Endogenous plasma erythropoietin, cardiovascular mortality and all-cause mortality in renal transplant recipients.

Cardiovascular disease (CVD) is the main cause of mortality in renal transplant recipients (RTR). Classical factors only partly explain the excess risk. We hypothesized that high EPO--a marker for inflammation, angiogenesis and hypoxia--is associated with CVD in RTR. A total of 568 RTR (51±12 years; 45% female; creatinine clearance (CrCl) 57±20 mL/min/1.73 m(2)) were included at median 6 [IQR 3-11] years after transplantation. Subjects on exogenous EPO and ferritin-depleted subjects were excluded. Median EPO level was 17.3 [IQR 11.9-24.2] IU/L. Gender-stratified tertiles of age-corrected EPO were positively associated with waist circumference (but not BMI), CVD history, time since transplantation, diuretics, azathioprine, CRP, mean corpuscular volume and triglyceride levels, and inversely with CrCl, RAAS-inhibition, cyclosporine, hemoglobin, total- and HDL-cholesterol. During follow-up for 7 [6-7] years, 121 RTR (21%) died, 64 of cardiovascular (CV) causes. Higher EPO (per 10 IU/L) was associated with total (HR1.16 [1.04-1.29], p = 0.01) and CV mortality (HR1.22 [1.06-1.40], p = 0.005), independent of age, gender, hemoglobin, inflammation, renal function and Framingham risk factors. Thus, EPO and mortality are linked in RTR, independent of potential confounders. This suggests that yet other mechanisms are involved. Dissecting determinants of EPO in RTR may improve understanding of mechanisms behind excess CV risk in this population.

Markers of the hepatic component of the metabolic syndrome as predictors of mortality in renal transplant recipients.

Cardiovascular disease (CVD) is a leading cause of mortality in renal transplant recipients (RTRs). Metabolic syndrome (MS) is highly prevalent in RTRs. Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of MS. We investigated associations of NAFLD markers with MS and mortality. RTRs were investigated between 2001 and 2003. NAFLD markers, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were measured. Bone and nonbone fractions of AP were also determined. Death was recorded until August 2007. Six hundred and two RTRs were studied (age 52+/-12 years, 55% men). At baseline 388 RTRs had MS. Prevalence of MS was positively associated with liver enzymes. During follow-up for 5.3[4.5-5.7] years, 95 recipients died (49 cardiovascular). In univariate Cox regression analyses, GGT (HR=1.43[1.21-1.69], p<0.001) and AP (HR=1.34[1.11-1.63], p=0.003) were associated with mortality, whereas ALT was not. Similar associations were found for cardiovascular mortality. Adjustment for potential confounders, including MS, diabetes and traditional risk factors did not materially change these associations. Results for nonbone AP mirrored that for total AP. ALT, GGT and AP are associated with MS. Of these three enzymes, GGT and AP are associated with mortality, independent of MS. These findings suggest that GGT and AP are independently related to mortality in RTRs.