A SIMULTANEOUS STUDY OF THE METABOLISM OF APOLIPOPROTEIN-B AND ALBUMIN IN NEPHROTIC PATIENTS

Background. The nephrotic syndrome is characterized by proteinuria, hy poalbuminemia and hyperlipidemia. Despite intensive research it is not clear at present what the causal links are between these pathological findings. Methods. Stable isotope labeled amino acid tracer kinetic a nalysis was used to simultaneously investigate the metabolism of four apolipoprotein B-containing lipoproteins (VLDL1, VLDL2, LDL and LDL) a nd albumin in seven patients with nephrotic syndrome and marked hyperc holesterolemia, in two additional nephrotic; patients with concomitant renal failure and mixed hyperlipidemia, and in a matched group of nor molipidemic controls. Results. Increased concentrations of VLDL2, IDL and LDL were due to (a) impaired VLDL2 and IDL delipidation, (b) reduc ed LDL catabolism, and (c) a trend towards an increased rate of total apolipoprotein B production. The rate of fractional albumin eliminatio n was three times higher in patients than in controls and the rate of albumin synthesis was increased by 45%. No correlations were detectabl e between rates of apolipoprotein B production and the rate of albumin synthesis. Conclusions. The results of this study suggest that hyperl ipidemia in nephrotic syndrome is predominantly the result of delayed lipoprotein delipidation and catabolism. There is no evidence that it is driven by a general increase of the rate of hepatic protein synthes is.