Graft Rejection Episodes Research Articles

De Novo Crohn’s Disease in a Renal Transplant Recipient

The prevalence of inflammatory bowel disease (IBD) after renal transplantation is affected by the immune tolerance and the modality of immunosuppression. Mycophenolate mofetil (MMF) may have a promoting effect on the development of posttransplantation erosive enterocolitis and a Crohn’s disease-like pattern of colitis. We have presented a 40-year-old man with end-stage renal disease due to chronic glomerulonephritis who commenced hemodialysis for 2 months before receipt of a live unrelated renal transplant. He developed early posttransplantation diabetes mellitus and an anti graft rejection episode, which responded to a methylprednisolone pulse and OKT3 treatment. His immunosuppressive regimen included prednisolone, MMF, and tacrolimus. Three years after transplantation, he developed mild constitutional symptoms, mouth ulcerations, and chronic intermittent bloody diarrhea. Colonoscopy showed active segmental colitis with aphthous ulcers, involving the proximal descending colon and the splenic flexure. Colonic biopsies showed distended and branched crypts in the ascending colon, moderate active chronic colitis with regenerative atypia, skipping appearance, and ulceration in the splenic flexure and descending colon. The edematous crypts were associated with ulcerations in the sigmoid colon and rectum. The features were highly suggestive of Crohn’s disease. He was successfully treated with high-dose steroids and 5-aminosalicylic acid. Subsequently, he developed chronic transplant glomerulopathy and restarted hemodialysis. We concluded that de novo Crohn’s disease may develop in renal transplant recipients despite immunosuppressive therapy especially with MMF immunosuppression.

Bilateral severe progressive idiopathic lipid keratopathy

To report a case with bilateral progressive lipid keratopathy. A 44-year-old healthy man without previous ocular disease presented with bilateral lipid keratopathy which was more severe in his right eye. Evidence of hyperlipidemia or clinical corneal neovascularization was not apparent. Penetrating keratoplasty (PKP) was performed, initially in the right eye and four years later in the left eye. Histochemical examination showed focal stromal vascularization and staining for lipids. During the follow-up period, one episode of graft rejection occurred in each eye; both responded to systemic steroid therapy. Severe bilateral progressive lipid degeneration can develop in previously healthy corneas in healthy patients without underlying pathology. The nature of the process remains unclear. When PKP is performed and neovascularization is identified in the removed corneal button, close follow-up is advisable because corneal grafts can be prone to rejection.

Risk Factors for the First Episode of Corneal Graft Rejection in Keratoconus

To evaluate the relationship between topical corticosteroids and other variables and the risk for rejection after penetrating keratoplasty for keratoconus. The records of all keratoconus patients who, after their first penetrating keratoplasty in that eye, experienced a first episode of corneal graft rejection during a specific 3-year period were retrospectively reviewed in a case-control fashion. Twenty-three cases were identified, and they were matched with 3 controls each, for a total of 69 controls and 92 total patients. Multiple variables including steroid potency, recent steroid tapering, and length of time on the current level of steroids were analyzed to see whether there were any significant relationships between postoperative changes in steroid management and rejection. In addition, other variables such as graft size, suture technique, recent suture removal, suture status at the time of the rejection episode, and prior grafting in the fellow eye were examined to determine if any of these factors were associated with a higher risk of graft rejection. Most of the proposed risk factors, including steroid dose and tapering, differing suturing techniques, loose and/or broken sutures at the time of rejection, percentage of sutures remaining at the time of rejection, and prior grafting in the fellow eye, did not correlate with the risk of rejection. Only graft size had a correlation, with host trephination size > or = 8.25 mm having a nearly sixfold increased risk of rejection (P = 0.015). Most patients (70%) were diagnosed with rejection at a scheduled office visit rather than at an emergency visit, and correspondingly, nearly one half (43%) had no symptoms when rejection was identified. There was no significant difference in final best-corrected visual acuities between the cases and controls, and 91% of the corneas that underwent rejection did not progress to graft failure, remaining centrally clear at most recent follow-up. In this study, the most important risk factor for rejection after corneal transplantation for keratoconus was the size of the graft. Physician detection of rejection is paramount, because a graft rejection episode is more often diagnosed at a scheduled office visit than at an emergency visit. Fortunately, progression to graft failure can usually be prevented if treatment is started promptly and intensively.

