Chronic renal failure is frequently accompanied by elevated plasma levels of lipoprotein (a) [Lp(a)]. Elevated Lp(a) levels have been proposed to contribute not only to increased risk of atherosclerotic and thrombotic complications but also to the progression of renal insufficiency. To investigate whether higher Lp(a) plasma concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of Lp(a) with the progressive decline of renal function in an observational study of human chronic renal disease. Forty-nine non-diabetic patients (40 men, nine women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.1 years, and the mean rate of decline in glomerular filtration rate (51Cr-EDTA clearance) was -2.8 (SD 4.1) ml/min/1.73 m2. The mean plasma concentration of Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100 ml with a median value of 12.2 mg/100 ml. There was no association between the initial plasma concentration of Lp(a) and the rate of progression as assessed by linear regression analysis. Furthermore, the progression rate in patients within the highest quartile of the Lp(a) distribution (> or = 30 mg/100 ml) did not differ from that in patients with lower levels of Lp(a). In contrast, increased levels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Based on these results, it was concluded that elevated plasma levels of Lp(a) are not associated with an increased rate of progression of renal insufficiency in human chronic renal disease. However, the results of this study suggest that other apoB-containing lipoproteins may play a significant role in this process.