Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

BACKGROUND

Declines in 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels and physical functioning follow the course of chronic kidney disease (CKD). Although the molecular actions of vitamin D in skeletal muscle are well known, and muscle weakness and atrophy are observed in vitamin D-deficient states, there is little information regarding vitamin D and muscle function and size in CKD.

OBJECTIVE

To examine associations of vitamin D with physical performance (PF) and muscle size.

METHODS

Cross-sectional.

METHODS

CKD clinic.

METHODS

Twenty-six patients (61 ± 13 years, 92% men) with CKD stage 3 or 4.

METHODS

Gait speed, 6-minute walk, sit-to-stand time, 1-legged balance, and thigh muscle cross-sectional area (MCSA), measured by magnetic resonance imaging (MRI).

RESULTS

Overall, 73% were 25-hydroxyvitamin D (25(OH)D) deficient (n = 10) or insufficient (n = 9) (Kidney Disease Outcomes Quality Initiative guidelines). 25(OH)D level was associated with normal gait speed only (r = 0.41, P = .04). Normal and fast gait speed, the distance walked in 6 minutes, and sit-to-stand time were best explained by 1,25(OH)₂D and body mass index (P < .05 for all) and 1-legged stand by 1,25(OH)₂D (r = 0.40, P < .05) only. There were no associations of age, estimated glomerular filtration rate (eGFR), intact parathyroid hormone (iPTH), or albumin with any PF measures. MCSA was associated with eGFR (r = 0.54, P < .01) only. Variance in MCSA was best explained by a model containing 1,25(OH)₂D, plasma Ca²⁺, and daily physical activity (by accelerometry) (P < .05 for all). Once these variables were in the model, there was no contribution of eGFR.

CONCLUSIONS

These results suggest that 1,25(OH)₂D is a determinant of PF and muscle size in patients with stage 3 and 4 CKD.

OBJECTIVE

To investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore.

METHODS

In total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD.

RESULTS

The mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine (P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip (P = .035) and the lumbar spine (P = .019). At levels <30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036).

CONCLUSIONS

Among this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations <30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health.

BACKGROUND

The aim of the study was to investigate whether serum levels of intact parathyroid hormone (iPTH) are associated with an increased risk of cardiovascular events, graft loss, or mortality in kidney transplant patients with optimal transplant function.

METHODS

From the Norwegian Renal Registry, we identified 522 patients who received a first kidney transplant from 2001 to 2008 with optimal transplant function defined as an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2, more than one yr after transplantation. Cox's proportional hazard models were used to assess the association between iPTH measured 10 wk after transplantation and the composite endpoint. The estimates were adjusted for age, gender, serum calcium, serum phosphate, diabetes mellitus, cardiovascular disease, and time on dialysis prior to transplantation.

RESULTS

Median follow-up time was 3.9 yr (interquartile range, IQR: 2.0-6.0 yr). Patients in the third iPTH quartile (9.3-14.4 pM) had the lowest risk for reaching the composite endpoint. Patients in the fourth iPTH quartile (>14.4 pM) had an increased risk compared to those in the third quartile (HR: 2.60, 95% CI: 1.10-6.16, p=0.03).

CONCLUSIONS

In patients with optimal transplant function, iPTH levels are associated with a clinical outcome consisting of cardiovascular events, graft loss, and all-cause mortality.

OBJECTIVE

Chronic kidney disease mineral- and bone disorder (CKD-MBD) has been studied more often in dialysis than in predialysis CKD patients. The association between efficacy of hyperphosphatemia control and chronic renal failure (CRF) progression, prevalence of bone disease and cardiovascular calcification was the objective of the present investigation.

METHODS

42 patients with CKD in Stage 5, regularly monitored for 5 years, were divided into Group 1 of 20 patients with normal serum phosphate (sPO4) levels and Group 2 of 22 patients with hyperphosphatemia registered at the majority of checks. Serum urea, creatinine, calcium (sCa) and sPO4 levels were regularly determined in the retrospective 5-year period. At the end of this period iPTH, bone alkaline phosphatase-BAP and inflammation markers (CRP, fetuin-A) were measured, valvular and arterial calcifications were detected by B mode echocardiogram and soft-tissue native radiograms of the pelvis and the wrist.

RESULTS

Progression of CRF (1/sCr over time) was faster in Group 2 than in Group 1 (b = -0.0577 vs. -0.0288, p = 0.003) during the study period. Average BAP and iPTH values were similar in both groups and 23/42 patients had PTH>> 300 pg/ml. Arterial and valvular calcifications were found in 5/23 patients from Group 1 and 14/22 patients from Group 2 (p = 0.011). Linear regression analysis revealed sPO4 as a predictor for total calcification number, inflammatory diseases as a predictor for valvular calcifications, while sPO4 and iPTH were predictors for arterial calcifications.

