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
BACKGROUND: Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown. MATERIAL AND METHODS: The study was performed on AAA wall-tissue samples obtained from 30 simvastatin-treated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. RESULTS: The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression. CONCLUSION: Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Aorta, Abdominal/drug effects , Aortic Aneurysm, Abdominal/drug therapy , Cyclophilin A/analysis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Mitogen-Activated Protein Kinase 1/analysis , Mitogen-Activated Protein Kinase 3/analysis , Simvastatin/therapeutic use , Aged , Aged, 80 and over , Aorta, Abdominal/enzymology , Aortic Aneurysm, Abdominal/enzymology , Aortic Aneurysm, Abdominal/genetics , Basigin/analysis , Basigin/genetics , Blotting, Western , Case-Control Studies , Cyclophilin A/genetics , Down-Regulation , Female , Humans , Linear Models , Male , Middle Aged , Phosphorylation , RNA, Messenger/analysis , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
It is found that youths at the ontogenesis stages from 11 to 21 years show a gradual increase in the parameters of their neurodynamic functions. The most significant increase in the growth rate of the functional mobility and of the strength of nervous processes is observed in youths at the initial stages of pubescence (14-15 years). At the final stages of their pubescence (16-17 years) the neurodynamic of youths is maximally approaching the adults' level.
