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Role Of Dietary Components In Modulating Hypertension, Andrew Feyh, Lucas Bracero, Hari Vishal Lakhani, Prasanna Santhanam, Joseph I. Shapiro Md, Zeid Khitan Md, Komal Sodhi

Joseph I Shapiro MD

Hypertension is a major health issue, particularly in medically underserved populations that may suffer from poor health literacy, poverty, and limited access to healthcare resources. Management of the disease reduces the risk of adverse outcomes, such as cardiovascular or cerebrovascular events, vision impairment due to retinal damage, and renal failure. In addition to pharmacological therapy, lifestyle modifications such as diet and exercise are effective in managing hypertension. Current diet guidelines include the DASH diet, a low-fat and low-sodium diet that encourages high consumption of fruits and vegetables. While the diet is effective in controlling hypertension, adherence to the diet is …

Attenuation Of Na/K-Atpase Mediated Oxidant Amplification With Pnaktide Ameliorates Experimental Uremic Cardiomyopathy, Jiang Liu, Jiang Tian, Muhammad Chaudhry, Kyle Maxwell, Yanling Yan, Xiaoliang Wang, Preeya T. Shah, Asad A. Khawaja, Rebecca Martin, Tylor J. Robinette, Adee El-Hamdani, Michael W. Dodrill, Komal Sodhi, Christopher A. Drummond, Steven T. Haller, David J. Keenedy, Nader G. Abraham, Zijian Xie, Joseph I. Shapiro Md

Joseph I Shapiro MD

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic …

Rapamycin Attenuates Cardiac Fibrosis In Experimental Uremic Cardiomyopathy By Reducing Marinobufagenin Levels And Inhibiting Downstream Pro-Fibrotic Signaling, Steven T. Haller Phd, Yanling Yan Phd, Christopher A. Drummond Phd, Joe Xie Md, Jiang Tian Phd, David J. Kennedy Phd, Victoria Y. Shilova Phd, Zijian Xie Phd, Jiang Liu Phd, Christopher J. Cooper Md, Deepak Malhotra Md, Phd, Joseph I. Shapiro Md, Olga V. Fedorova Phd, Alexei Y. Bagrov Md, Phd

Joseph I Shapiro MD

Background: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K‐ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K‐ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

Methods and Results: Biosynthesis of MBG by cultured human JEG‐3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 …

Cigarette Smoking And Cardio-Renal Events In Patients With Atherosclerotic Renal Artery Stenosis, Christopher A. Drummond, Pamela S. Brewster, Wencan He, Kaili Ren, Yanmei Xie, Katherine R. Tuttle, Steven T. Haller, Kenneth Jamerson, Lance D. Dworkin, Donald E. Cutlip, Timothy P. Murphy, Ralph B. D'Agostino Sr., William L. Henrich, Jiang Tian, Joseph I. Shapiro Md, Christopher J. Cooper

Joseph I Shapiro MD

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001). In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD). Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days) at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001). Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01) whereas creatinine and estimated glomerular filtration rate (eGFR) were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

The Trade-Off Between Dietary Salt And Cardiovascular Disease; A Role For Na/K-Atpase Signaling?, Joe X. Xie, Anna Pearl Shapiro, Joseph I. Shapiro Md

Joseph I Shapiro MD

It has been postulated for some time that endogenous digitalis-like substances, also called cardiotonic steroids (CTS), exist, and that these substances are involved in sodium handling. Within the past 20 years, these substances have been unequivocally identified and measurements of circulating and tissue concentrations have been made. More recently, it has been identified that CTS also mediate signal transduction through the Na/K-ATPase, and consequently been implicated in profibrotic pathways. This review will discuss the mechanism of CTS in renal sodium handling and a potential “trade-off” effect from their role in inducing tissue fibrosis.

Carbonylationmodificationregulatesna/K-Atpasesignalingandsaltsensitivity:Areviewandahypothesis, Preeya Shah Phd, Rebecca Martin, Yanling Yan, Joseph I. Shapiro Md, Jiang Liu

Joseph I Shapiro MD

Na/K-ATPase signaling has been implicated in different physiological and pathophysiological conditions. Accumulating evidence indicates that oxidative stress not only regulates the Na/K-ATPase enzymatic activity, but also regulates its signaling and other functions. While cardiotonic steroids (CTS)-induced increase in reactive oxygen species (ROS) generation is an intermediate step in CTS-mediated Na/K-ATPase signaling, increase in ROS alone also stimulates Na/K-ATPase signaling. Based on literature and our observations, we hypothesize that ROS have biphasic effects on Na/K-ATPase signaling, transcellular sodium transport, and urinary sodium excretion. Oxidative modulation, in particular site specific carbonylation of the Na/K-ATPase α1 subunit, is a critical step in proximal …

Systematic Review Of Metabolic Syndrome Biomarkers: A Panel For Early Detection, Management, And Risk Stratification In The West Virginian Population, Krithika Srikanthan, Andrew Feyh, Haresh Visweshwar, Joseph I. Shapiro Md, Komal Sodhi

Joseph I Shapiro MD

Introduction: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic …

Management Of Severe Hyponatremia: Infusion Of Hypertonic Saline And Desmopressin Or Infusion Of Vasopressin Inhibitors?, Antonios H. Tzamaloukas Md, Joseph I. Shapiro Md, Dominic S. Raj Md, Glen H. Murata Md, Deepak Malhotra Md, Phd, Robert H. Glew Phd

Joseph I Shapiro MD

Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution …

Adiposity Predicts Pulse Pressure In Subjects With Chronic Kidney Disease: Data From The Modification Of Diet In Renal Disease, Preeya T. Shah Phd, Rebecca Martin, Juan R. Sanabria, Zeid Khitan Md, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro Md

Joseph I Shapiro MD

Obesity is a known risk factor for hypertension, but the mechanisms by which this occurs are still unclear. As the body mass index (BMI) is frequently used to define obesity, but the BMI does not distinguish between adipose and other tissues, we sought to develop another index of obesity. We decided to look at the ratio of BMI to urinary creatinine excretion as the latter measurement is believed to be an index of muscle mass. We used data from the modification of diet in renal disease (MDRD) study as urinary creatinine collections and blood pressure measurements were readily available in …

Effect Of Removing Outliers On Statistical Inference: Implications To Interpretation Of Experimental Data In Medical Research, Todd W. Gress, James Denvir, Joseph I. Shapiro

Joseph I Shapiro MD

Background Data editing with elimination of “outliers” is commonly performed in the biomedical sciences. The effects of this type of data editing could influence study results, and with the vast and expanding amount of research in medicine, this effect would be magnified. Methods and Results We first performed an anonymous survey of medical school faculty at institutions across the United States and found that indeed some form of outlier exclusion was performed by a large percentage of the respondents to the survey. We next performed Monte Carlo simulations of excluding high and low values from samplings from the same normal …