Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis

<p>Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 ± 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 ± 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.</p

Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort

Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 −5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P =.0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 −5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 −7 ; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens

Additional file 1: Table S1. of Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis

Assessment of bias. Table S2. Baseline characteristics for individual study groups. Table S3. Comparison of baseline data in meta-analyses. Table S4. Events reported in trials analysed CVA- cerebrovascular accident; MI- myocardial infarction; CABG- coronary artery bypass graft. Figure S1. Plot of percentage reduction in proteinuria/albuminuria (any measure) SBP (mmHg) at final visit across all studies. Each study is represented by a single circle, scaled to number of participants in the study. Figure S2. Effect of addition of MRA on all-cause mortality in RRT studies. Figure S3. Funnel plot (pseudo 95 % confidence limits) showing no evidence of publication bias for GFR (Egger test p = 0.89). Figure S4. Funnel plot (pseudo 95 % confidence limits) showing no evidence of publication bias for hyperkalaemia (Egger test p = 0.81). Appendix 1. Search strategy. Appendix 2. Sample data extraction form. (DOCX 192 kb