BACKGROUND

In hemodialysis patients, adynamic bone disease has been reported to be closely associated with low levels of parathyroid hormone (PTH) due to exposure to high levels of serum calcium following the administration of calcium carbonate (CaCO3) or vitamin D agents. This study was conducted to clarify the therapeutic effect of a non-calcemic phosphate binder, sevelamer hydrochloride (sevelamer), for hypoparathyroidism in hemodialysis patients with or without diabetes mellitus.

METHODS

Based on entry criteria, 40 Japanese chronic hemodialysis patients (22 males and 18 females with a mean age of 60.6, 14 diabetic patients and 26 non-diabetic patients) were switched from CaCO3 to sevelamer for 48 weeks. Serum calcium, phosphate, intact (i) PTH and PTH-(1-84) were analyzed. Bone remodeling activity was evaluated by determining intact osteocalcine (iOC), bone-specific alkaline phosphatase (BAP).

RESULTS

The switch from CaCO3 to sevelamer significantly decreased the serum levels of calcium, resulting in the elevation of iPTH levels from 31+/-18 pg/mL to 95+/-96 pg/mL by 48 weeks. In contrast, serum phosphate levels remained similar to those in patients with CaCO3 treatment. Concomitantly, the levels of BAP and iOC were elevated. Further, these beneficial effects on bone turnover were observed in both diabetic and non-diabetic patients.

CONCLUSIONS

Sevelamer reduced the calcium concentration and thereby increased PTH levels, resulting in the improvement of markers of bone turnover. The administration of sevelamer is of therapeutic benefit for the improvement of bone remodeling activity even in hemodialysis patients with diabetes.

BACKGROUND

Chronic hemodialysis (HD) patients have bad prognosis and cardiovascular diseases (CVD) represent their main threatening complication. Fibroblast growth factor (FGF-23) has been associated with all kinds of evil consequences, including cardiovascular morbidity, but some studies demonstrated the contrary. Therefore, it is important to know whether FGF-23 is associated with cardiovascular risk or protection. The purpose of this study was to assess the links between FGF-23 and intimal vascular calcification (VC) and with the presence of CVD in chronic HD patients.

METHODS

This study was carried out on a cohort of randomly selected 88 prevalent HD patients. We recorded demographical, clinical, and biochemical data, including FGF-23. VC was evaluated on carotid ultrasound. CVD were registered.

RESULTS

The mean age was 59.68 ± 14.49 years, HD vintage was 59.61 ± 52.39 months, and 20 patients were diabetic (22.72 %). VC was present in 54 patients (61.4 %) and 25 patients (28.4 %) had CVD. FGF-23 correlated positively with HD vintage (r = 0.37; p < 0.001) and iPTH (r = 0.21; p = 0.048). FGF-23 did not correlate with VC score. Patients with CVD were older (p = 0.006), had lower FGF-23 (p = 0.008), higher VC score (p = 0.009), lower Hb (p = 0.008), albumin (p = 0.003), and creatinine (p = 0.03). Low FGF-23 was identified as a risk factor for CVD.

CONCLUSIONS

We report on a novel association between low FGF23 and CVD in chronic HD patients and a lack of correlation of FGF-23 with VC. FGF-23 could play a role in cardiovascular protection that remains to be confirmed in larger studies.

Hypocalcemia is characteristically observed in magnesium deficiency in a number of animal species. Previous studies demonstrated impaired release of PTH in magnesium-depleted hypocalcemic humans. However, an enigma remains in that, unlike in other animals, hypercalcemia, rather than hypocalcemia, accompanies magnesium deficiency in the rat. Because intact parathyroids are necessary for the development of this hypercalcemia, it has been postulated that magnesium depletion stimulates, rather than impairs, PTH secretion in the rat. In an effort to more directly evaluate this thesis, sequential measurements of circulating immunoreactive PTH (iPTH) were made over a 30-day period in rats maintained on a magnesium-deficient diet and in match-fed controls. In the control rats, serum calcium, magnesium, and iPTH remained relatively constant throughout the study. By contrast, during the first 4 days of a low magnesium diet, serum magnesium decreased to 1.0 mg/dl, serum calcium increased moderately, while serum iPTH increased to a mean level that was twice that in controls. After 5 days, when serum magnesium progressively fell to levels less than 0.6 mg/dl and serum calcium continued to rise, serum iPTH fell to levels significantly lower than the control value. In a second set of experiments, the effect of hypocalcemia on circulating iPTH in magnesium deficiency was evaluated. Circulating iPTH was greatly increased and not significantly different in magnesium-deficient and magnesium-replete animals who were rendered chronically hypocalcemic by diets deficient in either calcium or vitamin D. The results of this study indicate that: 1) in the rat, an increase in PTH secretion occurs early in the genesis of magnesium deficiency in the presence of a modest increase in serum calcium; however, the subsequent further increase in serum calcium counteracts the stimulatory effect of hypomagnesemia on PTH secretion; 2) unlike the human parathyroid gland, the rat parathyroid gland responds appropriately to both hypo- and hypercalcemia in magnesium deficiency; and 3) the hypercalcemia that occurs in the magnesium-deficient rat is not due to increased PTH secretion and must be accounted for by another mechanism.