Histology of Posterior Lamellar Keratoplasty

To report histology of a posterior lamellar graft performed to treat clinically significant endothelial disease in a patient with Fuchs dystrophy. A 78-year-old patient with Fuchs dystrophy underwent posterior lamellar keratoplasty (PLK), the original form of endothelial keratoplasty performed with manual lamellar dissection of the recipient and donor corneas. Eighteen months later, the patient had herpes simplex virus keratitis and graft rejection episodes. One year after the infection resolved (2.5 years after PLK), penetrating keratoplasty was performed, and the excised corneal button was examined. Histopathologic evaluation of the corneal button showed no discernible interface, opacity, or gapping between the anterior host stromal tissue and PLK donor tissue or any signs of significant migration of donor endothelial cells onto recipient tissue. This PLK histology showed firm attachment with no visible interface between the posterior donor and anterior host stromal tissue. Surprisingly, no significant donor endothelial cell migration was detected on adjacent recipient tissue where Descemet membrane had been excised or where endothelial cells were lost as a result of the procedure.

C-reactive protein induced activation of MAP-K and RANTES in human renal distal tubular epithelial cells in vitro

C-reactive protein (CRP) is a component of the acute-phase reaction to inflammation, severe tissue injury, and infection. Investigations have shown that CRP concentration is highly increased in the urine during acute renal graft dysfunction and, therefore, may affect tubular cell metabolism. Nevertheless, no data about the effects of CRP on human renal tubular epithelial cells are available. Human renal distal tubular cells (DTC) were isolated immunomagnetically and cultured. Cells were stimulated with affinity chromatography pure native CRP from human ascites (10 - 0.001 microg/ml). Phosphorylation of MAP-K was assessed by Westernblot analysis. Release of RANTES and interleukin-6 was evaluated with an enzyme immunoassay. Cytotoxic effects of CRP were determined by a commercially available Live/Dead assay and MTT assay. Effects on cell proliferation were analyzed by a fluorimetric assay. Westernblot analysis clearly showed that CRP activates the MAP-K pathway of DTC. CRP upregulated RANTES expression of DTC in a significant and dose-dependent manner. CRP (10 microg/ml) induced a 12.3-fold upregulation, CRP 1 or 0.1 microg/ml induced a 6.3-/2.8-fold RANTES upregulation, respectively. Interleukin-6 synthesis was not influenced. Cytotoxic, proliferative or apoptotic effects were not observed at the concentrations used. We demonstrated an activating effect of CRP on DTC in vitro. In vivo, this effect of CRP might be part of the immune activation cascade during episodes of renal graft rejection or bacterial infections.

Efficacy of Topical Cyclosporine 0.05% for Prevention of Cornea Transplant Rejection Episodes

To assess the incidence of immunologic corneal graft rejection episodes in a prospective case series of patients treated 4 times a day with topical cyclosporine 0.05%. Prospective, single-center, institutional review board-approved study. Fifty-two cornea transplant recipients considered low risk for graft rejection. Primary indications for transplantation were keratoconus, Fuchs' dystrophy, or nonherpetic, nonvascularized scars. Subjects completely tapered off prednisolone acetate 1% by 13 weeks after transplantation and used topical cyclosporine 0.05% 4 times a day, beginning either 1 or 10 weeks posttransplant, with use continued until 1 year posttransplant. One subgroup supplemented cyclosporine use with pulsed prednisolone acetate 1% dosing, 4 times a day for 4 days every 6 weeks. The incidence of immunologic corneal graft rejection episodes was compared with that in Fuchs' and keratoconus historical control subjects, who used topical steroids a median of 7 months after penetrating keratoplasty. Incidence of immunologic graft rejection episodes. Graft rejection episodes occurred earlier and with higher incidence in subjects using cyclosporine 0.05% compared with historical control subjects who used steroids for a longer period of time (P<0.0001). Cyclosporine subjects who pulse-dosed prednisolone had a significantly higher incidence of graft rejection compared with those who did not pulse steroids (P = 0.04). The results suggest that 4 times daily dosing with topical cyclosporine 0.05% is not as effective as use of topical prednisolone acetate 1% for prevention of graft rejection episodes in low-risk corneal transplants, and that periodic pulsing with corticosteroids may increase the risk of rejection episodes.

Anti-LFA-1 Antibody Postpones T-cell Receptor Triggering While Preserving Generation of Regulatory T Cells in T-cell Receptor Anti-HY Transgenic Mice

Anti-LFA-1 (CD11a) antibody increases allograft survival and/or induces tolerance in murine models, but its mechanisms of action remain to be elucidated. Rag-2-/- H-2b recipient mice, bearing a transgenic T-cell receptor specific for the male antigen HY presented by MHC class II molecule, were transplanted with a C57BL/6 (H-2b) male heart with or without administration of anti-LFA-1 antibody from days -1 to 9. Treatment prevented the transient episode of acute graft rejection observed in nontreated mice and maintained a naive phenotype and proliferative characteristics comparable to that of naive transgenic lymphocytes on day 7 during treatment, with decreased IFN-gamma mRNA and increased IL-4 mRNA. On day 14, phenotype and proliferative response of lymphocytes in treated mice was comparable to those of untreated animals. Furthermore, treatment did not interfere with the generation of CD4+Vbeta6+CD25+ (Foxp3) cells that were observed in long-term nontreated tolerant mice. This in vivo model demonstrates that anti-LFA-1 treatment induced a transient blockade of antigen recognition, which inhibited and postponed induction of signal 1 via the TCR and decreased the intensity of the Th1 response. Importantly, LFA-1 blockade did not disturb spontaneous generation of regulatory mechanism. This treatment would be compatible in clinical settings with other therapeutics inducing regulatory mechanisms.

Three-Year Observational Follow-up of a Multicenter, Randomized Trial on Tacrolimus-Based Therapy with Withdrawal of Steroids or Mycophenolate Mofetil after Renal Transplant

The challenge in renal transplantation is to improve long-term patient and graft survival without increasing early acute rejection by minimizing immunosuppression. This multicenter, observational study investigated the effects of withdrawal of steroids or mycophenolate mofetil (MMF) from a tacrolimus-based triple regimen (tac/MMF/steroids) 3 months posttransplant at 3 years; no additional interventions or assessments were undertaken. Adult patients, included in the intent-to-treat population of the THOMAS study, participated. Patient and graft survival, adverse events, rejection episodes, and immunosuppressive and concomitant medications were assessed. Data at Year 3 was available for 718 patients (triple therapy, n=237; steroid stop, n=235; MMF stop, n=246). The original randomized regimen was maintained in 45.6% of patients in the triple, 62.6% in the steroid stop, and 53.9% in the MMF stop groups. Graft survival rates were 88.1% (triple), 86.4% (steroid stop), and 85.8% (MMF stop); patient survival was 96.1%, 95.9%, and 95.7%, respectively. The incidence of biopsy-proven acute rejection was similar in all groups between Month 7 and Year 3: 1.2% (triple), 2.0% (steroid stop) and 2.0% (MMF stop). Patients in the steroid stop group had less hypertension and significantly lower mean total cholesterol and LDL-cholesterol at Year 3 compared with Month 3 (P=0.02). Median serum creatinine levels remained stable throughout the follow-up and were comparable between groups. Immunosuppression minimization initiated at Month 3 was maintained at Year 3 in over half of the patients. Steroid withdrawal was advantageous in reducing the cardiovascular risk factors hyperlipidemia, hypertension and diabetes mellitus. Renal function was stable in all groups.