CONCLUSIONS

More than half the patients with Stage 5 CKD not yet on dialysis exhibited elevated PTH. Faster CRF progression and frequent arterial and valvular calcifications were seen in patients with poor phosphate control and sPO4 was selected as an independent predictor of total calcification score.

Glucose absorption from peritoneal dialysis solutions causes a chronic stimulation of insulin secretion, which leads to hyperinsulinism. The use of solutions without glucose should correct this metabolic derangement together with the associated cardiovascular risk. To verify this hypothesis, we studied the entire non diabetic continuous ambulatory peritoneal dialysis (CAPD) population of our center: 27 patients with a mean age of 62 +/- 15 years, and a median 17 months on treatment. Morning fasting serum insulin was 32.8 +/- 9.3 microU/mL; glucose, 104.4 +/- 21.8 mg/dL; triglycerides, 162.4 +/- 125.7 mg/dL; cholesterol, 221.9 +/- 54.7 mg/dL; intact parathyroid hormone (iPTH), 212 +/- 189 pg/mL; fibrinogen, 519 +/- 112 mg/dL; body mass index, 24.1 +/- 4.1; and daily erythropoietin subcutaneous therapy dose, 17 +/- 6 U/kg. Insulin sensitivity, measured as ISI-HOMA (insulin sensitivity index, derived from the homeostasis model assessment) was 2.4 +/- 0.7. Daily glucose load, calculated from dialytic schedules, was 135 +/- 38 g. Of the 27 patients, 12 were treated with standard glucose solutions during the day and with one icodextrin dwell during the night for a median of 9 months (range: 1-28). The remaining 15 patients were treated with standard glucose solutions. The icodextrin group showed significantly lower serum insulin levels (28.6 +/- 6.0 microU/mL vs 36.1 +/- 10.2 microU/mL, p = 0.021) and significantly higher ISI-HOMA values (2.7 +/- 0.5 vs 2.2 +/- 0.7, p = 0.041) than the control group. The two groups showed no significant differences for glucose, triglycerides, cholesterol, iPTH, fibrinogen, body mass index, or erythropoietin therapy dose. Daily glucose load was lower in the icodextrin group, but without reaching statistical significance (128 +/- 31 g vs 142 +/- 43 g). This study shows, in a preliminary way, that the chronic use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

OBJECTIVE

Higher serum alkaline phosphatase predicts lower mortality in chronic kidney disease and hemodialysis patients without liver dysfunction because it reflects high bone turnover. The purpose of our study was to compare the significance of serum bone alkaline phosphatase (BAP) with that of other bone markers in prediction of all-cause mortality(ACM) in male hemodialysis patients.

METHODS

The study was performed for 5 years. Serum BAP, intact osteocalcin (iOC), ß-CrossLaps (CTX), and intact parathyroid hormone (iPTH) were measured in 196 male hemodialysis patients without radiographic fracture. Their day-to-day variation during 5 consecutive days and diurnal variation were determined in 13 healthy males.

RESULTS

The patients were divided into higher and lower groups based on serum levels of bone markers(mean±SD: iPTH 218.6±214.5 pg/ml, BAP 23.6±12.2 U/L, iOC 42.8±45.2 ng/ml, CTX 1.71±1.23 nmol/L BCE). In Kaplan-Meier analysis, the higher BAP group had significantly higher ACM than the lower BAP group (P=0.013), whereas mortality did not differ between the higher and lower groups in other markers. Cox regression hazard analysis identified higher log BAP as a significant independent predictor [hazard ratio(HR) 8.32(95%CI:1.18-58.98)] for ACM after adjustment for various factors including pre-existing cardiovasucular disease, presence of DM. The significant association of mortality with serum BAP alone, in contrast with other markers including CTX [HR0.64 (95%CI:0.16-2.47)], iOC [HR0.97(95%CI:0.36-2.64)], iPTH [HR0.84(95%CI:0.44-1.60)], it may be due to the narrower day-to-day variation and the absence of diurnal variation in serum BAP compared to other markers.

CONCLUSIONS

Higher serum BAP may be a predictor of ACM in male hemodialysis patients.

OBJECTIVE

To determine the incidence of coronary heart disease (CHD) in patients (pts) over 65 years (y) and its relation to common risk factors.

