Our faculty research broadens the knowledge of kidney disease.

Effects of diet and exercise on adipocytokine levels in patients with moderate to severe chronic kidney disease

Nihal Aydemira, Mindy M. Pike, Aseel Alsouqi, Samuel A. E. Headley, Katherine Tuttle, Elizabeth E. Evans, Charles M. Milch, Kelsey A. Moody, Michael Germain, Loren Lipworth, Jonathan Himmelfarb, T. A .Ikizler, Cassianne Robinson-Cohen

Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD.

From Local Explanations to Global Understanding With Explainable AI for Trees

Scott M Lundberg, Gabriel Erion, Hugh Chen, Alex DeGrave, Jordan M Prutkin, Bala Nair, Ronit Katz, Jonathan Himmelfarb, Nisha Bansal, Su-In Lee

These tools enable us to i) identify high magnitude but low frequency non-linear mortality risk factors in the US population, ii) highlight distinct population sub-groups with shared risk characteristics, iii) identify non-linear interaction effects among risk factors for chronic kidney disease, and iv) monitor a machine learning model deployed in a hospital by identifying which features are degrading the model's performance over time. Given the popularity of tree-based machine learning models, these improvements to their interpretability have implications across a broad set of domains.

Association of Cardiac Biomarkers With the Kansas City Cardiomyopathy Questionnaire in Patients With Chronic Kidney Disease Without Heart Failure

Sri Lekha Tummalapalli, Leila R. Zelnick, Amanda H. Andersen, Robert H. Christenson, Christopher R. deFilippi, Rajat Deo, Alan S. Go, Jiang He, Bonnie Ky, James P. Lash, Stephen L. Seliger, Elsayed Z. Soliman, Michael G. Shlipak, Nisha Bansal and the CRIC Study Investigators

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF‐15 (growth differentiation factor‐15), galectin‐3, sST2 (soluble suppression of tumorigenesis‐2), hsTnT (high‐sensitivity troponin T), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known.

Induced Pluripotent Stem Cells Provide Mega Insights Into Kidney Disease

Alessandro Luciani, Benjamin S Freedman

Rare mutations in the LRP2 gene encoding for the endocytic receptor megalin cause developmental abnormalities and kidney disease. However, the mechanisms governing the dysfunction of mutant megalin remain unclear. A new study utilizing patient-derived induced pluripotent stem cells is now putting the endolysosomal system into the spotlight, as it is proposed to play a central role in the regulation of megalin in health and disease.

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes

Alessandro Doria, Andrzej T. Galecki, Cathie Spino, Rodica Pop-Busui, David Z. Cherney,  Ildiko Lingvay, Afshin Parsa,  Peter Rossing, Ronald J. Sigal,  Maryam Afkarian,  Ronnie Aronson, M. Luiza Caramori,  Jill P. Crandall,  Ian H. de Boer, Thomas G. Elliott, Allison B. Goldfine,  J. Sonya Haw,  Irl B. Hirsch, Amy B. Karger,  David M. Maahs,  Janet B. McGill, Mark E. Molitch, Bruce A. Perkins, Sarit Polsky, Marlon Pragnell,  William N. Robiner, Sylvia E. Rosas, Peter Senior, Katherine R. Tuttle, Guillermo E. Umpierrez, Amisha Wallia, Ruth S. Weinstock, Chunyi Wu, Michael Mauer

Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease.

Associations Between Cardiac Biomarkers and Cardiac Structure and Function in CKD

Nathan R. Stein, Leila R. Zelnick, Amanda H. Anderson, Robert H. Christenson, Christopher R. de Filippi, Rajat Deo, Alan S. Go, Jiang He, Bonnie Ky, James P. Lash, Stephen L. Seliger, Elsayed Z. Soliman, Michael G. Shlipak, Nisha Bansal.  CRIC Study Investigators: Lawrence J. AppelHarold,  I. Feldman, Alan S.Go, Jiang He, John W. Kusek, James P. Lash, Panduranga S. Rao, Mahboob Rahman, Raymond R. Townsend

Subclinical changes to cardiac structure and function detected with echocardiography precede the development of clinical heart failure (HF) in persons with chronic kidney disease (CKD). Circulating cardiac biomarkers may reflect these pathophysiological changes.

Global transcriptomic changes occur in aged mouse podocytes

Yuliang Wang, Diana G. Eng, Natalya V. Kaverina, Carol J. Loretz, Abbal Koirala, Shreeram Akilesh, Jeffrey W. Pippin, Stuart J. Shankland

Glomerular podocytes undergo structural and functional changes with advanced age, that; increase susceptibility of aging kidneys to worse outcomes following superimposed glomerular; diseases. To delineate transcriptional changes in podocytes in aged mice, RNA-seq was performed on isolated populations of reporter-labeled (tdTomato) podocytes from multiple young (two to three months) and advanced aged mice (22 to 24 months, equivalent to 70 plus year old humans).

CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney

Hiroko Hamatani, Diana G. Eng, Keiju Hiromura, Jeffrey W. Pippin, Stuart J. Shankland

CD44 contributes to the activation of glomerular parietal epithelial cells (PECs). Although CD44 expression is higher in PECs of healthy aged mice, the biological role of CD44 in PECs in this context remains unclear. Accordingly, young (4 months) and aged (24 months) CD44−/− mice were compared to age‐matched CD44+/+ mice, both aged in a nonstressed environment.

Renaissance needed in conservative management of patients with ESKD

The need for a conservative option as an alternative to dialysis persists and has driven resurgent efforts to develop contemporary models of conservative care.

Distinct Functional Requirements for Podocalyxin in Immature and Mature Podocytes Reveal Mechanisms of Human Kidney Disease

Ido Refaeli, Michael R. Hughes, Alvin Ka-Wai Wong, Mei Lin Z. Bissonnette, Calvin D. Roskelley, A. Wayne Vogl, Sean J. Barbour, Benjamin S. Freedman, Kelly M. McNagny 

Dominant and recessive mutations in podocalyxin (PODXL) are associated with human kidney disease. Interestingly, some PODXL mutations manifest as anuria while others are associated with proteinuric kidney disease. PODXL heterozygosity is associated with adult-onset kidney disease and podocalyxin shedding into the urine is a common biomarker of a variety nephrotic syndromes. It is unknown, however, how various lesions in PODXL contribute to these disparate disease pathologies.