Cost effectiveness of ABO-incompatible kidney transplantations.
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ABO Blood-Group System↗
Biomedical subjects
Gunnar Tydén
Publications and source records attributed to Gunnar Tydén.
The Stockholm experience with ABO-incompatible kidney transplantations without splenectomy.
BACKGROUND: ABO-incompatible kidney transplantations have previously only been performed after several pre-operative sessions of plasmapheresis followed by splenectomy, and with the conventional triple-drug immunosuppressive protocol being reinforced with anti-lymphocyte globulin and B-cell-specific drugs. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. METHODS: The protocol called for a 1-month pre-transplantation conditioning period, starting with one dosage of rituximab and followed by full-dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pre-transplantation days -6, -5, -2 and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. RESULTS: Twenty-one patients have received transplants with this protocol. The ABO-antibodies (Abs) were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects, and all but one patient have normal renal transplant function. CONCLUSIONS: We conclude that after one infusion each of rituximab and IVIG, and antigen-specific immunoadsorption, blood-group incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy, and with excellent short- and long-term results.
ABO Blood-Group System↗
Clinical experience with a new apheresis filter that specifically depletes ABO blood group antibodies.
BACKGROUND: Although living kidney donors are increasingly being used, in most centers, 30 to 40 percent of potential donors are being turned down due to ABO mismatch. A protocol for ABO-mismatched kidney transplantation without splenectomy and with antigen-specific adsorption of ABO antibodies instead of nonspecific plasmapheresis was therefore designed. STUDY DESIGN AND METHODS: The immunosuppressive protocol used at the Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden, together with relevant clinical data for 11 of the studied patients, have been described previously. The protocol called for immunoadsorption of ABO antibodies on Days -6, -5, -2, and -1 and on Days +2, +5, and +8. Patient plasma was recirculated through a new apheresis filter, the Glycosorb ABO column (Glycorex Transplantation AB), containing synthetic terminal trisaccharide A or B blood group antigen linked to a Sepharose matrix. RESULTS: Since 2001, 15 patients, including 2 infants, have been successfully transplanted with ABO-mismatched kidneys from living donors. The donor-recipient blood groups were A1-O (n = 5), A2-O (n = 2), B-O (n = 4), B-A (n = 2), and A1B-B (n = 2). ABO antibody titers at transplantation did not exceed immunoglobulin G 4 or immunoglobulin M 4 levels. No humoral rejections and no late rebound of ABO antibodies were observed. No adverse effects related to immunoadsorption treatment have been recorded. CONCLUSION: It is concluded that ABO-mismatched kidney transplantations can be successfully performed without splenectomy and that ABO antibodies can be effectively and safely depleted with the Glycosorb ABO column.
ABO Blood-Group System↗
Photopheresis for the treatment of refractory renal graft rejection.
Acute rejection episodes still occur after kidney transplantation in spite of modern immunosuppressive protocols including combined tacrolimus, mycophenolate mofetil, and prednisolone. The authors present seven cases of biopsy-proven acute rejection after kidney transplantation refractory to conventional rejection therapy with repeated pulses of high-dose steroids followed by polyclonal or monoclonal antibodies that responded well to photopheresis treatment. Photopheresis is an atoxic immunomodulatory apheresis-based treatment with no generalized immunosuppressive action; rather, it is directed at suppressing donor-specific T-cell clones. At the last follow-up, 9 to 43 months after transplantation, all patients had functioning grafts, with serum creatinine levels ranging from 105 to 312 microM. The authors conclude that photopheresis treatment contributed to the favorable outcome. Therefore, the authors are presently designing a prospective, randomized trial to evaluate the effect of photopheresis as an adjuvant prophylactic treatment after renal transplantation.
Adult↗
ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab.
ABO incompatible kidney transplantations have previously only been performed after several preoperative sessions of plasmapheresis and splenectomy, with the conventional triple-drug immunosuppressive protocol being reinforced with antilymphocyte globulin and B-cell-specific drugs, such as cyclophosphamide or deoxyspergualine. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. The protocol calls for a 10-day pretransplantation conditioning period, starting with one dosage of rituximab and followed by full dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pretransplantation days -6, -5, -2 and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. Furthermore, if there was a significant increase in the antibody titers, extra sessions were considered. Eleven patients have received transplants with this protocol. The ABO antibodies were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects and all patients have normal renal transplant function. We conclude that after an infusion each of rituximab and IVIG, and antigen-specific immunoadsorption; blood group-incompatible renal transplantations can be performed with excellent results using standard immunosuppression and no splenectomy.
ABO Blood-Group System↗
Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in primary simultaneous pancreas-kidney transplantation: 1-year results of a large multicenter trial.
BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) transplantation has become an accepted therapy for type 1 diabetic patients with end-stage renal disease. This open-label, multicenter study compared the efficacy and safety of tacrolimus with the microemulsion (ME) formulation of cyclosporine in a clinical setting. The 1-year results are reported here. METHODS: The study was conducted in 10 European centers and one center in Israel. One hundred three patients were randomly assigned to tacrolimus and 102 to cyclosporine-ME. All patients received concomitant rabbit anti-T-cell globulin induction therapy, mycophenolate mofetil (MMF), and short-term cortico-steroids. The initial daily oral doses were 0.2 mg/kg for tacrolimus, 7 mg/kg for cyclosporine-ME, and 2 to 3 g for MMF. RESULTS: The 1-year incidence of biopsy-proven kidney or pancreas acute rejection was lower with tacrolimus (27.2%) than with cyclosporine-ME (38.2%; P = 0.09). Pancreas graft survival at 1 year was 91.3% with tacrolimus and 74.5% with cyclosporine-ME (P <0.0005). Renal graft survival was similar in the two study groups. There were no significant treatment-related differences in pancreatic or renal graft function. In total, 34 patients switched treatment from cyclosporine-ME to tacrolimus, but only 6 patients receiving tacrolimus required alternative therapy. Mean doses of MMF at 1 year were also lower in the tacrolimus group (1.36 vs. 1.67 g/day; P = 0.007). CONCLUSION: These findings support the use of tacrolimus therapy for uremic patients with type 1 diabetes who are undergoing SPK transplantation.
Acute Disease↗
Successful ABO-incompatible kidney transplantations without splenectomy using antigen-specific immunoadsorption and rituximab.
BACKGROUND: Historically, ABO-incompatible kidney transplantations have only been undertaken after splenectomy and unspecific plasmapheresis and with quadruple drug immunosuppression plus B-cell specific drugs. We have evaluated a protocol for ABO-incompatible kidney transplantation without splenectomy using antigen-specific immunoadsorption, rituximab, and a conventional triple-drug immunosuppressive regimen. METHODS: The protocol called for a 10-day pretransplant conditioning period starting with one dosage of rituximab and followed by full dose tacrolimus, mycophenolate mofetil, and prednisolone. Antigen-specific immunoadsorption was performed on pretransplant days -6, -5, -4, and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin was administered. Postoperatively, three more apheresis sessions were given every third day. Furthermore, if there was a significant increase in the antibody titers, extra sessions were considered. RESULTS: Four patients have received transplants with this protocol. The donor-recipient blood groups were A2/O, B/O, B/A, and A1/O. The ABO-antibodies were readily removed by the antigen-specific immunoadsorption and were kept at a low level posttransplantation by further adsorptions. There were no side effects, and all patients have normal renal-transplant function. CONCLUSIONS: We conclude that after one infusion each of rituximab and intravenous immunoglobulin and antigen-specific immunoadsorption, blood-group-incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy.
ABO Blood-Group System↗
A longitudinal study of children who received renal transplants 10-20 years ago.
BACKGROUND: We have previously reported on our 10-year experience of renal transplantation in children in the cyclosporine era, that is, from December 1981 until December 1991. In this paper, we report on the same children observed for another 10 years. METHODS: Of 53 children who received a renal transplant between 1981 and 1991, 47 survived and were observed for 10 to 20 years. Immunosuppression consisted of cyclosporine, prednisolone, and azathioprine. Yearly clinical examinations were performed. RESULTS: Overall, actual patient survival is 91%, 89%, and 89%, and actual graft survival 85%, 77%, and 66% at 1, 5, and 10 years, respectively. No patients have died during the last 10 years. Twenty-six grafts were lost over 20 years. Thirteen of those were lost during the present follow-up (10-20 years): 11 in chronic rejection and 2 because of development of renal cell carcinoma. No other malignancies were noted. Mean glomerular filtration rate decreased from 58+/-19 at 1 year (n=42) to 44+/-16 mL/min/1.73 m2 body surface area at 10 (n=33) years. Hypertension was treated in 46%, 40%, and 66% of the children at 1, 5, and 10 years, respectively; two of them showed left ventricular hypertrophy 10 years after transplant. Minor cataracts without visual disturbance were found in 45% of patients. All children except three with mental retardation are, or have been, attending normal day care or normal school. CONCLUSION: Social integration is good, and severe complications are scarce, even when renal transplantation occurred at a very young age.
Adult↗
Effects of immediate switch from cyclosporine microemulsion to tacrolimus at first acute rejection in renal allograft recipients.
