Our faculty research broadens the knowledge of kidney disease.

Clinical outcome of HCV-associated cryoglobulinemic glomerulonephritis following treatment with direct acting antiviral agents: a case-based review

Obrișcă, B.,  Jurubiță, R.,  Sorohan, B.,  Iliescu, L.,  Baston, C.,  Bobeică, R.,  Andronesi, A.,  Leca, N.,  Ismail, G. 

Newer treatment protocols involving direct-acting antiviral agents (DAAs) have been associated with high rates of sustained virologic response (SVR) and clinical remission in patients with hepatitis C virus (HCV) associated cryoglobulinemic vasculitis (HCV-CV), but clinical response in those with renal involvement is less clear. Our goal was to evaluate the clinical course following DAA therapy in one of the largest cohorts of patients with HCV-associated cryoglobulinemic glomerulonephritis (HCV-GN) reported to date.

Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals

Noordam, R.,  Young, W.J.,  Salman, R.,  Kanters, J.K., van den Berg, M.E.,  van Heemst, D.,  Lin, H.J.,  Barreto, S.M.,  Biggs, M.L.,  Biino, G.,  Catamo, E.,  Concas, M.P.,  Ding, J.,  Evans, D.S.,  Foco, L.,  Grarup, N., ...... Kestenbaum, B., Lima-Costa, M.F.,  Linneberg, A., .....et al, Newton-Cheh, C.H.,  Sotoodehnia, N.,  Mook-Kanamori, D.O.,  Munroe, P.B.,  Warren, H.R.

Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions. This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.

Dual lineage tracing shows that glomerular parietal epithelial cells can transdifferentiate toward the adult podocyte fate

Natalya V. Kaverina, Diana G. Eng, Benjamin S. Freedman, J. Nathan Kutz, Tyler J. Chozinski, Joshua C. Vaughan, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J.Shankland

Replacing lost adult podocytes in disease is a therapeutic goal to limit and even reverse proteinuria and glomerular scarring. The results from this experimental study add to the body of work that a subpopulation of PECs serves as podocyte progenitors and provides confidence of ongoing efforts to enhance these events in patients with glomerular diseases.

Recognizing diversity in parietal epithelial cells

D'Agati, V.D., Shankland, S.J

Parietal epithelial cells comprise a heterogeneous cell population lining Bowman's capsule. The study by Kuppe et al. focused on the peritubular region of Bowman's capsule and explored the cell biology of 2 poorly characterized subtypes—the intermediate and the cuboidal parietal epithelial cells. The early and exuberant proliferative response of these subgroups in murine focal segmental glomerulosclerosis (FSGS) and human glomerular tip lesions identified a novel hot spot for glomerular lesion formation.

An international Delphi survey helped develop consensus-based core outcome domains for trials in peritoneal dialysis

Karine E. Manera, Allison Tong, Jonathan C. Craig, Jenny Shen, Shilpa Jesudason, Yeoungjee Cho, Benedicte Sautenet, ArmandoTeixeira-Pinto, Martin Howell, Angela Yee-Moon Wang, Edwina A. Brown, Gillian Brunier, Jeffrey Perl, Jie Dong, Martin Wilkie, Rajnish Mehrotra, Roberto Pecoits-Filho, Saraladevi Naicker, Tony Dunning, Nicole Scholes-Robertson, David W. Johnson

Shared decision-making about clinical care options in end-stage kidney disease is limited by inconsistencies in the reporting of outcomes and the omission of patient-important outcomes in trials. Here we generated a consensus-based prioritized list of outcomes to be reported during trials in peritoneal dialysis (PD). In an international, online, three-round Delphi survey, patients/caregivers and health professionals rated the importance of outcomes using a 9-point Likert scale (with 7–9 indicating critical importance) and provided comments.

“Not Shared” Need Not Mean “Not Patient Centered”: Deciding That a Patient Is Not a Candidate—Reply

In Reply As Blythe and colleagues outline, the “best interest” approach to decision making gives clinicians discretion to unilaterally carry out or withhold treatments without soliciting input from or collaborating with patients when they believe that this is in patients’ best interest. This approach assumes that clinicians know what interventions will be most beneficial and least harmful for individual patients. The difficulty with this approach, however, is that it is impossible to know how patients might weigh the benefits and harms of treatment without knowing their values and goals. Furthermore, clinicians often do not agree with their patients on what is most important near the end of life1 and cannot always accurately predict prognosis or the effects of treatment in individual patients.

A catalog of genetic loci associated with kidney function from analyses of a million individuals

Matthias Wuttke, Yong Li, Man Li, Karsten B. Sieber.....Nisha Bansal, Daniela Baptista, Sven Bergmann, ..... et al

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ.

Albuminuria, the HDL (High-Density Lipoprotein) Proteome, and Coronary Artery Calcification in Type 1 Diabetes Mellitus.

Baohai Shao , Leila R. Zelnick , Jake Wimberger , Jonathan Himmelfarb , John Brunzell , W. Sean Davidson , Janet K. Snell-Bergeon , Karin E. Bornfeldt , Ian H. de Boer , Jay W. Heinecke , and for the DCCT/EDIC Research Group

Albuminuria is an important risk factor for cardiovascular disease in diabetes mellitus. We determined whether albuminuria associates with alterations in the proteome of HDL (high-density lipoprotein) of subjects with type 1 diabetes mellitus and whether those alterations associated with coronary artery calcification.

Early Glomerular Hyperfiltration and Long-Term Kidney Outcomes in Type 1 Diabetes: The DCCT/EDIC Experience

Mark E. Molitch, Xiaoyu Gao, Ionut Bebu, Ian H. de Boer, John Lachin, Andrew Paterson, Bruce Perkins, Amy K. Saenger, Michael Steffes, Bernard Zinman and for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group.

Glomerular hyperfiltration has been considered to be a contributing factor to the development of diabetic kidney disease (DKD). To address this issue, we analyzed GFR follow-up data on participants with type 1 diabetes undergoing 125I-iothalamate clearance on entry into the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications study.

Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study

Dominik Steubl, Petra Buzkova, Pranav S.Garimella, Joachim H. Ix, Prasad Devarajan, Michael R. Bennett, Paolo H.M. Chaves, Michael G.Shlipak, Nisha Bansal, Mark J. Sarnak

Uromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy.