Adiponectin predicts cardiovascular events in diabetes dialysis patients.

OBJECTIVES: Adiponectin is an insulin-sensitizing, anti-inflammatory adipokine with anti-atherogenic actions in the general population. In dialysis patients it is unclear whether adiponectin conserves its protective value or is, on the contrary, associated to worse prognosis. We assessed the predictive value of adiponectin for atherosclerosis related cardiovascular events in type 2 diabetic dialysis patients. DESIGN AND METHODS: Prevalent diabetic dialysis patients from three dialysis units (n=77) were enrolled in a 3years' prospective observational study. Serum adiponectin, clinical and laboratory parameters were determined at baseline; new occurrence of atherosclerosis related events (coronary events, atherosclerosis obliterans, and stroke) was recorded. RESULTS: Baseline adiponectin was 17.25(9.53-31.97) µg/mL and significantly correlated to HDL cholesterol (r=0.29, p=0.01), triglycerides (r=-0.40, p=0.0004), ferritin (r=-0.29, p=0.02), transferrin (r=-0.28, p=0.02), and uric acid (r=-0.24, p=0.04). In multivariate analysis association to triglycerides (p=0.001), HDL cholesterol (p=0.01) and ferritin (p=0.04) remained significant. 36 new fatal and non-fatal new cardiovascular events occurred, 29 patient died. Cox proportional regression analysis showed that adiponectin below or above a ROC-derived cut-off of 27.33µg/mL significantly influenced event-free survival: hazard ratio (HR) 2.48, 95% confidence interval (CI) (1.09-5.66), p=0.031 along with fasting glucose HR 1.01, 95%CI(1.00-1.02), p=0.01 and history of cardiovascular events at inclusion HR 3.16, 95%CI(1.36-7.32), p=0.007. In multivariate analysis baseline adiponectin HR 5.02, 95%CI(0.98-25.06), p=0.05 and glycemia HR 1.01, 95%CI(1.00-1.02), p=0.01 influenced event-free survival. Adiponectin also predicted cardiovascular events in patients without cardiovascular disease at inclusion but was not associated to overall mortality. CONCLUSIONS: In diabetes dialysis patients low adiponectin favors occurrence of atherosclerosis related cardiovascular events.

Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L-arginine and antioxidants.

AIM: Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. METHODS: Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. Nomega-nitro-l-arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). RESULTS: Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 +/- 4 vs. 33 +/- 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 +/- 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. CONCLUSION: Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation.