Guanidino compounds have been suggested to contribute to the complex neurological complications associated with
uremia. Several of them have previously been reported to accumulate in physiological fluids of renal insufficient subjects. We report on guanidino compound levels in 28 brain regions in control and uremic brains. In all brain regions studied, in controls as well as in uremic patients, concentrations of
alpha-keto-delta-guanidinovaleric acid, alpha-N-acetylarginine and
beta-guanidinopropionic acid remained below detection limits.
Creatine,
guanidinoacetic acid,
argininic acid,
gamma-guanidinobutyric acid,
arginine and
homoarginine were not increased in uremic patients.
Argininic acid and
homoarginine were detectable in some brain regions only.
Creatine concentrations varied from 2500 +/- 2100 nmol/g tissue in hypophysis to 10500 +/- 1200 nmol/g tissue in cerebellar cortex. Even more pronounced regional differences were found for
gamma-guanidinobutyric acid with the lowest concentration in the caudate nucleus (0.6 +/- 0.3 nmol/g tissue) and highest in substantia nigra, pallidum and cerebellar dentate nucleus (8.3 +/- 2.8 nmol/g tissue). The
guanidinosuccinic acid levels were below detection limit in controls in the majority of brain regions. Taking into account the detection limit of
guanidinosuccinic acid for a certain amount of tissue applied to the analytical system, important increases (approx. up to > 100 fold) were observed in all brain regions of uremic patients. Accumulation of
guanidinosuccinic acid increased with increasing degree of
renal failure with levels up to 65 nmol/g tissue in the hypophysis.
Creatinine concentrations were also found to be increased in uremic brain regions but increases seemed to be less strictly related to serum
urea levels.
Guanidine and
methylguanidine were found only occasionally in brain regions of controls while respectively 100- and 30-fold increases were found in brain regions of uremic subjects. Levels of
guanidinosuccinic acid and
creatinine in uremic brain were comparable to those previously observed in brain of experimental animals displaying convulsions following
intraperitoneal injection of the respective compounds. Our findings further establish guanidino compounds as probable
uremic toxins contributing to the neurological complications in
uremia.