Amino acid handling in uremic rats: Citrulline, a reliable marker of renal insufficiency and proximal tubular dysfunction☆

Abstract 

The kidney is involved in amino acid reabsorption and metabolism; consequently, in renal insufficiency, these important functions are disturbed, as has been reported in animals and patients. In a first experimental series, rats were subjected to degrees of nephrectomy (NX) varying between 10% and 90%. Three weeks later, amino acid levels were measured in plasma to correlate the levels with the degree of NX. The results indicate that in the range of 33% to 74% NX, the plasma concentration of only three to four amino acids was modified, whereas in rats with 84% NX, the concentration of 11 amino acids was disturbed, compared with sham-operated rats. Citrullinemia was enhanced in uremic rats and correlated with the degree of NX. More interestingly, citrullinemia was increased in the range of 10% to 33% NX without any changes in uremia and creatininemia, two well-known markers of uremic states. A second experimental series was designed to study the time course of changes in aminoacidemia to find a marker for the onset of renal failure. Rats were subjected to 36% NX for a period of 1 to 21 days. Uremia and creatininemia peaked 24 to 48 hours after NX, and creatinine clearance (CI_creat) concomitantly diminished. Unfortunately, these three markers of uremic states returned to control values during the next few days before increasing during the last 2 weeks. In contrast, citrullinemia increased twofold 48 hours after NX and plateaued over the next 20 days. We conclude that in rats, citrullinemia could be used (1) to detect acute and chronic renal failure, (2) as a specific marker of normal function of the proximal tubule, and (3) to estimate the degree of renal damage. From this study, renal insufficiency might be easily detected by measuring citrullinemia.

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