Influence of 72% injury in one kidney on several organs involved in guanidino compound metabolism: a time course study

Arginine (Ara) produced from citrulline originates mostly from kidneys. Arc , is involved in guanidino compound biosynthesis, which requires interorgan co-operation. In renal insufficiency, citrulline accumulates in the plasma in proportion to renal damage. Thus, disturbances in Ara and guanidino com pound metabolism are expected in several tissues. An original use of the mo del of nephrectomy based on ligating branches of the renal artery allowed u s to investigate Ara and guanidino compound metabolism simultaneously in in jured (left) and healthy (right) kidneys. The left kidney of adult rats was subjected to 72% nephrectomy. Nonoperated, sham-operated and nephrectomize d rats were studied for a period of 21 days. Constant renal growth was obse rved only in the healthy kidneys. Guanidino compound levels were modified t ransiently during the first 48 h. The metabolism and/or tissue content of s everal guanidino compounds were disturbed throughout the experimental perio d. Ara synthesis was greatly reduced in the injured kidney, while it increa sed in the healthy kidney. The renal production of guanidinoacetic acid dec reased in the injured kidney and its urinary excretion was reduced. The exp erimentally proven toxins alpha -keto-delta -gruanidinovaleric acid and gua nidinosuccinic acid (GSA) accumulated only in the injured kidney. The urina ry excretion of GSA and methylguanidine increased in nephrectomized rats. W hen the injured kidney grew again, the level of some guanidino compounds te nded to normalize. Nephrectomy affected the guanidino compound levels and m etabolism in muscles and liver. In conclusion, the specific accumulation of toxic guanidino compounds in the injured kidney reflects disturbances in r enal metabolism and function. The healthy kidney compensates for the injure d kidney's loss of metabolic functions (e.g. Arg: production). This model i s excellent for investigating renal metabolism when a disease destroys a li mited area in one kidney, as is observed in patients.