Areal and volumetric bone mineral density changes after renal transplantation in children: a longitudinal study.

INTRODUCTION: The effect of renal transplantation on areal bone mineral density (aBMD) in children has previously been studied. However, most previous reports did not include estimation of volumetric bone mineral density (vBMD) or analyze longitudinal data in these patients. In addition, updated reference standards for aBMD in children have recently been made available. METHODS: This retrospective study describes the longitudinal effect of renal transplantation on aBMD and vBMD in a cohort of 40 pediatric kidney transplant recipients. Lumbar spine aBMD measurements were obtained using dual-energy X-ray absorptiometry prior to transplant and yearly thereafter. vBMD values and z-scores were estimated as described in the most recently published references. RESULTS: A significant decrease in average aBMD and vBMD z-scores was observed within 1 year posttransplant, which did not recover during follow-up. The negative effect of transplantation on vBMD was blunted and vBMD z-scores were higher compared to aBMD. Linear mixed-effects model analysis demonstrated that lumbar spine aBMD and vBMD z-scores were inversely related to yearly prednisone dose (g/m2) but this effect was diminished as glomerular filtration rate was increased. CONCLUSIONS: Bone mineral density was negatively affected by renal transplantation in this cohort of pediatric patients. Estimation of vBMD appears to be appropriate for interpretation of the BMD changes occurring after renal transplant in children. The inverse relation between BMD z-scores and yearly prednisone dose suggests that ongoing posttransplant corticosteroid therapy may be responsible for the negative effect of transplantation on bone mineral density in this cohort.

Statistical issues in a metaregression analysis of randomized trials: impact on the dietary sodium intake and blood pressure relationship.

In a meta-analysis of randomized trials of the effects of dietary sodium interventions on blood pressure, we found substantial heterogeneity among the studies. We were interested in evaluating whether measurement error, known to be a problem for dietary sodium measures, publication bias, or confounding factors could be responsible for the heterogeneity. A measurement error correction was developed that corrects both the slope and the intercept and takes into account the sample size of each study and the number of measurements taken on an individual. The measurement error correction had a minimal effect on the estimates, although it performed well in simulated data. A smoothed scatter plot was used to assess publication bias. Metaregressions provide a convenient way to jointly assess the effects of several factors, but care must be taken to fit an appropriate model.

CLCN5 chloride-channel mutations in six new North American families with X-linked nephrolithiasis.

BACKGROUND: X-linked nephrolithiasis, or Dent's disease, encompasses several clinical syndromes of low molecular weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure, and is associated with mutations in the CLCN5 gene encoding a kidney-specific voltage-gated chloride channel. Some patients from Europe have rickets, and all symptomatic patients confirmed by mutation analysis have been male. METHODS: We analyzed the CLCN5 DNA sequence in six new families with this disease. RESULTS: In three probands, a single-base substitution yielded a nonsense triplet at codons 28, 34, and 343, respectively, and in two families, one of which was Hispanic, we found single-base deletions at codons 40 and 44, leading to premature termination of translation. In the sixth family, a single-base change from C to T predicted substitution of leucine for serine at codon 244, previously reported in two European families with prominent rickets, though this patient of Ashkenazi origin did not have rickets. Each of these mutations was confirmed by restriction endonuclease analysis, or repeat sequencing and CFLP. The R34X mutation occurred in a Canadian infant with severe rickets. The family with the R28X nonsense mutation included one woman with recurrent kidney stones and another woman with glomerular sclerosis. In another family, a woman heterozygous for the W343X mutation also had nephrolithiasis. CONCLUSIONS: These studies expand the range of mutations identified in this disease, and broaden the phenotypic range to include clinically affected women and the first North American case with severe rickets.

Effect of reduced dietary sodium on blood pressure: a meta-analysis of randomized controlled trials.

OBJECTIVE: - To ascertain whether restriction of dietary sodium lowers blood pressure in hypertensive and normotensive individuals. DATA SOURCES: - An English-language computerized literature search, restricted to human studies with Medical Subject Heading terms, "hypertension," "blood pressure," "vascular resistance," "sodium and dietary," "diet and sodium restricted," "sodium chloride," "clinical trial," "randomized controlled trial," and "prospective studies," was conducted. Bibliographies of review articles and personal files were also searched. TRIAL SELECTION: - Trials that had randomized allocation to control and dietary sodium intervention groups, monitored by timed sodium excretion, with outcome measures of both systolic and diastolic blood pressure were selected by blinded review of the methods section. DATA EXTRACTION: - Two observers extracted data independently, using purpose-designed forms, and discrepancies were resolved by discussion. DATA SYNTHESIS: - The 56 trials that met our inclusion criteria showed significant heterogeneity. Publication bias was also evident. The mean reduction (95% confidence interval) in daily urinary sodium excretion, a proxy measure of dietary sodium intake, was 95 mmol/d (71-119 mmol/d) in 28 trials with 1131 hypertensive subjects and 125 mmol/d (95-156 mmol/d) in 28 trials with 2374 normotensive subjects. After adjustment for measurement error of urinary sodium excretion, the decrease in blood pressure for a 100-mmol/d reduction in daily sodium excretion was 3.7 mm Hg (2.35-5.05 mm Hg) for systolic (P<.001) and 0.9 mm Hg (-0.13 to 1.85 mm Hg) for diastolic (P=.09) in the hypertensive trials, and 1.0 mm Hg (0.51-1.56 mm Hg) for systolic (P<.001) and 0.1 mm Hg (-0.32 to 0.51 mm Hg) for diastolic (P=.64) in the normotensive trials. Decreases in blood pressure were larger in trials of older hypertensive individuals and small and nonsignificant in trials of normotensive individuals whose meals were prepared and who lived outside the institutional setting. CONCLUSION: - Dietary sodium restriction for older hypertensive individuals might be considered, but the evidence in the normotensive population does not support current recommendations for universal dietary sodium restriction.