Mechanism of hypoalbuminemia in the 7/8-nephrectomized rat with chronic renal failure.
Hypoalbuminemia has been observed consistently in patients and experimental animals with chronic renal failure (CRF). A defect in albumin synthesis, catabolism, or distribution has been invoked as the cause, but there is no agreement as to which, if any, of these disorders results from the uremic state. We studied albumin homeostasis in 7/8-nephrectomized rats with CRF. Serum albumin concentration was lower in CRF (29.6 +/- 4.59 mg/ml) than in sham-operated control rats (36.3 +/- 4.3 mg/ml). Albumin synthesis, determined directly by measuring incorporation of 14CO2 into arginine in albumin, was increased in CRF rats as was total albumin clearance, measured using 125I-albumin disappearance. Rats with CRF were albuminuric. Albumin synthesis was increased by the amount necessary to replace urinary losses, but net albumin catabolism was the same as in control animals. Albuminuria was prevented by addition of excess tryptophan to the diet. Total albumin clearance and albumin synthesis were the same in these tryptophan-fed CRF animals as in CRF sham-operated animals, but these CRF rats were still hypoalbuminemic (33.6 +/- 5.27 vs. 36.3 +/- 4.3 mg/ml). Rats with CRF were plasma volume expanded. Institution of a low-sodium diet at the time of partial nephrectomy prevented plasma volume expansion and albuminuria as well. Serum albumin concentration, albumin distribution, pool sizes, and total albumin clearance remained the same as in CRF sham-operated animals. Hypoalbuminemia in CRF rats is due to two factors. Plasma volume expansion with pool dilution contributes 40% of the decrease and external albumin losses resulting from albuminuria contribute the other 60%. Albumin synthesis, catabolism, and distribution are intact.
D000419:Albuminuria; D000818:Animals; D001806:Blood Urea Nitrogen; D005243:Feces / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism*
D012709:Serum Albumin