Showing papers by "Gordon H. Williams published in 2021"

The Role of Thyroid in Renovascular Function: Independent Association of Serum TSH With Renal Plasma Flow

Abstract: Context There are well-established interactions between the thyroid and the kidney. Thyroid hypofunction is associated with reduced renal plasma flow and hypothyroidism is highly prevalent in chronic kidney disease; however, less is known about the thyroid-kidney axis in the euthyroid state. Objective To study the association of thyroid function with renovascular parameters in a well phenotyped cohort of euthyroid normotensive and hypertensive individuals. Design Cross sectional study, the HyperPATH Consortium. Setting Multi-center study in five US and European academic institutions. Participants 789 individuals aged 18-65 years with serum TSH 0.4-5.5 mIU/L. Subjects with uncontrolled or secondary hypertension or on medication affecting the hypothalamus-pituitary-thyroid axis were excluded. Interventions Hemodynamic parameters including renal plasma flow, thyroid function testing and the Thr92Ala deiodinase 2 polymorphism were assessed in the setting of liberal and restricted salt diet. Main outcome measures We searched for associations between thyroid function and renovascular parameters and accounted for confounding factors, such as older age, hypertension and diabetes. Results Serum TSH was inversely associated with renal plasma flow assessed in the setting of both liberal and restricted salt diets. This association remained significant and independent when accounting for confounding factors, whereas free thyroxine index (fTI) and the Thr92Ala polymorphism, associated with lower deiodinase 2 catalytic activity and disrupted thyroid hormone tissue availability, were not independently associated with renal plasma flow. Serum TSH remained an independent predictor of renal plasma flow on a liberal salt diet when the analysis was restricted to healthy young individuals. Conclusions Serum TSH levels, but not fTI nor the Thr92Ala deiodinase 2 polymorphism, were independently inversely associated with renal plasma flow in individuals of the HyperPATH Consortium. These findings suggest a direct interconnection of TSH and renovascular dynamics even with TSH within reference range, warranting further investigation.

Striatin genotype-based, mineralocorticoid receptor antagonist-driven clinical trial: study rationale and design.

Abstract: OBJECTIVES In human studies and genetically altered mouse studies, variants in the striatin gene (STRN) are associated with increased blood pressure (BP) and aldosterone on a liberal salt diet. This clinical trial is based on the presumed mechanism for striatin-associated HTN - increased aldosterone. It is designed to determine if participants with the STRN risk alleles will have a greater BP reduction on a liberal salt diet with a specific, mechanism-based therapy - a mineralocorticoid receptor antagonist, eplerenone - as compared with a nonspecific anti-hypertensive therapy - amlodipine. METHODS One hundred five hypertensive adults with the STRN risk alleles (SNP rs2540923 carriers or rs888083 homozygotes) will be enrolled in a 12-week, double-blind, dose-escalation, clinical trial. After a minimum 2-week washout period and baseline assessment of BP on a liberal salt diet, participants will be randomized to either daily eplerenone or amlodipine. Participants will take daily at-home BP recordings as a safety check. After 4 and 8 weeks of drug therapy, BP will be measured by the study team and medication will be increased, if needed, to achieve a participant goal BP of <140/90 mmHg.Anticipated results We anticipate that STRN risk allele carriers will demonstrate a greater reduction in BP with eplerenone and will require a lower dose of eplerenone to reach goal BP as compared with amlodipine. CONCLUSION This is a proof-of-concept clinical trial. Positive results support the feasibility of performing genetically-defined, mechanistically-driven trials in HTN. Clinically, it would suggest that genetic biomarkers can identify individuals highly responsive to specific treatment.

Predictors of home oxygen duration in chronic neonatal lung disease.

Abstract: AIMS In infants with chronic neonatal lung disease (CNLD), we aimed to identify predictors of home oxygen duration, predictors of discharge oxygen flow rates, and the association of oxygen flow rates with respiratory outcomes. METHODS Infants with CNLD requiring home oxygen in 2016 and 2017 were retrospectively reviewed. Hazard ratios (HR) were estimated from Cox proportional hazards regression models in the cohort. A multinomial logistic regression model examined the effects of maternal and infant variables on discharge oxygen flow rates. Kruskal-Wallis test with univariate linear regression and Fisher's exact test with binomial univariate logistic regression were used to examine associations between oxygen flow groups and post-discharge clinical variables. RESULTS One hundred and forty-nine infants were included. Median corrected gestational age (CGA) at oxygen cessation was 6.8 months (interquartile range, 4.4) with 87.2% of infants weaned by 12 months CGA. Shorter initial neonatal intensive care unit (NICU) stay predicted faster oxygen weaning at 9 months (HR, 0.99; 95% confidence interval [CI], 0.98-1.00, p = .02) and 12 months (HR, 0.99; 95% CI, 0.98-1.00, p = .02). Infants with hypercarbia at discharge or discharged from NICU at higher CGA had higher odds of requiring ≥ 200 ml/min relative to ≤ 125 ml/min oxygen. Infants discharged with > 250 ml/min oxygen were more likely to have a respiratory-related admission before 2 years chronological age. CONCLUSION Shorter initial NICU stay was the best predictor of earlier home oxygen cessation. At NICU discharge, infants with hypercarbia or a higher CGA may require more home oxygen and experience more respiratory-related hospital admission in the first 2 years of chronological age.

Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone

Abstract: Background In addition to its role on blood pressure, aldosterone (ALDO) also affects the hemostatic system leading to increased experimental thrombosis. Striatin is an intermediate in the rapid, n...