Comparison between bone alkaline phosphatase immunoassay and electrophoresis technique in hemodialysis patients.

BACKGROUND: Problem of the variability between the different methods using for bone alkaline phosphatase (bALP) determination greately influences the clinical significance of bALP as direct marker of bone metabolism. The aim of this study was to compare immunoassay with electrophoresis technique for bALP determination. METHODS: We measured bALP in 71 patients on hemo - dialysis with agar gel electrophoresis (ISO-PAL, SEBIA) and immunoassay (OSTASE, Beckman Coulter). RESULTS: The analyzed methods showed significant correlation (Spearman's rho: 0.776, P < 0.01), but we found statistically significant (P < 0.01) positive bias (27%) for the results measured by immunoassay. In support of this, using electrophoresis technique we have detected presence of the intestinal isoenzymes of alkaline phosphatase in 55% of patients with median value of 30% of the total alkaline phoshatase and presence of liver-2 alkaline phosphatase isoform in 42% of patients with median value of 16.6%. The Kendall's W of 0.787 (P<0.0001) revealed significant concordance between two analysed methods. Cusum test showed no significant deviation from linearity (P=0.850). CONCLUSIONS: Despite good agreement between immuno - assay methods and electrophoresis technique for bALP determination, interchangeability between these two methods is questionable. Although immunoassays are increasingly used, as fully automated methods, in a large number of laboratories and become routine methods for bALP determination, it should be beared in mind, besides various interferences, also the heterogeneity of the bALP itself, especially in patients on hemodialysis.

Significance of acPWV for Survival of Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Abnormal arterial stiffness (AS) is a major complication in end-stage kidney disease (ESKD) patients treated by dialysis. Our study aimed to determine the significance of AS for survival of prevalent dialysis patients, as well as its association with cardiovascular parameters or vascular calcification promoters/inhibitors or both and AS. MATERIALS AND METHODS: The study involved 80 adult hemodialysis patients. Besides standard laboratory analyses, we also determined promoters and inhibitors of vascular calcification (bone biomarkers): serum levels of fibroblast growth factor 23 (FGF23), soluble Klotho, intact parathormone (iPTH), 1,25-dihydroxyvitamin D3, osteoprotegerin, sclerostin, AS measured as ankle carotid pulse wave velocity (acPWV), Ankle Brachial Index (ABI), and vascular calcification (VC) score. Patients were monitored for up to 28 months. According to the median acPWV value, we divided patients into a group with acPWV ≤ 8.8 m/s, and a group with acPWV > 8.8 m/s, and the two groups were compared. RESULTS: Values for bone biomarkers were similar in both groups. Mean arterial blood pressure (MAP), central systolic and diastolic brachial blood pressure, heart rate, and pulse pressure were higher in the group with acPWV > 8.8 m/s than in the group with acPWV ≤ 8.8 m/s. The mortality was higher for patients with acPWV > 8.8 m/s at any given time over 28 months of follow-up. In multivariable analysis, predictors of higher acPWV were age >60.5, higher pulse rate, and higher central systolic or brachial diastolic blood pressure. CONCLUSIONS: According to our results, we advise the measurement of acPWV preferentially in younger dialysis patients for prognosis, as well as intervention planning before the development of irreversible changes in blood vessels. In addition, measuring central systolic blood pressure seems to be useful for monitoring AS in prevalent hemodialysis patients.

Correlation of bone alkaline phosphatase and iPTH with some basic biochemical markers in predialysis and dialysis patients.

BACKGROUND: Bone alkaline phosphatase (BALP) is a direct and independent indicator of impaired bone turnover. We intended to find out whether there are any significant changes in BALP and iPTH levels, in comparison to total Ca, total Mg, inorganic P, total alkaline phosphatase (ALP), and tartrate resistant acid phosphatase (TRAP) in predialysis and dialysis patients. METHODS: Out of 266 patients investigated, 114 were on continuous ambulatory peritoneal dialysis, 112 were on maintenance haemodialysis, while 40 predialysis patients had end stage renal disease. The parameters were analysed according to the manufacturers' instructions. RESULTS: Correlations were established for the bone marker concentrations analysed among the studied groups. The largest ranges were determined for BALP and iPTH. Predialysis and dialysis patients showed very low levels of BALP. Dialysis patients had lower levels of iPTH (p < 0.001), while in predialysis patients the levels were significantly higher (p < 0.05) than recommended for low bone turnover, according to K/DOQI. CONCLUSIONS: The observations made in this study identify BALP as a good indicator of decreased bone turnover in predialysis and dialysis patients. However, in order to reveal a difference between bone activity and the level of parathyroid activity and its effect on bone turnover, it is always necessary to observe both BALP and iPTH levels.

