Comparison of long-term outcomes between spousal transplants and other living unrelated donor transplants: single-center experience.

BACKGROUND/AIMS: The greater use of living unrelated donors (LUDs) as kidney donors is a worldwide trend in the current era of organ shortage, and spouses are an important source of LUDs. This study was to compare the long-term outcomes of spousal donor grafts with other LUD grafts. METHODS: Among 445 LUD grafts, 77 were spouses and 368 were other LUDs. The clinical characteristics and long-term survival rates for spousal transplants were compared with those for other LUD transplants, and risk factors affecting graft survival were assessed. RESULTS: Spousal donors had a significantly higher average number of human leukocyte antigen (HLA) mismatches (4.2 vs. 3.4, p < 0.001) and were older (41 vs. 33 years, p < 0.001) than LUDs. The 10-year survival rates for spousal donor grafts were 60.6%, similar to those for LUD grafts (58.5%, p = 0.61). The 10-year biopsy-proven acute rejection-free survival rates (85.5 vs. 89.6%, p = 0.45) and patient survival rates were also similar (84.3 vs. 79.6%, p = 0.35). The degree of HLA mismatching, the spousal donor type or donor age did not affect the graft survival. CONCLUSION: Renal transplants from spousal donors show similar long-term outcomes to those from better HLA-matched and younger LUDs.

Comparison of antibody monitoring system with flow cytometric crossmatch test in renal transplant recipients with high panel-reactive antibody.

BACKGROUND/AIMS: The antibody monitoring system (AMS) is a recently developed enzyme-linked immunosorbent assay (ELISA) crossmatch assay to detect donor-specific anti-HLA immunoglobulin G antibodies (DS-HLA Abs). This study was conducted to compare the AMS with the flow cytometric crossmatch (FCXM) test in renal transplant recipients with high panel-reactive antibody (PRA). METHODS: Thirty-two sera were obtained from 10 patients with panel reactivity above 50%. When anti-HLA Ab was detected by ELISA PRA and the matched donor had the corresponding HLA antigen, it was considered to indicate DS-HLA Ab. The results of the AMS assay and FCXM were compared with the DS-HLA Abs. RESULTS: Twenty-three (71.9%) sera were positive for DS-HLA Abs by ELISA PRA. The AMS assay showed that the number of compatible sera with DS-HLA Abs was 27 (84.4%), and it was significantly concordant (kappa = 0.649, p < 0.0001). For FCXM, the number of compatible sera with DS-HLA Abs was 26 (81.3%), and it was also significantly concordant (kappa = 0.614, p < 0.0001). There was a significant degree of concordance between the AMS assay and FCXM in detection of DS-HLA Abs (kappa = 0.452, p = 0.010). CONCLUSION: The AMS assay is comparable to FCXM in detecting DS-HLA Abs in high PRA recipients.

Cyclosporin a inhibits albumin synthesis in Huh7 cells.

BACKGROUND/AIMS: Hypoalbuminemia occurs frequently in renal transplant recipients immediately after renal transplantation. We studied the regulation of hepatic albumin synthesis by cyclosporin A (CsA) in Huh7 cells. METHODS: Huh7 cells were incubated with various concentrations of CsA for 4, 8, 16, and 24 hours. Albumin was measured in Huh7 cell-conditioned medium by sandwich enzyme-linked immunosorbent assay and Western blot. Albumin mRNA expression was analyzed by Northern blotting in CsA-treated cells. RESULTS: CsA (10(-7)-10(-4) M) inhibited albumin synthesis in Huh7 cells in a dose- dependent manner. A Western blot analysis for albumin in the conditioned medium released from CsA-treated (10(-7)-10(-5) M) cells also showed significant inhibition of albumin synthesis in a dose-dependent manner. Vehicle (olive oil) did not affect albumin synthesis. In contrast, a Northern blot analysis revealed no inhibition of albumin mRNA expression by CsA at any time point from 1-24 hours, indicating that the inhibition of albumin synthesis occurred at the translational level. CONCLUSIONS: Our results suggest that inhibition of hepatic albumin synthesis by high dose CsA contributes to the hypoalbuminemia in renal transplant recipients.

Clinical impacts of CD38+ B cells on acute cellular rejection with CD20+ B cells in renal allograft.

