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Meta-Analysis
. 2025 Aug 8;66(2):2402400.
doi: 10.1183/13993003.02400-2024. Print 2025 Aug.

Renal dysfunction and outcomes in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: an individual participant data meta-analysis

Amber Meservey  1 , Nadine Al-Naamani  1 , Jasleen Minhas  1 , Jason S Fritz  1 , Dina Appleby  2 , Guillaume Baudry  3 , Nicolas Girerd  3 , Rui Feng  2 , Steven M Kawut  1   2 , Jude Moutchia  4
Affiliations
Meta-Analysis

Renal dysfunction and outcomes in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: an individual participant data meta-analysis

Amber Meservey et al. Eur Respir J. .

Abstract

Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction with extrapulmonary sequelae including renal dysfunction. We sought to characterise renal dysfunction in PAH and CTEPH and to assess the effect of pulmonary hypertension treatment on renal function.

Methods: We performed an individual participant data meta-analysis of 6694 participants from 18 phase III randomised clinical trials of pulmonary hypertension therapies. We calculated estimated glomerular filtration rate (eGFR) using the race-agnostic 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Results: The mean±sd age was 49.6±15.5 years, 78% were female and 58% had idiopathic PAH. A total of 907 (13.5%) participants had a baseline eGFR <60 mL·min-1·1.73 m-2. Lower baseline eGFR correlated with higher mean right atrial pressure (mRAP) and lower cardiac index. At 12-16 weeks, a 10 mmHg decrease in mRAP from baseline or a 1 L·min-1·m-2 increase in cardiac index was associated with only a 1.7 mL·min-1·1.73 m-2 (95% CI -2.9--0.5 mL·min-1·1.73 m-2; p=0.006) or a 1.4 mL·min-1·1.73 m-2 (95% CI 0.5-2.4 mL·min-1·1.73 m-2; p=0.003) increase in eGFR, respectively. A 10 mL·min-1·1.73 m-2 lower baseline eGFR was associated with an increased risk of all-cause mortality (adjusted hazard ratio 1.16, 95% CI 1.08-1.23; p<0.001). Interestingly, pulmonary hypertension treatment was associated with only a small improvement in eGFR at 12-16 weeks (adjusted β 2.0 mL·min-1·1.73 m-2, 95% CI 1.4-2.6 mL·min-1·1.73 m-2; p<0.001).

Conclusion: Renal dysfunction remains highly prevalent in PAH and CTEPH and is associated with worse haemodynamics and worse clinical outcomes. In this cohort with relatively preserved renal function, pulmonary hypertension treatment was associated with only a minimal improvement in eGFR.

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Conflict of interest statement

Conflicts of interest: A. Meservey reports support for the present study from NIH Grant T32 HL007843 and support for attending meetings from NIH Grant T32 HL007843. N. Al-Naamani reports support for the present study from NIH/NHLBI K23 grant funding and NIH/NHLBI R01 grant funding. J. Minhas reports support for the present study from ATS early career investigator award in PVD, Jenesis Innovative research award (United Therapeutics), and NIH/NHLBI K23 – HL169930. J.S. Fritz reports grants from United Therapeutics. G. Baudry reports consulting fees from Abbott Medical France SAS, AstraZeneca, Boehringer Ingelheim France and Novartis Pharma SAS; payment or honoraria for lectures, presentations, manuscript writing or educational events from Abbott Medical France SAS, Amgen SAS, AstraZeneca, Bayer HealthCare SAS, Boehringer Ingelheim France, Les Laboratoires Servier, Novartis Pharma SAS, Novo Nordisk and Sanofi Aventis France; payment for expert testimony from Abbott Medical France SAS and Boehringer Ingelheim France; support for attending meetings from Abbott, AstraZeneca, Amgen, Bayer HealthCare SAS, Boehringer Ingelheim France, Les Laboratoires Servier, Novartis Pharma SAS and Novo Nordisk; and leadership roles with French group for heart failure, Cardiorenal group 24-26 HFA, and Advanced HF group 24-26 HFA. N. Girerd reports consulting fees from AstraZeneca, Novartis, Bayer, Novo Nordisk, Boehringer Ingelheim, Roche Diagnostics, Lilly, Echosens, Cardiostory and NP Medical; and support for attending meetings from AstraZeneca, Novartis, Bayer, Novo Nordisk, Boehringer Ingelheim, NP Medical and Lilly. S.M. Kawut reports support for the present study from CMREF; consulting fees from Janssen, Regeneron, PureTech Health, Morphic, Acuta and Amgen; payment or honoraria for lectures, presentations, manuscript writing or educational events from Janssen, Accredo, Actelion, Aerovate, Bayer, Inari Medical, Merck, United Therapeutics, Liquidia and Pfizer; support for attending meetings from Aerovate; participation on a data safety monitoring board or advisory board with United Therapeutics, Keros, Acceleron, Vivus, Aerovate, Proteo Biotech and Tiakis; and stock or stock options with Verve Therapeutics. The remaining authors have no potential conflicts of interest to disclose.

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