Acute Tubulointerstitial Rejection Research Articles

The high prevalence of severe early posttransplant renal allograft pathology in hepatitis C positive recipients.

In the USA approximately 10% of candidates for renal transplantation have serum antibodies to hepatitis C (HCV). To assess the possible impact of HCV infection on early posttransplant events we assessed allograft complications during the first 6 months following renal transplantation in three groups of adult renal allograft recipients: (1) HCV antibody positive recipients (R-HCV) (n=32); (2) HCV negative recipients who received kidneys from HCV antibody positive donors (D-HCV) (n=48); and (3) HCV negative recipients of HCV negative allografts who were transplanted during the same time period as R-HCV (Ctrl) (n=204). Allograft biopsies were done for evaluation of allograft dysfunction during the first 6 months posttransplant in 58% of Ctrl, 42% of D-HCV, and 63% of R-HCV (not significantly different). The prevalence of acute tubulointerstitial rejection was similar among the 3 groups of patients. In contrast, compared with Ctrl, both R-HCV and D-HCV had a significantly higher prevalence of acute transplant glomerulopathy (Ctrl, 6%; R-HCV, 55%, P<.0001; D-HCV 40%, P=.0004). Acute vascular rejection was more common in R-HCV (60%) than in Ctrl (28%) (P=.009) and the prevalence of chronic vascular rejection was also higher in R-HCV (60%) than in Ctrl (31%) (P=.01). Furthermore, chronic vascular rejection was diagnosed earlier in R-HCV (64% of cases within one month posttransplantation) than in Ctrl (19% within one month) (P=.01). Death censored renal allograft losses occurred in 14% of Ctrl, 17% of D-HCV, and 26% of R-HCV (not significant). In conclusion, R-HCV patients have a high prevalence of severe acute pathologic findings in renal allograft biopsies obtained early after transplantation and develop chronic vascular rejection more often and earlier than HCV negative recipients. These studies also confirm the previously reported association of HCV with acute transplant glomerulopathy.

Interstitial rejection, vascular rejection, and diffuse thrombosis of renal allografts. Predisposing factors, histology, immunohistochemistry, and relation to outcome.

Histological and immunohistochemical analyses were made of biopsy specimens from 50 consecutive patients who experienced putative graft rejection. The mean age of the patients was 44.5 years (range, 17-69 years) and 26 were men. There were 67 evaluable allograft specimens, which were grouped according to the histological diagnosis: group 1, acute tubulointerstitial rejection (n = 42); group 2, acute vascular rejection (n = 18); and group 3, diffuse thrombosis (n = 7). Over a follow-up period of 21-57 months, the mean number of rejection episodes was 1.7, 2.8, and 3.3 in groups 1, 2, and 3, respectively. Allograft loss occurred in 7 out of 30, 10 out of 16, and 4 out of 4 patients in groups 1, 2, and 3, respectively. The following histological parameters differed significantly (P < 0.05) among the groups: interstitial edema, congestion of peritubular capillaries, glomerular thrombosis, and glomerular ischemia (group 3 > group 2 > group 1). Interstitial bleeding was seen more often in group 2 and 3 tissues than in group 1 specimens (P < 0.01). Immunohistochemical analyses showed that vascular rejection was associated with WT14 staining for monocytes and macrophages around the tubuli and with interstitial deposition of complement factor 3. With regard to serology, positive anti-endothelial cell antibody-dependent cellular cytotoxicity was associated with vascular rejection and thrombosis of the graft in all patients tested, and with graft loss in 75%. Pre-existent positive anti-IgG immunofluorescence on peritubular capillaries in pretransplant biopsy specimens incubated with patient serum was found in only 3 of the 50 patients, but was associated with graft loss in 2 of the 3. Cytomegalovirus infection was associated with a higher percentage of graft loss. There were significant intergroup differences in panel reactive antibodies before transplantation (P < 0.001), with higher titers in groups 2 and 3. The findings in relation to interstitial rejection are compatible with cellular rejection, while the data on vascular rejection support a humorally mediated pathogenesis.

Chronic transplant rejection

A 30-year-old woman was admitted to the University of Minnesota Hospital to receive a second cadaveric renal transplant. Eighteen years earlier, she had received her first cadavenc renal transplant for renal failure due to chronic glomerulonephritis. She had been dialyzed for 4 months, during which time she underwent splenectomy and bilateral nephrectomy. Tissue from the latter procedure demonstrated end-stage renal disease consistent with chronic glomerulonephritis. She was treated with azathioprine, 100 mg/day, and prednisone, 20 mg/day, as a maintenance regimen initially; within one year, the prednisone dose was reduced to 10mg daily. The patient's first renal aflograft functioned well for several years; the serum creatinine concentration ranged between 0.9 mg/dl and 1.1 mg/dl. Eleven years ago, the serum creatinine concentration rose to 2.9 mg/dl over 2 months; a graft biopsy demonstrated acute tubulointerstitial rejection. The patient admitted to noncompliance with her immunosuppressive regimen over several weeks. The prednisone dosage was increased to 100 mg/day and then tapered over the succeeding one month to 15 mg/day; the serum creatinine concentration stabilized at 1.6 mg/dl. Because of a rise in the serum creatinine concentration to 2.0 mg/dl, a graft biopsy was repeated 5 years ago. The biopsy specimen demonstrated chronic tubulointerstitial rejection and focal scarring with changes of chronic vascular rejection. The immunosuppressive regimen was continued, but propranolol, 20 mg twice daily, was begun because of hypertension. Subsequently, the dose of propranolol was increased to 40 mg twice daily; her blood pressure was controlled at approximately 135/85 mm -Hg. Because of a subsequent rise in the serum creatinine concentration to 2.5 mg/dl 3 years prior to admission, the

Preferential rejection of the kidney in a simultaneous kidney-pancreas transplant.

A case of selective kidney allograft rejection with stable pancreas function in a patient who received simultaneous kidney-pancreas allograft from the same donor is reported. Pancreas function was shown to be normal within the first month posttransplant by both a glucose tolerance test (despite a high corticosteroid dose) and stable urinary amylase values during biopsy-proven acute renal allograft rejection. This patient subsequently rejected his kidney allograft as documented by histopathologic evidence of severe chronic vascular rejection and acute tubulointerstitial rejection, yet his pancreas function remained intact. He subsequently received a six-antigen-matched kidney, continues to have normal fasting glucose and normal glucose tolerance by oral glucose tolerance test, and is without evidence of glucosuria. He has never had a clinical rejection of his pancreas, as evidenced by either a decline in urinary amylase or hyperglycemia, and has not required insulin except in the perioperative period of his second kidney transplant, at which time he was receiving high doses of both corticosteroids and cyclosporin. It is suggested that preferential rejection and subsequent loss of the kidney, although infrequent, do occur in combined renal-pancreas allografts and that maintenance of immunosuppression is justified until retransplant of kidney is available.