Diagnosis and Management of Pulmonary Hypertension in Patients With CKD

Carl P Walther, Vijay Nambi, Nicola A Hanania, Sankar D Navaneethan, Carl P Walther, Vijay Nambi, Nicola A Hanania, Sankar D Navaneethan

Abstract

Pulmonary hypertension (PH) is a highly prevalent and important condition in adults with chronic kidney disease (CKD). In this review, we summarize the definition of PH, discuss its pathophysiology and classifications, and describe diagnostic and management strategies in patients with CKD, including those with kidney failure treated by kidney replacement therapy. In the general population, PH is classified into 5 groups based on clinical presentation, pathology, hemodynamics, and management strategies. In this classification system, PH in CKD is placed in a diverse group with unclear or multifactorial mechanisms, although underlying cardiovascular disease may account for most cases. CKD may itself directly incite pulmonary circulatory dysfunction and remodeling through uremic toxins, inflammation, endothelial dysfunction, and altered vasoregulation. Despite several studies describing the higher prevalence of PH in CKD and kidney failure, along with an association with poor outcomes, high-quality evidence is not available for its diagnostic and management strategies in those with CKD. In CKD not requiring kidney replacement therapy, volume management along with treatment of underlying risk factors for PH are critical. In those receiving hemodialysis, options are limited and transition to peritoneal dialysis may be considered if recurrent hypotension precludes optimal volume control.

Keywords: Chronic kidney disease (CKD); death; dialysis; end-stage renal disease (ESRD); heart failure; kidney failure; mean pulmonary arterial pressure (PAPm); pulmonary arterial hypertension (PAH); pulmonary circulatory dysfunction; pulmonary hypertension (PH); review; vascular remodeling; volume management.

Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Suggested algorithm for PH identification…
Figure 1.. Suggested algorithm for PH identification and management in persons with non-dialysis or dialysis-dependent CKD.
References: 1Galiè et al. 2Vachiery et al. Abbreviations: PH pulmonary hypertension; SLE, systemic lupus erythematosus; SS systemic sclerosis; HD hemodialysis; TRV tricuspid regurgitant velocity; RHC right heart catheterization; HTN hypertension; AF atrial fibrillation; LA left atrium; HRCT high resolution CT; PFTs pulmonary function tests; PAH pulmonary arterial hypertension; CTEPH chronic thromboembolic PH; AV access arteriovenous HD access

References

    1. Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and Diagnosis of Pulmonary Hypertension. Journal of the American College of Cardiology. 2013;62(25):D42–D50.
    1. Galiè N, Humbert M, Vachiery J-L, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2016;37(1):67–119.
    1. Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. European Respiratory Journal. 2019;53(1):1801913.
    1. Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. The European respiratory journal. 2009;34(4):888–894.
    1. Tang M, Batty JA, Lin C, Fan X, Chan KE, Kalim S. Pulmonary Hypertension, Mortality, and Cardiovascular Disease in CKD and ESRD Patients: A Systematic Review and Meta-analysis. American Journal of Kidney Diseases. 2018;72(1):75–83.
    1. Simonneau G, Gatzoulis MA, Adatia I, et al. Updated Clinical Classification of Pulmonary Hypertension. Journal of the American College of Cardiology. 2013;62(25):D34–D41.
    1. McGoon MD, Benza RL, Escribano-Subias P, et al. Pulmonary Arterial Hypertension:Epidemiology and Registries: Epidemiology and Registries. Journal of the American College of Cardiology. 2013;62(25):D51–D59.
    1. Peacock AJ, Murphy NF, McMurray JJV, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. The European respiratory journal. 2007;30(1):104.
    1. Ralph TS, Hossein AG, Martin RW, Friedrich G. Mechanisms of disease: pulmonary arterial hypertension. Nature Reviews Cardiology. 2011;8(8):443.
    1. Tuder RM, Abman SH, Braun T, et al. Development and Pathology of Pulmonary Hypertension. Journal of the American College of Cardiology. 2009;54(1):S3–S9.
    1. Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328(24):1732–1739.
    1. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43(12 Suppl S):13S–24S.
    1. Christman BW, McPherson CD, Newman JH, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992;327(2):70–75.
    1. Galie N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1).
    1. Nickel NP, O’leary JM, Brittain EL, et al. Kidney dysfunction in patients with pulmonary arterial hypertension. In. Vol 7 London, England: SAGE Publications; 2017:38–54.
    1. Webb DJ, Vachiery JL, Hwang LJ, Maurey JO. Sildenafil improves renal function in patients with pulmonary arterial hypertension. British Journal of Clinical Pharmacology. 2015;80(2):235–241.
    1. Guazzi AM, Borlaug AB. Pulmonary Hypertension Due to Left Heart Disease. Circulation. 2012;126(8):975–990.
    1. Guazzi M, Naeije R. Pulmonary Hypertension in Heart Failure: Pathophysiology, Pathobiology, and Emerging Clinical Perspectives. J Am Coll Cardiol. 2017;69(13):1718–1734.
    1. Tandon HD, Kasturi J. Pulmonary vascular changes associated with isolated mitral stenosis in India. British Heart Journal. 1975;37(1):26.
    1. West JB, Mathieu-Costello O. Vulnerability of Pulmonary Capillaries in Heart Disease. Circulation. 1995;92(3):622–631.
    1. Seeger W, Adir Y, Barberà JA, et al. Pulmonary Hypertension in Chronic Lung Diseases. Journal of the American College of Cardiology. 2013;62(25):D109–D116.
    1. Berger RM, Beghetti M, Humpl T, et al. Clinical features of paediatric pulmonary hypertension: a registry study. The Lancet. 2012;379(9815):537–546.
    1. Manika K, Pitsiou GG, Boutou AK, et al. The Impact of Pulmonary Arterial Pressure on Exercise Capacity in Mild-to-Moderate Cystic Fibrosis: A Case Control Study. Pulmonary medicine. 2012;2012(2012):252345–252345.
    1. Chaouat A, Bugnet A-S, Kadaoui N, et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine. 2005;172(2):189–194.
    1. Barberà JA, Peinado VI, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. The European respiratory journal. 2003;21(5):892–905.
    1. Chen C-Y, Liao K-M. Chronic Obstructive Pulmonary Disease is associated with risk of Chronic Kidney Disease: A Nationwide Case-Cohort Study. Scientific reports. 2016;6(1):25855.
    1. Navaneethan SD, Schold JD, Huang H, et al. Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease. American Journal of Nephrology. 2016;43(1):39–46.
    1. Simonneau G, Torbicki A, Dorfmüller P, Kim N. The pathophysiology of chronic thromboembolic pulmonary hypertension. European respiratory review : an official journal of the European Respiratory Society. 2017;26(143).
    1. Kim NH. Group 4 Pulmonary Hypertension: Chronic Thromboembolic Pulmonary Hypertension: Epidemiology, Pathophysiology, and Treatment: Chronic Thromboembolic Pulmonary Hypertension: Epidemiology, Pathophysiology, and Treatment. Cardiology Clinics. 2016;34(3):435–441.
