Impact of Late and Recurrent Acute Graft Pyelonephritis on Long-Term Kidney Graft Outcomes.

Background: While Urinary tract infections are the most common infections in kidney transplant recipients, the impact of late acute graft pyelonephritis (AGPN) on graft outcomes remains unknown. Our study was performed to more precisely evaluate the long-term impact of AGPN. Methods: We included 9052 kidney and combined kidney-pancreas recipients who underwent transplantation between 2008 and 2018 from a French multicenter cohort. The relationships between AGPN and patient and graft survival were analyzed with a time-dependent multivariate Cox model. Results: The cumulative incidence of AGPN was 20.9%. A first episode of early AGPN is associated with a non-significant increase in the risk of graft failure (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 0.90 to 1.79). Though, cumulative number of AGPN episodes (HR = 1.51; 95% CI, 0.89 to 2.57 for two episodes and HR = 2.08; 95% CI, 1.17 to 3.69 for three or more episodes) is associated with an increased risk of graft failure. In contrast, when the first episode of AGPN occurred late (i.e., 6 months post transplantation), the risk of graft failure is significantly increased (HR = 2.25; 95% CI, 1.65 to 3.07), and this risk remains relatively stable with the recurrence of late AGPN episodes. The onset of late AGPN were also associated with a higher risk of patient death. Conclusion: This analysis shows that late AGPN and recurrent AGPN are both risk factors for a poor long-term graft outcome and mortality. Late AGPN should not be considered benign infections in post-transplantation follow-up.

Microbiota and immunoregulation: A focus on regulatory B lymphocytes and transplantation.

The microbiota plays a major role in the regulation of the host immune functions thus establishing a symbiotic relationship that maintains immune homeostasis. Among immune cells, regulatory B cells (Bregs), which can inhibit effector T cell responses, may be involved in the intestinal homeostasis. Recent works suggest that the interaction between the microbiota and Bregs appears to be important to limit autoimmune diseases and help to maintain tolerance in transplantation. Short-chain fatty acids (SCFAs), recognized as major metabolites of the microbiota, seem to be involved in the generation of a pro-tolerogenic environment in the gut, particularly through the regulation of B cell differentiation, limiting mature B cells and promoting the function of Bregs. In this review, we show that this B cells-microbiota interaction may open a path toward new potential therapeutic applications not only for patients with autoimmune diseases but also in transplantation.