Pulmonary Hypertension Subtypes and Mortality in CKD

Abstract

Rationale & objective: Pulmonary hypertension (PH) contributes to cardiovascular disease and mortality in patients with chronic kidney disease (CKD), but the pathophysiology is mostly unknown. This study sought to estimate the prevalence and consequences of PH subtypes in the setting of CKD.

Study design: Observational retrospective cohort study.

Setting & participants: We examined 12,618 patients with a right heart catheterization in the Duke Databank for Cardiovascular Disease from January 1, 2000, to December 31, 2014.

Exposures: Baseline kidney function stratified by CKD glomerular filtration rate category and PH subtype.

Outcomes: All-cause mortality.

Analytical approach: Multivariable Cox proportional hazards analysis.

Results: In this cohort, 73.4% of patients with CKD had PH, compared with 56.9% of patients without CKD. Isolated postcapillary PH (39.0%) and combined pre- and postcapillary PH (38.3%) were the most common PH subtypes in CKD. Conversely, precapillary PH was the most common subtype in the non-CKD cohort (35.9%). The relationships between mean pulmonary artery pressure, pulmonary capillary wedge pressure, and right atrial pressure with mortality were similar in both the CKD and non-CKD cohorts. Compared with those without PH, precapillary PH conferred the highest mortality risk among patients without CKD (HR, 2.27; 95% CI, 2.00-2.57). By contrast, in those with CKD, combined pre- and postcapillary PH was associated with the highest risk for mortality in CKD in adjusted analyses (compared with no PH, HRs of 1.89 [95% CI, 1.57-2.28], 1.87 [95% CI, 1.52-2.31], 2.13 [95% CI, 1.52-2.97], and 1.63 [95% CI, 1.12-2.36] for glomerular filtration rate categories G3a, G3b, G4, and G5/G5D).

Limitations: The cohort referred for right heart catheterization may not be generalizable to the general population. Serum creatinine data in the 6 months preceding catheterization may not reflect true baseline CKD. Observational design precludes assumptions of causality.

Conclusions: In patients with CKD referred for right heart catheterization, PH is common and associated with poor survival. Combined pre- and postcapillary PH was common and portended the worst survival for patients with CKD.

Keywords: PH subtype; Pulmonary hypertension (PH); cardiovascular complication; chronic kidney disease (CKD); combined pre- and post-capillary PH; diagnostic catheterization; end-stage renal disease (ESRD); heart failure; hemodialysis; mortality; pulmonary capillary wedge pressure; pulmonary disease.

Figure 1.. Schematic of pulmonary hypertension subtypes

Pre-PH, pre-capillary pulmonary hypertension; Cpc-PH, combined pre- and post-capillary pulmonary hypertension; Ipc-PH, isolated post-capillary pulmonary hypertension; VC, vena cavae; RA, right atrium; RV, right ventricle; PA, pulmonary artery; PC, pulmonary capillaries; PV, pulmonary veins; LA, left atrium; LV, left ventricle; Ao, aorta.

Figure 2.. Flow diagram of exclusions and study participants

RHC, right heart catheterization; N, number; ACS, acute coronary syndrome; ILD, interstitial lung disease.

Figures 3A-3C.. Association between Mortality Risk and (A) Mean Pulmonary Artery Pressure, (B) Mean Pulmonary Capillary Wedge Pressure, and (C) Mean Right Atrial Pressure.

CKD, chronic kidney disease. Hazard ratio with 95% confidence interval is relative to the median value of the parameter.

Figures 3A-3C.. Association between Mortality Risk and (A) Mean Pulmonary Artery Pressure, (B) Mean Pulmonary Capillary Wedge Pressure, and (C) Mean Right Atrial Pressure.

CKD, chronic kidney disease. Hazard ratio with 95% confidence interval is relative to the median value of the parameter.

Figures 3A-3C.. Association between Mortality Risk and (A) Mean Pulmonary Artery Pressure, (B) Mean Pulmonary Capillary Wedge Pressure, and (C) Mean Right Atrial Pressure.

CKD, chronic kidney disease. Hazard ratio with 95% confidence interval is relative to the median value of the parameter.

Figure 4.. Pulmonary hypertension subtype prevalence stratified by chronic kidney disease severity

CKD, chronic kidney disease; PH, pulmonary hypertension; Pre-PH, pre-capillary pulmonary hypertension; Ipc-PH, isolated post-capillary pulmonary hypertension; Cpc-PH, combined pre- and post-capillary pulmonary hypertension.

Figures 5A & 5B.. Kaplan-Meier Survival Curves for patients (A) with chronic kidney disease and (B) without chronic kidney disease.

CKD, chronic kidney disease; PH, pulmonary hypertension; Pre-PH, pre-capillary pulmonary hypertension; Ipc-PH, isolated post-capillary pulmonary hypertension; Cpc-PH, combined pre- and post-capillary pulmonary hypertension.

Figures 5A & 5B.. Kaplan-Meier Survival Curves for patients (A) with chronic kidney disease and (B) without chronic kidney disease.

CKD, chronic kidney disease; PH, pulmonary hypertension; Pre-PH, pre-capillary pulmonary hypertension; Ipc-PH, isolated post-capillary pulmonary hypertension; Cpc-PH, combined pre- and post-capillary pulmonary hypertension.