Haptoglobin phenotype as a predictive factor of mortality in diabetic haemodialysis patients.

INTRODUCTION: The mortality rate in diabetic dialysis patients (DDPs) is over 15% per year, with the cause of death most often attributed to cardiovascular disease (CVD) or bacterial infection (sepsis). Identification of genetic markers predictive of early mortality would be useful in the evaluation of therapies for the reduction of mortality rate in this population. Haptoglobin (Hp) is a polymorphic protein which appears to confer differential susceptibility to bacterial infection and CVD. We therefore proposed that Hp phenotype can predict mortality in DDPs. METHODS: We tested this hypothesis prospectively in a longitudinal study of 392 dialysis patients from eight medical centres in Israel. Hp was determined by polyacrylamide gel electrophoresis. Patients were followed for all-cause mortality over a 3-year period. RESULTS: We found that Hp phenotype was a significant predictor of mortality in DDPs stratified by age. In diabetic individuals over 60 years of age there was a decrease in mortality associated with the Hp 1-1 phenotype (P = 0.03). However, in younger DDPs the Hp 2-2 phenotype was associated with a decreased mortality rate (P = 0.003). CONCLUSION: Hp phenotype may be useful in the risk stratification algorithm and management of DDPs.

Role of haptoglobin phenotype in end-stage kidney disease.

BACKGROUND: We recently reported that haptoglobin (Hp) phenotype 1-1 is protective against the development of nephropathy in normal creatinine diabetics. In the present study, we sought to determine if Hp phenotype also plays a role in renal deterioration by determining Hp phenotypes in a consecutive series of patients with chronic renal failure (CRF) in hemodialysis (HD) and predialysis clinics. METHODS: Three hundred and ninety-two patients on HD for less than 2 years and 182 predialysis patients (creatinine clearance time [CCT] <35 ml/min) were subjected to Hp phenotyping. Age, gender and presence of diabetes or hypertension were recorded. Patients were stratified according to age (above and below 60 years) and severity of renal dysfunction (CRF or HD). RESULTS: We observed a markedly lower prevalence of the Hp 1-1 phenotype in HD patients under 60 years of age compared to patients with CRF or compared to the general population. This was not due to differences in the threshold for dialysis initiation among patients with different Hp types or to decreased survival of patients with Hp 1-1 prior to entering HD. In HD patients 60 years and over, Hp 1-1 prevalence was increased, as observed with other diseases in this age group. CONCLUSIONS: The prevalence of Hp 1-1 is decreased in HD patients less than 60 years of age. This may be due to a fundamental difference in the rate of renal deterioration in patients with different Hp types. In addition, Hp 1-1 may provide a protective effect against mortality in elderly patients.