Health-related quality of life, treatment efficacy, and hemodialysis patient outcome.

The aim of the study was to examine the influence of improved treatment of hemodialysis (HD) patients on their health-related quality of life (HrQoL) and to assess the predictive value of HrQoL dimensions on patient outcome. The prospective cohort study involved 102 HD patients, and their clinical and laboratory parameters and HD adequacy indices were followed from 2001 to 2007. HrQoL was measured using KDQOL-SF Version 1.3 in 2001, 2004, and 2007. During a six-year period, quality of HD and anemia treatment improved and resulted in significant increase of mean Kt/V (1.2-1.56) and hemoglobin levels (86.5-115.6 g/L). All four HrQoL dimensions (i.e., physical, mental health, kidney disease target issues, and patient satisfaction) remained unchanged, but significant improvement in several HrQoL physical health domains and the effects of kidney disease domain was found. Mortality rate decreased from 18.6% to 7.14% per year. Age was associated positively, but kidney disease target issue score negatively, with patient death. Improved HD adequacy and anemia treatment in HD patients were followed with maintenance of all four HrQoL dimensions unchanged over six years. Moreover, an improvement in several physical health domains and the effects of kidney disease domain was found. Age and kidney disease target issue appeared as significant predictors of patients' death.

Relation between 25(OH)-vitamin D deficiency and markers of bone formation and resorption in haemodialysis patients.

Deficient serum 25-hydroxyvitamin D [25(OH)D] may contribute to the impaired bone turnover of end stage renal disease patients. In 112 hemodialysed patients we analysed the relation between 25(OH)D and bone alkaline phosphatase (BALP), beta-CrossLaps (beta-CTx) and iPTH. We analysed parameters according to the manufacturers' instructions. We found potentially significant vitamin D deficiency: 71% of patients had 25(OH)D levels below 50 nmol/L. In patients with iPTH below 150 pg/mL (n = 57), we observed significantly low 25(OH) (p < 0.01). In addition, patients with iPTH above 300 pg/mL had higher BALP levels (p < 0.05). There were negative correlations between serum 25(OH)D and both BALP and iPTH (r = -0.225, p < 0.05 and r = -0.331, p < 0.05). Beta-CTx levels were significantly higher in patients who did not receive vitamin D supplementation (p < 0.01). In addition, reduced BALP and iPTH levels indicate decreased bone turnover. Recorded data could signify that vitamin D deficiency may contribute to the impaired bone metabolism of hemodialysis patients.

Effects of lowering dialysate calcium concentration on mineral metabolism and parathyroid hormone secretion: a multicentric study.

This prospective study was conducted with the aim of examining the efficacy of lowering dialysate calcium (dCa) in order to: (i) stimulate bone turnover in hemodialysis patients with biochemical signs of adynamic bone disease (ABD) (hypercalcemia, normal alkaline phosphatase and intact parathyroid hormone (iPTH) <150 pg/mL); and (ii) diminish hypercalcemia in patients with secondary hyperparathyroidism (sHPT) (hypercalcemia, high alkaline phosphatase and iPTH > 400 pg/mL), thus permitting the use of calcium-containing phosphorus binders and vitamin D metabolites. Patients were divided into: an ABD-treated group (24 patients), a sHPT-treated group (18 patients), an ABD-control group (12 patients) and a sHPT-control group (11 patients). For the ABD- and sHPT-treated patients, hemodialysis was conducted with dCa 1.5 mmol/L for three months and then with dCa 1.25 mmol/L for an additional three months, while in the control groups hemodialysis was conducted with dCa 1.75 mmol/L during the entire study. Reduction of dCa in patients with ABD caused a slight but insignificant decrease of Ca, but a significant and permanent increase of bone-specific alkaline phosphatase and intact parathyroid hormone level serum levels. Reduction of dCa in patients with sHPT slightly but insignificantly decreased Ca and intact parathyroid hormone level values. Nevertheless, this enabled the calcium-based phosphate binder dose to be raised and vitamin D3 metabolites to be introduced. Logistic regression analysis indicated that milder bone disease (both ABD and sHPT) was associated with more the favorable effect of dCa reduction. Thus, low dCa stimulated parathyroid glands and increased bone turnover in ABD patients, and enabled better control of mineral metabolism in sHPT patients.

Ten years' experience in subtotal parathyroidectomy of hemodialysis patients.

Secondary hyperparathyroidism (SHP) is a frequent complication of long-term dialysis patients, and surgical parathyroidectomy remains necessary in patients resistant to medical therapy. The present paper reports single center results in subtotal parathyroidectomy, presenting diagnostic procedure, indications for parathyroidectomy, and postoperative course of metabolic and endocrine disorders. Forty-seven patients (25 males and 22 females), aged 25-60 years, regularly hemodialyzed between 3-23 years, have undergone parathyroidectomy at our Clinical Center during the last 10 years. The patients had plasma iPTH levels 8-45 times higher than the top normal limit, high values of alkaline phosphatase, calcemia on the upper normal level, and hyperphosphatemia. Radiographic changes characteristic for SHP were seen in all patients before parathyroidectomy, and the most common were subperiosteal resorptions (100%), bone cysts and periosteal neostosis (66%), and extraskeletal calcifications (98%). Enlarged parathyroid glands were seen by ultrasound in 62% of patients. All patients manifested pruritus and bone pain, 89% of them had myopathy, while other symptoms and signs were present in lower proportions. After parathyroidectomy, pruritus and myopathy reduced significantly, while pain in bones and joints remained. One patient had brown tumor at the maxillary bone that regressed gradually after parathyroidectomy. Significant decreases of phosphate and calcium levels were recorded in all but two patients on the very first postoperative day. Regular peroral and parenteral supplementations of calcium and vitamin D metabolites were used, but calcemia was not normalized until the end of the third week of the postoperative period. Serum alkaline phosphatase showed an increase after the surgery, thereupon a sudden and then slower decrease up to 1 year from the surgery. Plasma iPTH levels, checked on the 21st postoperative day, were close to the lower normal limit in all but two (4.3%) patients with persistent SHP, who required reoperation. In conclusion, subtotal parathyroidectomy was proved as a successful and safe treatment for patients with SHP resistant to medical therapy, and treatment was followed by improvement of clinical symptoms and metabolic disorders.

A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients.

BACKGROUND: Lanthanum carbonate (LC) (Fosrenol) is a novel new treatment for hyperphosphatemia. In this phase III, open-label study, we compared the effects of LC and calcium carbonate (CC) on the evolution of renal osteodystrophy (ROD) in dialysis patients. METHODS: Ninety-eight patients were randomized to LC (N = 49) or CC (N = 49). Bone biopsies were taken at baseline and after one year of treatment. Acceptable paired biopsies were available for static and dynamic histomorphometry studies in 33 LC and 30 CC patients. Blood samples were taken at regular intervals for biochemical analysis and adverse events were monitored. RESULTS: LC was well tolerated and serum phosphate levels were well controlled in both treatment groups. The incidence of hypercalcemia was lower in the LC group (6% vs. 49% for CC). At baseline, subtypes of ROD were similarly distributed in both groups, with mixed ROD being most common. At one-year follow-up in the LC group, 5 of 7 patients with baseline low bone turnover (either adynamic bone or osteomalacia), and 4 of 5 patients with baseline hyperparathyroidism, had evolved toward a normalization of their bone turnover. Only one lanthanum-treated patient evolved toward adynamic bone compared with 6 patients in the CC group. In the LC group, the number of patients having either adynamic bone, osteomalacia, or hyperpara decreased overall from 12 (36%) at baseline to 6 (18%), while in the calcium group, the number of patients with these types of ROD increased from 13 (43%) to 16 (53%). CONCLUSION: LC is a poorly absorbed, well-tolerated, and efficient phosphate binder. LC-treated dialysis patients show almost no evolution toward low bone turnover over one year (unlike CC-treated patients), nor do they experience any aluminum-like effects on bone.