Independent Association Between Paraoxonase 1 and Pulmonary Pulse Transit Time in Patients Undergoing Hemodialysis

Öz

Pulmonary hypertension (PH) and pulmonary fibrosis are significant complications of hemodialysis. Pulmonary pulse transit time (pPTT) is a valuable non-invasive marker for assessing these conditions. Paraoxonase 1 (PON1) has strong antioxidant and anti-inflammatory properties, making it effective in combatting oxidative stress and inflammation. Its effectiveness in these areas suggests that it may be associated with echocardiographic parameters in hemodialysis patients. This study examines the correlation between PON1 and echocardiographic parameters in this specific patient group. The study included a total of 36 patients receiving maintenance hemodialysis for at least three months were included in this study. Blood samples and echocardiographic assessments were obtained before and after the hemodialysis sessions. The mean age of the participants was 59.3 ± 13.27 years, with an average hemodialysis duration of 6.2 ± 5.5 years. Post-hemodialysis PON1 activity was significantly higher than pre-hemodialysis levels (r = 0.967, p < 0.0001). Negative correlations were observed between post-hemodialysis PON1 and post-hemodialysis pPTT (r = -0.410, p = 0.009), between pre-hemodialysis PON1 and pre-hemodialysis pPTT (r = -0.381, p = 0.014). Additionally, post-hemodialysis PON1 was positively correlated with post-hemodialysis early diastolic mitral annular velocity (E') (r = 0.345, p = 0.050). Multiple linear regression analysis revealed that pPTT (p < 0.05) was a statistically significant predictor of PON1 activity, while C- Reactive Protein (CRP) (p = 0.055) approached statistical significance (R = 0.527, p < 0.05). This study is the first to report an independent association between Pptt, an indicator of pulmonary hypertension (PH) and pulmonary fibrosis—and PON1 activity in hemodialysis patients. These findings suggest that PON1 may play a role in the pathophysiology of pulmonary complications in this population.

Anahtar Kelimeler

• hemodialysis
• pulmonary hypertension
• pulmonary fibrosis
• paraoxonase 1
• chronic kidney disease

Hemodiyaliz Hastalarında Paraoksonaz 1 ile Pulmoner Nabız Geçiş Süresi Arasındaki Bağımsız İlişki

Öz

Pulmoner hipertansiyon (PH) ve pulmoner fibrozis hemodiyalizde önemli komplikasyonlardır. Pulmoner nabız geçiş süresi (pPTT), bu durumları değerlendirmek için değerli bir non-invaziv belirteç görevi görür. Paraoksonaz 1 (PON1), güçlü antioksidan ve anti-inflamatuar özellikler sergiler ve bu da onu oksidatif stres ve inflamasyonla mücadelede güçlü bir ajan yapar. Bu alanlardaki etkinliği, potansiyel faydalarını vurgular ve hemodiyaliz hastalarında ekokardiyografik parametrelerle ilişkilendirilebilir. Bu çalışma, bu özel hasta grubunda PON1 ile ekokardiyografik parametreler arasındaki korelasyonu incelemeyi amaçlamaktadır. Bu çalışmaya en az üç ay boyunca rutin hemodiyaliz alan toplam 36 hasta dahil edildi. Kan örnekleri ve ekokardiyografik değerlendirmeler hemodiyaliz seanslarından önce ve sonra alındı. Katılımcıların ortalama yaşı 59,3 ± 13,27 yıldı ve ortalama hemodiyaliz süresi 6,2 ± 5,5 yıldı. Hemodiyaliz sonrası PON1 aktivitesi hemodiyaliz öncesi seviyelere kıyasla önemli ölçüde yüksekti (r = 0,967, p < 0,0001). Hemodiyaliz sonrası PON1 ile hemodiyaliz sonrası pPTT (r = -0,410, p = 0,009) ve hemodiyaliz öncesi PON1 ile hemodiyaliz öncesi pPTT (r = -0,381, p = 0,014) arasında negatif bir korelasyon gözlendi. Ek olarak, hemodiyaliz sonrası PON1, hemodiyaliz sonrası erken diyastolik mitral anüler hız (E') ile pozitif korelasyon gösterdi (r = 0,345, p = 0,050). Çoklu doğrusal regresyon analizi, pPTT'nin (p < 0,05) PON1'in istatistiksel olarak anlamlı bir öngörücüsü olduğunu, CRP'nin (p = 0,055) ise istatistiksel anlamlılığa yakın olduğunu (R = 0,527, p < 0,05) ortaya koydu. Bu çalışma, hemodiyaliz hastalarında PH ve pulmoner fibrozisin bir göstergesi olan pPTT ile PON1 aktivitesi arasında bağımsız bir ilişki olduğunu bildiren ilk çalışmadır. Bu bulgular, PON1'in bu popülasyonda pulmoner komplikasyonların patofizyolojisinde rol oynayabileceğini düşündürmektedir.

