dimethylarginine and Acute-Kidney-Injury

Leptospirosis is one of the most relevant zoonosis worldwide and a potentially life-threatening infectious disease. While it is frequent in tropic regions, it is uncommon in European industrialized countries. Angiopoietin-2 (Angpt-2) and asymmetric and symmetric dimethylarginine (ADMA and SDMA) are markers of endothelial activation and systemic inflammation. These parameters have been studied recently in the context of sepsis and MODS showing potential to determine disease severity and outcome specific parameters like acute kidney injury (AKI) and survival. These biomarkers were measured in 13 patients with leptospirosis. High levels of Angpt-2 were statistically significant associated with a complicated clinical course with occurrence of AKI, Sepsis and intensive care unit treatment. ADMA was significantly associated with occurrence of AKI and ICU treatment whereas SDMA was associated with AKI. Therefore these endothelial markers may serve as additional tools for risk stratification in these patients.

Topics: Acute Kidney Injury; Adult; Angiopoietin-2; Arginine; Biomarkers; Female; Humans; Inflammation; Intensive Care Units; Leptospirosis; Male; Middle Aged; Sepsis; Severity of Illness Index

Asymmetrical dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, is elevated in vascular pathologies such as hypertension and chronic kidney disease. Children undergoing cardiac surgery are at high risk of poor hemodynamic and renal outcomes secondary to cardiopulmonary bypass (CPB). This study tested the hypothesis that elevated preoperative ADMA levels are associated with overall worse clinical outcomes after pediatric CPB.. This was a prospective, observational study of 100 patients aged from 2 weeks to 18 years who underwent cardiac surgery involving CPB. Serum ADMA levels were obtained preoperatively and on postoperative days zero through four. Clinical outcomes measured included acute kidney injury (AKI) by pRIFLE criteria, low cardiac output syndrome (LCOS), length of mechanical ventilation, hospital and ICU length of stay, unplanned reoperation, and mortality.. The 29 patients with an elevated preoperative ADMA were more likely to have prolonged mechanical ventilation, increased ICU and hospital length of stay, unplanned reoperation, and LCOS than those with a normal preoperative level. ADMA levels inversely correlated with estimated glomerular filtration rate (eGFR), but did not differ between patients with and without AKI after CPB. Preoperative ADMA levels correlated with hospital length of stay (r(s) = 0.289), ICU length of stay (r(s) = 0.308), and length of mechanical ventilation (r(s) = 0.402); [all p < 0.05]. ADMA levels before surgery had good predictive power for prolonged mechanical ventilation (AUC-ROC 0.809; 95 % CI 0.704, 0.914; p < 0.001).. Patients with elevated ADMA before surgery were more likely to have prolonged mechanical ventilation, develop LCOS, require an extended length of stay, and require reoperation. ADMA levels inversely correlated with eGFR, but did not predict AKI. Preoperative serum ADMA appears to identify pediatric cardiac surgery patients at risk of poor postoperative outcomes following CPB.

Topics: Acute Kidney Injury; Adolescent; Arginine; Cardiac Output, Low; Cardiopulmonary Bypass; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Length of Stay; Male; Postoperative Complications; Preoperative Period; Prospective Studies; Respiration, Artificial; Risk Factors; Treatment Outcome

We studied the impact of acute glycerol-induced renal failure on blood levels and daily urinary excretion of arginine, monomethylarginine, and asymmetric and symmetric dimethylarginine. Acute renal failure was accompanied by enhanced daily excretion of asymmetric and symmetric dimethylarginine, increased plasma level of symmetric dimethylarginine, and decreased plasma level of arginine. Reabsorption of arginine and its methylated analogues decreased, thus compensating for reduced glomerular filtration rate. These data attest to increased production of dimethylarginines during acute renal failure. These changes can decrease NO bioavailability.

Topics: Acute Kidney Injury; Analysis of Variance; Animals; Arginine; Biological Availability; Chromatography, High Pressure Liquid; Cluster Analysis; Glycerol; Injections, Intramuscular; Male; Nitric Oxide; Rats; Rats, Wistar; Statistics, Nonparametric

Hyperhomocysteinaemia represents an important cause of morbidity in recipients of renal transplants, but few investigations have been carried out to evaluate the status of the methylation cycle and its relation with levels of new cardiovascular biomarkers, such as asymmetric dimethylarginine (ADMA).. Twenty-six children and adolescents aged 7-18 years (17 male, 9 female) with stable renal transplants were recruited for the study. None had received treatment with folate, vitamin B(12) or statins. Levels of ADMA in plasma and of components of the methylation cycle and arginine (Arg)-creatine pathway in plasma and urine were analysed by specific analytical methods. Results were compared to those obtained by us with identical methods in healthy children of similar age.. Concentrations of homocysteine (Hcys), S-adenosylhomocysteine (SAH) and ADMA were significantly higher, while S-adenosylmethionine (SAM)/SAH and Arg/ADMA ratios were significantly lower than controls. Arg/ADMA ratio correlated with plasma guanidinoacetate. The components of the methylation cycle, Hcys and SAH correlated with renal function.. Children with renal transplant showed low methylation power (SAM/SAH) mainly due to increased levels of SAH which acts as a cardiovascular biomarker. Elevated values of ADMA and low Arg/ADMA coefficients also represent a novel finding because it inhibits nitric oxide synthesis contributing to endothelial dysfunction and cardiovascular risk in such patients.

Topics: Acute Kidney Injury; Adolescent; Arginine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Child; Creatine; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Humans; Kidney Function Tests; Kidney Transplantation; Male; Methylation; Prognosis; Risk Factors; Survival Rate

Early detection of changes in the glomerular filtration rate (GFR) is crucial in detecting acute kidney injury. There is burgeoning evidence from preclinical and clinical studies that symmetrical dimethylarginine (SDMA) correlates well with different parameters of renal function. In some studies, SDMA even outperformed creatinine as a marker of GFR. It is however unknown how fast SDMA is increasing after reduction in GFR. The aim of our study was therefore to determine the temporal change of SDMA in comparison with cystatin C after a defined reduction in GFR.. Blood samples from 24 healthy living-related kidney donors (19 F/5 M), mean age 55.2 ± 8.3 years, were collected prior to donation of the kidney as well as 1, 6, 12, 24, 72 and 168 h after unilateral nephrectomy. SDMA levels were measured using a liquid chromatography-mass spectrometry-based method.. Within 6 h after unilateral nephrectomy, i.e. reduction of GFR by 50%, SDMA rose from 0.571 ± 0.120 to 0.659 ± 0.135 µmol/L (P < 0.001). Baseline cystatin C levels increased from 0.87 ± 0.16 to 1.07 ± 0.15 mg/L (P < 0.001). Also, serum creatinine rose significantly within 6 h after removal of one kidney from 65.4 ± 8.4 to 88.8 ± 10.2 µmol/L (P < 0.001).. SDMA might be a valuable and early marker of change in GFR in the clinical and experimental setting. Future studies will have to clarify whether sensitivity, specificity and temporal resolution of SDMA make it an attractive candidate for the assessment of renal function in both the experimental and clinical setting.

Topics: Acute Kidney Injury; Arginine; Biomarkers; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Humans; Kidney Function Tests; Kidney Transplantation; Living Donors; Male; Middle Aged; Nephrectomy; Prognosis; Survival Rate