Our faculty research broadens the knowledge of kidney disease.

Reevaluating the role of megalin in renal vitamin D homeostasis using a human cell-derived microphysiological system

Chapron BD, Chapron A, Phillips B, Okoli MC, Shen DD, Kelly EJ, Himmelfarb J, Thummel KE

The role of megalin in the regulation of renal vitamin D homeostasis has previously been evaluated in megalin-knockout mice and rat proximal tubule epithelial cells. We revisited these hypotheses that were previously tested solely in the rodent models, this time using a 3-dimensional proximal tubule microphysiological system incorporating primary human proximal tubule epithelial cells. Using this human cell-derived model, we confirmed that 25OHD3 is transported into the human proximal tubule epithelium via megalin-mediated endocytosis while bound to vitamin D binding protein. Building upon these findings, we then evaluated the role of megalin in modulating the cellular uptake and biological activity of 1α,25(OH)2D3.

Novel PAradigm to improve Inflammatory burden in end stage Renal disease (rePAIR): study protocol for a randomized controlled trial

Trivedi R, Fares G, Nunez VB, Campbell R, Clement M, Burleson J, Himmelfarb J, Ioannidou E

Given the importance of inflammation as a predictor of poor outcomes in End Stage Renal Disease (ESRD), reductions in inflammatory biomarkers have been proposed as a critical target in this population. This study targets chronic periodontitis, an oral inflammatory disease of microbial etiology causing persistent inflammation in ESRD.

Serum 25-Hydroxyvitamin D Concentrations Are Associated with Computed Tomography Markers of Subclinical Interstitial Lung Disease among Community-Dwelling Adults in the Multi-Ethnic Study of Atherosclerosis (MESA)

Kim SM, Zhao D, Podolanczuk AJ, Lutsey PL, Guallar E, Kawut SM, Barr RG, de Boer IH, Kestenbaum BR, Lederer DJ, Michos ED

Activated vitamin D has anti-inflammatory properties. 25-Hydroxyvitamin D [25(OH)D] deficiency might contribute to subclinical interstitial lung disease (ILD). We examined associations between serum 25(OH)D concentrations and subclinical ILD among middle-aged to older adults who were free of cardiovascular disease at baseline.

Volumetric, Nanoscale Optical Imaging of Mouse and Human Kidney via Expansion Microscopy

Chozinski, T, Mao, C, Halpern, A, Pippin, J, Alpers, C, Shankland, SJ, Najafian, B, Vaughan, J. Volumetric

Using ExM with a standard confocal microscope, we resolve fine details of structures that have traditionally required visualization by electron microscopy, including podocyte foot processes, the glomerular basement membrane, and the cytoskeleton. This inexpensive and accessible approach to volumetric, nanoscale imaging enables visualization of fine structural details of kidney tissues that were previously difficult or impossible to measure by conventional methodologies.

Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial

Tuttle KR, Lakshmanan MC, Rayner B, Busch RS, Zimmermann AG, Woodward DB, Botros FT

Many antihyperglycaemic drugs, including insulin, are primarily cleared by the kidneys, restricting treatment options for patients with kidney disease. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys, and confers a lower risk of hypoglycaemia than does insulin. We assessed the efficacy and safety of dulaglutide in patients with type 2 diabetes and moderate-to-severe chronic kidney disease.

SGLT2 Inhibition for the Prevention and Treatment of Diabetic Kidney Disease: A Review

Alicic RZ, Johnson EJ, Tuttle KR

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the United States and the world alike, and there is a great unmet need for treatments to reduce DKD development and progression. Inhibition of sodium/glucose co-transporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment, leading to regulatory approval of several first-generation SGLT2 inhibitors for the treatment of type 2 diabetes.

Diagnosing the Treatment

McGuffin SA, Trowbridge RL, O'Hare AM, Olson AP

A common clinical challenge: an older adult with several possibly unrelated concerns. In many patients, a new presentation is usually either a different manifestation of a known condition (eg, a complication of an established malignancy) or the emergence of something they are at risk for based on health behavior or other characteristics (eg, lung cancer in a smoker). The diagnostic process in older adults can be complicated because many have, or are at risk for, multiple chronic conditions.

Emotional Impact of Illness and Care on Patients with Advanced Kidney Disease

O'Hare AM, Richards C, Szarka J, McFarland LV, Showalter W, Vig EK, Sudore RL, Crowley ST, Trivedi R, Taylor JS

The highly specialized and technologically focused approach to care inherent to many health systems can adversely affect patients' emotional experiences of illness, while also obscuring these effects from the clinician's view. We describe what we learned from patients with advanced kidney disease about the emotional impact of illness and care.

Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

Philosophe B, Leca N, West-Thielke PM, Horwedel T, Culkin-Gemmell C, Kistler K, Stevens DR

The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers.

Noninvasive Assay for Donor Fraction of Cell-Free DNA in Pediatric Heart Transplant Recipients

Ragalie WS, Stamm K, Mahnke D, Liang HL, Simpson P, Katz R, Tomita-Mitchell A, Kindel SJ, Zangwill S, Mitchell ME.

There is a compelling clinical need for a noninvasive alternative to endomyocardial biopsy (EMB) for the surveillance of rejection in heart transplant recipients. We and others have reported on donor cell-free deoxyribonucleic acid (cfDNA), which is shed from the donor allograft and is elevated during acute rejection.