Serum 25-hydroxycholecalciferol (25-HCC) and serum parathyroid hormone (iPTH) were measured in 59 randomly selected adult epileptic outpatients receiving chronic anticonvulsant therapy. Quantitative morphometric analysis of iliac crest biopsies was performed. A mild degree of osteomalacia was found which was inversely correlated to dietary vitamin D intake. Serum 25-HCC was reduced in the epileptic patients compared to a control group, although dietary intake of vitamin D was higher than the mean daily intake in the Danish population. Serum 25-HCC was positively correlated to dietary vitamin D intake, but not correlated to the severity of bone changes, indicating that other factors than circulating 25-HCC are responsible for the development of anticonvulsant osteomalacia. Serum 25-HCG was inversely correlated to serum iPTH in patients with a low dietary calcium intake. The mean value of serum iPTH was not increased, and there was no correlation between serum iPTH and bone morphometry.

BACKGROUND

There is substantial evidence that low levels of serum intact parathyroid hormone (iPTH) are associated with vascular calcium deposition and subsequent increased cardiovascular risk in chronic kidney disease patients. The purpose of this study was to determine the relationship between the serum iPTH level, and vascular and coronary artery calcifications (VCs, CACs) and arterial stiffness in peritoneal dialysis (PD) patients.

METHODS

In this cross-sectional study, 93 PD patients were included. VCs, CACs and arterial stiffness were measured by simple X-rays of the hands and pelvis, multi-slice coronary CT and brachial-ankle pulse wave velocity (BaPWV).

RESULTS

Patients were divided into 3 groups according to iPTH levels. The prevalence of severe VCs (VC score ≥ 3) was highest in the low iPTH group (<150 pg/ml). In multivariate analysis, the presence of diabetes mellitus and a low iPTH were shown to be significant risk factors for severe VCs. In addition, a simple VC score of ≥ 1 was a significant variable for predicting severe CACs (CAC score ≥ 400).

CONCLUSIONS

Low iPTH and the presence of diabetes mellitus are thought to be independent risk factors for predicting VCs. VCs determined by simple X-ray can further predict the coexistence of CACs that ultimately might contribute to increased cardiovascular risk in PD patients.

OBJECTIVE

The objective of this study was to assess the response to recombinant human erythropoietin (rHuEPO) during treatment of anemia in dialysis patients with hyperparathyroidism.

METHODS

A total of 118 patients with stage 5 renal failure on dialysis therapy were selected for this study. Anemia was treated with rHuEPO. Laboratory data for each patient included intact parathyroid hormone (iPTH), hemoglobin (Hb), hematocrit (Hct), blood urea nitrogen, serum creatinine, calcium, phosphate, and alkaline phosphatase. Patients with iPTH >32 pmol/l were considered hyperparathyroid. Erythropoietin resistance index (ERI) was expressed as the ratio of weekly rHuEPO dose/Hct level.

RESULTS

Of the 118 patients, 83 (70.3%) were on hemodialysis (HD) and 35 (29.7%) were on continuous ambulatory peritoneal dialysis (CAPD). Sixty-three patients (64.3%) with iPTH >32 pmol/l had Hb <11 g/dl, while 34 (54.8%) with iPTH <32 had Hb >11 g/dl (p = 04). Thirty-three (56%) patients with iPTH >32 pmol/l had hemocrit <33%, while 38 (61.3%) with iPTH <32 had hemocrit <33% (p = 0.4). The median value of weekly rHuEPO dose in HD patients (12,000 units) was significantly higher in comparison with CAPD patients (6,000 units; p < 0.0001). ERI was significantly higher in HD than CAPD patients with iPTH <16 pmol/l (p = 0002) as well as with patients with 16-32 pmol/l (p = 0.012).

