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.

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Citation

Published Version (Please cite this version)

10.1053/j.ajkd.2019.08.027

Publication Info

Edmonston, Daniel L, Kishan S Parikh, Sudarshan Rajagopal, Linda K Shaw, Dennis Abraham, Alexander Grabner, Matthew A Sparks, Myles Wolf, et al. (2019). Pulmonary Hypertension Subtypes and Mortality in CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation. 10.1053/j.ajkd.2019.08.027 Retrieved from https://hdl.handle.net/10161/20057.

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Scholars@Duke

Edmonston

Daniel Len Edmonston

Assistant Professor of Medicine

My primary research focus lies at the intersection of kidney and cardiovascular disease including pulmonary hypertension, heart failure, and atherosclerotic disease in patients with chronic kidney disease. 

Parikh

Kishan S Parikh

Adjunct Associate in the Department of Medicine

Duke University Medical Center
Duke Clinical Research Institute

Rajagopal

Sudarshan Rajagopal

Associate Professor of Medicine

I am a physician-scientist with a research focus on G protein-coupled receptor signaling in inflammation and vascular disease and a clinical focus on pulmonary vascular disease, as I serve as Co-Director of the Duke Pulmonary Vascular Disease Center. My research spans the spectrum from clinical research in pulmonary vascular disease, to translational research in cardiovascular disease, to the basic science of receptor signaling. 

Our basic science resesarch focuses on understanding and untapping the signaling potential of G protein-coupled receptors (GPCRs) to regulate inflammation in vascular disease. GPCRs are the most common transmembrane receptors in the human genome (over 800 members) and are some of the most successful targets for drug therapies. While it has been known for some time that these receptors signal through multiple downstream effectors (such as heterotrimeric G proteins and multifunctional beta arrestin adapter proteins), over the past decade it has been better appreciated that these receptors are capable of signaling with different efficacies to these effectors, a phenomenon referred to as “biased agonism”. Ligands can be biased, by activating different pathways from one another, and receptors can be biased, by signaling to a limited number of pathways that are normally available to them. Moreover, this phenomenon also appears to be common to other transmembrane and nuclear receptors. While a growing number of biased agonists acting at multiple receptors have been identified, there is still little known regarding the mechanisms underlying biased signaling and its physiologic impact.

Much of our research focuses on the chemokine system, which consists of approximately twenty receptors and fifty ligands that display considerable promiscuity with each other in the regulation of immune cell function in inflammatory diseases. Research from our group and others have shown that many of these ligands act as biased agonists when signaling through the same receptor. We use models of inflammation such as contact hypersensitivity and pulmonary arterial hypertension (PAH). PAH is a disease of the pulmonary arterioles that results in right heart failure and most of its treatments target signaling by GPCRs. We use multiple approaches to probe these signaling mechanisms, including in-house pharmacological assays, advanced phosphoproteomics and single cell RNA sequencing.

Abraham

Dennis M Abraham

Assistant Professor of Medicine
Sparks

Matthew A. Sparks

Associate Professor of Medicine

I serve as the Program Director for the Nephrology Fellowship Program. My goal is to work with each fellow to ensure they develop a successful career in whatever direction they choose. I am the lead for the newly established Society for Early Education Scholars (SEEDS) in the Department of Medicine. The SEEDS Program is a year-long mentored education program designed for fellows planning careers as clinician educators or education scholars.

Nephrology Fellowship Program

My interest is in finding ways to promote medical education. My focus is on leveraging social media to enhance learning in nephrology. I serve as the associate director for the Nephrology Social Media Collective (NSMC) internship and member of the board of directors of nephrology journal club (NephJC), a non-profit organization dedicated to enhancing free online medical education in nephrology. I am also co-founder and advisory board member of the first nephrology blog associated with a journal- AJKD blog, the official blog of the American Journal of Kidney Diseases. Co-creator of the popular educational project NephMadness. Past deputy editor of Renal Fellow Network where I continue to remain as faculty lead. I am currently a member of the Nephrology Board of the American Board of Internal Medicine, the Scientific and Clinical Education Lifelong learning Committee Chair, Kidney in Cardiovascular Disease Council of the American Heart Association and am a fellow of the American Society of Nephrology, the American Heart Association, and the National Kidney Foundation. 


Listen to my podcast "The Nephron Segment"

@Nephro_Sparks on X

Wolf

Myles Selig Wolf

Charles Johnson, M.D. Distinguished Professor of Medicine

The focus of my research is disordered mineral metabolism across the spectrum of chronic kidney disease, including dialysis, kidney transplantation and earlier stages.

My research has been published in leading general medicine and subspecialty journals, including the New England Journal of Medicine, JAMA, the Journal of Clinical Investigation, Circulation, Cell Metabolism, Journal of the American Society of Nephrology, and Kidney International, among others.

My primary contributions have been in the area of hormonal regulation of phosphate homeostasis. I have helped to characterize the physiological role of fibroblast growth factor 23 in health and in chronic kidney disease, and the impact of elevated fibroblast growth factor 23 levels on adverse clinical outcomes in patients with kidney disease.


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