Pulmonary hypertension in patients with chronic kidney disease: the multifaceted pathogenesis
- Authors: Andriyashkina D.Y.1, Podoprigora V.V.1, Kamyshev S.S.1, Klimenko A.A.1
-
Affiliations:
- N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
- Issue: Vol 19, No 4 (2025)
- Pages: 43-52
- Section: REVIEW
- Published: 17.03.2026
- URL: https://klinitsist.abvpress.ru/Klin/article/view/690
- DOI: https://doi.org/10.17650/1818-8338-2025-19-4-K760
- ID: 690
Cite item
Abstract
Pulmonary hypertension (PH) is a group of diseases characterized by progressive increase in pulmonary vascular resistance, which leads to development of right ventricular failure and an unfavorable prognosis of life. There are 5 groups in the clinical classification, mainly based on the cause and pathophysiological changes in the pulmonary vessels. PH in patients with chronic kidney disease (CKD) is a common and severe complication and belongs to group 5 in the classification. PH is diagnosed in 21 % of patients with CKD who are not on dialysis and in 50–60 % of patients with end-stage kidney disease. On the other hand, development of CKD in patients with pulmonary hypertension doubles the risk of mortality, and with end-stage CKD it triples. In most patients in this group, the main causes of PH are volume overload and left ventricular dysfunction. However, many other factors both enhance and offset the effect of volume overload on PH. These factors include the effects of vascular access for dialysis, anemia, respiratory disorders and hypoxemia, inflammation, and changes in mineral metabolism. In addition, CKD can directly affect the blood vessels of the lungs through the action of nitric oxide, endothelin-1, prostacyclin. Catheterization of the right heart, as the basis for the diagnosis of PH, provides insight into the potential hemodynamic profile of pulmonary hypertension associated with CKD. The article summarizes current data undelying new theoretical mechanisms of pathogenesis of PH associated with CKD.
About the authors
Darya Yu. Andriyashkina
N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Author for correspondence.
Email: andryashkina.darya@yandex.ru
ORCID iD: 0000-0001-8266-6022
Russian Federation, 1 Ostrovityanova St., Moscow 117513
V. V. Podoprigora
N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Email: andryashkina.darya@yandex.ru
ORCID iD: 0009-0005-6472-300X
Russian Federation, 1 Ostrovityanova St., Moscow 117513
S. S. Kamyshev
N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Email: andryashkina.darya@yandex.ru
ORCID iD: 0009-0001-4162-6013
Russian Federation, 1 Ostrovityanova St., Moscow 117513
Alesya A. Klimenko
N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Email: andryashkina.darya@yandex.ru
ORCID iD: 0000-0002-7410-9784
MD, PhD, Associate Professor, Head of the Department of Acad. A.I. Nesterov of Faculty Therapy
Russian Federation, 1 Ostrovityanova St., Moscow 117513References
- Simonneau G., Montani D., Celermajer D.S. et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019;53(1):1801913. doi: 10.1183/13993003.01913-2018
- Moreira E.M., Gall H., Leening M.J. et al. Prevalence of pulmonary hypertension in the general population: the Rotterdam Study. PLoS One 2015;10(6):e0130072. doi: 10.1371/journal.pone.0130072
- Miller W.L., Grill D.E., Borlaug B.A. Clinical features, hemodynamics, and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction: pulmonary hypertension and heart failure. JACC Heart Fail 2013;1(4):290–9. doi: 10.1016/j.jchf.2013.05.001
- Yigla M., Fruchter O., Aharonson D. et al. Pulmonary hypertension is an independent predictor of mortality in hemodialysis patients. Kidney Int 2009;75(9):969–75. doi: 10.1038/ki.2009.10
- Rudenko T.E., Vasil’eva M.P., Bobkova I.N. Pulmonary hypertension in patients with chronic kidney disease: prevalence, mechanisms of development, treatment prospects. Consilium Med 2018;20(12):55–60. (In Russ.). doi: 10.26442/20751753.2018.12.000034
- Havluku Y., Kursat S., Ekmekci C. et al. Pulmonary hypertension in patients with chronic renal failure. Respiration 2007;74(5): 503–10. doi: 10.1159/000102953
- Admonston D.L., Sparks M.A. Therapeutic options for chronic kidney disease-associated pulmonary hypertension. Curr Opin Nephrol Hypertens 2020;29(5):497–507. doi: 10.1097/MNH.0000000000000624
- O’Leary J.M., Assad T.R., Xu M. et al. Pulmonary hypertension in patients with chronic kidney disease: invasive hemodynamic etiology and outcomes. Pulm Circ 2017;7(3):674–83. doi: 10.1177/2045893217716108
- Ghio S., Gavazzi A., Campana C. et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001;37(1):183–8. doi: 10.1016/s0735-1097(00)01102-5
- Shang W., Li Y., Ren Y. et al. Prevalence of pulmonary hypertension in patients with chronic kidney disease without dialysis: a meta-analysis. Int Urol Nephrol 2018;50(8):1497–504. doi: 10.1007/s11255-018-1853-6
- Ben Driss A., Devaux C., Henrion D. et al. Hemodynamic stresses induce endothelial dysfunction and remodeling of pulmonary artery in experimental compensated heart failure. Circulation 2000;101(23):2764–70. doi: 10.1161/01.cir.101.23.2764
- Kapustin A.N., Davies J.D., Reynolds J.L. et al. Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization. Circ Res 2011;109(1):e1–12. doi: 10.1161/CIRCRESAHA.110.238808
- Gumus F., Saricaoglu M.C. Assessment of right heart functions in the patients with arteriovenous fistula for hemodialysis access: right ventricular free wall strain and tricuspid regurgitation jet velocity as the predictors of right heart failure. Vascular 2020;28(1):96–103. doi: 10.1177/1708538119866616
- Andrukhova O., Slavic S., Smorodchenko A. et al. FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med 2014;6(6):744–59. doi: 10.1002/emmm.201303716
- Hu M.C., Shi M., Cho H.J. et al. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol 2015;26(6):1290–302. doi: 10.1681/ASN.2014050465
- Sakaguchi Y., Shoji T., Kawabata H. et al. High prevalence of obstructive sleep apnea and its association with renal function among nondialysis chronic kidney disease patients in Japan: a cross-sectional study. Clin J Am Soc Nephrol 2011;6(5):995–1000. doi: 10.2215/CJN.08670910
- Podszus T., Mayer J., Penzel T. et al. Nocturnal hemodynamics in patients with sleep apnea. Eur J Respir Dis Suppl 1986;146: 435–42. doi: 10.1007/978-3-642-72560-9_33
- Wu W., Platoshyn O., Firth A.L. et al. Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2007;293(4):L952–9. doi: 10.1152/ajplung.00203.2007
- Mukai H., Ming P., Lindholm B. et al. Lung dysfunction and mortality in patients with chronic kidney disease. Kidney Blood Press Res 2018;43(2):522–35. doi: 10.1159/000488699
- Portillo K., Torralba Y., Blanco I. et al. Pulmonary hemodynamic profile in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2015;10:1313–20. Erratum in: Int J Chron Obstruct Pulmon Dis 2015;10:2377. doi: 10.2147/COPD.S78180
- Fabbian F., Cantelli S., Molino C. et al. Pulmonary hypertension in dialysis patients: a cross-sectional italian study. Int J Nephrol 2010;2011:283475. doi: 10.4061/2011/283475
- Harp R.J., Stavropoulos S.W., Wasserstein A.G. et al. Pulmonary hypertension among end-stage renal failure patients following hemodialysis access thrombectomy. Cardiovasc Intervent Radiol 2005;28(1):17–22. doi: 10.1007/s00270-004-0223-1
- Droste D.W., Kühne K., Schaefer R.M. et al. Detection of microemboli in the subclavian vein of patients undergoing haemodialysis and haemodiafiltration using pulsed Doppler ultrasound. Nephrol Dial Transplant 2002;17(3):462–6. doi: 10.1093/ndt/17.3.462
- Weber T.J., Liu S., Indridason O.S. et al. Serum FGF23 levels in normal and disordered phosphorus homeostasis. J Bone Miner Res 2003;18(7):1227–34. doi: 10.1359/jbmr.2003.18.7.1227
- Drew D.A., Katz R., Kritchevsky S. et al. Association between soluble klotho and change in kidney function: the health aging and body composition study. J Am Soc Nephrol 2017;28(6): 1859–66. doi: 10.1681/ASN.2016080828
- Gutierrez O., Isakova T., Rhee E. et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005;16(7):2205–15. doi: 10.1681/ASN.2005010052
- Oliveira R.B., Cancela A.L., Graciolli F.G. et al. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol 2010;5(2):286–91. doi: 10.2215/CJN.05420709
- Akmal M., Barndt R.R., Ansari A.N. et al. Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and right ventricular hypertrophy. Kidney Int 1995;47(1):158–63. doi: 10.1038/ki.1995.18
- Pasch A., Farese S., Gräber S. et al. Nanoparticle-based test measures overall propensity for calcification in serum. J Am Soc Nephrol 2012;23(10):1744–52. doi: 10.1681/ASN.2012030240
- Dharmarajan S., Speer M.Y., Pierce K. et al. Role of Runx2 in calcific aortic valve disease in mouse models. Front Cardiovasc Med 2021;8:687210. doi: 10.3389/fcvm.2021.687210
- Jäger E., Murthy S., Schmidt C. et al. Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis. Nat Commun 2020;11(1):4243. doi: 10.1038/s41467-020-17749-6
- Aghagolzadeh P., Bachtler M., Bijarnia R. et al. Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-α. Atherosclerosis 2016;251:404–14. doi: 10.1016/j.atherosclerosis.2016.05.044
- Ito S., Osaka M., Edamatsu T. et al. Crucial role of the aryl hydrocarbon receptor (AhR) in indoxyl sulfate-induced vascular inflammation. J Atheroscler Thromb 2016;23(8):960–75. doi: 10.5551/jat.34462
- Nguyen C., Edgley A.J., Kelly D.J. et al. Aryl hydrocarbon receptor inhibition restores indoxyl sulfate-mediated endothelial dysfunction in rat aortic rings. Toxins 2022;14(2):100. doi: 10.3390/toxins14020100
- Dou L., Sallée M., Cerini C. et al. The cardiovascular effect of the uremic solute indole-3 acetic acid. J Am Soc Nephrol 2015;26(4):876–87. doi: 10.1681/ASN.2013121283
- Yu T.M., Chen Y.H., Hsu J.Y. et al. Systemic inflammation is associated with pulmonary hypertension in patients undergoing haemodialysis. Nephrol Dial Transplant 2009;24(6):1946–51. doi: 10.1093/ndt/gfn751
- Kim H.Y., Yoo T.H., Hwang Y. et al. Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD). Sci Rep 2017;7(1):3057. doi: 10.1038/s41598-017-03130-z
- Gorman S., Buckley A.G., Ling K.M. et al. Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity. Physiol Rep 2017;5(15):e13371. doi: 10.14814/phy2.13371
- Covic A., Goldsmith D.J., Gusbeth-Tatomir P. et al. Successful renal transplantation decreases aortic stiffness and increases vascular reactivity in dialysis patients. Transplantation 2003;76(11):1573–7. doi: 10.1097/01.TP.0000086343.32903.A8
- Reiter C.D., Wang X., Tanus-Santos J.E. et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 2002;8(12):1383–9. doi: 10.1038/nm1202-799
- Yigla M., Banderski R., Azzam Z.S. et al. Arterio-venous access in end-stage renal disease patients and pulmonary hypertension. Ther Adv Respir Dis 2008;2(2):49–53. doi: 10.1177/1753465808089456
- Beigi A.A., Sadeghi A.M., Khosravi A.R. et al. Effects of the arteriovenous fistula on pulmonary artery pressure and cardiac output in patients with chronic renal failure. J Vasc Access 2009;10(3):160–6. doi: 10.1177/112972980901000305
- Dschietzig T., Richter C., Bartsch C. et al. Flow-induced pressure differentially regulates endothelin-1, urotensin II, adrenomedullin, and relaxin in pulmonary vascular endothelium. Biochem Biophys Res Commun 2001;289(1):245–51. doi: 10.1006/bbrc.2001.5946
- Campia U., Cardillo C., Panza J.A. Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in hypertensive patients. Circulation 2004;109(25):3191–5. doi: 10.1161/01.CIR.0000130590.24107.D3
- Paneni F., Gregori M., Ciavarella G.M. et al. Right ventricular dysfunction in patients with end-stage renal disease. Am J Nephrol 2010;32(5):432–8. doi: 10.1159/000320755
- Mousavi S.A., Mahdavi-Mazdeh M., Yahyazadeh H. et al. Pulmonary hypertension and predisposing factors in patients receiving hemodialysis. Iran J Kidney Dis 2008;2(1):29–33. PMID: 19367006.
- Abdeen A.M.Z., Alagha Z., Clark C. et al. Paradoxical worsening of pulmonary hypertension following closure of arteriovenous fistula: a case report and literature review. Cureus 2023;15(12):e50064. doi: 10.7759/cureus.50064
- Jaar B.G., Coresh J., Plantinga L.C. et al. Comparing the risk for death with peritoneal dialysis and hemodialysis in a national cohort of patients with chronic kidney disease. Ann Intern Med 2005;143(3):174–83. doi: 10.7326/0003-4819-143-3-200508020-00003
- Mahiout A., Jörres A., Hiss R. et al. Effects of blood-dialyser interaction on prostaglandins in uremic patients and in healthy man. Nephrol Dial Transplant 1987;2(6):546–50. doi: 10.1093/oxfordjournals.ndt.a091597
- Parent F., Bachir D., Inamo J. et al. a hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med 2011;365(1):44–53. doi: 10.1056/NEJMoa1005565
- Lin C., Ge Q., Wang L. et al. Predictors, prevalence and prognostic role of pulmonary hypertension in patients with chronic kidney disease: a systematic review and meta-analysis. Ren Fail 2024;46(2):2368082. doi: 10.1080/0886022X.2024.2368082
- Seo B., Oemar B.S., Siebenmann R. et al. Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation 1994;89(3):1203–8. doi: 10.1161/01.cir.89.3.1203
- Rybalkin S.D., Rybalkina I.G., Feil R. et al. Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem 2002;277(5):3310–7. doi: 10.1074/jbc.M106562200
- Antoniades C., Shirodaria C., Leeson P. et al. Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis. Eur Heart J 2009;30(9):1142–50. doi: 10.1093/eurheartj/ehp061
- Zhou L., Chen Z., Vanderslice P. et al. Endothelial-like progenitor cells engineered to produce prostacyclin rescue monocrotaline-induced pulmonary arterial hypertension and provide right ventricle benefits. Circulation 2013;128(9):982–94. doi: 10.1161/CIRCULATIONAHA.113.003139
- Németh Á., Mózes M.M., Calvier L. et al. The PPARγ agonist pioglitazone prevents TGF-β induced renal fibrosis by repressing EGR-1 and STAT3. BMC Nephrol 2019;20(1):245. doi: 10.1186/s12882-019-1431-x
- Kawai T., Masaki T., Doi S. et al. PPAR-gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-beta. Lab Invest 2009;89(1):47–58. doi: 10.1038/labinvest.2008.104
- Pistrosch F., Passauer J., Herbrig K. et al. Effect of thiazolidinedione treatment on proteinuria and renal hemodynamic in type 2 diabetic patients with overt nephropathy. Horm Metab Res 2012;44(12):914–8. doi: 10.1055/s-0032-1314836
- Miller J.A., Anacta L.A., Cattran D.C. Impact of gender on the renal response to angiotensin II. Kidney Int 1999;55(1): 278–85. doi: 10.1046/j.1523-1755.1999.00260.x
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