OBJECTIVE

The processes involved in bone remodeling are under the control of a multitude of systemic and local factors. Receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) complex seems to be one of the major modulators of bone remodeling. In chronic renal failure, the cytokine systems involved in the regulation of bone turnover may be influenced, and are therefore likely to contribute to the pathogenesis of renal bone disease. The aim of the present study was the evaluation of RANKL/OPG complex in concert with other biochemical parameters in hemodialysis (HD) patients and the investigation of possible correlations between the serum levels of its components and several clinical parameters of these patients.

METHODS

We measured serum levels of intact PTH (iPTH), total serum RANKL (sRANKL), osteoprotegerin (OPG), alkaline phosphatase, osteocalcin (OC), and tartrate-resistant acid phosphatase (TRAP) in 104 HD patients and in 40 healthy controls.

RESULTS

The average serum OPG level was significantly higher, whereas the average serum concentration of RANKL was nonsignificantly lower in patients on HD therapy than in age-matched healthy controls. Consequently, the mean sRANKL/OPG ratio was significantly lower in patients. Among HD patients, serum level of OPG increased significantly with aging and with a longer duration of hemodialysis. RANKL levels were inversely correlated with age nonsignificantly in the whole group of patients and significantly in the female subgroup (r=-0.322, p=0.035), whereas RANKL/OPG ratio declined significantly with age in the entire cohort of patients (r=-0.259, p=0.008). In addition, iPTH, OC, TRAP were significantly higher in female, whereas RANKL/OPG ratio was significantly higher in male than female patients.

CONCLUSIONS

Lower values of sRANKL/OPG ratio in HD patients, as well as the age and duration of HD dependent increase of serum OPG and the age-dependent decrease of sRANKL concentration especially in women cannot be explained by the elimination of renal clearance only. Alterations in sRANKL/OPG ratio might reflect a compensatory mechanism to modulate bone remodeling in these patients.

The physiologic effects of epinephrine on mineral metabolism are not known. In six healthy men, insulin-induced hypoglycemia, a potent stimulus to endogenous epinephrine secretion, resulted in a decrement of 0.9+/-0.1 mg/dl (mean+/-SE, P < 0.001) in serum inorganic phosphorus and smaller increments in magnesium and total and ionized calcium. Plasma immunoreactive parathyroid hormone (iPTH) decreased and plasma immunoreactive calcitonin (iCT) increased appropriately with the increments in calcium and magnesium. We wished to determine to what extent these changes in mineral metabolism might be attributable to epinephrine. Therefore, in the same protocol, we infused the hormone over 60 min in these six men, in doses that resulted in steady-state plasma epinephrine concentrations ranging from 52 to 945 pg/ml (levels that span the physiologic range), for a total of 25 studies. Serum ionized calcium, iPTH, and iCT concentrations were unaltered by these physiologic elevations of plasma epinephrine. However, epinephrine resulted in dose-dependent decrements in serum inorganic phosphorus of 0.6+/-0.1 mg/dl (P < 0.005) for the highest epinephrine infusion rate. The plasma epinephrine concentration threshold for this hypophosphatemic effect was approximately 50-100 pg/ml. Thus, the sensitivity of the hypophosphatemic response to epinephrine is comparable to that of the cardiac chronotropic, systolic pressor, and lipolytic responses to epinephrine, and considerably greater than that of the diastolic depressor, glycogenolytic, glycolytic, and ketogenic responses to the hormone in human beings. In view of its rapidity, the hypophosphatemic effect of epinephrine is probably the result of a net shift of phosphate from the extracellular compartment to intracellular compartments. We suggest that it is a direct effect of epinephrine, in that it is not mediated by changes in availability of the primary regulatory hormones PTH and CT, although indirect effects mediated by changes in other hormones, such as insulin, cannot be excluded. The hypophosphatemic response is also not attributable to increments in plasma calcium. These data indicate that epinephrine in physiologic concentrations is a hypophosphatemic hormone in man.

BACKGROUND

Primary hyperparathyroidism is the leading cause of hypercalcemia in the United States. The goal of this study was to evaluate the feasibility of radioguided thoracoscopic mediastinal parathyroidectomy and intraoperative immunoreactive parathyroid hormone (iPTH) level testing to guide completeness of resection.

METHODS

Mediastinal parathyroidectomy was performed thoracoscopically with intraoperative radioguidance using a hand-held gamma probe after injection of 10 mci of TC-99m sestamibi. Parathyroid excision was confirmed by ex vivo measurement of specimen radioactivity greater than 20% of background. Complete resection was confirmed by a greater than 50% decrease in serum iPTH level at 5 minutes postresection.

RESULTS

Four patients had mediastinal parathyroid glands successfully localized and resected thoracoscopically. Mean weight of the excised parathyroid adenoma was 1,714 mg (range, 425 to 4,400 mg). Baseline iPTH levels decreased from a mean of 202 to 39 pg/dL 5 minutes postresection. One patient underwent radioguided resection of a second enlarged cervical parathyroid adenoma at the same setting when his intraoperative iPTH levels failed to fall below 50% of baseline, despite resection of a 440 mg mediastinal parathyroid gland. Median hospital stay was one day. All mediastinal parathyroid glands resected were confirmed adenomas on final histologic examination. All patients were normocalcemic at follow-up (mean, 25 months), indicating cure.