BACKGROUND: A number of institutions have reported favorable results in renal transplant patients after conversion from cyclosporine (CsA) to tacrolimus at the time of acute rejection, but no prospective, controlled study has been performed to date. Here, we report the first randomized study comparing patients whose therapy was changed at a first episode of acute rejection to tacrolimus with those who were maintained on CsA microemulsion (ME). METHODS: This 3-month, prospective, open, multicenter, parallel-group study was conducted at 15 centers in seven European countries. In total, 119 renal graft recipients experiencing a first biopsy-proven acute rejection episode while receiving CsA-ME were randomized (1:1) to start tacrolimus-based therapy (n=61) or to continue CsA-ME-based therapy (n=58). RESULTS: Baseline characteristics were comparable for both groups. The initial rejection episode responded to steroid treatment in 93.4% (tacrolimus) and 63.8% (CsA-ME) (P=0.001), respectively. In patients at risk, the incidence of recurrent rejection events within 3 months was significantly lower with tacrolimus therapy (5/57, 8.8%) compared with CsA-ME therapy (15/44, 34.1%) (P=0.002). Patient and graft survival were similar in both study groups 3 months after randomization. The most frequently reported adverse events were increased serum creatinine (29.5% vs. 22.4%), hypertension (24.6% vs. 22.4%), and urinary tract infection (18.0% vs. 20.7%) for tacrolimus versus CsA-ME. Tremor was more common in tacrolimus treated-patients (17.4% vs. 2.1%, P=0.011). CONCLUSIONS: Early conversion to tacrolimus therapy benefited the resolution of acute rejection episodes and significantly reduced the risk of recurrent rejection compared with continuation of CsA-ME.
Adult↗
Growth impairment at renal transplantation--a determinant of growth and final height.
Long-term outcome of growth and final adult height (FH) are a major concern of children after a renal transplantation (Tx). We therefore studied the yearly measurements of height (Ht), expressed as the Z-score and bone age (BA), in 58 children (28 girls) transplanted in our departments and followed-up for 5-18 (mean 9.6) yr after the operation. Twenty-four children reached final adult height. Renal function was evaluated as the glomerular filtration rate (GFR), which is estimated from the clearance of inulin. The mean Ht Z-score at Tx was -1.3 in girls and -2.7 in boys and increased to -0.6 and -1.5, respectively, at 5 yr after Tx. The greatest increase, seen in the shortest children and those transplanted before 7 yr of age, occurred during the first 3 yr. Children aged 7-12 yr at Tx showed an increase in height during the first years after the transplant, while those transplanted at >12 yr of age were not growth-retarded and therefore did not change their Ht Z-score. The most growth-retarded were also the most BA retarded. The mean FH Z-score was -1.1. A direct correlation was seen between GFR at 1 yr after Tx and the increase in height Z-score from Tx to 1 and 5 yr after Tx. In summary, the increment in height following Tx was the greatest in the most growth-retarded children and most marked during the first 3 yr after the transplant. FH was within normal range in 75% of the children. A high Ht Z-score at Tx had a positive effect on FH. Thus, growth after Tx was affected by the degree of stunting at Tx and renal function after Tx.
Adolescent↗
Better long-term functional adaptation to the child's size with pediatric compared to adult kidney donors.
BACKGROUND: Pros and cons for pediatric kidney donors have been debated, especially with respect to survival rates. However, the effect of donor age on kidney function remains conflicting. The aim of this study was to compare short and long-term renal function according to the age of the donor, in grafts from adult living related (LRD), adult cadaveric and pediatric cadaveric donors (PedCD) following pediatric transplantation (Tx). METHODS: One hundred and thirty-four children were repeatedly followed for four years, and 44 were followed for eight years. Absolute and relative glomerular filtration rate (GFR; inulin clearance, mL/min and mL/min/1.73 m(2), respectively) were determined within 6 months, and yearly thereafter. RESULTS: Absolute GFR increased along with body growth in the PedCD group (P < 0.001) during the 4 years following Tx, leading to stable relative GFR, whereas absolute GFR of the LRD group did not change, with a progressive decrease of relative GFR (P < 0.001). Relative GFR did not differ between PedCD and LRD recipients by the sixth month but became higher in PedCD 4 years post-Tx (70 +/- 25 vs 52 +/- 19 mL/min/1.73 m(2), P < 0.001). Among those followed for 8 years, relative GFR showed a slow decrease in both recipient groups from 6 years post-Tx. At 8 years post-Tx, relative GFR was still significantly higher in PedCD than in LRD (57 +/- 19 vs. 45 +/- 19; P < 0.05). CONCLUSIONS: Adult-sized grafts may adapt to pediatric recipients during the first months post-Tx, but graft function cannot improve thereafter along with the increase in body size of the recipient. Interestingly, the absolute GFR of children receiving pediatric grafts increased along with body growth, leading to a stable relative GFR up to 6 years post-Tx.
Adaptation, Physiological↗