Our faculty research broadens the knowledge of kidney disease.

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.

Strategies to Improve Patient Engagement in Young Kidney Transplant Recipients: A Review.

Richards VL, Johnson CK, Blosser CD, Sibulesky L.

Young adult and adolescent kidney transplant recipients have shorter graft survival than older and younger recipients. Although multifactorial, the tendency toward premature graft loss in young kidney transplant recipients has often been attributed to medication nonadherence and the transition from pediatric to adult care.

Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

Cassianne Robinson-Cohen, Traci M. Bartz, Dongbing Lai, T. Alp Ikizler, Munro Peacock, Erik A. Imel, Erin D. Michos, Tatiana M. Foroud, Kristina Akesson, Kent D. Taylor, Linnea Malmgren, Kunihiro Matsushita, Maria Nethander, Joel Eriksson, Claes Ohlsson, Daniel Mellström, Myles Wolf, Osten Ljunggren, Fiona McGuigan, Jerome I. Rotter, Magnus Karlsson, Michael J. Econs, Joachim H. Ix, Pamela L. Lutsey, Bruce M. Psaty, Ian H. de Boer, Bryan R. Kestenbaum

Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.

Chronic kidney disease attenuates the plasma metabolome response to insulin

Roshanravan B, Zelnick LR, Djucovic D, Gu H, Alvarez JA, Ziegler TR, Gamboa JL, Utzschneider K, Kestenbaum B, Himmelfarb J, Kahn SE, Raftery D, de Boer IH

Chronic kidney disease (CKD) leads to decreased sensitivity to the metabolic effects of insulin, contributing to protein energy wasting and muscle atrophy. Targeted metabolomics profiling during hyperinsulinemic-euglycemic insulin clamp testing may help identify aberrant metabolic pathways contributing to insulin resistance in CKD.

Young Kidney Professionals' Perspectives and Attitudes about Consuming Scientific Information: A Focus Group Study

Tong A, Crews DC, Schell JO, de Boer IH, Chonchol M, Mehrotra R

The digital era has seen rapid changes in how information is consumed. Traditional dissemination of scholarly work through biomedical journals may not be optimally tailored to the preferences of younger clinicians and researchers. We aimed to describe the perspectives of young clinicians and researchers in kidney disease on consuming scientific information. Three focus groups were conducted during the 2017 American Society of Nephrology Kidney Week with a total of 29 nephrologists and researchers (ages 40 years old and younger) purposively sampled through our networks and the American Society of Nephrology registration database. Data were analyzed thematically.

Complications of Immunosuppression in Glomerular Disease

This review describes the side effects of immunosuppressive agents used in recent randomized, controlled trials of glomerular disease, and highlights some of the key adverse events that determine the choice and prescription of these medications.