Abstract
Objective: Angiopoietin-2 (Ang-2) is a growth factor belonging to the angiopoietin (Ang)/Tie signaling pathway. Plasma levels of especially Ang- 2, are thought to be significantly increased in patients with acute kidney injury (AKI), independent of inflammation. Ang-2 is also important in dialysis and transplantation, as it plays an important role in the disruption of endothelial homeostasis. Our study aimed to investigate the relationship between anti-HLA antibody loads and Ang levels in patients with endstage renal disease (ESRD) who are on the organ transplant waiting list.
Material and Method: 80 ESRD patients who were on the waiting list between 2018 and 2020 and whose panel reactive antibody (PRA) screening and identification test were studied participated in our study. First, the PRA screening test was performed on the patients, and the class I-II identification tests were studied on the patients who were positive for PRA. The Ang-2 level was evaluated by the ELISA method. The relationship between Ang-2 levels and PRA percentages in PRA positive and negative patients was evaluated.
Results: A positive correlation was found between anti-HLA antibody and Ang-2 levels in patients with ESRD (class I, p=0.024; class II, p=0.032), and a statistically significant increase in Ang-2 level was found in patients with PRA ≥50% positive (class I, p=0.038) This finding suggests that Ang-2 may have an important role in the progression of chronic renal failure and may be effective in predicting graft survival after transplantation.
Conclusions: Further studies will be required to fully elucidate the effect of Ang-2 on renal progression.
References
- Kim KL, Shin IS, Kim JM, Choi JH, Byun J, Jeon ES, et al. Interaction between Tie receptors modulates angiogenic activity of angiopoietin2 in endothelial progenitor cells. Cardiovasc Res 2006;72(3):394-402. google scholar
- Xu J, Lan D, Li T, Yang G, Liu L. Angiopoietins regulate vascular reactivity after haemorrhagic shock in rats through the Tie2-nitric oxide pathway. Cardiovasc Res 2012;96(2):308-19. google scholar
- Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997; 277(5322):55-60. google scholar
- Yuan HT, Khankin EV, Karumanchi SA, Parikh SM. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol 2009;29(8):2011-22. google scholar
- Korhonen EA, Lampinen, A, Giri H, Anisimov A, Kim M, Allen B, et al. Tie1 controls angiopoietin function in vascular remodeling and inflammation. J Clin Investig 2016;126(9):3495-510. google scholar
- He FF, Zhang Di, Chen Q, Zhao Y, Wu L, Li ZQ, et el. Angiopoietin- Tie signaling in kidney disease: an updated review FEBS Lett 2019;593(19):2706-15. google scholar
- Biel NM, Siemann DW. Targeting the Angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference. Cancer Lett 2016;380(2):525-33. google scholar
- Rathnakumar K, Savant S, Giri H, Ghost A, Fisslthaler B, Fleming I. et al. Angiopoietin-2 mediates thrombin-induced monocyte adhesion and endothelial permeability J Thromb Haemost 2016;14(8):1655- 67. google scholar
- Fagiani E, Christofori G. Angiopoietins in angiogenesis. Cancer Lett 2013;328(1):18-26. google scholar
- Yuan HT, Suri C, Yancopoulos GD, Woolf AS. Expression of angiopoietin-1, angiopoietin-2, and the Tie-2 receptor tyrosine kinase during mouse kidney maturation. J Am Soc Nephrol 1999;10(8):1722-36. google scholar
- Kolatsi-Joannou M, Li XZ, Suda T, Yuan HT, Woolf AS. Expression and potential role of angiopoietins and Tie-2 in early development of the mouse metanephros. Develop Dynam 2001;222(1):120-26. google scholar
- Woolf AS, Yuan HT. Angiopoietin growth factors and Tie receptor tyrosine kinases in renal vascular development. Pediat Nephrol 2001;16(2):177-84. google scholar
- Kümpers P, David S, Haubitz M, Hellpap J, Horn R, Bröcker V, et al. The Tie2 receptor antagonist angiopoietin 2 facilitates vascular inflammation in systemic lupus erythematosus. Ann Rheum Dis 2009;68(10):1638-43. google scholar
- Peters E, Antonelli M, Wittebole X, Nanchal R, François B, Sakr Y, et al. Worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from. The Intensive Care Over Nations audit. Crit Care 2018;22(1):188. google scholar
- Leligdowicz A, Richard-Greenblatt M, Wright J, Crowley VM, Kain KC. Endothelial activation: the ang/tie axis in sepsis. Front Immunol 2018;9:838. google scholar
- Yu WK, McNeil JB, Wickersham NE, Shaver CM, Bastarache JA, Ware LB. Angiopoietin-2 outperforms other endothelial biomarkers associated with severe acute kidney injury in patients with severe sepsis and respiratory failure. Crit Care 2021;25(1):48. google scholar
- Shroff RC, Price KL, Kolatsi-Joannou M, Todd AF, Wells D, Deanfield J, et al. Circulating angiopoietin-2 is a marker for early cardiovascular disease in children on chronic dialysis. PLoS ONE 2013;8(2):e56273. doi:10.1371/journal.pone.0056273. google scholar
- David S, Kumpers P, Hellpap J, Horn R, Leitolf H, Haller H, et al. Angiopoietin 2 and cardiovascular disease in dialysis and kidney transplantation. Am J Kidney Dis 2009;53(5):770-8. google scholar
- de Vries DK, Khairoun M, Lindeman JH, Bajema IM, de Heer E, Roest M, et al. Renal ischemia-reperfusion induces release of angiopoietin-2 from human grafts of living and deceased donors. Transplant 2013;96(3):282-9 google scholar
- Khairoun M, van der Pol P, de Vries DK, Lievers E, Schlagwein N, de Boer HC, et al. Renal ischemia-reperfusion induces a dysbalance of angiopoietins, accompanied by proliferation of pericytes and fibrosis. Am J Physiol Renal Physiol 2013;305(6):901-10. google scholar
- Vlahu CA, Lemkes BA, Struijk DG, Koopman MG, Krediet RT, Vink H. Damage of the endothelial glycocalyx in dialysis patients. J Am Soc Nephrol 2012;23(11):1900-8. google scholar
- Parikh SM. The angiopoietin-Tie2 signaling axis in systemic inflammation. J Am Soc Nephrol 2017;28(7):1973-82. google scholar
- He FF, Zhang D, Chen Q, Zhao Y, Wu L, Li, ZQ, et al. Angiopoietin- Tie signaling in kidney diseases: an updated review. FEBS Lett 2019;593(19):2706-15. google scholar
- Lim HS, Lip GY, Blann AD. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis 2005;180(1):113-8. google scholar
- Tsai YC, Lee CS, Chiu YW, Kuo HT, Lee SC, Hwanget SJ, et al. Angiopoietin-2, angiopoietin-1 and subclinical cardiovascular disease in chronic kidney disease. Sci Rep 2016;6:39400. google scholar
- Yuan HT, Tipping PG, Li XZ, Long DA, Woolfet AS. Angiopoietin correlates with glomerular capillary loss in anti-glomerular basement membrane glomerulonephritis. Kidney Int 2002;61(6):2078-89 google scholar
- Hillege HL, Fidler V, Diercks GF, van Gilst WK, de Zeeuw D, van Veldhuisen DJ, et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002;106(14):1777-82. google scholar
- Zhang Q, Reed QZEF. The importance of non-HLA antibodies in transplantation. Nat Rev Nephrol 2016;12(8):484-95. google scholar
- Kamburova EG, Kardol-Hoefnagel T, Wisse BW, Joosten I, Allebes WA, Van Der Meer A, et al. Development and Validation of a Multiplex Non-HLA Antibody Assay for the Screening of Kidney Transplant Recipients. Front Immunol 2018;9:3002. google scholar
- Davis B, Dei Cas A, Long DA, White KE, Hayward A, Kuet CH, et al. Podocyte-specific expression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol 2007;18(8):2320-9. google scholar
Abstract
Amaç: Anjiyopoietin-2 (Ang-2), anjiyopoietin (Ang)/Tie sinyal yolağına ait bir büyüme faktörüdür. Akut böbrek hasarı (AKH) olan hastalarda inflamasyondan bağımsız olarak özellikle Ang-2’nin plazma düzeylerinin önemli ölçüde arttığı düşünülmektedir. Ang-2, endotel homeostazının bozulmasında önemli bir rol oynadığı için diyaliz ve transplantasyonda da önemlidir. Çalışmamızda organ nakli bekleme listesinde olan son dönem böbrekhastalığı (SDBY) hastalarında anti-HLA antikor yükleri ile Ang düzeyleri arasındaki ilişkinin araştırılması amaçlandı.
