The Arginine-Creatine Pathway is Disturbed in Children and Adolescents With Renal Transplants

Abstract

Cardiovascular disease is an important cause of morbidity in recipients of renal transplants. The aim of the present study was to analyze the status of the arginine-creatine pathway in such patients, given the relationship between the arginine metabolism and both renal function and the methionine-homocysteine cycle. Twentynine children and adolescents (median age 13, range 6 -18 years), who had received a renal allograft 14.5-82.0 months before, were recruited for the study. On immunosuppressive therapy, all patients evidenced an adequate level of renal function. Plasma concentrations of homocysteine and glycine were significantly higher, whereas urinary excretions of guanidinoacetate and creatine were significantly lower than controls. Urinary excretions of guanidinoacetate and creatine correlated positively with creatinine clearance. Urinary excretion of creatine was negatively correlated with plasma concentration of homocysteine. The demonstration of disturbances in the arginine-creatine pathway in patients with well-functioning renal transplants and in absence of chronic renal failure represents a novel finding. We speculate that the low urinary excretion of guanidinoacetate and creatine is probably related to the nephrotoxic effect of immunosuppressive therapy and to defective methylation associated with the presence of hyperhomocysteinemia. (Pediatr Res 64: [218][219][220][221][222] 2008)

Amino acids in a targeted versus a non-targeted metabolomics LC-MS/MS assay. Are the results consistent?

“…This is also consistent with the literature. It has been described before that transplant patients seem to be arginine-deficient and it has been hypothesized that, at least in part, this is associated with immunosuppressive drug treatment [21]. As these were pooled data sets from kidney transplant patients treated with two different immunosuppressant drug regimens (standard dose tacrolimus+ MMF or reduced dose tacrolimus+ everolimus), a potential treatment effect was assessed and no difference was found for any of the amino acids.…”

Creatine as Biomarker

“…4), several authors have studied their concentration in patients with renal dysfunction. Andrade et al (2008) found low urinary excretion of GAA and Cr in children and adolescents with renal transplants compared with age-matched healthy children. They also found a positive correlation of GAA and Cr excretion with respect to the estimated glomerular filtration rate (GFR) and the excretion of arginine and glycine and a negative correlation with the plasma levels of homocysteine.…”

“…SAM is converted into S-adenosylhomocysteine (SAH), which can be reversibly hydrolyzed to form homocysteine and adenosine. This part of the methylation cycle is known as "transmethylation" (Von Figura et al 2001;Andrade et al 2008; Fig. 4).…”

Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability

“…Intellectual disability (ID) is the most common neurodevelopmental disorder with a worldwide prevalence of about 1% [1,2] and is defined by impaired cognitive functioning and adaptive behavior arising before the age of 18 [3]. Its severity is usually measured by the intelligence quotient (IQ) score and classified as mild (IQ [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70], moderate (IQ [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55], severe (IQ [25][26][27][28][29][30][31][32][33][34][35][36][37][38]…”

“…The deleted nucleotides are shown in red. (C) Creatine metabolism pathway (derived from Andrade et al 2008)[42]. The protein encoded by SLC6A8 is named creatine transporter (CT1) and it is a transmembrane protein that is responsible for the creatine uptake.…”