Effect of membrane flux and dialyzer biocompatibility on survival in end-stage diabetic nephropathy.

AIMS: We examined the effects of dialyzer membrane flux and biocompatibility on mortality in diabetic dialysis patients. METHODS: We enrolled 402 prevalent chronic hemodialysis patients from 30 centers in Germany in 1999 for a prospective observational study until 2003. We compared 2 groups in post hoc analysis: high-flux (HF, n = 166) versus low-flux (LF, n = 236) membrane, and high biocompatibility (HB, n = 300) versus low biocompatibility (LB, n = 102). All-cause mortality (ACM) was the primary endpoint. Death causes were the secondary endpoints. RESULTS: Multivariate Cox regression analysis showed no significant difference in risk for ACM with respect to flux (hazard ratio, HR, 0.79; p = 0.08; ACM 63% in HF vs. 70% in LF dialysis) and biocompatibility level (HR 1.00; p = 0.98; ACM 67% for HB vs. 66% for LB). The multivariate analysis of different causes of death did not reveal any outcome differences dependent on flux and biocompatibility level apart from a slightly better cumulative survival regarding the death cause 'infectious' in our HF dialysis group (HR 0.48; p = 0.07, Kaplan-Meier analysis p = 0.03). CONCLUSION: Our data indicate that mortality of hemodialysis patients with type-2 diabetic nephropathy is influenced neither by dialyzer flux level nor by biocompatibility.

Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy.

BACKGROUND: The MTHFR C677T single nucleotide polymorphism TT genotype is associated with increased levels of plasma homocysteine and possibly an effect on cardiovascular mortality. We evaluated the effect of C677T genotype on mortality in a large end-stage renal disease (ESRD) cohort. METHODS: C677T genotype was determined in 439 Caucasians with end-stage diabetic nephropathy (DNP) (cases) recruited from 30 dialysis centres in Southern Germany. A total of 482 type 2 diabetes patients without DNP (no microalbuminuria) at inclusion served as a genotype control collective. Patients were prospectively followed for 4 years. Primary endpoint was all-cause mortality. RESULTS: In contrast to controls, the genotype distribution in cases was not in Hardy-Weinberg equilibrium (HWE, P = 0.003), due to a less than expected number of patients with the TT genotype. The requirements of HWE were met in cases with < 2 years dialysis therapy prior to study inclusion (n = 219). TT genotype was associated with a decreased body mass index (P = 0.002) and long diabetes duration in dialysis patients (P = 0.03). However, TT genotype was not associated with an increased risk of all-cause or cardiac mortality in the total dialysis collective or the subgroup. Also, we observed no association of MTHFR genotype with cardiovascular morbidity in cases or controls (P > 0.05), or with an increased rate of progression to novel microalbuminuria. CONCLUSION: MTHFR 677TT genotype was significantly underrepresented in patients with ESRD in our study, but was not associated with premature mortality in these patients. We found no evidence for survival bias due to C677T genotype in the ESRD cohort, or bias due to genetically determined accelerated progression to novel microalbuminuria in the controls. However, we cannot exclude that the TT genotype protects from progression from microalbuminuria to more advanced stages of DNP, or that TT genotype is associated with premature mortality before a patient progresses to ESRD.