Gereç ve Yöntem: Çalışmamıza 2018-2020 yılları arasında panel reaktif antikor (PRA) tarama ve tanımlama testi çalışılmış bekleme listesinde bulunan 80 SDBY (son dönem böbrek yetmezliği) hastası katıldı. Hastalara önce PRA tarama testi, PRA pozitif çıkan hastalara sınıf I-II tanımlama testleri çalışıldı. Ang-2 düzeyi ELISA yöntemi ile değerlendirildi. PRA pozitif ve negatif hastalarda Ang-2 düzeyleri ile PRA yüzdeleri arasındaki ilişki değerlendirildi.
Bulgular: SDBY olan hastalarda anti-HLA antikoru ile Ang-2 düzeyleri arasında pozitif korelasyon (sınıf I, p=0,024; sınıf II, p=0,032) ve PRA ≥%50 pozitif olan hastalarda Ang-2 düzeyinde istatistiksel olarak anlamlı bir artış bulundu (sınıf I, p=0,038). Bu bulgu, Ang-2’nin kronik böbrek yetmezliğinin ilerlemesinde önemli bir rolü olabileceğini ve nakil sonrası greft sağkalımını tahmin etmede etkili olabileceğini düşündürmektedir.
Sonuç: Ang-2’nin renal progresyon üzerindeki etkisini tam olarak aydınlatmak için daha ileri çalışmalara ihtiyaç duyulmaktadır.
Keywords
References
- Kim KL, Shin IS, Kim JM, Choi JH, Byun J, Jeon ES, et al. Interaction between Tie receptors modulates angiogenic activity of angiopoietin2 in endothelial progenitor cells. Cardiovasc Res 2006;72(3):394-402. google scholar
- Xu J, Lan D, Li T, Yang G, Liu L. Angiopoietins regulate vascular reactivity after haemorrhagic shock in rats through the Tie2-nitric oxide pathway. Cardiovasc Res 2012;96(2):308-19. google scholar
- Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997; 277(5322):55-60. google scholar
- Yuan HT, Khankin EV, Karumanchi SA, Parikh SM. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol 2009;29(8):2011-22. google scholar
- Korhonen EA, Lampinen, A, Giri H, Anisimov A, Kim M, Allen B, et al. Tie1 controls angiopoietin function in vascular remodeling and inflammation. J Clin Investig 2016;126(9):3495-510. google scholar
- He FF, Zhang Di, Chen Q, Zhao Y, Wu L, Li ZQ, et el. Angiopoietin- Tie signaling in kidney disease: an updated review FEBS Lett 2019;593(19):2706-15. google scholar
- Biel NM, Siemann DW. Targeting the Angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference. Cancer Lett 2016;380(2):525-33. google scholar
- Rathnakumar K, Savant S, Giri H, Ghost A, Fisslthaler B, Fleming I. et al. Angiopoietin-2 mediates thrombin-induced monocyte adhesion and endothelial permeability J Thromb Haemost 2016;14(8):1655- 67. google scholar
- Fagiani E, Christofori G. Angiopoietins in angiogenesis. Cancer Lett 2013;328(1):18-26. google scholar
- Yuan HT, Suri C, Yancopoulos GD, Woolf AS. Expression of angiopoietin-1, angiopoietin-2, and the Tie-2 receptor tyrosine kinase during mouse kidney maturation. J Am Soc Nephrol 1999;10(8):1722-36. google scholar
- Kolatsi-Joannou M, Li XZ, Suda T, Yuan HT, Woolf AS. Expression and potential role of angiopoietins and Tie-2 in early development of the mouse metanephros. Develop Dynam 2001;222(1):120-26. google scholar
- Woolf AS, Yuan HT. Angiopoietin growth factors and Tie receptor tyrosine kinases in renal vascular development. Pediat Nephrol 2001;16(2):177-84. google scholar
- Kümpers P, David S, Haubitz M, Hellpap J, Horn R, Bröcker V, et al. The Tie2 receptor antagonist angiopoietin 2 facilitates vascular inflammation in systemic lupus erythematosus. Ann Rheum Dis 2009;68(10):1638-43. google scholar
- Peters E, Antonelli M, Wittebole X, Nanchal R, François B, Sakr Y, et al. Worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from. The Intensive Care Over Nations audit. Crit Care 2018;22(1):188. google scholar
