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      Non-viral infections in children after renal transplantation

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          Abstract

          Renal transplantation has long been recognised as the gold standard treatment for children with end-stage renal failure. There has been an improvement over the years in patient and renal allograft survival because of improved immunosuppression, surgical techniques and living kidney donation. Despite reduced acute allograft rejection rates, non-viral infections continue to be a serious complication for paediatric renal transplant recipients (RTR). The risk of infections in RTR is determined by the pre-transplantation immunisation status, post-transplant exposure to potential pathogens and the amount of immunosuppression. The greatest risk of life-threatening and Cytomegalovirus infections is during the first 6 months post-transplant owing to a high immunosuppressive burden. The potential sources of bacterial infections are donor derived, transplant medium fluid, peritoneal and haemodialysis catheter and transplant ureteric stent. Urinary tract infections are frequent in patients with lower urinary tract dysfunction and can result in renal allograft damage. This review outlines the incidence, timing, risk factors, prevention and treatment of non-viral infections in paediatric RTR by critically reviewing current immunosuppressive regimens, their risk–benefit ratio in order to optimise renal allograft survival with reduced rates of rejection and infectious complications.

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          Most cited references93

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          Immunosuppressive drugs for kidney transplantation.

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            Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients.

            Everolimus, a novel proliferation inhibitor and immunosuppressive agent, may suppress cardiac-allograft vasculopathy. We conducted a randomized, double-blind, clinical trial comparing everolimus with azathioprine in recipients of a first heart transplant. A total of 634 patients were randomly assigned to receive 1.5 mg of everolimus per day (209 patients), 3.0 mg of everolimus per day (211 patients), or 1.0 to 3.0 mg of azathioprine per kilogram of body weight per day (214 patients), in combination with cyclosporine, corticosteroids, and statins. The primary efficacy end point was a composite of death, graft loss or retransplantation, loss to follow-up, biopsy-proved acute rejection of grade 3A, or rejection with hemodynamic compromise. At six months, the percentage of patients who had reached the primary efficacy end point was significantly smaller in the group given 3.0 mg of everolimus (27.0 percent, P<0.001) and the group given 1.5 mg of everolimus (36.4 percent, P=0.03) than in the azathioprine group (46.7 percent). Intravascular ultrasonography showed that the average increase in maximal intimal thickness 12 months after transplantation was significantly smaller in the two everolimus groups than in the azathioprine group. The incidence of vasculopathy was also significantly lower in the 1.5-mg group (35.7 percent, P=0.045) and the 3.0-mg group (30.4 percent, P=0.01) than in the azathioprine group (52.8 percent). The rates of cytomegalovirus infection were significantly lower in the 1.5-mg group (7.7 percent, P<0.001) and the 3.0-mg group (7.6 percent, P<0.001) than in the azathioprine group (21.5 percent). Rates of bacterial infection were significantly higher in the 3.0-mg group than in the azathioprine group. Serum creatinine levels were also significantly higher in the two everolimus groups than in the azathioprine group. Everolimus was more efficacious than azathioprine in reducing the severity and incidence of cardiac-allograft vasculopathy, suggesting that everolimus therapy may alleviate this serious problem. Copyright 2003 Massachusetts Medical Society
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              Mortality and causes of death of end-stage renal disease in children: a Dutch cohort study.

              To establish mortality rates, causes of death, and determinants of mortality in children with end-stage renal disease (ESRD), we performed a national long-term follow up study. Mortality rate was determined in all Dutch patients with onset of ESRD at ages 0 to 14 years in the period between 1972 and 1992. Causes of death and mortality determinants were investigated in all patients of this cohort who were born before 1979. Data were derived from the Dutch Registry for patients on renal replacement therapy (RRT), medical charts and National Health Database. Of all 381 patients 85 had died. The overall mortality rate (MR) was 1.57/100 patient-years, and the standardized mortality rate (SMR) was 31.0. The MR for patients 0 to 5 and 6 to 10 years old at onset of ESRD decreased from, respectively, 7.0 (range 0-14.9) to 3.9 (1.2-6.7) and 4.3 (1.1-7.5) to 1.6 (0.3-2.8) between the periods 1972-1981 and 1982-1992. The mortality hazard ratio of relatively long standing dialysis and of long standing hypertension were, respectively, 7.2 (4.4-11.8) and 3.1 (2.1-4.6), of cyclosporine-introduction in transplanted patients 0.3 (0.1-0.4). Overall cerebrovascular accidents (24%) and infections (21%) were the most common causes of death; after 10 years of RRT cardiac death (7/21) was most prevalent. Cardiovascular death was most prominent in dialysis as well as transplanted patients. Survival in children with ESRD has increased over the last 20 years, but the SMR remains high. Early transplantation and a more vigorous approach toward hypertension and infection may be mandatory in order to further reduce mortality.
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                Author and article information

                Contributors
                +44-20-74059200 , +44-20-78298841 , stephen.marks@gosh.nhs.uk
                Journal
                Pediatr Nephrol
                Pediatr. Nephrol
                Pediatric Nephrology (Berlin, Germany)
                Springer-Verlag (Berlin/Heidelberg )
                0931-041X
                1432-198X
                9 February 2012
                9 February 2012
                September 2012
                : 27
                : 9
                : 1465-1476
                Affiliations
                Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH England UK
                Article
                2099
                10.1007/s00467-011-2099-z
                3407356
                22318475
                8ca64bd1-3048-4bb6-8601-1f3e188d3034
                © IPNA 2012
                History
                : 16 January 2011
                : 5 November 2011
                : 11 November 2011
                Categories
                Educational Review
                Custom metadata
                © IPNA 2012

                Nephrology
                graft survival,risk of infection,non-viral infection,paediatric renal transplantation,immunosuppression minimisation

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