PCNA in assessment of progression rate of chronic renal allograft rejection

• Published in: Srpski arhiv za celokupno lekarstvo Vol. 130; no. 5-6; pp. 159 - 164
• Main Authors: Simic-Ogrizovic, Sanja, Starcevic-Bozovic, Angelina, Blagojevic, Radmila, Radivojevic, Dragana, Djukanovic, Ljubica
• Format: Journal Article
• Language: English
• Published: Serbian Medical Society 2002
• Subjects: PCNA marker; renal allograft rejection
• ISSN: 0370-8179; 2406-0895
• DOI: 10.2298/SARH0206159S

Chronic graft failure may occur due to CR, cyclosporine nephrotoxicity repeated acute rejection, recurrent glomerular diseases, surgical and urological complications, but CR was recognized as the most common cause of chronic graft failure and renal graft loss [7]. Progression of renal disease reflects the interactive effects of changes in the structure and function. This notion has been examined many times in the native kidneys by studies correlating glomerular filtration rate with architectural deterioration in the glomerular or interstitial compartment [8-10]. Meanwhile, the similar studies in human renal allograft are scarce. Increased PCNA immunodetection in glomerular cells as well as in interstitial infiltrates was described in acute and chronic renal graft rejection and diagnostic value of this finding was analyzed [12,15]. Similarly, PCNA was often examined immunohistochemically in lymphoma and solid tumors as a marker of cell proliferation, but its reliability as a prognostic factor was also evaluated [18-20]. In the present study the prognostic value of PCNA expression in different tissue compartments of renal grafts experiencing CR was examined for the first time. The present study revealed that two groups examined with the different chronic graft failure progression rate as the main difference had significantly different proliferation of cells in glomerular, TIN and vascular compartments. PCNA immunoreactivity scores in these three compartments were significantly higher in the fast than in slow progression group. The significant positive correlation between the slope of the regression line plotting 1/sCr vs. time and cell proliferation in glomerular, TIN and vascular compartments was also found. Therefore, it was suggested that the measurement of PCNA expression in renal graft tissue might be used as a prognostic index.
Hronicno odbacivanje transplantisanog bubrega je najvazniji i najcesci uzrok hronicne insuficijencije kalema. Cilj studije je ispitivanje ekspresije nuklearnog antigena proliferacije celija u vaskularnom, glomerulnom i tubulointersticijumskom delu tkiva, dobijenog biopsijom transplantisanog bubrega s hronicnim odbacivanjem, i mogucnost predvidjanja brzine progresije hronicne insuficijencije kalema pomocu ovog metoda. Retrospektivno, posle biopsije kalema, procenjivan je klinicki tok 27 bolesnika s dijagnozom hronicnog odbacivanja, a bolesnici su svrstani u dve grupe prema brzini progresije hronicne insuficijencije kalema: grupa s brzom progresijom od deset bolesnika i grupa sa sporom progresijiom od 17 bolesnika. Za ispitivanje ekspresije nuklearnog antigena proliferacije celija koriscen je imunohistohemijski streptavidin-biotin-peroksidazni metod bojenja s monoklonskim antitelom (PC-10, DACO). Ekspresija nuklearnog antigena proliferacije celija u celijama glatkih misica i limfocitima intime krvnih sudova, u mezangijumu glomerula i u limfocitima tubulointersticijumskog dela procenjivana je semikvantitativno (skala od nule do tri), a razlika izmedju grupa je statisticki testirana. Poredjenje izmedju grupa je pokazalo da je intenzitet proliferacije celija u grupi s brzom progresijom znacajno veci nego u grupi sa sporom progressom u sva tri posmatrana dela tkiva dobijenog biopsijom: vaskularni (2,6 vs 1,23), glomerulni (1,9 vs 0,88) i tubuloin-tersticijumski (2,0 vs 0,44). Takodje, postoji i statisticki znacajna pozitivna korelacija izmedju nagiba regresione linije i intenziteta proliferacije celija u vaskularnom (g= 0,671), glomerulnom (g- 0,552) i tubuloin-tersticijumskom (r= 0,567) delu. Ispitivanja su pokazala da intenzitet proliferacije celija u sva tri posmatrana delaznacajno korelise s brzinom progresije hronicne insuficijencije kalema i da je moguce predvideti brzinu progresije tubulointersticijumske hronicne insuficijencije kalema pomocu procene ekspresije nuklearnog antigena proliferacije celija.