Our faculty research broadens the knowledge of kidney disease.

Sodium glucose cotransporter 2 inhibition heralds a call-to-action for diabetic kidney disease

Katherine R. Tuttle, David Z. Cherney and on behalf of the Diabetic Kidney Disease Task Force of the American Society of Nephrology

Unmet Needs for Therapeutic Innovation: Diabetes is a global health emergency with 425 million people affected in the year 2017 and a projection for 629 million by 2045. Half develop diabetic kidney disease, and its prevalence is rising progressively in concert with the overall diabetes epidemic, largely driven by type 2 diabetes. In addition to being the most common cause of ESKD worldwide, diabetic kidney disease greatly amplifies risks of cardiovascular complications and death. Even with treatment of the major risk factors, hyperglycemia and hypertension, diabetic kidney disease risks remain high.

Podocyte biology and response to injury

Peter Mundel, Stuart J. Shankland

The visceral glomerular epithelial cell, also called podocyte, is a terminally differentiated cell that lines the outer aspect of the glomerular basement membrane (GBM). It therefore forms the final barrier to protein loss, which explains why podocyte injury is typically associated with marked proteinuria. Indeed, all forms of nephrotic syndrome are characterized by abnormalities in the podocyte. In this review, we will provide an update of the known functions of recent podocyte-specific proteins and focus on the slit diaphragm (SD) and the mechanisms underlying foot process (FP) flattening and how the podocyte responds to injury.

Trends in the timing and clinical context of maintenance dialysis initiation

Ann M. O’Hare, Susan P. Wong, Margaret K. Yu, Bruce Wynar, Mark Perkins, Chuan-Fen Liu, Jaclyn M. Lemon, Paul L. Hebert

Whether secular trends in eGFR at dialysis initiation reflect changes in clinical presentation over time is unknown. We reviewed the medical records of a random sample of patients who initiated maintenance dialysis in the Department of Veterans Affairs (VA) in fiscal years 2000–2009 (n=1691) to characterize trends in clinical presentation in relation to eGFR at initiation.

Reconciling Short- and Long-Term Outcomes of In-Hospital Cardiac Arrest in Patients undergoing Maintenance Dialysis

Simon Hsu, Susan P.Y. Wong

Conversations about cardiopulmonary resuscitation (CPR) between clinicians and patients are often conducted quickly and without nuance....There have been very few studies that have examined in-hospital cardiac arrests (IHCA) in patients with ESKD, and the findings are sobering. It is estimated that CPR for IHCA is 20 times more prevalent among patients with ESKD than in the general population.

Establishing a Core Outcome Set for Peritoneal Dialysis: Report of the SONG-PD (Standardized Outcomes in Nephrology-Peritoneal Dialysis) Consensus Workshop

Manera KE, Johnson DW, Craig JC, Shen JI, Gutman T, Cho Y, Wang AY, Brown EA, Brunier G, Dong J, Dunning T, Mehrotra R, Naicker S, Pecoits-Filho R, Perl J, Wilkie M, Tong A; SONG-PD Workshop Investigators.

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified.

Associations of innate and adaptive immune cell subsets with incident type 2 diabetes risk: the MESA study

Olson NC, Doyle MF, Sitlani CM, de Boer IH, Rich SS, Huber SA, Landay AL, Tracy RP, Psaty BM, Delaney JA

Cell-mediated immunity is implicated in glucose homeostasis and insulin resistance. Whether the levels of innate and adaptive immune cells in peripheral blood are risk factors for incident type 2 diabetes (T2D) remains unknown. We hypothesized the proportions of naive, memory, CD28-, Th17, and T regulatory CD4+ cells would be associated with incident T2D. In secondary analyses we evaluated the relationships of 28 additional immune cell phenotypes with T2D.

Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease

Mayeda L, Katz R, Ahmad I, Bansal N, Batacchi Z, Hirsch IB, Robinson N, Trence DL, Zelnick L, de Boer IH

Compared with hemoglobin A1c (HbA1c), continuous glucose monitoring (CGM) may better capture risk of diabetes complications in patients with chronic kidney disease (CKD), including diabetic peripheral neuropathy (DPN). We hypothesized that glucose time in range (TIR), measured by CGM, is associated with DPN symptoms among participants with type 2 diabetes mellitus (type 2 DM) and moderate-to-severe CKD.

Hospitalization Rates in Older Adults with Albuminuria: The Cardiovascular Health Study

Barzilay JI, Buzkova P, Shlipak MG, Bansal N, Garimella P, Mukamal KJ

Albuminuria is highly prevalent among older adults, especially those with diabetes. It is associated with several chronic diseases, but its overall impact on the health of older adults, as measured by hospitalization, has not been quantified. We followed 3110 adults, mean age 78 years, for a median 9.75 years, of whom 654 (21%) had albuminuria (>30 mg albumin / gram creatinine) at baseline.

Vascular access-specific health-related quality of life impacts among hemodialysis patients: qualitative development of the hemodialysis access-related quality of life (HARQ) instrument

Robert J. Nordyke, Gina Nicholson, Shawn M. Gage, Ted Lithgow, Jonathan Himmelfarb, Matthew B. Rivara, Ron D. Hays, Karen Woo, John Devin Peipert 

End stage kidney disease and hemodialysis dependence are associated with impairments in health-related quality of life (HRQOL), which may be related to vascular access (VA). Few HRQOL measures are VA-specific and none differentiate HRQOL impact by VA type. We developed a VA-targeted HRQOL measure to distinguish the impact of fistulas, grafts and catheters.

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study

Frank B. Cortazar, Zoe A. Kibbelaar, Ilya G. Glezerman, Ala Abudayyeh, Omar Mamlouk, Shveta S. Motwani, Naoka Murakami, Sandra M. Herrmann, Sandhya Manohar, Anushree C. Shirali, Abhijat Kitchlu, Shayan Shirazian, Amer Assal, Anitha Vijayan, Amanda DeMauro Renaghan, David I. Ortiz-Melo, Sunil Rangarajan, A. Bilal Malik, Jonathan J. Hogan, Alex R. Dinh, Daniel Sanghoon Shin, Kristen A. Marrone, Zain Mithani, Douglas B. Johnson, Afrooz Hosseini, Deekchha Uprety, Shreyak Sharma, Shruti Gupta, Kerry L. Reynolds, Meghan E. Sise and David E. Leaf

Despite increasing recognition of the importance of immune checkpoint inhibitor–associated AKI, data on this complication of immunotherapy are sparse. We conducted a multicenter study of 138 patients with immune checkpoint inhibitor–associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI.