Our faculty research broadens the knowledge of kidney disease.

GLP-1 Receptor Agonists in Diabetic Kidney Disease: from the Patient-Side to the Bench-Side

Dieter BP, Alicic RZ, Tuttle KR

Diabetic kidney disease (DKD), one of the most common and severe microvascular complications of diabetes, is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. This perspective summarizes clinical and experimental observations to give insight into biological mechanisms beyond glycemic control, such as natriuresis and anti-inflammatory actions, for preservation of kidney function in patients with diabetes.

Relation of multi-marker panel to incident chronic kidney disease and rapid kidney function decline in African Americans: the Jackson Heart Study

Mwasongwe SE, Young B, Bidulescu A, Sims M, Correa A, Musani SK

Few investigations have evaluated the incremental usefulness of multiple biomarkers representing varying physiological pathways for predicting risk of renal outcomes in African Americans. We related a multi-marker panel to incident chronic kidney disease (CKD) and rapid kidney function decline (RKFD) in 2813 Jackson Heart Study participants without prevalent CKD at exam 1 (2000-2004) and with complete assays at exam 1 for 9 biomarkers: adiponectin, aldosterone, B-natriuretic peptide [BNP], cortisol, high sensitivity C-reactive protein (hsCRP), endothelin, homocysteine, plasma renin activity and mass.

Identification of Acute Kidney Injury Sub-phenotypes with Differing Molecular Signatures and Response to Vasopressin Therapy

Bhatraju PK, Zelnick LR, Herting J, Katz R, Mikacenic C, Kosamo S, Morrell ED, Robinson-Cohen C, Calfee CS, Christie JD, Liu KD, Matthay MA, Hahn WO, Dmyterko V, Slivinski NSJ, Russell JA, Walley KR, Christiani DC, Liles WC, Himmelfarb J, Wurfel MM

The aim of this study was to identify and test whether AKI sub-phenotypes have prognostic and therapeutic implications.

Association of Soluble TNFR-1 Concentrations with Long-Term Decline in Kidney Function: The Multi-Ethnic Study of Atherosclerosis

Bhatraju PK, Zelnick LR, Shlipak M, Katz R, Kestenbaum B

Higher soluble TNF receptor-1 (sTNFR-1) concentrations are associated with kidney disease progression among persons with established diabetic kidney disease. However, no studies have assessed sTNFR-1's role in long-term kidney function changes in a multiethnic population without cardiovascular disease at baseline.

Treatment of Hyponatremia in End-Stage Liver Disease: New Tools in the Shed

In a retrospective cohort of hospitalized patients with cirrhosis, the administration of intravenous albumin was associated with a higher rate of hyponatremia resolution and better 30-day survival. We are excited by this study because the data supports what we have long observed to be true—that albumin has an important role to play in mitigating a number of the pathophysiological underpinnings of hyponatremia in patients with cirrhosis.

Automated quantification of bioluminescence images

Alexander D. Klose, Neal Paragas 

We developed a computer-aided analysis tool for quantitatively determining bioluminescent reporter distributions inside small animals. The core innovations are a body-fitting animal shuttle and a statistical mouse atlas, both of which are spatially aligned and scaled according to the animal’s weight, and hence provide data congruency across animals of varying size and pose.

Prediction of Arteriovenous Fistula Clinical Maturation from Postoperative Ultrasound Measurements: Findings from the Hemodialysis Fistula Maturation Study

Michelle L. Robbin, Tom Greene, Michael Allon, Laura M. Dember, Peter B. Imrey, Alfred K. Cheung, Jonathan Himmelfarb, Thomas S. Huber, James S. Kaufman, Milena K. Radeva, Prabir Roy-Chaudhury, Yan-Ting Shiu, Miguel A. Vazquez, Heidi R. Umphrey, Lauren Alexander, Carl Abts, Gerald J. Beck, John W. Kusek, Harold I. Feldman and the Hemodialysis Fistula Maturation Study Group

The utility of early postoperative ultrasound measurements in predicting arteriovenous fistula (AVF) clinical maturation is uncertain. We investigated the relationships of ultrasound parameters with AVF clinical maturation in newly created AVF, measured at 1 day and 2 and 6 weeks, in 602 participants of a multicenter, observational cohort study.

Kidneys on Chips: Emerging Technology for Preclinical Drug Development

Catherine K. Yeung, Jonathan Himmelfarb

Only approximately 12% of drug candidates in clinical trials will reach the market due to unpredicted liabilities in pharmacokinetics, pharmacodynamics, efficacy, and toxicity (1). Novel techniques, including organs-on-chips, are critical to accelerate drug development and better predict drug disposition and toxicity. Currently, a major focus of research is the creation of physiologic models of the proximal tubule, the primary site in the nephron for drug clearance and a primary target cell for drug-induced nephrotoxicity.

Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function

Xu J, Bartz TM, Chittoor G, Eiriksdottir G, Manichaikul AW, Sun F, Terzikhan N, Zhou X, Booth SL, Brusselle GG, de Boer IH, Fornage M, Frazier-Wood AC, Graff M, Gudnason V, Harris TB, Hofman A, Hou R, Houston DK, Jacobs DR, Kritchevsky SB, Latourelle J, Lemaitre RN, Lutsey PL, O'Connor G, Oelsner EC, Pankow JS, Psaty BM, Rohde RR, Rich SS, Rotter JI, Smith LJ, Stricker BH, Voruganti VS, Wang TJ, Zillikens MC, Barr RG, Dupuis J, Gharib SA, Lahousse L, London SJ, North KE, Smith AV, Steffen LM, Hancock DB, Cassano PA

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested.

Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension: The Multi-Ethnic Study of Atherosclerosis

Akhabue E, Vu TT, Vaidya A, Michos ED, de Boer IH, Kestenbaum B, Allison M, Szklo M, Ouyang P, Yancy CW, Wolf M, Isakova T, Carnethon MR.

Higher Fibroblast Growth Factor-23 (FGF23) concentrations have been found to be associated with incident heart failure (HF). Experimental data suggest FGF23 directly stimulates myocardial hypertrophy. FGF23 may also enhance renin-angiotensin-aldosterone system activity. Whether FGF23 is associated with increased HF risk in populations with hypertension and whether this association is weaker in the presence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy is unknown.