Emphysematous pyelonephritis (EPN) is a rare and serious necrotizing infection that is potentially life-threatening. It has been seldom reported in kidney grafts and is usually caused by Gram-negative bacteria, with some case reports caused by anaerobic bacteria, and has been closely associated with poorly controlled diabetes mellitus (DM) and urinary tract structural abnormalities. There are no reports of EPN of fungal etiology in kidney grafts. We present a case of a 53-year-old kidney transplant recipient with a history of DM, active vesicoureteral reflux, and recurrent urinary tract infections who developed EPN in the kidney allograft caused by Candida glabrata, 3 weeks after starting treatment with empagliflozin, with an aggressive course that required urgent transplant nephrectomy.

The +874 A/T polymorphism in the interferon gamma (IFNG) gene has been associated with Cytomegalovirus (CMV) infection risk in lung and kidney transplant recipients. To replicate this association, we performed a retrospective observational study of this polymorphism and immunosuppressive therapies considering the prophylactic treatment in 600 consecutive kidney transplanted recipients. We found no association of the aforementioned polymorphism with CMV infection in univariate and multivariate analyses regardless of the prophylactic treatment. In addition, the immunosuppressive treatment with mammalian target of rapamycin inhibitors (imTOR) showed a protective effect in all patients independently of prophylaxis. Moreover, in the adjusted model, we found interactions between prophylaxis with high-risk (Donor+/Recipient–, D+/R–) status (p-interaction = 0.01), with thymoglobulin induction therapy (p-interaction = 0.03) and with thymoglobulin anti-rejection therapy (p-interaction = 0.002). Data also revealed that prophylaxis was not an advantage in the not D+/R– and without thymoglobulin therapy group (HR = 0.98, p = 0.95). The benefit of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV infection group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, p < 0.001). In conclusion, the IFNG +874 polymorphism is not a predictive marker of CMV infection. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV infection, and prophylaxis is not effective in recipients with no high-risk CMV status and without thymoglobulin therapy.

Background: IgG4 is the least immunogenic subclass of IgG. Immunization with mRNA vaccines against SARS-CoV-2, unlike other vaccines, induces an increase in IgG4 against the spike protein in healthy populations. This study investigated whether immunosuppressive therapy affects the immune response, focusing on IgG subclass changes, to four doses of mRNA vaccine in kidney transplant recipients (KTRs). Methods: This study includes 146 KTRs and 23 dialysis patients (DPs) who received three mRNA-1273 vaccine doses and a BNT162b2 booster. We evaluated anti-spike IgG titers and subclasses, T-CD4+ and T-CD8+ cellular responses, and serum neutralizing activity (SNA). Results: At the fourth dose, 75.8% of COVID-19 naïve KTRs developed humoral and cellular responses (vs. 95.7% in DPs). There was a correlation between anti-spike IgG titers/subclasses and SNA (p < 0.001). IgG subclass kinetics after the third/fourth dose differed between COVID-19 naïve KTRs and DPs. Immunosuppressive therapy influenced IgG subclasses: mTOR inhibitors (mTORi) positively influenced IgG1 and IgG3 (p < 0.05), while mycophenolic acid negatively affected IgG1, IgG3, and IgG4 (p < 0.05). SNA is correlated with breakthrough infections after four doses of vaccine in KTRs. mTORi was the only factor associated with SNA > 65% in naïve KTRs [4.29 (1.21–15.17), p = 0.024]. Conclusions: KTRs show weaker cellular and humoral immune responses to mRNA vaccines and a class shift towards non-inflammatory anti-S IgG4 upon booster doses. IgG subclasses show a positive correlation with SNA and are influenced by immunosuppression. Increased SNA after four doses of vaccine is protective against infection. mTORi may benefit non-responding KTRs.

The management of diabetes and renal failure is changing thanks to the appearance of new drugs such as glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i) that have benefits in terms of survival and cardiorenal protection. Based on the potential mechanisms of GLP1-RA, kidney transplant recipients (KTRs) could benefit from their effects. However, high-quality studies are needed to demonstrate these benefits, in the transplant population, especially those related to cardiovascular benefits and renal protection. Studies with SGLT2i performed in KTRs are much less potent than in the general population and therefore no benefits in terms of patient or graft survival have been clearly demonstrated in this population to date. Additionally, the most frequently observed side effects could be potentially harmful to this population profile, including severe or recurrent urinary tract infections and impaired kidney function. However, benefits demonstrated in KTRs are in line with a known potential effects in cardiovascular and renal protection, which may be essential for the outcome of transplant recipients. Better studies are still needed to confirm the benefits of these new oral antidiabetics in the renal transplant population. Understanding the characteristics of these drugs may be critical for KTRs to be able to benefit from their effects without being damaged. This review discusses the results of the most important published studies on KTRs with GLP1-RA and SGLT2i as well as the potential beneficial effects of these drugs. Based on these results, approximate suggestions for the management of diabetes in KTRs were developed.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) preserve cardiac and renal function by mechanisms that are not completely elucidated. Among other things, SGLT2i promote nutrient-deprivation signalling, which might affect the immune function. As the fate of immune cells is controlled by their metabolism, we aimed to study the mitochondrial integrity of lymphocytes isolated from renal transplant recipients with type 2 diabetes (T2D) upon SGLT2i therapy instauration and six-month follow up. In this real-world pilot study, the mitochondrial respiration of isolated peripheral blood mononuclear cells was monitored in a Seahorse XFp extracellular-flux analyzer and cells were photographed with a confocal microscope. Mitochondrial mass, membrane potential, and superoxide content of lymphocyte subpopulations were measured by flow cytometry (MitoTracker^TM Green, TMRM, and MitoSOX^TM Red probes). Leveraging in vivo conditions of immune cells, we evaluated their metabolic profiles associated with immune activation. Herein, we identified changes in redox homeostasis with sustained membrane polarization, and an increased mitochondrial biogenesis upon PHA stimulation that significantly correlated with changes in body weight and LDL-cholesterol levels, and a resultant compensatory mitochondrial function of lymphocytes. Our data suggest novel mechanisms induced by SGLT2i to modulate immune cells, which probably underlie the observed beneficial effects in kidney transplant recipients. Nonetheless, further mechanistic studies are required to extend these exploratory findings and encourage the use of this therapeutic strategy.