CONCLUSIONS

Thoracoscopic mediastinal parathyroidectomy with intraoperative iPTH level monitoring is safe and effective. Radioguidance facilitates parathyroid localization. Ex vivo specimen radioactivity of greater than 20% of background confirms parathyroid resection and obviates the need for costly, time-consuming frozen section analysis. A 50% decrease in baseline iPTH level 5 minutes postresection confirms complete resection of parathyroid adenomas.

Minimally invasive parathyroidectomy is an accepted treatment option for primary hyperparathyroidism. The need for intraoperative parathyroid hormone assays (iPTH) to confirm adenoma removal remains controversial. We studied minimally invasive radio-guided parathyroidectomy (MIRP) performed using preoperative sestamibi localization studies, intraoperative gamma detection probe, and the selective use of frozen section pathology without the use of iPTH. This is a single institution review of patients with primary hyperparathyroidism treated with MIRP by surgeons experienced in radio-guided surgery between October 1, 1998 and July 15, 2005. Information was obtained by reviewing computer medical records as well as contacting primary care physicians. Factors evaluated included laboratory values, pathology results, and evidence of recurrence. One hundred forty patients were included with a median preoperative calcium level of 11.3 mg/dL (range, 9.6-17) and a PTH level of 147 pg/mL (range, 19-5042). The median postoperative calcium level was 9.3 mg/dL. All patients were initially eucalcemic postoperatively except for one who had normal parathyroid levels. However, five (4%) patients required re-exploration for various reasons. Of the failures, one was secondary to the development of secondary hyperparathyroidism, and therefore would not have benefited from iPTH, one had thyroid tissue removed at the first operation, and three developed evidence of a second adenoma. One of these three patients had a drop in PTH level from 1558 pg/mL preoperatively to 64 pg/mL on postoperative Day 1, indicating that iPTH would not have prevented this failure. Thus, only three (2.1%) patients could have potentially benefited from the use of iPTH. MIRP was successful in 96 per cent of patients using a combination of preoperative sestamibi scans, intraoperative localization with a gamma probe, and the selective use of frozen pathology. This correlates with reported success rates of 95 per cent to 100 per cent using iPTH. We conclude that minimally invasive parathyroidectomy can be successfully performed without using iPTH assays.

In the setting of total parathyroidectomy and autotransplantation surgery (TPT x AS) as treatment for secondary hyperparathyroidism (SHPT), we evaluated whether intraoperative parathyroid hormone (iPTH) monitoring is useful as a reference for total parathyroid removal. We conducted a prospective, open, single value measurement efficacy study of the intraoperative (i.o.) diagnostic monitoring of iPTH in a cohort of surgical patients. All patients (n = 25) underwent TPT x AS at the Department of Surgery, Donostia Hospital from January 2002 to October 2004. The primary outcome measures were kinetics of serum levels of iPTH during surgery and prediction time of the of descent of PTH levels (measured in the clinic on the day of admission and intraoperatively during induction of anesthesia, every 5 and 10 minutes after removal of the adenoma, and again 24 hours thereafter). iPTH levels returned to normal in all 25 patients, decreasing from pathological levels at the beginning of the operation (1302.24 + 424.9 pg/ml) to half (50%) values at the third intraoperative determination, minute 10 (614.8 +/- 196.62), becoming undetectable at 24 hours. Frozen sections were conclusive for parathyroid tissue (20.56 + 10.3 minutes after removal). Intraoperative measurement of iPTH is useful in the prediction complete removal of all parathyroid tissue prior to autotransplantation, thus avoiding persistence of disease because of incomplete surgery.

Physiologic adaptation to the high calcium demand during pregnancy and lactation may be different in adolescents than in adults, particularly at low calcium intake. The aim of this cross-sectional study was to compare biochemical markers of calcium and bone metabolism between adolescent (14-19 y) and adult (21-35 y) women with calcium intake approximately 500 mg/d, in three different physiologic states, i.e., control (nonpregnant, nonlactating; NPNL), pregnant and lactating. Markers of calcium metabolism [serum Ca, P and intact parathyroid hormone (iPTH); urinary Ca and P] and of bone turnover [urinary deoxypyridinoline (D-Pyr) and plasma bone alkaline phosphatase (BAP)] were measured in NPNL (adolescents, n = 12 and adults, n = 25), pregnant (adolescents, n = 30 and adults, n = 36) and lactating (adolescents, n = 19 and adults, n = 26) women. In the NPNL women, iPTH, D-Pyr and BAP were higher (P < 0.001) and urinary Ca was lower (P < 0.001) in adolescents than in adults. Serum iPTH was higher (P < 0.001) and urinary Ca was lower (P < 0.01) in adolescents than in adults also in pregnancy and lactation. Compared with NPNL women, serum Ca decreased (P < 0.001) with pregnancy in adolescents but not in adults. The increase in D-Pyr with pregnancy and lactation was very pronounced in adults ( approximately 130%, P < 0.001) but less in adolescents (<25%, P < 0.01). BAP increased (P < 0.001) with pregnancy and lactation in adults ( approximately 60%) but decreased (P < 0.001) with pregnancy in adolescents ( approximately 13%). Pregnancy and lactation appear to affect bone turnover in adolescent and adult women with low calcium intake differently.

