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Rusu CC, Kacso I, Moldovan D, Potra A, Tirinescu D, Ticala M, Maslyennikov Y, Urs A, Bondor CI. Exploring the Associations Between Inflammatory Biomarkers, Survival, and Cardiovascular Events in Hemodialysis Patients and the Interrelationship with Nutritional Parameters-The Experience of a Single Transylvanian Dialysis Center. J Clin Med 2025; 14:1139. [PMID: 40004669 PMCID: PMC11855970 DOI: 10.3390/jcm14041139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 01/27/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: In hemodialysis (HD), inflammatory biomarkers are discussed as prognostic markers for survival and cardiovascular events (CVEs). The results of the studies are not uniform and there are particularities related to population groups and comorbidities. In addition, it is known that inflammation determines protein malnutrition and less about the effect of adipose tissue on inflammation in HD. This study investigates the relationship between inflammatory molecules and nutritional biomarkers, and CVE and survival in HD patients. Methods: We included, in an observational, longitudinal study, 65 patients with chronic HD (53 without diabetes and 22 smokers), with a mean age of 60.1 ± 12.4 years. High-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta, tumor necrosis factor alpha (TNF-alpha), interleukin 6, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), soluble CD163 (sCD163), and fibroblast growth factor 21 were determined. We recorded survival and cardiovascular events for 60 months. Univariate and multivariate analyses were performed. Results: Hs-CRP was significantly associated with survival (p = 0.014) in the total group. In smokers and former smokers, TNF-α lower than 368.34 pg/mL was associated with better survival. In multivariate analysis, hs-CRP was correlated with adipose tissue biomarkers (p = 0.006), and sCD163 was correlated with total and LDL cholesterol (p = 0.002). In addition, in univariate analysis, sTWEAK was correlated with serum albumin (p = 0.026, r = -0.30). In conclusion, in HD patients, hs-CRP was significantly associated with survival, and low TNF-alpha values in smokers and former smokers were linked to better survival. Hs-CRP was also correlated with adipose tissue biomarkers, CD163 was correlated with total and LDL cholesterol, and albumin was inversely associated with sTWEAK. The relation between inflammatory molecules and adipose tissue biomarkers was less identified in HD patients until now.
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Affiliation(s)
- Crina Claudia Rusu
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Ina Kacso
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Diana Moldovan
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Alina Potra
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Dacian Tirinescu
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Maria Ticala
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Yuriy Maslyennikov
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Alexandra Urs
- Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Cosmina Ioana Bondor
- Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
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Eoli A, Ibing S, Schurmann C, Nadkarni GN, Heyne HO, Böttinger E. A clustering approach to improve our understanding of the genetic and phenotypic complexity of chronic kidney disease. Sci Rep 2024; 14:9642. [PMID: 38671065 PMCID: PMC11053134 DOI: 10.1038/s41598-024-59747-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 04/15/2024] [Indexed: 04/28/2024] Open
Abstract
Chronic kidney disease (CKD) is a complex disorder that causes a gradual loss of kidney function, affecting approximately 9.1% of the world's population. Here, we use a soft-clustering algorithm to deconstruct its genetic heterogeneity. First, we selected 322 CKD-associated independent genetic variants from published genome-wide association studies (GWAS) and added association results for 229 traits from the GWAS catalog. We then applied nonnegative matrix factorization (NMF) to discover overlapping clusters of related traits and variants. We computed cluster-specific polygenic scores and validated each cluster with a phenome-wide association study (PheWAS) on the BioMe biobank (n = 31,701). NMF identified nine clusters that reflect different aspects of CKD, with the top-weighted traits signifying areas such as kidney function, type 2 diabetes (T2D), and body weight. For most clusters, the top-weighted traits were confirmed in the PheWAS analysis. Results were found to be more significant in the cross-ancestry analysis, although significant ancestry-specific associations were also identified. While all alleles were associated with a decreased kidney function, associations with CKD-related diseases (e.g., T2D) were found only for a smaller subset of variants and differed across genetic ancestry groups. Our findings leverage genetics to gain insights into the underlying biology of CKD and investigate population-specific associations.
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Affiliation(s)
- A Eoli
- Digital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482.
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
- Hasso Plattner Institute for Digital Engineering gGmbH, Prof.-Dr.-Helmert-Str. 2-3, 14482, Potsdam, Germany.
| | - S Ibing
- Digital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Hasso Plattner Institute for Digital Engineering gGmbH, Prof.-Dr.-Helmert-Str. 2-3, 14482, Potsdam, Germany
| | - C Schurmann
- Digital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Hasso Plattner Institute for Digital Engineering gGmbH, Prof.-Dr.-Helmert-Str. 2-3, 14482, Potsdam, Germany
| | - G N Nadkarni
- Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- The Charles Bronfman Institute of Personalized Medicine, New York City, NY, USA
| | - H O Heyne
- Digital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Hasso Plattner Institute for Digital Engineering gGmbH, Prof.-Dr.-Helmert-Str. 2-3, 14482, Potsdam, Germany
| | - E Böttinger
- Digital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Hasso Plattner Institute for Digital Engineering gGmbH, Prof.-Dr.-Helmert-Str. 2-3, 14482, Potsdam, Germany
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Li C, Ng JKC, Chan GCK, Fung WWS, Lai KB, Poon PYK, Luk CCW, Chow KM, Szeto CC. Gut permeability, circulating bacterial fragments and measures of congestion in peritoneal dialysis. Clin Kidney J 2024; 17:sfae056. [PMID: 38516523 PMCID: PMC10956420 DOI: 10.1093/ckj/sfae056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Indexed: 03/23/2024] Open
Abstract
Background Limited data exist on the association between gut permeability, circulating bacterial fragment and volume overload in peritoneal dialysis (PD) patients. We measured circulating bacterial fragments, N-terminal pro B-type natriuretic peptide (NT-proBNP), calprotectin and zonulin levels, and evaluate their association with the clinical outcomes in PD patients. Methods This was a single-center prospective study on 108 consecutive incident PD patients. Plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels were measured. Primary outcomes were technique and patient survival, secondary outcomes were hospitalization data. Results There was no significant correlation between plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels. The Homeostatic Model Assessment for Insulin Resistance (HOMA)-2β index, which represents insulin resistance, positively correlated with plasma bacterial DNA (r = 0.421, P < .001) and calprotectin levels (r = 0.362, P = .003), while serum NT-proBNP level correlated with the severity of volume overload and residual renal function. Serum NT-proBNP level was associated with technique survival even after adjusting for confounding factors [adjusted hazard ratio (aHR) 1.030, 95% confidence interval 1.009-1.051]. NT-proBNP level was also associated with patient survival by univariate analysis, but the association became insignificant after adjusting for confounding factors (aHR 1.010, P = .073). Similarly, NT-proBNP correlated with the number of hospitalizations and duration of hospitalization by univariate analysis, but the association became insignificant after adjusting for confounding factors. Conclusion There was no correlation between markers of gut permeability, circulating bacterial fragments and measures of congestion in PD patients. Bacterial fragments levels and gut permeability are both associated with insulin resistance. Serum NT-proBNP level is associated with the severity of volume overload and technique survival. Further studies are required to delineate the mechanism of high circulating bacterial fragment levels in PD patients.
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Affiliation(s)
- Chuanlei Li
- Carol & Richard Yu Peritoneal Dialysis Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
- Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Jack Kit-Chung Ng
- Carol & Richard Yu Peritoneal Dialysis Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
| | - Gordon Chun-Kau Chan
- Carol & Richard Yu Peritoneal Dialysis Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
| | - Winston Wing-Shing Fung
- Carol & Richard Yu Peritoneal Dialysis Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
| | - Ka-Bik Lai
- Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Peter Yam-Kau Poon
- Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Cathy Choi-Wan Luk
- Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Kai-Ming Chow
- Carol & Richard Yu Peritoneal Dialysis Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
| | - Cheuk-Chun Szeto
- Carol & Richard Yu Peritoneal Dialysis Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
- Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
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Eoli A, Ibing S, Schurmann C, Nadkarni GN, Heyne H, Böttinger E. A clustering approach to improve our understanding of the genetic and phenotypic complexity of chronic kidney disease. RESEARCH SQUARE 2023:rs.3.rs-3424565. [PMID: 37886494 PMCID: PMC10602158 DOI: 10.21203/rs.3.rs-3424565/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2023]
Abstract
Chronic kidney disease (CKD) is a complex disorder that causes a gradual loss of kidney function, affecting approximately 9.1% of the world's population. Here, we use a soft-clustering algorithm to deconstruct its genetic heterogeneity. First, we selected 322 CKD-associated independent genetic variants from published genome-wide association studies (GWAS) and added association results for 229 traits from the GWAS catalog. We then applied nonnegative matrix factorization (NMF) to discover overlapping clusters of related traits and variants. We computed cluster-specific polygenic scores and validated each cluster with a phenome-wide association study (PheWAS) on the BioMe biobank (n=31,701). NMF identified nine clusters that reflect different aspects of CKD, with the top-weighted traits signifying areas such as kidney function, type 2 diabetes (T2D), and body weight. For most clusters, the top-weighted traits were confirmed in the PheWAS analysis. Results were found to be more significant in the cross-ancestry analysis, although significant ancestry-specific associations were also identified. While all alleles were associated with a decreased kidney function, associations with CKD-related diseases (e.g., T2D) were found only for a smaller subset of variants and differed across genetic ancestry groups. Our findings leverage genetics to gain insights into the underlying biology of CKD and investigate population-specific associations.
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Affiliation(s)
- Andrea Eoli
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai
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Eoli A, Ibing S, Schurmann C, Nadkarni G, Heyne H, Böttinger E. A clustering approach to improve our understanding of the genetic and phenotypic complexity of chronic kidney disease. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.10.12.23296926. [PMID: 37873472 PMCID: PMC10593036 DOI: 10.1101/2023.10.12.23296926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
Chronic kidney disease (CKD) is a complex disorder that causes a gradual loss of kidney function, affecting approximately 9.1% of the world's population. Here, we use a soft-clustering algorithm to deconstruct its genetic heterogeneity. First, we selected 322 CKD-associated independent genetic variants from published genome-wide association studies (GWAS) and added association results for 229 traits from the GWAS catalog. We then applied nonnegative matrix factorization (NMF) to discover overlapping clusters of related traits and variants. We computed cluster-specific polygenic scores and validated each cluster with a phenome-wide association study (PheWAS) on the BioMe biobank (n=31,701). NMF identified nine clusters that reflect different aspects of CKD, with the top-weighted traits signifying areas such as kidney function, type 2 diabetes (T2D), and body weight. For most clusters, the top-weighted traits were confirmed in the PheWAS analysis. Results were found to be more significant in the cross-ancestry analysis, although significant ancestry-specific associations were also identified. While all alleles were associated with a decreased kidney function, associations with CKD-related diseases (e.g., T2D) were found only for a smaller subset of variants and differed across genetic ancestry groups. Our findings leverage genetics to gain insights into the underlying biology of CKD and investigate population-specific associations.
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Affiliation(s)
- A. Eoli
- Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, Germany
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - S. Ibing
- Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, Germany
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - C. Schurmann
- Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, Germany
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Current address: Bayer AG, Research & Development, Pharmaceuticals, Berlin, Germany
| | - G.N. Nadkarni
- Windreich Dept. of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- The Charles Bronfman Institute of Personalized Medicine, New York City, NY, USA
| | - H.O. Heyne
- Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, Germany
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Windreich Dept. of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - E. Böttinger
- Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, Germany
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
- Windreich Dept. of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
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Martins S, António N, Carvalheiro T, Laranjeira P, Rodrigues R, Gonçalves L, Tomaz C, Paiva A. Reduced numbers of regulatory T cells in chronic heart failure seems not to be restored by cardiac resynchronization therapy. BMC Cardiovasc Disord 2023; 23:89. [PMID: 36792985 PMCID: PMC9933267 DOI: 10.1186/s12872-023-03109-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 02/03/2023] [Indexed: 02/17/2023] Open
Abstract
BACKGROUND T cells have been implicated in the development and progression of inflammatory processes in chronic heart failure (CHF). Cardiac resynchronization therapy (CRT) has beneficial effects on symptoms and cardiac remodeling in CHF. However, its impact on the inflammatory immune response remains controversial. We aimed to study the impact of CRT on T cells in heart failure (HF) patients. METHODS Thirty-nine HF patients were evaluated before CRT (T0) and six months later (T6). Quantification of T cells, their subsets, and their functional characterization, after in vitro stimulation, were evaluated by flow cytometry. RESULTS T regulatory (Treg) cells were decreased in CHF patients (healthy group (HG): 1.08 ± 0.50 versus (heart failure patients (HFP)-T0: 0.69 ± 0.40, P = 0.022) and remaining diminished after CRT (HFP-T6: 0.61 ± 0.29, P = 0.003). Responders (R) to CRT presented a higher frequency of T cytotoxic (Tc) cells producing IL-2 at T0 compared with non-responders (NR) (R: 36.52 ± 12.55 versus NR: 24.71 ± 11.66, P = 0.006). After CRT, HF patients presented a higher percentage of Tc cells expressing TNF-α and IFN-γ (HG: 44.50 ± 16.62 versus R: 61.47 ± 20.54, P = 0.014; and HG: 40.62 ± 15.36 versus R: 52.39 ± 18.66, P = 0.049, respectively). CONCLUSION The dynamic of different functional T cell subpopulations is significantly altered in CHF, which results in an exacerbated pro-inflammatory response. Even after CRT, it seems that the inflammatory condition underlying CHF continues to evolve with the progression of the disease. This could be due, at least in part, to the inability to restore Treg cells levels. TRIAL REGISTRATION Observational and prospective study with no trial registration.
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Affiliation(s)
- Sílvia Martins
- Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506, Covilhã, Portugal
- Ciências Biomédicas Laboratoriais, Instituto Politécnico de Castelo Branco, ESALD-Dr, Lopes Dias Health School, Castelo Branco, Portugal
- Department of Clinical Pathology, Unidade Local de Saúde de Castelo Branco, 6000-085, Castelo Branco, Portugal
- University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
| | - Natália António
- Cardiology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- Institute of Pharmacology and Experimental Therapeutics/iCBR, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Tiago Carvalheiro
- Centro do Sangue e da Transplantação de Coimbra, Instituto Português do Sangue e da Transplantação, Coimbra, Portugal
| | - Paula Laranjeira
- University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
- Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- Ciências Biomédicas Laboratoriais, Instituto Politécnico de Coimbra, ESTESC-Coimbra Health School, Coimbra, Portugal
| | - Ricardo Rodrigues
- Department of Clinical Pathology, Unidade Local de Saúde de Castelo Branco, 6000-085, Castelo Branco, Portugal
| | - Lino Gonçalves
- Cardiology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- Institute of Pharmacology and Experimental Therapeutics/iCBR, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Cândida Tomaz
- Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506, Covilhã, Portugal
- Chemistry Department, University of Beira Interior, Covilhã, Portugal
| | - Artur Paiva
- University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal.
- Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
- Ciências Biomédicas Laboratoriais, Instituto Politécnico de Coimbra, ESTESC-Coimbra Health School, Coimbra, Portugal.
- Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075, Coimbra, Portugal.
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Perkins RK, van Vliet S, Miranda ER, Fuller KNZ, Beisswenger PJ, Wilund KR, Paluska SA, Burd NA, Haus JM. Advanced Glycation End Products and Inflammatory Cytokine Profiles in Maintenance Hemodialysis Patients After the Ingestion of a Protein-Dense Meal. J Ren Nutr 2023; 33:181-192. [PMID: 34923111 PMCID: PMC10580815 DOI: 10.1053/j.jrn.2021.11.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 11/11/2021] [Accepted: 11/28/2021] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVE The goal of this investigation was to evaluate circulating and skeletal muscle inflammatory biomarkers between maintenance hemodialysis (MHD) and demographic-matched control subjects (CON) before and after ingestion of a protein-rich meal. DESIGN AND METHODS CON (n = 8; 50 ± 2 years; 31 ± 1 kg/m2) and MHD patients (n = 8; 56 ± 5 years; 32 ± 2 kg/m2) underwent a basal blood draw and muscle biopsy and serial blood draws after the ingestion of a mixed meal on a nondialysis day. Plasma advanced glycation end products (AGEs) and markers of oxidation were assessed via liquid chromatography-tandem mass spectrometry before and after the meal (+240 min). Circulating inflammatory cytokines and soluble receptors for AGE (sRAGE) isoforms (endogenous secretory RAGEs and cleaved RAGEs) were determined before and after the meal (+240 min). Basal muscle was probed for inflammatory cytokines and protein expression of related signaling components (RAGE, Toll-like receptor 4, oligosaccharyltransferase subunit 48, TIR-domain-containing adapter-inducing interferon-β, total IκBα, and pIκBα). RESULTS Basal circulating AGEs were 7- to 343-fold higher (P < .001) in MHD than those in CON, but only MG-H1 increased in CON after the meal (P < .001). There was a group effect (MHD > CON) for total sRAGEs (P = .02) and endogenous secretory RAGEs (P < .001) and a trend for cleaved RAGEs (P=.09), with no meal effect. In addition, there was a group effect (MHD < CON; P < .05) for circulating fractalkine, interleukin (IL)10, IL17A, and IL1β and a trend (P < .10) for IL6 and macrophage inflammatory protein 1 alpha, whereas tumor necrosis factor alpha was higher in MHD (P < .001). In muscle, Toll-like receptor 4 (P = .03), TIR-domain-containing adapter-inducing interferon-β (P = .002), and oligosaccharyltransferase subunit 48 (P = .02) expression was lower in MHD than that in CON, whereas IL6 was higher (P = .01) and IL8 (P = .08) tended to be higher in MHD. CONCLUSION Overall, MHD exhibited an exaggerated, circulating, and skeletal muscle inflammatory biomarker environment, and the meal did not appreciably affect the inflammatory status.
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Affiliation(s)
- Ryan K Perkins
- School of Kinesiology, University of Michigan, Ann Arbor, Michigan
| | - Stephan van Vliet
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Edwin R Miranda
- School of Kinesiology, University of Michigan, Ann Arbor, Michigan
| | | | | | - Kenneth R Wilund
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Scott A Paluska
- Department of Family Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Nicholas A Burd
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Jacob M Haus
- School of Kinesiology, University of Michigan, Ann Arbor, Michigan.
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Mediterranean Diet and Chronic Kidney Disease (CKD): A Practical Approach. Nutrients 2022; 15:nu15010097. [PMID: 36615755 PMCID: PMC9824533 DOI: 10.3390/nu15010097] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/12/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
Chronic kidney disease has become a serious public health issue, as well as others health problems such as hypertension, DM, and obesity. Mediterranean diet (MD) can reduce the risk of cardiovascular disease and cancer and can lead to weight loss in obesity. There are studies that suggest that MD could be the diet of choice for patients with CKD for its influence on endothelial function, inflammation, lipid profile and blood pressure. There are few studies that tell us how to adapt MD to this group of patients. This review aims to offer a practical approach to Mediterranean diet adaptation as nutritional treatment in CKD patients.
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Impact of Preoperative Handgrip Strength on Postoperative Outcome after Radical Gastrectomy for Gastric Cancer Patients. J Clin Med 2022; 11:jcm11237129. [PMID: 36498702 PMCID: PMC9737860 DOI: 10.3390/jcm11237129] [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] [Received: 10/08/2022] [Revised: 11/14/2022] [Accepted: 11/29/2022] [Indexed: 12/02/2022] Open
Abstract
In this study, we investigated whether preoperative low-handgrip strength (HGS) defined by the Asian working group for sarcopenia could be a predictor of postoperative outcomes in patients with gastric cancer. A total of 327 patients who underwent radical gastrectomy for c-stage I-III primary gastric cancer with pre-operative HGS records were included. The cut-off values of HGS were defined as 28 kg for males and 18 kg for females, with values below and above the cut-off defined as low-HGS and high-HGS, respectively. The primary outcome was infectious complications. We compared the postoperative outcomes of the groups after adjusting for the background using propensity score matching. Of the 327 patients, 246 (75.2%) and 81 (24.8%) were in the high and low-HGS groups, respectively. After adjusting for background, there were 57 patients in both groups. After matching, the low-HGS group had significantly more infectious complications (17.5% vs. 1.8%, p = 0.008). Multivariate analysis of infectious complications in the low-HGS group demonstrated chronic kidney disease and diabetes as independent risk factors (odds ratio 4.390, 95% confidence interval 1.120-17.20, p = 0.034). Preoperative low-HGS according to the Asian criteria was associated with infectious complications after gastrectomy. Chronic kidney disease and diabetes were independent risk factors for infectious complications among patients with low-HGS.
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10
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Canaud B, Morena-Carrere M, Leray-Moragues H, Cristol JP. Fluid Overload and Tissue Sodium Accumulation as Main Drivers of Protein Energy Malnutrition in Dialysis Patients. Nutrients 2022; 14:4489. [PMID: 36364751 PMCID: PMC9658859 DOI: 10.3390/nu14214489] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/17/2022] [Accepted: 10/19/2022] [Indexed: 01/15/2024] Open
Abstract
Protein energy malnutrition is recognized as a leading cause of morbidity and mortality in dialysis patients. Protein-energy-wasting process is observed in about 45% of the dialysis population using common biomarkers worldwide. Although several factors are implicated in protein energy wasting, inflammation and oxidative stress mechanisms play a central role in this pathogenic process. In this in-depth review, we analyzed the implication of sodium and water accumulation, as well as the role of fluid overload and fluid management, as major contributors to protein-energy-wasting process. Fluid overload and fluid depletion mimic a tide up and down phenomenon that contributes to inducing hypercatabolism and stimulates oxidation phosphorylation mechanisms at the cellular level in particular muscles. This endogenous metabolic water production may contribute to hyponatremia. In addition, salt tissue accumulation likely contributes to hypercatabolic state through locally inflammatory and immune-mediated mechanisms but also contributes to the perturbation of hormone receptors (i.e., insulin or growth hormone resistance). It is time to act more precisely on sodium and fluid imbalance to mitigate both nutritional and cardiovascular risks. Personalized management of sodium and fluid, using available tools including sodium management tool, has the potential to more adequately restore sodium and water homeostasis and to improve nutritional status and outcomes of dialysis patients.
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Affiliation(s)
- Bernard Canaud
- School of Medicine, Montpellier University, 34000 Montpellier, France
- Global Medical Office, FMC-France, 94260 Fresnes, France
| | - Marion Morena-Carrere
- PhyMedExp, Department of Biochemistry and Hormonology, INSERM, CNRS, University Hospital Center of Montpellier, University of Montpellier, 34000 Montpellier, France
| | | | - Jean-Paul Cristol
- PhyMedExp, Department of Biochemistry and Hormonology, INSERM, CNRS, University Hospital Center of Montpellier, University of Montpellier, 34000 Montpellier, France
- Charles Mion Foundation, AIDER-Santé, 34000 Montpellier, France
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11
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Liu YH, Chen YH, Ko CH, Kuo CW, Yen CC, Chen W, Chong KY, Chen CM. SOD3 and IL-18 Predict the First Kidney Disease-Related Hospitalization or Death during the One-Year Follow-Up Period in Patients with End-Stage Renal Disease. Antioxidants (Basel) 2022; 11:1198. [PMID: 35740095 PMCID: PMC9231321 DOI: 10.3390/antiox11061198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 06/14/2022] [Accepted: 06/16/2022] [Indexed: 01/27/2023] Open
Abstract
End-stage renal disease (ESRD) patients experience oxidative stress due to excess exogenous or endogenous oxidants and insufficient antioxidants. Hence, oxidative stress and inflammation cause endothelial damage, contributing to vascular dysfunction and atherosclerosis. Therefore, ESRD patients suffer more cardiovascular and hospitalization events than healthy people. This study aims to test the correlations between ROS, SOD3, IL-2, IL-6, and IL-18 and the first kidney disease-related hospitalization or death events in ESRD patients undergoing regular hemodialysis. A total of 212 participants was enrolled, including 45 normal healthy adults and 167 ESRD patients on regular dialysis. Blood samples from all participants were collected for ROS, SOD3, IL-2, IL-6, and IL-18 measurement at the beginning of the study, and every kidney disease-related admission or death was recorded for the next year. Multivariate analysis was conducted by fitting a linear regression model, logistic regression model, and Cox proportional hazards model to estimate the adjusted effects of risk factors, prognostic factors, or predictors on continuous, binary, and survival outcome data. The results showed that plasma SOD3 and serum IL-18 were two strong predictors of the first kidney disease-related hospitalization or death. In the Cox proportional hazards models (run in R), higher IL-18 concentration (>69.054 pg/mL) was associated with a hazard ratio of 3.376 for the first kidney disease-related hospitalization or death (95% CI: 1.2644 to 9.012), while log(SOD3) < 4.723 and dialysis clearance (Kt/V; 1.11 < value < 1.869) had a hazard ratio = 0.2730 (95% CI: 0.1133 to 0.6576) for reducing future kidney disease-related hospitalization or death. Other markers, including body mass index (BMI), transferrin saturation, total iron binding capacity, and sodium and alkaline phosphate, were also found to be significant in our study. These results reveal the new predictors SOD3 and IL-18 for the medical care of end-stage renal disease patients.
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Affiliation(s)
- Yu-Hsien Liu
- Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; (Y.-H.L.); (Y.-H.C.); (C.-H.K.); (C.-W.K.)
- Department of Internal Medicine, Jen-Ai Hospital, Dali Branch, Taichung 402, Taiwan
| | - Yu-Hsuan Chen
- Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; (Y.-H.L.); (Y.-H.C.); (C.-H.K.); (C.-W.K.)
| | - Chi-Hua Ko
- Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; (Y.-H.L.); (Y.-H.C.); (C.-H.K.); (C.-W.K.)
- Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Yunlin 638, Taiwan
| | - Chia-Wen Kuo
- Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; (Y.-H.L.); (Y.-H.C.); (C.-H.K.); (C.-W.K.)
- Department of Internal Medicine, Taichung Armed Forces General Hospital, Taichung 411, Taiwan
| | - Chih-Ching Yen
- Department of Internal Medicine, China Medical University Hospital, College of Health Care, China Medical University, Taichung 404, Taiwan;
| | - Wei Chen
- Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi 600, Taiwan;
| | - Kowit-Yu Chong
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Hyperbaric Oxygen Medical Research Lab, Bone and Joint Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
| | - Chuan-Mu Chen
- Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; (Y.-H.L.); (Y.-H.C.); (C.-H.K.); (C.-W.K.)
- The iEGG and Animal Biotechnology Center, The Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
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12
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Wu L, Liu Y, Wu L, Yang J, Jiang T, Li M. Effects of exercise on markers of inflammation and indicators of nutrition in patients with chronic kidney disease: a systematic review and meta-analysis. Int Urol Nephrol 2021; 54:815-826. [PMID: 34255271 DOI: 10.1007/s11255-021-02949-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 07/07/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE This meta-analysis aimed to reveal the effects of exercise training on markers of inflammation and indicators of nutrition in non-dialysis-dependent patients with chronic kidney disease (NDD-CKD). METHODS We searched the MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, CNKI, WANFANE, VIP, and CBM databases, from their inception up to October 2020 to identify randomized controlled trials that examined the effects of exercise training on inflammation and nutrition in NDD-CKD patients. A total of 16 trials, comprising 724 patients, were included in the analysis. RESULTS The BMI (P = 0.005) and waist circumference (P = 0.004) decreased significantly after exercise training in NDD-CKD patients. Similarly, IL-6 (P = 0.03) decreased after exercise training in NDD-CKD patients. However, serum albumin level, body fat, CRP and hs-CRP were not different between patients who received exercise training and those who received usual care. Furthermore, BMI (P = 0.009), body weight (P = 0.009), and waist circumference (P = 0.010) were decreased in overweight patients (BMI ≧ 25 kg/m2). Moreover, BMI (P = 0.003), body weight (P = 0.005), and waist circumference (P = 0.007) reduced when the length of intervention exceeded 48 weeks. Subgroup analyses revealed no significant alteration of serum albumin, body fat, CRP, or hs-CRP, when studies were divided based on BMI or intervention duration. CONCLUSION Overall, these findings suggest that exercise training may improve inflammation status in NDD-CKD patients, and enhance weight loss in obese adult CKD patients. Registration number: INPLASY2020100025.
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Affiliation(s)
- Lihua Wu
- Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Yu Liu
- Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Ling Wu
- Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Ju Yang
- Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Ting Jiang
- Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Mingquan Li
- Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China.
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13
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Aycart DF, Acevedo S, Eguiguren-Jimenez L, Andrade JM. Influence of Plant and Animal Proteins on Inflammation Markers among Adults with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Nutrients 2021; 13:1660. [PMID: 34068841 PMCID: PMC8153567 DOI: 10.3390/nu13051660] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 05/04/2021] [Accepted: 05/11/2021] [Indexed: 11/16/2022] Open
Abstract
Proteins, especially plant proteins, may reduce inflammation among adults with chronic kidney disease (CKD). This systematic review and meta-analysis were conducted to evaluate the effect protein types (animal or plant) have on inflammation markers (CRP, IL-6, TNF-α) among adults with varying stages of CKD. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) was conducted to identify articles from inception until January 2021, utilizing six databases. Controlled trials that compared the effects of different protein types were analyzed using random-effects meta-analysis. Quality assessment and risk of bias of the included articles were assessed by using Cochrane risk of bias instrument and ROBINS-I. Out of the 10 studies that met the criteria, there was a decreasing trend in CRP levels when consuming plant proteins compared to animal proteins among non-dialysis participants. There was a statistically significant decrease when comparing animal proteins to unspecified proteins in CRP levels among dialysis participants [Hedges' g = 2.11; 95% CI 1.12, 3.11; p ≤ 0.001], favoring unspecified proteins. Furthermore, animal proteins (eggs, red meat) showed increasing trends in CRP levels compared to whey protein isolate. Caution must be considered regarding these results as controlled, non-randomized, trials were included in the analysis, which may have contributed to high risk of bias. Future research should focus on protein types and the impact they have on kidney disease progression and inflammation markers.
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Affiliation(s)
| | | | | | - Jeanette Mary Andrade
- Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA; (D.F.A.); (S.A.); (L.E.-J.)
