Halil Kutlu Erol

Interests

Teaching

• Artificial Intelligence and Machine Learning in Nephrology and Endocrinology• Pre-emptive Medicine in Hypertension and Diabetes• Subacute and chronic thyroiditis

Research

• Prevention of Diabetic Kidney Disease• Renal Effects of Topical NSAID use in patients with CKD Stage 3a through Stage 4• Congenital Leptin Deficiency and Effects of Leptin Replacement Therapy in Adults and Children

Courses

No activities entered.

Scholarly Contributions

Journals/Publications

• Amir, S., Kim, H., Hu, E. A., Ricardo, A. C., Mills, K. T., He, J., Fischer, M. J., Pradhan, N., Tan, T. C., Navaneethan, S. D., Dobre, M., Anderson, C. A., Appel, L. J., Rebholz, C. M., & , C. S. (2023). Adherence to Plant-Based Diets and Risk of CKD Progression and All-Cause Mortality: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation.
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  Studies have shown that generally healthy individuals who consume diets rich in plant foods have a lower risk of incident chronic kidney disease (CKD) and cardiovascular disease. This study investigated the prospective associations of plant-based diets with the risk of CKD progression and all-cause mortality in individuals with CKD.
• Babroudi, S., Tighiouart, H., Schrauben, S. J., Cohen, J. B., Fischer, M. J., Rahman, M., Hsu, C. Y., Sozio, S. M., Weir, M., Sarnak, M., Yaffe, K., Tamura, M. K., Drew, D., & , C. S. (2023). Blood Pressure, Incident Cognitive Impairment, and Severity of CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation, 82(4), 443-453.e1.
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  Hypertension is a known risk factor for dementia and cognitive impairment. There are limited data on the relation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with incident cognitive impairment in adults with chronic kidney disease. We sought to identify and characterize the relationship among blood pressure, cognitive impairment, and severity of decreased kidney function in adults with chronic kidney disease.
• Dubin, R. F., Deo, R., Ren, Y., Wang, J., Zheng, Z., Shou, H., Go, A. S., Parsa, A., Lash, J. P., Rahman, M., Hsu, C. Y., Weir, M. R., Chen, J., Anderson, A., Grams, M. E., Surapaneni, A., Coresh, J., Li, H., Kimmel, P. L., , Vasan, R. S., et al. (2023). Proteomics of CKD progression in the chronic renal insufficiency cohort. Nature communications, 14(1), 6340.
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  Progression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.
• Fitzpatrick, J. K., Parikh, R. V., Hamilton, S. A., Ambrosy, A. P., Tan, T. C., Bansal, N., Go, A. S., & , C. S. (2023). The association between changes in echocardiography and risk of heart failure hospitalizations and death in adults with chronic kidney disease. Scientific reports, 13(1), 8863.
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  Adults with chronic kidney disease (CKD) are at increased risk for developing heart failure (HF). However, longitudinal cardiac remodeling in CKD has not been well-characterized and its association with HF outcomes remains unknown. We evaluated the association between change in echocardiographic parameters between baseline and year 4 with the subsequent risk of HF hospitalization and death using Cox proportional hazard models in a landmark analysis of a prospective multicenter CKD cohort. Among 2673 participants, mean ± SD age was 61 ± 11 years, with 45% women, and 56% non-white. A total of 472 hospitalizations for HF and 776 deaths occurred during a median (interquartile range) follow-up duration of 8.0 (6.3-9.1) years. Patients hospitalized for HF experienced larger preceding absolute increases in left ventricular (LV) volumes and decreases in LV ejection fraction. Adverse changes in LV ejection fraction, LV cavity volume, LV mass index, and LV geometry were independently associated with an increased risk of HF hospitalization and death. Among adults with CKD, deleterious cardiac remodeling occurs over a relatively short timeframe and adverse remodeling is associated with increased risk of HF-related morbidity and mortality.
• Hallan, S. I., Øvrehus, M. A., Darshi, M., Montemayor, D., Langlo, K. A., Bruheim, P., Sharma, K., & , C. S. (2023). Metabolic Differences in Diabetic Kidney Disease Patients with Normoalbuminuria versus Moderately Increased Albuminuria. Kidney360, 4(10), 1407-1418.
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  The pathophysiological mechanisms of diabetic kidney disease (DKD) with normal (nonalbuminuric DKD) versus moderately increased albuminuria (A-DKD) are not well-understood. Fatty acid biosynthesis and oxydation, gluconeogenesis, TCA cycle, and glucose-alanine cycle were more disturbed in patients with A-DKD compared with those with nonalbuminuric DKD with identical eGFR. DKD patients with and without microalbuminuria could represent different clinical phenotypes.
• Hannan, M., Chen, J., Hsu, J., Zhang, X., Saunders, M. R., Brown, J., McAdams-DeMarco, M., Mohanty, M. J., Vyas, R., Hajjiri, Z., Carmona-Powell, E., Meza, N., Porter, A. C., Ricardo, A. C., Lash, J. P., & , C. S. (2023). Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation.
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  Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD.
• Harhay, M. N., Kim, Y., Milliron, B. J., Robinson, L. F., & , C. S. (2023). Obesity Weight Loss Phenotypes in CKD: Findings From the Chronic Renal Insufficiency Cohort Study. Kidney international reports, 8(7), 1352-1362.
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  Although people with chronic kidney disease (CKD) and obesity have important motivations to lose weight, weight loss is also associated with health risks. We examined whether patterns of change in systolic blood pressure (SBP), serum albumin level, and fat-free mass (FFM) can help to differentiate between healthy and high-risk weight loss in this population.
• Hsu, S., Zelnick, L. R., Bansal, N., Brown, J., Denburg, M., Feldman, H. I., Ginsberg, C., Hoofnagle, A. N., Isakova, T., Leonard, M. B., Lidgard, B., Robinson-Cohen, C., Wolf, M., Xie, D., Kestenbaum, B. R., de Boer, I. H., & , C. S. (2023). Vitamin D Metabolites and Risk of Cardiovascular Disease in Chronic Kidney Disease: The CRIC Study. Journal of the American Heart Association, 12(14), e028561.
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  Background The ratio of 24,25-dihydroxyvitamin D/25-hydroxyvitamin D (vitamin D metabolite ratio [VDMR]) may reflect functional vitamin D activity. We examined associations of the VDMR, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]D) with cardiovascular disease (CVD) in patients with chronic kidney disease. Methods and Results This study included longitudinal and cross-sectional analyses of 1786 participants from the CRIC (Chronic Renal Insufficiency Cohort) Study. Serum 24,25-dihydroxyvitamin D, 25(OH)D, and 1,25(OH)D were measured by liquid chromatography-tandem mass spectrometry 1 year after enrollment. The primary outcome was composite CVD (heart failure, myocardial infarction, stroke, and peripheral arterial disease). We used Cox regression with regression-calibrated weights to test associations of the VDMR, 25(OH)D, and 1,25(OH)D with incident CVD. We examined cross-sectional associations of these metabolites with left ventricular mass index using linear regression. Analytic models adjusted for demographics, comorbidity, medications, estimated glomerular filtration rate, and proteinuria. The cohort was 42% non-Hispanic White race and ethnicity, 42% non-Hispanic Black race and ethnicity, and 12% Hispanic ethnicity. Mean age was 59 years, and 43% were women. Among 1066 participants without prevalent CVD, there were 298 composite first CVD events over a mean follow-up of 8.6 years. Lower VDMR and 1,25(OH)D were associated with incident CVD before, but not after, adjustment for estimated glomerular filtration rate and proteinuria (hazard ratio, 1.11 per 1 SD lower VDMR [95% CI, 0.95-1.31]). Only 25(OH)D was associated with left ventricular mass index after full covariate adjustment (0.6 g/m per 10 ng/mL lower [95% CI, 0.0-1.3]). Conclusions Despite modest associations of 25(OH)D with left ventricular mass index, 25(OH)D, the VDMR, and 1,25(OH)D were not associated with incident CVD in chronic kidney disease.
• Imaizumi, T., Fujii, N., Hamano, T., Yang, W., Taguri, M., Kansal, M., Mehta, R., Shafi, T., Taliercio, J., Go, A., Rao, P., Hamm, L. L., Deo, R., Maruyama, S., Fukagawa, M., Feldman, H. I., & , C. S. (2023). Excess risk of cardiovascular events in patients in the United States vs. Japan with chronic kidney disease is mediated mainly by left ventricular structure and function. Kidney international, 103(5), 949-961.
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  While patients receiving dialysis therapy in the United States are more likely to develop cardiovascular disease (CVD) than those in Japan, direct comparisons of patients with predialysis chronic kidney disease (CKD) are rare. To study this, we compared various outcomes in patients with predialysis CKD using data from the Chronic Renal Insufficiency Cohort (CRIC) and CKD Japan Cohort (CKD-JAC) studies and determined mediators of any differences. Candidate mediators included left ventricular (LV) indices assessed by echocardiography. Among 3125 CRIC and 1097 CKD-JAC participants, the mean LV mass index (LVMI) and ejection fraction (EF) were 55.7 and 46.6 g/m and 54% and 65%, respectively (both significant). The difference in body mass index (32 and 24 kg/m, respectively) largely accounted for the differences in LVMI and C-reactive protein levels across cohorts. Low EF and high LVMI were significantly associated with subsequent CVD in both cohorts. During a median follow-up of five years, CRIC participants were at higher risk for CVD (adjusted hazard ratio [95% confidence interval]: 3.66 [2.74-4.89]) and death (4.69 [3.05-7.19]). A three-fold higher C-reactive protein concentration and higher phosphate levels in the United States cohort were moderately strong mediators of the differences in CVD. However, echocardiographic parameters were stronger mediators than these laboratory measures. LVMI, EF and their combination mediated the observed difference in CVD (27%, 50%, and 57%, respectively) and congestive heart failure (33%, 62%, and 70%, respectively). Thus, higher LV mass and lower EF, even in the normal range, were found to be predictive of CVD in CKD.
• Ishigami, J., Jaar, B. G., Charleston, J. B., Lash, J. P., Brown, J., Chen, J., Mills, K. T., Taliercio, J. J., Kansal, S., Crews, D. C., Riekert, K. A., Dowdy, D. W., Appel, L. J., Matsushita, K., & , C. S. (2023). Factors Associated With Non-vaccination for Influenza Among Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation.
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  Vaccination for influenza is strongly recommended for people with chronic kidney disease (CKD) due to their immunocompromised state. Identifying risk factors for not receiving an influenza vaccine (non-vaccination) could inform strategies for improving vaccine uptake in this high-risk population.
• Ishigami, J., Kansal, M., Mehta, R., Srivastava, A., Rahman, M., Dobre, M., Al-Kindi, S. G., Go, A. S., Navaneethan, S. D., Chen, J., He, J., Bhat, Z. Y., Jaar, B. G., Appel, L. J., Matsushita, K., & , C. S. (2023). Cardiac Structure and Function and Subsequent Kidney Disease Progression in Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation, 82(2), 225-236.
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  Heart-kidney crosstalk is recognized as the cardiorenal syndrome. We examined the association of cardiac function and structure with the risk of kidney failure with replacement therapy (KFRT) in a chronic kidney disease (CKD) population.
• Jamal, N. E., Brooks, T. G., Cohen, J., Townsend, R. R., de Sosa, G. R., Shah, V., Nelson, R. G., Drawz, P. E., Rao, P., Bhat, Z., Chang, A., Yang, W., FitzGerald, G. A., Skarke, C., & , C. S. (2023). Prognostic utility of rhythmic components in 24-hour ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity. medRxiv : the preprint server for health sciences.
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  Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD.
• Larkin, C. T., Fernández-Yepez, A. K., Carmona-Powell, E., Meza, N., Chen, J., González, J. C., Hernández, V. E., Veraza, D. I., Lineares-Koloffon, C., Ricardo, A. C., Madero, M., Lash, J. P., & , C. S. (2023). Ideal Cardiovascular Health in Mexican Adults with CKD Living in Mexico City Versus Chicago. Journal of immigrant and minority health, 25(6), 1488-1492.
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  Evidence suggests that Mexican adults living in Mexico have a more favorable cardiovascular risk profile than Mexican adults living in the U.S. However, this relationship has not been evaluated among patients with chronic kidney disease (CKD), which is a question of importance given the high risk for cardiovascular disease among patients with CKD. Using data from two ongoing observational cohort studies, we compared the prevalence of ideal cardiovascular health metrics (assessed by the American Heart Association "Life's Simple 7" criteria) in 309 Mexican adults with CKD living in Mexico City to 343 Mexican adults with CKD living in Chicago. Mexican adults with CKD living in Mexico City had a significantly higher prevalence of ideal body mass index (25 vs. 10%), diet (17 vs. 8%), total cholesterol (80 vs. 63%), blood pressure (43 vs. 25%), and fasting glucose (54 vs. 42%). Mexican adults with CKD living in both Mexico City and Chicago had low levels of cardiovascular health scores. Future work is needed to better understand the lower prevalence of ideal cardiovascular health metrics in Chicago as compared to Mexico City.
• Leidner, A. S., Cai, X., Zelnick, L. R., Lee, J., Bansal, N., Pasch, A., Kansal, M., Chen, J., Anderson, A. H., Sondheimer, J. H., Lash, J. P., Townsend, R. R., Go, A. S., Feldman, H. I., Shah, S. J., Wolf, M., Isakova, T., Mehta, R. C., & , C. R. (2023). Fibroblast Growth Factor 23 and Risk of Heart Failure Subtype: The CRIC (Chronic Renal Insufficiency Cohort) Study. Kidney medicine, 5(11), 100723.
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  Heart failure (HF) is an important cause of morbidity and mortality among individuals with chronic kidney disease (CKD). A large body of evidence from preclinical and clinical studies implicates excess levels of fibroblast growth factor 23 (FGF23) in HF pathogenesis in CKD. It remains unclear whether the relationship between elevated FGF23 levels and HF risk among individuals with CKD varies by HF subtype.
• McCoy, I. E., Hsu, J. Y., Zhang, X., Diamantidis, C. J., Taliercio, J., Go, A. S., Liu, K. D., Drawz, P., Srivastava, A., Horwitz, E. J., He, J., Chen, J., Lash, J. P., Weir, M. R., Hsu, C. Y., & , C. R. (2023). Probing the Association between Acute Kidney Injury and Cardiovascular Outcomes. Clinical journal of the American Society of Nephrology : CJASN, 18(7), 850-7.
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  Patients hospitalized with AKI have higher subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality than their counterparts without AKI, but these higher risks may be due to differences in prehospitalization patient characteristics, including the baseline level of estimated glomerular filtration rate (eGFR), the rate of prior eGFR decline, and the proteinuria level, rather than AKI itself.
• Muiru, A. N., Hsu, J. Y., Zhang, X., Appel, L. J., Chen, J., Cohen, D. L., Drawz, P. E., Freedman, B. I., Go, A. S., He, J., Horwitz, E. J., Hsu, R. K., Lash, J. P., Liu, K. D., McCoy, I. E., Porter, A., Rao, P., Ricardo, A. C., Rincon-Choles, H., , Sondheimer, J., et al. (2023). Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study. Annals of internal medicine, 176(7), 961-968.
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  Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not.
• Pan, Y., Sun, X., Mi, X., Huang, Z., Hsu, Y., Hixson, J. E., Munzy, D., Metcalf, G., Franceschini, N., Tin, A., Köttgen, A., Francis, M., , N. T., Brody, J. A., Kestenbaum, B., Sitlani, C. M., Mychaleckyj, J. C., Kramer, H., Lange, L. A., , Guo, X., et al. (2023). Whole-exome sequencing study identifies four novel gene loci associated with diabetic kidney disease. Human molecular genetics, 32(6), 1048-1060.
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  Diabetic kidney disease (DKD) is recognized as an important public health challenge. However, its genomic mechanisms are poorly understood. To identify rare variants for DKD, we conducted a whole-exome sequencing (WES) study leveraging large cohorts well-phenotyped for chronic kidney disease and diabetes. Our two-stage WES study included 4372 European and African ancestry participants from the Chronic Renal Insufficiency Cohort and Atherosclerosis Risk in Communities studies (stage 1) and 11 487 multi-ancestry Trans-Omics for Precision Medicine participants (stage 2). Generalized linear mixed models, which accounted for genetic relatedness and adjusted for age, sex and ancestry, were used to test associations between single variants and DKD. Gene-based aggregate rare variant analyses were conducted using an optimized sequence kernel association test implemented within our mixed model framework. We identified four novel exome-wide significant DKD-related loci through initiating diabetes. In single-variant analyses, participants carrying a rare, in-frame insertion in the DIS3L2 gene (rs141560952) exhibited a 193-fold increased odds [95% confidence interval (CI): 33.6, 1105] of DKD compared with noncarriers (P = 3.59 × 10-9). Likewise, each copy of a low-frequency KRT6B splice-site variant (rs425827) conferred a 5.31-fold higher odds (95% CI: 3.06, 9.21) of DKD (P = 2.72 × 10-9). Aggregate gene-based analyses further identified ERAP2 (P = 4.03 × 10-8) and NPEPPS (P = 1.51 × 10-7), which are both expressed in the kidney and implicated in renin-angiotensin-aldosterone system modulated immune response. In the largest WES study of DKD, we identified novel rare variant loci attaining exome-wide significance. These findings provide new insights into the molecular mechanisms underlying DKD.
• Poudel, B., Rosenson, R. S., Kent, S. T., Bittner, V., Gutiérrez, O. M., Anderson, A. H., Woodward, M., Jackson, E. A., Monda, K. L., Bajaj, A., Huang, L., Kansal, M., Rahman, M., He, J., Muntner, P., Colantonio, L. D., & , C. S. (2023). Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study. Kidney medicine, 5(7), 100648.
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  Many adults with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) have high lipoprotein(a) levels. It is unclear whether high lipoprotein(a) levels confer an increased risk for recurrent ASCVD events in this population. We estimated the risk for recurrent ASCVD events associated with lipoprotein(a) in adults with CKD and prevalent ASCVD.
• Ren, Y., Ruan, P., Segal, M., Dobre, M., Schelling, J. R., Banerjee, U., Shafi, T., Ganz, P., Dubin, R. F., & , C. S. (2023). Evaluation of a large-scale aptamer proteomics platform among patients with kidney failure on dialysis. PloS one, 18(12), e0293945.
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  Patients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.0) that measures ~ 5000 proteins, in preparation for a larger study using this platform in cohorts with kidney failure.
• Schrauben, S. J., Sapa, H., Xie, D., Zhang, X., Anderson, A. H., Shlipak, M. G., Hsu, C. Y., Shafi, T., Mehta, R., Bhat, Z., Brown, J., Charleston, J., Chen, J., He, J., Ix, J. H., Rao, P., Townsend, R., Kimmel, P. L., Vasan, R. S., , Feldman, H. I., et al. (2023). Association of urine and plasma ADMA with atherosclerotic risk in DKD cardiovascular disease risk in diabetic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 38(12), 2809-2815.
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  Chronic kidney disease (CKD) is associated with atherosclerotic cardiovascular disease (ASCVD) risk, especially among those with diabetes. Altered metabolism of solutes that accumulate in CKD [asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and trimethylamine N-oxide (TMAO)] may reflect pathways linking CKD with ASCVD.
• Shao, B., Afshinnia, F., Mathew, A. V., Ronsein, G. E., Thornock, C., Irwin, A. D., Kansal, M., Rao, P. S., Dobre, M., Al-Kindi, S., Weir, M. R., Go, A., He, J., Chen, J., Feldman, H., Bornfeldt, K. E., Pennathur, S., & , M. K. (2023). Low concentrations of medium-sized HDL particles predict incident CVD in chronic kidney disease patients. Journal of lipid research, 64(6), 100381.
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  Patients with chronic kidney disease (CKD) are at high risk for CVD. However, traditional CVD risk factors cannot completely explain the increased risk. Altered HDL proteome is linked with incident CVD in CKD patients, but it is unclear whether other HDL metrics are associated with incident CVD in this population. In the current study, we analyzed samples from two independent prospective case-control cohorts of CKD patients, the Clinical Phenotyping and Resource Biobank Core (CPROBE) and the Chronic Renal Insufficiency Cohort (CRIC). We measured HDL particle sizes and concentrations (HDL-P) by calibrated ion mobility analysis and HDL cholesterol efflux capacity (CEC) by cAMP-stimulated J774 macrophages in 92 subjects from the CPROBE cohort (46 CVD and 46 controls) and in 91 subjects from the CRIC cohort (34 CVD and 57 controls). We tested associations of HDL metrics with incident CVD using logistic regression analysis. No significant associations were found for HDL-C or HDL-CEC in either cohort. Total HDL-P was only negatively associated with incident CVD in the CRIC cohort in unadjusted analysis. Among the six sized HDL subspecies, only medium-sized HDL-P was significantly and negatively associated with incident CVD in both cohorts after adjusting for clinical confounders and lipid risk factors with odds ratios (per 1-SD) of 0.45 (0.22-0.93, P = 0.032) and 0.42 (0.20-0.87, P = 0.019) for CPROBE and CRIC cohorts, respectively. Our observations indicate that medium-sized HDL-P-but not other-sized HDL-P or total HDL-P, HDL-C, or HDL-CEC-may be a prognostic cardiovascular risk marker in CKD.
• Shea, M. K., Wang, J., Barger, K., Weiner, D. E., Townsend, R. R., Feldman, H. I., Rosas, S. E., Chen, J., He, J., Flack, J., Jaar, B. G., Kansal, M., Booth, S. L., & , C. S. (2023). Association of Vitamin K Status with Arterial Calcification and Stiffness in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort. Current developments in nutrition, 7(1), 100008.
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  Arterial calcification and stiffness are common in people with chronic kidney disease (CKD). Higher vitamin K status has been associated with less arterial calcification and stiffness in CKD in cross-sectional studies.
• Sridhara, S., Gungor, A. B., Erol, H. K., Al-Obaidi, M., Zangeneh, T. T., Bedrick, E. J., Ariyamuthu, V. K., Shetty, A., Qannus, A. A., Mendoza, K., Murugapandian, S., Gupta, G., & Tanriover, B. (2023). Lack of effectiveness of Bebtelovimab monoclonal antibody among high-risk patients with SARS-Cov-2 Omicron during BA.2, BA.2.12.1 and BA.5 subvariants dominated era. PloS one, 18(4), e0279326.
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  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the real-world experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N = 1,091) compared to propensity score (PS) matched control (N = 1,091). The primary composite outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary composite outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence of the primary outcome (p = 0.67). In the subgroup analysis, we observed similar no-difference trends regarding the primary outcomes for the propensity rematched BEB MAb treated and untreated groups, stratified by patient vaccination status, age (
• Sullivan, V. K., Appel, L. J., Anderson, C. A., Kim, H., Unruh, M. L., Lash, J. P., Trego, M., Sondheimer, J., Dobre, M., Pradhan, N., Rao, P. S., Chen, J., He, J., Rebholz, C. M., & , C. S. (2023). Ultraprocessed Foods and Kidney Disease Progression, Mortality, and Cardiovascular Disease Risk in the CRIC Study. American journal of kidney diseases : the official journal of the National Kidney Foundation, 82(2), 202-212.
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  Ultraprocessed foods are widely consumed in the United States and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adults with chronic kidney disease (CKD).
• Sullivan, V. K., Appel, L. J., Anderson, C. A., Tan, T. C., Brown, J., Ricardo, A. C., Schrauben, S. J., Hsu, C. Y., Shah, V. O., Unruh, M., Nelson, R. G., Sondheimer, J., Chen, J., He, J., Charleston, J., Rebholz, C. M., & , C. S. (2023). Changes in Diet Quality, Risk of CKD Progression, and All-Cause Mortality in the CRIC Study. American journal of kidney diseases : the official journal of the National Kidney Foundation, 81(5), 621-624.
• Chiu, V., Gross, A. L., Chu, N. M., Segev, D., Hall, R. K., McAdams-DeMarco, M., & , C. S. (2022). Domains for a Comprehensive Geriatric Assessment of Older Adults with Chronic Kidney Disease: Results from the CRIC Study. American journal of nephrology, 53(11-12), 826-838.
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  A comprehensive geriatric assessment (CGA) tailored to the chronic kidney disease (CKD) population would yield a more targeted approach to assessment and care. We aimed to identify domains of a CKD-specific CGA (CKD-CGA), characterize patterns of these domains, and evaluate their predictive utility on adverse health outcomes.
• Cohen, J. B., Yang, W., Li, L., Zhang, X., Zheng, Z., Orlandi, P., Bansal, N., Deo, R., Lash, J. P., Rahman, M., He, J., Shafi, T., Chen, J., Cohen, D. L., Matsushita, K., Shlipak, M. G., Wolf, M., Go, A. S., Feldman, H. I., & , C. S. (2022). Time-Updated Changes in Estimated GFR and Proteinuria and Major Adverse Cardiac Events: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation, 79(1), 36-44.e1.
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  Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk.
• Dorans, K. S., Wright Nunes, J. A., Schaubel, D. E., Sha, D., Schrauben, S. J., Nelson, R. G., Rao, P. S., Cohen, D. L., Appel, L. J., Lash, J. P., Rahman, M., Feldman, H. I., & , C. S. (2022). Associations of Anxiety during the COVID-19 Pandemic with Patient Characteristics and Behaviors in CKD Patients: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. Kidney360, 3(8), 1341-1349.
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  Chronic kidney disease (CKD) is associated with anxiety and depression. Although the coronavirus disease 2019 (COVID-19) pandemic has increased stressors on patients with CKD, assessments of anxiety and its predictors and consequences on behaviors, specifically virus mitigation behaviors, are lacking.
• Hassanein, M., Arrigain, S., Schold, J. D., Nakhoul, G. N., Navaneethan, S. D., Mehdi, A., Sekar, A., Tabbara, J., Taliercio, J. J., & , C. I. (2022). Dysnatremias, Mortality, and Kidney Failure in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Kidney medicine, 4(12), 100554.
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  Dysnatremias have been associated with an increased risk of mortality in the chronic kidney disease (CKD) population. Our objective is to identify the prevalence of and risk factors associated with dysnatremias in a CKD population and assess the association of dysnatremias with kidney failure and mortality among patients with CKD enrolled in the Chronic Renal Insufficiency Cohort Study.
• Muiru, A. N., Yang, J., Derebail, V. K., Liu, K. D., Feldman, H. I., Srivastava, A., Bhat, Z., Saraf, S. L., Chen, T. K., He, J., Estrella, M. M., Go, A. S., Hsu, C. Y., & , C. S. (2022). Black and White Adults With CKD Hospitalized With Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation, 80(5), 610-618.e1.
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  Few studies have investigated racial disparities in acute kidney injury (AKI), in contrast to the extensive literature on racial differences in the risk of kidney failure. We sought to study potential differences in risk in the setting of chronic kidney disease (CKD).
• Rhee, E. P., Surapaneni, A., Zheng, Z., Zhou, L., Dutta, D., Arking, D. E., Zhang, J., Duong, T., Chatterjee, N., Luo, S., Schlosser, P., Mehta, R., Waikar, S. S., Saraf, S. L., Kelly, T. N., Hamm, L. L., Rao, P. S., Mathew, A. V., Hsu, C. Y., , Parsa, A., et al. (2022). Trans-ethnic genome-wide association study of blood metabolites in the Chronic Renal Insufficiency Cohort (CRIC) study. Kidney international, 101(4), 814-823.
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  Metabolomics genome wide association study (GWAS) help outline the genetic contribution to human metabolism. However, studies to date have focused on relatively healthy, population-based samples of White individuals. Here, we conducted a GWAS of 537 blood metabolites measured in the Chronic Renal Insufficiency Cohort (CRIC) Study, with separate analyses in 822 White and 687 Black study participants. Trans-ethnic meta-analysis was then applied to improve fine-mapping of potential causal variants. Mean estimated glomerular filtration rate was 44.4 and 41.5 mL/min/1.73m in the White and Black participants, respectively. There were 45 significant metabolite associations at 19 loci, including novel associations at PYROXD2, PHYHD1, FADS1-3, ACOT2, MYRF, FAAH, and LIPC. The strength of associations was unchanged in models additionally adjusted for estimated glomerular filtration rate and proteinuria, consistent with a direct biochemical effect of gene products on associated metabolites. At several loci, trans-ethnic meta-analysis, which leverages differences in linkage disequilibrium across populations, reduced the number and/or genomic interval spanned by potentially causal single nucleotide polymorphisms compared to fine-mapping in the White participant cohort alone. Across all validated associations, we found strong concordance in effect sizes of the potentially causal single nucleotide polymorphisms between White and Black study participants. Thus, our study identifies novel genetic determinants of blood metabolites in chronic kidney disease, demonstrates the value of diverse cohorts to improve causal inference in metabolomics GWAS, and underscores the shared genetic basis of metabolism across race.
• Taliercio, J. J., Nakhoul, G., Mehdi, A., Yang, W., Sha, D., Schold, J. D., Kasner, S., Weir, M., Hassanein, M., Navaneethan, S. D., Krishnan, G., Kanthety, R., Go, A. S., Deo, R., Lora, C. M., Jaar, B. G., Chen, T. K., Chen, J., He, J., , Rahman, M., et al. (2022). Aspirin for Primary and Secondary Prevention of Mortality, Cardiovascular Disease, and Kidney Failure in the Chronic Renal Insufficiency Cohort (CRIC) Study. Kidney medicine, 4(11), 100547.
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  Chronic kidney disease is a risk enhancing factor for cardiovascular disease (CVD) and mortality, and the role of aspirin use is unclear in this population. We investigated the risk and benefits of aspirin use in primary and secondary prevention of CVD in the Chronic Renal Insufficiency Cohort Study.
• London, E. D., Berman, S. M., Chakrapani, S., Delibasi, T., Monterosso, J., Erol, H. K., Paz-Filho, G., Wong, M. L., & Licinio, J. (2011). Short-term plasticity of gray matter associated with leptin deficiency and replacement. The Journal of clinical endocrinology and metabolism, 96(8), E1212-20.
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  Leptin affects neurogenesis, neuronal growth, and viability. We previously reported that leptin supplementation increased gray matter (GM) concentration in the anterior cingulate gyrus (ACG), cerebellum, and inferior parietal lobule, areas that are also involved in food intake.
• Paz-Filho, G. J., Andrews, D., Esposito, K., Erol, H. K., Delibasi, T., Wong, M. L., & Licinio, J. (2009). Effects of leptin replacement on risk factors for cardiovascular disease in genetically leptin-deficient subjects. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 41(2), 164-7.
• Paz-Filho, G. J., Delibasi, T., Erol, H. K., Wong, M. L., & Licinio, J. (2009). Cellular immunity before and after leptin replacement therapy. Journal of pediatric endocrinology & metabolism : JPEM, 22(11), 1069-74.
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  The few identified leptin-deficient children have immune deficiency.
• Paz-Filho, G., Delibasi, T., Erol, H. K., Wong, M. L., & Licinio, J. (2009). Congenital leptin deficiency and thyroid function. Thyroid research, 2(1), 11.
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  : Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four leptin-deficient humans (2 males aged 5 and 27, and 2 females aged 35 and 40), before and during leptin replacement with recombinant human methionyl leptin (r-metHuLeptin). The child was evaluated for four years, and the adults, for eight years. In addition, the adults were submitted to a brief withdrawal of leptin during six weeks in the sixth year. Our results show that, regardless of leptin replacement, our leptin-deficient patients have normal thyroid function. In spite of having an important role in regulating the hypothalamic-pituitary-thyroidal axis, leptin is not required for normal thyroid function.
• Paz-Filho, G. J., Ayala, A., Esposito, K., Erol, H. K., Delibasi, T., Hurwitz, B. E., Wong, M. L., & Licinio, J. (2008). Effects of leptin on lipid metabolism. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 40(8), 572-4.
• Paz-Filho, G. J., Babikian, T., Asarnow, R., Delibasi, T., Esposito, K., Erol, H. K., Wong, M. L., & Licinio, J. (2008). Leptin replacement improves cognitive development. PloS one, 3(8), e3098.
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  Leptin changes brain structure, neuron excitability and synaptic plasticity. It also regulates the development and function of feeding circuits. However, the effects of leptin on neurocognitive development are unknown.
• Delibasi, T., Ustun, I., Aydin, Y., Berker, D., Erol, H. K., Gul, K., Unal, M., & Guler, S. (2006). Early severe pre-eclamptic findings in a patient with Cushing's syndrome. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 22(12), 710-2.
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  Cushing's syndrome occurs rarely in pregnancy because of ovulatory disturbances including anovulation which is caused by hypercortisolism, but it can cause maternal complications such as hypertension, gestational diabetes, spontaneous abortion, premature birth, pre-eclampsia and stillbirth. Herein we present the case of a 22-year-old patient in the 11th week of pregnancy who was admitted to our hospital with Cushing's syndrome complicated by early pre-eclampsia. Severe pre-eclampsia has high maternal and perinatal morbidities, and therefore the possibility of this complication requires that Cushing's syndrome, although rare in pregnancy, be given a high clinical suspicion. Medical therapy and/or surgical therapy should be considered promptly to influence outcome favorably.