BACKGROUND

Pediatric patients with chronic kidney disease (CKD) are at increased risk of early cardiovascular disease and premature death. Abnormalities in microvascular structure and function may presage end-organ damage including vascular calcification and myocardial ischemia associated with disordered mineral metabolism. Early detection of microvascular rarefaction (reduced density of capillaries) may identify at-risk patients and prompt timely therapeutic interventions. Our objective was to study capillary rarefaction in pediatric hemodialysis (HD) patients and to determine possible associations with mineral metabolism and cardiac risk biomarkers.

METHODS

Capillary density (CD) was measured by nailfold capillaroscopy in 19 pediatric HD patients and 20 healthy controls. Demographic and biochemical markers were collected at entry and 6-month follow-up.

RESULTS

CD was significantly decreased in HD patients compared with controls with a deficit of 24 and 31% at baseline and subsequent follow-up. Maximal CD correlated significantly with intact parathyroid hormone (iPTH) (r = -0.45; P = 0.005), serum calcium (r = -0.38; P = 0.02) and 25(OH) vitamin D levels (r = +0.36; P = 0.03) in HD patients. Capillary functional measures were similar to controls. By multivariate analysis, the primary negative determinants of CD were African American race and hyperparathyroidism; whereas, glomerular disease had a positive influence on capillary rarefaction (R (2) = 64.2% variance; P = 0.001).

CONCLUSIONS

Pediatric HD patients demonstrate a 'structural deficit' in CD but show preserved 'functional integrity'. Capillary rarefaction, an early risk factor of incipient vascular calcification, was strongly associated with biomarkers of altered mineral metabolism. Further studies are warranted to determine the impact of optimizing blood pressure and metabolic control on changes in capillary rarefaction in young CKD patients.

OBJECTIVE

Quantity of oxidative stress (OS) is enhanced in every stage of chronic renal failure (CRF). OS and its effects on echocardiographic indexes in patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) were evaluated.

METHODS

Thirty-nine patients on CAPD, 32 patients on HD, and 30 healthy individuals with similar demographic features were included. Patients with diabetes mellitus and chronic inflammatory diseases were excluded. Blood samples were collected to examine hematological and biochemical parameters and levels of malonyldialdehyde (MDA), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) after a 12-hour fasting period in the middle of dialysis week. OS parameters were compared with ejection fraction (EF), interventricular septum diameter (IVSd), left ventricular posterior wall diameter (LVPWd), and left atrium diameter (LAd) determined in M-mod echocardiographic examination.

RESULTS

No significant difference was observed between MDA and GSH-px levels of patients and control group; however, SOD levels of patients group were significantly lower (p<0.0001). SOD levels of patients on HD were lower than that of patients on CAPD (p=0.039). Negative correlation was detected between MDA and EF (r=-0.380, p=0.001); SOD has negative correlation with systolic blood pressure (r=-0.265, p=0.011), diastolic blood pressure (r=-0.230, p=0.028), phosphorus (r=-0.327, p=0.001), intact parathyroid hormone (iPTH) (r=-0.259, p=0.013), C-reactive protein (CRP) (r=-0.235, p=0.024), fibrinogen (r=-0.342, p=0.001), and total cholesterol (r=-0.249, p=0.017); and positive correlation with hemoglobin (r=0.414, p<0.001) and albumin (r=0.367, p<0.001). MDA was independently related with age (beta=-0.258, p=0.035), male gender (beta=-0.312, p=0.004), and EF (beta=-0.461, p<0.001). No correlation was determined between antioxidants and cardiac indexes.

CONCLUSIONS

SOD levels decreased significantly especially in patients on HD, and it was observed that lower levels of SOD would lead to OS in patients on HD and CAPD when compared to healthy individuals; MDA levels were independently influenced from EF.

OBJECTIVE

this study evaluated the factors associated with bone mineral density (BMD) in chronic peritoneal dialysis (CPD) patients.

METHODS

in this cross-sectional study in 91 stable CPD patients, BMD was measured using dual-energy X-ray absorptiometry. Markers of bone turnover (iPTH, osteocalcin, bone alkaline phosphatase, serum C-telopeptide), 25-hydroxy (OH) vitamin D3 and nutritional markers (prealbumin, nPNA, BMI) were measured by standard techniques.

RESULTS

of the 91 patients, 48 were female and 22 (24%) had Type 2 diabetes. Mean age of the patients was 52.7, and patients had been on PD for about 44 months. For the lumbar spine (LS) and femoral neck (FN), the mean T-scores were -1.19 ± 1.53 and -1.24 ± 1.01, respectively, and the mean Z-scores were -0.78 ± 1.33 and -0.40 ± 0.92, respectively. Using the WHO-based criteria, osteopenia (-2.5 < T-score < -1.0) at the LS and FN was observed in 37 (41%) and 48 (53%) patients, respectively, and osteoporosis (T-score <= -2.5) at the LS and FN was observed in 15 (17%) and 6 (7%) patients, respectively. LS T-score was positively correlated with BMI (r = 0.40, p < 0.001) and albumin (r = 0.29, p = 0.005), and FN T-score was positively correlated with albumin (r = 0.40, p < 0.001), prealbumin (r = 0.38, p < 0.001), age (r = -0.32, p = 0.002) and BMI (r = 0.29, p < 0.006). Markers of bone turnover were not associated with BMD. In multiple linear regression models, independent predictors of FN T-score were age, BMI, albumin and prealbumin (r(2) = 0.259, F = 6.23, p < 0.001), whereas BMI was the only independent predictor of LS T-score (r(2) = 0.24, F = 6.63, p < 0.001).

CONCLUSIONS

nutritional markers, not markers of bone turnover, are correlated predictors of BMD in CPD patients.

Few reports are available regarding the promoting factors that affect Helicobacter pylori (H. pylori) infection in renal transplant (RTx) patients. We report a cross-sectional study that was conducted on a group of stable RTx patients to investigate the relationship of various demographic and biochemical parameters of these patients with serum H. pylori IgG antibody titer as a sign of H. pylori infection. A total of 72 patients who were referred to the clinic for continuing their treatment were enrolled in this study. These patients included 47 males and 25 females. The mean age of the study patients was 44 (±12) years. The mean length of time after they received a transplanted kidney was 67.5 (±42) months (median: 62 months). The mean value of serum H. pylori-specific IgG antibody titer among these patients was 3 (±4.6) U/mL (median: 1 U/mL), and that of intact parathormone (iPTH) was 18.4 (±8.2) pg/mL (median: 16.5 pg/mL). The mean serum magnesium (Mg) was 1.9 (±0.20) mg/dL (median: 1.9 mg/dL) and the mean creatinine clearance was 53 (±11) mL/min (median: 56 mL/min). In this study population, there was no significant difference in the H. pylori IgG antibody titers, serum iPTH, Mg, calcium, alkaline phosphatase and albumin levels as well as body mass index (BMI) between males and females or diabetics and non-diabetics. There was no significant relationship between serum H. pylori IgG antibody titers and the age of the patients, BMI, serum Alb, phosphorus, Ca, serum leptin and serum ALP. Significant negative correlation between serum H. pylori IgG antibody titers and serum Mg (r = -0.30, P = 0.01) and serum iPTH (r = -0.25, P = 0.03) was seen. A significant positive correlation was found between serum H. pylori IgG antibody titer and creatinine clearance (r = 0.26, P = 0.02), and a near-significant positive correlation was found with the duration of RTx (r = 0.20, P = 0.08). Our study shows that the correlation of H. pylori IgG antibody titer with some demographic and biochemical indices in RTx recipients may be different from what has been reported in hemodialysis patients. Larger clinical studies are needed to assess the clinical implications of our findings.

BACKGROUND

Vitamin D [25(OH)D] deficiency is a cardiovascular risk factor in the hemodialysis (HD) population. The aim of this study was to identify hypovitaminosis D in HD patients without signs of hyperparathyroidism and to analyze its association to inflammation and echocardiographic alterations.

METHODS

Patients on HD with iPTH <300 pg/ml not receiving vitamin D therapy were recruited. Hypovitaminosis D was defined as 25(OH)D <30 ng/ml. High-sensitivity C-reactive protein, interleukin-6 and serum albumin were used as inflammation markers. Echocardiograms were performed in an interdialytic mid-week day.

RESULTS

Sixty-one patients (mean age of 56 ± 15 years, 52% males, 93% Caucasians, 31% diabetic) were included, and 75% presented hypovitaminosis D. Inflammation was more prevalent among those with hypovitaminosis D, and these patients presented higher relative wall thickness (0.48 ± 0.11 vs. 0.42 ± 0.10 mm; p = 0.05) and lower left ventricular diastolic (49.8 ± 6.2 vs. 54.7 ± 5.8 mm; p = 0.013) and systolic (31.9 ± 5.7 vs. 36.8 ± 7.2 mm; p = 0.012) diameters.

CONCLUSIONS

Hypovitaminosis D is associated with inflammation and concentric geometric pattern of the left ventricle, even in the absence of high iPTH levels. Vitamin D repletion (aiming to reduce cardiovascular complications) should also be considered in HD patients with normal or low iPTH levels.

We carried out this retrospective study to examine the magnesium status of our chronic ambulatory peritoneal dialysis (CAPD) patients dialyzed with 0.75 mmol/L (group I) or 0.50 mmol/L (group II) magnesium peritoneal dialysis solution. A total of 34 anuric patients on CAPD (age:31-72 years; duration of CAPD:7-74 months) were studied. None of them received magnesium-containing phosphate binders or vitamin D. Biochemical parameters including magnesium, calcium, phosphate, parathormone, and albumin were measured in all patients. The corrected for hypoalbuminemia serum magnesium concentration in group I was significantly higher compared to that found in group II. However, there were no significant differences in the other measured parameters between the two groups of CAPD patients, though iPTH levels were somewhat increased in group II patients. Serum magnesium levels were weakly correlated with serum prealbumin levels in both groups of CAPD patients (r=0.16, P=0.08 and r=0.17, P=0.07). The incidence of hypermagnesemia was significantly higher in group I patients versus those in group II (13/19 68.4%] vs. 2/15 13.3%], P<0.01). On the other hand, no patient developed hypomagnesemia (corrected total magnesium <0.65 mmol/L), despite the trend toward decreased magnesium levels in group II patients. Our results point out that serum iPTH levels and nutritional parameters, such as prealbumin levels, should be taken into account in the choice of the magnesium concentration of the peritoneal dialysis fluid.

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

OBJECTIVE

Secondary hyperparathyroidism (SHP) is characterized by high bone turnover and elevated serum bone remodeling markers. Elevation of serum interleukin-6 (IL-6) levels is also characteristic of end-stage renal disease. This study investigates the effects of intravenous calcitriol on serum bone resorptive markers, namely, type 5b tartrate-resistant acid phosphatase (TRACP5b) and IL-6 in patients with SHP.

METHODS

Intravenous calcitriol therapy was given for 16 weeks to 24 patients on maintenance hemodialysis with plasma intact parathyroid hormone (iPTH) levels >300 pg/ml. Blood was drawn at baseline and every 4 weeks for 16 weeks for determination of the levels of biochemical parameters, iPTH, IL-6 and bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and TRACP5b.

RESULTS

Only 21 patients responded to the calcitriol therapy, with significant decrements in serum iPTH after 4 weeks of therapy and thereafter. After 16 weeks of calcitriol therapy, 21 patients had significant decrements in serum iPTH (707.9 +/- 317.8 vs. 205.0 +/- 63.1 pg/ml, p < 0.01). Prior to treatment, a significant correlation was found between increased levels of serum iPTH and IL-6 levels (r = 0.45, p < 0.05). After treatment, there was also a significant and parallel lowering of levels of serum iPTH, IL-6 (8.52 +/- 3.59 vs. 7.24 +/- 2.81 pg/ml, p < 0.01), bAP (54.68 +/- 36.17 vs. 24.55 +/- 13.84 U/l, p < 0.01) and TRACP5b (3.41 +/- 1.89 vs. 1.80 +/- 0.55 U/l, p < 0.01). Our results additionally showed significant positive correlationsbetween baseline levels of serum IL-6 and those of iPTH, bAP and TRACP5b. After 16 weeks of calcitriol treatment, the correlation between IL-6 and iPTH levels lost significance but levels of serum IL-6, bAP and TRACP5b remained significantly correlated.

CONCLUSIONS

Elevated levels of serum IL-6 and bone remodeling markers, namely, bAP and TRACP5b which are common features of SHP, are effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also aggravate inflammation in patients on maintenance hemodialysis.

OBJECTIVE

Bone alkaline phosphatase (bAP) is known to be an important biochemical marker of bone formation. Through the present study, we intended to find out whether there is any advantage in bAP determination, as a routine biochemical marker, besides intact parathyroid hormone (iPTH) in hemodialysis patients.

METHODS

In a population of 140 hemodialysis patients, bAP and iPTH were determined on four quarterly consecutive occasions. According to the values of iPTH (pg/ml) and bAP (ng/ml), patients were divided into four groups: group I: iPTH>> 200 and bAP>> 20, group II: iPTH>> 200 and bAP < 20, group III: iPTH < 200 and bAP < 20 and group IV: iPTH < 200 and bAP>> 20. Patients with higher serum phosphorus (P) (group A: P>> or = 7 mg/dl) were compared with those with lower serum P levels (group B: P < 7 mg/dl).

RESULTS

The global correlation between iPTH and bAP (total evaluations, n = 503) was 0.32 (p < 0.001). Group IV patients tended to show a slight increase of serum aluminum (sAl) levels, which were 12.48 +/- 5.35 microg/l higher than in the patients from group I (sAl = 9.97 +/- 4.39 microg/l), group II (sAl = 10.86 +/- 4.45 microg/l) or group III (sAl = 10.92 +/- 3.92 microg/l). Significance values (Mann-Whitney) in each group, in comparison with group IV, were the following: group I: 0.004; group II: 0.062; group III: < 0.001. Group A (n = 66) showed higher iPTH levels than group B (n = 430), although bAP and sAl were both similar in these two groups of patients (Mann-Whitney): iPTH (A) = 631.0 +/- 487.7 vs. iPTH (B) = 253.3 +/- 191.6, p < 0.001; bAP (A) = 22.9 +/- 17.4 vs. bAP (B) = 20.4 +/- 13.1, p = n.s.; sAl (A) = 10.2 +/- 3.5 vs. sAl (B) = 10.8 +/- 4.4, p = n.s. For similar Al and bAP values, group A showed a much stronger iPTH/bAP correlation than group B: r = 0.67 (p < 0.001) vs. r = 0.30 (p < 0.001), respectively.

CONCLUSIONS

Although iPTH and bAP are frequently in agreement, it seems important to separate parathyroid activity given by iPTH, from bone remodelling reflected by bAP, in the presence of either a higher aluminum exposition or a well-controlled phosphatemia.

