Hyperhomocysteinemia in chronic renal failure patients: relation to tissue factor and platelet aggregation

Background: A moderate increase in plasma total homocysteine (t-hcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in general population. One of the mechanisms by which hyperhomocysteinemia contributes to cardiovascular risk has been explained to be the increased thrombotic potential. Elevated t-hcy levels were also reported in chronic renal failure patients because the renal function is a major determinant of serum t-hcy levels. Patients and methods: We measured serum hey and ADP-induced platelet aggregation and plasma tissue factor as a major activator of the coagulation cascade in hemodialysis (HD), peritoneal dialysis (PD) and early stage chronic renal failure (early stage CRF) patients who are not receiving dialysis and compared with those of control. In addition, we also determined serum vitamin B12 and folat levels which are the important factors regulating the metabolism of t-hcy. Results: Hcy levels in all patient groups were significantly higher (HD: 20.42 +/- 1.91 mu mol/l, PD: 35.47 +/- 6.30, early stage CRF: 24.39 +/- 3.06) than the normal levels (10.74 +/- 0.74) in spite of standard multivitamin supplementation. The highest t-hcy values were found in peritoneal dialysis patients. Vitamin B12 levels in hemodialysis/peritoneal dialysis patients and folat levels in hemodialysis/early stage CRF patients were also significantly above those of control. On the other hand, the significant elevations in plasma tissue factor concentration were found in all patient groups (HD: 331.4 +/- 31.3 pg/ml, PD: 306.0 +/- 30.0, early stage CRF: 277.2 +/- 25.5 and Control: 69.5 +/- 13.5). t-hcy levels were positively correlated with creatinine (r: 0.791 p < 0.002) and tissue factor levels (r: 0.526 p < 0.05) in only early stage CRF group. The association between t-hcy and tissue factor persisted after these two parameters were adjusted for creatinine (r: 0.649 p < 0.05). On the other hand the same correlations were not observed in dialysis patient groups. In spite of the high tissue factor levels, ADP-induced platelet aggregations were found to be lower in all patient groups (HD: 102.6 +/- 6.7, PD: 98.6 +/- 7.6 and Early stage CRF: 84.9 +/- 7.6) than controls (154.9 +/- 13.7). Conclusion: These results suggest that hyperhomocysteinemia and increased tissue factor level are present in patients with renal failure, despite supplementation with vitamin B6 and B12 and folat. However, elevated levels of these thrombogenic factors are not linked with platelet aggregation

Influence of Cytokine Gene Polymorphisms on Graft Rejection in Turkish Patients with Renal Transplants from Living Related Donors

Background. Certain cytokine gene polymorphisms (CGPs). have been shown to be associated with renal transplant rejection episodes or graft outcomes. We sought to evaluate the relationships between gene polymorphisms and acute rejection episodes (RG, n = 19) versus stable graft function (NRG, n = 71) in transplant recipients compared with healthy control subjects (HCG, n = 150). The follow-up time period was 18 months. Using polymerase chain reaction sequence-specific primers with the Heidelberg kit we genotyped 22 single nucleotide polymorphisms distributed across 13 cytokine and cytokine receptor genes

The Effect of Glutathion S-Transferase Polymoprhisms and Anti-GSST1 Antibodies on Allograft Functions in Recipients of Renal Transplant

The balance between oxidative stress and anti-oxidant defense systems after renal transplantation may explain the development and progression of allograft dysfunction. Glutathione S-transferase (GST) decreases the damage from oxidative stress. In contrast, recipient antibodies against GSTT1 expressed on the graft are believed to cause its dysfunction. The aim of our research was to study the probable relationship to rejection between GST gene polymorphisms and anti-GSTT1. antibodies. We included 122 patients transplantations from living donors and 51 healthy individuals as controls group in our study. The patient groups were comprised of 57 patients who did and 65 who did not experienced rejection episode. Polymerase chain reactions were used to detect GSTM1 and GSTT1 polymorphisms, whereas PCR-.RFLP (restriction fragment length polymorphism), for GSTP1 polymorphism. An enzyme-linked immunosorbent assay method was used for anti-GSTT1. antibody scans. There was no significant difference between the groups for allele and genotype frequencies of GSTT1, GSTM1, GSTP1. polymorphisms of the recipients, donors, and controls. Within the rejection group the frequency of patients with the GSTM1 null genotype was higher among subjects prescribed cyclosporine A versus tacrolimus (P = .029). Among the entire patient group, 46 subjects with GSTT1 null genotype were scanned for anti-GSTT1 antibody which was detected in 5 of 8 patients with an acute rejection episode (P = .04). Anti-GSTT1. antibody was observed more frequently albeit not significantly, among the cyclosporine versus tacrolimus patient group (P = .16). This study suggested that GSTM1 genotype may be important for cyclosporine detoxification and for allograft outcomes clue to drug nephrotoxicity. After transplantation, antigens distinct from the HLA system such as GSTT1 protein may also be targets for alloimmune responses

Tac-MMF Versus CsA-MMF/CsA-AZA-Based Regimens in Development of De Novo Complement-Binding Anti-HLA Antibodies After Kidney Transplantation.

Background. Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA)were compared for graft-related outcomes in conjunction with complement-binding denovo donor-specific antibodies (DSAs).Methods. Non-sensitized adult patients without rejection episodes within 3 months aftertransplantation were screened for the presence of de novo DSAs and C1q binding. Clinicaland biopsy data were retrospectively obtained.Results. The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age andfollow-up of 36.1 11.4 and 7.2 4.8 years, respectively. As compared with tacrolimus, theCsA group had higher rates of both class II DSAs and C1q-binding DSAs (20% vs 4.4%,P .008, and 18% vs 0%, P .003, respectively). Rates of chronic antibody-mediatedrejection (cAMR), proteinuria &gt;500 mg/g, and levels of creatinine both at last visitswere also higher in the CsA group (20% vs 0%, P .002, 30% vs 5.9%, P .005, 1.67 1.31 vs 1.18 0.45 mg/dL, P .019, respectively).Class II DSAs and C1q-bindingclass II DSAs were significantly correlated with the clinical outcomes (creatinine levels,proteinuria, and cAMR).Conclusions. Compared with tacrolimus, CsA appears to pose a higher risk for thedevelopment of de novo anti-HLA antibodies with C1q-binding properties and,consequently, adverse graft-related outcomes

Deceased Donor Kidney Transplantation in a Human Immunodeficiency Virus–Infected Recipient: A Case Report

© 2019 Elsevier Inc.Human immunodeficiency virus (HIV)infection has traditionally been considered an absolute contraindication for transplantation because immunosuppression will accelerate the disease progression and increase mortality. New antiretroviral agents have given rise to new perspectives and transplantation practices. Now renal transplantation is the gold standard treatment for end-stage renal disease in HIV-infected patients, but increased rejection and toxicity rates and compliance with treatment are important issues. Therefore, patient selection and follow-up should be done carefully in this patient group. Here we present a 51-year-old, male, HIV-infected patient who was diagnosed with HIV at his routine serologic investigation at 2015. Highly active antiretroviral therapy was initiated. One haplotype-matched kidney transplantation from a deceased donor was performed on October 19, 2016. Induction therapy was not administered, and the immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisolone. After 26 months, serum creatinine was 1.1 mg/dL and proteinuria 0.1 g/day. There was no development of donor-specific antibodies. The patient's current HIV viral load remains undetectable (and had been the entire time post-transplantation)while his CD4+ T-cell count currently is 543/mm3