Our faculty research broadens the knowledge of kidney disease.

Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis

Øvrehus, M.A.,  Bruheim, P.,  Ju, W.,  Zelnick, L.R.,  Langlo, K.A.,  Sharma, K.,  de Boer, I.H.,  Hallan, S.I.

Hypertensive nephrosclerosis is among the leading causes of end-stage renal disease, but its pathophysiology is poorly understood. We wanted to explore early metabolic changes using gene expression and targeted metabolomics analysis. We analyzed gene expression in kidneys biopsied from 20 patients with nephrosclerosis and 31 healthy controls with an Affymetrix array. Thirty-one amino acids were measured by liquid chromatography coupled with mass spectrometry (LC-MS) in urine samples from 62 patients with clinical hypertensive nephrosclerosis and 33 age- and sex-matched healthy controls, and major findings were confirmed in an independent cohort of 45 cases and 15 controls.

The Association of Kidney Function and Albuminuria With the Risk and Outcomes of Syncope: A Population-Based Cohort Study

Massicotte-Azarniouch, D.,  Kuwornu, J.P.,  McCallum, M.K.,  Bansal, N.,  Lam, N.,  Molnar, A.O.,  Pun, P.,  Zimmerman, D.,  Garg, A.X.,  Sood, M.M.

The risks and subsequent outcomes of syncope among seniors with chronic kidney disease (CKD) are unclear. We conducted a population-based retrospective cohort study of 272,146 patients ≥ 66 years old, in Ontario, Canada, from April 1, 2006, to March 31, 2016. Using administrative health care databases, we examined the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with incident syncope and the association of incident syncope with the composite outcome of myocardial infarction, stroke, and death by levels of eGFR/ACR, using adjusted Cox proportional hazards models.

Comparative Assessment of Utilization and Hospital Outcomes of Veterans Receiving VA and Non-VA Outpatient Dialysis

Wang V, Coffman CJ, Stechuchak KM, Berkowitz TSZ, Hebert PL, Edelman D, O'Hare AM, Weidenbacher HJ, Maciejewski ML

Growing demand for VA dialysis exceeds its supply and travel distances prohibit many Veterans from receiving dialysis in a VA facility, leading to increased use of dialysis from non-VA providers. This study compared utilization and hospitalization outcomes among Veterans receiving chronic dialysis in VA and non-VA settings in 2008-2013

IgA-dominant glomerulonephritis with a membranoproliferative pattern of injury

Nicole K. Andeen, J. Ashley Jefferson, Shreeram Akilesh, Charles E . Alpers, Mei Lin Bissonnette, Laura S.Finn, John Higgins, Donald C.Houghton, Neeraja Kambham, Alex Magil, Behzad Najafian MD, Roberto F. Nicosia, Megan L.Troxell, Kelly D.Smith

Immunoglobulin A (IgA)-dominant membranoproliferative glomerulonephritis (MPGN) is a descriptive term for renal biopsies in which differential diagnoses of unusual IgA nephropathy (IgAN), infection-related GN, or other etiologies are considered. We sought to understand clinical and pathologic features of this finding. Native kidney biopsies with IgA-dominant immune deposits and diffuse MPGN features without significant exudative features or subepithelial deposits were retrospectively reviewed.

Soluble ST2 and Galectin-3 and Progression of CKD

Mariam L. Alam, Ronit Katz, Keith A. Bellovich, Zeenat Y. Bhat, Frank C. Brosius, Ian H.de Boer, Crystal A.Gadegbeku, Debbie S. Gipson, Jennifer J. Hawkins, Jonathan Himmelfarb, Bryan R. Kestenbaum, Matthias Kretzler, Cassianne Robinson-Cohen, Susan P. Steigerwalt, CourtneyTuegel, Nisha Bansal

Cardiac biomarkers soluble ST2 (sST2) and galectin-3 may reflect cardiac inflammation and fibrosis. It is plausible that these mechanisms may also contribute to the progression of kidney disease. We examined associations of sST2 and galectin-3 with kidney function decline in participants with chronic kidney disease (CKD).

An Investigation of Selection Bias in Estimating Racial Disparity in Stroke Risk Factors: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Long DL, Howard G, Long DM, Judd S, Manly JJ, McClure LA, Wadley VG, Safford MM, Katz R, Glymour MM

Selection due to survival or attrition may bias estimates of racial disparities in health, but few studies quantify the likely magnitude of such bias. In a large national cohort with moderate loss to follow-up, we contrast racial differences in two stroke risk factors, incident hypertension and incident left ventricular hypertrophy estimated by complete case analyses, inverse probability of attrition weighting, and the Survivor Average Causal Effect.

Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial

Charytan DM, Himmelfarb J, Ikizler TA, Raj DS, Hsu JY, Landis JR, Anderson AH, Hung AM, Mehrotra R, Sharma S, Weiner DE, Williams M, DiCarli M, Skali H, Kimmel PL, Kliger AS, Dember LM

The safety and efficacy of spironolactone is uncertain in end-stage renal disease. We randomized 129 maintenance hemodialysis patients to placebo (n=51) or spironolactone 12.5 mg (n=27), 25 mg (n=26), or 50 mg (n=25) daily for 36 weeks in a double-blind, placebo-controlled, multiple dosage trial to assess safety, tolerability and feasibility and to explore cardiovascular efficacy.

Fostering Innovation in Symptom Management among Hemodialysis Patients: Paths Forward for Insomnia, Muscle Cramps, and Fatigue

Flythe JE, Hilliard T, Lumby E, Castillo G, Orazi J, Abdel-Rahman EM, Pai AB, Rivara MB, St Peter WL, Weisbord SD, Wilkie CM, Mehrotra R

Individuals receiving in-center maintenance hemodialysis bear a high burden of both physical and mood symptoms. More than half of patients on hemodialysis report sleep disturbance, muscle cramps, and fatigue. Patients describe symptoms as having a deleterious effect on their quality of life, suggesting that symptom alleviation may meaningfully improve patient-reported outcomes.

Association of Monoclonal Gammopathy with Progression to ESKD among US Veterans

Burwick N, Adams SV, Todd-Stenberg JA, Burrows NR, Pavkov ME, O'Hare AM

Whether patients with monoclonal protein are at a higher risk for progression of kidney disease is not known. The goal of this study was to measure the association of monoclonal protein with progression to ESKD.

The Kidney Accelerator: Innovation Wanted, Nephrologists Needed

Innovation in nephrology is long overdue. The most impactful innovations in our field arguably arrived half a century ago with the invention of maintenance dialysis and novel federal funding policies, providing life-sustaining therapy to those with kidney failure. In the interim, we saw important advances, including the introduction of erythropoietin and improved immunosuppressants. However, we continue to reward kidney failure with a life on dialysis for many, while thousands die every year on the kidney transplant waitlist. Where are the novel ways to improve life with kidney disease, and where is the hope for a cure?