Renal Transplantation

Abstract

Abstract. How to combine antirejection drugs and which is the optimal dose of steroids and calcineurin inhibitors beyond the first year after kidney transplantation to maintain adequate immunosuppression without major side effects are far from clear.

Randomized Controlled Study Comparing Reduced Calcineurin Inhibitors Exposure Versus Standard Cyclosporine-Based Immunosuppression

“…In addition, the use of CsA full-dose has been associated with enhanced renal mRNA-expression of TGF-␤, contributing to interstitial fibrosis after KT (13). Thus, the preservation of renal function using immunosuppressive protocols with reduced exposure of both CNIs may be attributable to reversal of afferent arteriola constriction, stabilization/regression of arteriolar lesions or improvement of interstitial damage, as have been observed in protocol biopsies (14). The fact that calculated GFR did not reach significant differences between group B and C at 12 and 24 months posttransplantation, supports this argument.…”

Untreated Rejection in 6-Month Protocol Biopsies Is Not Associated with Fibrosis in Serial Biopsies or with Loss of Graft Function

“…At present, we lack a reliable metric to decide whether asymptomatic interstitial infiltrates represent ongoing rejection or the exponent of a regulatory response that is self-limiting, is not harmful to the graft, and does not need drug adjustments. We suggest delaying drug withdrawal or minimization until the risk for SAR is diminished or preferably ruled out by reliable biomarkers either in a surveillance biopsy (53) or in biologic fluids. The relevance of AUC-guided monitoring then may be found in the control over drug exposure for the remaining drug or the drug that is considered for conversion (54).…”

Early steroid withdrawal protocol with basiliximab, cyclosporine and mycophenolate mofetil in renal-transplant recipients

“…Early corticosteroid withdrawal is desirable to avoid the negative consequences of longterm corticosteroid use. However, lowering the dose of antirejection drugs to reduce the risk of serious adverse effects has led to equivocal results [5,6,14]. The risk of acute rejection after steroid withdrawal apparently increased in previous studies using corticosteroids, CsA and azathioprine for immunosuppression in renal-transplant recipients [14,15].…”

“…Long-term steroid therapy carries the additional risk of cardiovascular disease, a leading cause of post-transplant morbidity and mortality, by promoting hypertension, hyperlipidemia and glucose intolerance [3,4]. On the other hand, the untimely withdrawal of corticosteroids from conventional immunosuppressive regimens can increase the risk of acute rejection [5,6]. Although steroid withdrawal at different times after renal transplantation has been associated with considerable variability in rejection rates (ranging from 14% to 60%), the risk of rejection after steroid withdrawal has increased in all studies using a regimen of steroids, cyclosporine A (CsA) and azathiopurine.…”