Epidemiology of chronic kidney disease in children

In the past 30 years there have been major improvements in the care of children with chronic kidney disease (CKD). However, most of the available epidemiological data stem from end-stage renal disease (ESRD) registries and information on the earlier stages of pediatric CKD is still limited. The median reported incidence of renal replacement therapy (RRT) in children aged 0–19 years across the world in 2008 was 9 per million of the age-related population (4–18 years). The prevalence of RRT in 2008 ranged from 18 to 100 per million of the age-related population. Congenital disorders, including congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies, are responsible for about two thirds of all cases of CKD in developed countries, while acquired causes predominate in developing countries. Children with congenital disorders experience a slower progression of CKD than those with glomerulonephritis, resulting in a lower proportion of CAKUT in the ESRD population compared with less advanced stages of CKD. Most children with ESRD start on dialysis and then receive a transplant. While the survival rate of children with ERSD has improved, it remains about 30 times lower than that of healthy peers. Children now mainly die of cardiovascular causes and infection rather than from renal failure

High Hemoglobin A1c levels and glycemic variability increase risk of severe hypoglycemia in diabetic hemodialysis patients

While hyperglycemia is central to the pathogenesis and management of diabetes mellitus, hypoglycemia and glucose variability also contribute to outcomes. We previously reported on the relationship of glycemic control to outcomes in a large population of diabetic end-stage renal disease (ESRD) patients. Recognizing that ESRD is a risk factor for severe hypoglycemia, we have now analyzed the association between glycosylated hemoglobin A1c (HgbA1c) levels and glycemic variability in those with hypoglycemia. This is a retrospective study of patients with diabetes enrolled in a large hemodialysis program. Hypoglycemia was identified from hospital discharge diagnostic codes. Glycemic variability was assessed by the standard deviation of HgbA1c and glucose levels over time. Hypoglycemia as a discharge diagnosis was documented in 4.1% of patients. Higher baseline HgbA1c was associated with greater risk for hypoglycemia hospitalization, a finding confirmed by time-lagged HgbA1c levels drawn a quarter earlier. Higher baseline HgbA1c categories were also associated with greater variability in HgbA1c levels during the analysis period. Similarly, greater glucose variability was associated with higher mean glucose levels by trend analysis. High, not low, HgbA1c levels are associated with greater risk of severe hypoglycemia, which may derive from glucose variability in the setting of treatment for hyperglycemia. High HgbA1c and glycemic variability are associated with increased risk of hypoglycemia in individuals with diabetes and ESRD

Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress

BACKGROUND: Coenzyme Q(10) (CoQ(10)) supplementation improves mitochondrial coupling of respiration to oxidative phosphorylation, decreases superoxide production in endothelial cells, and may improve functional cardiac capacity in patients with congestive heart failure. There are no studies evaluating the safety, tolerability and efficacy of varying doses of CoQ(10) in chronic hemodialysis patients, a population subject to increased oxidative stress. METHODS: We performed a dose escalation study to test the hypothesis that CoQ(10) therapy is safe, well-tolerated, and improves biomarkers of oxidative stress in patients receiving hemodialysis therapy. Plasma concentrations of F(2)-isoprostanes and isofurans were measured to assess systemic oxidative stress and plasma CoQ(10) concentrations were measured to determine dose, concentration and response relationships. RESULTS: Fifteen of the 20 subjects completed the entire dose escalation sequence. Mean CoQ(10) levels increased in a linear fashion from 704 ± 286 ng/mL at baseline to 4033 ± 1637 ng/mL, and plasma isofuran concentrations decreased from 141 ± 67.5 pg/mL at baseline to 72.2 ± 37.5 pg/mL at the completion of the study (P = 0.003 vs. baseline and P < 0.001 for the effect of dose escalation on isofurans). Plasma F(2)-isoprostane concentrations did not change during the study. CONCLUSIONS: CoQ(10) supplementation at doses as high as 1800 mg per day was safe in all subjects and well-tolerated in most. Short-term daily CoQ(10) supplementation decreased plasma isofuran concentrations in a dose dependent manner. CoQ(10) supplementation may improve mitochondrial function and decrease oxidative stress in patients receiving hemodialysis. TRIAL REGISTRATION: This clinical trial was registered on clinicaltrials.gov [NCT00908297] on May 21, 2009