CONCLUSIONS

CAPD patients showed a reduced requirement for rHuEPO and better control of anemia compared with HD patients. ERI was also lower in CAPD than in HD patients. Hyperparathyroidism is a parameter predictive of rHuEPO hyporesponsiveness in dialysis patients.

BACKGROUND

Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease. Our primary objective was to evaluate the efficacy of oral paricalcitol versus oral calcitriol on serum intact parathyroid hormone (iPTH) and mineral bone parameters in continuous ambulatory peritoneal dialysis (CAPD) patients with SHPT. The secondary objective was to analyze highly sensitive C-reactive protein (hsCRP) and peritoneal membrane function in both groups.

METHODS

This was a prospective randomized control trial. CAPD patients with SHPT were randomized to paricalcitol or calcitriol for 15 weeks. Serum intact iPTH, calcium, phosphate and alkaline phosphatase (ALP) were measured at baseline and every 3 weeks. Serum hsCRP and peritoneal membrane functions were measured at baseline and at week 15.

RESULTS

A total of 26 patients were enrolled and randomized-12 to paricalcitol and 14 to calcitriol. Serum iPTH reduced significantly in both groups and there was no difference in the incidence of ≥50 % reduction of iPTH between both groups. There was a significant increase in serum calcium in both groups but there were no differences in serum phosphorus across the visits. The incidence of hypercalcemia was the same in both groups. Serum calcium-phosphorus (Ca × P) product increased in the paricalcitol group but decreased in the calcitriol group. Serum ALP decreased significantly in both groups. There were also no differences in pre- and post-treatment serum hsCRP and peritoneal function test (PFT) in both groups.

CONCLUSIONS

Both oral paricalcitol and calcitriol were equally efficacious in reducing serum iPTH but were associated with significantly higher serum calcium. Serum Ca × P product increased in the paricalcitol group and decreased in the calcitriol group. Serum hsCRP level and PFT were not affected by either treatment. A larger randomized controlled trial is indicated to confirm these initial findings.

BACKGROUND

Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX.

METHODS

We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years, mean body mass index of 23.6±3.73, and mean dialysis duration of 25.73±17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX.

RESULTS

At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 (P<.01), while it decreased in the control group from 0.897±0.17 to 0.817±0.16 (P<.001). There was also a significant increase in radius BMD (P<.001) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD (P<.001) in the control group at 6 months. Upon multivariate analysis, there was a significant correlation between alendronate and spine BMD (r=.45, P<.001) but no linear regression between age, sex, BMI, dialysis duration of or iPTH with femoral, spine, or radius BMD changes at month 6.

CONCLUSIONS

Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX.

BACKGROUND

Relapses of secondary hyperparathyroidism (SHPTH) after parathyroidectomy (PTx) in haemodialysis patients are relatively frequent. Calcimimetics (cinacalcet HCl) offer a new therapeutic opportunity for their treatment. However, no data about the treatment with cinacalcet of relapses of SHPTH after PTx are available in literature. The aim of this single-centre prospective study was to evaluate the therapeutic efficacy of cinacalcet in this high-risk category of patients.

METHODS

Twelve haemodialysis patients of our Dialysis Unit had a relapse of SHPTH after PTx, defined as serum levels of immunoreactive intact parathyroid hormone (iPTH)>300 pg/ml. They were stratified into a treatment group (the six patients having the highest serum levels of iPTH) and a control group (the remaining six patients): the former were treated for 6 months with a dose of cinacalcet ranging from 30 mg every other day to 60 mg a day; the latter continued to be administered the conventional treatment. Serum levels of albumin, iPTH, calcium (Ca), phosphate (P) and alkaline phosphatase were determined monthly. The treatment group included four cases of nodular hyperplasia and two cases of carcinoma of parathyroid glands, whereas the control group included four cases of nodular hyperplasia and two cases of diffuse hyperplasia.

RESULTS

At the start of the study, the six patients treated with cinacalcet showed a more severe picture of biochemical abnormalities when compared with the control patients. After 6 months of treatment, a statistically significant reduction in the serum levels of iPTH, Ca, P and CaxP product was obtained only in the patients treated with cinacalcet. Symptomatic episodes of hypocalcaemia (serum Ca<7.0 mg/dl) were observed in three patients of this group. The six patients undergoing the conventional treatment showed at 6 months a not significant decrease in the mean serum levels of iPTH and a not significant increase in the mean serum levels of Ca, P and CaxP product, when compared with the baseline values.

CONCLUSIONS

Our single-centre prospective study, even though small and of short duration, shows that cinacalcet is effective also in controlling relapses of SHPTH after PTx, thus representing a solid, and sometimes unique, therapeutic opportunity for this high-risk category of patients.

