Histopathological findings in well-functioning, long-term renal allografts.
One hundred and twenty-eight patients with a first cadaveric kidney allograft participated in a prospective, randomized, clinical trial comparing triple treatment, consisting of initial low-dose cyclosporine (CsA), azathioprine (Aza) and methylprednisolone (MP), with all possible combinations of two immunosuppressive drugs. A protocol core biopsy was performed on all patients with a functioning graft two years after transplantation. The histological findings were evaluated blindly and correlated to possible risk factors for renal allograft damage. The most common histological features were diffuse fibrosis in 62% of biopsies, tubular atrophy in 64% and diffuse inflammation in 30%. Two other important findings were glomerulosclerosis (43%) and vascular intimal proliferation (36%). The histological findings were scored mostly mild. A total of 77% (69 of 89) of patients had normal or only slightly increased serum creatinine. Decreased graft function was related to increased interstitial fibrosis, inflammation, glomerulosclerosis, mesangial matrix increase of glomeruli, intimal proliferation of vessels and tubular atrophy. These findings are characteristic, but not pathognomonic, of chronic renal allograft rejection both in experimental models and in humans. Possible risk factors were correlated to graft histology. Donor age correlated strongly with mesangial matrix increase, intimal proliferation, and tubular atrophy; there was no correlation with interstitial changes. The number of acute rejections and cold ischaemia time did not correlate with any one of the histological findings at two years following transplantation. Cyclosporine dose and concentration had a negative correlation to interstitial inflammation. A "chronic allograft damage index" was eventually created for the comparison of the four different treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Isoniemi
H M
HM
Fourth Department of Surgery, Helsinki University Central Hospital, Finland.
Krogerus
L
L
von Willebrand
E
E
Taskinen
E
E
Ahonen
J
J
Häyry
P
P
D000328:Adult; D003404:Creatinine / Q000097:blood; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000473:pathology; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D007684:Kidney Tubules / Q000473:pathology; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
D007166:Immunosuppressive Agents; D003404:Creatinine