Anahtar Kelimeler

• hemodiyaliz
• pulmoner hipertansiyon
• pulmoner fibrozis
• paraoksonaz 1
• kronik böbrek hastalığı

Kaynakça

1. Ambroz, D., Jansa, P., Kuchar, J., Belohlavek, J., Aschermann, M., Dytrych, V. ... Linhart, A. (2020). Predictors of survival in patients with pulmonary hypertension and acute right heart failure. Bratislavske Lekarske Listy, 121(3), 230-235.
2. Chang, C. T., Lim, Y. P., Lee, C. W., Liao, H. Y., Chen, F. Y., Chang, C. M. ... Chen, C. J. (2019). PON-1 carbamylation is enhanced in HDL of uremia patients. Journalf Food And Drug Analysis, 27(2), 542-550.
3. Daenen, K., Andries, A., Mekahli, D., Van Schepdael, A., Jouret, F., & Bammens, B. (2019). Oxidative stress in chronic kidney disease. Pediatric Nephrology, 34, 975-991.
4. Duni, A., Liakopoulos, V., Rapsomanikis, K. P., & Dounousi, E. (2017). Chronic kidney disease and disproportionally increased cardiovascular damage: does oxidative stress explain the burden?. Oxidative Medicine and Cellular Longevity, 2017(1), 9036450.
5. Duni, A., Liakopoulos, V., Roumeliotis, S., Peschos, D., & Dounousi, E. (2019). Oxidative stress in the pathogenesis and evolution of chronic kidney disease: untangling Ariadne’s thread. International Journal of Molecular Sciences, 20(15), 3711.
6. Efe, T. H., Ertem, A. G., Altunoglu, A., Koseoglu, C., Erayman, A., Bilgin, M., ... Bilge, M. (2016). Serum paraoxonase levels are correlated with impaired aortic functions in patients with chronic kidney disease. Acta Cardiologica Sinica, 32(1), 75.
7. Furlong, C. E., Marsillach, J., Jarvik, G. P., & Costa, L. G. (2016). Paraoxonases-1,-2 and-3: What are their functions?. Chemico-biological Interactions, 259, 51-62.
8. Gugliucci, A., Kinugasa, E., Kotani, K., Caccavello, R., & Kimura, S. (2011). Serum paraoxonase 1 (PON1) lactonase activity is lower in end-stage renal disease patients than in healthy control subjects and increases after hemodialysis. Clinical Chemistry and Laboratory Medicine, 49(1), 61-67.

