A retrospective study on the influence of apolipoprotein e and serum lipids in progressive renal failure.

BACKGROUND: Progression of renal failure is associated with altered lipoprotein metabolism. Apolipoprotein E polymorphism is an important genetic marker for dyslipidemia. The main purpose of this retrospective study was to examine the influence of apolipoprotein E polymorphism and serum lipids level on the progression rate in a group of patients with kidney diseases of diverse etiology. METHODS: Progression rate, with regard to apolipoprotein E polymorphism and initial serum creatinine value, median (162 micromol/l), was determined by reviewing the charts of 385 patients on renal replacement therapy with a median follow-up time of 4.85 years. RESULTS: Progression rate was negatively correlated to serum cholesterol in the group with type 2 diabetes (p= 0.001). In addition, the urine albumin excretion rate (UAER) was higher in type 2 diabetics carrying the epsilon2 allele (2.1 g/l) as compared to non-epsilon2 allele carriers (1.2 g/l) (p=0.009). Although serum cholesterol in patients with autosomal dominant polycystic kidney disease (ADPKD) carrying the apolipoprotein epsilon4 allele was 5.87 +/- 1.0 mmol/l, which was significantly higher compared to non-epsilon4 carriers, 4.97 +/- 1.1 mmol/l (p=0.026), progression rate was similar in the two groups, 4.4 +/- 0.8 micromol/l/year. An increase in the relative frequency of the apolipoprotein epsilon4 allele was found in patients with ADPKD (0.29), as compared to (0.16) in the rest of the diagnostic groups (p=0.0023). In addition, in the whole study population a positive correlation was found between progression rate and underlying disease (p < 0.005), UAER (p < 0.005) and blood pressure (p < 0.005). CONCLUSIONS: The results of the present study indicate that the decline of renal function in patients with diabetes type 2 may not be associated with levels of plasma cholesterol, but with triglyceride lipoproteins, considered remnant lipoproteins. Any association between cholesterol and apolipoprotein epsilon4 allele with progression in ADPKD may not necessarily be straightforward since this disease is influenced by other genetic and unidentified factors.

Apolipoprotein E polymorphism in 385 patients on renal replacement therapy in Sweden.

OBJECTIVE: To examine apolipoprotein (apo) E polymorphism and its possible link to kidney disease in all patients receiving renal replacement therapy in our region. MATERIAL AND METHODS: The apo E genotype, plasma (P) lipids, blood pressure and albumin excretion rate were determined retrospectively in 385 patients. RESULTS: No differences in apo E genotype or the allelic frequencies of epsilon2, epsilon3 or epsilon4 were found between the patient group and a control group of 343 healthy individuals. The apo E3/E4 genotype, however, was found in only 1/24 patients with non-insulin-dependent diabetes mellitus (NIDDM), a significantly lower frequency than that seen in the rest of the patient group (p = 0.041). Similarly, the apo E4/E4 genotype was absent in patients with glomerulonephritis (GN) (p = 0.027). The relative frequency of the epsilon4 allele in patients with GN (0.116) was significantly lower than that in the rest of the patients (0.193; p < 0.05) and that in the control group (0.186; p = 0.027). Furthermore, 19/47 patients (40.4%) with autosomal dominant polycystic kidney disease (ADPKD) had the E3/E4 genotype, as compared to 77/338 (22.8%) in the rest of the patient group (p = 0.035; odds ratio 2.07; CI 1.09-3.92). An increase in the relative frequency of the epsilon4 allele was seen in the same diagnostic group: 0.29 vs 0.16 in the rest of the patient group (p = 0.0023). The mean P-cholesterol level in patients with the epsilon4 allele was 5.9 +/- 1.0 mmol/l, compared to 5.0 +/- 1.1 mmol/l in patients without the epsilon4 allele (p = 0.026). CONCLUSIONS: In this study, variations in the frequencies of the apo epsilon4 allele and the apo E3/E4 and E4/E4 genotypes were found in patients with NIDDM, GN and ADPKD. This result may be a consequence of the effects of the apo epsilon4 and epsilon2 alleles on P-cholesterol and remnant lipoprotein levels. The decreased frequency of apo E3/E4 found in patients with NIDDM may be explained by the fact that the epsilon4 allele gives renoprotection against diabetic nephropathy by lowering plasma remnant lipoprotein levels. Conversely, there may be an association between the apo E3/E4 genotype and the epsilon4 allele in patients with ADPKD, due to the effect of the epsilon4 allele in elevating P-cholesterol levels. The most plausible explanation for the absence of the apo E4/E4 genotype and the lower prevalence of the epsilon4 allele in patients with GN, which is known to result in a higher P-cholesterol compared to the epsilon2 and epsilon3 alleles, ought to be an increase in cardiovascular morbidity, which is known to be associated with a higher P-cholesterol level.