Infection renal transplantation

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. 

Jamil, B. et al., Impact of acute rejection therapy on infections and malignancies in renal transplant recipients, Transplantation, 68, 1597, 1999. 

Targeting of anti-inflammatory and anti-fibrotic drugs to the proximal tubular cell may prevent tubulointerstitial inflammation and scarring secondary to systemic and glomerular infection and proteinuria. Furthermore, tubular drug dehvery may be beneficial during shock, renal transplantation, ureter obstruction, diabetes, proteinuria, renal carcinoma and some tubular defect diseases such as Fanconi and Bartter s s5mdrome. 

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use sirolimus. Manage patients receiving the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information needed for the follow-up of the patient. Liver transplantation-excess mortality, graft loss, and hepatic artery thrombosis (HAT) The use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant recipients. Many of these patients had evidence of infection at or near the time of death. 

Fox BC, Sollinger HW, Belzer FO, Maki DG. A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation clinical efiftcacy absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis. Am]Med. 1990 89 225-274. 

PFA has recently undergone clinical evaluation in humans for the treatment of recurrent genital herpes, hepatitis B viral infection, and acquired immunodeficiency syndrome (AIDS), as well as cytomegalovirus (CMV) infection of bone marrow and renal transplant patients. 

Azathioprine is administered to patients who do not respond to calcineurin inhibitors, sirolimus and glucocorticoids. Daily doses of 3-10 mg/kg of azathioprine are administered 1 or 2 days before renal transplantation or on the day of surgery for prophylactic therapy. Mycophenolate mofetil is increasingly used in place of azathioprine for tissue transplantation since it is less myelotoxic and causes few opportunistic infections. 

Povidone-iodine sclerosis has been suggested to be safe and effective in treating lymphoceles after renal transplantation, with only minor complications of the procedure, such as pericatheter cutaneous infections. However, a case of acute renal tubular necrosis has been reported (19). 

Hepatitis C virus infection has been associated with diabetes and is a significant risk in patients with renal transplants. In 427 patients with renal transplants and no previous diabetes mellitus, diabetes after transplantation occurred more often in hepatitis C virus-positive than hepatitis C virus-negative patients (39 versus 9.8%)... 

Comparisons with azathioprine in the renal transplantation literature show that MMF and azathioprine have similar gastrointestinal, hematopoietic, and hepatic toxicity profiles, with a possibly decreased incidence of fungal infections among patients treated with MMF. Hepatic toxicities are infrequent but must be monitored. 

Wdien administered on the day of renal transplantation, both anti-CD25 mAbs were highly effective in reducing the frequencies of first rejection episodes or graft loss (by approximately 20 to 30%) (29-32). Moreover, the number of rejection episodes subjected to antibody therapy was reduced by about 50% as compared with placebo. The safety profile of both mAbs was similar to that of placebo, at least within the first 6 to 12 months after administration. In particular, neither infections nor malignancies were found to be increased in incidence, and... 

In 79 renal transplant patients with chronic viral hepatitis, azathioprine maintenance treatment (n — 34) was associated with a poorer outcome than in 45 patients who discontinued azathioprine (32). Cirrhosis was more frequent in the first group (six versus one), and more patients died with a functioning graft (14 versus two), mostly because of liver dysfunction (n — 5) or infection (n — 6). These results suggest that azathioprine further accelerates the course of the fiver disease in these patients. 

Garcia VD, Keitel E, Almeida P, Santos AF, Becker M, Goldani JC. Morbidity after renal transplantation role of bacterial infection. Transplant Proc 1995 27(2) 1825-6. 

A 34-year-old renal transplant recipient taking a stable regimen of tacrolimus and methylprednisolone was given itraconazole 100 mg bd for a yeast infection of the urinary tract (115). Concomitant therapy with itraconazole led to a marked increase in tacrolimus trough concentrations on the second day of therapy (from 13 to 21 ng/ml) and an increase in serum creatinine concentrations, necessitating dosage reduction of tacrolimus by 50%. 

Patients who have undergone renal transplantation and then require treatment for cytomegalovirus infection are at special risk of renal damage due to foscarnet. 

One renal transplant recipient developed the nephrotic syndrome, with microscopic hematuria and non-ohguric acute renal insufficiency within 15 days after starting foscarnet therapy for cytomegalovirus infection (13). A kidney biopsy showed crystals in aU glomeruh and in the proximal tubules. The crystals consisted of several forms of foscarnet salts. Renal function and proteinuria nevertheless improved progressively, and a second transplant biopsy 8 months after the first one showed... 

Influenza infection has been a significant problem in cardiac transplant patients immunization of such patients could therefore be beneficial. However, its use has been limited by concern that stimulation of the immune system might in principle cause an increased risk of cardiac rejection. In the renal transplant experience, influenza infection itself can trigger an immunological response to cause graft rejection, as well as predisposing to other infections. Another concern is whether an immunosuppressed cardiac transplant recipient could seroconvert sufficiently. In a case-control study in 18 cardiac transplant recipients and 18 control patients 6 months or more beyond transplant surgery, there were no differences in the incidence of cardiac rejection or immune responses (28). 

Cheeseman SH, Rubin RH, Stewart JA, Tolkoff-Rubin NE, Cosimi AB, Cantell K, Gilbert J, Winkle S, Herrin JT, Black PH, Russell PS, Hirsch MS. Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections. N Engl J Med 1979 300(24) 1345-9. 

In patients with renal transplants, the overall incidence of infections during the first three posttransplantation months was significantly higher in one trial of patients treated with prophylactic muromonab or ciclosporin (39), but there was no significant difference in the severity of infections in another similar trial (40). Both studies failed to identify any adverse impact of infectious episodes on patient survival. In a comparison of prophylactic ATG-Fresenius with muromonab there were more common... 

A 49-year-old woman taking ciclosporin, prednisolone, and mycophenolate developed acute refractory rejection 4 days after renal transplantation. After an unsuccessful glucocorticoid pulse, her immunosuppressive regimen was successively changed to muromonab and tacrolimus with mycophenolate maintenance. Twelve days after transplantation she had abdominal pain and watery/bloody diarrhea. Colonoscopy showed multiple ulcers with mucosal injection and colon edema. A biopsy suggested ischemic cohtis and cytomegalovirus infection was ruled out. Her sjmptoms persisted until mycophenolate was withdrawn and further colonoscopy showed complete resolution. 

Rothwell WS, Gloor JM, Morgenstern BZ, Milliner DS. Disseminated varicella infection in pediatric renal transplant recipients treated with mycophenolate mofetil. Transplantation 1999 68(1) 158-61. 

Magee CC, Halligan RD, Milford EL, Sayegh MH. Nocardial infection in a renal transplant recipient on tacrolimus and mycophenolate mofetil. Clin Nephrol 1999 52(l) 44-6. 

In children undergoing renal transplantation and receiving ciclosporin, the mean daily dose of ciclosporin needed to maintain adequate trough concentrations fell when patients were treated with norfloxacin for urinary tract infections (14). 

Long-term follow-up (mean of 93 months) of tacroU-mus-based immunosuppression has been reported in 121 adult patients with liver transplants (10). Infections were the most common causes of deaths (17 patients out of 42), and half of them occurred during the first year after transplantation. Cardiovascular events (seven patients) or de novo malignancies (three patients) were also important causes of death. End-stage renal disease related to tacrolimus nephrotoxicity was noted in two patients who required renal transplantation At 7 years, other important adverse effects included hyperkalemia (30%) or... 

In 14 patients with renal transplants, there was a closed relation between individual tacrolimus whole blood trough concentrations and the occurrence of adverse effects (124). The incidence of tacrolimus adverse effects was 76% with tacrolimus concentrations above 30 ng/ml and only 5.3% with concentrations below 10 ng/ml. This relation was found in all separate groups of adverse effects analysed, that is nephrotoxicity, neurotoxicity, infections, and others. In contrast, there was no relation between tacrolimus concentrations and rejection episodes. Accordingly, the authors stressed that tacrolimus whole blood trough concentrations should be strictly kept under 20 ng/ml. 

Sharma AK, Holder FE. Clostridium difficile diarrhea after use of tacrolimus following renal transplantation. Clin Infect Dis 1998 27(6) 1540-1. 

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