9. Gugliucci, A., Kotani, K., & Kimura, S. (2012). Paraoxonase 1 in chronic kidney failure. Journal of Lipids, 2012(1), 726048.
10. Gugliucci, A., Mehlhaff, K., Kinugasa, E., Ogata, H., Hermo, R., Schulze, J. … Kimura, S. (2007). Paraoxonase-1 concentrations in end-stage renal disease patients increase after hemodialysis: correlation with low molecular AGE adduct clearance. Clinica Chimica Acta, 377(1-2), 213-220.
11. Gungor, O., Kircelli, F., Demirci, M. S., Tuncel, P., Sisman, A. R., Tatar, E. ... Toz, H. (2011). Serum paraoxonase 1 activity predicts arterial stiffness in renal transplant recipients. Journal of Atherosclerosis and Thrombosis, 18(10), 901-905.
12. Kawar, B., Ellam, T., Jackson, C., & Kiely, D. G. (2013). Pulmonary hypertension in renal disease: epidemiology, potential mechanisms and implications. American Journal of Nephrology, 37(3), 281-290.
13. Kunutsor, S. K., Bakker, S. J., James, R. W., & Dullaart, R. P. (2016). Serum paraoxonase-1 activity and risk of incident cardiovascular disease: The PREVEND study and meta-analysis of prospective population studies. Atherosclerosis, 245, 143-154.
14. Liakopoulos, V., Roumeliotis, S., Gorny, X., Dounousi, E., & Mertens, P. R. (2017). Oxidative stress in hemodialysis patients: a review of the literature. Oxidative Medicine and Cellular Longevity, 2017(1), 3081856.
15. Liakopoulos, V., Roumeliotis, S., Zarogiannis, S., Eleftheriadis, T., & Mertens, P. R. (2019, January). Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions. In Seminars in Dialysis (Vol. 32, No. 1, pp. 58-71).
16. Marques, F. S., Da Silva, A. L. M., Mattoso, R. J., Aras, R., De Oliveira, R. J. B., Santos, J. C. D. A. ... Couto, R. D. (2017). Low-Flow Polysulfone Hemodialysis Alters Lipoprotein Parameters, Paraoxonase Activity and in Vitro Incorporation of Phospholipids. Journal of Biophysical Chemistry, 8(03), 23.
17. Mohammed, C. J., Xie, Y., Brewster, P. S., Ghosh, S., Dube, P., Sarsour, T. ... Kennedy, D. J. (2019). Circulating lactonase activity but not protein level of PON-1 predicts adverse outcomes in subjects with chronic kidney disease. Journal of Clinical Medicine, 8(7), 1034.
18. Pabst, S., Hammerstingl, C., Hundt, F., Gerhardt, T., Grohe, C., Nickenig, G. ... Skowasch, D. (2012). Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study. PloS One, 7(4), e35310.
19. Reque, J., Garcia-Prieto, A., Linares, T., Vega, A., Abad, S., Panizo, N. ... López-Gómez, J. M. (2017). Pulmonary hypertension is associated with mortality and cardiovascular events in chronic kidney disease patients. American Journal of Nephrology, 45(2), 107-114.
20. Shih, D. M., Xia, Y. R., Wang, X. P., Miller, E., Castellani, L. W., Subbanagounder, G. ... Lusis, A. J. (2000). Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. Journal of Biological Chemistry, 275(23), 17527-17535.
21. Suematsu, Y., Goto, M., Park, C., Nunes, A. C., Jing, W., Streja, E., ... Moradi, H. (2019). Association of serum paraoxonase/arylesterase activity with all-cause mortality in maintenance hemodialysis patients. The Journal of Clinical Endocrinology & Metabolism, 104(10), 4848-4856.
22. Sztanek, F., Seres, I., Harangi, M., Lőcsey, L., Padra, J., Paragh, G. J. ... Paragh, G. (2012). Decreased paraoxonase 1 (PON1) lactonase activity in hemodialyzed and renal transplanted patients. A novel cardiovascular biomarker in end-stage renal disease. Nephrology Dialysis Transplantation, 27(7), 2866-2872.
23. Tang, M., Batty, J. A., Lin, C., Fan, X., Chan, K. E., & Kalim, S. (2018). Pulmonary hypertension, mortality, and cardiovascular disease in CKD and ESRD patients: a systematic review and meta-analysis. American Journal of Kidney Diseases, 72(1), 75-83.
24. Walther, C. P., Nambi, V., Hanania, N. A., & Navaneethan, S. D. (2020). Diagnosis and management of pulmonary hypertension in patients with CKD. American Journal of Kidney Diseases, 75(6), 935-945.
25. Wang, X., Hong, J., Zhang, T., & Xu, D. (2021). Changes in left ventricular and atrial mechanics and function after dialysis in patients with end-stage renal disease. Quantitative Imaging in Medicine and Surgery, 11(5), 1899.
26. Wibmer, T., Rüdiger, S., Scharnbeck, D., Radermacher, M., Markovic, S., Stoiber, K. M. ... Schumann, C. (2015). Pulmonary pulse transit time: a novel echocardiographic indicator of hemodynamic and vascular alterations in pulmonary hypertension and pulmonary fibrosis. Echocardiography, 32(6), 904-911.