Anaemia is a feature almost invariably complicating chronic renal failure. Its pathophysiology is multifactorial but the most important cause is erythropoietin (Epo) deficiency. However, either no relation or even a weakly positive relation generally exists between serum immunoreactive (i) Epo and haematocrit values in uraemic anaemia, whereas in anaemias of non-renal origin the correlation is most often strongly negative. Recent evidence indicates that growth hormone also stimulates erythropoiesis. Moreover, late erythroid progenitor cells (CFU-E) require insulin and/or insulin-like growth factor I (IGF-I) for development in vitro. IGF-I has been shown to have a synergistic action with Epo. We have measured serum iEpo and IGF-I levels in 17 haemodialysis patients with severe hyperparathyroidism (mean +/- SEM serum iPTH, 988 +/- 88 pg/ml). Mean age and duration of dialysis treatment were 46.1 +/- 3.4 and 8.8 +/- 1.0 years respectively. Mean haematocrit and haemoglobin values wer 28.1 +/- 1.7% and 9.39 +/- 0.54 g/dl respectively. Mean serum iEpo and IGF-I levels were 20.3 +/- 4.7 mU/ml and 320 +/- 20 ng/ml respectively (normal values for serum iEpo and IGF-I, 17.9 +/- 6 mU/ml and 91 +/- 23 ng/ml respectively). We found that serum IGF-I concentrations were well correlated with haematocrit values (r = 0.68, n = 15, P less than 0.004) whereas serum iEpo values were not (r = 0.41, n = 12, P = 0.18). IGF-I could therefore be an important factor regulating erythropoiesis in uraemic patients, at least when associated with severe hyperparathyroidism.

Mitral annulus calcification, a common lesion of the elderly (over age 60 years), has been detected with increased frequency and at younger ages in patients with uraemia. To date a pathogenic role for dialysis and secondary hyperparathyroidism has been suggested only on the basis of older dialytic age and increased serum iPTH observed in the affected individuals. Because this is a potentially dangerous lesion we deemed it useful to evaluate more completely the respective roles of possible pathogenetic factors in uraemic individuals. Evaluation included echocardiography, ECG, limb radiography, and serum assays. A total of 225 dialysis (HD) patients, 67 chronic renal failure (CRF) patients on conservative treatment and 67 normal subjects were studied. Mitral annulus calcification was detected in 87 of 225 (38.6%) HD patients, 11 of 67 (16.4%) CRF and six of 67 (8.9%) normals. In HD, patients with calcification were older and on longer-term renal replacement therapy compared to those without calcification. They also had greater values of iPTH, BGP, AP, and Rx score of secondary hyperparathyroidism. Mitral annulus calcification was associated more frequently (chi 2 = 14.8; P < 0.0001) with rhythm and cardiac conduction defects, but not with ectopic calcifications. Multiple stepwise regression analysis, with mitral annulus calcification score as dependent variable, selected dialysis duration, age, and iPTH (rm = 0.368) as the most predictive parameters, with the first two carrying most of the information. The stratification of patients according with these two parameters showed a progressive increase in the frequency of calcification both with HD duration and age.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND

The role ofparathyroid glands (PTG) ultrasonography (US) in hemodialysis patients with secondary hyperparathyroidism (SHPT) is still controversial. The present study aimed at evaluating the relationship between US findings and SHPT degree as well as therapeutic outcome.

METHODS

Twenty hemodialysis patients with moderate SHPT and 15 with severe SHPT underwent US to assess the PTG number, maximum longitudinal diameter (MLD), structural (1-hypoechoic, 2-slight heterogeneous, 3-high heterogeneous, 4-nodular) and vascular patterns (1-slight, 2-medium and 3-high).

RESULTS

PTG number, MLD and US patterns were correlated with iPTH levels. MLD of patients with moderate or severe SHPT was 7.2 +/- 2.3 and 15 +/- 5.1 mm (p < 0.001). Most patients with moderate SHPT showed a single PTG with an MLD <9 mm associated with 1-2 structural and vascular pattern, whereas patients with severe SHPT exhibited more than one PTG with MLD >9 mm and 3-4 structural and vascular patterns. Thirteen patients were responders to treatment and 22 nonresponders. In nonresponders, a higher number of PTG was observed as well as higher echostructural and vascular patterns. In 14 patients who underwent parathyroidectomy, no differences were found between PTG US MLD and pathology diameter. All PTG with evidence of 3-4 structural and vascular score at ultrasound showed nodular hyperplasia at pathological examination.

CONCLUSIONS

The adopted classification of US findings is correlated with SHPT degree and therapeutic outcome and might be an adjunctive predictive method useful to assess the SHPT severity and to plan the therapeutic strategy.

Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium-phosphorus product in patients with chronic kidney disease and secondary hyperparathyroidism who are receiving dialysis, and reduces elevated serum calcium associated with primary hyperparathyroidism and parathyroid carcinoma. Cinacalcet is administered orally, and thus concomitant administration with food may affect its bioavailability. The objective of this study was to examine the effect of fat and caloric intake on cinacalcet exposure. This phase 1, randomized, open-label, single-dose, 3-period, 3-treatment, 6-sequence crossover study enrolled 30 healthy subjects (19 men, 11 women) to receive a single oral dose of cinacalcet HCl (Sensipar/Mimpara; Amgen Inc. Thousand Oaks, CA) (90 mg) on 3 separate occasions: following a high-fat, high-caloric meal, a low-fat, low-caloric meal, and a 10-hour fast. Blood samples were obtained predose and up to 72 hours postdose for pharmacokinetic (AUCinfinity, Cmax) and safety evaluations. Twenty-nine subjects completed all the 3 treatment conditions. The mean (90% confidence intervals) AUCinfinity following high- and low-fat meals was increased by 68 (48 to 89)% and 50 (33 to 70)%, respectively, relative to fasting. The difference in mean AUCinfinity between high- and low-fat meals was small [12 (9.9-26)%]. The mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2beta was similar between treatment conditions. Adverse events (AE) were observed at a similar frequency across the treatment conditions [high fat (34%), low fat (23%), and fasting (31%)]; the type of AE did not differ among the treatment conditions. The most common treatment-related AEs were headache 6/30 (20%), nausea 5/30 (17%), and dyspepsia 4/30 (13%) subjects. Administration of cinacalcet with either high- or low-fat meals results in significant increases in exposure, relative to administration under fasting conditions. However, the small differences observed in exposure following the ingestion of the different types of meals suggest that although food has a significant effect, the type of food does not. The observed effect supports the labeling statement that cinacalcet be taken with food, or shortly after a meal.

BACKGROUND

Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation.

METHODS

Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis.

RESULTS

The mean age was 51 years, 57% were males and 21% were diabetic, with 72 months (median) post-transplantation. Most of the patients were in CKD stage 3. Serum phosphorus showed strong negative correlation with graft function in CKD stages 4-5 (r = -0.633, P < 0.001). Hyperphosphatemia was independently associated with the time spent on dialysis before transplantation, serum iPTH and CKD stages 4-5. iPTH showed negative correlation with eGFR in CKD stages 3-5 (rho = -0.289, P < 0.001) and weak positive correlation with time spent on dialysis prior to transplant (rho = 0.114, P < 0.001). Both hyperparathyroidism (42%) and relative hypoparathyroidism (15%) were frequent. The prescription of P-binders (6%) and vitamin D analogs (33%) was sporadic.

CONCLUSIONS

Disturbances of bone and mineral metabolism after transplantation are prevalent and are strongly correlated with the kidney function, similarly to non-transplanted CKD patients. MBD in this population is not adequately managed.

BACKGROUND

Despite substantial progress in medical care, the mortality rate remains unacceptably high in dialysis patients. Evidence suggests that bone mineral dismetabolism (CKD-MBD) might contribute to this burden of death. However, to date only a few papers have investigated the clinical relevance of serum mineral derangements and the impact of different therapeutic strategies on mortality in a homogeneous cohort of south European dialysis patients.

METHODS

The RISCAVID study was a prospective, observational study in which all patients receiving hemodialysis (HD) in the north-western region of Toscany in June 2004 were enrolled (N=757) and followed up for 24 months.

RESULTS

At study entry, only 71 (9%) patients of the entire study cohort exhibited an optimal control of serum phosphorous (Pi), calcium (Ca), calciumX-phosphorous product (CAXPi) and intact parathyroidhormone (iPTH) according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical guidelines. Despite a similar prevalence, the severity of CKD-MBD appeared different to the results reported in the USA. Interestingly, none of the serum biomarkers or number of serum biomarkers within KDOQI targets was independently associated with all-cause and cardiovascular (CV) mortality. Among treatments, Sevelamer was the only drug independently associated with lower all-cause and cardiovascular mortality (p<0.001).

CONCLUSIONS

The RISCAVID study highlights the difficulty of controlling bone mineral metabolism in HD patients and lends support to the hypothesis that a carefully chosen phosphate binder might impact survival in HD patients.

Renal osteodystrophy is a virtually universal complication of chronic renal failure (CRF). Varying degrees of calcium-phosphate metabolism derangement and different types of skeletal damage are observed in CRF for many reasons while the use of dialysis for the management of end-stage renal failure further affects these complications. This study was designed to evaluate the bone mineral density (BMD) that is measured by dual-energy x-ray in three groups of patients: A, 10 patients on continuous ambulatory peritoneal dialysis (CAPD); B, 10 patients on hemodialysis (HD); and C, 10 predialytic patients with advanced CRF. All patients were matched for age, sex, duration of dialysis >> 3 years), and the use of phosphate binders. Biochemical (serum iPTH levels, SAP, Ca, P) and radiological bone studies were compared in the three groups. The majority of predialytic patients had BMD values within the normal range, while the BMD values in PD patients were higher (0.985 g/cm2) in comparison with HD patients (0.949 g/cm2). Some patients, especially in the HD population, showed an increase in BMD with time on dialysis. From all other comparisons, radiological signs of high turnover bone disease and osteopenia were the only variables that were correlated with BMD. All these findings suggest that dialysis affects the bone status and that CAPD patients have better bone mineral metabolism as shown mainly with the use of BMD measurements.

