Evolution of coronary artery calcification in patients with chronic kidney disease Stages 3 and 4, with and without diabetes.

BACKGROUND: The purpose of this study was to report the evolution of coronary artery calcification (CAC) in subjects with chronic kidney disease Stages 3 and 4 comparing those with and without diabetes. We previously reported prevalence in the same population. METHODS: CAC was measured using multi-slice computer tomography. We prospectively followed up 103 patients for 2 years, 49 with diabetes and 54 without diabetes. Demographic, routine biochemistry, calcification inhibitors and bone mineral density data were collected and analysed. Evolution of CAC was defined as those with a difference of ≥ 2.5 U between baseline and final square root CAC scores. RESULTS: There were more progressors in the group with diabetes, 24 compared to 12 in the group without diabetes (P= 0.004). When diabetes was present, CAC progressed equally in men and women. Risk factors for evolution of CAC included age, baseline CAC score and serum phosphate levels. Baseline CAC score, phosphate and body mass index were independent predictors for the increase of CAC score during the study period. Severity of CAC was greater in the diabetes group (median CAC score at baseline in the group with diabetes 154 increased to 258 2 years later, P < 0.001). CONCLUSIONS: Evolution of CAC is greater in older patients and those with diabetes, where the gender advantage of being female is lost. Serum phosphate level, despite being within the normal range and virtually no use of phosphate binders, was also a risk factor. Further studies are required to determine the levels of serum phosphate required to minimize cardiovascular risk.

Relationship between vitamin D status, parathyroid hormone levels and bone mineral density in patients with chronic kidney disease stages 3 and 4.

AIM: Low vitamin D status is associated with secondary hyperparathyroidism and increased bone turnover in the general population and can aggravate the hyperparathyroidism of chronic kidney disease (CKD) patients. It is also correlated to low bone mineral density (BMD), but this correlation is less clear in CKD patients. Aims of our study were to investigate these associations in CKD stages 3 and 4 patients, and to identify significant predictors of BMD in this population. METHODS: Serum 25-hydroxyvitamin D (25OHD) levels, BMD at the femur and radius, and bone mineral metabolism parameters were measured in 89 CKD stages 3 and 4 patients. Vitamin D status was defined according to the NKF/KDOQI guidelines. RESULTS: Mean 25OHD levels were 53.8+/-32.1 nmol/L and correlated to the severity of proteinuria. Thirty-five patients (39%) had vitamin D insufficiency, 29 (33%) had vitamin D deficiency and five (6%) had severe deficiency. Of the 89 patients, two had osteoporosis and 31 had osteopenia either at femur or radius. Independent predictors for the total femur BMD were the intact parathyroid hormone (iPTH) levels and the body mass index (BMI). For the total radius BMD, independent predictor was only the BMI. Serum 25OHD levels were not directly associated with BMD, but they were independent predictors of iPTH. CONCLUSION: Vitamin D insufficiency and deficiency are very common in CKD stages 3 and 4 population and may indirectly affect, via effects on iPTH, the BMD of these patients.

Detection of coronary and peripheral artery calcification in patients with chronic kidney disease stages 3 and 4, with and without diabetes.

BACKGROUND: The purpose of this study was to describe the prevalence and extent of coronary artery calcification (CAC) in subjects with chronic kidney disease (CKD) stages 3 and 4 comparing those with and without diabetes. We also wished to determine if the presence of peripheral artery calcification (PAC) would assist in identifying patients positive for CAC. METHODS: CAC was detected by multi-slice computed tomography and PAC was detected by plain foot radiography. Study population was 112 patients, 54 with diabetes and 58 without, all asymptomatic for heart disease. Demographic and laboratory data were collected and analysed. RESULTS: The prevalence of CAC in CKD patients was 76 and 46.5% with and without diabetes, respectively. Patients with diabetes had higher CAC scores with more vessels affected, and in the presence of diabetes men and women had the same risk for CAC. In patients with diabetes, age was the unique explanatory variable for detecting the presence of CAC, while age and smoking history predicted severity. In patients without diabetes, age, male gender, body mass index, estimated glomerular filtration rate and serum phosphate levels predicted the presence of CAC, while parathyroid hormone predicted severity. Prevalence of PAC was 63 and 12% in subjects with and without diabetes. PAC detected by foot radiography was not an adequate alternative-screening marker for identifying patients with CAC. CONCLUSIONS: CAC is common in CKD stages 3 and 4 patients, especially in men and women with diabetes.