- Leligdowicz A, Richard-Greenblatt M, Wright J, Crowley VM, Kain KC. Endothelial activation: the ang/tie axis in sepsis. Front Immunol 2018;9:838. google scholar
- Yu WK, McNeil JB, Wickersham NE, Shaver CM, Bastarache JA, Ware LB. Angiopoietin-2 outperforms other endothelial biomarkers associated with severe acute kidney injury in patients with severe sepsis and respiratory failure. Crit Care 2021;25(1):48. google scholar
- Shroff RC, Price KL, Kolatsi-Joannou M, Todd AF, Wells D, Deanfield J, et al. Circulating angiopoietin-2 is a marker for early cardiovascular disease in children on chronic dialysis. PLoS ONE 2013;8(2):e56273. doi:10.1371/journal.pone.0056273. google scholar
- David S, Kumpers P, Hellpap J, Horn R, Leitolf H, Haller H, et al. Angiopoietin 2 and cardiovascular disease in dialysis and kidney transplantation. Am J Kidney Dis 2009;53(5):770-8. google scholar
- de Vries DK, Khairoun M, Lindeman JH, Bajema IM, de Heer E, Roest M, et al. Renal ischemia-reperfusion induces release of angiopoietin-2 from human grafts of living and deceased donors. Transplant 2013;96(3):282-9 google scholar
- Khairoun M, van der Pol P, de Vries DK, Lievers E, Schlagwein N, de Boer HC, et al. Renal ischemia-reperfusion induces a dysbalance of angiopoietins, accompanied by proliferation of pericytes and fibrosis. Am J Physiol Renal Physiol 2013;305(6):901-10. google scholar
- Vlahu CA, Lemkes BA, Struijk DG, Koopman MG, Krediet RT, Vink H. Damage of the endothelial glycocalyx in dialysis patients. J Am Soc Nephrol 2012;23(11):1900-8. google scholar
- Parikh SM. The angiopoietin-Tie2 signaling axis in systemic inflammation. J Am Soc Nephrol 2017;28(7):1973-82. google scholar
- He FF, Zhang D, Chen Q, Zhao Y, Wu L, Li, ZQ, et al. Angiopoietin- Tie signaling in kidney diseases: an updated review. FEBS Lett 2019;593(19):2706-15. google scholar
- Lim HS, Lip GY, Blann AD. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis 2005;180(1):113-8. google scholar
- Tsai YC, Lee CS, Chiu YW, Kuo HT, Lee SC, Hwanget SJ, et al. Angiopoietin-2, angiopoietin-1 and subclinical cardiovascular disease in chronic kidney disease. Sci Rep 2016;6:39400. google scholar
- Yuan HT, Tipping PG, Li XZ, Long DA, Woolfet AS. Angiopoietin correlates with glomerular capillary loss in anti-glomerular basement membrane glomerulonephritis. Kidney Int 2002;61(6):2078-89 google scholar
- Hillege HL, Fidler V, Diercks GF, van Gilst WK, de Zeeuw D, van Veldhuisen DJ, et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002;106(14):1777-82. google scholar
- Zhang Q, Reed QZEF. The importance of non-HLA antibodies in transplantation. Nat Rev Nephrol 2016;12(8):484-95. google scholar
- Kamburova EG, Kardol-Hoefnagel T, Wisse BW, Joosten I, Allebes WA, Van Der Meer A, et al. Development and Validation of a Multiplex Non-HLA Antibody Assay for the Screening of Kidney Transplant Recipients. Front Immunol 2018;9:3002. google scholar
- Davis B, Dei Cas A, Long DA, White KE, Hayward A, Kuet CH, et al. Podocyte-specific expression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol 2007;18(8):2320-9. google scholar
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences (Other) |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | October 24, 2023 |
| Submission Date | May 9, 2023 |
| Published in Issue | Year 2023 Volume: 6 Issue: 3 |
