Nephrology Commons^™

Employing Multi-Omics Analyses To Understand Changes During Kidney Development In Perinatal Interleukin-6 Animal Model, Ganesh Panzade, Tarak Srivastava, Daniel P. Heruth, Mohammad H. Rezaiekhaligh, Jianping Zhou, Zhen Lyu, Mukut Sharma, Trupti Joshi

Biomedical Sciences

Chronic kidney disease (CKD) is a leading cause of morbidity and mortality globally. Maternal obesity during pregnancy is linked to systemic inflammation and elevated levels of the proinflammatory cytokine interleukin-6 (IL-6). In our previous work, we demonstrated that increased maternal IL-6 during gestation impacts intrauterine development in mice. We hypothesized that IL-6-induced inflammation alters gene expression in the developing fetus. To test this, pregnant mice were administered IL-6 or saline during mid-gestation. Newborn mouse kidneys were analyzed using mRNA-seq, miRNA-seq and whole-genome bisulfite-seq (WGBS). A multi-omics approach was employed to quantify mRNA gene expression, miRNA expression and DNA methylation, using …

A Case Of Occlusive Myocardial Infarction Caused By Nephrotic Syndrome In A 26-Year-Old Type 1 Diabetic, Kyle Admire, Charlotta Jornlid, Chelsea Ryan, Rebecca Pauly

Marshall Journal of Medicine

Nephrotic syndrome is a rare condition distinguished by proteinuria exceeding 3g per day. Other associated characteristics include hematuria, hypoalbuminemia, edema, and hyperlipidemia. There is an array of complications of this syndrome, which are primarily due to the profound losses of protein in the urine. One such complication is thromboembolism, with most documented cases in the form of venous thromboembolism of the extremities which is in part due to urinary loss of antithrombin III and increased synthesis of prothrombotic factors. There are limited available data regarding arterial thrombi and especially few reports about coronary thromboses, which can be life-threatening. In this …

Management Of Asymptomatic Hypertension In The Inpatient Setting., Charles Meadows, Mehiar Elhamdani, Dial Larry, Murad Kheetan, Khaled Al-Baqain

Marshall Journal of Medicine

Hypertension is common in hospitalized patients and is most often asymptomatic. While there are no guidelines for management of such patients, aggressive blood pressure treatment, including the use of intravenous antihypertensives, is often undertaken. While evidence of benefit is lacking, emerging data suggest that treatment of asymptomatic hypertension in the inpatient setting is associated with adverse outcomes, including acute kidney injury and ischemic stroke. In addition, the intensification of a preexisting antihypertensive regimen at hospital discharge significantly increases the risk of readmission without significant improvement in outpatient hypertension control. Such a combination of a common problem with the demonstrable benefit …

Glomerular Biomechanical Stress And Lipid Mediators During Cellular Changes Leading To Chronic Kidney Disease, Mukut Sharma, Vikas Singh, Ram Sharma, Arnav Koul, Ellen T. Mccarthy, Virginia J. Savin, Trupti Joshi, Tarak Srivastava

Biomedical Sciences

Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their …

Predicting Adverse Outcomes In End Stage Renal Disease: Machine Learning Applied To The United States Renal Data System, Zeid Khitan, Alexis D. Jacob, Courtney Balentine, Adam N. Jacob, Juan R. Sanabria, Joseph I. Shapiro

Marshall Journal of Medicine

We examined machine learning methods to predict death within six months using data derived from the United States Renal Data System (USRDS). We specifically evaluated a generalized linear model, a support vector machine, a decision tree and a random forest evaluated within the context of K-10 fold validation using the CARET package available within the open source architecture R program. We compared these models with the feed forward neural network strategy that we previously reported on with this data set.

Urinothorax Caused By Xanthogranulomatous Pyelonephritis, Waiel Abusnina, Hazim Bukamur, Zeynep C. Koc

Internal Medicine

Xanthogranulomatous pyelonephritis is a rare form of chronic pyelonephritis that generally afflicts middle-aged women with a history of recurrent urinary tract infections. Its pathogenesis generally involves calculus obstructive uropathy and its histopathology is characterized by replacement of the renal parenchyma with lipid filled macrophages. This often manifests as an enlarged, nonfunctioning kidney that may be complicated by abscess or fistula. This case details the first reported case of xanthogranulomatous pyelonephritis complicated by urinothorax, which resolved on follow-up chest X-ray after robot-assisted nephrectomy.

Predicting Adverse Outcomes In Chronic Kidney Disease Using Machine Learning Methods: Data From The Modification Of Diet In Renal Disease, Zeid Khitan, Anna P. Shapiro, Preeya T. Shah, Juan R. Sanabria, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro

Marshall Journal of Medicine

Background: Understanding factors which predict progression of renal failure is of great interest to clinicians.

Objectives: We examined machine learning methods to predict the composite outcome of death, dialysis or doubling of serum creatinine using the modification of diet in renal disease (MDRD) data set.

Methods: We specifically evaluated a generalized linear model, a support vector machine, a decision tree, a feed-forward neural network and a random forest evaluated within the context of 10 fold validation using the CARET package available within the open source architecture R program.

