Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes.


Journal

Nature reviews. Nephrology
ISSN: 1759-507X
Titre abrégé: Nat Rev Nephrol
Pays: England
ID NLM: 101500081

Informations de publication

Date de publication:
18 Jun 2024
Historique:
accepted: 30 05 2024
medline: 19 6 2024
pubmed: 19 6 2024
entrez: 18 6 2024
Statut: aheadofprint

Résumé

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes. However, the complex, heterogenous pathophysiology and clinical profile of CKD-PH requires further characterization. CKD is often associated with elevated left ventricular filling pressure and volume overload, which presumably leads to pulmonary vascular stiffening and post-capillary PH. By contrast, a distinct subgroup of patients at high risk is characterized by elevated pulmonary vascular resistance and right ventricular dysfunction in the absence of pulmonary venous hypertension, which may represent a right-sided cardiorenal syndrome defined in principle by hypervolaemia, salt avidity, low cardiac output and normal left ventricular function. Current understanding of CKD-PH is limited, despite its potentially important ramifications for clinical decision making. In particular, whether PH should be considered when determining the suitability and timing of kidney replacement therapy or kidney transplantation is unclear. More research is urgently needed to address these knowledge gaps and improve the outcomes of patients with or at risk of CKD-PH.

Identifiants

pubmed: 38890546
doi: 10.1038/s41581-024-00857-7
pii: 10.1038/s41581-024-00857-7
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. Springer Nature Limited.

Références

Tang, M. et al. Pulmonary hypertension, mortality, and cardiovascular disease in CKD and ESRD patients: a systematic review and meta-analysis. Am. J. Kidney Dis. 72, 75–83 (2018).
pubmed: 29429751 doi: 10.1053/j.ajkd.2017.11.018
Bolignano, D., Pisano, A., Coppolino, G., Tripepi, G. L. & D’Arrigo, G. Pulmonary hypertension predicts adverse outcomes in renal patients: a systematic review and meta-analysis. Ther. Apher. Dial. 23, 369–384 (2019).
pubmed: 30565874 doi: 10.1111/1744-9987.12777
Edmonston, D. L. et al. Pulmonary hypertension subtypes and mortality in CKD. Am. J. Kidney Dis. 75, 713–724 (2020).
pubmed: 31732231 doi: 10.1053/j.ajkd.2019.08.027
Pabst, S. et al. Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study. PLoS One 7, e35310 (2012).
pubmed: 22530005 pmcid: 3329424 doi: 10.1371/journal.pone.0035310
Navaneethan, S. D. et al. Presence and outcomes of kidney disease in patients with pulmonary hypertension. Clin. J. Am. Soc. Nephrol. 9, 855–863 (2014).
pubmed: 24578332 pmcid: 4011456 doi: 10.2215/CJN.10191013
O’Leary, J. M. et al. Pulmonary hypertension in patients with chronic kidney disease: invasive hemodynamic etiology and outcomes. Pulm. Circ. 7, 674–683 (2017).
pubmed: 28660793 pmcid: 5841902 doi: 10.1177/2045893217716108
Wolfe, J. D. et al. Pulmonary vascular resistance determines mortality in end-stage renal disease patients with pulmonary hypertension. Clin. Transplant. 32, e13270 (2018).
pubmed: 29697854 doi: 10.1111/ctr.13270
Brinza, C. et al. Pulmonary arterial hypertension and adverse outcomes after kidney transplantation: a systematic review and meta-analysis. J. Clin. Med. 11, 1944 (2022).
pubmed: 35407552 pmcid: 8999673 doi: 10.3390/jcm11071944
Chakinala, M. M. et al. Impact of declining renal function on outcomes in pulmonary arterial hypertension: a REVEAL registry analysis. J. Heart Lung Transplant. 37, 696–705 (2018).
pubmed: 29174533 doi: 10.1016/j.healun.2017.10.028
Shah, S. J. et al. Association of serum creatinine with abnormal hemodynamics and mortality in pulmonary arterial hypertension. Circulation 117, 2475–2483 (2008).
pubmed: 18458173 doi: 10.1161/CIRCULATIONAHA.107.719500
Nickel, N. P. et al. Low-grade albuminuria in pulmonary arterial hypertension. Pulm. Circ. 9, 2045894018824564 (2019).
pubmed: 30632900 pmcid: 6557031 doi: 10.1177/2045894018824564
Benza, R. L. et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 122, 164–172 (2010).
pubmed: 20585012 doi: 10.1161/CIRCULATIONAHA.109.898122
Leopold, J. A. et al. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat. Med. 13, 189–197 (2007).
pubmed: 17273168 pmcid: 3648863 doi: 10.1038/nm1545
Cohn, J. N. & Tognoni, G. Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N. Engl. J. Med. 345, 1667–1675 (2001).
pubmed: 11759645 doi: 10.1056/NEJMoa010713
Velazquez, E. J. et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N. Engl. J. Med. 380, 539–548 (2019).
pubmed: 30415601 doi: 10.1056/NEJMoa1812851
Maron, B. A. et al. Aldosterone inactivates the endothelin-B receptor via a cysteinyl thiol redox switch to decrease pulmonary endothelial nitric oxide levels and modulate pulmonary arterial hypertension. Circulation 126, 963–974 (2012).
pubmed: 22787113 pmcid: 3534848 doi: 10.1161/CIRCULATIONAHA.112.094722
Maron, B. A. & Leopold, J. A. The role of the renin-angiotensin-aldosterone system in the pathobiology of pulmonary arterial hypertension (2013 Grover Conference series). Pulm. Circ. 4, 200–210 (2014).
pubmed: 25006439 pmcid: 4070776 doi: 10.1086/675984
Maron, B. A. et al. Plasma aldosterone levels are elevated in patients with pulmonary arterial hypertension in the absence of left ventricular heart failure: a pilot study. Eur. J. Heart Fail. 15, 277–283 (2013).
pubmed: 23111998 doi: 10.1093/eurjhf/hfs173
Zhang, J. et al. Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: results from PADN-CFDA trial. J. Heart Lung Transplant. 42, 1140-1151 (2023).
pubmed: 36990173 doi: 10.1016/j.healun.2023.03.015
Calvier, L. et al. Galectin-3 and aldosterone as potential tandem biomarkers in pulmonary arterial hypertension. Heart 102, 390–396 (2016).
pubmed: 26869635 doi: 10.1136/heartjnl-2015-308365
