Tryptophan distribution and metabolism in experimental chronic renal insufficiency

Several aspects of tryptophan distribution and metabolism in chronic renal insufficiency (CRI) were investigated in a rat model prepared by partial nephrectomy. Partially nephrectomized (pNx) rats with a moderate degree of CRI demonstrated a 40% decrease in plasma total tryptophan concentration between 5 and 11 weeks after the acute reduction of renal functional mass. This decrease was accompanied by hypoalbuminemia, polyuria, albuminuria, and tryptophanuria. After 5 weeks of sustained plasma total tryptophan deficiency (from Week 6 to Week 11), the plasma free tryptophan concentration, the plasma concentrations of large neutral amino acids, and the tryptophan levels in red cells, liver, and kidney of the pNx rats were similar to those of the controls. However, evidence for abnormal brain tryptophan metabolism in pNx rats after 11 weeks of CRI included 16% reductions of tryptophan levels in the midbrain and pons and 65% increases in the serotonin contents of the hypothalamus and medulla. Monoamine oxidase activities in hypothalamus and cerebellum of pNx rats were the same as those of the controls. These studies indicate that tryptophanuria is an important factor in the development of the plasma tryptophan deficiency in the pNx model. In addition, the results support the hypothesis that regional abnormalities in tryptophan metabolism contribute to the neurological and neuroendocrine dysfunction of CRI.