METHODS

We retrospectively studied 128 hemodialysis (HD) pts (80 M and 48 F), mean age 73+/-6.5 years, mean time on HD 44.4+/-26.4 months and BMI 25.4+/-3 kg/m2. They were evaluated for: age, sex, smoking, diabetes, hypertension, left ventricular hypertrophy, secondary hyperparathyroidism (SHP), inflammation, as evidence by elevated level of hsCRP, hyperhomocysteinemia (HOC), time on HD, fluid overload and adequacy of HD. Forty-eight pts (37%) had CAD diagnosed by coronary angiography in 22 (46%) and (201)TL-chloride dipyridamole stress test in 26 (54%).

RESULTS

There was a statistically significant correlation between CAD and increasing age (p<0.0001). The relative risk was significantly increased concerning: (1) male over female pts (RR: 1.95, p<0.01), (2) diabetic vs. non diabetic pts (RR: 2.09, p<0.001), (3) patients with SHP over pts with iPTH values<250 pg/ml (RR: 2.16, p<0.001), (4) hypertensive vs. non hypertensive pts (RR: 2.26, p=0.002), (5) smokers vs. non smokers (RR: 1.69, p<0.05), (6) pts with HOC over pts with normal homocysteine values (RR: 2.09, p<0.05), (7) pts with increased CRP levels over pts with normal CRP levels (RR: 1.8, p<0.01), (8) pts undergoing HD for 36 vs. 12 months (RR: 1.71, p=0.03), (9) between pts with inadequate or adequate HD (RR: 1.73, p=0.02). No significant correlation existed between CAD incidence and the other risk factors.

CONCLUSIONS

Coronary heart disease incidence in elderly HD patients increases with age, male sex, diabetes, SHP, hypertension, increased CRP levels, HOC, smoking, time on HD and inadequacy of HD.

BACKGROUND

Paricalcitol and cinacalcet are common therapies for patients on haemodialysis with secondary hyperparathyroidism (SHPT). We conducted a multi-centre study in 12 countries to compare the safety and efficacy of paricalcitol and cinacalcet for the treatment of SHPT.

METHODS

Patients aged ≥18 years with Stage 5 chronic kidney disease receiving maintenance haemodialysis and with intact parathyroid hormone (iPTH) 300-800 pg/mL, calcium 8.4-10.0 mg/dL (2.09-2.49 mmol/L) and phosphorus ≤6.5 mg/dL (2.09 mmol/L) were randomized within two strata defined by the mode of paricalcitol administration to treatment with paricalcitol- (intra-venous, US and Russian sites, IV stratum; oral, non-US and non-Russian sites, oral stratum) or cinacalcet-centred therapy. The primary endpoint is the proportion of patients in each treatment group who achieve a mean iPTH value of 150-300 pg/mL during Weeks 21-28 of treatment. Assuming efficacy response rates of 36 and 66% for cinacalcet and paricalcitol, respectively, and a 20% discontinuation rate, 124 subjects in each stratum were estimated to provide 81% power to detect a 30% absolute difference in the primary endpoint.

RESULTS

Of 746 patients screened, 272 (mean age, 63 years; mean iPTH, 509 pg/mL) were randomized. Mean duration of haemodialysis at baseline was 3.7 years. Comorbidities included hypertension (90.4%), Type 2 diabetes (40.4%), congestive heart failure (17.3%), coronary artery disease (34.6%) and gastrointestinal disorders (75%).

CONCLUSIONS

The study participants are representative of a multinational cohort of patients on haemodialysis with elevated iPTH. The study results will provide valuable information on the best available treatment of SHPT in patients on haemodialysis.

Subtotal parathyroidectomy or total parathyroidectomy (PTx) with autotransplantation are surgical procedures considered while the patient is included on the waiting list for renal transplantation. Total PTx alone is based in the possibility that a fragment of tissue (nodular hyperplasia in particular) left in the same pathophysiological environment of long term dialysis would show the same behavior and reproduce in time the same clinicopathological picture. The persistence of uremia induces a continued growth stimulus developing residual hyperplasia and consequently a very high risk of recurrence. We performed total PTx alone in 15 uremic patients excluded for renal transplantation 10 patients with undetectable iPTH serum concentration and were followed up for 37 to 144 months. There was no evidence of clinical bone disease (bone pain or fractures). Bone mineral lumbar spine and hip density was measured at the end of follow-up. The z score data showed that all patients had a bone mass similar than that expected for their age. Bone biopsies performed in four patients showed a uniform picture of low turnover without aluminium staining. Calcification of small arteries (digital and arcade vessels in hands and feet) were evaluated pre and post total PTx alone in nine out of the 10 patients with undetectable PTH levels. The small vessel calcification was present in five patients at the moment of PTx. At the end of the long term follow-up only one patient showed progression. In conclusion, total PTx without autotransplantation is a very effective and adequate treatment for refractory severe hyperparathyroidism in patients excluded for renal transplantation. Aluminium related osteopathy post PTx is a risk to be controlled with aluminium "free" dialysis water and avoiding aluminium containing phosphate binders.

For Korean dialysis patients, chronic kidney disease-mineral bone disorder is a serious burden because of cardiovascular calcification and mortality. However, recent epidemiologic data have demonstrated that many patients undergoing maintenance hemodialysis are out of the target ranges of serum calcium, phosphorus, and intact parathyroid hormone. Thus, we felt the necessity for the development of practical recommendations to treat abnormal serum phosphorus, calcium, and iPTH in dialysis patients. In this paper, we briefly comment on the measurement of serum calcium, phosphorus, iPTH, dialysate calcium concentration, dietary phosphorus restriction, use of phosphate binders, and medical and surgical options to correct secondary hyperparathyroidism. In particular, for the optimal management of secondary hyperparathyroidism, we suggest a simplified medication adjustment according to certain ranges of serum phosphorus and calcium. Large-scale, well-designed clinical studies are required to support our strategies to control chronic kidney disease-mineral bone disorder in this country. Based on such data, our practice guidelines could be established and better long-term outcomes should be anticipated in our dialysis patients.

Primed antidonor alloreactive T cells are detrimental to transplant outcome, but factors that impact the strength of this immune response prior to transplantation are unknown. We tested peripheral blood mononuclear cells from dialysis patients, against panels of allogeneic, primary B-cell lines in a newly standardized IFNγ ELISPOT panel of reactive T cell (PRT) assay. Results were correlated with known alloantibody-sensitizing events and other clinical parameters. As 25-OH-vitamin D deficiency is associated with enhanced cellular immunity, is common in dialysis patients and is correctable, we assessed the relationship between serum 25-OH-vitamin D and the PRT. Using independent test and validation cohorts we found that low serum levels of 25-OH-vitamin D (<26 ng/mL) correlated with high-PRT values (in the upper 50th percentile, OR 0.02, p = 0.01) independent of age, sex, race, previous transplant, transfusion, pregnancy, time on dialysis, panel of reactive antibody, iPTH, and treatment with 1,25-OH-vitamin D. The data provide a potential mechanism for the possible relationship between vitamin D deficiency and poor posttransplant outcome, and support studies to test the impact of 25-OH-vitamin D repletion on alloimmunity and allograft injury in kidney transplant candidates.

BACKGROUND

Renal osteodystrophy is very common in hemodialysis (HD) patients. HD is a chronic inflammatory state. Studies in other pathological entities have shown an impact of chronic inflammation on bone metabolism. In the present study, the impact of chronic inflammation on bone turnover in HD patients was evaluated.

METHODS

Thirty-three anuric HD patients free of other pathological conditions or medications that affect immune system or bone metabolism and 30 healthy volunteers enrolled into the study. Intact parathyroid hormone (iPTH), the markers of inflammation IL-6 and CRP, as well as the markers of bone turnover osteocalcin (OCN) and beta-isomerized C-terminal cross-linked peptide of collagen type I (beta-CTx) were measured in the serum.

RESULTS

All evaluated factors were increased in HD patients. In the HD group, the serum marker of osteoblastic activity OCN was related inversely to patients' age (r = -0.469, p = 0.006), CRP (rho = -0.460, p = 0.007), and IL-6 (r = -0.485, p = 0.004) but positively to iPTH (r = 0.707, p < 0.001). Similarly, the serum marker of osteoclastic activity beta-CTx was related inversely to patients' age (r = -0.383, p = -0.028), CRP (rho = -0.466, p = 0.006), and IL-6 (r = -0.460, p = 0.007) but positively to iPTH (r = 0.657, p < 0.001). Multiple linear regression analysis revealed that IL-6 affects bone turnover independently of PTH and to the opposite direction.

CONCLUSIONS

Chronic inflammation has a negative impact on bone turnover in HD patients. Certainly, further research and large clinical trials are needed for definite conclusions and for clarifying the exact molecular mechanisms implicated in the interaction between the immune system and bone metabolism in HD patients.

BACKGROUND

Iron deficiency is the most common cause of suboptimal response to recombinant human erythropoietin (rHuEPO) in chronic hemodialysis (HD) patients. Iron supply can correct this situation, however, optimal dosage, route of administration, and monitoring of iron status during rHuEPO therapy in maintenance HD patients remains controversial.