Humbert, M. et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Respir. J. 61, 2200879 (2023).
pubmed: 36028254 doi: 10.1183/13993003.00879-2022
Leber, L., Beaudet, A. & Muller, A. Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: identification of the most accurate estimates from a systematic literature review. Pulm. Circ. 11, 2045894020977300 (2021).
pubmed: 33456755 pmcid: 7797595 doi: 10.1177/2045894020977300
Maron, B. A. & Galie, N. Diagnosis, treatment, and clinical management of pulmonary arterial hypertension in the contemporary era: a review. JAMA Cardiol. 1, 1056–1065 (2016).
pubmed: 27851839 pmcid: 5177491 doi: 10.1001/jamacardio.2016.4471
Stevens, P. E., Levin, A. & Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann. Intern. Med. 158, 825–830 (2013).
pubmed: 23732715 doi: 10.7326/0003-4819-158-11-201306040-00007
Ronco, C., Bellasi, A. & Di Lullo, L. Cardiorenal syndrome: an overview. Adv. Chronic Kidney Dis. 25, 382–390 (2018).
pubmed: 30309455 doi: 10.1053/j.ackd.2018.08.004
Ronco, C., Haapio, M., House, A. A., Anavekar, N. & Bellomo, R. Cardiorenal syndrome. J. Am. Coll. Cardiol. 52, 1527–1539 (2008).
pubmed: 19007588 doi: 10.1016/j.jacc.2008.07.051
Hoeper, M. M. et al. A global view of pulmonary hypertension. Lancet Respir. Med. 4, 306–322 (2016).
pubmed: 26975810 doi: 10.1016/S2213-2600(15)00543-3
GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 395, 709–733 (2020).
doi: 10.1016/S0140-6736(20)30045-3
Wang, L. et al. Prognostic effect of pulmonary hypertension in patients with chronic kidney disease: univariate and multivariate analyses of factors associated with survival. Front. Med. 9, 972937 (2022).
doi: 10.3389/fmed.2022.972937
Yang, Q. M. & Bao, X. R. Pulmonary hypertension in patients with stage 1–3 chronic kidney disease. Genet. Mol. Res. 13, 5695–5703 (2014).
pubmed: 25117327 doi: 10.4238/2014.July.25.25
Verbrugge, F. H., Guazzi, M., Testani, J. M. & Borlaug, B. A. Altered hemodynamics and end-organ damage in heart failure: impact on the lung and kidney. Circulation 142, 998–1012 (2020).
pubmed: 32897746 pmcid: 7482031 doi: 10.1161/CIRCULATIONAHA.119.045409
Bitker, L. et al. Presence of kidney disease as an outcome predictor in patients with pulmonary arterial hypertension. Am. J. Nephrol. 47, 134–143 (2018).
pubmed: 29471290 doi: 10.1159/000487198
Nickel, N. P. et al. Kidney dysfunction in patients with pulmonary arterial hypertension. Pulm. Circ. 7, 38–54 (2017).
pubmed: 28680564 pmcid: 5448543 doi: 10.1086/690018
Rossi, G. P., Cavallin, M., Nussdorfer, G. G. & Pessina, A. C. The endothelin-aldosterone axis and cardiovascular diseases. J. Cardiovasc. Pharmacol. 38, 49 (2001).
doi: 10.1097/00005344-200111002-00013
Kopitko, C., Gondos, T., Fulop, T. & Medve, L. Reinterpreting renal hemodynamics: the importance of venous congestion and effective organ perfusion in acute kidney injury. Am. J. Med. Sci. 359, 193–205 (2020).
pubmed: 32089228 doi: 10.1016/j.amjms.2020.01.012
Mullens, W., Verbrugge, F. H., Nijst, P. & Tang, W. H. W. Renal sodium avidity in heart failure: from pathophysiology to treatment strategies. Eur. Heart J. 38, 1872–1882 (2017).
pubmed: 28329085 doi: 10.1093/eurheartj/ehx035
Selektor, Y. & Weber, K. T. The salt-avid state of congestive heart failure revisited. Am. J. Med. Sci. 335, 209–218 (2008).
pubmed: 18344695 doi: 10.1097/MAJ.0b013e3181591da0
Testani, J. M. & Damman, K. Venous congestion and renal function in heart failure … it’s complicated. Eur. J. Heart Fail. 15, 599–601 (2013).
pubmed: 23603089 doi: 10.1093/eurjhf/hft060
Dilley, J. R., Corradi, A. & Arendshorst, W. J. Glomerular ultrafiltration dynamics during increased renal venous pressure. Am. J. Physiol. 244, 650 (1983).
Braam, B., Cupples, W. A., Joles, J. A. & Gaillard, C. Systemic arterial and venous determinants of renal hemodynamics in congestive heart failure. Heart Fail. Rev. 17, 161–175 (2012).
pubmed: 21553212 doi: 10.1007/s10741-011-9246-2
Mullens, W. et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J. Am. Coll. Cardiol. 53, 589–596 (2009).
pubmed: 19215833 pmcid: 2856960 doi: 10.1016/j.jacc.2008.05.068
Uthoff, H. et al. Central venous pressure and impaired renal function in patients with acute heart failure. Eur. J. Heart Fail. 13, 432–439 (2011).
pubmed: 21097472 doi: 10.1093/eurjhf/hfq195
Gambardella, I. et al. Congestive kidney failure in cardiac surgery: the relationship between central venous pressure and acute kidney injury. Interact. Cardiovasc. Thorac. Surg. 23, 800–805 (2016).
pubmed: 27422971 doi: 10.1093/icvts/ivw229
Damman, K. et al. Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease. J. Am. Coll. Cardiol. 53, 582–588 (2009).
pubmed: 19215832 doi: 10.1016/j.jacc.2008.08.080
Marik, P. E., Baram, M. & Vahid, B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 134, 172–178 (2008).
pubmed: 18628220 doi: 10.1378/chest.07-2331
Castrop, H. Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine. Acta Physiol. 189, 3–14 (2007).
doi: 10.1111/j.1748-1716.2006.01610.x
Bell, T. D. & Welch, W. J. Regulation of renal arteriolar tone by adenosine: novel role for type 2 receptors. Kidney Int. 75, 769–771 (2009).
pubmed: 19337216 pmcid: 5858198 doi: 10.1038/ki.2009.18
Agarwal, R. Prevalence, determinants and prognosis of pulmonary hypertension among hemodialysis patients. Nephrol. Dial. Transplant. 27, 3908–3914 (2012).
pubmed: 22290987 pmcid: 3484729 doi: 10.1093/ndt/gfr661
Abedini, M., Sadeghi, M., Naini, A. E., Atapour, A. & Golshahi, J. Pulmonary hypertension among patients on dialysis and kidney transplant recipients. Ren. Fail. 35, 560–565 (2013).
pubmed: 23438072 doi: 10.3109/0886022X.2013.766567
Ramasubbu, K., Deswal, A., Herdejurgen, C., Aguilar, D. & Frost, A. E. A prospective echocardiographic evaluation of pulmonary hypertension in chronic hemodialysis patients in the United States: prevalence and clinical significance. Int. J. Gen. Med. 3, 279–286 (2010).
pubmed: 21042428 pmcid: 2962323
Issa, N. et al. Pulmonary hypertension is associated with reduced patient survival after kidney transplantation. Transplantation 86, 1384–1388 (2008).
pubmed: 19034007 doi: 10.1097/TP.0b013e318188d640
de Albuquerque Suassuna, P. G., Sanders-Pinheiro, H. & de Paula, R. B. Uremic cardiomyopathy: a new piece in the chronic kidney disease-mineral and bone disorder puzzle. Front. Med. 5, 206 (2018).
doi: 10.3389/fmed.2018.00206
Ma, Z. et al. β-Arrestin-mediated angiotensin II type 1 receptor activation promotes pulmonary vascular remodeling in pulmonary hypertension. JACC Basic. Transl. Sci. 6, 854–869 (2021).
pubmed: 34869949 pmcid: 8617598 doi: 10.1016/j.jacbts.2021.09.006
de Man, F. S. et al. Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 186, 780–789 (2012).
pubmed: 22859525 doi: 10.1164/rccm.201203-0411OC
Houston, B. A., Brittain, E. L. & Tedford, R. J. Right ventricular failure. N. Engl. J. Med. 388, 1111–1125 (2023).
pubmed: 36947468 doi: 10.1056/NEJMra2207410
Wu, D. & Birukov, K. Endothelial cell mechano-metabolomic coupling to disease states in the lung microvasculature. Front. Bioeng. Biotechnol. 7, 172 (2019).
pubmed: 31380363 pmcid: 6658821 doi: 10.3389/fbioe.2019.00172
Silva, P. L. et al. Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury. Crit. Care 14, R114 (2010).
pubmed: 20546573 pmcid: 2911760 doi: 10.1186/cc9063
Tonelli, A. R., Plana, J. C., Heresi, G. A. & Dweik, R. A. Prevalence and prognostic value of left ventricular diastolic dysfunction in idiopathic and heritable pulmonary arterial hypertension. Chest 141, 1457–1465 (2012).
pubmed: 22207680 doi: 10.1378/chest.11-1903
Stern, A. B. & Klemmer, P. J. High-output heart failure secondary to arteriovenous fistula. Hemodial. Int. 15, 104–107 (2011).
pubmed: 21223485 doi: 10.1111/j.1542-4758.2010.00518.x
Reddy, Y. N. V., Melenovsky, V., Redfield, M. M., Nishimura, R. A. & Borlaug, B. A. High-output heart failure: a 15-year experience. J. Am. Coll. Cardiol. 68, 473–482 (2016).
pubmed: 27470455 doi: 10.1016/j.jacc.2016.05.043
Holman, E. Abnormal arteriovenous communications. Great variability of effects with particular reference to delayed development of cardiac failure. Circulation 32, 1001–1009 (1965).
pubmed: 5846098 doi: 10.1161/01.CIR.32.6.1001
Warren, J. V., Elkin, D. C. & Nickerson, J. L. The blood volume in patients with arteriovenous fistulas. J. Clin. Invest. 30, 220–226 (1951).
