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PubMed2004

Cytomegalovirus and lung transplantation.

Cytomegalovirus (CMV) infection remains a serious problem in lung transplant recipients. Development of potent oral antiviral agents, molecular techniques for the detection of infection and its response to therapy and the emergence of isolates with antiviral resistance have had significant impacts on the approach to CMV in these patients. This article discusses the following issues as part of a comprehensive CMV management strategy in lung transplant recipients: (1) Prevention strategies in the era of potent oral antiviral agents, (2) the role of new diagnostic techniques in the management of CMV, (3) treatment regimens for established CMV infection or disease, (4) the potential impact of treatment of CMV on the indirect effects on long-term allograft function, and (5) the incidence, risk factors for and impact of ganciclovir resistance following lung transplantation.

Antiviral Agents↗

PubMed2004

Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy.

The majority of preconditioning protocols developed to allow ABO-incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful engraftment. Our center has developed a preconditioning protocol that includes plasmapheresis (PP), low-dose CMV hyperimmune globulin (CMVIg), and anti-CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy. Our initial experience has included treatment of six recipients and successful transplantation from blood group A(1), A(2), and group B living donors. Mean (+/- SD) serum creatinine was 1.3 +/- 0.1 mg/dL among the six recipients and no episodes of antibody-mediated rejection (AMR) occurred at a median follow-up of 12 months. ABO antibody titers have remained below pretreatment levels. The absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation. The use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post-splenectomy infections.

ABO Blood-Group System↗

PubMed2004

Steroid sparing with tacrolimus and mycophenolate mofetil in renal transplantation.

Evidence suggests that steroid sparing in renal transplantation is associated with good outcomes, although there are limited data regarding steroid sparing in Tacrolimus and Mycophenolate Mofetil (MMF)-based regimes. In this study we describe the use of these agents in 101 consecutive patients undergoing renal transplantation using only a 7-day course of prednisolone. Median follow-up was 33 months (range 18-44). Patient and graft survival at 1 year were 100% and 98%, respectively. The acute rejection rate at both 6 and 12 months was 19%, with two episodes beyond 12 months. Anti-CD25 monoclonal antibody (anti-CD25 mAb) was administered to 25 patients at high immunological risk: a trend toward a lower rejection rate was seen in these patients compared with those at lower risk but not receiving induction therapy (8% vs. 22%; p = 0.11). Two patients experienced recurrent rejection. Of the twenty-three rejection episodes in total, 26% showed vascular involvement. Allograft function was preserved at 12 months with a mean creatinine of 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. At 12 months, the incidence of post-transplant diabetes mellitus was 3.5%. This steroid-sparing regime is associated with excellent patient and graft outcomes, and a low incidence of side effects.

Creatinine↗

PubMed2005

Early subclinical coronary artery calcification in young adults who were pediatric kidney transplant recipients.

Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron-beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10-40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality.

Adult↗

PubMed2005

Calcineurin inhibitor withdrawal from sirolimus-based therapy in kidney transplantation: a systematic review of randomized trials.

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.

Acute Disease↗

PubMed2005

Alemtuzumab induction and prednisone-free maintenance immunotherapy in kidney transplantation: comparison with basiliximab induction--long-term results.

This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (<3 months) rejection was observed in the alemtuzumab (4.1%) versus the basiliximab (11.6%) group, but the rates for both groups were equivalent at 1 year. Patient and kidney survival and rejection rates were nearly identical between Caucasians and African Americans that received alemtuzumab. Quality of renal function and incidence of infectious complications were similar in the two groups. Alemtuzumab induction therapy was similar in efficacy to basiliximab in a prednisone-free maintenance immunosuppressive protocol for an ethnically diverse population of kidney transplant recipients.

Adolescent↗

PubMed2005

Obesity is associated with worsening cardiovascular risk factor profiles and proteinuria progression in renal transplant recipients.

Obesity is associated with adverse cardiovascular (CV) parameters and may be involved in the pathogenesis of allograft dysfunction in renal transplant recipients (RTR). We sought the spectrum of body mass index (BMI) and the relationships between BMI, CV parameters and allograft function in prevalent RTR. Data were collected at baseline and 2 years on 90 RTR (mean age 51 years, 53% male, median transplant duration 7 years), categorized by BMI (normal, BMI < or = 24.9 kg/m2; pre-obese, BMI 25-29.9 kg/m2; obese, BMI > or = 30 kg/m2). Proteinuria and glomerular filtration rate (eGFR(MDRD)) were determined. Nine percent RTR were obese pre-transplantation compared to 30% at baseline (p < 0.001) and follow-up (25 +/- 2 months). As BMI increased, prevalence of metabolic syndrome and central obesity increased (12 vs 48 vs 85%, p < 0.001 and 3 vs 42 vs 96%, p < 0.001, respectively). Systolic blood pressure, fasting blood glucose and lipid parameters changed significantly with BMI category and over time. Proteinuria progression occurred in 65% obese RTR (23 (13-59 g/mol creatinine) to 59 (25-120 g/mol creatinine)). BMI was independently associated with proteinuria progression (beta 0.01, p = 0.008) but not with changing eGFR(MDRD.) In conclusion, obesity is common in RTR and is associated with worsening CV parameters and proteinuria progression.

