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The long-term adverse consequences of early renal mass reduction in mice have not yet been investigated. The effects of partial surgical nephrectomy (NX) in 2-month-old mice on some biological parameters, on histopathologic and morphometric features of the kidney, and on urea and guanidino compound (GC) levels in plasma, urine, and brain were examined at 10 days, and 1, 2, 4, and 12 months postsurgery. Body weight, urinary volume, and plasma urea were most affected at 10 days and 12 months post-NX. NX-induced changes in the remaining renal tissue (including hypertrophy, glomerular mesangial expansion, and presence of protein casts) increased with age. As in human renal insufficiency, NX mice showed significantly higher plasma guanidinosuccinic acid (GSA) and creatinine (CTN) levels at all studied periods. The same tendency could be seen for most other plasma GCs examined, except for arginine (Arg), guanidinoacetic acid (GAA), and homoarginine (HA). As seen in human pathobiochemistry, the latter 2 compounds tended to be lower in NX mice in our follow-up study. Remarkably, and also similar to humans, NX mice excreted less GAA and more GSA than controls during the entire follow-up study. During the follow-up, excretion levels of GAA were unchanged in NX and sham-operated mice. In brain, GAA and gamma-guanidinobutyric acid (GBA) levels were always higher in NX mice with a tendency to respectively increase or decrease over time in NX as well as sham-operated mice. Although urea and GC metabolism were influenced by time post-NX and aging, the model was confirmed to display a mild stable chronic impairment of renal function. Histopathologic and morphometric changes of the kidney increased with age., (Copyright 2001 by W.B. Saunders Company)

Background: This study investigates the effect of nephrectomy in young and aged mice on some biochemical, histological and behavioural aspects., Methods: Each age group, 2- and 12-months-old, comprised a sham-operated group, a unilaterally nephrectomized group and a subtotally nephrectomized group. Consequences of nephrectomy were examined 10 days postsurgery on urea and guanidino compound levels in body fluids and brain; the remaining kidney by light-microscopic examination; and learning and memory abilities using the Morris water maze task., Results: Effect of nephrectomy on urea and guanidino compound levels in plasma, urine and brain was significantly more pronounced in the young age group. Some guanidino compounds show a tendency to decrease with aging in the sham-operated group and the two nephrectomized groups. Higher compensatory kidney hypertrophy was found in younger nephrectomized mice whereas in older mice glomerular mesangial expansion was a common feature. Finally, young mice with subtotal nephrectomy displayed a slight but significant impairment in memory and learning; whilst old nephrectomized mice manifested no impairment., Conclusions: Nephrectomy induces more changes in younger mice than in older mice as observed in higher variation of urea and guanidino compound levels, glomerular volume and kidney hypertrophy and decline in spatial learning and memory., (Copyright 2001 S. Karger AG, Basel)

Arginine (Arg) produced from citrulline originates mostly from kidneys. Arg 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 Arg and guanidino compound metabolism are expected in several tissues. An original use of the model of nephrectomy based on ligating branches of the renal artery allowed us to investigate Arg and guanidino compound metabolism simultaneously in injured (left) and healthy (right) kidneys. The left kidney of adult rats was subjected to 72% nephrectomy. Non-operated, sham-operated and nephrectomized rats were studied for a period of 21 days. Constant renal growth was observed only in the healthy kidneys. Guanidino compound levels were modified transiently during the first 48 h. The metabolism and/or tissue content of several guanidino compounds were disturbed throughout the experimental period. Arg synthesis was greatly reduced in the injured kidney, while it increased in the healthy kidney. The renal production of guanidinoacetic acid decreased in the injured kidney and its urinary excretion was reduced. The experimentally proven toxins alpha-keto-delta-guanidinovaleric acid and guanidinosuccinic acid (GSA) accumulated only in the injured kidney. The urinary excretion of GSA and methylguanidine increased in nephrectomized rats. When the injured kidney grew again, the level of some guanidino compounds tended to normalize. Nephrectomy affected the guanidino compound levels and metabolism in muscles and liver. In conclusion, the specific accumulation of toxic guanidino compounds in the injured kidney reflects disturbances in renal metabolism and function. The healthy kidney compensates for the injured kidney's loss of metabolic functions (e.g. Arg: production). This model is excellent for investigating renal metabolism when a disease destroys a limited area in one kidney, as is observed in patients.

Amino acid and biogenic amine changes were investigated in nephrectomized mice ten days postsurgery. Uremic mice exhibited changes in amino acid concentrations in plasma, urine and brain. Particularly plasma methionine, citrulline and arginine levels were significantly enhanced in nephrectomized mice compared to controls whereas serine was decreased. Urinary excretion of methionine, citrulline and alanine was higher in nephrectomized mice compared to controls whereas many amino acids were increased in brain of nephrectomized mice. Brain and urinary amino acid changes were more pronounced in the 75% than in the 50% nephrectomized mice. Brain norepinephrine and dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly increased whereas serotonin was decreased comparing the 75% nephrectomized mice to the sham-operated mice. This study demonstrates that at very early stages of renal insufficiency, specific amino acid and biogenic amine changes occur in plasma, urine and brain. These alterations might depend qualitatively and quantitatively on the degree of functional renal mass reduction.