pubmed: 14814216 pmcid: 436249 doi: 10.1172/JCI102436
Rao, N. N., Dundon, B. K., Worthley, M. I. & Faull, R. J. The impact of arteriovenous fistulae for hemodialysis on the cardiovascular system. Semin. Dial. 29, 214–221 (2016).
pubmed: 26756565 doi: 10.1111/sdi.12459
MacRae, J. M., Pandeya, S., Humen, D. P., Krivitski, N. & Lindsay, R. M. Arteriovenous fistula-associated high-output cardiac failure: a review of mechanisms. Am. J. Kidney Dis. 43, 17 (2004).
doi: 10.1053/j.ajkd.2004.01.016
Ori, Y. et al. The contribution of an arteriovenous access for hemodialysis to left ventricular hypertrophy. Am. J. Kidney Dis. 40, 745–752 (2002).
pubmed: 12324909 doi: 10.1053/ajkd.2002.35685
Malik, J. et al. Hemodialysis vascular access affects heart function and outcomes: tips for choosing the right access for the individual patient. J. Vasc. Access. 22, 32–41 (2021).
pubmed: 33143540 doi: 10.1177/1129729820969314
Iwashima, Y. et al. Effects of the creation of arteriovenous fistula for hemodialysis on cardiac function and natriuretic peptide levels in CRF. Am. J. Kidney Dis. 40, 974–982 (2002).
pubmed: 12407642 doi: 10.1053/ajkd.2002.36329
Reddy, Y. N. V. et al. Long-term cardiovascular changes following creation of arteriovenous fistula in patients with end stage renal disease. Eur. Heart J. 38, 1913–1923 (2017).
pubmed: 28329100 doi: 10.1093/eurheartj/ehx045
Unger, P., Wissing, K. M., de Pauw, L., Neubauer, J. & van de Borne, P. Reduction of left ventricular diameter and mass after surgical arteriovenous fistula closure in renal transplant recipients. Transplantation 74, 73–79 (2002).
pubmed: 12134102 doi: 10.1097/00007890-200207150-00013
van Duijnhoven, E. C., Cheriex, E. C., Tordoir, J. H., Kooman, J. P. & van Hooff, J. P. Effect of closure of the arteriovenous fistula on left ventricular dimensions in renal transplant patients. Nephrol. Dial. Transplant. 16, 368–372 (2001).
pubmed: 11158414 doi: 10.1093/ndt/16.2.368
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 28, 96–103 (2020).
pubmed: 31362595 doi: 10.1177/1708538119866616
Manzur-Pineda, K. et al. Echocardiographic changes after arteriovenous fistula creation in hemodialysis patients. Clin. Nephrol. 98, 229–238 (2022).
pubmed: 36168799 pmcid: 9990444 doi: 10.5414/CN110816
Hetz, P. et al. Prophylactic ligature of AV fistula prevents high output heart failure after kidney transplantation. Am. J. Nephrol. 51, 511–519 (2020).
pubmed: 32659755 doi: 10.1159/000508957
Stoumpos, S. & Mark, P. B. Should we ligate arteriovenous fistulas in asymptomatic patients after kidney transplantation? Circulation 139, 2819–2821 (2019).
pubmed: 31206325 doi: 10.1161/CIRCULATIONAHA.119.040361
Rodriguez-Espinosa, D. et al. Multimodal strategies for the diagnosis and management of refractory congestion. an integrated cardiorenal approach. Front. Physiol. 13, 913580 (2022).
pubmed: 35874534 pmcid: 9304751 doi: 10.3389/fphys.2022.913580
Southgate, L., Machado, R. D., Graf, S. & Morrell, N. W. Molecular genetic framework underlying pulmonary arterial hypertension. Nat. Rev. Cardiol. 17, 85–95 (2020).
pubmed: 31406341 doi: 10.1038/s41569-019-0242-x
Hassoun, P. M. Pulmonary arterial hypertension. N. Engl. J. Med. 385, 2361–2376 (2021).
pubmed: 34910865 doi: 10.1056/NEJMra2000348
Kaiser, R., Seiler, S., Held, M., Bals, R. & Wilkens, H. Prognostic impact of renal function in precapillary pulmonary hypertension. J. Intern. Med. 275, 116–126 (2014).
pubmed: 24011362 doi: 10.1111/joim.12131
D’Apolito, M. et al. Urea-induced ROS cause endothelial dysfunction in chronic renal failure. Atherosclerosis 239, 393–400 (2015).
pubmed: 25682038 pmcid: 4361277 doi: 10.1016/j.atherosclerosis.2015.01.034
Giaid, A. et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 328, 1732–1739 (1993).
pubmed: 8497283 doi: 10.1056/NEJM199306173282402
Chester, A. H. & Yacoub, M. H. The role of endothelin-1 in pulmonary arterial hypertension. Glob. Cardiol. Sci. Pract. 2014, 62–78 (2014).
pubmed: 25405182 pmcid: 4220438
Shao, D., Park, J. E. S. & Wort, S. J. The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension. Pharmacol. Res. 63, 504–511 (2011).
