The association between cytomegalovirus immune globulin and long-term recipient and graft survival following liver transplantation.

The association between cytomegalovirus (CMV) immune globulin (CMVIG) and long-term clinical outcomes has not been well defined. We examined the association between CMVIG and long-term recipient and graft survival in liver transplant recipients. Data were from the Scientific Registry of Transplant Recipients and included recipients transplanted between January 1995 and October 2008; follow-up was through March 2009. All recipients≤80 years of age with primary, single-organ liver transplants, given CMVIG with (n=2350) or without antivirals (n=455), antivirals without CMVIG (n = 32,939), or no CMV prophylaxis (n=28,508) before discharge were included. Kaplan-Meier analysis was used to examine rates of acute rejection (AR), graft loss, and death, over 7 years post transplantation. The adjusted risk of AR, graft loss, and death associated with CMVIG with and without antivirals vs. no prophylaxis was estimated using the Cox proportional hazards regression. In the univariate analysis, CMVIG, with and without antivirals, was associated with increased AR rates, but decreased mortality; CMVIG with antivirals was also associated with decreased graft loss compared with no prophylaxis. From the multivariable model, CMVIG with antivirals was associated with increased risk for AR, but decreased risk for graft loss and death; after adjustment, the association between CMVIG alone and mortality was not significant. CMVIG with antivirals is associated with increased risk of AR but greater long-term patient and graft survival after liver transplantation.

Expression of angiotensin II type I receptor on erythroid progenitors of patients with post transplant erythrocytosis.

BACKGROUND: The pathogenesis of posttransplant erythrocytosis (PTE) has been elusive. Angiotensin converting enzyme inhibitors (ACEI) are efficacious in lowering the hematocrit of patients with PTE and angiotensin II (AII) type I receptors (AT1R) were recently detected on red blood cell precursors, burst-forming unit-erythroid- (BFU-E) derived cells. The purpose of this study was to determine whether there is increased expression of the AT1R on BFU-E-derived cells of patients with PTE, which might contribute to the pathogenesis of PTE. METHODS: Twelve healthy volunteers and 25 transplant recipients (13 patients with and 12 without PTE) were studied. BFU-E from peripheral blood were cultured in methylcellulose and BFU-E-derived colonies were harvested on day 10. Western blotting was used to detect AT1R and erythropoietin receptor (EpoR) expression. Intracellular free calcium in response to AII and erythropoietin (Epo) was measured with digital video imaging. RESULTS: There were no differences between transplant patients, with and without PTE, with respect to weight, age, sex, blood pressure, serum creatinine, circulating renin, angiotensin II, and Epo levels. Hematocrit, red blood cell number, BFU-E-derived colony number,and size were significantly increased in PTE compared with other two groups. AT1R expression was increased by 44% on the erythroid progenitors of PTE versus non posttransplant erythrocytosis patients and by 32% in PTE patients versus normal volunteers. AT1R expression correlated significantly with the hematocrit in PTE (Spearman r=0.68, P=0.01). In contrast, EpoR expression was equivalent in all groups. The AT1R was functional since a significant increase in [Ca(i)] was observed in Fura-2 loaded day 10 cells when stimulated with AII (182%, P<0.0001). CONCLUSION: An increase in AT1R density was observed in erythroid precursors of transplant patients with PTE compared to those without PTE and normal volunteers, and the level of AT1R expression in PTE correlated significantly with the hematocrit. In contrast, EpoR expression was not different in PTE compared with non posttransplant erythrocytosis or normal controls. This study supports a role for the AT1 receptor signaling pathway in the pathogenesis of PTE.

New strategies using 'low-dose' mycophenolate mofetil to reduce acute rejection in patients following kidney transplantation.

CONTEXT: Tacrolimus, microemulsion cyclosporine (Neoral), and mycophenolate mofetil (MMF) at 2 and 3 grams daily have demonstrated superior immunosuppressive properties in several recent clinical trials involving solid-organ transplants. An effective immunosuppression may be maintained with lower doses of MMF administered with either tacrolimus or microemulsion cyclosporine. OBJECTIVE: To compare tacrolimus plus "low-dose" MMF-based immunosuppressive regimen (TMBIR) with Neoral plus "low-dose" MMF-based immunosuppressive regimens (NMBIR) among kidney transplant recipients. DESIGN: Prospective, randomized study. PATIENTS: 53 consecutive adult recipients of kidney transplant. Both groups (TMBIR and NMBIR) were equally matched on demographic characteristics. INTERVENTIONS: Participants were randomized to receive orally either tacrolimus (0.08 mg/kg twice daily) (n = 27) or Neoral (4 mg/kg twice daily) (n = 26). Both regimens were started before surgery and continued when allograft demonstrated no postoperative acute tubular necrosis. Both groups received similar "low-dose" MMF (500 mg twice daily) and prednisone (2 mg/kg/day to taper off after 1 year). Switch from tacrolimus to Neoral or vice versa was allowed after refractory rejection or serious adverse events. MAIN OUTCOME MEASURE: Acute rejection and patient and graft survival 1 year following kidney transplant. RESULTS: One-year patient survival rates were 88.9% for the TMBIR group and 100% for the NMBIR group; 1-year graft survival rates were 88.9% for the TMBIR group and 96.1% for the NMBIR group. No significant differences were found in the incidence of biopsy-confirmed acute rejection (14.8% TMBIR vs 23% NMBIR). Steroid-resistant rejections requiring cytolytic antibody therapy were higher in the NMBIR group (50% vs 25%). Three patients crossed over from NMBIR to TMBIR for refractory rejections and 1 patient crossed over from TMBIR to NMBIR for new onset seizure. Three episodes of cytomegalovirus infection were observed in the TMBIR group. Other adverse events were similar in both groups. CONCLUSIONS: Both tacrolimus and microemulsion cyclosporine combined with "low-dose" MMF and corticosteroids provide effective immunosuppression and have similar adverse events in kidney transplant recipients.