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- Genberg, Helena
(författare)
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AB0-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 5As the demand for kidney transplantation is constantly growing methods to expand the donor pool have become increasingly important. AB0-incompatibility has hitherto been regarded as an absolute contraindication to living donor donation. However, as AB0-incompatibility has accounted for the majority of living donor exclusions, efforts have been made to overcome this immunologic barrier. Successful desensitization protocols thus far, have combined plasmapheresis for antibody removal with splenectomy to reduce the antibodyproducing B-cell pool, in addition to quadruple immunosuppression. Although good graft function has been achieved, the high risks involved have been deterrent. A protocol for AB0-incompatible kidney transplantation based on antigen-specific immunoadsorption and rituximab, in combination with standard maintenance immunosuppression (tacrolimus, mycophenolate mofetil and corticosteroids) was developed. We hypothesized that the anti-A/B antibodies could be effectively eliminated and good graft function achieved, without the complications of coagulopathy and transfusion reactions associated with plasmapheresis. Furthermore, we hypothesized that the substitution of splenectomy with a single dose of the B-lymphocyte depleting antibody, rituximab, would abolish thesurgical risk and reduce the risk of infectious complications related to splenectomy. From Sept 2001 to Oct 2007 a total of 39 patients underwent conditioning for AB0-incompatible kidney transplantation according to the protocol. Median follow-up was 2 years. In 38 out of 39 patients the anti-A/B antibodies could be effectively removed and transplantation performed as planned. The antigen-specific immunoadsorption was well tolerated without any serious side effects. Overall patient survival was 97.4% and graft survival was 86.8%. Kidney function was evaluated in a short and long term perspective, the results being equivalent to those of AB0-compatible living donor kidney transplantation. The incidence of antibody-mediated rejection was 2.6% and there was no significant rebound of anti-A/B antibodies during the study period. However, AB0-incompatible kidney transplantation was associated with an additional cost of approximately 32,000 compared with standard AB0-compatible living donor kidney transplantation. B-lymphocytes were effectively eliminated long-term in peripheral blood as well as within the kidney transplant. In the lymphoid compartment, the B-lymphocytes were reduced. Despite B-lymphocyte depletion, there was no increased risk of infection following AB0-incompatible kidney transplantation compared with AB0-compatible transplantation. We conclude that AB0-incompatible kidney transplantation using a protocol based on antigen-specific immunoadsorption and rituximab, in combination with triple immunosuppressive therapy is safe and effective. AB0-incompatibility following this protocol does not have a negative impact on graft function. AB0-incompatible kidney transplantation using this protocol is equivalent to standard AB0-compatible living donor kidney transplantation.
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| 3. |
- Sabelström, Helena, et al.
(författare)
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Luft & miljö 2017 Barns hälsa
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Barn ar sarskilt utsatta for luftfororeningar, dels genom sin fysik, men aven genom sina dagliga rorelsemonster. Manga barn vaxer idag upp i miljoer dar dalig luftkvalitet kan paverka deras framtida halsa. For att vi ska kunna skapa en luftmiljo som ar bra for barns halsoutveckling, behover vi tanka pa hur vi utformar stader och narmiljo och vi behover kunskap om hur barn paverkas av den luftkvalitet som omger dem. Idag behover vi aven ta hansyn till de konsekvenser som klimatforandringarna for med sig och som paverkar barns fysiska och psykiska halsa.Overvakning av luftkvalitet ar viktig i bade tatorten och pa landsbygden for att vi ska kunna folja hur halterna av luftfororeningar utvecklas, bade over tid och hur de varierar i olika miljoer. Forskare kombinerar uppgifter om barns halsa med luftkvalitetsdata vid relevanta platser och kan pa sa vis se vilken paverkan luftfororeningarna har.Den har skriften har tagits fram inom ramen for Naturvardsverkets arbete med nationell miljoovervakning, och ar fylld med innehall dels av dem som utfor overvakningen, men aven av forskare vid universitet och hogskolor, myndigheter och andra aktorer. Skriften ar tankt att vara ett inspirationsdokument for handlaggare pa kommuner och lansstyrelser som arbetar med miljo- och planeringsfragor med koppling till barn och deras halsa samt for politiker. Med ett barnperspektiv vid planering och beslut hoppas vi att samhallet banar vagen for en framtid med battre luft for alla.Lat er inspireras och verka for en battre luftmiljo for barn!
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| 4. |
- Tyden, Gunnar, et al.
(författare)
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A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation
- 2009
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Ingår i: Transplantation. - 1534-6080 .- 0041-1337. ; 87:9, s. 1325-1329
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Tidskriftsartikel (refereegranskat)abstract
- We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. Results. We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depiction of CD 19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66 +/- 22 mL/min in the study group and 67 +/- 23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. Conclusion. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.
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| 5. |
- Tydén, Gunnar, et al.
(författare)
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Implementation of a Protocol for ABO-incompatible kidney transplantation--a three-center experience with 60 consecutive transplantations
- 2007
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 7, s. 157-158
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Tidskriftsartikel (refereegranskat)abstract
- Background. A new protocol for ABO-incompatible kidney transplantation has recently been introduced. We report here on the joint experience of the implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany. Methods. The new protocol utilizes antigen-specific immunoadsorption to remove existing ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney transplantations were included in the study. The outcome is compared with the results of 274 ABO-compatible live donor transplantations performed during the same period. Results. Two of the ABO-incompatible grafts have been lost (non-compliance and death with functioning graft). All the remaining 58 grafts had good renal function at a follow-up of up to 61 months. We did not observe any late rebound of antibodies and there were no humoral rejections. Graft survival was 97% for the ABO-incompatible compared with 95% for the ABO-compatible. Patient survival was 98% in both groups. There was a significant variation in preoperative A/B-antibody titer between the centers, with a median 1:8 in Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative antibody adsorptions were therefore needed in Freiburg than in Stockholm and Uppsala. Conclusions. The new protocol was easily implemented and there were no graft losses that could be related to ABO-incompatibility. A significant inter-institutional variation in the measurement of anti-AB-antibodies was found, having a substantial impact on the number of immunoadsorptions and consequently on the total cost for the procedure. A standardized fluorescence-activated cell sorting technique for antibody quantification is much needed.
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