Our faculty research broadens the knowledge of kidney disease.

Complications of Immunosuppression in Glomerular Disease

Most glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of immunosuppressive agents are used in the management of patients with these conditions. Immunosuppression requires a careful balance of risk and benefits, and many of these agents have a narrow therapeutic window and require close monitoring. 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.

Commentary on Complications of Immunosuppressive Treatments for Glomerulonephritis

Kestenbaum BR, Seliger SL

Commentary

Multicolor Flow Cytometry and Cytokine Analysis Provides Enhanced Information on Kidney Transplant Biopsies

Muczynski KA, Leca N, Anderson AE, Kieran N, Anderson SK.

Current processing of renal biopsy samples provides limited information about immune mechanisms causing kidney injury and disease activity. We used flow cytometry with transplanted kidney biopsy samples to provide more information on the immune status of the kidney.

Association of Inpatient Palliative Care with Health Care Utilization and Postdischarge Outcomes among Medicare Beneficiaries with End Stage Kidney Disease

Chettiar A, Montez-Rath M, Liu S, Hall YN, O'Hare AM, Kurella Tamura M.

Palliative care may improve quality of life and reduce the cost of care for patients with chronic illness, but utilization and cost implications of palliative care in ESKD have not been evaluated. We sought to determine the association of inpatient palliative care with health care utilization and postdischarge outcomes in ESKD.

Management of Physical Frailty in Patients Requiring Hemodialysis Therapy

Matsuzawa R, Roshanravan B.

This review focuses on the underscoring the importance of identifying physical frailty in hemodialysis patients and proposes an algorithm integrating frailty assessment into the routine care of patients treated with dialysis.

Alteration of HDL Protein Composition with Hemodialysis Initiation

Wang K, Zelnick LR, Hoofnagle AN, Vaisar T, Henderson CM, Imrey PB, Robinson-Cohen C, de Boer IH, Shiu YT, Himmelfarb J, Beck GJ, Kestenbaum B; HFM Study

HDL particles obtained from patients on chronic hemodialysis exhibit lower cholesterol efflux capacity and are enriched in inflammatory proteins compared with those in healthy individuals. Observed alterations in HDL proteins could be due to effects of CKD, but also may be influenced by the hemodialysis procedure, which stimulates proinflammatory and prothrombotic pathways. We compared HDL-associated proteins in 143 participants who initiated hemodialysis within the previous year with those of 110 participants with advanced CKD from the Hemodialysis Fistula Maturation Study.

Cause-Specific Mortality in Patients with Chronic Kidney Disease and Atrial Fibrillation

Airy M, Schold JD, Jolly SE, Arrigain S, Bansal N, Winkelmayer WC, Nally JV Jr, Navaneethan SD

Atrial fibrillation (AF) is associated with death in patients with chronic kidney disease (CKD). We examined the associations between AF and cause-specific mortality in a large CKD population. We included 62,459 patients with estimated glomerular filtration rate 15-59 mL/min/1.73 m2 (6,639 patients with AF and 55,820 without AF) followed in a large health care system

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients

Bostom A, Pasch A, Madsen T, Roberts MB, Franceschini N, Steubl D, Garimella PS, Ix JH, Tuttle KR, Ivanova A, Shireman T, Gohh R, Merhi B, Jarolim P, Kusek JW, Pfeffer MA, Liu S, Eaton CB

"T50," shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization.

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.