Long-term effects of recombinant human erythropoietin on bone marrow progenitor cells

Eleven uraemic patients were treated with recombinant humanerythropoietin (rHuEpo). Seven haemodialysis patients and fourperitoneal dialysis patients received a starting dose of 80IU/kg i.v. and 40 IU/kg s.c. respectively, thrice weekly. Thenumber of burst-forming-unit erythroid (BFU-E), colony-forming-uniterythroid (CFU-E), granulocyte-monocyte (CFU-GM) and megakaryocyte(CFU-Mk) were assayed 2 weeks before (DO), and 1 (M1) and 6months (M6) after the initiation of rHuEpo treatment by meansof a commonly applied in-vitro clonal assay. All the patientsshowed the same haematopoietic response. A significant increaseof CFU-E and CFU-Mk could be observed within 1 month of treatment.At this time, no significant modification was observed in BFU-Eand CFU-GM number. At the 6th month the increase of CFU-E wasmaintained, whereas a significant fall of BFU-E, CFU-GM andCFU-Mk was observed. These results suggest that in-vivo effects of rHuEpo are notrestricted to the erythroid lineage but that erythropoietinmight also act as a co-factor of megakar-yopoiesis. In the longterm erythropoietin might induce erythroid differentiation inmultipotent progenitor cells at the expense of the non-erythroidprogenitors.     

Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers

Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.     

Disparities in Provision of Transplant Education by Profit Status of the Dialysis Center

Kidney transplant education is associated with higher transplantation rates; however national policies regarding optimal timing and content of transplant education are lacking. We aimed to characterize nephrologists’ attitudes regarding kidney transplant education, and to compare practices between nephrologists at for-profit and nonprofit centers. We surveyed 906 nephrologist practicing in the United States. Most respondents (81%) felt the ideal time to spend on transplant education was >20 min, but only 43% reported actually doing so. Spending >20 min was associated with covering more topics, having one-on-one and repeated conversations, involving families in discussions and initiating discussions at CKD-stage 4. Providers at for-profit centers were significantly less likely to spend >20 min (RR = 0.89, 95%CI: 0.80–0.99) or involve families (RR = 0.57, 95%CI: 0.38–0.87); they reported that fewer of their patients received transplant counseling (RR = 0.58, 95%CI: 0.37–0.96), initiated transplant discussions (RR = 0.58, 95%CI: 0.38–0.88), or were eligible for transplantation (RR = 0.45, 95%CI: 0.30–0.68). Of nephrologists who spent ≤20 min, those at for-profit centers more often cited lack of reimbursement as a reason (30.0% vs. 18.9%, p = 0.02). Disparities in quality of education at for-profit centers might partially explain previously documented disparities in access to transplantation for patients at these centers. National policies detailing the optimal timing and content of transplant education are needed to improve equity.     

Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study

Background

Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD).

Methods/design

The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community.

Discussion

The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies’ impact on clinical care and patients’ outcomes.

     

Racial differences in chronic kidney disease incidence and progression among individuals with HIV

This Practice Point commentary discusses the findings of Lucas et al.'s longitudinal cohort study of chronic kidney disease (CKD) in African American and white individuals with HIV. The study found that--compared with whites--African Americans had a slightly increased risk of incident CKD, but markedly increased rates of estimated glomerular filtration rate decline and progression to end-stage renal disease. This commentary details the clinical implications and limitations of these findings in the context of known racial differences in CKD prevalence and progression to end-stage renal disease in the general population and highlights the importance of screening high-risk HIV patients for kidney disease. CKD is common among HIV patients, and-as in the general population-has a more-aggressive course among African Americans than whites.     

Novel and traditional cardiovascular risk factors for peripheral arterial disease in incident-dialysis patients

Peripheral arterial disease (PAD), which threatens limb viability and patient survival, is increasing in frequency in the dialysis population, but associated risk factors remain poorly defined. We conducted a cross-sectional analysis of the association of novel and traditional cardiovascular risk factors with PAD in incident-dialysis patients enrolled in the CHOICE study by application of multivariate logistic-regression models with adjustment for confounders. Risk factors were determined by interview, record review, and laboratory analysis of frozen specimens. Among 922 patients, 25% had a diagnosis of PAD. After adjustment, higher prevalence of PAD was associated with increasing age (odds ratio [OR], 95% CI = 1.28 [range: 1.12 to 1.48] per 10-year increase in age); presence of diabetes mellitus (OR, 95% CI = 2.76 [range: 1.72 to 4.42]); higher Index of Co-Existent Disease (ICED), ICED 2 and ICED 3 versus ICED 0-1, (OR, 95% CI = 2.04; [range: 1.24 to 3.35] and OR, 95% CI = 2.81 [range: 1.83 to 4.30], respectively). After adjustment, we found no statistically significant association between CRP and prevalence of PAD. The prevalence of PAD diagnosis was 34% higher per quartile increase in Lp(a) (OR, 95% CI = 1.34 [range: 1.13 to 1.59]). Similarly, the prevalence of PAD diagnosis was 19% higher per quartile increase in total homocysteine (OR, 95% CI = 1.19 [range: 1.05 to 1.35]). The prevalence of PAD is high in incident-dialysis patients and is associated with several novel and traditional cardiovascular risk factors. This study identifies several novel risk factors (eg, Lp(a) and total homocysteine) and underscores the need for further research to reduce the burden of PAD in this high-risk group of patients.