RESUMO
To study the impact of four gene polymorphisms on acute renal allograft rejection (AR) and graft survival among Egyptian population. These 4 gene polymorphisms include: (1) CD 28 (rs3116496), (2) CD86 (rs1129055), (3) CTLA-4 (rs3087243), (4) PD-1 (rs2227982). This is a non-concurrent cohort study including 50 kidney transplant recipients diagnosed histopathologically as (AR) [study group] and another 50 matched allograft recipients without AR [control group]. Blood samples were taken from both groups and subjected to genotyping for the selected four genetic polymorphisms by TaqMan genotyping assay. The difference in genotypic distribution of CD 28: rs3116496 and CD86: rs1129055 wasn't statistically significant between the study and control groups (P = 0.22 and 0.33 respectively) and also both polymorphisms had no effect on graft survival (P = 0.36 and 0.74 respectively) while the addition of C allele to IVS3 +17T/C polymorphism in CD28 gene showed a protective effect against AR (P = 0.03). CTLA-4: rs3087243 AG genotype showed a protective effect against AR as it was more frequent in no rejection group compared to those with AR (P = 0.001) with a statistically significant impact on graft survival (P < 0.001), while PD-1: rs2227982 AG genotype was equally distributed between both groups (variant of unknown significance). There was no detected association between CD86 polymorphism: rs1129055 and CD 28 polymorphism: rs3116496 with the development of AR. However, C allele of CD 28 IVS3 +17T/C polymorphism and CTLA-4 polymorphism: rs3087243AG genotype both demonstrated a protective effect against AR.
Assuntos
Transplante de Rim , Receptor de Morte Celular Programada 1 , Humanos , Receptor de Morte Celular Programada 1/genética , Antígeno CTLA-4/genética , Sobrevivência de Enxerto/genética , Estudos de Coortes , Egito , Transplante de Rim/efeitos adversos , Polimorfismo Genético , AloenxertosRESUMO
BACKGROUND: De novo malignancy is a worrying complication after kidney transplantation; the type of which may vary due to factors such as the prevalence of viral infection and race. Kaposi sarcoma used to be the most common malignancy among our patients constituting more than one-third of cancers. Nevertheless, we noticed that Kaposi sarcoma has not been observed for a long period. Therefore, we conducted this study to explore such observation. METHODS: Data of all kidney transplant recipients were retrieved and retrospectively analyzed. Their total number was 3126 patients. Their mean age was 28.71 ± 10.97 years and of them, 823 (26.3%) were females. The pattern of Kaposi sarcoma throughout the last decade as well as the preceding three decades was studied. The possible relation between the disappearance of Kaposi sarcoma and three paradigm shifts in our practice, namely the use of mTOR inhibitors, steroid-free regimen and CMV prophylaxis was explored. RESULTS: Since 2010, no new cases of Kaposi sarcoma have been observed. In addition, patients who have been transplanted after 2006 did not develop such malignancy. Patients who received CMV prophylaxis and/or were maintained on mTOR inhibitor or steroid-free regimens have not developed Kaposi sarcoma. Moreover, CMV prophylaxis had a statistically significant difference when compared to a homogenous group without CMV prophylaxis. However, Kaplan-Meier analysis of patients of the three policies and their counterpart groups showed comparable results. CONCLUSION: Kaposi sarcoma, which was previously the most common malignancy, is no longer observed for almost a decade among our kidney transplant recipients. m-TOR inhibitors, steroid-free regimen and CMV prophylaxis policy are possible contributing factors. Nevertheless, only CMV prophylaxis policy had a statistically significant relation to the disappearance of Kaposi sarcoma.