Renal transplants

Another natural product, mizoribiae (39), a nucleoside antibiotic produced by the fungus Eupenicillium brefeldianum has cytotoxic and immunosuppressive activity. It has been evaluated for use ia renal transplantation and neoplasia (68). 

Tedesco SH Jr, Pinheiro MP, Rosso FC et al (2006) Immunotherapy for de novo renal transplantation what s in the pipeline Drugs 36 1665-1684... 

The introduction of PP2B (calcinemin) inhibitors revolutionized kidney transplantation. Cyclosporine A and tacrolimus (FK506) are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. Cyclosporine A was in use clinically long before its mechanism of action was elucidated. 

Rapamycin has been known for many years to possess immunosuppressive activity by interfering with the activation of B- and T-cells by interleukin-2. Indeed the first clinically approved indication for rapamycin was renal transplantation. Currently, rapamycin and RAD001 also show promise in liver transplantation and cardiac transplantation, respectively. Generally, treatment protocols utilize a combination of an mTORCl inhibitor, a calcineurin inhibitor and steroids to optimize immunosuppression and minimize nephrotoxicity and other side effects. Rapalogs are also... 

TABLE 24.2 Results of Renal Transplant Model Using Multiple Data Sets (Adapted from Lewis et al. [17])... 

Figure 24.1 A health state model depicting all five transitional health states for patients undergoing renal transplant.

Figure 24.2 The Markov decision-analytic model shows cost and cost-effectiveness evaluations for patients undergoing renal transplant [17]. a = cost b = cost per functioning graft c = cost per rejection-free clinical course.

Lewis R, Canafax D, Pettit K, et al. Use of Markov model for evaluating the cost-effectiveness of immunosuppressive therapies in renal transplant recipients. Transpl Proc 1996 28 2214-17. 

Kim, H.S. and Lee, B.M., Protective effects of antioxidant supplementation on plasma lipid peroxidation in smokers, J. Toxicol. Environ. Health A, 63, 583, 2001. Gaziano, J.M. et al.. Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation. Atherosclerosis, 112, 187, 1995. Sutherland, W.H.F. et al.. Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients, Clin. Nephrol, 52, 30, 1999. 

Westhoff, T. H., Vergoulidou, M., Loddenkemper, C., Schwartz, S., Hofmann, J., Schneider, T., Zidek, W., and van der Giet, M. (2009). Chronic norovirus infection in renal transplant recipients. Nephrol. Dial. Transplant. 24,1051-1053. 

JJ is a 52-year-old woman who presents to your transplant center for a living, related renal transplant. 

ESRD secondary to PCKD and failed previous transplant. One prior renal transplant that occurred in 1995 (received kidney from husband), which failed secondary to chronic allograft nephropathy in 2004 (presumably from multiple rejection episodes within the first few years after transplant). For the previous transplant, the patient was maintained on cyclosporine, mycophenolate, and prednisone. 

Several studies have assessed the clinical efficacy of cyclosporine versus tacrolimus. Most of the studies have shown similar longterm patient and allograft survival, whereas some renal transplant studies have demonstrated improved renal function in tacrolimus-treated patients. The most significant difference between the two agents appears to be their adverse-reaction profiles (Table 52-4). 

Azathioprine was originally approved by the FDA in 1968 as an adjunct immunosuppressant for use in renal transplant recipients. It is available in oral and IV dosage forms.11 Prior to the advent of cyclosporine, the combination of azathioprine and corticosteroids was the mainstay of immunosuppressive therapy. Over the past 10 years, the use of azathioprine has declined markedly due in large part to the success of the MPA derivatives, which are more specific inhibitors of T cell proliferation. 

The most common adverse events associated with these agents are GI (18% to 54%, namely, diarrhea, nausea, vomiting, and gastritis) and myelosuppression (20% to 40%).7,11,26-28 Despite its enteric coating, to date, mycophenolic acid has shown no significant benefit in terms of reduction in GI adverse events compared with mycophenolate mofetil in renal transplant recipients.26... 

MPA derivatives have replaced azathioprine as the antiproliferative agent of choice in most organ transplant centers. The MPA derivatives generally are considered to provide a more specific immunosuppressive effect compared with azathioprine. Mycophenolate mofetil and enteric-coated mycophe-nolic acid have similar safety and efficacy data in renal transplant recipients. 

Hyperlipidemia is seen in up to 60% of heart, lung, and renal transplant patients and greater than 30% of liver transplant patients.64 66 As a result of elevated cholesterol levels, transplant recipients are not only at an increased risk of atherosclerotic events, but emerging evidence also shows an association between hyperlipidemia and allograft vasculopathy.66 Hyperlipidemia, along with other types of cardiovascular disease, is now one of the primary causes of morbidity and mortality in long-term transplant survivors.67... 

Tacrolimus has shown the propensity to cause less severe hyperlipidemia when compared with cyclosporine. Thus conversion from cyclosporine-based immunosuppression to tacrolimus-based immunosuppression may be one way to counteract this disease in transplant recipients.66 Studies demonstrate that steroid withdrawal in renal transplant patients lowered total cholesterol by 17% and LDL-C by 16% unfortunately, an 18% decrease in high-density lipoprotein (HDL) levels also was noted in these patients.66... 

New-onset DM after transplantation (NODAT) is a serious complication that often is underestimated by transplant practitioners.74 Kasiske and colleagues attempted to quantify the cumulative incidence of NODAT in renal transplant recipients and found that 8% of patients developed NODAT at 3 months after transplantation, 13% at 12 months, and... 

Assess appropriate selection of these medications for pharmacokinetic and pharmacodynamic DDIs (Table 52-6), need (e.g., do renal transplant recipients need to continue to take erythropoietin ), and efficacy. 

Baroletti SA, Gabardi S, Magee CC, Milford EL. Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients Fact or fiction. Pharmacotherapy 2003 23(6) 788-801. 

Hardinger KL, Koch MJ, Brennan DC. Current and future immunosuppressive strategies in renal transplantation. Pharmacotherapy 2004 24(9) 1159-1176. 

Several risk factors are known to exist in men and women. The common risk factors for UTI in women include sexual intercourse, lack of voiding after intercourse, use of a diaphragm, use of spermicidal jellies, diabetes, and pregnancy. In men, the risks are different, and are primarily centered on lack of circumcision, and at an older age include prostatic hyperplasia. Common risk factors for both men and women include urologic instrumentation, renal transplantation, neurogenic bladder, and urinary tract obstruction.26... 

Ishikawa A, Flechner SM, Goldfarb DA, et al. Quantitative assessment of the first acute rejection as a predictor of renal transplant outcome. Transplantation 1999 68 1318-1324. 

Grone HJ, Weber C, Weber KS, et al. Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection blocking monocyte arrest and recruitment. FASEB J 1999 13 1371-1383. 

Segerer S, Cui Y, Eitner F, et al. Expression of chemokines and chemokine receptors during human renal transplant rejection. Am J Kidney Dis 2001 37 518-531. 

Fischereder M, Luckow B, Hocher B, et al. CC chemokine receptor 5 and renal-transplant survival. Lancet 2001 357 1758-1761. 

Kanmaz T, Feng P, Torrealba J, et al. Surveillance of acute rejection in baboon renal transplantation by elevation of interferon-gamma inducible protein-10 and monokine induced by interferon-gamma in urine. Transplantation 2004 78 1002-1007. 

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