Pulmonary Hypertension Subtypes and Mortality in CKD.
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2019-11-12
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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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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
Daniel Len Edmonston
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.
Kishan S Parikh
Duke University Medical Center
Duke Clinical Research Institute
Sudarshan Rajagopal
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.
Dennis M Abraham
Matthew A. Sparks
Nephrology Fellowship Program & Medical Education Leadership
I serve as the Program Director for the Nephrology Fellowship Program, where my primary goal is to support each fellow in building a successful and fulfilling career—whether in clinical practice, research, education, or advocacy. I am also the lead for the Society for Early Education Scholars (SEEDS) within the Department of Medicine. SEEDS is a year-long, mentored education program designed for fellows pursuing careers as clinician educators or education scholars.
My passion lies in advancing medical education, particularly in nephrology. I am the co-founder and advisory board member of the AJKD Blog, the first nephrology blog affiliated with a major journal—the American Journal of Kidney Diseases. I co-created NephMadness, a widely recognized and innovative educational initiative. I previously served as deputy editor of the Renal Fellow Network, where I remain actively involved as faculty lead.
I am also a member of the Board of Directors of NephJC, a nonprofit organization that champions free, open-access medical education in nephrology. Nationally, I serve on the Nephrology Board of the American Board of Internal Medicine, past chair of the Scientific and Clinical Education Lifelong Learning Committee of the American Heart Association’s Kidney in Cardiovascular Disease Council, and am a Fellow of the American Society of Nephrology (ASN), American Heart Association (AHA), and National Kidney Foundation (NKF). I serve as advisory board member and associate director of NephSIM Nephrons virtual mentorship program for trainees interested in nephrology.
Additionally, I serve as the Director of Communication for the ASN Portfolio of Journals, including JASN, CJASN, and Kidney360.
Past Research
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Hypertension and Kidney Hemodynamics: My past research delved into the mechanisms of blood pressure regulation, focusing on the renin-angiotensin system and prostanoid pathways. Utilizing genetically modified mouse models, you investigate how alterations in renal microcirculation influence sodium excretion and blood pressure, aiming to identify novel therapeutic targets for hypertension.
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SGLT2 Inhibitors and Kidney Disease: I have contributed to understanding the pathophysiology of kidney diseases and the mechanisms of action of SGLT2 inhibitors, highlighting their role in managing chronic kidney disease and associated cardiovascular risk.
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My clinical interests are glomerular diseases- particularly IgA nephropathy, membranous nephropathy, C3 glomerulopathy, and lupus nephritis.
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I also have expertise in genetic kidney diseases, ADPKD, quality improvement in outpatient nephrology, and CKRT in the ICU.
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I serve as the director of the Duke Nephrology Fellow Clinic
Awards and Honors
- Excellence in Education Award, Duke Department of Medicine, 2016
- Young Physician-Scientist Award, American Society for Clinical Investigation (ASCI), 2017
- Midcareer Distinguished Educator Award, American Society of Nephrology (ASN), 2022
Listen to my podcasts:
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The Nephron Segment
Connect with me on BlueSky: @NephroSparks
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