It would be useful to predict the future development of hyperparathyroidism before treatment with active vitamin D agents. Fibroblast growth factor 23 (FGF23) is a newly identified humoral phosphaturic factor. Positive correlation was found between parathyroid function and serum FGF23 levels in dialysis patients. Interestingly, FGF23 levels showed even better correlation with intact parathyroid hormone (iPTH) levels 2 years after the sample collection for the FGF23 measurement. In long-term dialysis patients with mild secondary hyperparathyroidism, serum FGF23 level was the best screening test to discriminate patients with future advanced secondary hyperparathyroidism within 2 years. In dialysis patients with advanced secondary hyperparathyroidism, the pretreatment FGF23 levels, as well as iPTH levels, significantly affected the outcome of calcitriol therapy. Thus, the measurement of serum FGF23 level is a promising laboratory examination to predict the future development of secondary hyperparathyroidism. The mechanism of this phenomenon, however, remains to be revealed.

Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism, but its efficacy and safety are still under discussion. The present randomized multicenter study compares the effect of an 8-week course of daily versus intermittent (twice weekly) calcitriol therapy on parathyroid hormone (PTH) suppression in 59 children (mean age 8.4+/-4.7 years) with chronic renal insufficiency (mean Ccr 22.4+/-11.6 ml/min per 1.73 m2) and secondary hyperparathyroidism. After a 3-week washout period, the patients were randomly assigned to treatment with daily oral calcitriol (10 ng/kg per day) or intermittent oral calcitriol (35 ng/kg given twice a week). The calcitriol dose was not changed throughout the study period of 8 weeks. At start of the study, the median intact PTH (iPTH) level was 485 pg/ml (range 83-2032) in the daily group (n=29) and 315 pg/ml (range 93-1638) in the intermittent group (n=30). After 8 weeks, the respective median iPTH concentrations were 232 pg/ml (range 63-1614) and 218 pg/ml (range 2-1785) (ns). The mean iPTH decrease from baseline was 19.2+/-57.8% and 13.7+/-46.7% respectively (not significant). Calcitriol reduced the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group. One episode of hypercalcemia (>11.5 mg/dl) was observed in both groups and a single episode of hyperphosphatemia (>7.5 mg/dl) was observed in the daily group. It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively than the daily administration of calcitriol in children with chronic renal failure prior to dialysis.

OBJECTIVE

To evaluate the compassionate use of cinacalcet for the management of secondary hyperparathyroidism in patients who are not on dialysis.

METHODS

Patients with stage 4-5 chronic kidney disease (CKD) who were not on dialysis, had an intact parathyroid hormone (iPTH) level greater than 300 pg/mL, and had not responded satisfactorily to treatment with phosphate binders and vitamin D were prospectively studied. Patients received 6 months of compassionate treatment with cinacalcet, which was initiated at a dose of 30 mg/day orally and flexibly dosed thereafter based on iPTH levels.

RESULTS

Twenty-six patients with a mean age±standard deviation (SD) of 58.8±16.1 years were enrolled in the study and included in the statistical analysis. The mean percentage change in iPTH levels from baseline after 6 months of treatment was -67.9±17.0%, with 92.3% (95% confidence interval (CI), 75.9-97.9) of patients showing an iPTH level within the limits recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. The mean serum calcium concentrations had decreased significantly at the end of the study (-8.0±6.9%), while the mean serum phosphorus concentration had significantly increased (+8.3±17.0%).

CONCLUSIONS

Our results suggest that cinacalcet may be a useful alternative for the treatment of secondary hyperparathyroidism in pre-dialysis patients who are unresponsive to other treatments. The hypocalcemia and hyperphosphatemia reported in previous studies may not occur if a moderate dose of calcimimetics is used in patients with marginal glomerular filtration rates, especially if combined with vitamin D analogues and calcium-based phosphate binders.

BACKGROUND

The IMPACT SHPT [Improved Management of Intact Parathyroid Hormone (iPTH) with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism] study compared the effectiveness of paricalcitol and cinacalcet in the management of secondary hyperparathyroidism in haemodialysis patients but did not report the costs or cost effectiveness of these treatments.

OBJECTIVE

The aim of this study was to compare the cost effectiveness of a paricalcitol-based regimen versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients from a US payer perspective, using a 1-year time horizon.

METHODS

This was a post hoc cost-effectiveness analysis of data collected for US patients enrolled in the IMPACT SHPT study-a 28-week, randomized, open-label, phase 4, multinational study (ClinicalTrials.gov identifier: NCT00977080). Patients eligible for the IMPACT SHPT study were aged≥18 years with stage 5 chronic kidney disease, had been receiving maintenance haemodialysis three times weekly for at least 3 months before screening and were to continue haemodialysis during the study. Only US patients who reached the evaluation period (weeks 21-28) were included in this secondary analysis. US subjects in the IMPACT SHPT study were randomly assigned to receive intravenous paricalcitol, or oral cinacalcet plus fixed-dose intravenous doxercalciferol, for 28 weeks. Patients in the paricalcitol group could also receive supplemental cinacalcet for hypercalcaemia. The primary effectiveness endpoint in the IMPACT SHPT study was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) level of 150-300 pg/mL during the evaluation period. In this secondary analysis, we estimated the incremental cost-effectiveness ratio (ICER), comparing paricalcitol-treated patients with cinacalcet-treated patients on the basis of this primary endpoint and several secondary endpoints. Costs were estimated by examining the dosage of the study drug (paricalcitol or cinacalcet) and phosphate binders used by each participant during the trial. Nonparametric bootstrap analysis was used to examine the accuracy of the ICER point estimates.

