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Bansal M, Kasliwal RR, Chandra P, Kapoor R, Chouhan N, Bhan A, Trehan N. The relevance of remnant cholesterol as a guide for lipid management in Indian subjects undergoing coronary revascularization. Diabetes Metab Syndr 2025; 19:103183. [PMID: 39733493 DOI: 10.1016/j.dsx.2024.103183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 12/21/2024] [Accepted: 12/26/2024] [Indexed: 12/31/2024]
Abstract
BACKGROUND The atherogenic potential of remnant cholesterol, which refers to the cholesterol content of triglyceride-rich, non-low-density lipoprotein (LDL) particles in circulation, has gained increasing attention recently. Unfortunately, very limited information is available regarding remnant cholesterol levels in Indian subjects. METHODS This was a retrospective study conducted at a premier, tertiary care center in North India. A total of 3064 consecutive subjects [mean age 61.3 ± 10.3 years, 2550 (83.2%) men] with newly diagnosed coronary artery disease (CAD) undergoing coronary revascularization were included. Enzymatic assays were used for measuring various lipid parameters. Remnant cholesterol was calculated by subtracting LDL cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol. A value >30 mg/dL was considered elevated. RESULTS The mean LDL-C was 79.1 ± 33.1 mg/dL with 46.4% of all subjects having LDL-C <70 mg/dL and only 16.9% having LDL-C <50 mg/dL. The median remnant cholesterol level was 17.0 mg/dL (interquartile range 12.0-24.0 mg/dL) with only 11.9% of subjects having values >30 mg/dL. Only 4.5% of the patients with LDL-C <70 mg/dL and 2.9% of those with LDL-C <50 mg/dL had elevated remnant cholesterol. These proportions were significantly greater in patients with serum triglycerides >200 mg/dL. CONCLUSION Our study shows that in a North-Indian population with CAD, elevated remnant cholesterol was present in only a small proportion. The prevalence of elevated remnant cholesterol decreased further as the LDL-C control improved. These findings suggest that elevated remnant cholesterol may not be a clinically relevant therapeutic target in most patients with LDL-C below the currently recommended goals.
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Affiliation(s)
- Manish Bansal
- Division of Clinical and Preventive Cardiology, Medanta- The Medicity, Gurgaon, India.
| | - Ravi R Kasliwal
- Division of Clinical and Preventive Cardiology, Medanta- The Medicity, Gurgaon, India
| | - Praveen Chandra
- Division of Interventional Cardiology, Medanta- The Medicity, Gurgaon, India
| | - Rajneesh Kapoor
- Division of Interventional Cardiology, Medanta- The Medicity, Gurgaon, India
| | - Nagendra Chouhan
- Division of Interventional Cardiology, Medanta- The Medicity, Gurgaon, India
| | - Anil Bhan
- Division of Cardiothoracic Surgery, Medanta- The Medicity, Gurgaon, India
| | - Naresh Trehan
- Division of Cardiothoracic Surgery, Medanta- The Medicity, Gurgaon, India
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Kononikhin AS, Starodubtseva NL, Brzhozovskiy AG, Tokareva AO, Kashirina DN, Zakharova NV, Bugrova AE, Indeykina MI, Pastushkova LK, Larina IM, Mitkevich VA, Makarov AA, Nikolaev EN. Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals. Biomedicines 2024; 12:2403. [PMID: 39457715 PMCID: PMC11504031 DOI: 10.3390/biomedicines12102403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/18/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. METHODS In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. RESULTS The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer's disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). CONCLUSIONS The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels.
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Affiliation(s)
- Alexey S. Kononikhin
- Project Center of Advanced Mass Spectrometry Technologies, 121205 Moscow, Russia;
- Institute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, Russia; (D.N.K.); (L.K.P.); (I.M.L.)
| | - Natalia L. Starodubtseva
- V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997 Moscow, Russia; (N.L.S.); (A.O.T.); (A.E.B.)
