Our faculty research broadens the knowledge of kidney disease.

The relationship of volume overload and its control to hypertension in hemodialysis patients

Flythe JE, Bansal N

Hypertension is highly prevalent and associated with poor clinical outcomes among individuals receiving maintenance hemodialysis (HD). Volume overload is a key modifiable contributor to hypertension and cardiovascular disease in the HD population. Despite their importance, assessment and treatment of volume overload and hypertension remain major clinical challenges and have substantial implications for both clinical outcomes and patient experiences of care. This review will summarize current data on the diagnosis, epidemiology, pathophysiology, and clinical consequences of hypertension and volume overload in HD patients. We will also identify priorities for future research studies.

Cardiac and Stress Biomarkers and Chronic Kidney Disease Progression: The CRIC Study

Bansal N, Zelnick L, Shlipak MG, Anderson A, Christenson R, Deo R, Defilippi C, Feldman H, Lash J, He J, Kusek J, Ky B, Seliger S, Soliman EZ, Go AS; CRIC Study Investigators.

Increases in cardiac and stress biomarkers may be associated with loss of kidney function through shared mechanisms involving cardiac and kidney injury. We evaluated the associations of cardiac and stress biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), soluble ST-2 (sST-2)] with progression of chronic kidney disease (CKD).

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Tin A, Marten J, Halperin Kuhns VL, Li Y, Wuttke M, Kirsten H, Sieber KB, Qiu C, Gorski M, Yu Z, Giri A, Sveinbjornsson G, Li M, Chu AY, Hoppmann A, O'Connor LJ, Prins B, Nutile T, Noce D, Akiyama M, Cocca M, Ghasemi S, van der Most PJ, Horn K, Xu Y, Fuchsberger C, Sedaghat S, Afaq S, Amin N, Ärnlöv J, Bakker SJL, Bansal N, [...] Stefansson K, Susztak K, Scholz M, Heid IM, Hung AM, Teumer A, Pattaro C, Woodward OM, Vitart V, Köttgen A.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy.

Experiences of US Nephrologists in the Delivery of Conservative Care to Patients With Advanced Kidney Disease: A National Qualitative Study

Author links open overlay panelSusan P.Y. Wong, Saritha Boyapati, Ruth A. Engelberg, Bjorg Thorsteinsdottir, Janelle S.Taylor, Ann M. O’Hare

It is relatively unusual for US patients with advanced chronic kidney disease (CKD) to forgo initiation of maintenance dialysis. Our objective was to describe practice approaches of US nephrologists who have provided conservative care for members of this population.

Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

Rany M. Salem, Jennifer N. Todd, Niina Sandholm, Joanne B. Cole, Wei-Min Chen, Darrell Andrews, Marcus G. Pezzolesi, Paul M. McKeigue, Linda T. Hiraki, Chengxiang Qiu, Viji Nair, Chen Di Liao, Jing Jing Cao, [....] Maria Luiza Caramori, Ian H. de Boer,[...], Stephen S. Rich, Joel N. Hirschhorn, Jose C. Florez and SUMMIT Consortium, DCCT/EDIC Research Group, GENIE Consortium

Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Alexander Teumer, Yong Li, Sahar Ghasemi, Bram P. Prins, Matthias Wuttke, Tobias Hermle, Ayush Giri, Karsten B. Sieber, Chengxiang Qiu, Holger Kirsten, Adrienne Tin, Audrey Y. Chu, Nisha Bansal, Mary F. Feitosa, (...), Cristian Pattaro, Anna Köttgen

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension.

Apolipoprotein L1 Testing in African Americans: Involving the Community in Policy Discussions

Young B.A., Blacksher E., Cavanaugh K.L., Freedman B.I., Fullerton S.M., Kopp J.B., Umeukeje E.M., West K.M., Wilson J.G., Burke W.,  APOL1 Stakeholders Project

Apolipoprotein A1 (APOL1) gene variants occurring in people of West African descent contribute to the greater burden of kidney disease among African Americans. These variants are associated with increased risk of nondiabetic nephropathy, more rapid progression of chronic kidney disease, and shorter survival of donor kidneys after transplantation. However, only a minority of people with APOL1-associated risk develops kidney disease and specific clinical measures to address APOL1-associated risk are lacking. Given these uncertainties, we sought to engage members of the African American public in discussions with other stakeholders about the appropriate use of APOL1 testing.

Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice

Tomoaki Miyazaki, Sina A. Gharib, Yun-Wei A. Hsu, Katherine Xu, Pavlo Khodakivskyi, Akio Kobayashi, Jason Paragas, Alexander D. Klose, Kevin P. Francis, Elena Dubikovskaya, Patrick S. Page-McCaw, Jonathan Barasch, Neal Paragas

In highly heterogenous organs such as the kidney, associating pathophysiological changes such as generation of reactive oxygen species (ROS) with transcriptional signals at the cell-type level are challenging, if not impossible. Furthermore, monitoring these pathophysiological intercellular changes non-invasively and longitudinally has not been shown in the kidney. Here we present a coupled cell-specific image-guided transcriptomics approach to visualize ROS generation and associate it with gene expression changes in the injured kidney.

Differentiation of human kidney organoids from pluripotent stem cells

Cruz NM, Freedman BS

Organoid technology has great potential for kidney regeneration and has already been proven to be suitable for modeling kidney disease. However, the methodologies that are used for the generation of kidney organoids require expertise and can be daunting for the inexperienced. Here, we describe in detail a well-established and relatively simple method for the generation of human kidney organoids. We include notes on technical and design considerations for these experiments, and highlight key advantages and limitations of the system.

Cardiac Biomarkers and Risk of Atrial Fibrillation in Chronic Kidney Disease: The CRIC Study

Lamprea-Montealegre JA, Zelnick LR, Shlipak MG, Floyd JS, Anderson AH, He J, Christenson R, Seliger SL, Soliman EZ, Deo R, Ky B, Feldman HI, Kusek JW, deFilippi CR, Wolf MS, Shafi T, Go AS, Bansal N; CRIC Study Investigators

We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients.