Guanidino compound metabolism in rats subjected to 20% to 90% nephrectomy

In mammalian kidney, the proximal convoluted tubule (PCT) is the main site of arginine (Arg) production. Arginine can be used in the biosynthesis of guanidino compounds (GC). Since uremic rats have a lower functional mass of PCT, GC synthesis might be modified, especially that of guanidinoacetic acid (GAA) which occurs in PCT. In order to study GC metabolism at different steps of uremia, rats were subjected to either 42% or 80% nephrectomy (NX); the experiment lasted for three weeks. Results show that: (1) in plasma, the pattern of GC levels in 42% NX rats was similar to that of controls except for a clear increase of beta-guanidinopropionic acid (beta-GPA), whereas in 80% NX rats, all GC levels sharply increased except that of creatine which decreased. (2) Urinary excretion of GC in control and 42% NX rats is quite similar except for GAA which strongly decreased, and for homoarginine (HArg) and argininic acid (ArgA) which increased. In rats with 80% NX, the principal modification in GC excretion was a four- to five-fold reduction in GAA output. (3) After induction of renal failure, Arg, creatine and guanidinosuccinic acid reabsorption remained unchanged, and that of HArg decreased. For guanidine and methylguanidine the negative renal balance remained unchanged, and that of gamma-guanidinobutyric acid, GAA and alpha-keto-delta-guanidinovaleric acid became smaller, suggesting a better reabsorption. In conclusion, uremia strongly modified GC metabolism involving mainly those synthesized from Arg; both GAA and creatine synthesis were strongly decreased probably because of the loss of renal tissue, mainly PCT.