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14
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Fatonah S, Sulchan M, Sofro MAU. Macronutrients, micronutrients intake and inflammation in hemodialysis patients. POTRAVINARSTVO 2019. [DOI: 10.5219/1193] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Inflammation in hemodialysis patients occurs since before undergoing hemodialysis. Inflammation is associated with an increase in oxidative stress. Hemodialysis patients are at risk for macronutrients and micronutrients deficiencies which can influence the increase in oxidative stress and inflammation. The purpose of this study was to evaluate the intake of micronutrients and inflammatory status in hemodialysis patients. This study was a cross-sectional study with 76 hemodialysis patients (40 male and 36 female) who attended in two hemodialysis centers of Kendal, Indonesia. After obtaining the written consent, then patients were interviewed food intake consisting of macronutrient and micronutrient intake. Macronutrient and micronutrient intake are obtained by the semi quantitative food frequency method and classified as a deficit (<100% adequacy level) and normal/ more (≥100% adequacy level), according to specific recommendations for individuals undergoing dialysis. Serum albumin was examined using the Brom Cresol Purple (BCP) method with a low category (<3.5 mg.dL-1) and normal (3.5 – 4.5 mg.dL-1). The hs-CRP serum was examined using the ELISA method and categorized as low (<1 mg.L-1), moderate (1 – 3 mg.L-1) and high (> 3 mg.L-1). A descriptive analysis was performed. The results of this study showed that 88.2% deficit energy intake, 84.2% deficit protein intake, 85.5% deficit of vitamin A intake, 85.5% deficit of vitamin C intake, 100% deficit of vitamin E intake, 98, 7% deficit zinc intake , 92.1% deficit copper intake. 63.2% subjects are low level of serum albumin and 61.8% subjects is high level of hs-CRP serum. Macronutrient and micronutrient intake in most hemodialysis patients shows deficit. The serum albumin of most hemodialysis patients shows low level. Serum hs-CRP most hemodialysis patients show high level.
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15
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Yuan Y, Hu JW, Wang Y, Wang KK, Zheng WL, Chu C, Ma Q, Yan Y, Liao YY, Mu JJ. Association between atherogenic index of plasma and subclinical renal damage over a 12-year follow-up: Hanzhong adolescent hypertension study. Eur J Clin Nutr 2019; 74:278-284. [DOI: 10.1038/s41430-019-0530-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 10/30/2019] [Accepted: 11/01/2019] [Indexed: 12/19/2022]
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16
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Kleine CE, Moradi H, Streja E, Kalantar-Zadeh K. Racial and Ethnic Disparities in the Obesity Paradox. Am J Kidney Dis 2019; 72:S26-S32. [PMID: 30343719 DOI: 10.1053/j.ajkd.2018.06.024] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 06/25/2018] [Indexed: 11/11/2022]
Abstract
Obesity is a major risk factor for cardiovascular disease and worse survival in the general population. However, in patients with end-stage renal disease (ESRD), higher body mass index and indexes of body fat and muscle are associated with better survival. Furthermore, these associations, which some have described as the obesity paradox, are more consistent in African American patients being treated with hemodialysis when compared with other racial-ethnic groups. This is in view of data indicating that although the rate of progression to ESRD is faster in African American patients, they have a survival advantage after transition to ESRD when compared with their white counterparts. These observations indicate that there may be significant interaction between race/ethnicity and association of body mass index with outcomes in patients with ESRD. In addition, it is possible that mechanisms underlying improved survival in African American hemodialysis patients are partly related to the association of body mass index with outcomes observed in this patient population. Some of these potential mechanisms may include comparatively reduced risk for protein-energy wasting and malnutrition, possible salutary effects of factors that play a role in energy preservation, resistance to deleterious effects of inflammation, and enhanced muscle mass and body composition. Given that ESRD is associated with significantly increased risk for morbidity and mortality, understanding the pathophysiologic mechanisms responsible for the obesity paradox across race-ethnic populations might help identify potential therapeutic targets that can be used to improve survival in this patient population.
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Affiliation(s)
- Carola-Ellen Kleine
- Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA; Department of Medicine, Long Beach Veteran Affairs Health System, Long Beach, CA
| | - Hamid Moradi
- Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA; Department of Medicine, Long Beach Veteran Affairs Health System, Long Beach, CA.
| | - Elani Streja
- Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA; Department of Medicine, Long Beach Veteran Affairs Health System, Long Beach, CA; Program for Public Health, University of California Irvine, Irvine, CA
| | - Kamyar Kalantar-Zadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA; Department of Medicine, Long Beach Veteran Affairs Health System, Long Beach, CA; Program for Public Health, University of California Irvine, Irvine, CA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA.
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17
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Campbell GA, Patrie JT, Gaylinn BD, Thorner MO, Bolton WK. Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study. Nephrol Dial Transplant 2019; 33:523-530. [PMID: 28340044 DOI: 10.1093/ndt/gfw474] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 12/27/2016] [Indexed: 01/09/2023] Open
Abstract
Background Protein-energy wasting (PEW) in end-stage renal disease (ESRD) patients is associated with increased morbidity and mortality, but options for treatment are limited. Growth hormone (GH) increases insulin-like growth factor 1 (IGF-1), with improved nutritional parameters, but must be given subcutaneously and does not provide normal GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), maintains normal GH secretion and increases lean body mass in normal subjects; it has not been studied in dialysis patients, an essential step in assessing efficacy and safety prior to clinical trials. Methods We performed a randomized crossover double-blind study in assessing the effect of MK-0677 versus placebo on IGF-1 levels, the primary outcome, in hemodialysis patients. In total, 26 subjects enrolled and 22 completed the 3-month crossover study. Results The geometric mean IGF-1 was 1.07-fold greater [95% confidence interval (CI) 0.89-1.27; P = 0.718] after placebo. In patients receiving MK-0677, the geometric mean IGF-1 were 1.76-fold greater (95% CI 1.48-2.10; P < 0.001) following MK-0677. When the data were adjusted for preintervention IGF-1 concentration, the ratio of geometric means (MK-0677 relative to placebo) for the pre- versus postintervention change in the IGF-1 was 1.65 (95% CI 1.33-2.04; P < 0.001). These data demonstrate a 65% greater increase (95% CI 33-104%) in IGF-1 in MK-0677-dosed subjects compared with placebo. There were no serious adverse effects attributable to MK-0677. Conclusions MK-0677 increased serum IGF-1 levels with minimal adverse effects in hemodialysis subjects. Studies are needed to evaluate whether long-term therapy with MK-0677 improves PEW, lean body mass, physical strength, quality of life and survival in CKD/ESRD patients.
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Affiliation(s)
- Garland A Campbell
- Division of Nephrology, University of Virginia Health Sciences Center, Charlottesville, VA, USA
| | - James T Patrie
- PBHS Public Health Sciences Administration, Public Health Sciences, University of Virginia Health Sciences Center, Charlottesville, VA, USA
| | - Bruce D Gaylinn
- Division of Endocrinology, University of Virginia Health Sciences Center, Charlottesville, VA, USA
| | - Michael O Thorner
- Division of Endocrinology, University of Virginia Health Sciences Center, Charlottesville, VA, USA
| | - Warren K Bolton
- Division of Nephrology, University of Virginia Health Sciences Center, Charlottesville, VA, USA
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18
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Twardowski ZJ, Misra M. A need for a paradigm shift in focus: From Kt/V urea to appropriate removal of sodium (the ignored uremic toxin). Hemodial Int 2018; 22:S29-S64. [PMID: 30457224 DOI: 10.1111/hdi.12701] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Hemodialysis for chronic renal failure was introduced and developed in Seattle, WA, in the 1960s. Using Kiil dialyzers, weekly dialysis time and frequency were established to be about 30 hours on 3 time weekly dialysis. This dialysis time and frequency was associated with 10% yearly mortality in the United States in 1970s. Later in 1970s, newer and more efficient dialyzers were developed and it was felt that dialysis time could be shortened. An additional incentive to shorten dialysis was felt to be lower cost and higher convenience. Additional support for shortening dialysis time was provided by a randomized prospective trial performed by National Cooperative Dialysis Study (NCDS). This study committed a Type II statistical error rejecting the time of dialysis as an important factor in determining the quality of dialysis. This study also provided the basis for the establishment of the Kt/Vurea index as a measure of dialysis adequacy. This index having been established in a sacrosanct randomized controlled trial (RCT), was readily accepted by the HD community, and led to shorter dialysis, and higher mortality in the United States. Kt/Vurea is a poor measure of dialysis quality because it combines three unrelated variables into a single formula. These variables influence the clinical status of the patient independent of each other. It is impossible to compensate short dialysis duration (t) with the increased clearance of urea (K), because the tolerance of ultrafiltration depends on the plasma-refilling rate, which has nothing in common with urea clearance. Later, another RCT (the HEMO study) committed a Type III statistical error by asking the wrong research question, thus not yielding any valuable results. Fortunately, it did not lead to deterioration of dialysis outcomes in the United States. The third RCT in this field ("in-center hemodialysis 6 times per week versus 3 times per week") did not bring forth any valuable results, but at least confirmed what was already known. The fourth such trial ("The effects of frequent nocturnal home hemodialysis") too did not show any positive results primarily due to significant subject recruitment issues leading to inappropriate selection of patients. Comparison of the value of peritoneal dialysis and HD in RCTs could not be completed because of recruitment problems. Randomized controlled trials have therefore failed to yield any meaningful information in the area of dose and or frequency of hemodialysis.
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Affiliation(s)
| | - Madhukar Misra
- Department of Medicine, University of Missouri, Columbia, Missouri, USA
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19
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Bansal N, Zelnick LR, Himmelfarb J, Chertow GM. Bioelectrical Impedance Analysis Measures and Clinical Outcomes in CKD. Am J Kidney Dis 2018; 72:662-672. [PMID: 29885923 DOI: 10.1053/j.ajkd.2018.03.030] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 03/27/2018] [Indexed: 11/11/2022]
Abstract
RATIONALE & OBJECTIVE Bioelectrical impedance analysis (BIA) provides a noninvasive assessment of body composition. BIA measures of cell integrity (phase angle) and hydration (vector length) have been associated with mortality among patients receiving dialysis. Whether these measures are associated with clinical outcomes in patients with chronic kidney disease (CKD) is unknown. STUDY DESIGN Observational study. SETTINGS & PARTICIPANTS We studied 3,751 participants with CKD in the prospective multicenter Chronic Renal Insufficiency Cohort (CRIC) who had baseline single-frequency BIA performed. PREDICTORS Predictors included phase angle and vector length, which were calculated from measurements of resistance and reactance from BIA. We ranked phase angle and vector length into quartiles and compared the 2 narrower quartiles of phase angle and shorter quartiles of vector length with the 2 upper quartiles. OUTCOMES Mortality, heart failure, atherosclerotic cardiovascular disease, and progression of CKD (30% decline in estimated glomerular filtration rate or end-stage kidney disease). ANALYTIC APPROACH We tested associations of phase angle and vector length with risks for mortality and progression of CKD using Cox proportional hazard models and the association with heart failure and atherosclerotic cardiovascular disease using Fine and Gray models. All models were adjusted for demographics, comorbid conditions, and kidney function. RESULTS Mean phase angle and vector length were 6.6°±1.8° and 470 ± 96 Ω/m, respectively. Relative to phase angle ≥ 6.40o, narrower phase angle (<5.59o) was significantly associated with mortality (HR, 1.31; 95% CI, 1.09-1.58). Relative to vector length ≥ 459 Ω/m, shorter vector length (<401 Ω/m) was significantly associated with heart failure (HR, 1.28; 95% CI, 1.01-1.61). Neither measure was associated with atherosclerotic cardiovascular disease or a composite renal end point. LIMITATIONS Observational study. CONCLUSIONS Adjusted for key confounders, BIA-derived measures of cellular integrity and tissue hydration were significantly associated with death and incident heart failure, respectively.
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Affiliation(s)
- Nisha Bansal
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA.
| | - Leila R Zelnick
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA
| | - Jonathan Himmelfarb
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA
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20
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Hassan K, Elimeleh Y, Shehadeh M, Hassan F, Rubinchik I. Associations of Peritoneal Glucose Load With Male Sexual Dysfunction and Depression in Peritoneal Dialysis Patients. Ther Apher Dial 2018; 22:380-388. [DOI: 10.1111/1744-9987.12663] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Revised: 10/31/2017] [Accepted: 12/01/2017] [Indexed: 11/26/2022]
Affiliation(s)
- Kamal Hassan
- Faculty of Medicine in the Galilee; Bar-Ilan University; Safed Israel
- Department of Nephrology and Hypertension; Galilee Medical Center; Nahariya Israel
| | - Yotam Elimeleh
- Faculty of Medicine in the Galilee; Bar-Ilan University; Safed Israel
| | - Mona Shehadeh
- Biochemistry Laboratory; Galilee Medical Center; Nahariya Israel
| | - Fadi Hassan
- Internal Medicine Department E; Galilee Medical Center; Nahariya Israel
| | - Irina Rubinchik
- Department of Nephrology and Hypertension; Galilee Medical Center; Nahariya Israel
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21
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Hassan K, Elimeleh Y, Shehadeh M, Fadi H, Rubinchik I. The relationship between hydration status, male sexual dysfunction and depression in hemodialysis patients. Ther Clin Risk Manag 2018; 14:523-529. [PMID: 29559788 PMCID: PMC5856048 DOI: 10.2147/tcrm.s147723] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background Disturbances in sexual function are common among dialysis patients. Normal erections require a complex balance of physiological, psychological, emotional, hormonal, neurological and vascular factors. This study examined a possible association of overhydration (OH) with male sexual dysfunction and depression in hemodialysis (HD) patients. Patients and methods This cross-sectional study assessed hydration status by whole-body bioimpedance spectroscopy in patients on maintenance HD for more than 12 months. Patients were categorized according to OH to extracellular water (ECW) ratio: OH/ECW ratio >0.15 and OH/ECW ratio ≤0.15. Sexual function was assessed using the International Index of Erectile Function (IIEF) score. Psychological status was evaluated using the Beck Depression Inventory (BDI) score. Serum sex hormones were determined. Results Of 39 stable participants on HD, 53.8% were overhydrated (OH/ECW ratio >0.15) and 46.2% not overhydrated (OH/ECW ratio ≤0.15). Of participants with OH/ECW ratio >0.15, 85.7% had mild to severe ED, and 71.4% had abnormal BDI scores, ranging from mild mood disturbance to severe depression. Compared to patients with OH/ECW ratio ≤0.15, BDI scores, serum estradiol and plasma hsCRP were higher (18.48±8.34 vs 10.61±5.46, p<0.001; 140.10±44.51 vs 126.10±32.26, p=0.034; and, 17.70±12.14 vs 9.76±8.79, p=0.013; respectively) in those with OH/ECW ratio >0.15, while their IIEF score, serum total testosterone and dehydroepiandrosterone (DHEA) were lower (12.81±7.31 vs 41.44±23.79, p<0.001; 8.97±5.43 vs 14.10±8.30, p=0.013; and 85.31±55.14 vs 133.3±95.48, p=0.029; respectively). The OH/ECW ratio correlated inversely with the IIEF score (r=−0.69, p<0.001) and positively with BDI scores (r=0.64, p<0.001). IIEF scores were inversely correlated with BDI scores (r=−0.54, p<0.001). Conclusion OH in HD patients was found to be associated with a higher prevalence of sexual dysfunction and depression, lower serum levels of total testosterone and DHEA, and higher levels of serum estradiol.
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Affiliation(s)
- Kamal Hassan
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.,Department of Nephrology and Hypertension, Galilee Medical Center, Nahariya, Israel
| | - Yotam Elimeleh
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Mona Shehadeh
- Biochemistry Laboratory, Galilee Medical Center, Nahariya, Israel
| | - Hassan Fadi
- Internal Medicine Department E, Galilee Medical Center, Nahariya, Israel
| | - Irina Rubinchik
- Department of Nephrology and Hypertension, Galilee Medical Center, Nahariya, Israel
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Twardowski ZJ. Short, Thrice-Weekly Hemodialysis is Inadequate Regardless of Small Molecule Clearance. Int J Artif Organs 2018; 27:452-66. [PMID: 15291076 DOI: 10.1177/039139880402700603] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Chronic hemodialysis sessions, as developed in Seattle in the 1960s, were long procedures with minimal intra- and interdialytic symptoms. Over the next three decades, financial and logistical pressures related to the overwhelming number of patients requiring hemodialysis created an incentive to shorten dialysis time to four, three, and even two hours per session in a thrice weekly schedule. This method spread rapidly, particularly in the United States, after the National Cooperative Dialysis Study suggested that time of dialysis is of minor importance as long as urea clearance multiplied by dialysis time and scaled to total body water (Kt/Vurea) equals 0.95–1.0. This number was later increased to 1.3, but the assumption that hemodialysis time is of minimal importance, as long as it is compensated by increased urea clearance, remained unchanged. Patients accepted short dialysis as a godsend, believing that it would not be detrimental to their well being and longevity. However, Kt/Vurea measures only removal of low molecular weight substances and does not consider removal of larger molecules. Nor does it correlate with the other important function of hemodialysis, namely ultrafiltration. Whereas patients with substantial residual renal function may tolerate short dialysis sessions, patients with little or no urine output tolerate short dialyses poorly because at a given interdialytic weight gain the ultrafiltration rate is inversely proportional to dialysis time. Rapid ultrafiltration is associated with cramps, nausea, vomiting, headache, fatigue, hypotensive episodes during dialysis, and hangover after dialysis; patients remain fluid overloaded with subsequent poor blood pressure control leading to left ventricular hypertrophy, diastolic dysfunction, and high cardiovascular mortality. Short, high-efficiency dialysis requires high blood flow, which increases demands on blood access. The classic, wrist arteriovenous fistula, the access with the best longevity and lowest complication rates, provides “insufficient” blood flow and is replaced with an arteriovenous graft fistula or an intravenous catheter. Moreover, to achieve high blood flows, large diameter intravenous catheters are used; these fit veins “too tightly” and so predispose to central-vein thrombosis. Longer hemodialysis sessions (5–8 hours, thrice weekly), as practiced in some centers, are associated with lower complication rates and better outcomes. Frequent dialyses (four or more sessions per week) with total weekly dialysis time sufficient to allow gentle ultrafiltration rates provide the best clinical results, but are associated with increased costs which are not properly reimbursed in the USA at present. Therefore, it is my strong belief that before a more appropriate reimbursement is available, a wide acceptance of longer, gentler dialysis sessions, in the current thrice weekly schedule, would improve overall hemodialysis results, decrease access complications, hospitalizations and mortality, particularly in anuric patients. Kt/Vurea should be abandoned as a measure of dialysis quality. The formula suggests that it is possible to decrease t as long as K is proportionately increased, but this is not true. The use of rigid, quantitative guidelines (e.g., spKt/Vurea of 1.3 per dialysis) assumes that all patients behave identically in response to therapeutic maneuvers, like the mean of the group, but this is also not true. The individual, clinical approach assumes that there are differences among patients, which require adjustment of dialysis schedule for each patient.
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Affiliation(s)
- Z J Twardowski
- Division of Nephrology, Department of Medicine, University of Missouri, Columbia, Missouri, USA.
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23
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Abstract
Inflammation is one of the well-recognized nontraditional risk factors that contributes to the excessive cardiovascular mortality in peritoneal dialysis (PD) patients. Serum C-reactive protein and interleukin-6 levels are common surrogate markers used to measure inflammatory burden and predict adverse clinical outcomes in PD patients. Causes of inflammation are complex and can be categorized into factors related to a decrease in renal function and factors related to dialysis. They interact with each other and finally result in systemic and intraperitoneal inflammation. This review discusses the various causes and clinical implications of inflammation in PD patients. More importantly, potential therapeutic options that target the underlying pathogenic mechanisms are explored.
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Affiliation(s)
- Philip Kam-Tao Li
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
| | - Jack Kit-Chung Ng
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Christopher William Mcintyre
- Division of Nephrology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
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24
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Pérez-Torres A, González Garcia ME, San José-Valiente B, Bajo Rubio MA, Celadilla Diez O, López-Sobaler AM, Selgas R. Protein-energy wasting syndrome in advanced chronic kidney disease: prevalence and specific clinical characteristics. Nefrologia 2017; 38:141-151. [PMID: 28755901 DOI: 10.1016/j.nefro.2017.06.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Revised: 05/19/2017] [Accepted: 06/06/2017] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Protein-energy wasting (PEW) is associated with increased mortality and differs depending on the chronic kidney disease (CKD) stage and the dialysis technique. The prevalence in non-dialysis patients is understudied and ranges from 0 to 40.8%. OBJECTIVE To evaluate the nutritional status of a group of Spanish advanced CKD patients by PEW criteria and subjective global assessment (SGA). PATIENTS AND METHODS Cross-sectional study of 186 patients (101 men) with a mean age of 66.1±16 years. The nutritional assessment consisted of: SGA, PEW criteria, 3-day dietary records, anthropometric parameters and bioelectrical impedance vector analysis. RESULTS The prevalence of PEW was 30.1%, with significant differences between men and women (22.8 vs. 33.8%, p < 0.005), while 27.9% of SGA values were within the range of malnutrition. No differences were found between the 2methods. Men had higher proteinuria, percentage of muscle mass and nutrient intake. Women had higher levels of total cholesterol, HDL and a higher body fat percentage. The characteristics of patients with PEW were low albumin levels and a low total lymphocyte count, high proteinuria, low fat and muscle mass and a high Na/K ratio. The multivariate analysis found PEW to be associated with: proteinuria (OR: 1.257; 95% CI: 1.084-1.457, p=0.002), percentage of fat intake (OR: 0.903; 95% CI: 0.893-0.983, p=0.008), total lymphocyte count (OR: 0.999; 95% CI: 0.998-0.999, p=0.001) and cell mass index (OR: 0.995; 95% CI: 0.992-0.998). CONCLUSION Malnutrition was identified in Spanish advanced CKD patients measured by different tools. We consider it appropriate to adapt new diagnostic elements to PEW criteria.
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Affiliation(s)
| | | | | | | | - Olga Celadilla Diez
- Servicio de Nefrología, Hospital Universitario La Paz. IdiPAZ, Madrid, España
| | - Ana M López-Sobaler
- Departamento de Nutrición y Bromatología I, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, España
| | - Rafael Selgas
- Servicio de Nefrología, Hospital Universitario La Paz. IdiPAZ, Madrid, España
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25
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Piccoli GB, Moio MR, Fois A, Sofronie A, Gendrot L, Cabiddu G, D'Alessandro C, Cupisti A. The Diet and Haemodialysis Dyad: Three Eras, Four Open Questions and Four Paradoxes. A Narrative Review, Towards a Personalized, Patient-Centered Approach. Nutrients 2017; 9:E372. [PMID: 28394304 PMCID: PMC5409711 DOI: 10.3390/nu9040372] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Revised: 03/17/2017] [Accepted: 03/31/2017] [Indexed: 12/25/2022] Open
Abstract
The history of dialysis and diet can be viewed as a series of battles waged against potential threats to patients' lives. In the early years of dialysis, potassium was identified as "the killer", and the lists patients were given of forbidden foods included most plant-derived nourishment. As soon as dialysis became more efficient and survival increased, hyperphosphatemia, was identified as the enemy, generating an even longer list of banned aliments. Conversely, the "third era" finds us combating protein-energy wasting. This review discusses four questions and four paradoxes, regarding the diet-dialysis dyad: are the "magic numbers" of nutritional requirements (calories: 30-35 kcal/kg; proteins > 1.2 g/kg) still valid? Are the guidelines based on the metabolic needs of patients on "conventional" thrice-weekly bicarbonate dialysis applicable to different dialysis schedules, including daily dialysis or haemodiafiltration? The quantity of phosphate and potassium contained in processed and preserved foods may be significantly different from those in untreated foods: what are we eating? Is malnutrition one condition or a combination of conditions? The paradoxes: obesity is associated with higher survival in dialysis, losing weight is associated with mortality, but high BMI is a contraindication for kidney transplantation; it is difficult to limit phosphate intake when a patient is on a high-protein diet, such as the ones usually prescribed on dialysis; low serum albumin is associated with low dialysis efficiency and reduced survival, but on haemodiafiltration, high efficiency is coupled with albumin losses; banning plant derived food may limit consumption of "vascular healthy" food in a vulnerable population. Tailored approaches and agreed practices are needed so that we can identify attainable goals and pursue them in our fragile haemodialysis populations.
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Affiliation(s)
- Giorgina Barbara Piccoli
- Dipartimento di Scienze Cliniche e Biologiche, University of Torino, 10100 Torino, Italy.
- Nephrologie, Centre Hospitalier le Mans, Avenue Roubillard, 72000 Le Mans, France.
| | - Maria Rita Moio
- Nephrologie, Centre Hospitalier le Mans, Avenue Roubillard, 72000 Le Mans, France.
| | - Antioco Fois
- Nefrologia, Ospedale Brotzu, 09100 Cagliari, Italy.
| | - Andreea Sofronie
- Nephrologie, Centre Hospitalier le Mans, Avenue Roubillard, 72000 Le Mans, France.
| | - Lurlinys Gendrot
- Nephrologie, Centre Hospitalier le Mans, Avenue Roubillard, 72000 Le Mans, France.
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26
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Kordinas V, Tsirpanlis G, Nicolaou C, Zoga M, Ioannidis A, Ioannidou V, Bersimis S, Petrihou C, Savva L, Legakis NJ, Chatzipanagiotou S. Is there a connection between inflammation, telomerase activity and the transcriptional status of telomerase reverse transcriptase in renal failure? Cell Mol Biol Lett 2016. [PMID: 26204404 DOI: 10.1515/cmble-2015-0016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Telomerase is involved in the elongation of telomeres. It remains active in very few types of cell in mature organisms. One such cell type is the lymphocytes. In this study, we investigated the activity and expression of telomerase in lymphocytes from renal failure patients and compared it to that for normal controls. Inflammation status was determined at the same time. The enzyme activity was measured using PCR-ELISA with peripheral blood mononuclear cells (PBMCs) from three groups: 53 healthy individuals, 50 patients with chronic kidney disease (CKD) and 50 dialysis patients. In the same cell populations, the expression of the reverse transcriptase of the human telomerase gene (hTERT) was measured via real-time PCR. The inflammationstatus of these individuals was determined by calculating the interleukin 6 (IL-6), IL-10, C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-a) serum concentrations via ELISA. The lowest levels of telomerase activity were detected in CKD, and this group had the highest IL-6 and CRP values and the lowest hTERT expression. The dialysis group showed significant differences in comparison to the normal subjects and to the CKD patients. Further studies are warranted in order to explore the way inflammation influences telomerase activity and hTERT expression.
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27
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Tu J, Cheung WW, Mak RH. Inflammation and nutrition in children with chronic kidney disease. World J Nephrol 2016; 5:274-282. [PMID: 27152263 PMCID: PMC4848150 DOI: 10.5527/wjn.v5.i3.274] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 09/02/2015] [Accepted: 03/09/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic inflammation and nutritional imbalance are important comorbid conditions that correlate with poor clinical outcomes in children with chronic kidney disease (CKD). Nutritional disorders such as cachexia/protein energy wasting, obesity and growth retardation negatively impact the quality of life and disease progression in children with CKD. Inadequate nutrition has been associated with growth disturbances in children with CKD. On the other hand, over-nutrition and obesity are associated with poor outcomes in children with CKD. The exact mechanisms leading to these unfavorable conditions are not fully elucidated and are most likely multifactorial. In this review, we focus on the pathophysiology of nutrition disorders and inflammation and their impact on clinical outcomes in children with CKD.
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28
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Bambha KM, Dodge JL, Gralla J, Sprague D, Biggins SW. Low, rather than high, body mass index confers increased risk for post-liver transplant death and graft loss: Risk modulated by model for end-stage liver disease. Liver Transpl 2015; 21:1286-94. [PMID: 26097202 DOI: 10.1002/lt.24188] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 05/13/2015] [Accepted: 05/31/2015] [Indexed: 12/12/2022]
Abstract
With increasing attention being paid to optimizing patient outcomes, it has been proposed that liver transplantation (LT) for individuals with elevated body mass index (BMI) values and high Model for End-Stage Liver Disease (MELD) scores may adversely affect post-LT outcomes. We investigated the impact of BMI on post-LT outcomes in the context of MELD at LT. Using United Network for Organ Sharing data, we identified all adult (≥ 18 years) primary LT recipients from March 1, 2002 to September 30, 2011. BMI categories included the following: underweight, normal, overweight, class I obese, class II obese, and class III obese (<18.5; 18.5-24.9; 25-29.9; 30-34.9; 35-39.9; ≥ 40 kg/m(2), respectively). One-year post-LT death and graft loss were modeled using Cox regression, including interactions between BMI and MELD. A total of 45,551 adult recipients were identified: 68% male; median (interquartile range [IQR]) age 55 years (IQR, 49-60 years); MELD, 19 (IQR, 13-26); and donor risk index, 1.39 (IQR, 1.12-1.69). Representations in the BMI categories were underweight (n = 863, 2%), normal (n = 13,262, 29%), overweight (n = 16,329, 36%), class I obese (n = 9639, 21%), class II obese (n = 4062, 9%), and class III obese (n = 1396, 3%). In adjusted analyses, elevated BMI was not associated with increased risk for death or graft loss. Among the underweight, there were significant interactions between BMI and MELD with respect to death (P = 0.02) and graft loss (P = 0.01), with significantly increased risks for death (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.38-2.09; P = 0.006) and graft loss (HR, 1.45; 95% CI, 1.21-1.74; P = 0.02) among those with low MELD (≤ 26), compared to normal BMI recipients with low MELD. In conclusion, overweight and obese LT recipients do not have increased risk of death or graft loss regardless of MELD. Underweight patients are at increased risk for poor outcomes post-LT, specifically underweight recipients with low MELD have increased risk for death and graft loss. Mechanisms underlying this phenomenon warrant further investigation.
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Affiliation(s)
- Kiran M Bambha
- Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO
| | - Jennifer L Dodge
- Division of Transplant Surgery, University of California, San Francisco, CA
| | - Jane Gralla
- Department of Pediatrics, University of Colorado Denver, Aurora, CO
| | - David Sprague
- Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO
| | - Scott W Biggins
- Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO
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29
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Peng H, Cao J, Yu R, Danesh F, Wang Y, Mitch WE, Xu J, Hu Z. CKD Stimulates Muscle Protein Loss Via Rho-associated Protein Kinase 1 Activation. J Am Soc Nephrol 2015; 27:509-19. [PMID: 26054539 DOI: 10.1681/asn.2014121208] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Accepted: 04/27/2014] [Indexed: 11/03/2022] Open
Abstract
In patients with CKD, muscle wasting is common and is associated with morbidity and mortality. Mechanisms leading to loss of muscle proteins include insulin resistance, which suppresses Akt activity and thus stimulates protein degradation via the ubiquitin-proteasome system. However, the specific factors controlling CKD-induced suppression of Akt activity in muscle remain undefined. In mice with CKD, the reduction in Akt activity in muscle exceeded the decrease in upstream insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity, suggesting that CKD activates other pathways that suppress Akt. Furthermore, a CKD-induced increase uncovered caspase-3 activity in muscle in these mice. In C2C12 muscle cells, activated caspase-3 cleaves and activates Rho-associated protein kinase 1 (ROCK1), which enhances the activity of phosphatase and tensin homolog (PTEN) and reduces Akt activity. Notably, constitutive activation of ROCK1 also led to increased caspase-3 activity in vitro. In mice with either global ROCK1 knockout or muscle-specific PTEN knockout, CKD-associated muscle proteolysis was blunted. These results suggest ROCK1 activation in CKD and perhaps in other catabolic conditions can promote loss of muscle protein via a negative feedback loop.
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Affiliation(s)
- Hui Peng
- Department of Internal Medicine, Nephrology Division, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Jin Cao
- Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Rizhen Yu
- Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas; Renal Section, Changhai Hospital, Shanghai, China; and
| | - Farhad Danesh
- Nephrology Division, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Yanlin Wang
- Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - William E Mitch
- Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Jing Xu
- Nephrology Division, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Zhaoyong Hu
- Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas;
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30
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Chai C, Yan S, Chu Z, Wang T, Wang L, Zhang M, Zuo C, Haacke EM, Xia S, Shen W. Quantitative measurement of brain iron deposition in patients with haemodialysis using susceptibility mapping. Metab Brain Dis 2015; 30:563-71. [PMID: 25182196 DOI: 10.1007/s11011-014-9608-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2014] [Accepted: 08/12/2014] [Indexed: 10/24/2022]
Abstract
To compare the susceptibility of different brain structures in patients with haemodialysis with that in healthy controls using susceptibility mapping and explore the correlations with neuropsychiatric tests and clinical parameters. Fifty three patients with haemodialysis and forty-five age-and sex-matched healthy controls were recruited in this prospective study. Susceptibility maps (SM) were reconstructed from original phase data and used to compare the susceptibility of different brain structures between patients and healthy controls. The SM was compared with iron predictions from a classic cadaver brain study. Spearman's correlation and stepwise multiple regression analysis between susceptibility and neuropsychiatric tests and clinical parameters were calculated. In patients with haemodialysis, the susceptibility of the bilateral caudate head, putamen, substantia nigra, red nucleus and dentate nucleus were significantly higher than those in healthy controls (P < 0.01). There was positive correlation between susceptibility both from normal controls and patients and iron concentration from a classic post-mortem brain study (both r = 0.900, both P = 0.037). In patients with haemodialysis, the susceptibility of the left putamen (r = 0.944), right putamen (r = 0.882) and right thalamus (r = 0.852) were correlated to dialysis duration (all P < 0.05). The susceptibility of the left caudate head (r = -0.415) and right caudate head (r = -0.311) were mildly negatively correlated with neuropsychiatric test scores (all P < 0.05). In summary, our findings indicated that increased brain iron deposition does occur in patients with haemodialysis and correlated with duration of dialysis.
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Affiliation(s)
- Chao Chai
- Department of Medical Imaging, Tianjin First Central Hospital, Tianjin, 300192, China
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31
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Campbell R, Augustine T, Hurst H, Pararajasingam R, van Dellen D, Armstrong S, Bartley C, Birtles L, Summers A. Anthropometrics Identify Wasting in Patients Undergoing Surgery for Encapsulating Peritoneal Sclerosis. Perit Dial Int 2014; 35:471-80. [PMID: 24584612 DOI: 10.3747/pdi.2013.00098] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Accepted: 11/11/2013] [Indexed: 12/22/2022] Open
Abstract
UNLABELLED ♦ INTRODUCTION Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis in which gastrointestinal (GI) symptoms reduce appetite and dietary intake. Adequate nutrition is important, especially if surgery is required. Although the incidence of EPS is low, the present report is able to detail preoperative nutrition status and treatment in a large cohort of patients from a national EPS referral center. ♦ METHODS Of 51 patients admitted to this EPS specialist center hospital for their first peritonectomy in the study period, 50 had a preoperative dietetic assessment, and 49 underwent upper-arm anthropometry. ♦ RESULTS Mean body mass index (BMI) was 20.6 kg/m(2). Mean weight loss was 14% of body weight in the preceding 6 months, with 35 of 50 patients losing more than 10%. On anthropometry, 25 of 49 patients were below the 5th percentile for mid-arm circumference (MAC), 17 of 49 were below for triceps skinfold thickness (TSF), and 21 of 49 were below for mid-arm muscle circumference (MAMC). Mean handgrip strength (HGS) was 60% of normal, with 43 of 49 patients being below 85% of normal. Appetite was poor in 21 of 50 patients, and 37 of 50 had upper and 40 of 50 had lower GI symptoms. By subjective global assessment, 27 of 51 patients were graded as severely malnourished, and 5 of 51, as well-nourished. Mean serum albumin was 28 g/L and did not correlate with BMI, MAC, TSF, MAMC, or HGS. In most patients, C-reactive protein was elevated (mean: 111 mg/L). Preoperative parenteral nutrition was given to 46 of 51 patients for a mean of 21 days. ♦ DISCUSSION Our findings demonstrate the poor nutrition status of patients admitted for EPS surgical intervention. Anthropometrics reveal depleted fat and lean body mass in EPS patients, which might be a result of anorexia and inflammation, and the reason that albumin was not an accurate marker of nutrition. Poor nutrition status is likely to negatively affect outcome in this patient group. ♦ CONCLUSIONS Early recognition of GI symptoms may herald a diagnosis of EPS. Optimization of preoperative nutrition status with intensive nutrition support is needed.
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Affiliation(s)
- Rosalind Campbell
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Titus Augustine
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Helen Hurst
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Ravi Pararajasingam
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - David van Dellen
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Sheilagh Armstrong
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Carol Bartley
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Linda Birtles
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Angela Summers
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
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Beberashvili I, Sinuani I, Azar A, Kadoshi H, Shapiro G, Feldman L, Sandbank J, Averbukh Z. Decreased IGF-1 levels potentiate association of inflammation with all-cause and cardiovascular mortality in prevalent hemodialysis patients. Growth Horm IGF Res 2013; 23:209-214. [PMID: 23958273 DOI: 10.1016/j.ghir.2013.07.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2013] [Revised: 07/20/2013] [Accepted: 07/21/2013] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Insulin-like growth factor-1 (IGF-1) and inflammation have both been linked to high cardiovascular risk and mortality in the general population, as well as in hemodialysis (HD) patients. We hypothesized that the association of low IGF-1 with chronic inflammation may increase the mortality risk in HD patients. DESIGN We investigated the interactions between inflammatory biomarkers (IL-6 and TNF-α) and IGF-1 as predictors of death over a 4 years of follow-up (median--47 months, interquartile range--17.5-75 months) in 96 prevalent HD patients (35% women, mean age of 64.9 ± 11.6 years). RESULTS A significant interaction effect of low IGF-1 (defined as a level less than median) and high IL-6 (defined as a level higher than median) on all-cause and cardiovascular mortality was found: crude Cox hazard ratios (HR) for the product termed IGF-1 × IL-6 were 4.27, with a 95% confidence interval (CI): 2.10 to 8.68 (P<0.001) and 7.49, with a 95% CI: 2.40-24.1 (P=0.001), respectively. Across the four IGF-1-IL-6 categories, the group with low IGF-1 and high IL-6 exhibited the worse outcome in both all-cause and cardiovascular mortality (multivariable adjusted hazard ratios were 4.92, 95% CI 1.86 to 13.03, and 14.34, 95% CI 1.49 to 137.8, respectively). The main clinical characteristics of patients in the low-IGF-1-high IL-6 group didn't differ from other IGF-1-IL-6 categorized groups besides gender that consequently was inserted in all multivariable models together with the other potential confounders. CONCLUSIONS An increase in mortality risk was observed in HD patients with low IGF-1 and high IL-6 levels, especially cardiovascular causes.
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Affiliation(s)
- Ilia Beberashvili
- Nephrology Division, Assaf Harofeh Medical Center, Zerifin, Affiliated to Sackler Faculty of Medicine Tel Aviv University, Israel.
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Rattanasompattikul M, Molnar MZ, Lee ML, Dukkipati R, Bross R, Jing J, Kim Y, Voss AC, Benner D, Feroze U, Macdougall IC, Tayek JA, Norris KC, Kopple JD, Unruh M, Kovesdy CP, Kalantar-Zadeh K. Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients (AIONID) study: results of the pilot-feasibility, double-blind, randomized, placebo-controlled trial. J Cachexia Sarcopenia Muscle 2013; 4:247-57. [PMID: 24052226 PMCID: PMC3830006 DOI: 10.1007/s13539-013-0115-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Accepted: 07/19/2013] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Low serum albumin is common and associated with protein-energy wasting, inflammation, and poor outcomes in maintenance hemodialysis (MHD) patients. We hypothesized that in-center (in dialysis clinic) provision of high-protein oral nutrition supplements (ONS) tailored for MHD patients combined with anti-oxidants and anti-inflammatory ingredients with or without an anti-inflammatory appetite stimulator (pentoxifylline, PTX) is well tolerated and can improve serum albumin concentration. METHODS Between January 2008 and June 2010, 84 adult hypoalbuminemic (albumin <4.0 g/dL) MHD outpatients were double-blindly randomized to receive 16 weeks of interventions including ONS, PTX, ONS with PTX, or placebos. Nutritional and inflammatory markers were compared between the four groups. RESULTS Out of 84 subjects (mean ± SD; age, 59 ± 12 years; vintage, 34 ± 34 months), 32 % were Blacks, 54 % females, and 68 % diabetics. ONS, PTX, ONS plus PTX, and placebo were associated with an average change in serum albumin of +0.21 (P = 0.004), +0.14 (P = 0.008), +0.18 (P = 0.001), and +0.03 g/dL (P = 0.59), respectively. No related serious adverse events were observed. In a predetermined intention-to-treat regression analysis modeling post-trial serum albumin as a function of pre-trial albumin and the three different interventions (ref = placebo), only ONS without PTX was associated with a significant albumin rise (+0.17 ± 0.07 g/dL, P = 0.018). CONCLUSIONS In this pilot-feasibility, 2 × 2 factorial, placebo-controlled trial, daily intake of a CKD-specific high-protein ONS with anti-inflammatory and anti-oxidative ingredients for up to 16 weeks was well tolerated and associated with slight but significant increase in serum albumin levels. Larger long-term controlled trials to examine hard outcomes are indicated.
