Immune response regulation by cytokines is a key to understanding AGR. The influence of the functional polymorphisms in genes coding for TNF-alpha (-308G > A), IL-10 (-819C > T, and -1082A > G), IFN-gamma [(CA)n], TGF-beta1 (+869T > C), and iCAM-1 (R241G and E469K), in addition to HLA and gender matching on the presentation of AGR in 51 pediatric renal recipients during a 36-month post-transplantation follow-up were analyzed. Also, donors and a control group were genotyped. All groups were within Hardy-Weinberg equilibrium for all polymorphisms except IL-10-819C > T and TNF-alpha (p < 0.005 and p < 0.01, respectively) in recipients. Transplants with gender mismatch showed a higher risk for AGR than those between individuals with gender match (OR, 4.227; p = 0.010). Recipients with a high-production compared with low-production TNF-alpha allele experienced earlier AGR (p = 0.030), and those with high-production alleles of both TNF-alpha and IFN-gamma showed a further increased risk (OR = 11.129, p = 0.024). These findings support the notion that a single genotype cannot by itself explain an event as complex as AGR. The sum or combination of different specific alleles of these genes could better account for the immune response to an allograft.

The aim of this pilot clinical trial was to evaluate the safety of a new formulation of prolonged-release Pirfenidone (PR-PFD) in chronic kidney disease (CKD), specifically focal and segmental glomerular hyalinization (FSGH). Open-label, pilot, nonrandomized trial. Eighteen patients previously diagnosed with CKD stages 1– 5 according to “Kidney Disease: Improving Global Outcomes” were enrolled in the study. Target dos-age of PFD was 1200 mg twice a day in the form of prolonged-release tablets to reach a full dosage of 2400 mg daily. Clinical trial was carried out for 60 months to evaluate the safety and efficacy of a newly formulated PR-PFD in patients with CKD. After the treatment for 60 months, it was found that PR-PFD kept renal function from declining significantly in CKD patients, as the glomerular filtration rate (GFR) showed only minimal variations throughout the study. Estimated glomerular filtration rate (eGFR) showed no differences at both baseline and the end points. Proteinuria improved, and creatinine, cystatin C, urea, hemoglobin and hepatic transaminases remained constant without any considerable changes across the study. Minor side effects were noticed when compared with those found in previous studies, indicating an increased tolerance to this pharmaceutical formulation of PFD. Prolonged-released PFD could be safely used as an adjuvant therapy in patients with CKD.Registry number was obtained from ClinicalTrials.gov (NCT02408744).