Genetic association of interleukin-1β and receptor antagonist (IL-1Ra) gene polymorphism with allograft function in renal transplant patients

Cytokines are known to be important mediators during renal graft outcome. The present study was therefore, conducted to determine the impact of IL-1β and its receptor antagonist polymorphism on allograft outcome. We evaluated single nucleotide polymorphism (SNPs) in interleukin-1 gene cluster, IL-1β (promoter region − 511 and exon-5 + 3954) and IL-1Ra (86-bp VNTR) in 136 renal transplant recipients and 150 normal healthy controls by polymerase chain restriction based (PCR-RFLP) analysis. Recipients were HLA matched and clinically characterized including delayed graft function (DGF), rejection episode (RE) and stable graft function (SGF). Haplotypes and linkage disequilibrium (LD) were determined using SNPAnalyzer software. Significant difference was observed for the frequency distribution of the three sites of IL-1 gene among patients and controls ( p < 0.001, 0.022 and < 0.001 respectively). When RE and DGF were compared to SGF, only IL-1Ra showed significant differences among RE and SGF ( p = 0.014) and DGF and SGF ( p = 0.020). The presence of 1 / 2 genotype showed 18 folds risk in RE and 10 folds in DGF (OR = 18.000 and OR = 10.667 respectively). The majority of recipients with SGF had 1–4 HLA mismatch whereas RE had 5–8 mismatches. Risk for rejection increased > 6 folds (OR = 6.571; p < 0.01) for 5–8 mismatches. Haplotypes constructed with the combination of three polymorphisms in IL-1 gene cluster showed significant difference between RE and SGF group. LD value for IL-1β (promoter region) and IL-1Ra and IL-1β promoter and exon-5 gene in the control group indicated strong association among the variants ( D′ = 0.37, p < 0.0001 and D′ = 0.29, p = 0.002). Our study demonstrate that genetically determined low production of IL-1Ra may be a risk factor for RE and DGF and that IL-1β/IL-1Ra haplotype influences the impact of allograft outcome. These findings may significantly abet in better perception of the survival of the graft.

Topical Cyclosporine A in Corneal Graft Rejection

Corneal graft rejection is now the most common cause of graft failure after penetrating keratoplasty. This study was designed to determine whether, addition of 2% topical cyclosporine (CSA) to local and systemic steroids in treatment of endothelial corneal allograft rejection, would improve the outcome. A prospective randomized treatment trial was carried out on 40 consecutive corneal graft recipients, presenting with the first episode of endothelial graft rejection in two groups. Group one (20 patients) received topical steroids eye drops and systemic prednisolone (1 mg/kg) by oral route plus placebo. Group two (20 patients) received the same topical and systemic steroid therapy plus 2% cyclosporine A (CSA) eye drop. The patients were followed up for three months and their clinical outcomes were evaluated by the rates and time of rejection reversal. In group one, 14 (70%) cases had total reversal of graft rejection episode but in CSA group, it occurred in 18 (90%) cases (P=0.21) .Improvement were started within a mean period of 3 and 1.5 days respectively (P value<0.001). Among patients who sought treatment early (<6 days), the survival rates were 85% and 100% respectively (P=0.2). In high risk patients the rejection reversal rate was 66% in CSA group and 25% in the control group (P=0.5). Our study indicates addition of 2% CSA eye drop to topical and systemic steroids in graft rejection decreases the interval between treatment intervention and improvement of clinical signs. In high risk patients it may improve the reversal rate, however it needs further studies.

