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Immunosuppressive maintenance therapy after kidney transplantation leads to various undesired side effects such as calcineurin inhibitor (CNI)-associated nephrotoxicity or elevated cardiovascular risk due to posttransplantation diabetes and hypertension. These effects show negative impacts on long-term allograft function as well as patient morbidity and mortality. Therefore, we used an immunosuppressive regimen with early corticosteroid withdrawal (ESW), maintenance therapy containing tacrolimus, sirolimus (SRL), and mycophenolate sodium for 3 months followed by a prospective randomized trial comparing a CNI free versus a low-dose CNI therapy. The primary endpoint was 6-month graft function. Among 75 patients, ESW was performed after 4 days in 65 patients. Over the following 3 months before randomization to CNI-free maintenance therapy, we experienced a high number (25%) of SRL discontinuations due to adverse events, including leukopenia, anemia, arthritis, and pneumonitis. In addition there were significantly more allograft rejection episodes in the CNI-free group (P = .017) during the study period leading to a switch from SRL to a CNI. Despite the higher rate of rejection episodes in the CNI-free groups, glomerular filtration rates (GFR) at 6 months were comparable between the study groups (P = .25). After 1 year only 9.2% (6/65) of all patients treated with SRL remained on this drug. Conclusion, there was an unacceptably high rate of SRL intolerance using an ESW and CNI-free immunosuppressive regimen combined with a significantly higher rate of rejection episodes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on various cell types and mediates homophilic cell adhesion. CEACAM1 plays an important role in cell morphogenesis and angiogenesis. Furthermore, CEACAM1 regulates adhesive activity of immune-competent cells, suggesting an additional role in inflammatory processes., Methods: Therefore, in the present study the expression of CEACAM1 was analysed retrospectively in renal biopsies from kidney transplant recipients (stable graft [Ctr; n = 18], acute vascular rejection [AVR; n = 14], acute tubulointerstitial rejection [AIR; n = 9], and combined vascular and interstitial rejection [AVIR; n = 7]). Expression patterns of CEACAM1 were determined using immunohistochemistry and quantitative morphometry., Results: All biopsy specimens from patients with stable grafts showed low CEACAM1 levels, suggesting a constitutive expression in renal transplants. In patients with acute rejection, CEACAM1 was markedly up-regulated. AVR revealed the highest tubular CEACAM1 levels (4.9 +/- 0.5% [AVR] vs 2.2 +/- 0.3% [Ctr] of tubular area; P < .05), whereas interstitial rejections showed the highest glomerular expressions (4.5 +/- 0.5% [AIR] vs 0.9 +/- 0.1% [Ctr] of glomerular area; P < .05)., Conclusions: An up-regulated expression of CEACAM1 in tubular and/or glomerular cells is an indicator of acute inflammatory processes in biopsy specimens from patients with acute renal allograft rejections and, therefore, might be used as a new clinical marker.

Chronic CSA nephrotoxicity is the second most important diagnosis responsible for the late graft failure. CSA associated arteriolopathy (CAA) is a well-known lesion of chronic CSA nephrotoxicity. The clinicopathological characteristics and the significance of CSA nephrotoxicity have changed following reduction in CSA doses and implementation of monitoring of blood levels. Seventy-four CAA patients on CSA therapy were classified as functioning (n=30) or loss groups (n=44). There was no significant difference in severity of CAA. The concomitant lesion of chronic rejection, but not the severity of CAA, was the most important risk factor for graft loss. Among 54 recipients with focal segmental glomerulosclerosis lesions (FGS), 32 (59%) were diagnosed as CAA associated glomerulopathy (CAG). Eighteen of the 32 CAG patients lost their grafts upon follow-up. Decreasing the CSA dosage to maintain lower blood levels than the usually optimal concentrations, but not discontinuation of CSA, has been useful to retard the progression of graft dysfunction in half of 15 isolated pure CAG patients. Patients with increasing daily proteinuria exceeding 2 grams lost their graft function despite CSA reductions. CAA is not a specific lesion of chronic CSA nephrotoxicity; the FGS lesion is also a nonspecific lesion often seen in renal allografts. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. The FGS lesion accompanying CAA is considered to be CSA-associated glomerulopathy. These data contribute to therapeutic plans for renal transplant patients during long-term CSA treatment.