- Moscow Center for Advanced Studies, 123592 Moscow, Russia
| | - Alexander G. Brzhozovskiy
- Project Center of Advanced Mass Spectrometry Technologies, 121205 Moscow, Russia;
- Institute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, Russia; (D.N.K.); (L.K.P.); (I.M.L.)
| | - Alisa O. Tokareva
- V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997 Moscow, Russia; (N.L.S.); (A.O.T.); (A.E.B.)
| | - Daria N. Kashirina
- Institute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, Russia; (D.N.K.); (L.K.P.); (I.M.L.)
| | - Natalia V. Zakharova
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia; (N.V.Z.); (M.I.I.)
| | - Anna E. Bugrova
- V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997 Moscow, Russia; (N.L.S.); (A.O.T.); (A.E.B.)
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia; (N.V.Z.); (M.I.I.)
| | - Maria I. Indeykina
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia; (N.V.Z.); (M.I.I.)
| | - Liudmila Kh. Pastushkova
- Institute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, Russia; (D.N.K.); (L.K.P.); (I.M.L.)
| | - Irina M. Larina
- Institute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, Russia; (D.N.K.); (L.K.P.); (I.M.L.)
| | - Vladimir A. Mitkevich
- Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia; (V.A.M.); (A.A.M.)
| | - Alexander A. Makarov
- Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia; (V.A.M.); (A.A.M.)
| | - Evgeny N. Nikolaev
- Project Center of Advanced Mass Spectrometry Technologies, 121205 Moscow, Russia;
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Berry P, Amarchand R, Ramakrishnan L, Gupta R, Kondal D, Bharadiya V, Krishnan A, Tandon N, Prabhakaran D, Roy A. Establishing Apolipoprotein-B and non-high-density-lipoprotein-C goals in Indian population: A Cross-sectional study. Indian Heart J 2024; 76:154-158. [PMID: 38871221 PMCID: PMC11329058 DOI: 10.1016/j.ihj.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 04/13/2024] [Accepted: 06/10/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. METHODS A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. RESULTS Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. CONCLUSION Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.
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Affiliation(s)
- Parul Berry
- CT Centre, AIIMS, Ansari Nagar, New Delhi, 110023, India
| | | | | | - Ruby Gupta
- CT Centre, AIIMS, Ansari Nagar, New Delhi, 110023, India
| | - Dimple Kondal
- CT Centre, AIIMS, Ansari Nagar, New Delhi, 110023, India
| | | | - Anand Krishnan
- CT Centre, AIIMS, Ansari Nagar, New Delhi, 110023, India
| | - Nikhil Tandon
- CT Centre, AIIMS, Ansari Nagar, New Delhi, 110023, India
| | | | - Ambuj Roy
- CT Centre, AIIMS, Ansari Nagar, New Delhi, 110023, India.