OBJECTIVE

The purpose of our study was to determine the frequency and imaging features of atypical femoral fractures in a consecutive asymptomatic patient population on long-term bisphosphonate treatment and search for distinguishing clinical and laboratory parameters in the subset of patients with fractures.

METHODS

Two hundred femoral radiographs in 100 asymptomatic patients (93 women and seven men; age range, 47-94 years; mean age, 69.3 years) were prospectively reviewed by two radiologists. All patients had received bisphosphonate treatment for at least 3 years and had no history of pain or recent trauma. MRI studies were performed when a fracture was suspected on radiographs. Bone mineral density, serum calcium, albumin, 25-hydroxy vitamin D, intact parathyroid hormone (iPTH), serum C-telopeptide, and urine N-telopeptide values were obtained.

RESULTS

Two of 100 patients (2%) had three insufficiency fractures. Both patients, 50 and 57 years old, were white, active, and had been receiving bisphosphonate therapy for 8 years. The patient with bilateral atypical femoral fractures showed typical features of bisphosphonate-related incomplete atypical femoral fractures. MRI confirmed the radiographic findings in both patients. The two patients with incomplete atypical femoral fractures were significantly younger than those without atypical femoral fractures. There were no significant differences among the fracture and nonfracture groups in terms of clinical or laboratory results, except for mean iPTH, which was significantly decreased in the fracture group.

CONCLUSIONS

The 2% frequency of incomplete atypical femoral fractures in asymptomatic patients on long-term bisphosphonate therapy is higher than suggested in the literature. Aside from age and mean iPTH, there were no significant differences in clinical or laboratory data between the two groups.

BACKGROUND

To date, few studies have used ambulatory pressure monitoring (ABPM) in patients with chronic kidney disease (CKD) before the start of dialysis treatment. The aim of this study was therefore to ascertain the correlates of arterial hypertension assessed by ABPM in CKD patients at their first referral to a nephrologist.

METHODS

We studied 244 (164 men; mean age 63 years) nondiabetic patients with CKD. Each patient had blood pres-sure (BP) measured by 24-hour ABPM, creatinine clearance (CrCl) estimated according to the Cockcroft-Gault formula, and Hgb concentration, serum lipids, iPTH, daily urinary protein (Uprot) and sodium (UNa) excretion assessed using routine methods.

RESULTS

According to ABPM data analysis, 81 patients were normotensives, 78 were stable hypertensives, 26 had day-time hypertension and 59 had nocturnal hypertension. ANOVA showed both lower CrCl (p=0.0033), and higher Uprot (p<0.0001) in stable and nighttime hypertensives as compared with normotensives and daytime hypertensives. In the whole group each set of both systolic (SBP) and pulse pressure (PP) readings was directly associated with both age and Uprot (p<0.05), and inversely with both CrCl and Hgb (p<0.05). In multivariate analysis, however, Uprot emerged among modifiable risk factors, as the most significant predictor of both SBP and PP; the strength of this association was in the order nighttime PP>> nighttime SBP>> 24-hour PP>> daytime PP>> daytime SBP>> 24-hour SBP.

CONCLUSIONS

In CKD patients, proteinuria is the strongest correlate of arterial hypertension and particularly of increased nocturnal PP, possibly as an expression of vascular damage. On the basis of these results, ABPM appears to be the most reliable tool for detecting the associations between raised BP (particularly nighttime hypertension) and renal damage in CKD patients not yet on renal replacement therapy (RRT).

BACKGROUND

Paricalcitol and doxercalciferol are effective in reducing parathyroid hormone PTH concentrations in patients with secondary hyperparathyroidism. The purpose of this study was to determine the relative dose of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH concentrations in dialysis patients.

METHODS

Chronic hemodialysis patients treated with a stable dose of paricalcitol for at least 3 months were randomized to receive doxercalciferol at either 35, 50, or 65% of the paricalcitol dose for 6 weeks. Serum iPTH, calcium, phosphorus, and albumin were determined at baseline and monitored every 2 weeks. A linear regression analysis of percent change in iPTH values by dose group was performed to determine the conversion factor.

RESULTS

27 patients were enrolled. Initial iPTH, adjusted serum calcium, serum phosphorus, and CaxP were similar among the treatment groups. Linear regression analysis demonstrated a conversion factor of 0.57 for the dose of doxercalciferol relative to paricalcitol resulting in equivalent suppression of iPTH. Corrected serum calcium, phosphorus, CaxP product, as well as incidence of hypercalcemia, hyperphosphatemia and CaxP >50 were similar for all groups.

