in the mean values of total calcium, phosphorus, alkaline phosphatase, and PTH were seen compared with healthy participants ( p < 0.0001). Furthermore, there was a significant positive correlation between serum PTH with serum phosphorous ( R 2 : 0.33; p < 0.0001), serum creatinine ( R 2 : 0.084; p < 0.0259), serum potassium ( R 2 : 0.068; p < 0.0467), and a significant negative correlation with serum total calcium ( R 2 : 0.37; p < 0.0001). Conclusions CKD patients are at risk of or may already have developed secondary hyperparathyroidism apparent from PTH-linked derangements in mineral metabolism in predialysis CKD patients. These abnormalities start in early stages of CKD and worsen with disease progression. This accentuates the significance of early recognition of mineral bone disorder, understanding its pathophysiological consequences and scheduling necessary interventions/management strategies to protect the CKD patients from a plethora of complications.
RESUMO
Murine studies stipulate Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1) as a key mediator of PTH mRNA stability and is acknowledged by genome-wide-association-studies as secondary hyperparathyroidism defining trait in chronic kidney disease. Therefore, we hypothesize that molecular variants of the PIN-1 gene might affect the incidence and predisposition to secondary hyperparathyroidism in chronic renal insufficiency. A total of 281 adult participants, including 124 chronic kidney disease patients with secondary hyperparathyroidism and 157 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci (PIN-1 gene; - 667C > T; rs2233679) on the susceptibility to secondary hyperparathyroidism in chronic kidney disease. Suitable descriptive statistics was used for different variables. The genotype (x2: 8.03, 2 d. f. p = 0.0181) and allele distribution (x2: 7.27, 2 d. f. p: 0.007) of the - 667C > T variant differed significantly in cases and controls, with no deviation from Hardy-Weinberg equilibrium in either affected or control group. The observed frequencies of T allele of PIN-1 - 667 C > T SNP was significantly high in CKD-SHPT group compared to control group (52.41% vs. 41.71%; p: 0.0118). TT variant of PIN-1 - 667C > T SNP was associated with increased risk for occurrence of CKD-SHPT in univariate analysis (OR: 4.6, p: 0.0032, 95% CI: 1.66-12.76). Further in multivariate analysis, both TT (OR: 3.84, p: 0.002, 95% CI: 0.79-9.26) and CT + TT (OR: 2.51, p: 0.031, 95% CI: 0.64-8.68) variants were independently associated with increased risk for CKD-SHPT, emphasizing the deleterious effect of minor T allele. Serum PTH, phosphorus levels were significantly high in CT and TT genotypes compared to CC genotype of PIN-1 - 667C > T SNP (p = 0.001). PIN-1 promoter functional SNP (- 667C > T; rs2233679) appeared to be an important genetic determinant in etiopathogenesis of CKD-SHPT and genetic variants of this SNP influences the risk stratification and might serve as a predictive marker. Thus, rs2233679 can be useful for outcome predictions during diagnostic processes.