METHODS

We conducted a 12-month intravenous iron substitution trial in 149 iron-replete chronic HD patients receiving subcutaneous rHuEPO therapy. The available iron pool was maintained with 100 mg iron every 2 weeks or 1 month depending on serum ferritin and transferrin saturation levels, the rHuEPO dosage titrated depending on hematocrit (Hct) levels.

RESULTS

After 12-month protocol, the Hct increased (28.7 +/- 4.1 vs 27.7 +/- 2.6, p = 0.003), rHuEPO requirement reduced 25% (46.1 +/- 28.9 vs 61.5 +/- 67.8 U/kg/week, p = 0.006), serum ferritin increased (1,383 +/- 727 vs 930 +/- 857 ng/ml, p < 0.001), so did the transferrin saturation (36.1 +/- 12.7 vs 27.5 +/- 12.8%, p < 0.001). The serum albumin decreased slightly but reached statistical significance (4.1 +/- 0.48 vs 4.2 +/- 0.36 g/dl, p = 0.006), so did the cholesterol levels (166 +/- 41 vs 173 +/- 38 mg/dl, p = 0.044) and pre-dialysis creatinine (11.3 +/- 2.3 vs 11.5 +/- 2.4 mg/dl, p = 0.015). Besides, the iPTH levels did not interfere with the rHuEPO dosage reduction and Hct increment in our patients.

CONCLUSIONS

We conclude that maintaining high levels of serum ferritin and transferrin saturation could further reduce the requirement of rHuEPO in chronic HD patients, but the long-term effect of iron overloading to patients' nutritional status must be further evaluated in contrast to the economic saving.

OBJECTIVE

Changes in serum magnesium (Mg) may affect some clinical features of patients on maintenance hemodialysis (HD). The aims of our study were to evaluate the correlation between serum Mg concentration and clinical characteristics in Chinese HD patients, and to determine whether it has any relevance for cardiovascular outcomes.

METHODS

98 chronic HD patients were recruited, and clinical features related to cardiovascular disease (CVD) were measured: the correlation between Mg and these characteristics was analyzed.

RESULTS

In patients who were hypomagnesemic, serum Mg, creatinine (Scr), albumin (Alb), pre-albumin (pre-Alb) levels, protein catabolic rate per normalized body weight (nPCR), dietary protein intake (DPI), triceps skin fold (TSF) thickness, mid-arm circumference (MAC), mean mid-arm circumference (MAMC), subjective global assessment (SGA) scores and Kt/V were lower than in hypermagnesemic patients. On the other hand, the incidence of intradialytic hypotension (IDH), levels of serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), C reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c) levels, carotid artery plaque (CAP), and carotid intima-media thickness (CIMT) (all p<0.05, respectively) were higher in patients with low serum magnesium. Correlation analysis showed Mg to be not only positively associated with the nutritional status index, but also negatively correlated with other characteristics, such as IDH incidence, Kt/V, Ca, P, iPTH, CRP, HDL-c, CAP, CIMT (p<0.05, respectively). There was no significant correlation between Mg and low-density lipoprotein cholesterol (LDL-c), lipoprotein-a (LP-a), cholesterol (TC), serum triglycerides (TG), or subjective global assessment (SGA) scores (p>0.05, respectively). Multiple linear regression analysis showed that Mg was negatively associated with CIMT, a direct predictor of CVD (β coefficient=-0.260, p=0.009).

CONCLUSIONS

It is suggested that lower serum Mg reflects poorer nutritional status and that it is also associated with other risk factors for cardiovascular disease in hemodialysis patients, such as greater incidence of IDH, poorer HD adequacy, deteriorating calcium-phosphate metabolism, inflammation and CIMT.

OBJECTIVE

Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO(4)) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO(4) product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.

METHODS

This was a single centre randomized open label study. Patients with serum intact iPTH of 50 pmol/L or more were randomized to receive either i.v. calcitriol (0.01 ug/kg) or i.v. paricalcitol (0.04 ug/kg) during every haemodialysis treatment. Serum iPTH, calcium, phosphorus and alkaline phosphatase were measured at the beginning of the study and every 3 weeks for 12 weeks.

RESULTS

Twenty-five patients were enrolled into the study - 12 were randomized into the calcitriol group and 13 into the paricalcitol group. There were no differences in the baseline study parameters between both groups. Serum iPTH levels were significantly reduced (P = 0.003) only in the paricalcitol group but not in the calcitriol group (P = 0.101). On the other hand, serum calcium levels were significantly increased only in the calcitriol group (P = 0.004 vs P = 0.242). Serum phosphorus, alkaline phosphatase and Ca X PO(4) product were not different.

