Treatment kidney transplantation

OKT-3 was first approved for general medical use in the USA in 1986. Its indication was the treatment of acute kidney transplant rejection (Table 10.4). OKT-3 is produced via ascites grown in mice. The intact antibody is subsequently purified by a combination of ammonium sulphate fractionation and anion exchange chromatography. Despite its therapeutic effectiveness, the product does display some limitations. Its antigenicity in humans (the HAMA response) is one obvious factor which limits its prolonged use. 

Many attempts have been made to link monoclonal antibodies specific for antigenic determinants on cancer cells to protein toxins such as ricin (Box 29-A). It is hoped that this may provide an effective way of carrying toxins into cancer cells/ 1 r Therapeutic human monoclonal antibodies are already in use as antirejection drugs for kidney transplantation, for treatment of rheumatoid arthritis, Crohn disease, and for some types of cancer/... 

Talalaj M, Gradowska L, Marcinowska-Suchowierska E, Durlik M, Gaciong Z, Lao M. Efficiency of preventive treatment of glucocorticoid-induced osteoporosis with 25-hydroxyvitamin D3 and calcium in kidney transplant patients. Transplant Proc 1996 28(6) 3485-7. 

Haffner D, Nissel R, Wuhl E, Schaefer F, Bettendorf M, Tonshoff B, Mehls O. Metabolic effects of long-term growth hormone treatment in prepubertal children with chronic renal failure and after kidney transplantation. 

The effect was observed in those with renal transplants (9.8% versus 2.7%) and those with other organ transplants (11.1% versus 6.2%), and among patients who were taking equal doses of concomitant medications in both treatment arms (12% versus 3%). Further factors associated with diabetes mellitus after kidney transplantation were older recipient age, a cadaveric organ, hepatitis C antibody status, an episode of rejection, and the use of tacrolimus (versus ciclosporin) cumulative glucocorticoid dose and calcineurin inhibitor trough concentration were not associated factors (1100). 

The second approach to prolonged therapeutic action is based on the controlled rate of conversion of the promoiety into the active compound in vivo. This approach requires particularly detailed study of the kinetics of prodrug-drug conversion. A classic example is bioconversion of azathioprine to 6-mercaptopurine. Azathioprine is used commonly in kidney transplantation, rheumatoid arthritis, and the treatment of various skin disorders. After administration, azathioprine undergoes slow... 

Besides glucose, other analytes of clinical value can be possibly quantified by noninvasive spectral analysis. In vivo concentrations of lactate and urea are examples. The concentration of lactate in blood is used clinically to follow intensive care treatments, to identify cardiac or liver failure, to determine hypoxia of tissues from atherosclerosis, and to detect bacterial infection. In vivo urea levels are valuable for optimizing hemodialysis treatments and tracking the accumulation of toxins for people with end-stage renal failure or recent kidney transplant recipients. 

Monoclonal antibodies (MAb) or MAb fragments have been described above as homing devices for soluble and participate carriers however, they can also be used in their own right as soluble carriers. The first marketed (1986) MAb for therapeutic use was the anti-CD3 antibody OKT3, for the prevention of rejection of kidney transplants. More recently, MAb for the treatment of post angioplasty complications (ReoPro) and for the treatment of colorectal cancers (Panorex) have been introduced. 

Gender-related variability in drug response has also been suggested to be clinically important. For example, in treatment of HIV infections, mycophenolate metabolism is higher in male than female kidney transplant recipients. 

Azoulay D, Castaing D, Lemoine A, Samuel D, Majno P, Reynes M, Charpentier B, Bismuth H. Successful treatment of severe azathioprine-induced hepatic veno-occlu-sive disease in a kidney-transplanted patient with transjugular intrahepatic portosystemic shunt. Clin Nephrol 1998 50(2) 118-22. 

Wynckel A, Toupance O, Melin JP, David C, Lavaud S, Wong T, Lamiable D, Chanard J. Traitement des legionelloses par ofloxacine chez le transplante renal. Absence d interference avec la ciclosporine A. [Treatment of legionellosis with ofloxacin in kidney transplanted patients. Lack of interaction with cyclosporin A.] Presse Med 1991 20(7) 291-3. 

Rostaing L, Izopet J, Baron E, Duffaut M, Puel J, Durand D. Treatment of chronic hepatitis C with recombinant interferon alpha in kidney transplant recipients. Transplantation 1995 59(10) 1426-31. 

The effect of ketoconazole in ciclosporin-treated kidney transplant recipients has been the subject of a prospective randomized study (37). In 51 ketoconazole-treated patients and 49 controls there was a similar frequency of acute rejection episodes. However, in the control group, rejection episodes were more recurrent, with a poorer response to treatment. Acute ciclosporin nephrotoxicity was more common in the ketoconazole group, but this was encountered more at induction and rapidly reversed on further reduction of the dose of ciclosporin. Chronic graft dysfunction was significantly less in... 

Tendinopathy has been reported with levofloxacin. Four cases of Achilles tendinitis have been reported in patients taking levofloxacin (29). Two were on chronic dialysis, one was a kidney transplant recipient, and one had chronic vasculitis. In all four cases, tendinitis had an acute onset with bilateral involvement and was incapacitating. In three cases the onset was early during levofloxacin treatment and in one case it began 10 days after the end of treatment. AH the patients recovered completely after 3-8 weeks. 

Mycophenolate mofetil has been compared with azathioprine in combination with ciclosporin and glucocorticoids in 65 children after kidney transplantation (32). The main adverse effects of this treatment were infections of the urinary tract and the upper respiratory tract, abdominal pain, and diarrhea. Opportunistic infections with cytomegalovirus or cytomegalovirus syndrome occurred in 20% within the first 6 months and tissue-invasive cytomegalovirus disease in 3.1%. These results were similar to those in adults. 

Rifampicin enhances the catabolism of many glucocorticoids. For example, it increases the plasma clearance of prednisolone by 45 % and may reduce the amount of drug available to the tissues by as much as 66% (SEDA-8,288). Glucocorticoid therapy for concomitant diseases should therefore be adjusted in the light of plasma concentrations and clinical effects during rifampicin treatment (SEDA-10,272). For example, rejection of a kidney transplant occurred after 7 weeks of rifampicin therapy (109). 

Berg KJ, Nordby G, Rootwelt K, Djoseland O, Eauchald P, Mehl A, et al. Effects on renal function of combined treatment with trimethoprim and cyclosporine A in kidney transplant patients. Transplantation proceedings. 1988 Jun 20(3) 413-5. 

Cidofovir is an acyclic nucleotide analogue of the monophosphate of cytosine. When phosphoiylated by host cellular enzymes, the active compound cidofovir diphosphate has broad activity against the herpes viruses, including CMV, HSV 1 and 2, VZV, Epstein-Barr virus, and the BK polyomavirus. Cidofovir has primarily been used in the treatment of CMV retinitis in patients who have failed treatment with ganciclovir or foscarnet and in acyclovir-resistant herpes simplex infections. More recently, there is also a growing experience with the use of this medication in kidney transplant patients who have BK virus-associated nephropathy [31], although this interest has been dampened by significant toxicity and only modest clinical activity [32]... 

Gatti S, Arru M, Reggiani P, Como G, Rossi F, Fassati LR, Ponticelli C. Successful treatment of hemolytic uremic syndrome after liver-kidney transplantation. J Nephrol 2003 16 586-590. 

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