Improve Kidney Allograft Research Articles

Rituximab and Intravenous Immunoglobulin Treatment of Chronic Antibody-Mediated Kidney Allograft Rejection

Kidney transplant rejections are classified into T-cell-mediated and antibody-mediated rejections (AMR). C4d staining on allograft biopsies and solid-phase assays to measure donor-specific alloantibodies have helped to precisely define the latter. Although for acute AMRs, therapy mainly relies on plasmapheresis or immunoadsorption, no studies for treatment of chronic AMR are available. Here, we report on four kidney allograft recipients suffering from chronic AMR 1 to 27 years posttransplant, who were treated with a combination of rituximab and intravenous immunoglobulin (IVIG). Rituximab/IVIG improved kidney allograft function in all four patients, whereas donor-specific antibodies were reduced in 2 of 4 patients. However, in one patient an acute rejection episode occurred 12 months after this treatment, and another patient had severe, possibly rituximab-associated lung toxicity. Thus, rituximab/IVIG may be a useful strategy for the treatment of chronic AMR, but further randomized multicenter studies are necessary to establish its efficacy and safety profile.

Kidney Graft Function in Long-term Cyclosporine and Tacrolimus Treatment: Comparative Study With Nephrotoxicity Markers

Calcineurin inhibitors improve kidney allograft survival in the posttransplantation period; however, they may cause nephrotoxicity. The objective of this study was to compare the effect of cyclosporine (CsA) and tacrolimus (Tac) treatment on the transplanted kidney. The study included 219 patients aged 21 to 65 years. Of these, 120 (39 women and 81 men) were treated with CsA and 99 (38 women and 61 men) were treated with Tac. Patients were divided into 4 groups depending on the time since kidney transplantation. We evaluated urine markers of nephrotoxicity: proximal tubular cells lysosomal enzymes (N-acetyl-beta-d-glucosaminidase [NAG] and its isoform NAG-B, beta-d-galactosidase, and beta-glucouronidase) and brush border enzymes (alanyl aminopeptidase and gamma-glutamyl transpeptidase). Urine activities of nephrotoxicity markers were compared in CsA- and Tac-treated patients groups depending on the duration of treatment and allograft function as measured by serum creatinine concentration. Correlation studies between CsA and Tac levels and enzyme activities were performed in both groups and in the entire patient cohort. NAG and its isoform NAG-B seemed to be the most reliable markers of nephrotoxicity. Despite the significant correlation between NAG urine activity and serum creatinine concentration in the CsA group, there were no significant differences in NAG or NAG-B activities between CsA- and Tac-treated graft recipients.

Blood Volume Expansion With Hyperoncotic Colloids Deteriorates Allograft Function in a Canine Model of Renal Transplantation

Purpose We investigated the effects of acute maximal hydratation with hemoce (H) and dextran-40 (D40) on the postoperative graft function, following renal transplantation (RT) in a canine model. Methods After induction of anesthesia with pentobarbital (5 mg/kg), 18 beagle dogs were randomized to receive either saline solution to increase the central venous pressure (CVP) to 5 mm Hg (GI); H solution to increase the CVP to 10 mm Hg (GII); or D40 to achieve 15 mm Hg (GIII), before reperfusion. A pulmonary artery catheter was used to measure CVP, mean pulmonary artery pressure, and cardiac output (CO). The surgical procedure consisted of autotransplantation of the dog’s left kidney an hour prior to cold ischemia with University of Wisconsin solution, followed by contralateral nephrectomy. Diuresis, creatinine (Cr), and BUN levels were measure at 24 hours before RT, as well as 24, 48, and 72 hours after the procedure. Results Only in the treated groups did cardiac filling presures and CO increase as a result of hydration. Only in the GI group did serum Cr and blood urea nitrogen significantly peak at the second postoperative day while it continued to increase at two (GII) and three (GIII) times greater than GI on the third day. Histological examination showed osmotic nephrosis like-lesions only among treated grafts. Conclusion We concluded that maximal hydration with H and D40 colloid deteriorated postoperative graft function after RT. We believe that in the future the effects of any colloid solution should be tested in an animal model in the fashion as we have described, in order to know which one, and at what dose, is the safest to improve kidney allograft outcome.

Alternative Applications of Cyclosporin a to Improve Kidney Allograft Survival

This study applies cyclosporin A as a donor pretreatment prior to organ harvesting or as a graft pretreatment during preservation of canine kidney allografts by hypothermic pulsatile perfusion or hypothermic storage. All recipients except those in Group IX received minimal immunosuppression with azathioprine after transplantation (5 to 2.5mg. per kg. per day). No significant differences in survival (X±SD) were observed between the 3 control groups which were either 1) flushed with untreated Ringer’s lactate solution and immediately transplanted (Group I, no.=8, 14±3.33 days), 2) preserved by hypothermic pulsatile perfusion for 24 hours (Group II, no.=7, 12.0±8.92 days), or 3) hypothermically stored for 24 hours (Group III, no.=7 13.1±11.6 days). A trend towards improved survival was seen in the 2 groups of animals that received kidneys that had been graft pretreated with cyclosporin A (12.5mg.) during 24 hours preservation by either hypothermic pulsatile perfusion (Group IV, no =10, 17.4±13.32 days, p <25) or hypothermic storage (Group V, no =6, 8±12.75 days, p <.25). Survival of recipients in Groups VI (no.=6) and VII (no.=9) who received kidneys whose donors had been pretreated with 25 and 50mg. per kg. respectively was dependent on the dosage of cyclosporin A used. Donor pretreatment at 50mg. per kg. was deleterious to kidney function (Group VI, 2.16±1.47 days, p <0.0005). Donor pretreatment with 25mg. per kg. did not significantly improve survival over control groups (15.66±12.9 days). Recipients in Groups VIII (no.=10) and IX (no.=6) were transplanted with kidneys from cyclosporin A pretreated donors (15mg. per kg.). These kidneys also received cyclosporin A graft pretreatment (10mg.) during 24 hours of hypothermic storage. The only difference between Groups VIII and IX was that the animals in Group IX received minimal amounts of cyclosporin A (5mg. per kg. per day) after transplantation. Combined donor and graft pretreatment yielded improved kidney allograft survival (Group VIII, 21.7±13.36 days, p >.10, Group IX, 20.83±14.2 days, p >.10). However, there was no significant difference observed as a result of the different immunosuppressive protocols used in Groups VIII and IX. These results indicate a trend towards improved renal allograft survival under certain conditions, after donor and graft pretreatment with cyclosporin A.