MECHANISMS OF HYPOALBUMINEMIA IN HEMODIALYSIS-PATIENTS

Hypoalbuminemia is the most powerful predictor of mortality in end-sta ge renal disease. Since protein-calorie malnutrition can decrease albu min synthesis it is assumed that hypoalbuminemia results principally f rom malnutrition in these patients, but albumin synthesis may also be decreased as part of the acute-phase response, and hypoalbuminemia can also result from redistribution of albumin pools or from albumin loss es, We measured albumin synthesis, fractional catabolic rate, and dist ribution from the turnover of [I-125] human albumin in six hemodialysi s patients with plasma albumin less than 35 mg/ml and in six patients with plasma albumin greater than 40 mg/ml. Patients with liver disease , HIV, or other infection were excluded. Both groups were maintained w ith high-flux polysulfone dialyzers for more than three months. Kt/V-u rea and PCR were measured during each dialysis (N = 12 to 18/patient). A four-day calorie and protein intake was determined by dietary histo ry and long-term nutritional status was determined anthropometrically. Measured variables included serum urea, creatinine, transferrin, and the positive acute-phase proteins alpha(2)-macroglobulin, C-reactive p rotein, ferritin, and IGF-1. Albumin synthesis was significantly reduc ed in the low albumin group. There were no differences in dietary inta ke, body composition, PCR, BUN, creatinine, or Kt/V-urea. Plasma album in concentration correlated negatively with ferritin, C-reactive prote in and alpha(2)-macroglobulin. Albumin synthesis rate correlated negat ively with both alpha(2)-macroglobulin and Kt/V-urea. Both plasma albu min concentration and synthesis rate correlated positively with IGF-1, and both were independent of PCR and all other nutrition-related vari ables. Hypoalbuminemia was due to decreased albumin synthesis. The dat a suggest that albumin concentration and synthesis were primarily dete rmined by non-nutritional factors in this well-dialyzed population, an d that both were reduced partially as part of the acute-phase response .