240: Matrix metalloprotease (MMP)-1 Serum levels correlate with incidence of acute graft rejection episodes in patients undergoing cardiac transplantation

240: Matrix metalloprotease (MMP)-1 Serum levels correlate with incidence of acute graft rejection episodes in patients undergoing cardiac transplantation

Outcome of Four High-Risk Pregnancies in Female Liver Transplant Recipients on Tacrolimus Immunosuppression

Pregnancies in women after liver transplantation are considered high risk due to the greater rate of complications observed in immunosuppressed graft recipients. We report successful outcomes of four high-risk pregnancies in female liver transplant recipients on tacrolimus-based immunosuppression. The patients, aged 23 to 32 years, at the time of conception were 12 to 59 months from transplantation (mean 30 months). Preterm labor was the most important pregnancy complication observed in these patients. One episode of acute graft rejection was observed. A variable demand for tacrolimus was noted during pregnancy. Despite complications all four pregnancies were successful. The mean gestational age at delivery was 34.4 weeks. The birth weight of the newborns varied from 1410 to 3490 g (mean 2303 g) and the mean Apgar score was 8. No structural malformations or early complications were observed in the newborns. Excluding the patient with acute rejection, the remaining three cases showed all liver parameters to remain stable.

Prior renal transplantation does not facilitate subsequent canine islet allograft survival

Successful islet allografts can be established in rats bearing long surviving renal allografts, without additional immunosuppression, when kidney and islet donor animals are of the same strain. The applicability of such a scheme to clinical practice has been investigated in a large animal model of diabetes: the pancreatectomized dog. Eight dogs with previously established renal allografts and immunosuppressed with cyclosporin A received islet allografts from their respective original kidney donors. The median islet graft functional survival was only 10.5 days, significantly less than for six similarly immunosuppressed dogs receiving islet allografts alone (48.5 days, P less than 0.05). Three of the sequentially transplanted dogs had had no renal graft rejection episodes before islet transplantation, yet their islet grafts were all rejected within 19 days. In the pancreatectomized dog, prior donor specific renal transplantation has an adverse effect upon subsequent islet graft survival.

Optical penetrating keratoplasty in eyes with severe keratomycosis after therapeutic keratoplasty

To observe and evaluate secondary optical penetrating keratoplasty (PKP) in the eyes with severe keratomycosis after therapeutic keratoplasty using cryopreserved donor tissue. There were 35 eyes in 35 cases for whom therapeutic PKP using cryopreserved donor tissue had been carried out to treat severe fungal keratitis. At least 6 months after the PKP, when the fungal infection had been eradicated and ocular inflammation had resolved, a secondary optical penetrating keratoplasty was further performed for visual rehabilitation. If the crystal lens was found to be opaque, it was also simultaneously removed through extracapsular cataract removal with an IOL implantation. Surgical or postoperative complications, visual outcome, graft rejection episode, and graft survival were analyzed. Among 35 eyes, 18 eyes received optical PKP only, and 17 received combined optical PKP with ECCE and IOL implantation. During the follow-up period of 6.8 - 36.8 (15.7 +/- 7.6) months after optical PKP, 3 eyes experienced graft failure due to immunologic rejection and 32 retained clear grafts. Postoperative visual acuity was 0.4 or better in 24 eyes, and 0.1 or better in 32 eyes, and less than 0.1 in 3 eyes. Optical PKP performed in the eyes after therapeutic PKP due to severe fungal keratitis can recover satisfactory visual acuity, with low frequency of graft rejection, long-term graft survival and few complications.

Transplantation of Haplo-Identical Bone Marrow-Derived Mesenchymal Stem Cells Together with Hematopoietic Stem Cells To Promote Engraftment in Children. A Phase I/II Multicenter Study.