CONCLUSIONS

Intravenous paricalcitol may be superior to i.v. calcitriol for the treatment of severe SHPT in our chronic haemodialysis population. A larger randomized controlled trial is indicated to confirm these initial findings.

BACKGROUND

Patients on continuous ambulatory peritoneal dialysis (CAPD) have increased risk of low-turnover bone disease and relative hypoparathyroidism. Recently, it has been believed that magnesium plays an important role in regulating secretion of parathyroid hormone (PTH). The aim of this study was to evaluate the relationship between serum PTH and serum magnesium as a factor increasing the frequency of relative hypoparathyroidism.

METHODS

We analyzed the data of 56 patients who had been on CAPD for more than 6 months without any significant problems. No patient had been previously treated with vitamin D or aluminum hydroxide. The patients had used peritoneal dialysate with the magnesium concentration of 0.5 mEq/L. Biochemical parameters, such as BUN, creatinine, alkaline phosphatase bony isoenzyme, total protein, albumin, total calcium, ionized calcium and intact parathyroid hormone level were measured.

RESULTS

The mean serum magnesium level was 1.99 +/- 0.36 mEq/L. Among total 56 patients, 15 patients (26.8%) showed hypermagnesemia (serum magnesium>> 2.2 mEq/L) and 5 patients (8.9%) showed hypomagnesemia (serum magnesium < 1.6 mEq/L). Among all 56 patients, serum iPTH (intact PTH) level was not correlated with serum magnesium level. However, it was inversely correlated with serum total calcium and ionized calcium levels, respectively (r = -0.365, p = 0.006; r = -0.515 p < 0.001). Among 49 patients whose serum iPTH level was less than 300 pg/mL, serum iPTH level was inversely correlated with serum magnesium level (r = -0.295, p = 0.039) and inversely correlated with serum total calcium and ionized calcium levels, respectively (r = -0.546, p < 0.001; r = -0.572 p < 0.001). Among 49 patients whose serum iPTH level was less than 300 pg/mL, lower iPTH group (serum iPTH < 120 pg/mL) showed higher serum magnesium level (p = 0.037), higher serum total calcium level (p < 0.001) and lower bone isoenzyme of alkaline phosphatase level (p < 0.001) than those of higher iPTH group (120 pg/mL < or = serum iPTH < 300 pg/mL).

CONCLUSIONS

Among the CAPD patients whose serum iPTH level was less than 300 pg/mL, there was a significant inverse correlation between serum iPTH level and serum magnesium level. This study indicates that not only serum calcium level but also serum magnesium level are important in the regulation of serum iPTH levels of CAPD patients who have been dialyzed by low-magnesium peritoneal dialysate.

Serum bone Gla-protein (S-BGP) and other serum biochemical parameters, including alkaline phosphatase (S-AP) and immunoreactive PTH (S-iPTH), were measured in 42 patients undergoing chronic hemodialysis. Each patient also had a tetracycline-labeled transiliac bone biopsy, allowing correlations between the biochemical and trabecular bone histomorphometric parameters, S-BGP was markedly increased [64.0 +/- 74.8 (+/- SD) vs. 6.2 +/- 2.2 ng/ml in normal subjects] significantly correlated with S-AP (r = 0.53) and S-iPTH (r = 0.55) levels. S-BGP was significantly higher in the 14 patients with high turnover renal osteodystrophy (HT-ROD; S-BGP, 138.5 +/- 90.8 ng/ml) than in the 28 patients with low turnover (LT-ROD; S-BGP, 26.8 +/- 14.8 ng/ml). S-BGP was significantly correlated with the cellular parameters of bone resorption and formation (r = 0.57-0.69) and with the dynamic parameters of bone formation (r = 0.62-0.82). The extent of stainable bone aluminum was significantly negatively correlated with S-BGP (r = -0.51) and serum iPTH (r = -0.33), but not with S-AP. S-BGP measurement allowed better discrimination between LT-ROD and HT-ROD groups than did S-AP measurement. However, in the patients with LT-ROD, S-BGP did not discriminate between patients with or without osteomalacia. We conclude that S-BGP is a valuable marker for evaluating bone remodeling and, more specifically, the bone formation rate at the tissue level in hemodialyzed patients.

