M Andújar

Influence of intrarenal deposits of ciclosporin A on acute renal transplant rejection.

Immunohistochemical techniques were used to study the presence of ciclosporin A (CsA) and leukocyte subsets in 36 posttransplant renal biopsy specimens histologically diagnosed as acute graft rejection. Glomeruli from patients with CsA deposits contained more leukocytes (p < 0.05) than glomeruli from tissues without deposits. In contrast, the interstitium from patients without deposits contained significantly more B lymphocytes than interstitia from kidneys with CsA deposits. In both glomeruli and interstitia, the CD4/CD8 ratios were higher in tissues without deposits, although the difference was not significant. The plasma levels of creatinine increased with the intensity of renal CsA deposits, and significantly more patients on hemodialysis had deposits as compared with patients not on hemodialysis. Our findings suggest two types of acute nonvascular rejection: (1) predominantly interstitial, with a good prognosis, characterized by low numbers of intrarenal CsA deposits and a predominance of B lymphocytes and (2) predominantly glomerular, with a poor prognosis, characterized by high levels of intrarenal CsA and a predominance of CD8-positive cells and macrophages.

Presence of Cytomegalovirus Genome and Leucocyte Subsets in Renal Transplant Biopsies: Relationship with Prognosis

The influence of immunosuppressant therapy and of the presence of CMV genome on the distribution of lymphoid subpopulations of the inflammatory infiltrate in renal graft rejection was analyzed, as was the role of both factors in the evolution and survival of the graft. The study included 22 patients treated with Cyclosporin A (CsA) and 22 patients treated with Azathioprine (AZA). Inflammatory infiltrate was studied by immunostaining with a panel of monoclonal antibodies, and CMV DNA was detected by in situ hybridization on tissue sections. In patients treated with CsA, increased cellularity was found at both glomerular and interstitial levels, consisting mainly of macrophages and T-cells, which was consistent with the higher rate of glomerulointerstitial rejection found in this group. In contrast, the vascular type of rejection predominated in AZA treated patients. However, the presence of CMV DNA did not influence the phenotype of the inflammatory infiltrate, and was not associated with any specific lesion. Furthermore, the final outcome of the renal graft was independent of the detection of CMV. Therefore, this study provides no evidence of any active role of the CMV genome in renal graft rejection, and suggests that therapy should be adapted to the type of rejection as defined on morphologic and immunophenotypic grounds.