pubmed: 21419223 doi: 10.1016/j.phrs.2011.03.003
Din, S., Sarathchandra, P., Yacoub, M. H. & Chester, A. H. Interaction between bone morphogenetic proteins and endothelin-1 in human pulmonary artery smooth muscle. Vasc. Pharmacol. 51, 344–349 (2009).
doi: 10.1016/j.vph.2009.09.001
Ern Yeoh, S. et al. Endothelin-1, outcomes in patients with heart failure and reduced ejection fraction, and effects of dapagliflozin: findings from DAPA-HF. Circulation 147, 1670–1683 (2023).
doi: 10.1161/CIRCULATIONAHA.122.063327
Rossi, G. P., Belloni, A. S., Nussdorfer, G. G. & Pessina, A. C. Endothelin-1 and the adrenal gland. J. Cardiovasc. Pharmacol. 35, 17 (2000).
doi: 10.1097/00005344-200000002-00005
Miller, W. L., Redfield, M. M. & Burnett, J. C. J. Integrated cardiac, renal, and endocrine actions of endothelin. J. Clin. Invest. 83, 317–320 (1989).
pubmed: 2642921 pmcid: 303677 doi: 10.1172/JCI113876
Cao, L. Q. & Banks, R. O. Cardiorenal actions of endothelin, Part II: effects of cyclooxygenase inhibitors. Life Sci. 46, 585–590 (1990).
pubmed: 2106603 doi: 10.1016/0024-3205(90)90126-C
Boehm, M. et al. Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension. BMC Pulm. Med. 18, 41–4 (2018).
pubmed: 29499691 pmcid: 5833097 doi: 10.1186/s12890-018-0604-x
Lariviere, R. et al. Increased immunoreactive endothelin-1 levels in blood vessels and glomeruli of rats with reduced renal mass. Kidney Blood Press. Res. 20, 372–380 (1997).
pubmed: 9453448 doi: 10.1159/000174251
Zager, R. A., Johnson, A. C. M., Andress, D. & Becker, K. Progressive endothelin-1 gene activation initiates chronic/end-stage renal disease following experimental ischemic/reperfusion injury. Kidney Int. 84, 703–712 (2013).
pubmed: 23698233 pmcid: 3788861 doi: 10.1038/ki.2013.157
Raina, R. et al. Relationship of urinary endothelin-1 with estimated glomerular filtration rate in autosomal dominant polycystic kidney disease: a pilot cross-sectional analysis. BMC Nephrol. 17, 22–28 (2016).
pubmed: 26923419 pmcid: 4770683 doi: 10.1186/s12882-016-0232-8
Long, L. et al. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat. Med. 21, 777–785 (2015).
pubmed: 26076038 pmcid: 4496295 doi: 10.1038/nm.3877
Yeh, C. H., Chang, C. K., Cheng, M. F., Lin, H. J. & Cheng, J. T. Decrease of bone morphogenetic protein-7 (BMP-7) and its type II receptor (BMP-RII) in kidney of type 1-like diabetic rats. Horm. Metab. Res. 41, 605–611 (2009).
pubmed: 19440953 doi: 10.1055/s-0029-1220736
Jiang, Q. et al. Dysregulation of BMP9/BMPR2/SMAD signalling pathway contributes to pulmonary fibrosis and pulmonary hypertension induced by bleomycin in rats. Br. J. Pharmacol. 178, 203–216 (2021).
pubmed: 33080042 doi: 10.1111/bph.15285
Star, G. P., Giovinazzo, M. & Langleben, D. Bone morphogenic protein-9 stimulates endothelin-1 release from human pulmonary microvascular endothelial cells: a potential mechanism for elevated ET-1 levels in pulmonary arterial hypertension. Microvasc. Res. 80, 349–354 (2010).
pubmed: 20594999 doi: 10.1016/j.mvr.2010.05.010
Park, J. E. S. et al. BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production. PLoS One 7, e30075 (2012).
pubmed: 22299030 pmcid: 3267722 doi: 10.1371/journal.pone.0030075
Tu, L. et al. Selective BMP-9 inhibition partially protects against experimental pulmonary hypertension. Circ. Res. 124, 846–855 (2019).
pubmed: 30636542 doi: 10.1161/CIRCRESAHA.118.313356
Zhu, D. et al. BMP-9 regulates the osteoblastic differentiation and calcification of vascular smooth muscle cells through an ALK1 mediated pathway. J. Cell. Mol. Med. 19, 165–174 (2015).
pubmed: 25297851 doi: 10.1111/jcmm.12373
Zeisberg, M. et al. BMP-7 counteracts TGF-β1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat. Med. 9, 964–968 (2003).
pubmed: 12808448 doi: 10.1038/nm888
Wang, S., Lapage, J. & Hirschberg, R. Loss of tubular bone morphogenetic protein-7 in diabetic nephropathy. J. Am. Soc. Nephrol. 12, 2392–2399 (2001).
pubmed: 11675415 doi: 10.1681/ASN.V12112392
Kong, L. et al. Sulforaphane ameliorates diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7. Diabetes Metab. J. 45, 909–920 (2021).
pubmed: 34082508 pmcid: 8640156 doi: 10.4093/dmj.2020.0168
