[Progression of chronic renal insufficiency in chronic rejection: the role of chronic transplantation glomerulopathy].
Chronic rejection of kidney transplant is a chronic and progressive decline of kidney transplant function related to certain morphologic changes, such as obliterate vasculopathy, interstitial fibrosis, tubular atrophy, and transplant glomerulopathy [1]. The purpose of this study was to investigate the involvement of chronic transplant glomerulopathy in the progression of chronic renal failure.
Of 16 transplant patients with histologic diagnosis of chronic kidney transplant rejection in biopsy specimens, 8 patients had chronic transplant glomerulopathy (ChR-1), and in the other 8 patients glomeruli were relatively preserved (ChR-2). Transplant biopsies were performed between the seventh and the 15th month in ChR-1, and between the ninth and the 34th month in ChR-2 group. Morphologic vasculopathy cv2 changes, tubular atrophy ct1 and ct2 in the half of each group, and interstitial fibrosis ci2, were graded according to the BANFF criteria [2]. During the follow up the patients received similar doses of prednisone, as well as of azathioprine and cyclosporine A.
The expression of MHC I antigen, MHC II antigens, CD3, CD25, CD54 (ICAM-1) was analyzed by indirect immunoperoxidase technique of staining on the frozen sections, (DAKOPATTS). The immunoreactivity score was 0 to 3.
The renal function was expressed as reciprocal serum creatinine values (1/mumol/L) reflecting the mean monthly levels, over the period between the third and the 22nd month following the transplantation. In each patient a decline in kidney functioning was determined in two ways: 1. by the slope of the curve representing the function of regression of the reciprocal serum creatinine over time, started from the third month after the transplantation, 2. by the rate of regression (percent) of the reciprocal serum creatinine values at the sixth, the ninth, the 18th and the 22nd month, compared to the attained serum creatinine level at the third posttransplantation month.


CONCLUSIONS
Glomeruli with present chronic transplant glomerulopathy (patients of the ChR-1 group) had moderate expression of MHC I antigen [1-2], week expression of ICAM-1 (CD54), whereas DR antigens were almost absent. In cortical tubuli the expression of MHC I antigen was very low. The relatively preserved glomeruli in patients without chronic transplant glomerulopathy (ChR-2 group) showed high expression of MHC I antigen [2], moderate expression of ICAM-1, and low (up to 1) DR expression. The CD25 molecules were not detected in any analyzed glomeruli (62 in total), except a positive cellular crescent formation, seen in 3 patients with chronic transplant glomerulopathy. The regression slopes of reciprocal serum creatinine values according to months, over the third and the 22nd month were similar in both groups of patients, and the speculating mean graft survival time was 44 months, in both groups. However, 4 of 8 patients of the ChR-1 group, and only 1 of 8 patients of the ChR-2 group returned to the haemodialyses because of the graft functioning loss. Besides, the mean percentual rate of the decline in renal functioning, as the rate of decrease of serum reciprocal creatinine values in the chosen growing periods in time after the third month were higher in group ChR-1 with present chronic transplant glomerulopathy in biopsy specimens. The difference was of statistical significance at the end of the 18th month, t = 4.10, p less than 0.01. In this period proteinuria exceeding 3 grams a day was discovered in 6 patients of ChR-1 group, and in 4 patients in ChR-2 group. Our results suggest that the early appearance of chronic transplant glomerulopathy induces a slightly higher loss of function of the kidney transplant with chronic rejection, despite of the absence of the immune activation in the glomeruli with the present chronic transplant glomerulopathy. (ABSTRACT TRUNCATED)
Savić
M
M
Department of Nephrology, Clinical Centre of Serbia, Belgrade.
Djukanović
Lj
Lj
Sinkjić
M
M
Blagojević
R
R
Ostrić
V
V
D002908:Chronic Disease; D018450:Disease Progression; D006084:Graft Rejection / Q000150:complications* / Q000473:pathology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology; D011183:Postoperative Complications / Q000473:pathology
Progresija hronicne insuficijencije bubrega kod hronicnog odbacivanja: ucesće hronicne transplantacione glomerulopatije.