Myeloperoxidase and the Risk of CKD Progression, Cardiovascular Disease, and Death in the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Myeloperoxidase (MPO) catalyzes the formation of reactive nitrogen species and levels are elevated in patients with chronic kidney disease (CKD). Although increased oxidative stress and inflammation are associated with progression of CKD and cardiovascular disease (CVD), relationships between MPO concentration, CKD progression, CVD, and death remain unclear. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 3,872 participants from the Chronic Renal Insufficiency Cohort (CRIC) who had MPO measured at baseline. EXPOSURE: Baseline MPO concentration. OUTCOMES: CKD progression (kidney transplantation, dialysis initiation, or 50% decline in baseline estimated glomerular filtration rate [eGFR] and eGFR≤15mL/min/1.73m2), CVD (heart failure, myocardial infarction, or stroke), and death. ANALYTICAL APPROACH: Cox proportional hazards models. RESULTS: In adjusted analyses, higher MPO level (per 1-SD increase in log-transformed MPO) was associated with 10% higher risk for CKD progression (adjusted HR, 1.10; 95% CI, 1.01-1.19; P=0.03), 12% higher risk for CVD (adjusted HR, 1.12; 95% CI, 1.03-1.22; P<0.01), and 13% increased risk for death (adjusted HR, 1.13; 95% CI, 1.04-1.22; P<0.01). There was evidence for effect modification of the association of MPO level with CKD progression by baseline eGFR (P interaction=0.02), but not for CVD (P interaction=0.2) or death (P interaction=0.1). In stratified analyses, MPO level (per 1-SD increase in log-transformed MPO) was associated with greater risk for CKD progression among participants with eGFR>45mL/min/1.73m2 (adjusted HR, 1.23; 95% CI, 1.03-1.46; P=0.02) compared with those with eGFR≤45mL/min/1.73m2 (adjusted HR, 1.10; 95% CI, 1.02-1.20; P=0.02). The association of MPO level with CVD and death was no longer significant after adjustment for cardiac biomarkers. LIMITATIONS: Potential residual confounding, lack of repeated measurements of MPO. CONCLUSIONS: Higher MPO level was associated with increased risk for CKD progression, but not with CVD and death in patients with CKD from CRIC. Whether therapies aimed at reducing MPO activity can result in improved clinical outcomes is yet to be determined.

Ultrafiltration rate adjusted to body weight and mortality in hemodialysis patients.

BACKGROUND AND AIMS: Mortality among hemodialysis patients remains high. An elevated ultrafiltration rate adjusted by weight (UFR/W) has been associated with hypotension and higher risk of death and/or cardiovascular events. METHODS: We evaluated the association between UFR/W and mortality in 215 hemodialysis patients. The mean follow-up was 28 ±â€¯6.12 months. We collected patients' baseline characteristics and mean UFR/W throughout the follow-up. RESULTS: Mean UFR/W was 9.0 ±â€¯2,4 and tertiles 7.1 y 10.1 mL/kg/h. We divided our population according to the percentage of sessions with UFR/W above the limits described in the literature associated with increased mortality (10.0 ml/kg/h and 13.0 mL/kg/h). Patients with higher UFR/W were younger, with higher interdialytic weight gain and weight reduction percentage but lower dry, pre and post dialysis weight. Throughout the follow-up, 46 (21.4%) patients died, the majority over 70 years old, diabetic or with cardiovascular disease. There were neither differences regarding mortality between groups nor differences in UFR/W among patients who died and those who did not. Contrary to previous studies, we did not find an association between UFR/W and mortality, maybe due to a higher prevalence in the use of cardiovascular protection drugs and lower UFR/W. CONCLUSIONS: The highest UFR/W were observed in younger patients with lower weight and were not associated with an increased mortality.