Graft failure or rejection is an identified problem in haplo-identical or second attempt transplantation. In the bone marrow, mesenchymal stem cells (MSCs) have been identified and shown in animal models to enhance hematopoietic stem cell (HSC) engraftment. Advances in techniques and higher quality culture components have allowed the development of an MSC expansion procedure resulting in sufficient MSCs for clinical application. Adult studies have suggested that co-transplantation of MSCs and HSCs in the HLA-identical setting, is feasible and safe.Here we present the first combined clinical experience within the EBMT MSC expansion consortium with respect to co-transplantation of haplo-identical MSCs in the pediatric allogeneic transplantation setting.Six weeks before the SCT, 50 cc of bone marrow are sampled under sterile conditions. Density gradient-separated MNCs are plated into tissue culture flasks in low-glucose DMEM supplemented with 10% fetal calf serum and incubated at 370C with 5% CO2. At 70% confluence, the cells are trypsinized and re-plated at 4x103 cells/ cm2 until the target dose of 1–2 x106/kg recipient body weight is obtained. Enrichment and expansion of MSCs is performed under GMP conditions in nationally accredited laboratories. MSCs (either fresh or cryopreserved) are administered i.v. 4 hours before infusion of donor HSCs. To date 4 children have undergone co-transplantation. Patient characteristics are summarized in the table. All toxicities associated with the procedure were documented, as were the engraftment kinetics and immune recovery. The study was carried out with approval of the respective local ethical committees.The data indicate that expansion and co-transplantation of MSCs is feasible and well tolerated. While the study is ongoing initial engraftment and immune recovery data (compared to historical data) is encouraging and to date there have been no episodes of graft rejection or severe adverse events related to this treatment.Patient characteristicsPatient demographicsHSC characteristicsMSC characteristicsUPNGenderAgeDiagnosisDonorCD34 dose (106/kg)DonorCell dose (106/kg)1M15ANLLmother-haplo16mother1.52M2XLPDfather-haplo20father1.93M2XLPDfather-haplo18.7father1.564M8SAAURD (2 loci mismatched)2.65mother1.0

Impact of HLA-C and Bw Epitopes Disparity on Liver Transplantation Outcome

The occurrence of graft rejection episodes after orthotopic liver transplantation (OLT) despite the use of immunosuppressive drugs designed to suppress T lymphocyte functions, indicates the involvement of other types of cells in this process. The activity of natural killer cells and their killer immunoglobulin-like receptors (KIR) is regulated by human leukocyte antigen (HLA) class I determinants; C and Bw epitopes. Because recipient/donor pairs are usually HLA mismatched, recipient natural killer alloreactivity may be the mediating factor in rejection. In this retrospective study, we have analyzed rejection occurrence and outcome in 66 OLT recipients, 42 with and 24 without C or Bw epitope disparity in the rejection direction. Recipients transplanted from donors with no C epitope disparity had significantly fewer rejection episodes in the first year after transplantation compared with recipients transplanted across C epitope disparity ( p = 0.0002). Moreover, this effect was more pronounced when the outcome was analyzed in OLT recipients across negative crossmatching for the anti-HLA class I and II antibodies. In contrast, Bw epitope disparity did not affect the outcome. In conclusion, C epitopes disparity between recipients and donors in the rejection direction appears to influence posttransplant liver outcome. This finding may be helpful in the choice of appropriate liver donor and planning immune suppression.

Antibody-mediated organ-allograft rejection

Recent studies show that alloantibodies mediate a substantial proportion of graft-rejection episodes, contributing to both early and late graft loss. Rejection that is caused by antibody is mediated by different mechanisms from rejection that is caused by T cells, thereby requiring other approaches to treatment and prevention. Antibody induces rejection acutely through the fixation of complement, resulting in tissue injury and coagulation. In addition, complement activation recruits macrophages and neutrophils, causing additional endothelial injury. Antibody and complement also induce gene expression by endothelial cells, which is thought to remodel arteries and basement membranes, leading to fixed and irreversible anatomical lesions that permanently compromise graft function.

