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Renal function: defining long-term success
Julio Pascual1, Roberto Marcén, Joaquín Ortuño
1Department of Nephrology, Ramón y Cajal Hospital, Ctra Colmenar Viejo Km9.1, Madrid 28034, Spain. jpascual.hrc@salud.madrid.org
Insights
Early assessment of renal function post-transplant predicts long-term graft survival. Tacrolimus-based immunosuppression, particularly with mycophenolate mofetil (MMF), shows superior graft survival rates compared to ciclosporin, even with similar serum creatinine levels.
Area of Science:
- Nephrology
- Transplantation Immunology
- Clinical Pharmacology
Background:
- Chronic allograft nephropathy is a major cause of late graft loss, characterized by declining renal function.
- Early post-transplant renal function, specifically serum creatinine levels, is a critical predictor of long-term kidney transplant outcomes.
- Registry data and pooled analyses highlight the significance of serum creatinine concentrations at 6 or 12 months for predicting 5-year graft survival.
Purpose of the Study:
- To evaluate the impact of different immunosuppressive therapies on long-term renal function and graft survival after kidney transplantation.
- To compare the efficacy of tacrolimus-based regimens (with azathioprine or MMF) versus ciclosporin-based regimens in maintaining renal function and graft survival.
- To determine if early post-transplant serum creatinine levels can predict long-term transplant success.
Main Methods:
- Retrospective analysis of 216 renal transplantations performed between 1996 and 2000.
- Patients were treated with immunosuppressive therapy based on tacrolimus/azathioprine (n=51), tacrolimus/mycophenolate mofetil (MMF; n=70), or ciclosporin microemulsion/azathioprine/corticosteroids (n=95).
- Graft survival and serum creatinine concentrations were assessed at 3 years post-transplant.
Main Results:
- Tacrolimus/MMF therapy demonstrated the best 3-year graft survival.
- Despite similar serum creatinine levels between tacrolimus (1.69 mg/dl) and ciclosporin (1.65 mg/dl) groups, the tacrolimus group had significantly higher functioning graft rates (84% vs 67%, P=0.007).
- Early serum creatinine levels (as early as 1 month) may predict long-term survival.
Conclusions:
- Tacrolimus-based immunosuppression, particularly when combined with MMF, offers superior graft survival compared to ciclosporin-based regimens.
- Good long-term renal function can be maintained with tacrolimus as the cornerstone of immunosuppression, often without needing CNI minimization strategies.
- Early post-transplant renal function monitoring is crucial for predicting long-term kidney transplant outcomes.
Abstract:
One of the leading causes of late graft loss is chronic allograft nephropathy, characterized in part by deteriorating renal function. Registry data have demonstrated that renal function within the first year post-transplant is an important predictor of long-term transplant outcome, with serum creatinine concentrations < or =1.5 mg/dl at 6 or 12 months being associated with the highest rate of 5 year graft survival. These findings are supported by a retrospective, pooled analysis of two multicentre trials in the USA, as well as by our own data showing that serum creatinine concentrations may be predictive of long-term survival as early as 1 month post-transplant. Analysis of 216 renal transplantations carried out at our centre (1996-2000) using immunosuppressive therapy based on tacrolimus, corticosteroids and azathioprine (n = 51) or mycophenolate mofetil (MMF; n = 70) vs ciclosporin microemulsion, azathioprine and corticosteroids (n = 95) showed that the best 3 year graft survival was achieved with tacrolimus/MMF therapy. While serum creatinine concentrations at this time point were similar for the tacrolimus and ciclosporin treatment groups (1.69 and 1.65 mg/dl, respectively), the proportion of patients with functioning grafts was significantly higher in the tacrolimus group (84 vs 67%, P = 0.007). Similar findings of improved renal function or graft outcomes with tacrolimus- vs ciclosporin-based therapy have been reported in other single-centre and multicentre trials and a USRDS registry survey. Accumulating data suggest that renal function compares well between tacrolimus-based and calcineurin inhibitor (CNI)-sparing regimens. Consequently, the vast majority of renal transplant recipients maintain good long-term renal function with tacrolimus cornerstone immunosuppression without adopting CNI minimization or withdrawal strategies.
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