Adult↗

PubMed2006

Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction - long-term results.

This study compared the effects of using two T-cell depleting antibodies, alemtuzumab (anti-CD 52, Campath-1H) and rabbit antithymocyte globulin (Thymoglobulin), as induction immunosuppression for recipients of simultaneous pancreas-kidney transplantation given a prednisone-free maintenance regimen. We used a single-center, nonrandomised, retrospective, sequential study design to evaluate the efficacy and safety of alemtuzumab (n = 50) or antithymocyte globulin (n = 38) induction in combination with a prednisone-free, tacrolimus/sirolimus-based immunosuppression protocol. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent. Secondary endpoints included the quality of renal allograft function, incidence of infectious and malignant complications, and cost considerations. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and antithymocyte globulin. Rejection rates were also nearly equivalent at 1 and 2 years. Viral infectious complications were statistically significantly lower in the alemtuzumab group. The cost of alemtuzumab induction was lower than antithymocyte globulin. Alemtuzumab induction followed by steroid-free maintenance therapy with a tacrolimus/sirolimus-based immunosuppression regimen provided an effective, safe and cost-conscious approach to SPK transplantation.

Acute Disease↗

PubMed2006

Elective liver transplantation for the treatment of classical maple syrup urine disease.

An 8.5-year-old girl with classical maple syrup urine disease (MSUD) required liver transplantation for hypervitaminosis A and was effectively cured of MSUD over an 8-year clinical follow-up period. We developed a collaborative multidisciplinary effort to evaluate the effects of elective liver transplantation in 10 additional children (age range 1.9-20.5 years) with classical MSUD. Patients were transplanted with whole cadaveric livers under a protocol designed to optimize safe pre- and post-transplant management of MSUD. All patients are alive and well with normal allograft function after 106 months of follow-up in the index patient and a median follow-up period of 14 months (range 4-18 months) in the 10 remaining patients. Leucine, isoleucine and valine levels stabilized within 6 hours post-transplant and remained so on an unrestricted protein intake in all patients. Metabolic cure was documented as a sustained increase in weight-adjusted leucine tolerance, normalization of plasma concentration relationships among branched-chain and other essential and nonessential amino acids, and metabolic and clinical stability during protein loading and intercurrent illnesses. Costs and risks associated with surgery and immune suppression were similar to other pediatric liver transplant populations.

Adolescent↗

PubMed2006

Measles-associated encephalopathy in children with renal transplants.

Two children, boys of 8 and 13 years, presented with measles-associated encephalopathy several years after kidney transplantation for congenital nephrotic syndrome. In the absence of prior clinical measles, the neurological symptoms initially eluded diagnosis, but retrospective analysis of stored samples facilitated the diagnosis of measles-associated encephalopathy without recourse to biopsy of deep cerebral lesions. Each had received a single dose of measles mumps and rubella vaccine before 12 months of age. Prior vaccination, reduction of immunosuppression and treatment with intravenous immunoglobulin and ribavirin may have contributed to their survival. Persistent measles virus RNA shedding, present in one child, was not controlled by treatment with i.v. ribavirin. Two years later, both patients continue to have functioning allografts with only minimal immunosuppression. These cases illustrate the difficulty in diagnosing measles-associated encephalopathy in the immunocompromised host, even in the era of molecular diagnostics, and highlight the renewed threat of neurological disease in communities with incomplete herd immunity.

Adolescent↗

PubMed2006

Recurrent glomerulonephritis after kidney transplantation.

Thirty to fifty percent of kidney transplant recipients have glomerular diseases as the underlying causes of end-stage renal failure. While recurrence of glomerulonephritis is an important cause of late renal allograft failure, the risk factors for recurrence are largely unknown or imprecise and prediction remains difficult. Recurrent disease usually presents with similar manifestations as the native disease. With regard to treatment of recurrent glomerular disease in the renal allograft, plasma exchange may be effective in reducing proteinuria in patients with early recurrence of focal and segmental glomerulosclerosis, but immunosuppressive therapy is generally ineffective in the prevention or treatment of recurrent disease. General supportive measures including strict blood pressure control and inhibition or blockade of the rennin-angiotensin pathway are helpful in retarding the rate of deterioration in renal allograft function. Despite the risk of recurrence, kidney transplantation following primary glomerulonephritides enjoys graft and patient survival rates comparable to other causes of end-stage renal failure. With a few exceptions, living related renal transplantation is not contraindicated in view of the favorable outcome and the donor shortage. This review discusses commonly encountered recurrent glomerulonephritides, with special emphasis on the influence of post-transplant prophylactic immunosuppression and emerging treatments.

Diabetic Nephropathies↗

PubMed1974

Kidney transplantation: analysis of 200 cases.

The first 200 renal allograft operations performed at Addenbrooke's Hospital, Cambridge, have been analysed. At the time of writing the fractional graft survivals at one, two, and three years were 53%, 49%, and 39% respectively, and these showed no observable change through the seven years of the programme. On the other hand, the survival of patients undergoing renal transplantation steadily improved, the most recent survival rates at one, two, and three years being 83%, 78%, and 67%, whereas the overall rates were 74%, 66%, and 54% respectively. The survival of second allografts was similar to that of first allografts. Ninety per cent. of the patients whose allografts functioned for a year or more returned to active and gainful employment. The return of children to school and of housewives to running a household was similarly gratifying. We conclude on both social and economic grounds that renal transplantation is fully justified as a therapeutic procedure.

Adolescent↗

PubMed1992

Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation.

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function.

Adolescent↗

PubMed1983

Management of children with progressive renal failure.

The strategy of management in childhood renal failure is to integrate available therapeutic modalities with the natural history of the disease in such a manner that linear growth is preserved. Attention to psychosocial growth is necessary for full rehabilitation. Treatment is ordered to provide hope and confidence to family and patient. Conservative medical therapy provides chemical stabilization and prophylaxis against bone disease and growth retardation. Planned progression to replacement of renal function by dialysis or renal transplant is made when growth or control of bone disease is no longer possible, but before complications occur. Therapy is effective; 90% of patients survive 5-10 years with 65% retaining a functioning allograft. Full rehabilitation is attained in 85-90% of post-transplant and 50% of dialysis patients. Technical advances now allow safe dialysis for all age groups. Although growth maintenance remains a major problem, it is possible that earlier metabolic control and transplantation to protect growth in the critical early years, together with improved control of rejection, may allow close approximation to optimal growth potential.

Adolescent↗

PubMed1998

Resolution of hepatitis B viremia in a renal transplant recipient treated with alpha-2b interferon.

A renal transplant patient developed symptomatic hepatitis after withdrawal from corticosteroids. Tests for hepatitis B e antigen and hepatitis B viral DNA were both positive prior to treatment with 1 million units alpha interferon three times weekly for 3 weeks followed by an increase to 3 million units alpha interferon three times weekly for a total of 16 weeks. At the end of treatment, hepatitis had clinically resolved with conversion to a hepatitis B e antibody positive and hepatitis B e antigen and viral DNA negative state. The renal allograft function remained excellent throughout the course of therapy with interferon.

Adult↗

PubMed1989

Changes in serum bile acid composition in relation to histological findings after liver transplantation in piglets.

Changes in the composition of serum bile acids were investigated after orthotopic liver transplantation in piglets. Serum levels of all bile acid components rapidly increased during the anhepatic phase and then quickly decreased, returning to the preoperative state within 6 h of revascularization of the allograft. In the animals in which extrahepatic biliary stenosis was a complication, serum total bile acids (TBA) increased remarkably. A marked increase of hyocholic acid and marked decrease of hyodeoxycholic acid were noted; as percentages of TBA, the average levels per day were 91.3 +/- 1.3 and 5.0 +/- 1.3%, respectively. No change in chenodeoxycholic acid (CDCA) was observed. In the animals suffering acute rejection without extrahepatic biliary stenosis, serum TBA increased slightly and the percentage of CDCA rose, the average level being 29.6 +/- 1.5%. These results suggest that the measurement of the composition of serum bile acids may serve as a useful means of assessing allograft function after liver transplantation.

Animals↗

PubMed1987

Meningitis due to Campylobacter fetus intestinalis in a kidney transplant recipient. A case report.

A 47-year-old man developed Campylobacter fetus intestinalis meningitis 3 years after cadaver renal transplantation. The infection was successfully controlled with chloramphenicol followed by erythromycin. There were no relapses during the past 5 years and the allograft function remains normal. The available evidence suggests that the campylobacter sepsis was associated with nutritional therapy, the patient received in a Mexican clinic. The present case is reported because of its clinical importance and epidemiological implications.

Campylobacter Infections↗

PubMed1996

Renal failure in a living-related kidney donor: case report and review of the literature.

End-stage renal disease developed in a 37-year-old Saudi patient who donated a kidney to his brother 11 years previously. Biopsy of the remaining kidney showed focal-segmental glomerulosclerosis. Dialysis support was needed, and finally the patient received a living-nonrelated kidney transplant. The allograft function in the recipient brother remains very good 11 years after transplantation.

Adult↗