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 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.