Zeisberg, M. et al. Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am. J. Physiol. Renal Physiol. 285, 1060 (2003).
doi: 10.1152/ajprenal.00191.2002
Mitu, G. & Hirschberg, R. Bone morphogenetic protein-7 (BMP7) in chronic kidney disease. Front. Biosci. 13, 4726–4739 (2008).
pubmed: 18508541 doi: 10.2741/3035
Morrissey, J. et al. Bone morphogenetic protein-7 improves renal fibrosis and accelerates the return of renal function. J. Am. Soc. Nephrol. 13, 14 (2002).
doi: 10.1681/ASN.V13suppl_1s14
Schrankl, J. et al. Localization of angiotensin II type 1 receptor gene expression in rodent and human kidneys. Am. J. Physiol. Renal Physiol. 320, F644–F653 (2021).
pubmed: 33615887 doi: 10.1152/ajprenal.00550.2020
Rianto, F., Hoang, T., Revoori, R. & Sparks, M. A. Angiotensin receptors in the kidney and vasculature in hypertension and kidney disease. Mol. Cell. Endocrinol. 529, 111259 (2021).
pubmed: 33781840 doi: 10.1016/j.mce.2021.111259
Betjes, M. G. H., Sablik, K. A., Litjens, N. H. R., Otten, H. G. & de Weerd, A. E. ARHGDIB and AT1R autoantibodies are differentially related to the development and presence of chronic antibody-mediated rejection and fibrosis in kidney allografts. Hum. Immunol. 82, 89–96 (2021).
pubmed: 33358038 doi: 10.1016/j.humimm.2020.12.003
Xu, Z. et al. Gentiopicroside ameliorates diabetic renal tubulointerstitial fibrosis via inhibiting the AT1R/CK2/NF-κB pathway. Front. Pharmacol. 13, 848915 (2022).
pubmed: 35814242 pmcid: 9260113 doi: 10.3389/fphar.2022.848915
Block, G. A. et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J. Am. Soc. Nephrol. 15, 2208–2218 (2004).
pubmed: 15284307 doi: 10.1097/01.ASN.0000133041.27682.A2
Tentori, F. et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am. J. Kidney Dis. 52, 519–530 (2008).
pubmed: 18514987 doi: 10.1053/j.ajkd.2008.03.020
Kestenbaum, B. et al. Survival following parathyroidectomy among United States dialysis patients. Kidney Int. 66, 2010–2016 (2004).
pubmed: 15496173 doi: 10.1111/j.1523-1755.2004.00972.x
Komaba, H. et al. Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int. 88, 350–359 (2015).
pubmed: 25786097 doi: 10.1038/ki.2015.72
Ivarsson, K. M. et al. The effect of parathyroidectomy on patient survival in secondary hyperparathyroidism. Nephrol. Dial. Transplant. 30, 2027–2033 (2015).
pubmed: 26374600 pmcid: 4832998 doi: 10.1093/ndt/gfv334
Ulrich, S. et al. Bone mineral density and secondary hyperparathyroidism in pulmonary hypertension. Open. Respir. Med. J. 3, 53–60 (2009).
pubmed: 19461899 pmcid: 2684713 doi: 10.2174/1874306400903010053
Genctoy, G., Arikan, S. & Gedik, O. Secondary hyperparathyroidism is associated with pulmonary hypertension in older patients with chronic kidney disease and proteinuria. Int. Urol. Nephrol. 47, 353–358 (2015).
pubmed: 25537827 doi: 10.1007/s11255-014-0889-5
Amin, M., Fawzy, A., Hamid, M. A. & Elhendy, A. Pulmonary hypertension in patients with chronic renal failure: role of parathyroid hormone and pulmonary artery calcifications. Chest 124, 2093–2097 (2003).
pubmed: 14665485 doi: 10.1378/chest.124.6.2093
Acarturk, G. et al. The relationship between arteriovenous fistula blood flow rate and pulmonary artery pressure in hemodialysis patients. Int. Urol. Nephrol. 40, 509–513 (2008).
pubmed: 17985208 doi: 10.1007/s11255-007-9269-8
Akmal, M., Barndt, R. R., Ansari, A. N., Mohler, J. G. & Massry, S. G. Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and right ventricular hypertrophy. Kidney Int. 47, 158–163 (1995).
pubmed: 7731141 doi: 10.1038/ki.1995.18
Komaba, H. & Fukagawa, M. The role of FGF23 in CKD — with or without Klotho. Nat. Rev. Nephrol. 8, 484–490 (2012).
pubmed: 22714041 doi: 10.1038/nrneph.2012.116
Miri, M., Ahmadi, M. & Hatami, M. Correlation between fibroblast growth factor-23 and pulmonary arterial hypertension in hemodialysis patients. Iran. J. Kidney Dis. 15, 300–305 (2021).
pubmed: 34279001
Widmann, L. et al. Fibroblast growth factor 23 as a biomarker of right ventricular dysfunction in pulmonary hypertension. Clin. Res. Cardiol. 112, 1382–1393 (2023).
pubmed: 36790465 pmcid: 10562503 doi: 10.1007/s00392-023-02162-y
