ABSTRACT
BACKGROUND: There is no consistent association between individual histological lesions and composite scores in donor kidney biopsy and transplant outcomes. OBJECTIVE: To evaluate which acute or chronic individual histological lesions and composite scores in donor kidney were associated with graft survival in the recipient. METHODS: We investigated the association of individual histological lesions and 8 composite scoring systems in implantation biopsies of cadaveric (n=101) and living (n=29) kidneys with 5-year death-censored graft survival. RESULTS: We found a high frequency of chronic lesions in donor kidneys, mostly associated with arteriosclerosis, and less dependent from donor age. Acute, chronic, and total Banff scores for post-transplant biopsies, chronic and total Banff scores for pre-implant biopsies, donor damage score and chronic damage score predicted death-censored graft loss. However, only chronic and total Banff-scores had significant effects in multivariate model. Chronic pre-implant and total post-transplant Banff scores demonstrated the highest area under the curve (AUC) of 0.722 and 0.717, respectively. Among individual lesions, glomerulosclerosis ≥20%, interstitial inflammation >0, arteriosclerosis =3, arteriolar hyalinosis >0, and interstitial fibrosis >0, assessed with Banff-grading criteria, were associated with lower allograft survival. We created the Donor Kidney Damage Index (DKDI), by summing regression coefficients for these lesions, which yielded the AUC of 0.747. When combined with retransplantation, cold ischemia time and acute rejection, DKDI, chronic pre-implant and total post-transplant Banff scores further improved their predictive accuracy, yielding AUCs of 0.842, 0.807, and 0.802, respectively. CONCLUSION: DKDI, chronic pre-implant and total post-transplant Banff scores alone and combined with clinical variables may facilitate decision making in post-transplant period.
ABSTRACT
The study was organized to provide additional characteristic of chronic dysfunction of renal allo-transplant using such biomarkers of serum and urine as enzymes (alanine aminotransferase), aspartate aminotransferase, gamma- glutamiltransferase, alkaline phosphatase, N-acetyl-ß-D-glucosaminidase, interleukins (IL-2, IL-8, IL-10), beta-2- microglobulin. The chronic dysfunction of renal allo-transplant is characterized by increasing of concentration of IL-10 and beta-2-microglobulin in serum and increasing of concentration of beta-2-microglobulin, IL-2, IL-8 in urine and increasing of activity of N-acetyl-ß-D-glucosaminidase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamiltransferase as compared with patients with satisfactory function of renal allo-transplant. The multivariant logistic regression analysis established that only activity of N-acetyl-ß-D-glucosaminidase in urine was reliably independently related to chronic dysfunction of renal allo-transplant. It is assumed that increasing of concentration of beta-2-microglobulin in serum testifies glomerular dysfunction and in urine--tubular dysfunction of renal allo-transplant. The enzymeuria indicates continuing damage of epithelium of proximal tubules of nephron. The classification of patients with satisfactory function and chronic dysfunction of renal allo-transplant established that the highest indicators of square under ROC-curves had concentration of beta-2-microglobulin in serum (0.858 ± 0.061) and urine (0.733 ± 0.079) and activity of N-acetyl-ß-D-glucosaminidase in urine (0.701 ± 0.061). To specify diagnosis of chronic dysfunction of renal allo-transplant the most useful (ratio of likelihood of positive result 10 and 11 correspondingly) are tests of beta-2- microglobulin in serum (more than 8.55 mkg/ml) and N-acetyl-ß-D-glucosaminidase/creatinine in urine (more than 34 nmol/(sl)/ mmol/l). These discoveries require further validation and confirmation by implementation of morphological analysis of bioptat of renal allo-transplant.
