Background: Pulmonary arterial hypertension (PAH) may lead to right heart failure and subsequently alter glomerular filtration rates (GFR). Chronic kidney disease (CKD, GFR <60 mL/min/1.73 m2) may also adversely affect PAH prognosis. This study aimed to assess how right heart hemodynamics was associated with reduced estimated GFR (eGFR) and the association of CKD with survival in PAH patients. Methods: In a prospective PAH cohort (2003–2012), invasive hemodynamics and eGFR were collected at diagnosis (179 patients) and during follow-up (159 patients). The prevalence of CKD was assessed at PAH diagnosis. Variables, including hemodynamics, associated with reduced eGFR at diagnosis and during follow-up were tested in multivariate analysis. The association of CKD with survival was evaluated using a multivariate Cox regression model. Results: At diagnosis, mean age was 60.4 ± 16.5 years, mean pulmonary arterial pressure was 43 ± 12 mm Hg, and eGFR was 74.4 ± 26.4 mL/min/1.73 m2. CKD was observed in 52 incident patients (29%). Independent determinants of reduced eGFR at diagnosis were age, systemic hypertension, and decreased cardiac index. Independent determinants of reduced eGFR during follow-up were age, female gender, PAH etiology, systemic hypertension, decreased cardiac index, and increased right atrial pressure. Age ≥60 years, female gender, NYHA 4, and CKD at diagnosis were independently associated with decreased survival. The adjusted hazards ratio for death associated with CKD was 1.81 (95% confidence interval [1.01–3.25]). Conclusion: CKD is frequent at PAH diagnosis and is independently associated with increased mortality. Right heart failure may induce renal hypoperfusion and congestion, and is associated with eGFR decrease.

Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, Langleben D, Manes A, Satoh T, Torres F, Wilkins MR, Badesch DB: Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 2013; 62:D42–D50.
Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R: Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62:D34–D41.
Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, Naeije R, Newman J, Oudiz RJ, Provencher S, Torbicki A, Voelkel NF, Hassoun PM: Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 2013; 62:D22–D33.
Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Cottin V, Degano B, Jais X, Montani D, Souza R, Simonneau G: Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156–163.
D&apos;Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al: Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343–349.
Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, Frost A, Barst RJ, Badesch DB, Elliott CG, Liou TG, McGoon MD: Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 2010; 122: 164–172.
Campbell RC, Sui X, Filippatos G, Love TE, Wahle C, Sanders PW, Ahmed A: Association of chronic kidney disease with outcomes in chronic heart failure: a propensity-matched study. Nephrol Dial Transplant 2009; 24: 186–193.
Ronco C, Haapio M, House AA, Anavekar N, Bellomo R: Cardiorenal syndrome. J Am Coll Cardiol 2008; 52: 1527–1539.
Shamseddin MK, Parfrey PS: Mechanisms of the cardiorenal syndromes. Nat Rev Nephrol 2009; 5: 641–649.
Angelini A, Castellani C, Virzi GM, Fedrigo M, Thiene G, Valente M, Ronco C, Vescovo G: The role of congestion in cardiorenal syndrome type 2: new pathophysiological insights into an experimental model of heart failure. Cardiorenal Med 2015; 6: 61–72.
Damman K, van Deursen VM, Navis G, Voors AA, van Veldhuisen DJ, Hillege HL: 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 2009; 53: 582–588.
Pabst S, Hammerstingl C, Hundt F, Gerhardt T, Grohe C, Nickenig G, Woitas R, Skowasch D: Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study. PLoS One 2012; 7:e35310.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–1305.
Shah SJ, Thenappan T, Rich S, Tian L, Archer SL, Gomberg-Maitland M: Association of serum creatinine with abnormal hemodynamics and mortality in pulmonary arterial hypertension. Circulation 2008; 117: 2475–2483.
Leuchte HH, El Nounou M, Tuerpe JC, Hartmann B, Baumgartner RA, Vogeser M, Muehling O, Behr J: N-terminal pro-brain natriuretic peptide and renal insufficiency as predictors of mortality in pulmonary hypertension. Chest 2007; 131: 402–409.