RESULTS

The percentages of patients achieving the treatment goal of a mean iPTH level between 150-300 pg/mL during weeks 21-28 of therapy were 56.9% in the paricalcitol group and 34.0% in the cinacalcet group (a difference of 23%, p=0.0235). Paricalcitol was also more effective for each of the secondary endpoints. When annualized, the total drug costs were US$10,153 in the paricalcitol group and US$15,967 in the cinacalcet group, a difference of US$5,814 (57.3%, p=0.0053). Because the paricalcitol-based treatment was less expensive and more effective, it was 'dominant', compared with cinacalcet, in this cost-effectiveness analyses. In our bootstrap analysis, 99.1% of bootstrap replicates for the ICER of the primary endpoint fell within the lower right quadrant of the cost-effectiveness plane-where paricalcitol is considered dominant. For all of the other endpoints, paricalcitol was dominant in 100% of replicates.

CONCLUSIONS

On the basis of dosing and effectiveness data from US patients in the IMPACT SHPT study, we found that a regimen of intravenous paricalcitol was more cost effective than cinacalcet plus low-dose vitamin D in the management of iPTH in patients with SHPT requiring haemodialysis.

BACKGROUND

Despite extensive use of standard therapy for secondary hyperparathyroidism (sHPT) in dialysis patients, still most patients do not achieve the recommended treatment targets. In a pan-European observational study (ECHO), the effectiveness of the calcimimetic cinacalcet for the treatment of sHPT was evaluated in real-world clinical practice. A sub-analysis of the entire Austrian study cohort is presented.

METHODS

Adult dialysis patients who had initiated cinacalcet therapy were included. Data on biochemical parameters of bone and mineral metabolism (intact parathyroid hormone [iPTH], calcium [Ca] and phosphorus [P]) and concurrent medication were collected 6 months prior to the initiation of cinacalcet, at initiation (baseline) and after up to 12 months of active treatment.

RESULTS

A total of 320 patients (mean age (±SD): 56 (±14) years) from 34 Austrian dialysis centres were enrolled. At baseline, patients presented with elevated serum iPTH (median 605 pg/ml) and hyperphosphataemia (median 2.1 mmol/l). After 12 months of cinacalcet treatment, serum iPTH (median percentage change -48%), calcium (-2%) and phosphorus (-6%) decreased. The greatest iPTH reduction (-66%) was found in patients with most severe sHPT (>800 pg/ml at baseline). The proportion of patients achieving the recommended NKF/K-DOQI(™) treatment targets increased from baseline to month 12 for iPTH (3-36%) and phosphorus (24 to 39%) and remained stable for calcium (51 to 50%), respectively. No patient had all 3 parameters simultaneously within NKF/K-DOQI(™) treatment targets at baseline, while 7% of patients achieved this treatment goal after 12 months. During the study the use of the phosphate binder sevelamer remained fairly stable, while the relative percentage use of calcium-based phosphate binders increased and the usage of aluminium-containing binders decreased; vitamin D analogue use remained stable.

CONCLUSIONS

Additional use of cinacalcet improved biochemical parameters of bone and mineral metabolism and enabled more patients to achieve and maintain the KDOQI(™) treatment targets for serum iPTH, calcium and phosphorus.

BACKGROUND

The place of parathyroid gland imaging by [(99m)Tc](technetium)-sestamibi scintigraphy in uraemic patients with secondary hyperparathyroidism remains a matter of debate. The purpose of the present study was (i) to assess its value with respect to plasma intact parathyroid hormone (iPTH) levels and to surgical parathyroidectomy (PTx), and (ii) to explore the possibility of suppressing parathyroid [(99m)Tc]-sestamibi uptake by calcitriol.

METHODS

In a first cross-sectional, static study 52 chronic haemodialysis (HD) patients with plasma iPTH levels between 14 and 2791 pg/ml (normal, 10-65 pg/ml) had a [(99m)Tc]-sestamibi scan, and 21 of them underwent surgical PTx. In a second longitudinal, dynamic study 14 chronic HD patients with advanced secondary hyperparathyroidism received short-term calcitriol treatment in an attempt to suppress [(99m)Tc]-sestamibi imaging of parathyroid glands. Calcitriol was given intravenously for 2 weeks, 2 microg after each haemodialysis session. Scintigraphy was carried out before and at the end of this inhibition test.