CONCLUSIONS

In patients on a maintenance dose of paricalcitol, dosing doxercalciferol at 55-60% of the paricalcitol dose results in comparable inhibition of PTH.

BACKGROUND

Information on renal bone disease (RBD) is sparse in Nigeria. The prevalence of RBD in a dialysis population worldwide ranges between 33% and 67% and it increases with progression of renal insufficiency.

OBJECTIVE

To determine the prevalence and magnitude of RBD in patients with end stage renal disease (ESRD).

METHODS

Thirty consecutive ESRD patients were recruited. They had thorough clinical evaluation and investigations which included serum calcium, phosphate, alkaline phosphatase, albumin and skeletal survey. The serum iPTH, osteocalcin, and 1,25 (OH2) D3 were assessed in 20 patients.

RESULTS

The patients were aged 18-72 years with a mean of 38.93+/-15.7 years. There was a male:female ratio of 4:1. Uraemic symptoms were the major presenting complaints. None of the patients complained of bone pain or fracture. The mean values for serum creatinine, urea, creatinine clearance, calcium, phosphate, albumin, alkaline phosphatase, iPTH, osteocalcin and 1,25 (OH)2 Vit D3 were 1478.96 +/- 771.12 micromol/L, 22.33 +/- 7.42 mmol/L, 3.38 +/-2.22 mls/min, 1.8 +/- 0.5 mmol/L, 1.61 +/- 0.65 mmol/L, 30.2 +/- 6.1 g/L, 124.33 +/- 63.37 IU/L, 22.66 +/- 24.72, 45.14 +/- 43.8, 37.7 +/- 22.3 respectively. There were hypocalcaemia and hyper-phosphataemia in 80% and 60% of the patients respectively. Alkaline phosphatase was elevated in 44% of the patients while 11.8% had hyperparathyroidism. Level of 1,25 (OH)2 Vit D3 was low in 83.3% of the patients. There was a significant negative correlation between serum calcium and iPTH levels (r = -0.915, p=0.029). There was also significant negative correlation between alkaline phosphatase and 1,25 (OH)2 Vit D3 and serum albumin. Radiological evidence of RBD occurred in only 16.7% of the patients.

CONCLUSIONS

Renal bone disease is common in our patients with ESRD associated most commonly with low bone turnover while occurrence of hyperparathyroid bone disease appears low.

BACKGROUND

Mortality in dialysis patients is higher than in the general population, and cardiovascular disease represents the leading cause of death. Hypertension and volume overload are important risk factors for the development of left ventricular hypertrophy (LVH) in hemodialysis (HD) and peritoneal dialysis (PD) patients. Other factors are mainly represented by hyperparathyroidism, vascular calcification, arterial stiffness and inflammation. The aim of this study was to compare blood pressure (BP) and metabolic parameters with cardiovascular changes [cardiothoracic ratio (CTR), aortic arch calcification (AAC) and LV mass index (LVMI)] between PD and HD patients.

METHODS

45 patients (23 HD and 22 PD patients) were enrolled. BP measurements, echocardiography and chest X-ray were performed in each patient to determine the LVMI and to evaluate the CTR and AAC. Inflammatory indexes, intact parathyroid hormone (iPTH) and arterial blood gas analysis were also evaluated.

RESULTS

LVMI was higher in PD than HD patients (139 ŷ 19 vs. 104 ŷ 22; p = 0.04). In PD patients, a significant correlation between iPTH, C-reactive protein and the presence of LVH was observed (r = 0.70, p = 0.04; r = 0.70, p = 0.03, respectively). The CTR was increased in PD patients as compared to HD patients, while no significant differences in cardiac calcifications were determined.

CONCLUSIONS

Our data indicate that HD patients present more effective BP control than PD patients. Adequate fluid and metabolic control are necessary to assess the adequacy of BP, which is strongly correlated with the increase in LVMI and with the increased CTR in dialysis patients. PD is a home therapy and allows a better quality of life, but PD patients may present a further increased cardiovascular risk if not adequately monitored.

BACKGROUND

The aim of our study was to evaluate the relevance of magnesium and FGF-23 in terms of cardiovascular disease in a population of type 2 diabetic patients with nephropathy.

METHODS

In a cross-sectional study, we included 80 type 2 diabetic patients with chronic kidney disease (CKD) stages 2, 3 and 4. We analysed mineral metabolism, inflammation, oxidative stress and insulin resistance. Our population was divided into two groups according to their pulse pressure (PP) as follows: G-1 with PP < 50 mmHg (n = 34) and G-2 with PP ≥ 50 mmHg (n = 46).

RESULTS

We found that G-2 patients showed lower calcium (P = 0.004), eGFR (P = 0.001), magnesium (P = 0.0001), osteocalcin (P = 0.0001) and 25(OH)D3 (P = 0.001), and higher iPTH (P = 0.001), FGF-23 (P = 0.0001), malonaldehyde (P = 0.0001), interleukin 6 (P = 0.001) and HOMA-IR (P = 0.033). No differences were found between the two groups regarding age, duration of disease, haemoglobin, HgA1c and phosphorus. In a multivariate analysis, we found that FGF-23 and magnesium independently influenced the PP [OR = 1.239 (1.001-2.082), P = 0.039 and OR = 0.550 (0.305-0.727), P = 0.016, respectively].

CONCLUSIONS

In our diabetic population with early stages of CKD, FGF-23 as well as lower magnesium levels were significantly and independently associated with higher PP levels, an established marker of cardiovascular morbidity and mortality.

Bone histologic parameters and serum iPTH and 25-OHD were measured in 20 patients with end-stage renal failure treated with hemodialysis. By bone histologic criteria, the patients were divided into three groups: mild, osteomalacic, and fibrotic. The increase in serum iPTH was much greater in the fibrotic group than in the mild or osteomalacic groups. In the uremic patients as a group, there were significant correlations between serum iPTH and both percent marrow fibrosis and percent resorbing surface. In the mild and fibrotic groups together, serum iPTH was also correlated with percent forming surface. This and other findings suggested that most of the bone changes in the mild and fibrotic groups could be explained by excess PTH. The difference in bone changes and in serum iPTH between the mild and fibrotic groups could be related to our eariler findings that duration of renal disease was much greater in the fibrotic than in the mild group. The lowest increment in serum iPTH was found in the osteomalacic group. In this group, percent resorbing surface was not increased and there was only a slight increase in marrow fibrosis. Thus in all three groups, serum iPTH appeared to reflect parathyroid status. The cause of the elevated serum iPTH and for the intergroup differences was not apparent inasmuch as serum calcium was normal in all three groups. Serum 25-OHD was significantly elevated in the osteomalacic and fibrotic groups. Because none of our patients had received preparations containing vitamin D, the elevated serum 25-OHD in the osteomalacic and fibrotic groups is consistent with altered vitamin D metabolism in these two groups. There was a direct relationship between percent osteroid area and serum 25-OHD. However, whether or not altered vitamin D metabolism contributed to the mineralization defect in uremic bone disease could not be established.

BACKGROUND

There is limited knowledge of the effectiveness and safety profile of cinacalcet in pediatric patients with secondary hyperparathyroidism (sHPT) treated with dialysis.

METHODS

This was an open-label, single-dose study conducted on 12 pediatric subjects with chronic kidney disease treated with dialysis. Subjects were stratified by four age cohorts and given a single 15-mg oral dose of cinacalcet. Multiple blood samples were collected up to 72 h post-dose for the assessment of serum calcium (Ca), serum intact parathyroid hormone (iPTH), and plasma cinacalcet concentrations.

RESULTS

Overall, cinacalcet was well tolerated with no serious adverse events. Mean (standard deviation) percentage change in serum Ca over the first 12 h post-dose was -2.93 % (5.70 %) with a nadir of -4.34 % (6.04 %) at 8 h; Ca values returned to baseline by 48 h post-dose. Mean percentage change in iPTH over the first 12 h post-dose was 57.94 % (71.82 %) with a nadir of -35.65 % (55.82 %) at 2 h. There was an inverse relationship between peak serum Ca concentration and body surface area (BSA) (r (2) = 0.41), although no relationship was found between area under the curve and age or BSA.

CONCLUSIONS

These data support future analysis to determine the therapeutic starting dose of cinacalcet for pediatric patients with sHPT on dialysis.

OBJECTIVE

The aim of the study was to determine the prevalence of hyper and hypo-parathyroid state in prevalent dialysis patients. The second part of the study was to look for the prevalence of vascular calcification (abdominal aortic) and factors predicting calcification in these patients.

METHODS

All adult patients, who were more than 1 month on dialysis, were included in the study. A total of 68 patients, of which 75% were on hemodialysis and 25% on peritoneal dialysis, were finally studied. Patients' parathyroid status was defined as per target recommendation of KDOQI--hypoparathyroid with iPTH < or = 150 pg/ml and hyperparathyroid with iPTH>> 300 pg/ml. Vascular calcification was determined by X ray of lateral lumbar spine to look for abdominal aortic calcification (AAC). The AAC was scored as validated. The prevalence of hyper- and hypoparathyroidism in dialysis patients was determined as percentage of total dialysis patients. The prevalence of AAC and factors predicting it was analyzed by 'univariate' and 'multiple logistic regression analyses.

RESULTS

The mean age of patients was 50.04 +/- 14.15 years, 58.82% were males and 42.64% were diabetics. Mean duration of dialysis was 22.36 +/- 19.17 months. Hyperparathyroidism was seen in only 27.94% of all dialysis patients, while hypoparathyroidism was in 45.58%. Abdominal aortic calcification was seen in 79.41% of overall patients and 13.23% had significant calcification (score 7-24). On univariate analysis, age (0.000) and iPTH (0.03) were the only variables predicting AAC and on logistic regression analysis, age was the only independent predictor of abdominal aortic calcification (p = 0.002, OR 1.11, CI 1.038-1.186).

CONCLUSIONS

Hypoparathyroidism is more common (46%) in our dialysis patients as compared to hyperparathyroidism (28%). There is high prevalence of vascular (abdominal aortic) calcification (80%) in our dialysis patients.

Intermittent bolus administration of calcitriol--i.e., 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3--is highly efficacious in dialysis patients. In experimental studies, intermittent administration of calcitriol is superior to continuous administration in suppressing preproparathyroid hormone (PTH) mRNA and circulating PTH concentrations. In a randomized, prospective, open multicenter trial 45 dialysis patients with elevated 1,84-iPTH >> or = 20 pmol/l, normal 1-6 pmol/l) levels were randomly allocated to daily administration of 0.75 microgram calcitriol (continuous) or twice weekly administration (intermittent); the two protocols provided an identical total weekly doses of 5.25 micrograms calcitriol. Patients were dialyzed with a dialysate Ca concentration of 1.75 mmol/l and had oral CaCO3 or Ca acetate. 1,84-iPTH (immunoradiometric assay) and serum Ca and Pi levels were measured weekly. At the beginning of the study, the median 1,84-iPTH value was 37 pmol/l (range 20-115) in the intermittent versus 36 pmol/l (range 21-72) in the continuous calcitriol group. After 2 weeks, the median 1,84-iPTH level was 18.5 pmol/l (range 1.4-106) versus 18 pmol/l (range 1.2-48). After 12 weeks, 11 of 21 of the patients in the intermittent and 18 of 24 patients in the continuous group had reached the treatment goal, i.e., 1,84-iPTH < or = 10 pmol/l without hypercalcemia or hyperphosphatemia. There were seven episodes of hypercalcemia >> 2.7 mmol/l) in the intermittent versus two in the continuous group; the mean peak Ca level was 2.8 mmol/l (range 2.76-3.0) versus 2.9 mmol/l (range 2.74-3.06). There were 21 versus 17 episodes, respectively, of hyperphosphatemia >> 2.2 mmol/l).

BACKGROUND

Haemodialysis patients are ageing and have with a high rate of comorbidities. The impact of this novel clinical setting on intact parathyroid hormone (iPTH) is not well established.

METHODS

For this observational, prospective multicentre cohort study, incident haemodialysis patients were recruited in 40 Italian centres and followed up for a mean period of 18 +/- 6.7 months. Clinical characteristics and biochemistry were recorded at baseline. Comorbid conditions were scored by the Charlson comorbidity index (CCI).

RESULTS

Data of 411 patients (mean age: 66.5 +/- 14.8 years; 17.3% >80 years old) were recorded. The mean CCI was 4.17 +/- 2.8. In patients with CCI >0, an inverse correlation was observed between CCI (excluding age) and iPTH (P = 0.00002). Independently of CCI, patients with iPTH <150 pg/ml had 76% as high as the risk of all-cause mortality. After multivariable adjustment, the combination of the first tertile of iPTH with second and third tertiles of CCI was significantly associated with all-cause mortality (RR = 3.83, P = 0.02; RR = 3.79, P = 0.01, respectively).

CONCLUSIONS

Incident haemodialysis patients suffer from a high rate of clinical complications. In these patients, low iPTH and high CCI are often associated and very likely responsible for an adverse outcome.