Webb DJ, Vachiery JL, Hwang LJ, Maurey JO: Sildenafil improves renal function in patients with pulmonary arterial hypertension. Br J Clin Pharmacol 2015; 80: 235–241.
Navaneethan SD, Wehbe E, Heresi GA, Gaur V, Minai OA, Arrigain S, Nally JV Jr, Schold JD, Rahman M, Dweik RA: Presence and outcomes of kidney disease in patients with pulmonary hypertension. Clin J Am Soc Nephrol 2014; 9: 855–863.
Kaiser R, Seiler S, Held M, Bals R, Wilkens H: Prognostic impact of renal function in precapillary pulmonary hypertension. J Intern Med 2014; 275: 116–126.
Galie N, Corris PA, Frost A, Girgis RE, Granton J, Jing ZC, Klepetko W, McGoon MD, McLaughlin VV, Preston IR, Rubin LJ, Sandoval J, Seeger W, Keogh A: Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol 2013; 62:D60–D72.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461–470.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group: KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3: 1–150.
Peake M, Whiting M: Measurement of serum creatinine – current status and future goals. Clin Biochem Rev 2006; 27: 173–184.
Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology C: Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007; 53: 766–772.
R Development Core Team: R: A Language and Environment for Statistical Computing. Vienna, Austria, R Foundation for Statistical Computing, 2008.
Bates D, Maechler M, Bolker B, Walker S: Fitting linear mixed-effects models using lme4. J Stat Software 2015; 67: 1–48.
Therneau TM: A Package for Survival Analysis in S, 2015.
Cnaan A, Laird NM, Slasor P: Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Stat Med 1997; 16: 2349–2380.
Snyder JJ, Foley RN, Collins AJ: Prevalence of CKD in the United States: a sensitivity analysis using the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Am J Kidney Dis 2009; 53: 218–228.
Breda AP, Pereira de Albuquerque AL, Jardim C, Morinaga LK, Suesada MM, Fernandes CJ, Dias B, Lourenco RB, Salge JM, Souza R: Skeletal muscle abnormalities in pulmonary arterial hypertension. PLoS One 2014; 9:e114101.
Rognant N, Lemoine S: Evaluation of renal function in patients with cirrhosis: where are we now? World J Gastroenterol 2014; 20: 2533–2541.
Lindeman RD, Tobin JD, Shock NW: Association between blood pressure and the rate of decline in renal function with age. Kidney Int 1984; 26: 861–868.
Cirillo M, Anastasio P, De Santo NG: Relationship of gender, age, and body mass index to errors in predicted kidney function. Nephrol Dial Transplant 2005; 20: 1791–1798.
Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE, Shulman NB, Stamler J: Blood pressure and end-stage renal disease in men. N Engl J Med 1996; 334: 13–18.
Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, Nakanishi N, Miyatake K: Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 2000; 161: 487–492.
Messerli FH, De Carvalho JG, Christie B, Frohlich ED: Systemic and regional hemodynamics in low, normal and high cardiac output borderline hypertension. Circulation 1978; 58: 441–448.
Sise ME, Courtwright AM, Channick RN: Pulmonary hypertension in patients with chronic and end-stage kidney disease. Kidney Int 2013; 84: 682–692.
Nootens M, Kaufmann E, Rector T, Toher C, Judd D, Francis GS, Rich S: Neurohormonal activation in patients with right ventricular failure from pulmonary hypertension: relation to hemodynamic variables and endothelin levels. J Am Coll Cardiol 1995; 26: 1581–1585.
Damman K, Kjekshus J, Wikstrand J, Cleland JG, Komajda M, Wedel H, Waagstein F, McMurray JJ: Loop diuretics, renal function and clinical outcome in patients with heart failure and reduced ejection fraction. Eur J Heart Fail 2016; 18: 328–336.
Dzau VJ, Colucci WS, Hollenberg NK, Williams GH: Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure. Circulation 1981; 63: 645–651.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604–612.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.