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Nammi JY, Pasala R, Kotaru S, Bandikolla SS, Andhe N, Gouravaram PR. Cardiovascular Disease Prevalence in Asians Versus Americans: A Review of Genetics, Diet, and the Call for Enhanced Prevention and Screening. Cureus 2024; 16:e58361. [PMID: 38756312 PMCID: PMC11096806 DOI: 10.7759/cureus.58361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2024] [Indexed: 05/18/2024] Open
Abstract
Cardiovascular disease (CVD) continues to pose a global health challenge, demonstrating significant disparities in occurrence among various populations. A wide number of research studies have indicated a higher prevalence of cardiovascular disease in South Asian immigrants compared to the local American population. The demand to improve the cardiovascular benefits of immigrants is increasing, which calls for further research with larger and more diverse population samples. This study will investigate the major causes of this variation, which include genetically diverse characteristics and changes in nutritional status among the study population groups. To assess the increase in the prevalence of cardiovascular disease among South Asian populations compared to the US population, a narrative review of accessible data is carried out. The data in support of the present document are from the Centre for Disease Prevention and Control, Statistics for Heart Diseases and Stroke 2023, a trend analysis about incidences of cardiac diseases and global burden in 2017, all dating back to the last two decades. Relevant articles from PubMed and Google Scholar have also been included, as appropriate, and their references are provided wherever necessary. Graphs for the geographical variations in disease incidence are produced using Microsoft Excel (Microsoft® Corp., Redmond, WA). The review shows that there is a significant decline in the prevalence of CVD among American citizens when compared to the steady increase in the number of cases among South Asians, which is attributed to the unique genetic predisposition of South Asians to be more prone to CVDs. The changing dietary habits also play an important role in the fall in HDL levels in South Asians when compared to Americans. This is driven by genetic disparities, including the APOA1 and APOA2 genes, and nutritional disparities, including variance in quality and quantity of dietary consumption. Addressing the escalating cases of CVD among South Asians necessitates additional research to enhance proactive preventive measures and implement screening programs specifically tailored to address prevalent risk factors within the population.
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Affiliation(s)
| | | | | | | | - Nikhil Andhe
- Medicine, Siddhartha Medical College, Vijayawada, IND
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Singh K, Prabhakaran D. Apolipoprotein B - An ideal biomarker for atherosclerosis? Indian Heart J 2024; 76 Suppl 1:S121-S129. [PMID: 38599726 PMCID: PMC11019329 DOI: 10.1016/j.ihj.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/02/2023] [Indexed: 04/12/2024] Open
Abstract
This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a predictor of atherosclerotic cardiovascular disease and recommendations of (inter)national treatment guidelines regarding Apo B in dyslipidemia management. A single Apo B molecule is present in every particle of very low-density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and lipoprotein(a). This unique single Apo B per particle ratio makes plasma Apo B concentration a direct measure of the number of circulating atherogenic lipoproteins. This review of global evidence on Apo B as a biomarker for atherosclerosis confirms that Apo B is a single atherogenic lipid marker present in all lipids sub-fractions except HDL-C, and thus, Apo B integrates and extends the information from triglycerides and cholesterol, which could simplify and improve care for atherosclerotic cardiovascular disease.
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Affiliation(s)
- Kavita Singh
- Public Health Foundation of India, Gurugram, Haryana, India; Heidelberg Institute of Global Health, Heidelberg University, Germany
| | - Dorairaj Prabhakaran
- Public Health Foundation India, Gurugram, Haryana, India; Centre for Chronic Disease Control, New Delhi, India; London School of Hygiene & Tropical Medicine, United Kingdom.
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Muniyappa R, Narayanappa SBK. Disentangling Dual Threats: Premature Coronary Artery Disease and Early-Onset Type 2 Diabetes Mellitus in South Asians. J Endocr Soc 2023; 8:bvad167. [PMID: 38178904 PMCID: PMC10765382 DOI: 10.1210/jendso/bvad167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Indexed: 01/06/2024] Open
Abstract
South Asian individuals (SAs) face heightened risks of premature coronary artery disease (CAD) and early-onset type 2 diabetes mellitus (T2DM), with grave health, societal, and economic implications due to the region's dense population. Both conditions, influenced by cardiometabolic risk factors such as insulin resistance, hypertension, and central adiposity, manifest earlier and with unique thresholds in SAs. Epidemiological, demographic, nutritional, environmental, sociocultural, and economic transitions in SA have exacerbated the twin epidemic. The coupling of premature CAD and T2DM arises from increased obesity due to limited adipose storage, early-life undernutrition, distinct fat thresholds, reduced muscle mass, and a predisposition for hepatic fat accumulation from certain dietary choices cumulatively precipitating a decline in insulin sensitivity. As T2DM ensues, the β-cell adaptive responses are suboptimal, precipitating a transition from compensatory hyperinsulinemia to β-cell decompensation, underscoring a reduced functional β-cell reserve in SAs. This review delves into the interplay of these mechanisms and highlights a prediabetes endotype tied to elevated vascular risk. Deciphering these mechanistic interconnections promises to refine stratification paradigms, surpassing extant risk-prediction strategies.
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Affiliation(s)
- Ranganath Muniyappa
- Clinical Endocrine Section, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
| | - Satish Babu K Narayanappa
- Department of Medicine, Sri Madhusudan Sai Institute of Medical Sciences and Research, Muddenahalli, Karnataka 562101, India
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Gupta K, Al Rifai M, Hussain A, Minhas AMK, Patel J, Kalra D, Samad Z, Virani SS. South Asian ethnicity: What can we do to make this risk enhancer a risk equivalent? Prog Cardiovasc Dis 2022; 75:21-32. [PMID: 36279943 DOI: 10.1016/j.pcad.2022.10.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 10/12/2022] [Indexed: 11/06/2022]
Abstract
South Asians account for around 25% of the global population and are the fastest-growing ethnicity in the US. This population has an increasing burden of atherosclerotic cardiovascular disease (ASCVD) which is also seen in the diaspora. Current risk prediction equations underestimate this risk and consider the South Asian ethnicity as a risk-enhancer among those with borderline-intermediate risk. In this review, we discuss why the South Asian population is at a higher risk of ASCVD and strategies to mitigate this increased risk.
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Affiliation(s)
- Kartik Gupta
- Department of Medicine, Henry Ford Hospital, Detroit, MI, USA
| | - Mahmoud Al Rifai
- Section of Cardiology and Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Aliza Hussain
- Section of Cardiology and Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | | | - Jaideep Patel
- Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University Medical Center, Richmond, VA, USA; Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA
| | - Dinesh Kalra
- Rudd Heart & Lung Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - Zainab Samad
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Salim S Virani
- Section of Cardiology and Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Health Policy, Quality & Informatics Program, Health Services Research and Development Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA; Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
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Prasad GVR, Bhamidi V. Managing cardiovascular disease risk in South Asian kidney transplant recipients. World J Transplant 2021; 11:147-160. [PMID: 34164291 PMCID: PMC8218347 DOI: 10.5500/wjt.v11.i6.147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/12/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
South Asians (SA) are at higher cardiovascular risk than other ethnic groups, and SA kidney transplant recipients (SA KTR) are no exception. SA KTR experience increased major adverse cardiovascular events both early and late post-transplantation. Cardiovascular risk management should therefore begin well before transplantation. SA candidates may require aggressive screening for pre-transplant cardiovascular disease (CVD) due to their ethnicity and comorbidities. Recording SA ethnicity during the pre-transplant evaluation may enable programs to better assess cardiovascular risk, thus allowing for earlier targeted peri- and post-transplant intervention to improve cardiovascular outcomes. Diabetes remains the most prominent post-transplant cardiovascular risk factor in SA KTR. Diabetes also clusters with other metabolic syndrome components including lower high-density lipoprotein cholesterol, higher triglycerides, hypertension, and central obesity in this population. Dyslipidemia, metabolic syndrome, and obesity are all significant CVD risk factors in SA KTR, and contribute to increased insulin resistance. Novel biomarkers such as adiponectin, apolipoprotein B, and lipoprotein (a) may be especially important to study in SA KTR. Focused interventions to improve health behaviors involving diet and exercise may especially benefit SA KTR. However, there are few interventional clinical trials specific to the SA population, and none are specific to SA KTR. In all cases, understanding the nuances of managing SA KTR as a distinct post-transplant group, while still screening for and managing each CVD risk factor individually in all patients may help improve the long-term success of all kidney transplant programs catering to multi-ethnic populations.
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Affiliation(s)
- G V Ramesh Prasad
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, ON, Canada
| | - Vaishnavi Bhamidi
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, ON, Canada
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