Our faculty research broadens the knowledge of kidney disease.

Likelihood-based analysis of outcome-dependent sampling designs with longitudinal data.

Zelnick LR, Schildcrout JS, Heagerty PJ

The use of outcome-dependent sampling with longitudinal data analysis has previously been shown to improve efficiency in the estimation of regression parameters.

Common α-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease

Raffield LM, Ulirsch JC, Naik RP, Lessard S, Handsaker RE, Jain D, Kang HM, Pankratz N, Auer PL, Bao EL, Smith JD, Lange LA, Lange EM, Li Y, Thornton TA, Young BA, Abecasis GR, Laurie CC, Nickerson DA, McCarroll SA, Correa A, Wilson JG

Co-inheritance of α-thalassemia has a significant protective effect on the severity of complications of sickle cell disease (SCD), including stroke. However, little information exists on the association and interactions for the common African ancestral α-thalassemia mutation (-α3.7 deletion) and β-globin traits (HbS trait [SCT] and HbC trait) on important clinical phenotypes such as red blood cell parameters, anemia, and chronic kidney disease (CKD).

Inflammatory Mechanisms as New Biomarkers and Therapeutic Targets for Diabetic Kidney Disease

Alicic RZ, Johnson EJ, Tuttle KR

Diabetic kidney disease (DKD) is the leading cause of CKD and end-stage kidney disease (ESKD) worldwide. Approximately 30-40% of people with diabetes develop this microvascular complication, placing them at high risk of losing kidney function as well as of cardiovascular events, infections, and death. Current therapies are ineffective for arresting kidney disease progression and mitigating risks of comorbidities and death among patients with DKD.

Palliative Care Disincentives in CKD: Changing Policy to Improve CKD Care

Tamura MK, O'Hare AM, Lin E, Holdsworth LM, Malcolm E, Moss AH

The dominant health delivery model for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States, which focuses on provision of dialysis, is ill-equipped to address many of the needs of seriously ill patients. Although palliative care may address some of these gaps in care, its integration into advanced CKD care has been suboptimal due to several health system barriers.

Patient-Centered Care in Renal Medicine: Five Strategies to Meet the Challenge

There is growing interest in patient-centered care, defined by the Institute of Medicine as "care that is respectful of and responsive to individual patient preferences, needs, and values." Although generally accepted as uncontroversial, the notion of "centering" care on our patients is in fact quite revolutionary.

Symptom Prioritization among Adults Receiving In-Center Hemodialysis: A Mixed Methods Study

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

Individuals receiving in-center hemodialysis experience a high symptom burden that detrimentally affects their quality of life. There are few evidence-based interventions for symptom relief in this population. To stimulate innovation in symptom management, data on patient symptom prioritization and treatment preferences are needed. We undertook this study to (1) identify patient-prioritized symptoms for the development of symptom relief therapies and (2) elicit preferences for treatments among individuals receiving hemodialysis.

Proximal Tubular Secretory Clearance: A Neglected Partner of Kidney Function

Wang K, Kestenbaum B

The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane. Despite its central physiologic importance, tubular secretory clearance is rarely measured or even estimated in clinical or research settings.

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.

Kestenbaum B, et al

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent).

Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline

Drew DA, Katz R, Kritchevsky S, Ix JH, Shlipak MG, Newman AB, Hoofnagle A, Fried L, Sarnak MJ, Gutierrez OM

Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes.

Urinary Biomarkers of Kidney Tubular Damage and Risk of Cardiovascular Disease and Mortality in Elders

Jotwani V, Katz R, Ix JH, Gutiérrez OM, Bennett M, Parikh CR, Cummings SR, Sarnak MJ, Shlipak MG

Novel urinary biomarkers have enabled earlier detection of kidney tubular damage, but their prognostic value for adverse cardiovascular outcomes is uncertain. We hypothesized that tubular damage, measured by urine α1-microglobulin (A1M), amino-terminal propeptide of type III procollagen (PIIINP), and neutrophil gelatinase-associated lipocalin (NGAL), would be associated with higher risks for cardiovascular events and mortality among elders.