BACKGROUND: There is an increasing evidence that the presence of CD20 B cells is associated with poor clinical outcomes in acute cellular rejection (ACR), but clinical significance of CD38 B cells is undetermined. We attempted to examine the clinical significance of the CD38 B cells alone or in combination with CD20 B cells in renal transplant recipients with ACR. METHODS: Fifty-four patients with ACR were included. Biopsy specimens were stained for CD20 and CD38. The clinical outcomes of CD20 or CD38 B cells were evaluated with late-onset and repeated ACR, steroid resistance, incomplete recovery after rejection treatment, and allograft survival. RESULTS: Twenty-three patients (42.6%) had CD20 and 25 (46.3%) patients had CD38 B cells. Of these, 15 patients (27.8%) were positive for both CD20 and CD38 (CD20CD38). CD38 patients had higher rates of late-onset or repeated ACR and incomplete recovery compared with CD38 patients (P<0.05). The patients with CD20CD38 had a higher incomplete recovery rate than did patients with only CD20 or CD38 (P<0.05). The 5-year allograft survival was lower in CD20 and CD38 patients than in CD20 or CD38 patients (P<0.05 for each). CD20CD38 patients had lower graft survival than did patients with CD20 or CD38 alone (P<0.05). CONCLUSION: Infiltration of CD38 B cells alone or in combination with CD20 B cells is a predictor for poor clinical outcomes of ACR in renal allograft.

Clinical significance of slow recovery of graft function in living donor kidney transplantation.

BACKGROUND: The clinical significance of slow recovery of graft function (SGF) in living donor kidney transplantation is unclear. We evaluated the incidence, risk factors, and clinical outcome of SGF in living donor transplantation. METHODS: Three hundred ten living donor kidney recipients were included and categorized into immediate recovery of graft function (IGF; n=239) and SGF (n=71), according to estimated glomerular filtration rate (60 mL/min/1.73 m) at posttransplant day 14. We compared the clinical parameters, protocol biopsy findings, acute rejection (AR), and 10-year graft survival between the two groups. RESULTS: The SGF group had an older recipient age, lower ratio of donor to recipient body mass index, and higher incidence of AR than IGF group, as shown by protocol biopsies. The SGF group had significantly more AR episodes than IGF group within 12 months (21.1% vs. 13.4%, P<0.05) and during follow-up period (32.4% vs. 20.1%, P<0.05). The 10-year graft survival rate did not differ between groups, but AR presence was significantly associated with a lower graft survival in the SGF group than the IGF group (64.9% vs. 78.9%, P<0.05). CONCLUSIONS: SGF in the early posttransplant period is immunologically active and should be considered as one of the risk factors for determining long-term graft survival in living donor kidney transplantation.

The efficacy and safety of ezetimibe and low-dose simvastatin as a primary treatment for dyslipidemia in renal transplant recipients.

BACKGROUND/AIMS: The efficacy and safety of a combination of ezetimibe and low-dose statin as primary treatment for dyslipidemia in renal transplant patients were evaluated prospectively. METHODS: The study enrolled 77 renal transplant recipients with dyslipidemia. They were given ezetimibe (10 mg) and simvastatin (10 mg) for 6 months as the initial treatment for dyslipidemia. Efficacy and safety were evaluated using lipid profiles, trough calcineurin inhibitor levels, allograft function, and adverse effects. The effects on proteinuria and high sensitivity C-reactive protein (hsCRP) levels were also evaluated. RESULTS: Ezetimibe and low-dose simvastatin significantly decreased the levels of total cholesterol (34.6%), triglyceride (16.0%), and low-density lipoprotein cholesterol (LDL-C) (47.6%), and 82.5% of the patients reached the target LDL-C level of <100 mg/dL. No significant change in the trough calcineurin inhibitor levels or allograft function occurred, and no serious adverse effects were observed. Fourteen patients (18.2%) discontinued treatment; eight patients (11.7%) developed muscle pain or weakness without an increase in creatinine kinase levels, and two patients (2.6%) developed elevated liver transaminase levels. The proteinuria and hsCRP levels did not change significantly. CONCLUSIONS: Ezetimibe and low-dose statin treatment is safe and effective as a primary treatment for dyslipidemia in renal transplant patients.

Successful renal transplantation with desensitization in highly sensitized patients: a single center experience.

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients.