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Development of Transplant Glomerulopathy in Recipients With Antibody Mediated Rejection: Activation of Inflammatory Pathway Through Renal Poly (ADP-Ribose) Polymerase (PARP)

Ozdemir, B. Handan1; Ozdemir, F. Nurhan2; Baskin, Esra2; Moray, Gökhan3; Haberal, Mehmet3

doi: 10.1097/01.tp.0000520364.45828.da
211.2
Free

1Pathology, Baskent University, Ankara, Turkey; 2Nephrology, Baskent University, Ankara, Turkey; 3Transplant Surgery, Baskent University, Ankara, Turkey.

Introduction: Activation of PARP is a critical factor in the pathogenesis of various inflammatory and fibrotic process. Thus, we aimed to show the integral of PARP in the inflammatory process of glomeruli and the development of transplant glomerulopathy (TG).

Methods: Biopsies of 82 patients with antibody-mediated rejection were included to study. PARP, α-SMA, and TNF-α, expression of glomeruli studied. The mean number of neutrophil, macrophage, and lymphocyte infiltration per glomerulus evaluated. The degree of the peritubular capillary (PTC) inflammation and the presence of neutrophil and macrophage in PTCs investigated. PTC C4d, PARP, and HLA-DR expression graded. The decreasing intensity of PTC HLA-DR (PTC-DR) expression accepted as the increasing degree of the destruction of PTC’s. Follow-up biopsies analyzed for the development of transplant glomerulopathy.

Results: Of 82 recipients, only 40 showed TG. The time of the development of TG decreased with increasing degree of PTC neutrophil and macrophage infiltration, PTC inflammation, intraglomerular macrophage, and neutrophil infiltration (p < 0.001). TG development is increased with increasing amount of C4d expression and with decreasing degree of PTC-DR expression (p < 0.001). TG was found earlier in recipients who had a higher degree of glomerular, and PTC PARP expression (p < 0.001). Also, patients with a greater degree of glomerular PARP expression showed a higher amount of glomerular α-SMA and TNF-α expression. The intensity of the glomerular and PTC macrophage and neutrophil infiltration increases with increasing amount of glomerular and PTC PARP expression (p < 0.001).

The 5-year graft survival was 78% and 15% for recipients with negative and positive glomerular PARP expression respectively (p < 0.001). Also, the5-year survival was 84%, 41% and %0 for patients with grade1, 2 and 3 PTC PARP expression respectively (p < 0.001).

Conclusion: Increased PARP activation both in glomeruli and PTCs leads to early TG and early graft loss. Thus, it will be beneficial to use PARP inhibitor drugs in recipients with a high risk of transplant glomerulopathy.

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