Reduced bone mineral density in male renal transplant recipients: evidence for persisting hyperparathyroidism.

BACKGROUND: Osteoporosis is increasingly recognized as a major source of morbidity following renal transplantation. The aim of this cross-sectional study was to determine the prevalence of osteoporosis in a cohort of male transplant recipients and examine factors that may influence their bone loss. METHODS: Bone mineral density (BMD) and biochemical markers of bone metabolism were measured in 134 out of 154 male renal allograft recipients in our center. RESULTS: The mean age of the patients was 49.7 years (range 26-76) with a median of 6 years post-transplant. Only 17% had normal BMD, 30% were osteoporotic at either hip or spine, and this proportion rose to 41% if the ultradistal radius was included. Parathyroid hormone (PTH) was negatively correlated with BMD at all skeletal sites. In a multiple regression model, independent predictors of femoral neck BMD included body mass index (p=0.004), diabetes (p=0.025), and PTH (p=0.049). The only independent predictor of BMD at the ultradistal radius was PTH (p<0.001). Nineteen men sustained a total of 25 appendicular fractures after transplantation (median time to fracture was 3 years). Prevalent vertebral fractures were only identified in five men. PTH was elevated in 72.4% of patients (mean PTH 142 +/- 118 pg/ml). Bone resorption markers were increased in 48% of patients. PTH was positively correlated with serum carboxyterminal telopeptide of type 1 collagen (r=0.473, p<0.001) and procollagen type 1 amino terminal propeptide (r=0.419, p<0.001). CONCLUSIONS: Osteopenia and osteoporosis are common in male transplant recipients, and the hip and radius are the most severely affected sites. Elevated rates of bone resorption driven by hyperparathyroidism appear to be the most important contributing factor.

Comparison of intact and 'whole molecule' parathyroid hormone assays in patients with histologically confirmed post-renal transplant osteodystrophy.

BACKGROUND: Fragments of parathyroid hormone (PTH) have been identified (amino acids 7-84) which may interfere with commercially available 'intact molecule' PTH assays. Novel assays which employ an antibody directed to the first seven amino acids of the N-terminus of PTH are thought to be free from cross-reactivity with the 7-84 fragments, and therefore measure true 'whole molecule' PTH. Transplant recipients (as well as those in end-stage renal failure) have been reported to have elevated levels of 'intact' in comparison with 'whole molecule' PTH. METHODS: PTH concentrations were assessed in serum samples obtained from female renal transplant recipients previously classified as either having hyperparathyroid (n = 14) or adynamic bone disease (n = 14) by transiliac crest bone biopsy. PTH was measured as 'whole molecule' (Scantibodies 'whole molecule' PTH) and 'intact' (DPC Immulite 2000 intact PTH and Scantibodies total PTH). RESULTS: Scantibodies 'whole molecule' PTH (all-subject mean 48.7 ng/L, +/- 53.0) were significantly lower than DPC intact (83.5 ng/L, +/- 88.1; P < or = 0.0001) and Scantibodies total PTH (80.5 ng/L, +/- 92.4; P < or = 0.0001). However, the differences between the 'whole molecule' and 'intact' measurements were similar across the two patient groups, and reflected the lower reference range employed by the 'whole molecule' assay. CONCLUSION: The 'whole molecule' PTH assay was unable to discriminate between the two patient populations and provided very little additional clinical information to that obtained from the intact PTH assays.