RESULTS

[(99m)Tc]-Sestamibi scan led to imaging of one or more (maximum three) parathyroid glands in most, but not all, HD patients with plasma iPTH values >600 pg/ml. Based on surgical findings, overall sensitivity of [(99m)Tc]-sestamibi scan in correctly locating parathyroid glands was only 50%, whereas specificity was 100%. In contrast, its sensitivity was 100% in locating single glands in the subgroup of five patients with recurrent hyperparathyroidism. The calcitriol inhibition test showed suppression of [(99m)Tc]-sestamibi uptake by at least one parathyroid gland in eight patients (57%), with complete suppression in five of them (36%). Basal plasma iPTH or decrease of plasma iPTH in response to calcitriol was not predictive of suppressible [(99m)Tc]-sestamibi uptake in the individual case, although mean iPTH was markedly higher in patients with non-suppressible parathyroid glands.

CONCLUSIONS

Because of its relatively low sensitivity the [(99m)Tc]-sestamibi scan is of limited help in the exploration of uraemic patients with severe secondary hyperparathyroidism before a first surgical PTx. However, it is very useful in locating the remaining parathyroid gland(s) in case of reoperation. The novel calcitriol inhibition test of [(99m)Tc]-sestamibi uptake could help to better distinguish parathyroid glands with non-suppressible, autonomous activity from glands whose activity might be amenable to long-term suppression.

BACKGROUND

Vitamin D deficiency is highly prevalent in dialysis patients. Whether substitution of native vitamin D in these patients is beneficial is a matter of ongoing discussion, as is the optimal dosing schedule. The purpose of this study was to investigate the efficacy and safety of a body-weight adapted oral dosing regimen of cholecalciferol in dialysis patients.

METHODS

In a prospective single-center study 56 prevalent dialysis patients with a baseline 25OHD3 level <20 ng/mL received 100 IU of cholecalciferol per kg body weight once weekly orally for 26 weeks. 25OHD3 was measured at baseline and at study end, iPTH every three months, serum calcium and phosphorous monthly. Concurrent medication including phosphate binders, calcitriol and cinacalcet and dialysate calcium concentration remained unchanged throughout the study.

RESULTS

Baseline 25OHD3 was 9.9 ± 4.1 ng/mL and increased to 26.1 ± 8.8 ng/mL (P = 0.01). Fourteen patients (27 %) achieved a level>> 30 ng/mL and all others above 20 ng/mL. Cinacalcet therapy was positively associated with the increase in 25OHD3 (P = 0.024). The plasma iPTH level significantly decreased from median 362 pg/mL to 297 pg/mL (P = 0.01). This decline was more pronounced in patients with higher baseline iPTH levels (P < 0.01) and differed significantly dependent on concurrent calcitriol therapy. A significant iPTH decrease was observed in patients receiving calcitriol (P = 0.031). Serum calcium and phosphorous did not change significantly throughout the study period. Cholecalciferol substitution was well tolerated without adverse effects.

CONCLUSIONS

The dosing regimen of oral cholecalciferol supplementation with 100 IU per kg body weight per week for 26 weeks in dialysis patients with vitamin D deficiency causes a significant increase in 25OHD3 close to the supposed target level of 30 ng/mL and a significant reduction in iPTH, without affecting serum calcium or phosphorous levels.

BACKGROUND

This study evaluated the proportion of patients who met National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) guidelines for mineral status, and assessed the cost of therapy for mineral management of patients under haemodialysis treatment in Spain.

METHODS

Demographic and biochemical data were collected for 1312 patients undergoing standard three-times weekly maintenance haemodialysis at six Spanish centres during December 2003. Age, gender, diabetic nephropathy, haemodialysis duration, serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone (iPTH) levels were monitored. Exploratory analyses of associations between demographic and biochemical parameters, were undertaken using bivariate and multivariate regression techniques.

RESULTS

Mean age of patients was 62 years. 97% were Caucasian, 23% were diabetic. In total, 51% of patients received calcium binders, 21% sevelamer, 16% aluminium hydroxide, and 29% received no binders; 33% of patients received calcitriol. Prevalence of patients outside K/DOQI targets was: calcium 50%, phosphorus 46%; Ca x P 33%; iPTH 77%. Elevated phosphorus (>5.5 mg/dl) was independently associated with younger age [OR 0.972 (95% CI 0.963-0.980), P<0.001] and higher iPTH [OR 1.0005 (95% CI 1.0002-1.0008), P<0.001]. Elevated Ca x P >>or=55 mg(2) x dl(2)) showed a similar relationship. High iPTH levels (>300 pmol/l) were associated with female gender [OR 1.574 (95% CI 1.213-2.041), P<0.001], high serum phosphorus [OR 1.230 (95% CI 1.130-1.338), P<0.001], and longer duration of dialysis [OR 1.003 (95% CI 1.001-1.005), P<0.01]. Poorly controlled serum phosphorus, Ca x P and iPTH were associated with more expensive therapy for mineral management.

CONCLUSIONS

One in three haemodialysis patients in Spain remains above the upper target range defined in current mineral metabolism guidelines. This abnormal profile is more common in younger patients and females and therapy is more expensive in younger patients.