Evaluation of TH17 and TH1 Immune Response Profile in Patients After Renal Transplant.

BACKGROUND: Renal transplantation (RT) is the best treatment option for patients with end-stage renal disease (ESRD) because it improves both quality of life and survival. However, allograft rejection remains the most important barrier to successful transplantation. Underlying immunologic mechanisms should be understood to develop appropriate treatment strategies. METHODS: In this prospective study, we followed renal transplant recipients for 6 months. The study population comprised 50 recipients of renal transplants, and these were divided into 2 groups: 44 patients with stable graft function (SGF) and 6 patients with rejection (RX). Peripheral blood samples were drawn from patients on the pre-RT day, at post-RT day 7, month 1, and month 6, and on the day of rejection for analysis of the percentages of cytokines interleukin (IL) 17 and interferon (IFN) γ with the use of flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The percentages of intracellular IFN-γ were not significant in the group with RX compared with SGF. Levels of intracellular IL-17 obtained at the 6th month after RT were significantly higher in the RX group than in the SGF group. Plasma levels of pre-RT IL-17 were also higher in the RX group; therefore, it may be a predictive biomarker of acute rejection of renal transplants. CONCLUSIONS: The present study provides information about pre-RT and post-RT cytokine profiles of Turkish patients with ESRD. We consider cytokine analysis to be a valuable biomarker panel in the prevention of rejection and in assisting with new treatment strategies for patients undergoing renal transplant.

Effect of MDR1 polymorphisms on the blood concentrations of tacrolimus in Turkish renal transplant patients.

BACKGROUND: Tacrolimus, a calcineurin inhibitör, is prescribed to prevent allograft rejection in renal transplantation. Tacrolimus not only has a narrow therapeutic index, but also shows significant interindividual differences. The absorption and metabolism of this drug are affected by multidrug resistance (MDR) 1 gene polymorphisms that correlated with single-nucleotide polymorphisms (SNPs) affecting in vivo P-glycoprotein activity. This study investigated associations of MDR1 gene C3435T polymorphism with tacrolimus blood concentrations and dose requirements as well as acute rejection episodes among Turkish renal transplant patients. METHODS: One hundred living-donor transplant recipients and 150 healthy control subjects underwent C3435T genotyping using polymerase chain reaction-restriction fragment length polymorphism. Blood concentrations of tacrolimus were determined with the cloned enzyme donor immunoassay. RESULTS: The CC, CT, and TT genotype frequencies among patients were, respectively, 44.0%, 33.0%, and 23.0% versus 36.7%, 43.3%, and 20.0% among control subjects. There was no significant difference between (P = .061; P = .102; P = .211; respectively). The ratio of blood concentration to dose of tacrolimus for patients with mutant homozygous 3435 TT genotype was higher than that of wild-type 3435 CC genotype homozygous individuals. The doses for these patients were lower at 1, 3, and 12 months (P = .048; P = .03; P = .041, respectively). There were no significant differences between the groups regarding coprescription of drugs that affect tacrolimus concentrations, such as diltiazem. Acute rejection episodes were not associated with the CC vs CT or TT genotypes: odds ratio (OR), 0.517 (95% confidence interval [CI], 0.190-1.407; P = .192); OR 1.558 (95% CI, 0.587-4.136; P = .372); OR 1.346; (95% CI, 0.456-3.968; P = .590), respectively. CONCLUSIONS: Determination of MDR1 polymorphism may help to achieve target of tacrolimus blood concentrations.

Acute renal failure due to leukaemic infiltration in chronic lymphocytic leukaemia: case report.

A 73-year-old woman was presented with altered mental status and disorientation. She was diabetic and hypertensive, and she had experienced an ischemic cerebrovascular accident 3 years ago. Physical examination revealed the findings of chronic obstructive pulmonary disease, cor pulmonale and congestive heart failure. Hepatomegaly, splenomegaly and ascites were found and might be associated with postsinusoidal portal hypertension secondary to congestive heart failure. Laboratory tests showed uremia, lymphocytosis and thrombocytopenia. Neurologic findings were related with uremia and hypoxia. Multiple pathologic lymphadenopathies were seen in abdominal ultrasonography and thoracic computed tomography. Bone marrow histology indicated chronic lymphocytic leukaemia (CLL). The reason for acute renal failure was leukaemic infiltration of the kidneys due to CLL that was shown with renal biopsy. Blood urea nitrogen (BUN) and serum creatinine responded well to cyclophosphamide and methyl prednisolone treatment. In CLL, direct renal involvement is frequently seen in autopsy studies especially in advanced disease, however, renal failure due to leukaemic infiltration is extremely rare.