Editorial: Factors Affecting Graft Survival After Renal transplant: Prevention of Failure and Follow-up Strategiesanything beyond immunology?

Laila-Yasmin Mani ^*

• Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, Bern, Bern, Switzerland

Since its first introduction in 1951 1 , kidney transplantation has become the best therapeutic option for patients affected by end-stage kidney disease. Indeed, kidney transplant recipients experience a clear survival benefit when compared to their matched counterparts on the waiting list. 2 Thanks to the development of highly effective immunosuppressive regimens, the much-feared threat of acute organ rejection could be well mastered. Surprisingly, despite these major advancements, a trend for decreased graft survival has been recorded over recent decades. 3 Considered the final common pathway of all transplanted kidneys, the interstitial fibrosis and tubular atrophy (IFTA)-lesion of the kidney graft is thought to be multifactorial in origin secondary to immunological, cardiovascular, toxic and infectious causes. 4 In this Research Topic, 15 articles of various formats from different geographic regions in the world invite us to shed light on diverse aspects of long-term kidney graft function.Biopsy-proven causes for graft failure after a very long follow-up up to 26 years were examined by Betjes et al. in a prospective Dutch cohort of 737 kidney transplant recipients (Betjes et al.). The category of rejection accounted for the main part of death-censored graft survival while recipient's age, time after transplantation, and the presence of donor-specific antibodies before transplantation determined the relative contribution to overall graft loss and the type of rejection involved.The influence of age and sex on graft survival was analysed by Sancho and colleagues in a retrospective Spanish cohort of 1101 kidney transplant recipients (Sancho et al.). The lower graft survival of female patients under 60 years of age was attributed to a more frequent use of expanded criteria donors and a higher prevalence of pre-transplant human leukocyte antigen sensitization.Furthermore, the influence of donor race was examined in a retrospective clinicopathological analysis from Columbia University NY on roughly 1900 kidney transplant recipients. The authors confirmed a shorter allograft survival of kidney grafts from black donors and revealed a higher risk for the development of collapsing glomerulopathy in grafts from black donors (DiFranza).Infections as cause of late graft loss and complicated post-transplant course were the topic of several reports in this collection. Brune et al. found no impact of first year urinary tract infection (UTI) episodes with extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella species on graft survival in 389 kidney transplant recipients within the Swiss Transplant Cohort while hospitalization and UTI recurrence rates were higher compared to patients affected by UTI with non-ESBL-producing strains (Brune et al.). In an Italian retrospective cohort of 939 kidney transplant recipients, MRI-confirmed acute graft pyelonephritis was associated with reduced death-censored graft survival influenced by donor age, multifocal presentation and abcedation as well as anti-thymocyte glogulin induction (Tarragoni et al. Finally, functional kidney graft ischemia has been evoked as cause for the development of IFTA. In our center, we have examined the hypothesis that grafts are less oxygenated during the sitting position due to kinking or bending of the iliacal vessels analogous to iliacal claudication described in professional cyclists. Using a multiparametric functional kidney MRI protocol including blood oxygen level-dependent (BOLD)-MRI, diffusion-MRI and arterial spin labeling-MRI during neutral and flexed hip position, the Bent Knee Study showed an acute impact of hip flexion on graft perfusion and oxygenation (Mani et al.).Immune-dependent factors play a well-known role for kidney graft survival with rejection episodes contributing to early and late graft loss. Therefore monitoring of immunosuppression has a major role in preventing rejection and avoiding infectious and toxic complications. Reineke et al. correlated Torque teno virus load in 106 kidney transplant recipients undergoing indication biopsies to histological findings and conclude that Torque teno virus load may reflect changes in immunosuppressive therapy even after the first year post-transplant (Reineke et al.). In a proof-of-principle study by Born et al. in