Our faculty research broadens the knowledge of kidney disease.

Circulating testican-2 is a podocyte-derived marker of kidney health

Debby Ngo,  Donghai Wen, Yan Gao, Michelle J. Keyes, Erika R. Drury,  Dan H. Katz,  Mark D. Benson, Sumita Sinha, Dongxiao Shen,  Laurie A. Farrell, Bennet D. Peterson, David J. Friedman,  Sammy Elmariah, Bessie A. Young,  J. Gustav Smith,  Qiong Yang,  Ramachandran S. Vasan,  Martin G. Larson, Adolfo Correa,  Benjamin D. Humphreys,  Thomas J. Wang, Martin R. Pollak, James G. Wilson, Robert E. Gerszten, Eugene P. Rhee

All existing blood biomarkers of kidney function such as creatinine and cystatin C undergo renal clearance and are thus inversely correlated with estimated glomerular filtrate rate (eGFR). Using a proteomic approach, we highlight the renal release of testican-2 among individuals undergoing invasive catheterization and show that higher blood testican-2 levels are associated with higher eGFR and slower rate of subsequent eGFR decline in two large racially diverse cohorts. In conjunction with microscopy and single-cell RNA sequencing of human kidney samples, these studies advance the concept that a protein released by the podocyte can provide insight into the kidney’s health and prognosis. Cell-based studies also raise the possibility that this protein has functional effects on neighboring glomerular endothelial cells.

Homelessness and CKD: A Cohort Study

Yoshio N. Hall, Andy I. Choi, Jonathan Himmelfarb, Glenn M. Chertow, Andrew B. Bindman

Background and objectives: This study examined the associations between homelessness and clinical outcomes of CKD among adults from the urban healthcare safety net. Design, setting, participants, & measurements: This retrospective cohort study examined 15,343 adults with CKD stages 3–5 who received ambulatory care during 1996–2005 from the Community Health Network of San Francisco. Main outcome measures were time to ESRD or death and frequency of emergency department visits and hospitalizations.

Improved automated segmentation of human kidney organoids using deep convolutional neural networks

Michael MacDonald, Theron R. Fennel, Asha Singanamalli, Nelly M. Cruz, Mohammad Yousefhussein, Yousef Al-Kofahi, Benjamin S. Freedman

Organoids are multicellular structures grown in the lab that resemble tissues or organs of the body. We recently generated human kidney organoids compatible with high throughput screening for developmental and disease phenotypes. Accurately segmenting large-scale image collections of organoids remains a challenge. We investigated automated segmentation of these structures using both conventional image processing algorithms and two different deep convolutional neural network architectures. Our dataset consisted of multi-channel images of organoids in 384-well plates, labeling distal tubules, proximal tubules, and podocytes as distinct segments. These images were used either for training and validation, or for testing.

Sleep-HD trial: short and long-term effectiveness of existing insomnia therapies for patients undergoing hemodialysis

Mark Unruh, Daniel Cukor, Tessa Rue, Kashif Abad, Maria-Eleni Roumelioti, Susan M. McCurry, Patrick Heagerty, Rajnish Mehrotra

Patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) experience many distressing symptoms. One frequently reported symptom is insomnia. There are unique issues about HD treatments and schedules that disrupt regular sleep/wake routines and possibly contribute to the high severity of insomnia. Despite evidence for broad-ranging health effects of insomnia, very few clinical trials have tested the efficacy of treatments for HD patients. Cognitive-behavioral therapy for insomnia (CBT-I) is a recommended first-line therapy but largely inaccessible to HD patients in the United States, partly because they commit considerable amounts of time to thrice-weekly dialysis treatments. Another important reason could be the logistical and reimbursement challenges associated with providing behavioral health care at the dialysis center. CBT-I delivered by telehealth can overcome barriers to access, but its efficacy has never been rigorously tested for these patients. Pharmacotherapy is the most widely used treatment for insomnia; however, some drugs presently used are unsafe as they are associated with a higher risk for death for HD patients (benzodiazepines and zolpidem-like drugs). The efficacy and safety of other medications (trazodone) for the treatment of insomnia has never been tested for patients treated with HD.

Race, Ancestry, and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis

Simon Hsu, Andrew N Hoofnagle, Deepak K Gupta, Orlando M Gutierrez, Carmen A Peralta, Steven Shea, Norrina B Allen, Gregory Burke, Erin D Michos, Joachim H Ix, David Siscovick, Bruce M Psaty, Karol E Watson, Bryan Kestenbaum, Ian H de Boer, Cassianne Robinson-Cohen

A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D–related diseases. Objective: Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry.

Cardiac Biomarkers and Risk of Mortality in CKD (the CRIC Study)

Ke Wang, Leila R. Zelnick, Amanda Anderson, Jordana Cohen, Mirela Dobre, Rajat Deo, Harold Feldman, Alan Go, Jesse Hsu, Bernard Jaar, Mayank Kansal, Michael Shlipak, Elsayed Soliman, Panduranga Rao, Matt Weir, Nisha Bansal

Cardiovascular disease (CVD) is the leading cause of mortality among individuals with chronic kidney disease (CKD). Cardiac biomarkers of myocardial distention, injury, and inflammation may signal unique pathways underlying CVD in CKD. In this analysis, we studied the association of baseline levels and changes in 4 traditional and novel cardiac biomarkers with risk of all-cause, CV, and non-CV mortality in a large cohort of patients with CKD.

Optimism is associated with chronic kidney disease and rapid kidney function decline among African Americans in the Jackson Heart Study

LáShauntá M. Glovera, Crystal Butler-Williams, Loretta Cain-Shields, Allana T. Forded, Tanjala S. Purnelle, Bessie Young, Mario Sims

Investigate the association of dispositional optimism with chronic kidney disease (CKD) and rapid kidney function decline (RKFD) and determine if there is modification by age, sex, and educational attainment among African Americans. Optimism was measured using the 6-item Life Orientation Test-Revised scale (categorized into tertiles and log transformed) among participants from the Jackson Heart Study

Do-not-resuscitate orders among patients with ESKD admitted to the intensive care unit: A bird's eye view

Jennifer S. Scherer and Ann M. O’Hare

The goal of advance care planning (ACP) is to help elucidate, clarify, and communicate patients’ values, goals, and care preferences. Engaging patients and their families in an iterative and ongoing process of ACP can help to ensure that they receive care that is congruent with their core values in situations where they may be unable to speak or advocate for themselves. During ACP, patients’ preferences related to cardiopulmonary resuscitation and other treatments along with their preferred surrogate decision maker(s) are typically documented in their medical record (e.g., advance directive, do-not-resuscitate [DNR] order, Provider Orders for Life Sustaining Treatment, and Medical Orders for Life Sustaining Treatment). To uphold personhood throughout the course of illness and across the continuum of care, ACP should ideally be integrated with patients’ other care processes; informed by their evolving experience of illness, prognostic awareness, and understanding of treatment options; and grounded in their cultural and social identities.

End-of-life care among US adults with ESKD who were waitlisted or received a kidney transplant, 2005-2014

Butler, C.R., Reese, P.P., Perkins, J.D., Hall, Y.N., Randall Curtis, J., Tamura, M.K., O'Hare, A.M

For patients with ESKD, hoping for or receiving a kidney transplant can shape prognostic expectations and care processes. In this manuscript, the authors describe more intensive, inpatient-oriented patterns of end-of-life care for patients with ESKD who had been waitlisted for a kidney transplant or received a transplant, compared with other patients with ESKD. Patients who died while on the transplant waitlist were also less likely to have received hospice services and less likely to have discontinued dialysis before death. Because there are powerful defaults favoring use of aggressive interventions to prolong life in most health systems in the United States, these findings suggest that the broad relevance of advance care planning for patients with ESKD extends to the relatively healthy segment of this population that has engaged in the transplant process.

How Safe Is a Native Kidney Biopsy?

Kidney biopsies are performed to investigate the cause of suspected parenchymal disease. Although these biopsies provide important diagnostic and prognostic information guiding therapeutic decisions, the benefits must be weighed against the potential harms of the biopsy procedure.