This study compared the efficacy of a cinacalcet-based regimen with unrestricted conventional therapy (vitamin D and phosphate binders) for achieving Kidney Disease Outcome Quality Initiative (K/DOQI) targets for dialysis patients. In this multicenter, prospective study, hemodialysis patients with poorly controlled secondary hyperparathyroidism (SHPT) were randomized to receive a cinacalcet-based regimen (n=55) or a conventional therapy (n=27). Doses of cinacalcet, vitamin D sterols, and phosphate binders were adjusted during a 12-week dose-titration phase to achieve intact parathyroid hormone (iPTH) levels ≤ 31.8 pmol/L. The primary end point was the percentage of patients with values in this range during a 24-week efficacy-assessment phase. The clinical response to 36-week cinacalcet treatment was evaluated. A dual energy X-ray absorptiometry was performed before and after 36 weeks of cinacalcet therapy. Fifty-eight percent of the cinacalcet group reached the primary end point, as compared with 19% of the conventional therapy group (P=0.001). A higher percentage of patients receiving the cinacalcet-based regimen versus conventional therapy achieved the targets for calcium, phosphorus and Ca×P. Achievement of targets was greatest in patients with less severe disease (intact PTH range, 31.8 to 53 pmol/L). Cinacalcet therapy increased proximal femur bone mineral density (BMD), but did not affect the lumbar spine. Itching intensity decreased significantly. Cinacalcet based treatment facilitates achievement of the K/DOQI targets for iPTH and bone mineral metabolism compared with conventional therapy in hemodialysis patients. Suppression of iPTH with cinacalcet reverses bone loss in the proximal femur. Cinacalcet alleviated itching.

BACKGROUND

The aim of this study was to investigate the factors influencing serum parathyroid (PTH) levels, including medications for treating chronic kidney disease-mineral and bone metabolism disorder (CKD-MBD) in patients with end-stage renal disease.

METHODS

We enrolled 1,076 patients in nine Japanese facilities who had begun hemodialysis (HD) due to ESRD. We investigated the relationships between intact PTH (iPTH) levels and clinical parameters and medications just prior to beginning HD.

RESULTS

Significant decreases in serum iPTH levels were seen in males, in the presence of diabetes mellitus (DM), and with administration of renin-angiotensin system inhibitors (RASIs). Significant correlations were found between serum calcium and iPTH levels. In the patients administered RASIs, there was a significant decrease in serum iPTH levels with DM, male gender, and administration of active vitamin D sterols (VDs) compared with those not administered RASIs, although serum-corrected calcium levels were not different. Multiple regression analysis found gender, age, presence of DM, and serum calcium and phosphate levels to be significant contributing factors. In addition, administration of angiotensin II receptor blockers (ARBs) may also be a contributing factor to iPTH levels at the beginning HD (p = 0.050).

CONCLUSIONS

In this study, serum iPTH levels were related to administration of ARBs besides gender, age, the presence of DM and serum calcium levels. Our study suggests that the RA system involve serum iPTH levels in uremic patients.

OBJECTIVE

This paper reports longitudinal changes in bone mineral density (BMD), calcium homeostasis and dietary calcium intake in a group of Hong Kong breastfeeding women during the first year postpartum.

METHODS

Nine mothers who breastfed exclusively or almost exclusively for at least 3 months and 14 formula feeding mothers aged 20-40 y were interviewed after delivery, 2 and 6 weeks, 3, 6 and 12 months postpartum. BMD at L2-L4 lumbar spine (LS), trochanter (Tro) and femoral neck (FN), serum intact parathyroid hormone (iPTH), serum bone-specific alkaline phosphatase (b-ALP), urinary deoxypyridinoline (Dpd), serum and urinary calcium (Ca) and phosphorus (P) and dietary intake of macronutrients were assessed.

RESULTS

Compared to the formula feeding group, BMD assessed at LS, Tro and FN decreased significantly in the breastfeeding group over the first 6 months, with rebound to approximate baseline values at 12 months for the latter two sites. Serum iPTH increased in both groups, whereas serum b-ALP was consistently higher in the breastfeeders. Urinary Ca and P excretion decreased early postpartum in both groups, but the breastfeeders had higher excretion at 3 and 6 months. Breastfeeding mothers consumed significantly more Ca than the formula feeding mothers in the early postpartum.

CONCLUSIONS

Increased calcium requirement during early lactation is affected through mobilisation of bone and renal calcium conservation. Bone mineral loss during lactation is temporary. Further studies are warranted to investigate the effects of diet and other hormonal factors on the calcium homeostasis during lactation.

OBJECTIVE

We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1-34) on bone turnover markers in women with postmenopausal osteoporosis.

METHODS

Forty-four Caucasian women (age 65.1 +/- 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 microg once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation.

RESULTS

P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them.

CONCLUSIONS

Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment.