The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving

Abstract

Abstract. The 6-mo function and the stability of function posttransplantation in 429 cadaver renal transplants was investigated from 1990 to 2000. The 6-mo creatinine clearance (CrCl) and the rate of change of CrCl beyond 6 mo posttransplantation were calculated. The mean 6-mo CrCl was 64.6 Ϯ 1.1 ml/min and was stable between 1990 and 2000. The net slope of CrCl was Ϫ1.4 Ϯ 0.5 ml/min per yr. The slope has improved in recent years, such that the mean slopes in the period after 1997 are actually positive (ϩ3.5 ml/min per yr). The slope of CrCl beyond 6 mo was not related to the actual value of the 6 mo CrCl, i.e., there was no accelerated loss of function at low CrCl levels. The 6-mo CrCl was independently determined by donor factors (age, gender), recipient factors (age, gender), and immune factors (rejection episodes, regraft status). The slope of the CrCl correlated independently with the transplant year, recipient gender, rejection episodes, diastolic BP, and the choice of immunosuppressive drugs. Cytomegalovirus infection and mismatch status and lipid levels and treatment were not independently associated with slope or 6-mo CrCl. Thus, the most striking change in the course of renal transplants over the past decade is the new stability of function, correlating with reduced rejection and probably due at least in part to the new immunosuppressive agents. Despite continued calcineurin inhibitor use, late improvement in function now occurs in many cadaver kidney transplants, suggesting a previously unappreciated capacity for functional adaptation.With improved control of early rejection and graft loss (1), the emphasis in renal transplantation has now shifted to improving the long-term transplant course. This includes a focus on reducing late graft loss by stabilizing and improving renal function, controlling immunosuppressive side effects, and reducing risk factors for patient survival. The frequency of late graft loss remains excessive: approximately 7% of renal transplants currently functioning in Canada and the United States will fail each year, with approximately half of the losses being due to patient death and the remainder being due to loss of function. In studying the failures that are due to loss of renal function, transplant population studies have usually examined outcomes such as graft survival and half-life. However, these approaches are limited because they give information only about grafts that have failed completely and do not distinguish grafts with poor function from the outset from grafts with excellent function that subsequently deteriorate.Additional information can be gained by looking at renal function outcomes and change in function, permitting examination of the whole population, not just failures. Renal function has long been recognized as a critical determinant of the probability of graft survival (2), and its critical role as a predictor of survival has recently been confirmed in the United Network for Organ Sharing (UNOS) database (3). Serum creatinine and calculated and measured cr...

Chronic Calcineurin Inhibitor Nephrotoxicity

“…The first is the undeniable improvement in allograft outcomes that has occurred under CNI-based therapy, even as the field has witnessed significant aging of the donor and recipient populations, less MHC similarity between donor and recipient, and, in kidney transplantation, commonplace use of kidneys with preexisting injury (34,35). Although some studies have indeed documented excellent outcomes with CNI-free immunosuppression, CNI-based protocols have been shown over and over again in clinical trials to result in renal function at least as stable as proposed alternatives and graft survival equivalent or superior to those available with any other option, as shown in the Symphony (Efficacy Limiting Toxicity Elimination [ELITE]-Symphony) trial, the CAESAR (Cyclosporine Avoidance Eliminates Serious Adverse Renal toxicity) trial, the ORION (Optimizing Renal Transplant Immunosuppression to Overcome Nephrotoxicity) trial, and numerous single-center studies (36 -39).…”

“…Subsequently, the Westmeade group documented the addition of mycophenolate to cyclosporinebased immunosuppression not only to reduce adverse immunologic events but also to diminish the lesions thought to be the sine qua non of CNI nephrotoxicity: arteriolar hyalinosis and striped interstitial fibrosis (43). Indeed, several series have documented much greater stability of renal function, despite ongoing use of CNI-based therapy, in the current era (35,44). The reversibility and relative stability of renal dysfunction that can occur after CNI withdrawal (as in the Spare-the-Nephron trial, among others), as long as rejection does not supervene, also argues against the concept of irreversible chronic nephrotoxicity (45).…”

Cellular Senescence Limits Regenerative Capacity and Allograft Survival

“…Tubulointerstitial changes are a common feature in many chronic renal diseases and eventually are the cause for returning to dialysis after transplantation. [3][4][5] An explanation for the strong predictive value of donor age and transplantation-dependent tissue injury for the development of interstitial fibrosis and tubular atrophy 6,7 could be changes in cell fate programming, such as senescence, that lead to the inability of tubular epithelial cells to repair and maintain nephron integrity. [8][9][10] Cellular senescence is reached through two main pathways: telomere-dependent and telomereindependent senescence.…”

Persistent hyperparathyroidism after kidney transplantation; updates on the risk factors and its complications

“…Persistent post-transplant HPT is thought to be primarily attributed to some degree of CKD and parathyroid gland hyperplasia retained by kidney-transplant patients (9,23). Postkidney transplant recipients have eGFR approximately 30 to 60 mL/min/1.73 m 2 (9,23) and hence manifest some degree of reduced kidney function, resulting in CKD-related HPT (19).…”