Results: We found that using clinical parameters available at entry into the …

Mrsa Induced Pulmonary-Renal Syndrome, Mohammed Megri, Majdi Al-Dliw, Yousef Shweihat, Zeid Khitan

Internal Medicine

We present a rare case of pulmonary-renal syndrome secondary to recurrent MRSA spondylodiscitis. The mechanism of involvement of each organ system is unique. The organs, lung and kidneys, have been affected by different pathologic processes that were induced, we think, by the chronic MRSA infection.

Chronic Kidney Disease And Acute Myocardial Infarction: The Story After 1 Year, Paulette S. Wehner, William A. Nitardy

Internal Medicine

When chronic kidney disease (CKD) is part of the clinical history for a patient with acute myocardial infarction, the interventional cardiologist experiences an increased anxiety level. An acute myocardial infarction with renal disease requires more attention to dye load and fluid status, and general opinion exists regarding the negative outcomes of these “sicker” patients.

Mark Navarro and colleagues completed a thorough study from a different angle. We know the interventionalists’ concerns are justified acutely as these CKD patients have a higher level of inpatient complications, but these authors chose to look at the patients 1 year from their event to …

Use Of Surface-Enhanced Laser Desorption/Ionization With Time Of Flight (Seldi-Tof) Of The Urine In The Assessment Of Acute Kidney Injury (Aki), David J. Kennedy, Phd, Joseph M. Chan, Dinkar Kaw, Md, Anand M. Ravindaran, Md, Shobha Ratnam, Md, Phd, Deepak Malhotra, Md, Phd, Joseph I. Shapiro Md

Marshall Journal of Medicine

Background: Urinalysis is an important component in the assessment of acute kidney injury (AKI). Proteonomics is a rapidly developing approach in the analysis of physiological states. Several techniques have been developed to screen for protein populations. In this regard SELDI-TOF is a technique based on mass spectroscopy that is being utilized in proteonomics research.

Methods:For this study, clean catch or catheterized urine was collected from normals (n=18) and patients referred to the renal service with AKI. Based upon urine and serum chemistries, clinical parameters, and microscopic urinalysis, the urines were separated into those consistent with prerenal azotemia (n=17) and acute …

Why Does Obesity Lead To Hypertension? Further Lessons From The Intersalt Study., Preeya T. Shah, Anna P. Shapiro, Zeid Khitan Md, Prasanna Santhanam Md, Joseph I. Shapiro Md

Marshall Journal of Medicine

Objectives

To analyze correlations between major determinants of blood pressure (BP), in efforts to generate and compare predictive models that explain for variance in systolic, diastolic, and mean BP amongst participants of the Intersalt study.

Methods

Data from the Intersalt study, consisting of nearly 10,000 subjects from 32 different countries, were reviewed and analyzed. Published mean values of 24 hour urinary electrolyte excretion (Na+, K+), 24 hour urine creatinine excretion, body mass index (BMI, kg/m^2), and blood pressure data were extracted and imported into Matlab™ for stepwise linear regression analysis.

Results

As shown earlier, strong correlations between urinary sodium excretion …

Alkali Therapy In Lactic Acidosis, Zeid J. Khitan, Md, Deepak Malhotra, Md, Dominic S. Raj, Md, Antonios H. Tzamaloukas, Md, Joseph I. Shapiro, Md

Marshall Journal of Medicine

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

Elevated Serum Bicarbonate Concentration In Chronic Kidney Disease: A Call To Find The Cause, Zeid J. Khitan

Internal Medicine

In this issue, Dobre et al1 reported an observational study looking at results of annually measured serum bicarbonate concentration in participants with chronic kidney disease (CKD) enrolled in the Chronic Renal Insufficiency Cohort (CRIC) using the marginal structural model, a validated statistical method,2 to estimate the cumulative effect over the period of the study and their effects on adjudicated heart failure events, atherosclerotic events, renal disease progression, and mortality. In their analysis, they included patients aged 21 to 74 years with estimated glomerular filtration rate of 20 to 70 mL/min per 1.73 m2 and excluded patients with NYHA Class III/IV …

Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher A. Drummond, George Buddny, Steven T. Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph I. Shapiro Md, Jiang Tian

Biochemistry and Microbiology

Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed …

Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson

Theses, Dissertations and Capstones

Glucuronidation is primarily a pathway of detoxification in most species, but many glucuronide conjugates are associated with toxicity. Numerous drugs are excreted in the urine as glucuronide conjugates. Being organic anions, it is likely that glucuronides are secreted into the urine by organic anion transporters found in renal proximal tubule cells (PTCs). Some drugs that are metabolized by glucuronidation have been shown to cause renal toxicity, yet little is known about the renal handling of glucuronide conjugates. It is hypothesized that glucuronides are transported into renal PTCs by an organic anion transporter (OAT) on the basolateral membrane of the cell. …

Renal Basolateral Transport Of Glucuronides And Other Organic Anions In Rat In Vitro Models, Sarah L. Miles

Theses, Dissertations and Capstones

Glucuronidation is a common Phase II biotransformation reaction that increases the hydrophilicity, and thus elimination, of toxins, xenobiotics, and endogenous compounds. Previous studies suggest that the kidney can secrete glucuronide conjugates, but the renal transport mechanisms for glucuronide secretion have not been determined. Based on the chemical nature of glucuronide metabolites, it is hypothesized that organic anion transporter (OAT) proteins along the basolateral membrane of the renal proximal tubule promote renal accumulation of glucuronide conjugates. The purpose of this study was to develop a rat renal proximal tubule model which demonstrates OAT activity and by which the contribution of OAT …