TCF7L2 rs7903146 Is Associated With Increased Risk of New-Onset Diabetes After Transplant: A Meta-analysis of Literature.

BACKGROUND: Single nucleotide polymorphisms may influence the risk of development of new-onset diabetes after transplant (NODAT), a post-transplant clinical complication that is often implicated in allograft rejection and mortality. We performed a meta-analysis of association between transcription factor 7-like-2 (TCF7L2) rs7903146 and risk of NODAT. METHODS: A systematic search was conducted using PubMed and ScienceDirect electronic databases for studies published between January 2001 and January 2021. Case-control or cohort studies reporting association between NODAT (diagnosis based on American Diabetes Association criteria) and TCF7L2 rs7903146 were included. MetaGenyo was used for meta-analysis (random-effects model). Pooled odds ratios with 95% confidence intervals were reported to evaluate the strength of association. RESULTS: Two reviewers independently screened for articles. A total of 6 case-control studies were included for full-text review and quantitative analysis after screening for eligibility. Genotypic distributions were in Hardy-Weinberg equilibrium for included studies. All articles reported statistically significant association of TCF7L2 rs7903146 for risk of NODAT except for 1 study. There was moderate heterogeneity among studies (I2 = 60.6%). Pooled analysis revealed 51% odds of developing NODAT with TCF7L2 rs7903146 T allele (allele contrast model: odds ratio, 1.51; 95% confidence interval, 1.13-2.02; P = .005). CONCLUSIONS: The present meta-analysis demonstrated association between TCF7L2 variant rs7903146 and risk of developing NODAT. This finding suggest clinical implications for individuals undergoing kidney transplant.

Clinical Characteristics, Biochemical Markers, and Outcomes of Postrenal Transplant Patients with Coronavirus Diseases 2019: A Single-Center Experience.

The transplant recipient stays in an immunocompromised state for a definite period of time to reduce the risk of rejection and hence has more susceptibility to acquiring infections given the current coronavirus disease 2019 (COVID-19) pandemic. This study is aimed to document the clinical features of COVID-19 and biochemical markers in postrenal transplant population. This study was conducted at the renal transplant department of Dow University Hospital, Karachi, for a duration of one month and was designed as a retrospective observational study. It included all postrenal transplant patients who were assessed for COVID-19 through either nasopharyngeal or oropharyngeal swab for polymerase chain reaction. A total of 159 individuals were assessed and 28.30% were found COVID-19 positive. The mortality rate was 8.88% out of the 45 infected patients. The mean age of COVID-19-infected patients was 34.75 ± 11.50 years with 60% of males and 40% of females. The most frequent comorbidities were hypertension and diabetes mellitus. The current use of immunosuppressants either tacrolimus or cyclosporine was independently associated with acquiring COVID-19 (P <0.001) with an adjusted odds ratio [aOR] [95% confidence interval (CI)] of 1.703 (0.842-2.683) while diabetes was not associated with acquiring COVID-19 (P = 0.001) with an aOR (95% CI) of 0.513 (0.240-1.095). The frequent symptoms were fever, dry cough, sore throat, dyspnea, and arthralgia/myalgia. Diabetes mellitus was associated with early onset (P = 0.031), while the use of mycophenolate mofetil (P = 0.008) and corticosteroids (P = 0.002) was associated with delayed onset of bilateral pulmonary infiltrates. Our study brings the most recent data on postrenal transplant COVID-19 infection.

Multiple Drug Resistant Urinary Tract Infection in Kidney Transplant Recipients: A Retrospective Cohort Study.

Urinary tract infection (UTI) is the most common infectious disease in post-kidney transplantation patients. The objective of the study was to investigate the prevalence, impact and risk factors of multiple drug resistant (MDR) UTI in kidney transplant recipients. This retrospective cohort study recruited 72 kidney transplant recipients between March 2017 and February 2018. Urine cultures performed during the 1st year of posttransplantation with reference to clinical data were evaluated. Predesigned questionnaire was used to collect data regarding demographic, transplant related, and microbiological information. Multivariate analysis was performed to ascertain risk factors of MDR UTI. Out of 72 patients, 28 (38.9%) had culture guided clinical UTI. Overall, 59 UTI episodes were noted throughout the duration of this study. Eschericia coli were found to be the most frequent uropathogen of UTI among kidney transplant recipients (n = 32, 54.2%). MDR bacteria were responsible for 27.1% (n = 16) of the post-transplantation UTI episodes among patients, with E. coli (n = 9, 56.3%) being the predominant bacterial pathogen. Most of the MDR strains of E. coli (n = 7, 77.8%) were extended spectrum beta-lactamase positive. Female gender (P <0.001), prolonged Foley's catheterization (P = 0.002), coexisting diabetes mellitus (DM) (P <0.001) and induction of anti-thymocyte globulin (ATG) therapy (P <0.001) were independently associated with high risk of MDR UTI. The allograft rejection was found to be significantly higher in patients of posttransplantation UTI with MDR uropathogen (P = 0.009). In conclusion, E. coli were the most prominent uropathogen of UTI with and without MDR pathogen in the present study. Female gender, prolonged Foley's catheterization, coexisting DM, and induction of ATG therapy were the risk factors independently associated with MDR UTI in kidney transplant recipients. MDR organisms were significantly associated with allograft rejection.

Successful desensitization and kidney transplantation in the presence of donor-specific anti-human leukocyte antigen antibodies in kidney transplant recipients.

Kidney transplantation has indisputably revamped renal medicine and restored hope among patients coming across fatal end-stage renal disease. However, sensitization of human leukocyte antigen (HLA) triggers extensive immunological fences to successful kidney transplantation and henceforth, transplant candidates are frequently demoted to the ever-growing waiting list owing to preformed donor specific antibodies (DSAs). Over the past few years, the advent of desensitization protocols has significantly overpowered the immunological barriers and enhanced the outcomes of kidney transplant recipients with DSAs against HLA. Those desensitization protocols include combination of plasmapheresis, high-dose intravenous immunoglobulin (IVIG), low-dose IVIG, rituximab, and/or bortezomib. These immunomodulatory treatments either eliminate DSAs or prevent their production. Lately, our transplant center developed and used a desensitization protocol (Two sessions of plasmapheresis on day 1 and 2 → injection rituximab on day 2 after plasmapheresis →no plasmapheresis on day 3 → eight sessions of plasmapheresis after day 3 and IVIG 100 mg/Kg/dose after each session of plasmapheresis → repeat HLA antibody detection test to confirm if DSAs are present against HLA with median fluorescence intensity (MFI)values <1000 and complement dependent cytotoxicity (CDC) crossmatch is negative for both T and B lymphocytes; if NO then continue plasmapheresis sessions with IVIG 100 mg/kg/dose till MFI values are <1000 and CDC crossmatch is negative for both T and B lymphocytes or if YES then proceed for transplantation → repeat dose of rituximab post-transplantation) to evaluate its effectiveness in improving kidney function in patients post-desensitization and kidney transplantation.

Living-unrelated kidney donor transplantation: Legalization in exceptional circumstances?

The prevalence of end-stage renal disease (ESRD) morbidity and mortality is mounting. Kidney transplantation offers a good means of survival and improves longevity of patients with ESRD. However, not everyone is fortunate to benefit from this lifesaving renal replacement therapy due to the lack of available kidneys, one of the many reasons. It eventually expands the number of patients on waiting list of kidney transplantation. At present, deceased and living-related kidney donor transplantation models are widely used, but with limited success to keep up with the pace of burgeoning ESRD. A debate over the legalization of unrelated living kidney donor transplantation has erupted lately. This short review articles focuses on issues surrounding kidney transplantation in Pakistan and draws an informed conclusion regarding pragmatic legalization of unrelated living kidney donor transplantation in exceptional circumstances. Finally, this article also offers a food for thought for countries facing analogous picture in the field of kidney transplantation.

Short- and Intermediate-Term Outcomes in Living-Related Renal Transplant Donors.

OBJECTIVES: The aim of the present study was to evaluate the short- and intermediate-term outcomes of living-related kidney donors in terms of renal function and postnephrectomy complications at a single center in Pakistan. MATERIALS AND METHODS: Our study included healthy donors who underwent unilateral nephroureterectomy for living-related renal transplant procedures at the Sindh Institute of Urology and Transplantation (Karachi, Pakistan) between January 2005 and January 2006. All patients were evaluated for early postoperative complications and renal functions at last follow-up. The mean follow-up duration was 1.7 ± 1.3 years. RESULTS: A total of 256 living-related donors underwent nephroureterectomy during the study period, which included 142 men (55.5%) and 114 women (44.5%). The mean age of donors was 33.7 ± 10.0 years. Most donors were between 21 and 40 years old. Of total donors, most were siblings (n = 143, 55.8%), followed by offspring, parents, and spouses. Left nephrectomy was performed in 206 donors (80.4%) and right in 50 donors (19.5%). There were no deaths during transplant. The mean postoperative hospital stay was 6.37 ± 0.95 days. A total of 38 donors (14.8%) had one or more surgical complication. Hypertension developed in 25 (9.7%) and diabetes mellitus in 9 donors (5%). Creatinine clearance was > 90 mL/min in 96 (41%), 60 to 90 mL/min in 120 (51%), and ≤ 60 mL/min in 18 donors (8%). CONCLUSIONS: Living-related donor nephrectomy remains a valuable source of kidneys for transplant procedures and carries a small risk. With careful donor selection and good surgical management, operative complications can be minimized.