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Summary.: Nephrectomy in mice provokes a decrease in creatinine clearance (CTNCl) and an increase in urea and specific guanidino compound (GC) concentrations in blood and other tissues. Our purpose was to investigate the influence of high protein diet (HPD) on CTNCl, urea and GC levels in NX mice. Mice were nephrectomized or sham-operated and subdivided in groups to study five diet conditions. At the end of each experiment, 10 days and 30 days postsurgery, urine and blood were collected for determination of urea and GCs, including creatinine. HPD resulted in significantly higher CTNCl values in sham-operated mice than those observed in mice under normal protein diet, 10 days as well as 30 days postnephrectomy. HPD induced significant increases in plasma urea, guanidinosuccinic acid, argininic acid and α-keto-δ-guanidinovaleric acid concentration 10 days postsurgery but not 30 days postsurgery. HPD coincided with significantly higher excretion of urea, guanidinosuccinic acid, α-keto-δ-guanidinovaleric acid, creatine, argininic acid and γ-guanidinobutyric acid in sham-operated and nephrectomized mice 10 days postsurgery. Our results show that HPD induces supplementary (to nephrectomy) increases of urea and GCs in the early postsurgery period but not in the later phase.

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.

Summary.: 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.

Partially nephrectomized (NX) and sham-operated mice were biochemically and behaviourally compared, 10 days, 1 month and 1 year post-surgery. Plasma urea and creatinine concentrations were mildly increased in all NX groups, but creatinine clearance was significantly decreased, 10 days post-surgery only. NX mice showed lower body weights and reduced growth. Wire suspension and rotarod indicated unaffected motor functions, but NX mice did show reduced ambulation and swimming velocity, 10 days post-surgery. Hidden-platform water maze indicated a spatial learning impairment in NX mice, 10 days post-surgery, which could not be entirely reduced to motor incapacity. The acute behavioural deficits in these mildly uremic mice may relate to analogous symptoms in uraernic encephalopathy, a poorly understood brain syndrome occurring in uraernic patients.