Our faculty research broadens the knowledge of kidney disease.

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.

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

Pavan K. Bhatraju, Leila R. Zelnick, Michael Shlipak, Ronit KatzBryan Kestenbaum

TNF receptor-1 (TNFR-1), which plays a causative role in endothelial cell dysfunction and inflammation, is expressed on the cell surface in glomerular and peritubular capillary endothelium of the kidneys. 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.

Vitamin D and OmegA-3 TriaL to prevent and treat diabetic kidney disease: Rationale, design, and baseline characteristics

de Boer IH, Zelnick LR, Lin J, Schaumberg D, Wang L, Ruzinski J, Friedenberg G, Duszlak J, Bubes VY, Hoofnagle AN, Thadhani R, Glynn RJ, Buring JE, Sesso H, Manson JE.

Diabetic kidney disease (DKD), defined as reduced glomerular filtration rate (GFR), elevated urine albumin excretion, or both that is clinically attributable to diabetes, is a common and morbid diabetes complication. Animal-experimental data, observational human studies, and short-term clinical trials suggest that vitamin D and omega-3 fatty acid supplements may be safe and inexpensive interventions to reduce the incidence and progression of DKD.