Type I collagen represents more than 90% of bone matrix. Quantitative analysis of collagen cross-link molecules such as pyridinoline (PYD) provides valuable information on bone resorption rate. We have studied 37 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Eighteen of them had tetracycline double labeling, allowing to determine dynamic, in addition to static bone parameters. Measurement of serum-free PYD was performed using a new competitive enzyme immunoassay. Serum PYD values were compared with those of three other serum markers of bone metabolism, namely intact PTH (iPTH), bone-specific alkaline phosphatase (bAP), and osteocalcin, for the correlations with bone histomorphometric parameters. Serum PYD levels (mean +/- SD) were significantly higher in dialysis patients than in normal individuals, 90.6 +/- 99.6 nM versus 1.9 +/- 0.4 nM, respectively. Patients with high turnover bone disease had significantly higher serum PYD levels than patients with normal or low bone turnover, 108.8 +/- 108.0 nM versus 34.1 +/- 12.8 nM, respectively. Serum PYD levels were positively correlated with bone resorption parameters including osteoclast surface (r = 0.59, p < 0.0001) and osteoclast number/mm2 (r = 0.61, p < 0.0001), and also with bone formation parameters, osteoblast surface (r = 0.43, p < 0.008), double-labeled surface (r = 0.81, p < 0.001), and BFR (r = 0.91, p < 0.0001). The BFR was better correlated with serum PYD levels than with either serum iPTH or osteocalcin concentrations. However, correlation with serum bAP was comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

The case records of 327 patients who underwent bone biopsy in late or terminal renal failure, before any form of dialysis or transplantation, were examined for clues to the aetiology of renal osteomalacia and its manifestations. Fifty four per cent of the biopsies showed pure osteitis fibrosa, 34 per cent osteomalacia with osteitis fibrosa and 12 per cent showed neither abnormality. Osteomalacia was strongly associated with chronic pyelonephritis and obstructive uropathy as primary renal disease. In two matched groups of 100 each, and within the major primary diseases, it was associated with acidosis, hypocalcaemia and normophosphataemia (as opposed to hyperphosphataemia). There was no association with known length or uraemia and only a weak and inconsistent relationship with severity of uraemia. In the few patients studied, there was no relationship between osteomalacia and serum 25-hydroxycholecalciferol level. In contrast to the state of patients treated by haemodialysis, osteomalacia in this undialysed group was manifested by a higher level of serum alkaline phosphatase than pure osteitis fibrosa, serum iPTH did not differ between the groups, there was no predominance of symptoms in one group, other than proximal myopathy which had a weak association with osteomalacia, and Looser zones were more common than complete fractures. Our study shows that osteomalacia has different manifestations, and probably different causes, before and after the start of haemodialysis. These two stages of renal failure should be clearly distinguished in reports of renal bone disease.

The presence of Helicobacter pylori (HP) infection may adversely influence outcome in renal transplant candidates because of its strong association with gastrointestinal disorders. We examined the association between HP infection and nutritional parameters in symptom-free hemodialysis patients and assessed prospectively the nutritional changes in patients who received therapy for the disease. The 163 study patients, including 114 men and 69 women of mean age 41.5 +/- 12.9 years on dialysis for 67.2 +/- 47.6 months, were selected from among the group who underwent routine endoscopic evaluation according to our renal transplant protocol. Patients with active peptic ulcer, acute gastritis, chronic inflammatory disease, malignancy, or diabetes mellitus were excluded. Endoscopy results revealed normal findings in 60 (group 1), gastritis in 86 (group 2), or gastritis with HP in 17 patients (group 3). Group 3 patients received a 2-week course of triple therapy (omeprazole, amoxicillin, clarithromycin). The patient groups were compared for nutritional metrics (albumin, phosphorus, interdialytic weight gain [IDWG], body mass index [BMI]), inflammatory indices (CRP, fibrinogen), and iPTH levels. Group 3 patients were observed to be malnourished when compared with groups 1 and 2, namely abnormal values of albumin (P <.0001), phosphorus (P <.009), IDWG (P <.03), and BMI (P <.02). Repeat endoscopy revealed a 94% rate of eradication of HP with increased levels of albumin and phosphorus in group 3. Although symptom-free hemodialysis patients with HP-associated gastritis displayed a state of malnutrition; its eradication improved the nutritional status. Therefore, the presence of HP infection should be sought and its eradication mandatory for this patient population.

Fractional intestinal 47Ca calcium absorption (alpha) in 12 epileptic outpatients receiving chronic high-dose anticonvulsant therapy was reduced (p less than 0.05) compared to 12 matched normal controls. Six of the epileptics were treated orally with 0.5 microgram of 1,25-dihydroxycholecalciferol (1,25-DHCC) per day and six with 10 microgram of 25-hydroxycholecalciferol (25-HCC) per day for 10 days. The alpha was determined before and after treatment and compared with the effect of 0.5 microgram of 1,25-DHCC per day given for 10 days to 6 controls. An increase of the same order in alpha was found in all groups (p less than 0.05). No changes were observed in the serum levels of calcium, phosphorus, alkaline phosphatase or iPTH during treatment. Urinary calcium excretion was low in the epileptic patients and rose during treatment. The investigation demonstrates that the sensitivity of the intestine to 1,25-DHCC is normal in epileptic patients on anticonvulsant therapy and that 1,25-DHCC and 25-HCC in the given doses had an equal effect on the reduced intestinal calcium absorption.

OBJECTIVE

To study vitamin D status and bone metabolism of premenopausal vegetarians and omnivores during a 1-year period.

METHODS

Longitudinal, observational study. Bone mineral density was measured, blood samples from fasting subjects were obtained, and 24-hour urinary samples were collected in February 1994, August 1994, and January 1995. Serum 25-hydroxyvitamin D [S-25(OH)D] and intact parathyroid hormone (S-iPTH) concentrations were measured and intestinal calcium absorption was estimated. Dietary intakes of vitamin D and calcium were calculated.

METHODS

Six vegans, 6 lactovegetarians, and 16 omnivores living in Helsinki, Finland.

METHODS

Student-Newman-Keuls test; unbalanced, repeated-measures multiple analysis of variance; analysis of covariance; Pearson correlation test; and linear regression analysis.

RESULTS

Dietary intake of vitamin D was significantly lower in vegans (P < .05, yearly mean +/- standard deviation = 0.09 +/- 0.06 microgram/day) and in lactovegetarians (P < .05, 0.7 +/- 0.4 microgram/day) compared with omnivores (4.0 +/- 2.1 micrograms/day). Throughout the year S-25(OH)D (P = .01) concentrations were lower and S-iPTH (P = .01) concentrations were higher in vegans than in omnivores and lactovegetarians. Bone mineral density in the lumbar region of the spine was lower in vegans (yearly mean +/- standard deviation = 1.034 +/- 0.174 g/cm2) than in omnivores (P = .05, 1.177 +/- 0.099 g/cm2) and tended to be lower than that in lactovegetarians (P = .17, 1.138 +/- 0.06 g/cm2). Bone mineral density in the neck of the femur tended to be lower in vegans (0.843 +/- 0.116 g/cm2) than in omnivores (P = .07, 0.999 +/- 0.138 g/cm2) and lactovegetarians (P = .15, 0.961 +/- 0.059 g/cm2). No seasonal variation was found in bone mineral density in the study groups.

CONCLUSIONS

At northern latitudes, dietary intake of vitamin D in vegans was insufficient to maintain S-25(OH)D and S-iPTH concentrations within normal ranges in the winter, which seems to have negative effects on bone mineral density in the long run.

CONCLUSIONS

An increase in vitamin D intake should generally be recommended for vegans at least during winter, or selections of foodstuffs fortified with vitamin D should be broadened in northern latitudes.

BACKGROUND

We examined the hypothesis that high FGF-23 levels early after transplantation contribute to the onset of hypophosphatemia, independently of parathyroid hormone (PTH) and other factors regulating phosphate metabolism.

METHODS

We measured serum phosphate levels (sPi), renal tubular reabsorption of Pi (TmPi/GFR), estimated GFR (eGFR), intact PTH (iPTH), calcitriol, intact (int) and C-terminal (Cter) FGF-23, dietary Pi intake and cumulative doses of glucocorticoids in 69 patients 12 days (95% confidence interval, 10-13) after renal transplantation.

RESULTS

Hypophosphatemia was observed in 43 (62%) of the patients 12 days after transplantation. Compared with non-hypophosphatemic subjects, their post-transplantation levels of intact and CterFGF-23 were higher (195 (108-288) vs 48 (40-64) ng/l, P<0.002 for intFGF-23; 205 (116-384) vs 81 (55-124) U/ml, P<0.002, for CterFGF-23). In all subjects, Cter and intFGF-23 correlated inversely with sPi (r=-0.35, P<0.003; -0.35, P<0.003, respectively), and TmPi/GFR (r=-0.50, P<0.001; -0.54, P<0.001, respectively). In multivariate models, sPi and TmPi/GFR were independently associated with FGF-23, iPTH and eGFR. Pre-transplant iPTH levels were significantly higher in patients developing hypophosphatemia after renal transplantation. Pre-transplant levels of FGF-23 were not associated with sPi at the time of transplantation.

CONCLUSIONS

In addition to PTH, elevated FGF-23 may contribute to hypophosphatemia during the early post-renal transplant period.