Hu, M. C. et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J. Am. Soc. Nephrol. 22, 124–136 (2011).
pubmed: 21115613 pmcid: 3014041 doi: 10.1681/ASN.2009121311
Kurosu, H. et al. Suppression of aging in mice by the hormone Klotho. Science 309, 1829–1833 (2005).
pubmed: 16123266 pmcid: 2536606 doi: 10.1126/science.1112766
Mitani, H. et al. In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension 39, 838–843 (2002).
pubmed: 11967236 doi: 10.1161/01.HYP.0000013734.33441.EA
Varshney, R., Ali, Q., Wu, C. & Sun, Z. Monocrotaline-induced pulmonary hypertension involves downregulation of antiaging protein Klotho and eNOS activity. Hypertension 68, 1255–1263 (2016).
pubmed: 27672025 doi: 10.1161/HYPERTENSIONAHA.116.08184
Batlahally, S. et al. Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants. Sci. Rep. 10, 12368 (2020).
pubmed: 32704023 pmcid: 7378054 doi: 10.1038/s41598-020-69296-1
Chadban, S. J. et al. KDIGO clinical practice guideline on the evaluation and management of candidates for kidney transplantation. Transplantation 104, S11–S103 (2020).
pubmed: 32301874 doi: 10.1097/TP.0000000000003136
Abramowicz, D. et al. European renal best practice guideline on kidney donor and recipient evaluation and perioperative care. Nephrol. Dial. Transplant. 30, 1790–1797 (2015).
pubmed: 25007790 doi: 10.1093/ndt/gfu216
Knoll, G. et al. Canadian Society of Transplantation: consensus guidelines on eligibility for kidney transplantation. CMAJ 173, 1 (2005).
doi: 10.1503/cmaj.1041588
Frost, A. E. et al. The echocardiographic course of pretransplant pulmonary hypertension following kidney transplantation and associated outcomes. Pulm. Circ. 12, e12030 (2022).
pubmed: 35506107 pmcid: 9052995 doi: 10.1002/pul2.12030
Hoeper, M. M. et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N. Engl. J. Med. 388, 1478–1490 (2023).
pubmed: 36877098 doi: 10.1056/NEJMoa2213558
Stickel, S., Gin-Sing, W., Wagenaar, M. & Gibbs, J. S. R. The practical management of fluid retention in adults with right heart failure due to pulmonary arterial hypertension. Eur. Heart J. Suppl. 21, K46–K53 (2019).
pubmed: 31857800 pmcid: 6915055 doi: 10.1093/eurheartj/suz207
Webb, D. J., Vachiery, J., Hwang, L. & Maurey, J. O. Sildenafil improves renal function in patients with pulmonary arterial hypertension. Br. J. Clin. Pharmacol. 80, 235–241 (2015).
pubmed: 25727860 pmcid: 4541971 doi: 10.1111/bcp.12616
Heerspink, H. J. L. et al. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. Lancet 393, 1937–1947 (2019).
pubmed: 30995972 doi: 10.1016/S0140-6736(19)30772-X
Krowka, M. J. et al. International Liver Transplant Society practice guidelines: diagnosis and management of hepatopulmonary syndrome and portopulmonary hypertension. Transplantation 100, 1440–1452 (2016).
pubmed: 27326810 doi: 10.1097/TP.0000000000001229
Nevola, R. et al. Cardiorenal impact of SGLT-2 inhibitors: a conceptual revolution in the management of type 2 diabetes, heart failure and chronic kidney disease. Rev. Cardiovasc. Med. 23, 106 (2022).
pubmed: 35345273 doi: 10.31083/j.rcm2303106
Nassif, M. E. et al. Empagliflozin effects on pulmonary artery pressure in patients with heart failure: results from the EMBRACE-HF trial. Circulation 143, 1673–1686 (2021).
pubmed: 33550815 doi: 10.1161/CIRCULATIONAHA.120.052503
Pellicori, P. et al. Ultrasound imaging of congestion in heart failure: examinations beyond the heart. Eur. J. Heart Fail. 23, 703–712 (2021).
pubmed: 33118672 doi: 10.1002/ejhf.2032

Auteurs

Katarina Zeder (K)

Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
The University of Maryland-Institute for Health Computing, Bethesda, MD, USA.

Edward D Siew (ED)

Division of Nephrology and Hypertension, Vanderbilt Center for Kidney Disease and Integrated Program for Acute Kidney Injury, Nashville, TN, USA.

Gabor Kovacs (G)

Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Evan L Brittain (EL)

Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Bradley A Maron (BA)

Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. BMaron@som.umaryland.edu.
The University of Maryland-Institute for Health Computing, Bethesda, MD, USA. BMaron@som.umaryland.edu.

Classifications MeSH