The Impact of Thiopurine S-Methyltransferase Polymorphism on Azathioprine-Induced Myelotoxicity in Renal Transplant Recipients

Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TMPT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. It has previously been reported that 3 variant alleles: TPMT*2, *3A, and *3C are responsible for over 95% cases of low enzyme activity. The purpose of this study was to explore the association between these polymorphisms and the occurrence of azathioprine adverse effects in 112 renal transplant recipients undergoing triple immunosuppressive therapy including azathioprine, cyclosporine, and prednisone. TPMT genetic polymorphism was determined using PCR-RFLP and allele-specific PCR methods. Azathioprine dose, leukocyte, erythrocyte, and platelet counts, graft rejection episodes, as well as cyclosporine levels were analyzed throughout the first year after organ transplantation. We found the frequency of leukopenia episodes (WBC < 4.0 x 10(9)/L) significantly higher in heterozygous patients (53.8%) compared with those with TPMT wild-type genotype (23.5%). One patient, who was a compound homozygote (3A/*3C), experienced severe azathioprine-related myelotoxicity each time after receiving the standard drug dose. Our results suggest that polymorphisms in TPMT gene may be responsible for approximately 12.5% of all leukopenia episodes in renal transplant recipients treated with azathioprine. Genotyping for the major TPMT variant alleles may be a valuable tool in preventing AZA toxicity and optimization of immunosuppressive therapy.

Pregnancy outcome after renal allograft transplantation: 15 years experience

Objective: To present our 15 years’ experience in the management of 67 pregnancies in renal allograft recipients in Egypt. Methods: A retrospective study of 67 pregnancies that occurred in 41 renal allograft recipients over the last 15 years. The study was performed in Department of Obstetrics & Gynecology, and Nephrology & Urology Center at Mansoura University, Egypt. Results: Gestational diabetes occurred in 5.7%, infection in 13.4% and proteinuric hypertension in 19.2% of pregnancies. Graft dysfunction and obstructive uropathy occurred in 30.7% and 9.6% of pregnancies, respectively, but no episodes of graft rejection were reported. Pre-term labour was found in 40.9% and fetal growth retardation occurred in 19.2% of pregnancies. Perinatal mortality was in the order of 9.6%. Pregnancy outcome was better in non-cyclosporine group, in non-proteinuric hypertensive groups and in repeated pregnancies compared to the counter groups. Conclusion: Although pregnancy in renal transplant recipients is high-risk, successful outcome is expected for singleton pregnancy and is even better with repeated pregnancies in those cases with stable and good graft function. This satisfactory outcome is generally achieved if the graft is stable and the post-transplant interval is more than 2 years.

Improved Graft Survival in ABO-Incompatible Living Donor Kidney Transplantation

Introduction We reviewed ABO-incompatible living donor kidney transplantations (LDKT) performed in our institute. Patients Fourteen ABO-incompatible LDKT were carried out in the first era (September 1990–August 1996) and 13 were in the second era (October 2001–July 2004). All patients were treated with sessions of plasmapheresis before transplantation to reduce antibody titers <1:8. In the second era, those with rebound increase of antibody titers >1:64 after repeated plasmapheresis were not subjected to transplantation. Posttransplantation immunosuppression consisted of cyclosporin, predonisone, azathioprine, gusperimus hydrochloride (DSG), and antilymphocyte globulin (ALG) in the first era, and tacrolimus, mycophenolate mofetil, predonisone, and DSG in the second era. Splenectomy was performed during the transplantation. Anticoagulant therapy was introduced in the second era. Results One-, 2-, and 5-year graft survival in the first era was 57%, 57%, and 50%, respectively, values that were significantly lower than those of ABO-compatible cases in the same period (n = 101), namely, 1-, 3-, and 5-year graft survival rates 93%, 83%, and 76%, respectively. The main reason for graft and patient losses was infectious complications. In the second era, no recipient suffered a severe infectious complication and 1- and 2-year graft survival rates were both 100%. Four patients in the first era and 1 in the second era experienced a graft rejection episode between 10 days and 14 months after transplantation, but they were successfully treated with steroid pulse therapy. Conclusion Although patients with high blood group antibody titers remain problematic, ABO-incompatible LDKT is an increasingly viable option for patients whose only donor is blood group-incompatible.