ascorbic-acid and Delayed-Graft-Function

Delayed graft function (DGF) is a consequence of ischemia-reperfusion injuries in kidney allografts, for which no definite treatment is available. The neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are introduced as the most promising urine biomarkers to detect DGF. N-acetylcysteine (NAC) and vitamin C, well-known potent antioxidants that scavenge free radicals, may alleviate kidney injury. This study investigated the protective effects of NAC alone and in combination with vitamin C on DGF, by measuring IL-18 and NGAL in living donor kidney transplantations.. Patients transplanted between January 2011 and February 2013 were randomly divided into 3 groups to receive routine anti-rejection medication only (n = 32), NAC plus routine immunosuppressive regimen (NAC group; n = 33), and NAC and vitamin C plus routine regimen (NAC and vitamin C group; n = 19). Urine samples were taken 4 hours and 24 hours after transplantation. Enzyme-linked immunosorbent assay kits were utilized for measuring urine NGAL and IL-18.. There were no significant differences in the DGF prevalence and its duration between the study arms. Although the levels of NGAL and IL-18 decreased in the NAC and NAC and vitamin C groups, these reductions were not significant. Glomerular filtration rate at 30 and 60 days after transplantation were not significantly different between study groups, either.. Our results showed that NAC is a safe drug without significant adverse effects in kidney transplant recipients; however, its potential useful effects on urinary biomarkers of DGF were not illustrated in the present study.

Topics: Acetylcysteine; Acute-Phase Proteins; Adolescent; Adult; Allografts; Antioxidants; Ascorbic Acid; Biomarkers; Delayed Graft Function; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-18; Iran; Kidney Transplantation; Lipocalin-2; Lipocalins; Living Donors; Male; Middle Aged; Predictive Value of Tests; Proto-Oncogene Proteins; Time Factors; Treatment Outcome; Young Adult

More extensive use of non-heart-beating donors (NHBD) could reduce mortality on liver transplantation waiting lists, but this is associated with more primary nonfunction (PNF). We assessed which parameters are involved in the development of PNF in livers from NHBD in a previously validated pig liver transplantation model, in which livers were transplanted after exposure to incremental periods of warm ischemia. The risk of PNF was unacceptably high (>50%) when livers were exposed to >30 minutes' warm ischemia before a short cold ischemic period. This study examined how PNF is affected by Kupffer cell activation (beta-galactosidase), the generation of cytokines tumor necrosis factor alpha and interleukin 6, antioxidant mechanisms (ascorbic acid, alpha-tocopherol, reduced glutathione), circulating redox-active iron, and sinusoidal endothelial cell function (hyaluronic acid clearance). Kupffer cells were more activated in PNF recipients, as suggested by higher beta-galactosidase levels (15 minutes after reperfusion), and secondarily, by higher production of tumor necrosis factor alpha and interleukin 6 (180 minutes after reperfusion). In addition, alpha-tocopherol and reduced glutathione were lower, and ascorbic acid and redox-active iron higher in PNF recipients. Finally, PNF grafts displayed progressively decreasing hyaluronic acid clearance (suggesting sinusoidal endothelial cell dysfunction) and parenchymal edema. Consequently, a reduced-flow phenomenon was documented. In grafts from NHBD that are destined to fail, beta-galactosidase activity (a surrogate of Kupffer cell activation) is higher, proinflammatory cytokines are overproduced, some antioxidant mechanisms fail, and circulating redox-active iron is more rapidly released. A no-flow phenomenon is eventually observed in these failing grafts.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; beta-Galactosidase; Cytokines; Delayed Graft Function; Glutathione; Iron; Kupffer Cells; Liver; Liver Transplantation; Macrophage Activation; Oxidation-Reduction; Regional Blood Flow; Swine; Warm Ischemia

Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplant recipients.. The AGE accumulation was assessed using a validated skin-autofluorescence reader (AFR) in 285 consecutive renal transplant recipients (57% male, aged 50+/-12 years) visiting the outpatient clinic at a median (interquartile range) time of 73 (32-143) months after transplantation. Furthermore, various transplant- and recipient-related factors of interest were collected.. Average skin-autofluorescence of lower arm and leg was 2.7+/-0.8 a.u. Skin-autofluorescence was positively determined by recipient age, systolic blood pressure, smoking, high-sensitivity C-reactive protein, duration of pre-transplant dialysis, and negatively by plasma vitamin C levels, creatinine clearance at baseline, and change in creatinine clearance since one year after transplantation in linear multivariate regression analysis. Together, these factors explained 41% of the variance of skin-autofluorescence.. Skin-autofluorescence was associated with several risk factors for cardiovascular disease and chronic renal transplant dysfunction. These results are in line with the hypothesis that AGEs play a role in the pathogenesis of these conditions in renal transplant recipients. Prospective studies are required to investigate whether the AFR can be used as a simple, non-invasive tool to identify and monitor patients at risk for chronic renal transplant dysfunction and cardiovascular disease.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; C-Reactive Protein; Cardiovascular Diseases; Comorbidity; Creatinine; Delayed Graft Function; Diabetes Complications; Female; Fluorometry; Forearm; Glycated Hemoglobin; Glycation End Products, Advanced; Histocompatibility; Humans; Hypercholesterolemia; Hypertension; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Leg; Linear Models; Male; Middle Aged; Obesity; Risk Factors; Skin; Smoking; Vitamin E