Uric Acid as a Potential Biomarker of Pulmonary Arterial Hypertension in Patients with Sickle Cell Disease

SummarySome biomarkers play important roles in the endothelial dysfunction of patients with pulmonary arterial hypertension (PAH), including nitric oxide (NO), endothelin‐1 (ET‐1), asymmetric dimethylarginine (ADMA), galectin‐3 (Gal‐3), B‐type natriuretic peptide (BNP), and uric acid (UA). However, studies on these biomarkers in pulmonary artery blood in congenital heart disease‐PAH (CHD‐PAH) and the effect of iloprost on the regulation of biomarkers are lacking. This study investigated potential CHD‐PAH biomarkers and their association with the severity of disease. The effect of iloprost on the regulation of these biomarkers was also studied. A total of 31 patients with CHD‐PAH were enrolled. Seven with positive effects of iloprost (the average reduction in mPAP 11.13±1.73 mm Hg) and 19 with negative effects of iloprost (the average reduction in mPAP 4.21±4.87 mm Hg; iloprost positive group [IPG] vs iloprost negative group [ING], P<.01) and five age‐matched controls were studied. The pulmonary artery blood sample was collected before and after inhaling iloprost, and the plasma concentrations of Gal‐3, ADMA, ET‐1, and NO were measured. A significant positive linear relationship was observed between mPAP and plasma ET‐1, BNP, ADMA, and UA levels in all patients with CHD‐PAH. ET‐1, ADMA, BNP, and UA levels had a significant linear relationship with mean pulmonary arterial pressure, which could be used to predict the severity of CHD‐PAH. ET‐1 might be a potential biomarker to pre‐evaluate the effect of iloprost on CHD‐PAH. Iloprost could affect the expression of Gal‐3 and, therefore, the process of fibrosis could be influenced by iloprost.

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“…Two studies reported that UA in patients with PAH than in healthy subjects, which was coherent with the present results.…”

Section: Discussionsupporting

confidence: 93%

Effect of iloprost on biomarkers in patients with congenital heart disease‐pulmonary arterial hypertension

Zheng

Long

et al. 2017

Clin Exp Pharma Physio

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“…Hyperuricemia in SCA patients has been associated with leg ulcers and pulmonary hypertension [24, 25]. In non-SCA pediatric and adult populations, hyperuricemia has been associated with a decrease in eGFR and progression to CKD [17, 39-41].…”

Section: Discussionmentioning

confidence: 99%

“…Hyperuricemia has been associated with hypertension and cardiovascular events in other diseases but, despite the high prevalence of hyperuricemia in SCA, the association of hyperuricemia and sickle cell nephropathy has not been explored [18, 19]. Hyperuricemia has been associated with leg ulcers and pulmonary hypertension in SCA [23-25]. …”

Section: Introductionmentioning

confidence: 99%

Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia

et al. 2017

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Background Patients with Sickle Cell Anemia (SCA) have an increased prevalence of nephropathy and mortality from chronic kidney disease (CKD). Methods We evaluated the association of hyperuricemia and nocturnal hypertension with lower estimated glomerular filtration rate (eGFR) by cystatin-C among patients 10-21 years old with HbSS or SB0 thalassemia during a non-acute clinic visit. eGFR was obtained in 83 participants, uric acid in 81, and 24 hour ambulatory blood pressure monitoring (ABPM) was performed in 44 participants. Vital signs, CBC, CMP, LDH, medications, and urine microalbumin/creatinine were measured. Hyperuricemia was defined as a uric acid level ≥5.5 mg/dL. Nocturnal hypertension was defined as >25 % of nocturnal readings >95th percentile according to norms established by the American Heart Association Statement on ABPM in children and adolescents. Results The mean eGFR was statistically significantly lower among patients with hyperuricemia than with normal uric acid levels (143 vs 161 mL/min/1.73m2, respectively). Fourteen of 44 (32 %) participants had systolic nocturnal hypertension and 12 of 44 (27 %) had diastolic nocturnal hypertension. The mean eGFR was statistically significantly lower among participants with nocturnal systolic and diastolic hypertension than normal nocturnal blood pressure. In a regression model, nocturnal hypertension and hyperuricemia were associated with a lower eGFR. Conclusion Two risk factors for CKD, nocturnal hypertension and hyperuricemia, were associated with lower eGFR in older children and adolescent patients with SCA, and warrant long-term studies of their association with progression to CKD in this population.

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“…The particular contributions of all these factors are yet to be established. However, some of them have been already reported as promising biomarkers associated with PAH (74, 111, 137, 145). It, therefore, follows that further validation of such biomarkers that could be routinely screened, at least in the PAH patient's family members or in high-risk patients, could help to identify this deadly disease at the early, curable stage.…”

Section: Vascular Damage and Inflammationmentioning

confidence: 99%

Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development

Rafikova

Ghouleh

Rafikov

2019

Antioxidants & Redox Signaling

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Significance: Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature characterized by the proliferation of all vascular wall cell types, including endothelial, smooth muscle, and fibroblasts. The disease rapidly advances into a form with extensive pulmonary vascular remodeling, leading to a rapid increase in pulmonary vascular resistance, which results in right heart failure. Recent Advances: Most current research in the PAH field has been focused on the late stage of the disease, largely due to an urgent need for patient treatment options in clinics. Further, the pathobiology of PAH is multifaceted in the advanced disease, and there has been promising recent progress in identifying various pathological pathways related to the late clinical picture. Critical Issues: Early stage PAH still requires additional attention from the scientific community, and although the survival of patients with early diagnosis is comparatively higher, the disease develops in patients asymptomatically, making it difficult to identify and treat early. Future Directions: There are several reasons to focus on the early stage of PAH. First, the complexity of late stage disease, owing to multiple pathways being activated in a complex system with intra-and intercellular signaling, leads to an unclear picture of the key contributors to the pathobiology. Second, an understanding of early pathophysiological events can increase the ability to identify PAH patients earlier than what is currently possible. Third, the prompt diagnosis of PAH would allow for the therapy to start earlier, which has proved to be a more successful strategy, and it ensures better survival in PAH patients. Antioxid. Redox Signal. 31, 933-953.

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Uric Acid as a Potential Biomarker of Pulmonary Arterial Hypertension in Patients with Sickle Cell Disease

Cited by 8 publications

References 21 publications

Effect of iloprost on biomarkers in patients with congenital heart disease‐pulmonary arterial hypertension

Effect of iloprost on biomarkers in patients with congenital heart disease‐pulmonary arterial hypertension

Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia

Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development

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