The vitamin D status of 179 Korean women between the ages of 20 and 75 were measured by the use of high performance liquid chromatography (HPLC). Related biochemical indices such as iPTH, alkaline, phosphatase, creatinine, albumin, Ca, Mg, and P were also measured. Factors such as demographic characteristics, intake of foods containing vitamin D, and proxy measure of sunlight exposure (time spent outdoors) were assessed to determine their effect on vitamin D status and used in the analysis. The purpose of this study was twofold. The first was to define reference data for the distribution of vitamin D status and to explore the relationship between vitamin D and the variables that affect the vitamin D status in Korean women. The second was to analyze the risk factors of the vitamin D status and the relation between the factors. The results of this study will provide valuable information regarding the role of vitamin D in Korean women. The mean serum 25-hydroxyvitamin D (25-OHD) level was 25.8 ng/ml. Of the total subjects, 16.5% showed vitamin D deficiency (i.e. s-25-OHD < 10 ng/ml). Serum 25-OHD was inversely related to iPTH and alkaline phosphatase. There were significant changes in serum 25-OHD level from the pre- to the post-menopausal women with a positive correlation between vitamin D intake and serum at the 25-OHD level. Significant seasonal variation of serum 25-OHD and PTH were noted in 26 of the subjects and the serum 25-OHD level also correlated with sunlight exposure especially at 12.00 p.m. to 2.00 p.m. as assessed by the time spent outdoors. The relative importance of the two sources of vitamin D such as dietary intake (33.6% explained) and endogenous production of the time spent outdoors (19.7% explained) in serum 25-OHD were also evaluated. Multiple regression analysis revealed that the effects of aging on serum 25-OHD could largely be accounted for. Both the decline in dietary vitamin D intake and the time spent outdoors were closely related to the decreasing serum 25-OHD level. Among the determinants of low serum 25-OHD were age, dietary vitamin D intake, serum calcium level and dietary calcium intake, and serum alkaline phosphatase.

Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95 out of 297 patients with angiographically confirmed PAD stages II (pain in the calves and/or thighs only during exercise) or IV (history of, or presence of local ulcers) and compared them with 44 matched healthy controls regarding their medical history, bone density measurements of the femoral neck and calcaneal bone ultrasound. Bone pain, myalgias and mobility restriction as well as routine laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and analysed. 25(OH)D was significantly lower in PAD IV patients (9.6+/-4.6 ng/ml, P<0.0001) as compared to PAD II stages and controls (19.0+/-7.6 and 19.1+/-9.1 ng/ml), paralleled by lower serum calcium [2.24+/-0.02 mmol/l, P=0.0002 versus PAD II (2.36+/-0.02) and P<0.0001 versus controls (2.39+/-0.02)] and higher iPTH serum levels (66.3+/-3.6 pg/ml, P<0.0001) as compared to PAD II patients (45.3+/-3.5) and healthy controls (38.5+/-2.4). Alkaline phosphatase and serum crosslaps values were significantly higher and age-adjusted bone density and bone ultrasound measurements significantly lower in PAD IV patients, who were also twice as likely to have bone pain and myalgias as PAD II patients. Bone ultrasound measurements correlated significantly with both clinical severity and pain as well as serological parameters of bone metabolism. Underlying PAD has a significant impact on bone density and metabolism as well as on bone and muscular pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and should be regularly monitored and treated for their vitamin D deficiencies.

OBJECTIVE

Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function.

METHODS

Participants (n = 29) received an oral dose of 10,000 IU day(-1) vitamin D3 (VITD) or a visually identical placebo (PLB) for 3 months. Serum 25[OH]D and intact parathyroid hormone (iPTH) were measured at baseline and at week 4, 8 and 12. Muscle function was assessed in n = 22 participants by isokinetic dynamometry and percutaneous isometric electromyostimulation at baseline and at week 6 and 12.

RESULTS

Baseline mean total serum 25[OH]D was 40 ± 17 and 41 ± 20 nmol L(-1) for PLB and VITD, respectively. VITD showed a significant improvement in total 25[OH]D at week 4 (150 ± 31 nmol L(-1)) that remained elevated throughout the trial (P < 0.005). Contrastingly, PLB showed a significant decrease in 25[OH]D at week 12 (25 ± 15 nmol L(-1)) compared with baseline. Despite marked increases in total serum 25[OH]D in VITD and a decrease in PLB, there were no significant changes in any of the muscle function outcome measures at week 6 or 12 for either group (P>> 0.05).

CONCLUSIONS

Elevating total serum 25[OH]D to concentrations>> 120 nmol L(-1) has no effect on skeletal muscle function. We postulate that skeletal muscle function is only perturbed in conditions of severe deficiency (<12.5 nmol L(-1)).

BACKGROUND

Bone disease has been described in patients after surgical treatment for obesity, but few studies have dealt with the impact of vertical banded gastroplasty on mineral metabolism. We have examined bone mineral metabolism in morbidly obese patients before and after 3 months after vertical banded gastroplasty without vitamin D supplementation.

METHODS

Sixteen morbidly obese patients (14 women, 2 men) with a mean (+/-SD) age of 38 +/- 9 years and a body mass index (BMI) of 47.1 +/- 8.1 kg/m2 were studied. No vitamin D supplementation was given. Body weight, fat mass, calcium, 25OHD, iPTH, bone remodeling markers, and leptin levels were measured at baseline and after weight loss.

RESULTS

Mean weight loss was 28 +/- 11 kg; BMI and body fat mass decreased by 20 and 35%, respectively. Bone resorption markers and albumin-corrected serum calcium increased after operation, whereas iPTH fell. Serum 25OHD levels rose. Leptin levels decreased. Serum iPTH was positively correlated with weight, BMI, and fat mass before operation (p < 0.05), and its decline after weight reduction was negatively associated with the increase in bone resorption markers (p < 0.01). Leptin concentration was correlated with BMI and body fat mass (p < 0.05) both before and after surgery.

CONCLUSIONS

Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.

High doses of calcitriol were used prospectively for 11 to 29 months to raise serum calcium levels in an effort to control renal osteodystrophy in 16 children undergoing CAPD. Serum Ca, P, iPTH and alkaline phosphatase were measured monthly; hand radiographs were obtained every six months, and a semiquantitative score of bone abnormalities was evaluated by two independent observers. During the study, serum Ca increased from 9.9 +/- 0.9 to 11.0 +/- 0.6 mg/dl (P less than 0.001); serum iPTH decreased by 113 +/- 131 microliter Eq/ml (P less than 0.005); serum P was unchanged; and serum alkaline phosphatase fell by 33 +/- 46% (P less than 0.02), 530 +/- 397 to 204 +/- 551 IU/liter. The radiographic score fell from 4.8 +/- 4.6 to 0.9 +/- 1.2 (P less than 0.005). The average and maximal doses of calcitriol were 0.61 +/- 0.37 and 0.95 +/- 0.56 microgram/day or 28 +/- 18 and 46 +/- 28 ng/kg body wt/day, respectively. Transient and asymptomatic hypercalcemia occurred in nine patients and two patients had reversible conjunctivitis in association with the hypercalcemia. Thus, "high dose" calcitriol prevented or controlled progression of hyperparathyroid bone disease in most pediatric CAPD patients. The failure to suppress PTH or reverse secondary hyperparathyroidism until the serum Ca rose to 10.5 to 11.0 mg/dl could reflect an increase in the "set point" for PTH suppression by serum calcium in many uremic children.

A male patient, afflicted with malignant congenital osteopetrosis, was studied over a 5 year period. Hypocalcemia (less than 8 mg/dl) with lack of an appropriate increase in serum immunoreactive parathyroid hormone (iPTH) prevailed at all times. Under a calcium restricted diet, a 6-hour infusion of parathyroid extract normalized serum calcium, and increased the urinary hydroxyproline excretion suggesting that bone resorption had been induced. A second attempt to induce resorption was made by infusing a synthetic amino terminal fragment of bovine PTH over a period of 3 weeks at the dose of 1.5 units/kg/hr. This infusion evoked an increase in serum calcium (8.1 to 10.5 mg/dl), urinary calcium (0.03 to 0.65 mg/g creatinine) and urinary hydroxyproline (160 to 372 mg/g creatinine); and urinary hydroxyproline (160 to 372 mg/g creatinine); increases which were reversed by calcitonin administration. Iliac crest bone biopsies were obtained before and on the last day of the 3-week infusion. Quantitative comparison of the two specimens showed that, during PTH infusion, there was a 23% decrease in bone volume due to the increase in marrow space, a 93% increase in the number of osteoclasts and 136% increment in the osteoclastic resorption surface. Electron microscopic examination of the osteoclasts in the first tissue sample showed no evidence of ruffled borders, while in the second biopsy, numerous cytoplasmic processes indicative of resorptive activity were visible at the matrix-cell interface. It is proposed that, in our patient, the osteopetrotic phenotype is the consequence of an abnormality in the interaction between PTH and osteoclasts that may be related to the synthesis of a physiologically "defective" PTH.

FBH is characterized by symptomless hypercalcemia, low urinary calcium excretion, normal iPTH values, generally normal parathyroid histology, and failure of subtotal parathyroidectomy is normalize serum calcium. We studies six patients with FBH from three kindreds, six patients with sporadic 1 omicron HPT, and six healthy volunteers. To characterize the renal response to PTH, 14 of the subjects had infusions of bovine PTE (300 U intravenously over 15 min) and, separately, stimulation of endogenous PTH release by infusion of disodium EDTA (50 mg/kg over 2 hr). PTE induced striking increases of UcAMP (nM/100 ml of GF) that were indistinguishable between controls and subjects having FBH. However, the rise of UcAMP in 1 omicron HPT was significantly reduced (p < 0.001) compared to controls or the FBH group. EDTA-induced hypocalcemia raised serum iPTH and UcAMP in all three groups; the increases of iPTH (two assays of differing specificity) were greatest in 1 omicron HPT and least in FBH. In contrast, increases of UcAMP were greatest in FBH and 1 omicron HPT and indistinguishable from one another. The increase of UcAMP considered as a function of the increase in PTH showed significantly greater UcAMP responses in FBH than in the other groups. These results are consistent with primary or secondary alterations of renal responsiveness to PTH in both FBH and 1 omicron HPT, which may in part explain the different renal tubular calcium handling in the two conditions.

BACKGROUND

Our study aimed to investigate the factors associated with elevated plasma FGF23 (cFGF23) levels in maintenance hemodialysis (MHD) patients and to determine whether plasma FGF23 level is related to aortic artery calcification (AAC).

METHODS

This study included 120 MHD patients and 20 controls. The FGF23 level was measured using a C-terminal assay and AAC was detected by a lateral lumbar X-ray plain.

RESULTS

Plasma FGF23 levels were significantly higher among dialysis patients compared to controls: FGF23 level of 27691.42 ± 55646.41 RU/mL in MHD patients versus 49.89 ± 23.94 RU/mL in health people. Significant correlations were observed between FGF23 levels and vintage, intact parathyroid hormone (iPTH), serum phosphate, total calcium, 25(OH)D, urea nitrogen (BUN), and serum creatinine (SCR). Stepwise multiple regression analysis showed that the independent parameters associated with FGF23 level were serum phosphate, total calcium, parathyroid hormone (PTH), SCR, and prealbumin. There were 73 patients (60.83%) with visible calcification in the abdominal aorta. Bivariate analysis showed that AAC score correlated with FGF23, phosphate, total calcium, vintage, age, and diastolic blood pressure. Forward logistic analysis showed that the independent parameters associated with AAC were age, total protein, and Lg FGF23.

CONCLUSIONS

Plasma FGF23 level is significant increased in hemodialysis patients and is independently associated with AAC.

OBJECTIVE

We conducted this review to assess the relative efficacy and safety of lanthanum carbonate versus calcium-based phosphate binders in chronic kidney disease.

METHODS

We systematically searched PubMed, EMBASE, the Cochrane Controlled Trial Register of Controlled Trials and Chinese Biological Medical Database for randomized controlled trials comparing lanthanum carbonate with calcium-based phosphate binders in adult patients with chronic kidney disease. Study quality was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of intervention. Meta-analysis was conducted by reviewer manager software, version 5.3.

RESULTS

Eleven trials with 1,501 participants were included. Lanthanum carbonate appeared to be associated with a significant reduction in progression of vascular calcification and a beneficial effect on bone outcomes without aluminum-like toxicity. Lanthanum carbonate achieved similar proportions of phosphate-controlled patients (RR 0.63, 95% CI 0.27-1.44) with lower incidence of hypercalcemia (RR 0.13, 95% CI 0.05-0.35) in comparison with calcium-based phosphate binders. Lanthanum carbonate was associated with significantly lower serum calcium, similar serum Ca × P product and higher serum iPTH compared with calcium salts in patients with chronic kidney disease.

CONCLUSIONS

Lanthanum carbonate could delay the progression of vascular calcification and benefit chronic kidney disease patients on bone outcomes. Lanthanum carbonate could achieve similar proportion of phosphate-controlled patients as calcium-based phosphate binders with lower incidence of hypercalcemia.

BACKGROUND

Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively.

METHODS

In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid.

RESULTS

In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP>> or = 27 U/1 or iPTH>> 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism.

CONCLUSIONS

A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial.

Reports on acid-base side effects of sevelamer hydrochloride (SH), a new aluminum (Al)- and calcium (Ca)-free phosphate binder are rare and conflicting. In a retrospective analysis, we evaluated SH impact on metabolic acidosis and serum potassium (K) in hemodialysis (HD) patients. Two groups of stable HD patients were studied. Group A included 17 patients, M/F=15/2, 64 (42-80) years old, dialyzed since 130 (34-253) months, under SH for 24 months. Group B serving as controls was made of 7 patients, M/F=4/3, 67 (48-91) years old, dialyzed since 67 (27-174) months, under CaCO3 and/or Al(OH)3 as phosphate binders also for 24 months. Bicarbonate (BIC), K, Ca, phosphorus (P), Ca x P, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were recorded before (MO) and at the end (M24) of 24-month SH or CaCO3-Al(OH)3 treatment in group A and B patients. In group A, BIC fell from 20.02 +/- 1.43 to 17.89 +/- 2.30 mEq/ L, P=.002; and K rose from 5.45 +/- 0.51 to 5.75 +/- 0.49 mEq/L, P=0.02. In group B, BIC (19.8 +/- 3.03 to 19.0 +/- 3.3 mEq/L) and K (5.01 +/- 0.8 to 4.9 +/- 1.1 mEq/L) had nonsignificant changes. In group A, iPTH rose from 132.82 +/- 124.08 to 326.89 +/- 283.91 pg/mL, P=.0008; P fell from 5.92 +/- 1.48 to 4.9 +/- 1.01, P=.02; and Ca x P decreased from 52.04 +/- 9.7 to 45.58 +/- 10.42 mg2/dL2, P=.04. In group B, changes in iPTH from 240.71 +/- 174.7 to 318.57 +/- 260.2 pg/mL, P from 4.9 +/- 0.5 to 4.8 +/- 1.3 mg/dL, and CaxP product from 44.3 +/- 6.6 to 44 +/- 11.2 mg2/dL2 were nonsignificant. The changes observed in Ca and ALP in both groups were nonsignificant. Correlations in group A between metabolic acidosis (BIC) and SH doses, or iPTH and BIC, Ca, or P changes, were also found to be nonsignificant. Long-term use of SH, effectively controlling serum P levels and Ca x P values, is associated with acidosis aggravation and hyperkaliemia. Worsening of secondary hyperparathyroidism, also noted, needs to be confirmed and could be related to Ca/Al salt discontinuation and to metabolic acidosis aggravation itself.

BACKGROUND

In the last two decades considerable advances have been made in the development of imaging tests of the skeletal system. This progress in diagnostic techniques, along with the growing availability of the tests, renders it necessary to review and evaluate their suitability for daily clinical practice. The aim of this article is to compare the results of radiological testing of bone with densitometrical, histomorphometric, and biochemical tests in children with chronic renal failure.

METHODS

The research involved 31 children with renal failure, of whom 10 were being treated conservatively, 17 by continuous ambulatory peritoneal dialysis (CADO), and 4 by hemodialysis (HD). In all these children, radiological examinations of bone were performed in the arms, knees, and hips, along with tests for the serum concentration of parathormone (iPTH), calcium (Ca), and phosphates (P), and for the activity of alkaline phosphatase (AP). Bone density tests by the DXA method and bone biopsies were also performed. On the basis of radiological evaluation, the patients were divided into two groups: Group I, consisting of 14 children with a normal bone structure image, and Group II, consisting of 17 children with bone atrophy.

RESULTS

No statistically significant differences were discovered in the mean values of the tested biochemical parameters between the two groups. The mineral density of total body was normal in 9 of the 14 patients in Group I (64%), and in 7 of 17 (41%) from Group II. The mineral density of total lumbar spine gave similar results. Lower bone density results were obtained in Group II than in Group I, though only in the case of the lumbar spine were the differences statistically significant. In Group I, 5 cases were discovered of chronic osteodystrophy without osteomalacia and hyperparathyroidism (NB), 2 cases of adynamic bone disease (ABD), 4 cases of hyperparathyroidism (HP), 2 cases of moderate hyperparathyroidism (MHP), and one mixed form (Mix); in Group II, there were 6 NBs, 2 ABDs, 1 case of osteomalacia (OM), 5 HPs, and 3 mixed. Radiological examinations revealed one male in Group I with features of prior Perthes's disease, one with fibrous cortical defect, and four cases of valgity of the coxa valga. In Group II, there were 3 children with radiological changes typical for osteomalacia, and in 1 case typical radiological signs of hyperparathyroidism.

CONCLUSIONS

Given the lack of consistency in the results of the tests here presented, an entire panel of available tests should be performed for the comprehensive evaluation of the status of the skeleton.

Mineral bone disorder (MBD) is an important complication of chronic kidney disease (CKD). However, there are limited data on the pattern of MBD in Indian CKD population. The aim of this study was to describe spectrum of MBD in patients with CKD in our center. This was a hospital-based cross-sectional observational study. Patients with stage 4 and 5 CKD were included in this study. Those receiving calcium supplement, vitamin D or its analogues, and calcimimetic were excluded. Serum/plasma levels of creatinine, albumin, calcium, phosphate, total alkaline phosphatase (TAP), intact parathormone (iPTH), and 25-OH vitaminD (25-vitD) were measured. Radiological survey of bones was carried out in all cases, and echocardiography done in selected patients. Statistical analysis was done using Sigmaplot 10.0 software. A total of 150 patients (114 males, 36 females) were included in this study. Mean age was 45.67±16.96 years. CKD stage 4 and 5D were found in 26% (n=39) and 74% (n=111) of study population, respectively. The most common underlying native kidney diseases in patients of CKD 4 and 5D were diabetic nephropathy (41.03%) and CGN (41.44%), respectively. Median (first quartile, third quartile) values for serum levels of corrected calcium (cCa), phosphate, cCaXPO4 product, TAP, plasma iPTH, and 25-vitD in stage 4 CKD were 8.36 (7.79, 8.91) mg/dL, 4.9 (3.92, 6.4) mg/dL, 41.11 (34.01, 53.81) mg(2)/dL(2), 97 (76.5, 184.25) IU/L, 231 (124.5, 430.75) pg/mL, and 12 (6.98, 23.55) ng/mL, respectively; and in stage 5D CKD were 8.36 (7.66, 8.95) mg/dL, 5.7 (4.23, 6.95) mg/dL, 46.5 (37.16, 54.47) mg(2)/dL(2), 180 (114.5, 276.25) IU/L, 288 (169.75, 625.0) pg/mL, and 18.4 (10.0, 26.4) ng/mL, respectively. Prevalence of hypocalcemia (56.41% vs. 54.95%), hyperphosphatemia (64.10% vs. 70.27%), and hyperparathyroidism (84.62% vs. 88.29%) was not different between patients with CKD 4 and 5D. However, iPTH level outside the target range and increased TAP level were significantly (P<0.001) more common in CKD stage 5D. Multiple logistic regression analysis for hyperparathyroidism revealed significant inverse correlation with cCa in CKD 5D. There were no significant differences in vitamin D status and prevalence of valvular calcification between CKD stage 4 and 5D. X-ray revealed renal osteodystrophy in 8 (5.33%) patients, while it was normal in 118 (78.67%) patients. Secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, increased TAP, and 25-OH vitamin D deficiency and insufficiency were quite common in CKD 4 and 5 patients. The commonest type of MBD in CKD 4 and 5D was secondary hyperparathyroidism.

BACKGROUND

BsmI vitamin D receptor (VDR) gene polymorphism has been associated with the severity of hyperparathyroidism in patients on hemodialysis. The aim of this study was to analyze the influence of this polymorphism on parathyroid function and serum calcitriol levels in patients with different degrees of chronic renal failure (CRF) before dialysis.

METHODS

A total of 248 CRF patients, divided into three groups according to creatinine clearance (CCr; mild CRF group> 60 to </=85 ml/min, N = 54; moderate CRF group> 35 to </=60 ml/min, N = 113; severe CRF group> 10 to </=35 ml/min, N = 81), had their serum intact parathyroid hormone (<em>iPTH</em>) and calcitriol levels measured and BsmI genotype frequencies estimated by polymerase chain reaction (PCR) analysis. Diabetics, those on treatment with steroids, vitamin D or derivatives, and phosphorus binding agents were excluded. All those with serum calcium levels of <2.25 mmol/liter or> 2.5 mmol/liter and serum phosphorus levels of> 1.6 mmol/liter or who needed phosphorus binding agents were excluded. The statistical analysis was done with the general factorial analysis of variance entering first PTH and then calcitriol as the dependent variable; the genotype (BB, Bb and bb), sex and CCr group were defined as factors; and covariables included serum calcium, serum phosphorus, 1/creatinine versus time slope, PTH when calcitriol was the dependent variable, and calcitriol when PTH was the dependent variable.

RESULTS

When serum PTH levels were entered as the dependent variable, serum calcium, CCr group, and the interaction of genotype with the CCr group were found to be significant factors (P = 0.025, P <0.001 and P = 0.039, respectively). When serum calcitriol levels were entered as the dependent variable, genotype, the interaction of genotype with CCr, the CCr group, and the 1/creatine versus time slope were found to be significant (P = 0.027, P = 0.028, P <0.001 and P = 0.044, respectively). The marginal means of PTH, adjusted with the general factorial analysis of variance across the three groups were: (a) mild CRF group, BB 5.3 pmol/liter (CI 0 to 13.8), Bb 5.5 pmol/liter (CI 2 to 9), bb 5.4 pmol/liter (CI 0.6 to 10.2); (b) moderate CRF group, BB 6.2 pmol/liter (CI 1.5 to 10.9), Bb 7.8 pmol/liter (CI 5.3 to 10.3), bb 7.5 pmol/liter (CI 4.8 to 10.1); (c) severe CRF group, BB 9.3 pmol/liter (CI 4.2 to 14.3), Bb 17.1 pmol/liter (CI 13.9 to 20.2), bb 21.9 pmol/liter (CI 18.7 to 25.2). The marginal means of calcitriol adjusted with the general factorial analysis of variance across the three groups were: (a) mild CRF group, BB 47 pg/ml (CI 37 to 57), Bb 40.9 pg/ml (CI 37 to 44.8), bb 32.6 pg/ml (CI 26.8 to 38. 4); (b) moderate CRF group, BB 24.1 pg/ml (CI 18.3 to 29.8), Bb 26.6 pg/ml (CI 23.5 to 29.7), bb 25.3 pg/ml (CI 22 to 28.6); (c) severe CRF group, BB 27.4 pg/ml (CI 21.3 to 33.5), Bb 19.4 pg/ml (CI 15.5 to 23.2), bb 20.4 pg/ml (CI 16.1 to 24.7).

CONCLUSIONS

The progression of hyperparathyroidism is slower in predialysis patients with BB genotypes than in the other genotypes. Also, calcitriol levels are less reduced in the BB genotype, which may act to lessen the severity of secondary hyperparathyroidism.

Predicting mortality in dialysis patients based on low intact parathyroid hormone levels is difficult, because aluminum intoxication, malnutrition, older age, race, diabetes, or peritoneal dialysis may influence these levels. We investigated the clinical implications of low parathyroid hormone levels in relation to the mortality of dialysis patients using sensitive, stratified, and adjusted models and a nationwide dialysis database. We analyzed data from 2005 to 2012 that were held on the Taiwan Renal Registry Data System, and 94,983 hemodialysis patients with valid data regarding their intact parathyroid levels were included in this study. The patient cohort was subdivided based on the intact parathyroid hormone and alkaline phosphatase levels. The mean hemodialysis duration within this cohort was 3.5 years. The mean (standard deviation) age was 62 (14) years. After adjusting for age, sex, diabetes, the hemodialysis duration, serum albumin levels, hematocrit levels, calcium levels, phosphate levels, and the hemodialysis treatment adequacy score, the single-pool Kt/V, the crude and adjusted all-cause mortality rates increased when alkaline phosphatase levels were higher or intact parathyroid hormone levels were lower. In general, at any given level of serum calcium or phosphate, patients with low intact parathyroid hormone levels had higher mortality rates than those with normal or high iPTH levels. At a given alkaline phosphatase level, the hazard ratio for all-cause mortality was 1.33 (p < 0.01, 95% confidence interval 1.27-1.39) in the group with intact parathyroid hormone levels < 150 pg/mL and serum calcium levels>> 9.5 mg/dL, but in the group with intact parathyroid hormone levels>> 300 pg/mL and serum calcium levels>> 9.5 mg/dL, the hazard ratio was 0.92 (95% confidence interval 0.85-1.01). Hence, maintaining albumin-corrected high serum calcium levels at>> 9.5 mg/dL may correlate with poor prognoses for patients with low intact parathyroid hormone levels.

BACKGROUND

Coronary artery calcification scores (CACS) calculated by electron beam computed tomography (EBCT) have been correlated with atherosclerotic burden in the non-uraemic population. However, the validity of this test in chronic haemodialysis patients (HD) is currently uncertain. In the present cross-sectional study, associations between carotid atherosclerosis and coronary calcification in HD patients are investigated.

METHODS

We studied 79 chronic HD patients (39 male, 40 female; mean age, 45+/-12 years). The mean time on HD was 68+/-54 months (range, 6-187 months). In these patients, we measured serum calcium, phosphorus, total cholesterol, cholesterol subgroups and iPTH levels. EBCT, echocardiography, and high-resolution B-mode carotid Doppler ultrasonography were also performed.

RESULTS

Plaque-positive HD patients had significantly higher CACS than plaque-negative patients (851+/-199 vs 428+/-185, mean+/-SE, P = 0.006). Coronary calcification scores were correlated with serum phosphorus (r = 0.37; P = 0.001). Only 8 of the 24 HD patients without coronary calcification had carotid plaques (33%), whereas 34 of the 53 patients with coronary calcification had carotid plaques (64%) (P = 0.015). Carotid plaque scores were correlated with CACS (r = 0.40; P = 0.001). A stepwise linear regression (model r = 0.72; P<0.001) revealed that CACS (log-transformed data of CACS) was associated with age (P<0.001), time on dialysis (P = 0.004), serum phosphorus level (P = 0.016) and carotid plaque scores (P = 0.037).

CONCLUSIONS

Atherosclerosis is independently associated with coronary artery calcification and with hyperphosphataemia in chronic HD patients. CACS appeared to be predictive of both coronary atherosclerosis and carotid atherosclerosis.

BACKGROUND

The usefulness of bone mass measurements and bone turnover markers to estimate the risk of fracture and the type of underlying renal osteodystrophy are not well established in patients on peritoneal dialysis (PD).

OBJECTIVE

To assess bone mass using total and regional bone densitometry in a group of patients on PD and to determine if serum markers of bone turnover identify patients with low bone mass.

METHODS

Bone densitometry was studied by dual-energy x-ray absorptiometry (DEXA), and bone turnover using several serum markers, in 65 patients on PD. Bone mass was classified as normal, osteopenic, or osteoporotic according to World Health Organization criteria based on bone mineral density (BMD) T scores.

RESULTS

T scores in the osteopenia range were present at the lumbar spine (LS) in 44.6% (45% of men and 44.4% of women) of patients and at the femoral neck (FN) in 56.9% (55% of men and 58% of women). T scores in the osteoporosis range were present at the LS in 13.8% of patients (10% of men and 15.5% of women) and at the FN in 21.5% (30% of men and 17.7% of women). Patients with BMD T scores in the osteoporosis range at both regions had increased serum intact parathyroid hormone (iPTH) levels compared to patients in the osteopenic/normal range. Bone mineral content in the whole skeleton (TBMC) correlated negatively with iPTH (r = -0.34) and with total time on dialysis (r = -0.26); in multivariate analysis, only iPTH correlated negatively with TBMC (B = -0.26, p = 0.03). No correlations were found between the other bone markers and BMD T scores at the FN or LS. There were no significant differences in absolute BMD or BMD T scores at the LS or FN between patients with and patients without fractures.

CONCLUSIONS

BMD T scores in the osteopenia/osteoporosis range were observed at the LS in 58.4% of these patients on PD and at the FN in 78.4%. TBMC correlated negatively with iPTH. There were no correlations between markers of bone turnover and bone mass measurements at the two skeletal regions, although patients with BMD T scores in the osteoporosis range had increased serum iPTH levels. Bone mass measurements were not different between patients with and patients without fractures.

BACKGROUND

Patients with chronic renal failure (CRF) are at high risk of renal osteodystrophy. Our study aimed to identify predictors of bone mass and cumulative fracture rate at the time of renal transplantation (RTx). This is important since the patients experience further substantial bone loss the first month post-transplant.

METHODS

Altogether 133 renal transplant patients were examined for bone mineral density (BMD) using dual-energy X-ray absorptiometry shortly after RTx.

RESULTS

The patients'Z-scores were significantly lower at the time of RTx compared to the reference population (p < 0.05), 32% were osteopenic and 11% had osteoporosis. Independent predictors of low bone mass were age (p < 0.001), female sex (p < 0.001), intact parathyroid hormone (iPTH) level (p < 0.001), former transplantation (p = 0.001) and time on hemodialysis (HD) (p = 0.005). Body mass index (BMI) (p < 0.001) and physical activity (p = 0.027) were associated with high BMD. Cumulative fracture rate (29%) was associated with physical inactivity (p = 0.003), BMI (p = 0.036) and osteopenia (p < 0.001) at the time of RTx.

CONCLUSIONS

In a representative CRF population, BMD was reduced. Independent predictors of BMD were as for the general population, and uremia associated predictors were time on HD, previous transplantation and serum iPTH level. Fracture rate was high, and physical inactivity had the strongest association with fractures.