guanidinosuccinic-acid and argininic-acid

Specific guanidino compounds have been described as uraemic toxins and their concentrations are increased in renal failure due to dimished glomerular filtration, whereas the guanidino compound creatine is used as a performance-enhancing substance in athletes. The present study investigates the effects of creatine supplementation on plasma guanidino compounds in a chronic haemodialysis population.. Twenty male haemodialysis patients were included in a placebo-controlled cross-over trial. Patients were treated with creatine (2 g/day) or placebo during two treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma guanidino compounds and routine biochemical parameters were determined, as well as the prognostic inflammatory and nutritional index (PINI).. Upon creatine supplementation, guanidinoacetate concentrations decreased by 15%, due to inhibition of creatine synthesis. Concentrations of alpha-keto-delta-guanidinovaleric acid increased three-fold and argininic acid concentrations doubled. Guanidinosuccinate concentrations did not change, but correlated inversely with CRP (r = -0.736; P = 0.001), PINI-score (r = -0.716; P = 0.002) and correlated positively with plasma urea concentration (r = 0.54; P = 0.02).. Creatine supplementation in haemodialysis patients significantly altered the concentration of specific guanidino compounds. Guanidinosuccinate correlated positively with plasma urea and negatively with inflammation markers.

Topics: Administration, Oral; Aged; Arginine; Biomarkers; C-Reactive Protein; Creatine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Glycine; Guanidines; Humans; Inflammation; Male; Nephelometry and Turbidimetry; Prognosis; Renal Dialysis; Renal Insufficiency; Severity of Illness Index; Succinates; Treatment Outcome; Urea

Serum levels of twelve guanidino compounds (GCs) and nerve conduction velocities were determined in a dialyzed renal insufficient pediatric population. Two dialytic groups were considered: one subjected to hemodialysis (HD, 11 patients) and one subjected to continuous cycle peritoneal dialysis (CCPD, 13 patients). Before HD, marked increases were found for guanidino-succinic acid (207 times), methylguanidine (> or = 67 times), argininic acid (24 times), creatinine and alpha-N-acetylarginine (18 times) and guanidine (> or = 14 times) when compared to controls. Important significant increases were still present after an HD session for guanidinosuccinic acid (49 times), methylguanidine (34 times), creatinine (7 times) and alpha-N-acetylarginine and guanidine (6 times). After HD, creatine, arginine and homoarginine were lower than in controls. All GCs, with the exception of creatine, decreased significantly after a single HD session with percentage decrease ranging between 40% (for arginine) and 77% (for guanidinosuccinic acid). Creatine decreased in a statistically nonsignificant manner by 48%. Marked increases were found in the CCPD group for guanidinosuccinic acid (114 times), alpha-N-acetylarginine (12 times), argininic acid (15 times), creatinine (22 times), guanidine (> or = 11 times) and methylguanidine (> or = 48 times). Concentrations of guanidinosuccinic acid before and after HD and in CCPD were comparable to those reported to be toxic in vitro and in vivo. No clinical or electrophysiological indications of polyneuropathy were observed in our population. Sensory and motor nerve conduction studies showed few abnormalities apart from a significant correlation between argininic acid concentration or guanidine levels and the peroneal nerve conduction velocity in the CCPD-treated group.

Topics: Adolescent; Adult; Arginine; Child; Child, Preschool; Creatinine; Female; Guanidine; Guanidines; Humans; Male; Methylguanidine; Neural Conduction; Peritoneal Dialysis; Renal Dialysis; Succinates; Urea; Uremia

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.

Topics: Acute Kidney Injury; Animals; Arginine; Creatine; Creatinine; Glycine; Guanidines; Homoarginine; Kidney; Kidney Failure, Chronic; Male; Methylguanidine; Muscle, Skeletal; Nephrectomy; Propionates; Rats; Rats, Sprague-Dawley; Succinates; Time Factors; Urea; Uremia