Influence of Intrarenal Deposits of Ciclosporin A on Acute Renal Transplant Rejection

Abstract

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.

Protective effects of FTY720 on chronic allograft nephropathy by reducing late lymphocytic infiltration

“…Allograft biopsies of patients undergoing chronic rejection demonstrated lymphocytic infiltration of perivascular as well as fibrotic interstitial areas, and even within atophic tubules [4,5,42,43]. In agreement, we observed massive CD5-positive T cells infiltrating the interstitial areas of renal allografts in the control animals of our present model.…”

P Glycoprotein: A New Mechanism to Control Drug-Induced Nephrotoxicity

“…The upregulation of P-gp showed a strong inverse relationship with the incidence of hyaline arteriopathy and periglomerular and peritubular fibrosis [see addendum]. These findings support a hypothetical role for P-gp as a detoxifying agent in the regulation of pharmacological nephrotoxicity [24, 42, 44]. …”