Research

We are dedicated to pursuing innovative kidney research, discovering new models, and applying technological advancements.

Recent publications highlight our commitment. 

eGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study

Nisha Bansal, Leila R. Zelnick, Alvaro Alonso, Emelia J. Benjamin, Ian H. de Boer, Rajat Deo‖, Ronit Katz, Bryan Kestenbaum, Jehu Mathew, Cassianne Robinson-Cohen, Mark J. Sarnak, Michael G. Shlipak, Nona Sotoodehnia, Bessie Young, Susan R. Heckbert

kidney_afib_va_8_14_2017_nocjasn

See article on this research: Kidney Disease May Boost Risk of Abnormal Heartbeat
US News and World Report 

Heart failure in patients with kidney disease

Tuegel C, Bansal N

This review provides a comprehensive overview of the epidemiology, pathophysiology and treatment of heart failure in patients with kidney disease. Heart failure (HF) is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), and the population of CKD patients with concurrent HF continues to grow. The accurate diagnosis of HF is challenging in patients with CKD in part due to a lack of validated imaging and biomarkers specifically in this population.  The pathophysiology between the heart and the kidneys is complex and bidirectional. Patients with CKD have greater prevalence of traditional HF risk factors as well as unique kidney-specific risk factors including malnutrition, acid-base alterations, uremic toxins, bone mineral changes, anemia, and myocardial stunning.  These risk factors also contribute to the decline of kidney function seen in patients with subclinical and clinical HF. The exact mechanisms that link kidney disease with HF are not fully elucidated but likely include inflammation, hemodynamic changes, and alterations in hormonal pathways. More targeted HF therapies may improve outcomes in patients with kidney disease as current HF therapies are under-utilized in this population. 

Blood Pressure and Risk of Cardiovascular Events in Patients on Chronic Hemodialysis: The CRIC Study (Chronic Renal Insufficiency Cohort)

 

Bansal N, McCulloch CE, Lin F, Alper A, Anderson AH, Cuevas M, Go AS, Kallem R, Kusek JW, Lora CM, Lustigova E, Ojo A, Rahman M, Robinson-Cohen C, Townsend RR, Wright J, Xie D, Hsu CY; CRIC Study Investigators

In this paper, we explored the relationship between systolic blood pressure (SBP) with cardiovascular (CVD) events, which has important treatment implications but has not been well-elucidated. Among 383 HD participants enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study, multivariable splines and Cox models were used to study the association between SBP and adjudicated CVD events (heart failure, myocardial infarction, ischemic stroke, peripheral artery disease), controlling for differences in demographics, CVD risk factors and dialysis parameters. Dialysis-unit-SBP and out-of-dialysis-unit-SBP were modestly correlated (r=0.34, p<0.001). We noted a U-shaped association of dialysis-unit-SBP and risk of CVD events, with the nadir risk between 140-170 mmHg. In contrast, there was a linear stepwise association between out-of-dialysis-unit-SBP with risk of CVD events.  In conclusion, among HD patients, although there is a U-shaped (“paradoxical”) association of dialysis-unit-SBP and risk of CVD, there is a linear association of out-of-dialysis-unit-SBP with risk of CVD.  Out-of-dialysis-unit BP provides key information and may be an important therapeutic target.   

Kidney function is associated with an altered protein composition of high-density lipoprotein

Rubinow KB, Henderson CM, Robinson-Cohen C, Himmelfarb J, de Boer IH, Vaisar T, Kestenbaum B, Hoofnagle AN

High-density lipoprotein cholesterol (HDL-C) is a circulating construction of lipids and proteins that play a major role in cardiovascular disease. In this study, we evaluated 37 HDL-C associated proteins across the spectrum of kidney function. We found significant differences in four HDL-C proteins associated with lower estimated GFR. These alterations provide new insight into impaired lipoprotein metabolism and its potential treatment in chronic kidney disease.

Identification, Confirmation, and Replication of Novel Urinary MicroRNA Biomarkers in Lupus Nephritis and Diabetic Nephropathy

Cardenas-Gonzalez M, Srivastava A, Pavkovic M, Bijol V, Rennke HG, Stillman IE, Zhang X, Parikh S, Rovin BH, Afkarian M, de Boer IH, Himmelfarb J, Waikar SS, Vaidya VS

MicroRNAs are small RNA molecules that are not transcribed to protein but may affect expression of genes. In this study of people with diabetes or systemic lupus erythematosus, we identified mircoRNAs excreted in the urine that differed in abundance for people with versus without kidney disease. These microRNAs were likely made in the kidney. The microRNAs may serve as targets to prevent or treat disease or biomarkers to better diagnose kidney damage among people with diabetes or lupus.

Relation of Serum Vitamin D to Risk of Mitral Annular and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis)

Tibuakuu M, Zhao D, de Boer IH, Guallar E, Bortnick AE, Lutsey PL, Budoff MJ, Kizer JR, Kestenbaum BR, Michos ED

Low vitamin D promotes pathways of inflammation and calcification; however, associations with human calcific diseases are not well understood. Herein, we determined the association of 25-hypdroxyvitamin D (25-OHD) concentrations with mitral and aortic calcification in 5,530 participants in a multi-ethnic cohort study. Serum 25-OHD concentrations were not associated with incident or prevalent valve calcification after adjustment. These findings diminish enthusiasm for 25-OHD levels as a marker of cardiac valve disease in humans.

Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD

Batacchi Z, Robinson-Cohen C, Hoofnagle AN, Isakova T, Kestenbaum B, Martin KJ, Wolf MS, de Boer IH

Vitamin D supplements are used widely in people with and without chronic kidney disease (CKD). However, it’s not clear how supplementation affects underlying vitamin D metabolism, and vitamin D metabolism is altered in CKD. In this physiology study, we found that vitamin D supplementation induced the catabolism of circulating 25-hydroxyvitamin D and slowed the rate of conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the active vitamin D hormone. These changes were blunted in participants with CKD. These results suggest that vitamin D metabolism changes during vitamin D supplementation to maintain vitamin D homeostasis. These changes are less robust in CKD, suggesting that CKD is a state of stagnant vitamin D metabolism.

Does Secretory Clearance Follow Glomerular Filtration Rate in Chronic Kidney Diseases? Reconsidering the Intact Nephron Hypothesis

Chapron A, Shen DD, Kestenbaum BR, Robinson-Cohen C, Himmelfarb J, Yeung CK

 

Standardized outcomes in nephrolgoy-peritoneal dialysis (SONG-PD): Study protocol for establishing a core outcome set in PD

Manera KE, Tong A, Craig JC, Brown EA, Brunier G, Dong J, Dunning T, Mehrotra R, Naicker S, Pecoits-Filho R, Perl J, Wang AY, Wilkie M, Howell M, Sautenet B, Evangelidis N, Shen JI, Johnson DW

The aim of the Standardised Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) study is to establish a set of core outcomes for trials in patients on PD based on the shared priorities of all stakeholders, so that outcomes of most relevance for decision- making can be evaluated, and that interventions can be compared reliably. This manuscript describes the methods the researchers will use to develop these core outcomes

Timing of Dialysis Initiation: What Has Changed Since IDEAL?

Rivara MB, Mehrotra R

The optimal timing of initiation of maintenance dialysis in patients with end stage renal disease is currently unknown. The null results of the Initiating Dialysis Early and Late (IDEAL) study, the only randomized trial to have tested the impact of dialysis initiation at two different levels of kidney function on outcomes, have challenged the established paradigm of using estimates of glomerular filtration as the primary guide for initiation of maintenance dialysis.  In this article, we discuss the recent evolution of research findings and trends in dialysis initiation practices in the United States, and suggest that future directions should incorporate comprehensive standardized symptoms assessment, modern shared decision-making practices, and should further explore measurement of novel uremic solutes.”

Retinoic acid improves nephrotoxic serum-induced glomerulonephritis through activation of podocyte retinoic acid receptor α

Image for Shankland publication

Dai Y, Chen A, Liu R, Gu L, Sharma S, Cai W, Salem F, Salant DJ, Pippin JW, Shankland SJ, Moeller MJ, Ghyselinck NB, Ding X, Chuang PY, Lee K, He JC

This recent publication in Kidney International was led by Dr. John Cijiang He, Icahn School of Medicine at Mount Sinai. It extends previous work on the effects of the vitamin A derivative retinoic acid (RA) in glomerular disease. The group has previously shown RA reduces proteinuria and glomerulosclerosis in a murine model of HIV-associated nephropathy, by activating the RA receptor-. In this study, the RA receptor- was ablated specifically in podocytes, and nephrotoxic serum induced crescentic nephritis was induced in mice. RA treatment had a beneficial effect on crescent formation, kidney function, glomerular cell proliferation and podocyte injury. These beneficial effects were blunted by the absence of the RA receptor- in podocytes, indicating an important role for the RA receptor- in the pathogenesis of crescentic GN. Additionally, RA itself had direct effects on proliferation and increasing differentiation of parietal epithelial cells (PEC) on Bowman’s capsule to podocytes. Treatment of GN is currently limited to immunosuppressive therapy. Taken together, the results of this study indicate RA and RA receptor- agonists hold great potential in minimizing podocyte injury, decreasing proliferation and increasing PEC differentiation to podocytes in crescentic GN. 

Association between Endothelin-1 Levels and Kidney Disease among Blacks

Rebholz CM, Harman JL, Grams ME, Correa A, Shimbo D, Coresh J, Young BA