| 1. |
- Fehrman-Ekholm, Ingela, 1947, et al.
(författare)
-
Incidence of end-stage renal disease among live kidney donors.
- 2006
-
Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 82:12, s. 1646-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The increasing use of living kidney donors requires knowledge about long-term effects, especially number and causes of donors with end-stage renal disease (ESRD). METHODS: A retrospective data analysis of 1,112 consecutive living kidney donors who underwent nephrectomy from 1965 until 2005 at Sahlgrenska University Hospital. Case reports were sought with help from nephrologists in the region and data from Swedish Registry of Active Uremic Treatment (SRAU). RESULTS: The number of cases with end stage kidney failure among living kidney donors was 6/1112, that is 0.5%. The donors had reached ESRD during the years 2001-2006, that means 36-41 years after start of the living donor program. The donors were 45-89 years old, median 77 years, and five of six were males. Time since donation was 14-27 years, median 20 years, for the donors developing ESRD. The diagnoses were nephrosclerosis (4 cases), postrenal failure (1 case), and renal carcinoma (1 case). The expected incidence for development of ESRD according to incidence in the general population would have been two donors but we found six. However, considering the high age of the donors in this follow up, the age-matched incidence is calculated to be closer to six donors due to higher incidence in the aged. CONCLUSION: In all 0.5% of the donors developed ESRD. Due to high age of the uremic donors, there seems to be no increased incidence.
|
|
| 2. |
- Gustafsson, Bengt I., 1955, et al.
(författare)
-
Retransplantation of the liver.
- 2006
-
Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:5, s. 1438-9
-
Tidskriftsartikel (refereegranskat)abstract
- Retransplantation (re-TX) is the only available therapy for irreversible liver graft dysfunction. The outcome of a second procedure depends upon several factors, some of which are not defined at the time of the decision to retransplant. This study is an analysis of all re-TX of the liver performed at our unit between January 1995 and January 2004. Among the 474 liver TX were 55 (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2) indication for re-TX and time lapse; (3) donor age and cold ischemia time (CIT); (4) duration of operation, peroperative bleeding, and complications; (5) ICU and ward periods; and (6) patient and graft survivals. Patients who underwent re-TX did not differ from those transplanted once with regard to age, gender, or diagnosis. The indications for re-TX were roughly one-third biliary tract complications/chronic rejection, one-third hepatic artery thrombosis, and one-third others, including primary nonfunction, acute rejection, portal vein thrombosis, sepsis, and B/C hepatitis. The re-TX were "urgent" in 29 and "elective" in 26 cases. Complications were common; about half of the patients were reoperated due to bleeding or biliary problems. To date (May 2004), 15 patients have died (12 "urgent" and 3 "elective"), of whom 5 had well functioning grafts. In summary, liver re-TX is a complicated procedure associated with significant mortality and morbidity, but considering that the actual patient group has a poor prognosis without re-TX, the results are nevertheless encouraging.
|
|
| 3. |
- Olausson, Michael, 1956, et al.
(författare)
-
Adjuvant treatment with ursodeoxycholic acid prevents acute rejection in rats receiving heart allografts.
- 1992
-
Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 5 Suppl 1
-
Tidskriftsartikel (refereegranskat)abstract
- Adjuvant treatment with ursodeoxycholic acid (UDCA) for liver-transplant recipients has been reported to reduce the frequency of acute rejection episodes. To explore this effect further, UDCA was given to rats in an experimental heart transplantation model, with or without concomitant immunosuppressive treatment with antihymocyte globulin (ATG). UDCA was administered orally 7 days before and 14 days after transplantation. Rats treated with UDCA alone or in combination with ATG were compared with untreated controls and ATG-treated recipients. Adjuvant treatment with UDCA was found to induce prolonged graft survival and increase the amount of transplant tolerance in rats. Serum levels of bilirubin and aminotransferases were not altered irrespective of the UDCA dose given. The results indicate that UDCA has an immunomodulatory capacity that might not be restricted to the liver, but also might apply to other transplanted organs as well.
|
|
| 4. |
- Olausson, Michael, 1956, et al.
(författare)
-
Successful combined partial auxiliary liver and kidney transplantation in highly sensitized cross-match positive recipients
- 2007
-
Ingår i: American journal of transplantation. - 1600-6135. ; 7:1, s. 130-6
-
Tidskriftsartikel (refereegranskat)abstract
- Combined liver and renal transplantations can be performed against a positive cross-match, indicating that the liver protects the kidney from the harmful HLA antibodies. This led us to the hypothesis that a partial auxiliary liver graft may have a similar protective effect when performed together with the kidney in highly sensitized patients. Seven patients, with broadly reacting HLA antibodies and positive crossmatches, were transplanted with a partial liver and a kidney from the same donor. In one of the cases a living donor was used. We performed lymphocytotoxic and flow cross-matches before and after the transplantation. Cross-matches turned negative after grafting in five of seven cases. The kidney function was excellent, without rejections, during the follow-up (24-60 months) in these patients. In two cases the cross-match remained positive after transplantation, one with a never-functioning renal graft and the other with an early graft failure, probably due to humoral rejection. A simultaneous transplantation of a partial auxiliary liver graft from the same donor, with the sole purpose of protecting the kidney from harmful lymphocytotoxic antibodies, can be performed successfully despite a positive cross-match and may thus be a new option of treatment for highly sensitized patients waiting for a kidney transplant.
|
|
| 5. |
- Streichart, Lillian, et al.
(författare)
-
Tocilizumab in chronic active antibody-mediated rejection : rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study)
- 2024
-
Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 25
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.Methods: The INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05.The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.Discussion: No effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.
|
|
| 6. |
- Streichart, Lillian, 1983, et al.
(författare)
-
Tocilizumab in chronic active antibody-mediated rejection: rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study)
- 2024
-
Ingår i: TRIALS. - : BioMed Central (BMC). - 1745-6215. ; 25:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundChronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.MethodsThe INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05.The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.MethodsThe INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05.The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.DiscussionNo effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.
|
|
| 7. |
- Bredewold, Obbo W, et al.
(författare)
-
Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients : A Randomized Clinical Trial
- 2023
-
Ingår i: Kidney Medicine. - : Elsevier. - 2590-0595. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- RATIONALE & OBJECTIVE: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.STUDY DESIGN: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.SETTING & PARTICIPANTS: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion.INTERVENTION: Continuation with a CNI-based regimen or switch to belatacept for 12 months.OUTCOMES: Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.RESULTS: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.LIMITATIONS: The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year.CONCLUSIONS: We found no effects on the calculated CV risk by switching to the belatacept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate.FUNDING: The trial has received a financial grant from Bristol-Myers Squibb.TRIAL REGISTRATION: EudraCT no. 2013-001178-20.
|
|
| 8. |
- Ekberg, Henrik, et al.
(författare)
-
Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study.
- 2010
-
Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 25, s. 2004-2010
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens. METHODS: Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels. RESULTS: The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels. CONCLUSIONS: Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs.
|
|
| 9. |
|
|
| 10. |
|
|
