METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.
RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.
CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.
Materials and Methods: We used three online databases, i.e., PubMed, ScienceDirect, and Cochrane Central Registry of Clinical Trials. Randomized controlled trials (RCTs) on the use of prophylactic chemotherapeutic agents used in treating nonpregnant women with recurrent urinary tract infections (RUTIs) published between 2002 and 2016 were selected. Only published papers in English were assessed for study quality, and meta-analyses were performed using fixed-effects model with NetMetaXL.
Results: Six RCTs fulfilled the criteria. When all three variables, i.e., efficacy, adverse effects and cost were considered, nitrofurantoin 50 mg once daily for 6 months appears to rank high for prophylaxis against RUTI. When efficacy was the only factor, fosfomycin had the highest superiority compared to D-mannose, nitrofurantoin, estriol, trimethoprim-sulfamethoxazole, and cranberry juice, respectively. However, fosfomycin was also ranked highest by adverse events. When cost alone is considered, nitrofurantoin appeared the most cost-effective agent while placed third for efficacy alone.
Conclusion: Selecting appropriate chemotherapeutic agents for RUTI will need to factor in effectiveness, adverse effects, and cost. While it is difficult to select an ideal drug, evaluation using network analysis may guide choice of medication for best practice.