Calcineurin Nephrotoxicity

Abstract

Calcineurin inhibitors, cyclosporine and tacrolimus, have improved allograft survival in solid organ transplantation. Indeed, they have reduced the incidence of acute rejection episodes of cadaveric allograft recipients. Although marked progression has been made in initial survival rates, long-term kidney graft survival has yet to show such encouraging results. Chronic allograft dysfunction is the major hindrance to long-term graft survival and many components contribute to this entity, both immunologic and nonimmunologic. Chronic calcineurin nephrotoxicity is a major factor in chronic allograft dysfunction. This review will highlight the current understanding and management of calcineurin nephrotoxicity in kidney transplantation.

Tacrolimus and Cyclosporine Nephrotoxicity in Native Kidneys of Pancreas Transplant Recipients

“…The suggestion that TAC may be less nephrotoxic than CSA (2) remains controversial (4), as recently outlined (5). Most studies comparing renal injury associated with these agents were in renal allografts where it is often impossible to discriminate between structural changes from drug toxicity versus other causes of cortical scarring (1). Whereas there are several biopsy studies in native kidneys of CSA patients (1), there is little information on TAC lesions in native kidneys.…”

“…Most studies comparing renal injury associated with these agents were in renal allografts where it is often impossible to discriminate between structural changes from drug toxicity versus other causes of cortical scarring (1). Whereas there are several biopsy studies in native kidneys of CSA patients (1), there is little information on TAC lesions in native kidneys. Studies in liver transplantation described similar renal pathologic findings in patients treated with CSA and TAC (6); however, kidney biopsies were performed for clinical indications and cannot be considered as representative of the liver transplant population.…”

“…Nevertheless, cyclosporine (CSA) and tacrolimus (TAC) have important adverse effects, especially nephrotoxicity (1). Thus, 5 years after liver transplantation, renal failure prevalence is 18% (2) and progressive renal damage in nonrenal organ transplant recipients is a significant contributor to ESRD (2).…”

“…Thus, 5 years after liver transplantation, renal failure prevalence is 18% (2) and progressive renal damage in nonrenal organ transplant recipients is a significant contributor to ESRD (2). Both CSA and TAC have renal hemodynamic effects leading to rapid reductions in GFR which, early on, are reversible upon dose reduction or cessation (1). Eventually, GFR loss may become irreversible, reflecting structural changes, including tubular atrophy, interstitial fibrosis, glomerulosclerosis, and arteriolopathy (3).…”

Protective Role of Polyphenols in Cyclosporine A-induced Nephrotoxicity During Rat Pregnancy

“…FOR NEARLY THREE DECADES cyclosporine A (CsA) has been demonstrated to be a powerful immunosuppressive agent commonly used for organ transplantation and treatment of various autoimmune diseases (Ponticelli 2005;Williams and Haragsim 2006). Yet numerous adverse effects appear to be related to CsA, most notably nephrotoxicity (Rezzani 2004;Hong et al 2005) but also hypertension (Nishiyama et al 2003;Rezzani 2004), hepatotoxicity (Durak et al 2004;Rezzani 2004), lymphoproliferative diseases (van den Borne et al 1998;Fozza et al 2005), atherosclerosis of the graft, or interstitial myocardial fibrosis (RedondoHorcajo and Lamas 2005).…”