Research

We are dedicated to pursuing innovative kidney research, discovering new models, and applying technological advancements.

Recent publications highlight our commitment. 

Associations of Vitamin D-Binding Globulin and Bioavailable Vitamin D Concentrations with Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Robinson-Cohen C, Zelnick LR, Hoofnagle AN, Lutsey PL, Burke G, Michos ED Shea SJC, Tracy R, Siscovick DS, Psaty B, Kestenbaum Bde Boer IH

Chronic kidney disease (CKD) causes multiple interrelated disturbances in vitamin D metabolism, including impaired synthesis and catabolism. These disturbances are suspected to interfere with normal vascular functioning. We measured multiple interrelated vitamin D metabolites and vascular functions in 558 people awaiting arteriovenous fistula creation surgery.
Serum concentrations of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and bioavailable vitamin D were not associated with statistical or biologically meaningful differences in flow mediated or nitroglycerine mediated vasodilation. Vitamin D metabolites were also not associated with carotid-femoral or carotid-radial pulse wave velocity.
Despite compelling rationales for CKD related vitamin D disturbances to cause vascular disease, multiple serum markers of vitamin D metabolism were not associated with vascular functions in patients with late stage CKD. Current laboratory measurements of vitamin D are unlikely to provide useful information regarding vascular functions in this setting.

Nephrotic syndrome in pregnancy poses risks with both maternal and fetal complications

De Castro I, Easterling TR, Bansal N, Jefferson JA

This study shows that in pregnant women with nephrotic syndrome, the maternal and fetal complications are high, even in the absence of significant renal impairment or uncontrolled hypertension.

Persistent Gaps in Use of Advance Directives Among Nursing Home Residents Receiving Maintenance Dialysis

Kurella Tamura M, Liu S, Montez-Rath ME, O'Hare AM, Hall YN, Lorenz KA

Comparison between Different Measures of Body Fat with Kidney Function Decline and Incident CKD

Madero M, Katz R, Murphy R, Newman A, Patel K, Ix J, Peralta C, Satterfield S, Fried L, Shlipak M, Sarnak M

Over the past two decades the increase in the prevalence of chronic kidney disease (CKD) has paralleled the increase in the prevalence of obesity. Obesity as measured by BMI, has been associated with incident CKD and ESRD. The gold standard and most accurate assessment of subcutaneous, visceral and intermuscular adipose tissue is by computed tomography (CT) scan. The study by Madero and colleagues sought to evaluate whether adiposity assessed by CT was associated with kidney function decline and/or incident CKD and whether it provided a better measure of risk assessment than BMI and waist circumference (WC). Our group compared anthropometric CT and anthropometric measures of obesity with kidney outcomes in the Health Aging and Body Composition Study. The data consisted of 2,489 individuals with mean age 74 years. CKD developed in 17% of participants over a median follow-up of 9 years. Visceral fat, intermuscular fat, BMI, and waist circumference—but not subcutaneous fat—were all associated with kidney function decline and the development of CKD. However, our results demonstrated that CT measures of visceral adiposity do not appear superior to the conventional anthropometric measures of BMI and WC for incident CKD and kidney function decline prognosis assessment.  The results further confirm the link between obesity and CKD and obesity’s importance as an independent risk factor for CKD in elderly people. Future research should be directed to determine whether measures to treat obesity could have an impact on kidney outcomes.

Repression of Interstitial Identity in Nephron Progenitor Cells by Pax2 Establishes the Nephron-Interstitium Boundary during Kidney Development

Natalie Naiman, Kaoru Fujioka, Mari Fujino, M. Todd Valerius, S. Steven Potter, Andrew P. McMahon, Akio Kobayashi

During embryogenesis, multiple cell types are generated to establish the body plan. Although studies in the past revealed how different cell types are induced during development, molecular regulatory mechanisms to maintain different cell lineages are currently much less clear, including in the kidney. In the article in Developmental Cell, Naiman et al. showed that repression of interstitial cell identity in nephron progenitor cells by the Pax2 gene establishes the lineage boundary between the nephron parenchyma and renal interstitium throughout kidney development. Because direct reprogramming to create nephron parenchyma cells requires to overcome the lineage boundary segregating the nephron compartment from other cell lineages, the authors’ observations should ultimately lead to establish novel regenerative therapy by restoring new nephrons, eliminating the need for dialysis and kidney transplantation in patients with kidney disease in the future. 

The article is highlighted by the following perspective articles:

Sex Differences in Hospitalizations with Maintenance Hemodialysis

Adams SV, Rivara M, Streja E, Cheung AK, Arah OA, Kalantar-Zadeh K, Mehrotra R

Patients with end-stage kidney disease treated with hemodialysis in the United States are admitted, on average, twice every year and over 30% are readmitted within 30-days of discharge. This work using a nationally representative data shows for the first time that the risk for hospitalization and readmission within 30 days is greatest for younger women. This study helps identify a high-risk group of patients that may benefit from closer oversight and care. 

Choice of Hemodialysis Access in Older Adults: A Cost-Effectiveness Analysis

Hall RK, Myers ER, Rosas SE, O'Hare AM, Colón-Emeric CS

Among older adults, the cost-effectiveness of an arteriovenous fistula placed within the first month of dialysis diminishes with increasing age and lower life expectancy and is not the most cost-effective option for those with the most limited life expectancy.

Targeting Access to Kidney Care Via Telehealth: The VA Experience

Crowley ST, Belcher J, Choudhury D, Griffin C, Pichler R, Robey B, Rohatgi R, Mielcarek B

The Department of Veterans Affairs (VA) is the largest integrated health care system in the USA.  Part of the challenge for the VA is that Nephrologists only are located in large metropolitan areas.  For example, the area of VISN 20 (which includes the states of Washington, Oregon, Idaho and Alaska) only has Nephrologists in Seattle and Portland.  Renal Specialty Care for Veterans in rural communities, therefore can be challenging, given geographical barriers.   Many Veterans also have severe PTSD and avoid coming to large centers. 
The VA has therefore embraced the use of Telemedicine to overcome some of these barriers to care.  Some of the forms of Telemedicine nclude the use of e-consults that involve a review of the electronic medical record by a specialist.  The VA has also used a provider-to-provider form of Telemedicine that connect PCPs working in rural areas with Nephrologists.  Nephrologist meet with PCPs on a weekly basis using Video Conferencing to provide weekly CME lectures and to actively review cases submitted by the PCPs.  This case based learning has been shown to improve patient care, provider knowledge and patient satisfaction.  The Seattle based Nephrology Telemedicine program for the VA has been identified as one of the most successful renal telemedicine programs in the country. 

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD

Roshanravan B, Gamboa J, Wilund K

Reduced kidney function leads to the retention of uremic toxins, culminating in inflammation, oxidative stress, and insulin resistance promoting skeletal muscle dysfunction. Skeletal muscle serves as a debilitating target of chronic kidney disease (CKD) resulting in fatigue, weakness, and poor physical function. Left unabated, skeletal muscle dysfunction can lead to loss of functional independence, mobility disability and further vulnerability to major disease complications. Impaired skeletal muscle metabolism is a sentinel pathologic event in the disablement process among patients with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disability process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability.

The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age

Sweetwyne MT, Pippin JW, Eng DG, Hudkins KL, Chiao YA, Campbell MD, Marcinek DJ, Alpers CE, Szeto HH, Rabinovitch PS, Shankland SJ

The mechanisms underlying the changes in the kidney are unknown, and any reversibility has not been adequately shown. This study shows that giving the mitochondrial stabilizing peptide SS-31 to very old mice reduced parietal epithelial cell activation, and improved podocyte and endothelial cell integrity. These studies also showed that under certain conditions, there is some reversibility to the aged kidney.

Diabetic Kidney Disease: Challenges, Progress, and Possibilities

Alicic RZ, Rooney MT, Tuttle KR

This is a state-of-the art review on the current status of diabetic kidney disease (DKD), the most common cause of chronic kidney disease worldwide. The global pandemic of obesity is driving unprecedented rates of diabetes, and consequently, diabetic complications including DKD. The paper takes the reader on a deep dive into epidemiology, risk factors, structural changes in the kidney, natural history, pathophysiology, diagnosis and treatment, as well as novel therapies and population-based approaches to DKD management. The call to action is clear – Transformative efforts, including advocacy with the patient voice, dissemination and implementation of best practices, and strategic research to improve clinically meaningful outcomes, are vital to reduce the devastating consequences of DKD.

Factors associated with maintenance of body mass index in the Jackson Heart Study: A prospective cohort study secondary analysis

Auerbach BJ, Katz R, Tucker K, Boyko EJ, Drewnowski A, Bertoni A, Dubbert P, Hickson DA, Correa A, Young BA

The purpose of the study was to compare the association of diet quality, physical activity, and environmental factors with body mass index (BMI) maintenance in African American adults. The study looked at 4401 participants from the Jackson Heart Study, a prospective cohort study based in Jackson, Mississippi.. The outcome measured was weight loss or weight maintenance over a mean of 5 years. During this time, 63% of participants lost or maintained weight; 37% gained weight. An ideal diet quality was associated with increased likelihood of BMI maintenance; living in an unsafe environment was associated with lower likelihood of BMI maintenance. A poor food environment and physical activity were not associated with BMI maintenance. Diet was associated with BMI maintenance whereas exercise was not in black adults in Mississippi.