    1. Dorfmüller P, Günther S, Ghigna M-R, et al. Microvascular disease in chronic thromboembolic pulmonary hypertension: a role for pulmonary veins and systemic vasculature. The European respiratory journal. 2014;44(5):1275–1288.
    1. Kalantari S, Gomberg-Maitland M. Group 5 Pulmonary Hypertension. Cardiology Clinics. 2016;34(3):443–449.
    1. Bolignano D, Rastelli S, Agarwal R, et al. Pulmonary Hypertension in CKD. American Journal of Kidney Diseases. 2013;61(4):612–622.
    1. Navaneethan SD, Roy J, Tao K, et al. Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in CKD. Journal of the American Society of Nephrology : JASN. 2016;27(3):877–886.
    1. O’leary JM, Assad TR, Xu M, et al. Pulmonary hypertension in patients with chronic kidney disease: invasive hemodynamic etiology and outcomes. Pulmonary Circulation. 2017;7(3):674–683.
    1. Edmonston DL, Parikh KS, Rajagopal S, et al. Pulmonary Hypertension Subtypes and Mortality in CKD. American Journal of Kidney Diseases. 2019. doi: 10.1053/j.ajkd.2019.08.027
    1. Pabst S, Hammerstingl C, Hundt F, et al. Pulmonary Hypertension in Patients with Chronic Kidney Disease on Dialysis and without Dialysis: Results of the PEPPER-Study (PH in Patients with Chronic Kidney Disease). PLoS ONE. 2012;7(4):e35310.
    1. Schwarz U, Buzello M, Ritz E, et al. Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2000;15(2):218–223.
    1. London GM, Safar ME, Pannier B. Aortic Aging in ESRD: Structural, Hemodynamic, and Mortality Implications. Journal of the American Society of Nephrology : JASN. 2016;27(6):1837–1846.
    1. Paloian NJ, Giachelli CM. A current understanding of vascular calcification in CKD. American journal of physiology Renal physiology. 2014;307(8):F891–F900.
    1. Loutradis C, Sarafidis PA, Papadopoulos CE, Papagianni A, Zoccali C. The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRD. Journal of the American Society of Nephrology. 2018;29(5):1372.
    1. Kawar B, Ellam T, Jackson C, Kiely DG. Pulmonary Hypertension in Renal Disease: Epidemiology, Potential Mechanisms and Implications. American Journal of Nephrology. 2013;37(3):281–290.
    1. Oberg BP, Elizabeth M, Lucas FL, et al. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney International. 2004;65(3):1009.
    1. Bernelot Moens SJ, Verweij SL, van der Valk FM, et al. Arterial and Cellular Inflammation in Patients with CKD. Journal of the American Society of Nephrology. 2017;28(4):1278.
    1. Wang X, Shapiro JI. Evolving concepts in the pathogenesis of uraemic cardiomyopathy. Nature reviews Nephrology. 2019;15(3):159–175.
    1. Kennedy JD, Shrestha SK, Sheehey MB, et al. Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart Failure. Circulation: Heart Failure. 2015;8(6):1068–1076.
    1. Acarturk G, Albayrak R, Melek M, et al. The relationship between arteriovenous fistula blood flow rate and pulmonary artery pressure in hemodialysis patients. International Urology and Nephrology. 2008;40(2):509–513.
    1. Unal A, Tasdemir K, Oymak S, et al. The long‐term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients. Hemodialysis International. 2010;14(4):398–402.
    1. Yigla M, Banderski R, Azzam ZS, Reisner SA, Nakhoul F. Arterio-venous access in end-stage renal disease patients and pulmonary hypertension. Therapeutic Advances in Respiratory Disease. 2008;2(2):49–53.
    1. Nakhoul F, Yigla M, Gilman R, Reisner SA, Abassi Z. The pathogenesis of pulmonary hypertension in haemodialysis patients via arterio-venous access. Nephrology Dialysis Transplantation. 2005;20(8):1686–1692.
    1. Macrae JM, Pandeya S, Humen DP, Krivitski N, Lindsay RM. Arteriovenous fistula-associated high-output cardiac failure: a review of mechanisms. American Journal of Kidney Diseases. 2004;43(5):e21.21–e21.26.
    1. Matura LA, McDonough A, Carroll DL. Cluster analysis of symptoms in pulmonary arterial hypertension: a pilot study. European Journal of Cardiovascular Nursing. 2012;11(1):51–61.
    1. Salerno FR, Parraga G, McIntyre CW. Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease. In. Vol 302017:50–57.
    1. Shlipak MG, Lash JP, Yang W, et al. Symptoms characteristic of heart failure among CKD patients without diagnosed heart failure. Journal of cardiac failure. 2011;17(1):17–23.
    1. Frost A, Badesch D, Gibbs JSR, et al. Diagnosis of pulmonary hypertension. Eur Respir J. 2019;53(1):1801904.
    1. Sirnes PA, Tendera M, Vardas P, Widimsky P. Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2009;30:2493–2537.
