MO978EFFECT OF MYCOPHENOLIC ACID AND TACROLIMUS ON THE INCIDENCE OF INFECTIOUS COMPLICATIONS AFTER KIDNEY TRANSPLANTATION IN CONTRAST WITH THE INCIDENCE OF ACUTE KIDNEY REJECTION

Background and Aims Kidney transplantation (KTx) remains the most effective type of kidney replacement therapy. Infectious complications remain a common cause of mortality, especially during the first year after KTx. Goal of effective immunosuppressive treatment (IS) must be balanced between the decreasing incidence of acute rejection by maintaining effective levels of IS and at the same time avoiding the incidence of infectious complications caused by dose-dependent toxicity of IS. Method The aim of our analysis was to identify the risk of fixed daily doses of mycophenolic acid (MPA) and concentration controlled doses of tacrolimus (TAC) in the development of a single, recurrent infection and acute rejection after KTx. Results Our analysis consisted of 100 patients after KTx (66 males, 34 females) with anti-thymocyte globulin as an induction IS. We monitored the incidence of single, recurrent infection in 1st month, from 1st to 6th month and from 6th to 12th month after KTx and the incidence of acute kidney rejection in 1st year after KTx. According to multivariant analysis, Daily dose of MPA > 1080 mg and levels of TAC above recommended levels were not independent risk factors for the incidence of the infection. Daily dose of MPA > 1080 mg was a risk factor for recurrent infection in general (OR 1.2964; P = 0.0277), for recurrent bacterial infection from 1st to 6th month (OR 1.2674; P = 0.0151), recurrent bacterial infection (OR 1.2574; P = 0.0436), single viral infection (OR 1.2640; P = 0.0398) from 6th to 12th month after KTx We did not confirmed levels of TAC, above recommended levels in observed periods, as a risk factor for single or recurrent infection regardless of its etiology. We confirmed, incidence of mycotic infection in 1st month after KTx correlated with average level of TAC (13.4 ± 3.2 ng/ml) (P = 0.0300) and with average MPA daily doses (1200 ± 360 mg/day) (P = 0.0203). Correlation between the average daily doses of MPA (730 ± 380 mg/day) and the incidence of bacterial infection (P = 0.0161) and viral infection (P = 0.0161) from 1st to 6th month after KTx were found. We confirmed correlation between the incidence of bacterial infection and the average daily doses of MPA (630 ± 340 mg/day) from 6th to 12th month after KTx (P = 0.0479). By probit dose regression, we confirmed statistical significance between levels of TAC and the incidence of bacterial, mycotic and multidrug-resistant (MDR) infection, correlation between the daily dose of MPA and the incidence of mycotic infection in 1st month after KTx. We found statistical significance between levels of TAC and MDR infection and daily dose of MPA and the incidence of bacterial, mycotic and MDR infection from 1st to 6th month after KTx and we found statistical significance between the daily dose of MPA and the incidence of MDR infection from 6th to 12th month after KTx. In our study, we did not confirmed statistical significance between levels of TAC, daily dose of MPA and the incidence of acute kidney rejection. By logistic regression, neither levels of TAC below recommended values nor daily dose of MPA < 1080 mg were found as an independent risk factors for the incidence of acute kidney rejection. Conclusion In our analysis, we found dose of MPA > 1080 mg/day as a risk factor for recurrent infection starting in the 1st month after KTx and correlation between the incidence of the infections and daily dose of MPA 1 month after KTx, with significant association between the incidence of infections and daily doses of MPA and levels of TAC, without increased risk of acute kidney rejection. In the centers with fixed dosing of IS, this can lead to lowering the risk of infections by decreasing daily doses of MPA 1 month after KTx without increasing risk of infections.

A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation

In this work a novel point of care test to detect sIL-2R during acute kidney rejection with high specificity and sensitivity was developed.

Circular RNAs in Urine of Kidney Transplant Patients with Acute T Cell-Mediated Allograft Rejection

BACKGROUND Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They are detectable in the blood of patients with acute kidney injury. We tested whether circRNAs were present in urine and could serve as new predictors of outcome in renal transplant patients with acute rejection. METHODS A global circRNA expression analysis using RNA from urine of patients with acute T cell-mediated renal allograft rejection and control transplant patients was performed. Dysregulated circRNAs were confirmed in a cohort of 62 patients with acute rejection, 10 patients after successful antirejection therapy, 18 control transplant patients without rejection, and 13 stable transplant patients with urinary tract infection. RESULTS A global screen revealed several circRNAs to be altered in urine of patients with acute rejection. Concentrations of 2 circRNAs including hsa_circ_0001334 and hsa_circ_0071475 were significantly increased. These were validated in the whole cohort of patients. hsa_circ_0001334 was upregulated in patients with acute rejection compared with controls. Concentrations of hsa_circ_0001334 normalized in patients with acute rejection following successful antirejection therapy. hsa_circ_0001334 was associated with higher decline in glomerular filtration rate 1 year after transplantation. CONCLUSIONS CircRNA concentrations are significantly dysregulated in patients with acute rejection at subclinical time points. Urinary hsa_circ_0001334 is a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.