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

Background Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction with extrapulmonary sequalae including renal dysfunction. We sought to characterize 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 randomized clinical trials of pulmonary hypertension therapies. We calculated estimated glomerular filtration rate (eGFR) using the race-agnostic 2021 CKD-EPI equation. Results The mean age was 49.6±15.5 years, 78% were female and 58% had idiopathic PAH. A total of 907 participants (13.5%) 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; p=0.006) or a 1.4 mL·min −1 ·1.73 m −2 (95% CI: 0.5, 2.4; 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 (aHR: 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 (aβ: 2.0 mL·min −1 ·1.73 m −2 [95% CI: 1.4, 2.6]; p <0.001). Conclusion Renal dysfunction remains highly prevalent in PAH and CTEPH and is associated with worse hemodynamics and worse clinical outcomes. In this cohort with relatively preserved renal function, pulmonary hypertension treatment was associated with only a minimal improvement in eGFR.