    1. Vachiery JL, Tedford RJ, Rosenkranz S, et al. Pulmonary hypertension due to left heart disease. Eur Respir J. 2019;53(1).
    1. Meghan ES, Andrew MC, Richard NC. Pulmonary hypertension in patients with chronic and end-stage kidney disease. Kidney International. 2013;84(4).
    1. Dupuis J, Hoeper MM. Endothelin receptor antagonists in pulmonary arterial hypertension. The European respiratory journal. 2008;31(2):407–415.
    1. Channick RN, Sitbon O, Barst RJ, Manes A, Rubin LJ. Endothelin receptor antagonists in pulmonary arterial hypertension. Journal of the American College of Cardiology. 2004;43(12):S62–S67.
    1. Liu C, Chen J, Gao Y, Deng B, Liu K. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst Rev. 2013(2):CD004434.
    1. Lau EMT, Giannoulatou E, Celermajer DS, Humbert M. Epidemiology and treatment of pulmonary arterial hypertension. Nature Reviews Cardiology. 2017;14:603.
    1. Ruan CH, Dixon RA, Willerson JT, Ruan KH. Prostacyclin therapy for pulmonary arterial hypertension. Tex Heart Inst J. 2010;37(4):391–399.
    1. Barnes H, Yeoh HL, Fothergill T, Burns A, Humbert M, Williams T. Prostacyclin for pulmonary arterial hypertension. Cochrane Database Syst Rev. 2019;5(5):CD012785.
    1. Wardle AJ, Seager MJ, Wardle R, Tulloh RM, Gibbs JS. Guanylate cyclase stimulators for pulmonary hypertension. Cochrane Database Syst Rev. 2016(8):CD011205.
    1. Barnes H, Brown Z, Burns A, Williams T. Phosphodiesterase 5 inhibitors for pulmonary hypertension. Cochrane Database Syst Rev. 2019;1(1):CD012621.
    1. Fan Z, Chen Y, Liu H. Calcium channel blockers for pulmonary arterial hypertension. Cochrane Database of Systematic Reviews. 2015(9).
    1. Robbins MI, Hemnes RA, Pugh EM, et al. High Prevalence of Occult Pulmonary Venous Hypertension Revealed by Fluid Challenge in Pulmonary Hypertension. Circulation: Heart Failure. 2014;7(1):116–122.
    1. Agarwal R, Andersen MJ, Pratt JH. On the importance of pedal edema in hemodialysis patients. Clinical journal of the American Society of Nephrology : CJASN. 2008;3(1):153–158.
    1. Domenic AS. Diuretic use in renal disease. Nature Reviews Nephrology. 2011;8(2):100.
    1. Panagiotis IG, Rajiv A. Epidemiology, diagnosis and management of hypertension among patients on chronic dialysis. Nature Reviews Nephrology. 2016;12(10).
    1. Agarwal PR, Alborzi PP, Satyan PS, Light PR. Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP): A Randomized, Controlled Trial. Hypertension. 2009;53(3):500–507.
    1. Lentine LK, Villines CT, Axelrod RD, Kaviratne PS, Weir PM, Costa PS. Evaluation and Management of Pulmonary Hypertension in Kidney Transplant Candidates and Recipients: Concepts and Controversies. Transplantation. 2017;101(1):166–181.
    1. Zlotnick DM, Axelrod DA, Chobanian MC, et al. Non-invasive detection of pulmonary hypertension prior to renal transplantation is a predictor of increased risk for early graft dysfunction. Nephrology Dialysis Transplantation. 2010;25(9):3090–3096.
    1. Davide B, Simone L, Daniela L, et al. High estimated pulmonary artery systolic pressure predicts adverse cardiovascular outcomes in stage 2–4 chronic kidney disease. Kidney International. 2015;88(1).
    1. Selvaraj JS, Shah JS, Ommerborn RM, et al. Pulmonary Hypertension Is Associated With a Higher Risk of Heart Failure Hospitalization and Mortality in Patients With Chronic Kidney Disease: The Jackson Heart Study. Circulation: Heart Failure. 2017;10(6):e003940–e003940.
    1. Reque J, Garcia-Prieto A, Linares T, et al. Pulmonary Hypertension Is Associated with Mortality and Cardiovascular Events in Chronic Kidney Disease Patients. American journal of nephrology. 2017;45(2):107–114.
    1. Xu Q, Xiong L, Fan L, et al. Association of Pulmonary Hypertension with Mortality in Incident Peritoneal Dialysis Patients. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2015;35(5):537–544.
    1. Li Z, Liu S, Liang X, et al. Pulmonary hypertension as an independent predictor of cardiovascular mortality and events in hemodialysis patients. International Urology and Nephrology. 2014;46(1):141–149.
    1. Prevalence Agarwal R., determinants and prognosis of pulmonary hypertension among hemodialysis patients. Nephrology Dialysis Transplantation. 2012;27(10):3908–3914.
    1. Lentine KL, Costa SP, Weir MR, et al. Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Journal of the American College of Cardiology. 2012;60(5):434–480.

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