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.
These results support a direct linkage between diabetic vascular disease and the Hp genotype. These Hp-modified mice may serve as a platform on which to test a variety of pharmacological agents in order to decrease diabetic vascular disease.
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