Persistent mixed chimerism protects against rejection of HLA-matched and mismatched kidney transplants without graft-versus-host disease.

The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19−23%), an intensive care unit admission rate of 26% (95% CI: 22–31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62–81%), an acute kidney injury rate of 44% (95% CI: 39–49%), a kidney replacement therapy rate of 12% (95% CI: 9–15%), and a graft loss rate of 8% (95% CI: 5–15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.

Over-immunosuppressed kidney transplant recipients are susceptible to malignancies and BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN). This study aimed to verify the association between BKPyV infection and urinary tract cancers (UTC). A total of 244 kidney transplant recipients were enrolled at Chang Gung Memorial Hospital from June 2000 to February 2020. Biopsy-proven BKPyVAN patients (n = 17) had worse kidney function (eGFR: 26 ± 13.7 vs. 47.8 ± 31.0 mL/min/1.73 m²). The 5-year allograft survival rates for patients with and without BKPyVAN were 67% and 93%, respectively (p = 0.0002), while the 10-year patient survival was not different between the two groups. BKPyVAN patients had a significantly higher incidence of UTC compared to the non-BKPyVAN group (29.4% vs. 6.6%). Kaplan–Meier analysis showed that the UTC-free survival rate was significantly lower in BKPyVAN patients, and the onset of UTC was significantly shorter in BKPyVAN patients (53.4 vs. 108.9 months). The multivariate logistic regression analysis demonstrated that age (RR = 1.062) and BKVAN (RR = 6.459) were the most significant risk factors for the development of UTC. Our study demonstrates that BKPyVAN patients have greater allograft losses, higher incidence, a lower cancer-free survival rate, and an earlier onset with a higher relative risk of developing UTC compared to non-BKPyVAN patients.

BK Polyomavirus (BKPyV) infection is a common complication in kidney transplant recipients and can result in poor outcomes and graft failure. Currently, there is no known effective antiviral agent. This study investigated the possible antiviral effects of Interferon alpha (IFNα) and its induced protein, MxA, against BKPyV. In vitro cell culture experiments were conducted using human primary renal proximal tubular epithelial cells (HRPTECs). We also did animal studies using Balb/c mice with unilateral kidney ischemic reperfusion injury. Our results demonstrated that IFNα effectively inhibited BKPyV in vitro and murine polyomavirus in animal models. Additionally, IFNα and MxA were found to suppress BKPyV TAg and VP1 production. Silencing MxA attenuated the antiviral efficacy of IFNα. We observed that MxA interacted with BKPyV TAg, causing it to remain in the cytosol and preventing its nuclear translocation. To determine MxA's essential domain for its antiviral activities, different mutant MxA constructs were generated. The MxA mutant K83A retained its interaction with BKPyV TAg, and its antiviral effects were intact. The MxA T103A mutant, on the other hand, abolished GTPase activity, lost its protein-protein interaction with BKPyV TAg, and lost its antiviral effect. IFNα and its downstream protein, MxA, have potent antiviral properties against BKPyV. Furthermore, our findings indicate that the interaction between MxA and BKVPyV TAg plays a crucial role in determining the anti-BKPyV effects of MxA.

Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease. A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively. A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p < 0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS. Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.