Pulmonary hypertension in chronic kidney disease: a hemodynamic characterization

Pulmonary hypertension (PH) is a common co-morbidity in patients with chronic kidney disease (CKD) and end-stage renal disease. More importantly, the presence of PH is associated with increased risk of hospitalization and mortality in patients with CKD. Despite its prognostic significance, the true prevalence of PH in CKD is unclear. The majority of prior studies reporting the prevalence of PH in patients with CKD have defined PH based on echocardiography, which is frequently inaccurate. In addition, the pathogenesis of PH in CKD are not well defined. Many different mechanisms may play a role. In light of this, the current World Health Organization (WHO) categorizes PH due to CKD and end-stage renal disease under WHO group 5, ‘‘miscellaneous causes’’. Patients with CKD often have coexisting left heart disease, chronic lung disease, thromboembolic disease, autoimmune diseases including scleroderma and systemic lupus erythematosus, and liver disease, that are well-established risk factors for developing PH. Additionally, CKD, especially endstage renal disease, by itself has also been proposed to cause pulmonary vascular remodeling and PH. Possible mechanisms that have been suggested include endothelial dysfunction due to increased oxidative stress from uremic toxins, chronic inflammation resulting from exposure of the blood to dialysis membrane, vascular calcification, and increased flow from arteriovenous fistula (reviewed in Kawar et al.). However, these mechanisms are not supported by robust preclinical or clinical studies. In this issue of Pulmonary Circulation, O’Leary et al. sought to address these knowledge gaps by studying the prevalence, associated risk factors, and prognostic importance of PH in a large, electronic record-based cohort of patients who were referred to the Vanderbilt University cardiac catheterization lab for a right heart catheterization (RHC). Renal function was determined by estimated glomerular filtration rate using the CKD-EPI creatinine equation. Only patients with stage 3 or worse CKD were included and those with stage 2 or less kidney disease were excluded. Clinical, laboratory, and hemodynamic data were extracted from the electronic health records. Co-morbidities were defined by International Classification of Diseases (ICD)-9 codes. Notably, patients with complex congenital heart disease, chronic thromboembolic disease, acute myocardial infarction, and previous lung or cardiac transplantation were excluded. Vital statistics were obtained using Social Security death index. PH, defined as mean pulmonary artery pressure (mPAP) 25mmHg, was present in 68% of patients in this cohort. Post-capillary PH, defined as mPAP 25mmHg with a pulmonary capillary wedge pressure (PCWP)> 15mmHg, was more common than precapillary PH, defined as mPAP 25mmHg with a PCWP 15mmHg (76% vs. 24%, respectively). PH was more likely to be present in CKD patients who were younger, African Americans, and those who had diabetes, obesity, scleroderma, left heart disease, obstructive sleep apnea, and chronic obstructive pulmonary disease. Although many of the patients with pre-capillary PH had established risk factors for pulmonary vascular disease such as scleroderma, systemic lupus erythematosus, cirrhosis, human immunodeficiency virus infection, and chronic hypoxic lung disease, 58% of them had no known risk factors. The presence of CKD was associated with 1.4-fold increased risk of having PH after adjusting for other independent risk factors for PH in this cohort. Finally, consistent with prior reports, the presence of PH was associated with increased risk of mortality in patients with stage 3 or worse CKD. O’Leary et al. should be congratulated for this informative study. To the best of our knowledge, this is the largest study to use invasive hemodynamics to diagnosis and characterize PH in patients with CKD as opposed to using Doppler estimated pulmonary artery pressures. This is crucial, as the echocardiogram cannot only underor over-estimate PAPs, but it is also limited in differentiating whether the elevated PAPs are due to pre-capillary pulmonary vascular remodeling, increased left sided filling pressure, or high cardiac output. All these mechanisms may cause PH in patients with CKD. Several aspects of this study are noteworthy. First, the prevalence of PH in CKD reported in this study is