Retrospective international cohort of 555 incident PAH patients (diagnosed 2001-2023). 42% (n=234) had chronic kidney disease and/or diabetes (renal-diabetic, RD): 45 DM only, 135 CKD only, 54 both. RD patients were older, had greater comorbidity burden, worse WHO functional class and higher pulmonary artery wedge pressure. At PAH diagnosis, RD patients were less often treated with endothelin receptor antagonists (61% vs 69%) and more often with single-agent therapy (55% vs 45%). Over 2.5 years of follow-up, the composite of death or PAH hospitalisation was significantly higher in RD (HR 1.45; 95% CI 1.07-1.98), as was all-cause mortality (HR 1.47). PAH with renal-diabetic overlap is common, under-treated and prognostically worse.
Comorbidities add complexity to pulmonary arterial hypertension (PAH), but also open opportunities to use therapies with benefits beyond the cardiovascular (CV) system, particularly preserving renal function and maintaining glucose homeostasis.
We retrospectively analysed an international cohort of incident patients with PAH diagnosed in 2001-2023, with available outcome data. Patients with chronic kidney disease (CKD) and/or diabetes mellitus (DM) were defined as renal-diabetic (RD). The relationship between RD overlap, all-cause mortality (ACM) or PAH hospitalisation or ACM alone was assessed by Kaplan-Meier curves and Cox proportional hazard regression.
Of 555 eligible subjects, 234 (42%) were classified as RD: 45 had DM, 135 CKD and 54 both. At baseline, RD patients were older and had greater comorbidity burden, higher WHO functional class and higher pulmonary artery wedge pressure than non-RD patients; 36% vs 26% (p<0.01) were estimated at high mortality risk. On PAH diagnosis, RD patients were less treated with endothelin receptor antagonists (61% vs 69%, p=0.04) and more with single PAH therapy (55% vs 45%, p=0.06). After 9 months, treatment patterns were similar, but 19% and 32% of RD patients were at high or intermediate-high risk, respectively, as compared with 4% and 23% of non-RD patients (p<0.001).During a follow-up of 2.5 (1-5) years, ACM/PAH hospitalisation and ACM alone were more frequent in RD patients than non-RD patients, with HR 1.45 (95% CI 1.07 to 1.98, p=0.02) and HR 1.47 (95% CI 1.05 to 2.04, p=0.02), respectively.
PAH with RD overlap is common, and has unmet therapeutic needs and worse outcomes.
