guanidinosuccinic-acid and alpha-keto-delta-guanidinovaleric-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

Antidiuresis and renal diseases alter the levels of guanidino compounds (GCs) in various tissues. Therefore, we hypothesized that diuresis could also disturb GC metabolism, storage, and elimination. In this study, rats were made diuretic to analyze GC levels in plasma, urine, and kidneys. Furosemide was chosen because of its wide use in various human pathologies. Rats were injected intraperitoneally 5 or 10 mg furosemide spread over a 24-hour cycle. Urine was collected over a period of 24 hours before and during furosemide treatment. Plasma was obtained from arterial blood. Renal zones were dissected. The GCs were determined by liquid chromatography. Five milligrams of furosemide provoked a significant increase in plasma and urine levels of GCs compared with those of the controls. The renal distribution and content of GCs were weakly modified by furosemide except for methylguanidine (MG). The level of MG was enhanced by 10 to 16 times in all renal zones. The MG level was 60% higher in renal zones of rats treated with 10 rather than 5 mg furosemide. The fractional excretion of MG was decreased by furosemide. Our data suggest that MG accumulation in kidney and plasma was caused by furosemide, which might induce MG synthesis, and that MG washout from tissue cells into urine by furosemide through the kidney may cause an increase in MG in the kidney.

Topics: Animals; Creatinine; Diuretics; Furosemide; Guanidines; Kidney; Male; Methylguanidine; Propionates; Rats; Rats, Sprague-Dawley; Succinates

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

Renal failure is characterized by the retention of nitrogenous metabolites such as urea, creatinine (CTN) and other guanidino compounds (GCs), uric acid, and hippuric acid, which could be related to the clinical syndrome associated with renal insufficiency. A model of renal failure has been developed in male C57BL x Swiss-Webster mice using nephrectomy (NX) and/or arterial ligation. A sham group (group A) and two nephrectomized groups, group B (one kidney removed) and group C (one kidney removed and ligation of the contralateral anterior artery branch), were studied. Ten days postsurgery, morphological and functional indices of renal failure were investigated. Nephrectomized mice manifested features of renal failure like polyuria and wasting. CTN clearance (CTN[Cl]) decreased by +/-26% in group B and +/-33% in group C as compared with the control values. Marked increases in the plasma concentration of guanidinosuccinic acid ([GSA] fourfold) and guanidine ([G] twofold) were observed in the experimental animals. CTN and alpha-keto-delta-guanidinovaleric acid (alpha-keto-delta-GVA) reached levels of, respectively, 1.5-fold and twofold those of controls. Urinary GSA excretion increased and guanidinoacetic acid (GAA) excretion decreased about twofold in group C. GSA increases (2.6-fold) were also observed in the brain in group C, in addition to a significant increase of G (2.5-fold) and gamma-guanidinobutyric acid ([GBA] 1.5-fold). Finally, the extent of NX was found to be 45.2% in group B and 71.4% in group C. Light microscopy revealed an expansion and increase in cellularity of the mesangium of the glomeruli, particularly in group C. A significant correlation (r = .574, P < .0001) was found between CTN(Cl) and the degree of NX as calculated from the remaining functional area. These data suggest that the model can be used as a tool for further pathophysiological and/or behavioral investigations of renal failure.

Topics: Animals; Arginine; Brain; Creatinine; Glycine; Guanidine; Guanidines; Ligation; Male; Mice; Mice, Inbred C57BL; Nephrectomy; Renal Artery; Renal Insufficiency; Succinates

1. Guanidino compounds (GCs) have been quantified in different mammalian tissues such as brain, liver, muscle and kidney. The high anatomical heterogeneity of the kidney suggests that GCs could be unevenly distributed along the corticopapillary axis of the kidney in different species. 2. This study was designed to quantify twelve GCs in the different zones of rat and rabbit kidney. The kidneys were sliced and pieces of seven definite zones were weighed and homogenized for further GC extraction. GCs were determined by liquid chromatography. 3. The results indicate that: (1) GCs were unevenly distributed along rat and rabbit kidney; (2) qualitative and quantitative studies proved that each GC shows a particular distribution pattern along the corticopapillary axis for a given species; (3) in rats, alpha-keto-delta-guanidinovaleric acid, guanidinosuccinic acid, creatinine (CTN), methylguanidine and to a lesser extent gamma-guanidinobutyric acid increased steeply along the inner medulla in parallel to urea, whereas in rabbits, most of the GCs reached a plateau in the inner medulla and remained constant at this level; (4) gamma-guanidinobutyric acid was specifically found in the rat kidney; (5) argininic acid was higher in rabbit compared with rat kidney; (6) significantly higher levels of homoarginine were found in all zones of the rat kidney compared with the rabbit kidney. 4. The results suggest that: (1) GCs are mostly localized within the nephron segments; (2) an accumulation of GCs in the inner medulla might be explained either by a recycling process or by an intracellular storage as has been reported for urea, amino acids and organic osmolytes; (3) some GCs might be synthesized in nephron segments as reported for arginine (Arg) and guanidinoacetic acid (GAA); (4) several metabolic pathways of the GCs seemed to differ between rat and rabbit; (5) except for creatine, CTN, Arg and GAA, it seems unlikely that GCs might significantly increase the intracellular osmolality.

Topics: Affinity Labels; Animals; Arginine; Creatine; Glycine; Guanidines; Kidney; Male; Methylguanidine; Propionates; Rabbits; Rats; Rats, Sprague-Dawley; Succinates; Tissue Distribution; Urea

Topics: Amino Acid Metabolism, Inborn Errors; Arginine; Chromatography, Liquid; Chromatography, Thin Layer; Female; Gas Chromatography-Mass Spectrometry; Glycine; Guanidines; Humans; Hyperargininemia; Succinates