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Affiliation(s)
- Manoch Rattanasompattikul
- Harold Simmons Center for Kidney Disease Research & Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, CA, USA
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Tbahriti HF, Meknassi D, Moussaoui R, Messaoudi A, Zemour L, Kaddous A, Bouchenak M, Mekki K. Inflammatory status in chronic renal failure: The role of homocysteinemia and pro-inflammatory cytokines. World J Nephrol 2013; 2:31-37. [PMID: 24175263 PMCID: PMC3782222 DOI: 10.5527/wjn.v2.i2.31] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Revised: 03/21/2013] [Accepted: 05/18/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate determinants of inflammatory markers in chronic renal failure patients according to the level of glomerular filtration rate.
METHODS: One hundred fifty four patients (Age: 44 ± 06 years; male/female: 66/88) with chronic renal failure (CRF) were divided into 6 groups according to the National Kidney Foundation (NKF) classification. They included 28 primary stage renal failure patients (CRF 1), 28 moderate stage renal failure patients (CRF 2), 28 severe stage renal failure patients (CRF 3), 18 end-stage renal failure patients (CRF 4), 40 hemodialysis (HD) patients, and 12 peritoneal dialysis (PD) patients. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and C-reactive protein (CRP) were analyzed by immunosorbent assay kit (ELISA) (Cayman Chemical’s ACETM EIA kit). Immunoassay methods were used for total homocysteine (tHcy) (fluorescence polarization immunoanalysis HPLC, PerkinEmer 200 series), transferrin (MININEPHTM human transferin kit: ZK070.R), ferritin (ADVIA Centaur) and fibrinogen analysis (ACL 200). Differences between groups were performed using SPSS 20.0 and data are expressed as the mean ± SD.
RESULTS: Results showed that in comparison with CRF 1 group and other groups, TNF-α and IL-6 levels were respectively more elevated in HD (16.38 ± 5.52 pg/mL vs 0.39 ± 0.03 pg/mL, 11.05 ± 3.59 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001) and PD (14.04 ± 3.40 pg/mL vs 0.39 ± 0.03 pg/mL, 10.15 ± 1.66 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001). IL-1β levels were increased in HD (9.63 ± 3.50 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) and CRF 4 (7.76 ± 0.66 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) patients than in CRF 1 and in the other groups. Plasma tHcy levels were higher in HD (32.27 ± 12.08 μmol/L) and PD (28.37 ± 4.98 μmol/L) patients compared to the other groups of CRF (P < 0.001). The serum CRP level was significantly increased in HD (18.17 ± 6.38 mg/L) and PD (17.97 ± 4.85 mg/L) patients compared to the other groups of CRF patients (P < 0.001). The plasma fibrinogen level was more elevated in HD (6.86 ± 1.06 g/L) and CRF 4 (6.05 ± 0.57 g/L) than in the other groups (P < 0.001). Furthermore; the ferritin level was higher in HD (169.90 ± 62.16 ng/mL) and PD (90.08 ± 22.09 ng/mL) patients compared to the other groups of CRF (P < 0.001). The serum transferrin value was significantly decreased especially in PD (1.78 ± 0.21 g/L) compared to the other groups (P < 0.001). We found a negative correlation between glomerular filtration rate (GFR), TNF-α levels (r = -0.75, P < 0.001), and tHcy levels (r = -0.68, P < 0.001). We observed a positive correlation between GFR and transferrin levels (r = 0.60, P < 0.001).
CONCLUSION: CRF was associated with elevated inflammatory markers. The inflammation was observed at the severe stage of CRF and increases with progression of renal failure.
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Ma SH, Park BY, Yang JJ, Jung EJ, Yeo Y, Whang Y, Chang SH, Shin HR, Kang D, Yoo KY, Park SK. Interaction of body mass index and diabetes as modifiers of cardiovascular mortality in a cohort study. J Prev Med Public Health 2012; 45:394-401. [PMID: 23230470 PMCID: PMC3514470 DOI: 10.3961/jpmph.2012.45.6.394] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Accepted: 10/10/2012] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVES Diabetes and obesity each increases mortality, but recent papers have shown that lean Asian persons were at greater risk for mortality than were obese persons. The objective of this study is to determine whether an interaction exists between body mass index (BMI) and diabetes, which can modify the risk of death by cardiovascular disease (CVD). METHODS Subjects who were over 20 years of age, and who had information regarding BMI, past history of diabetes, and fasting blood glucose levels (n=16 048), were selected from the Korea Multi-center Cancer Cohort study participants. By 2008, a total of 1290 participants had died; 251 and 155 had died of CVD and stroke, respectively. The hazard for deaths was calculated with hazard ratio (HR) and 95% confidence interval (95% CI) by Cox proportional hazard model. RESULTS Compared with the normal population, patients with diabetes were at higher risk for CVD and stroke deaths (HR, 1.84; 95% CI, 1.33 to 2.56; HR, 1.82; 95% CI, 1.20 to 2.76; respectively). Relative to subjects with no diabetes and normal BMI (21 to 22.9 kg/m(2)), lean subjects with diabetes (BMI <21 kg/m(2)) had a greater risk for CVD and stroke deaths (HR, 2.83; 95% CI, 1.57 to 5.09; HR, 3.27; 95% CI, 1.58 to 6.76; respectively), while obese subjects with diabetes (BMI ≥25 kg/m(2)) had no increased death risk (p-interaction <0.05). This pattern was consistent in sub-populations with no incidence of hypertension. CONCLUSIONS This study suggests that diabetes in lean people is more critical to CVD deaths than it is in obese people.
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Affiliation(s)
- Seung Hyun Ma
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Bo-Young Park
- Cancer Epidemiology Branch, National Cancer Center, Goyang, Korea
| | - Jae Jeong Yang
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - En-Joo Jung
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yohwan Yeo
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yungi Whang
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
| | - Soung-Hoon Chang
- Department of Preventive Medicine, Konkuk University School of Medicine, Chungju, Korea
| | - Hai-Rim Shin
- Non-communicable Disease and Health Promotion, Western Pacific Regional Office, World Health Organization, Manila, Philippines
| | - Daehee Kang
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
| | - Keun-Young Yoo
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sue Kyung Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
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Nassar GM. Preventing and treating inflammation: role of dialysis access management. Semin Dial 2012; 26:28-30. [PMID: 23043614 DOI: 10.1111/sdi.12023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- George M Nassar
- The Methodist Hospital-Texas Medical Center, Weill Cornell University, Houston, Texas 77054-1801, USA.
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Khazaei M, Nematbakhsh M. Effect of experimentally induced metabolic acidosis on aortic endothelial permeability and serum nitric oxide concentration in normal and high-cholesterol fed rabbits. Arch Med Sci 2012; 8:719-23. [PMID: 23056086 PMCID: PMC3460509 DOI: 10.5114/aoms.2012.30296] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2010] [Revised: 01/13/2011] [Accepted: 01/22/2011] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Metabolic acidosis is present in end stage renal disease. There is a link between enhanced endothelial permeability and accelerated atherosclerosis. In this study, we investigated the effect of experimentally induced metabolic acidosis on aortic endothelial permeability and serum nitric oxide (NO) concentration in normal and high-cholesterol fed rabbits. MATERIAL AND METHODS Twenty-four male rabbits were divided into four groups: normal, hypercholesterolemic, acidemic, and hypercholesterolemic plus acidemic. Acidosis and hypercholesterolemia were induced by drinking water containing ammonium chloride (NH(4)Cl), and cholesterol-rich animal chow (1%), respectively. After 6 weeks, blood samples were taken and endothelial permeability was measured using the Evans blue dye injection method. RESULTS Hypercholesterolemic animals had higher aortic endothelial permeability compared with normal groups (16.18 ±0.91 µg EB/g tissue vs. 12.89 ±0.66 µg EB/g tissue, p < 0.05). Acidosis significantly increased endothelial permeability in the normal group (17.10 ±0.56 µg/g tissue vs. 12.89 ± 0.66 µg/g tissue; p < 0.05) but did not further increase endothelial permeability in hypercholesterolemic animals (16.18 ±0.91 µg EB/g tissue vs. 17.29 ±0.46 µg EB/g tissue; p > 0.05). Serum total cholesterol, low density lipoprotein (LDL) and NO concentrations in hypercholesterolemic animals were significantly higher than the normal group and acidosis could not change them either in the normal or in the high-cholesterol diet group. CONCLUSIONS Alterations of serum lipids and NO are not the main mechanism for accelerated atherosclerosis during metabolic acidosis. Acidosis increases aortic endothelial permeability at least in a normal diet which may be a possible mechanism for progression of atherosclerosis processes in end-stage renal disease.
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Affiliation(s)
- Majid Khazaei
- Department of Physiology, Isfahan University of Medical Sciences, Iran
| | - Mehdi Nematbakhsh
- Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences, Iran
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Salehi M, Sohrabi Z, Ekramzadeh M, Fallahzadeh MK, Ayatollahi M, Geramizadeh B, Hassanzadeh J, Sagheb MM. Selenium supplementation improves the nutritional status of hemodialysis patients: a randomized, double-blind, placebo-controlled trial. Nephrol Dial Transplant 2012; 28:716-23. [DOI: 10.1093/ndt/gfs170] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Canaud B, Lertdumrongluk P. Ultrapure dialysis fluid: a new standard for contemporary hemodialysis. Nephrourol Mon 2012; 4:519-23. [PMID: 23573478 PMCID: PMC3614300 DOI: 10.5812/numonthly.3060] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2011] [Revised: 12/15/2011] [Accepted: 01/09/2012] [Indexed: 12/18/2022] Open
Affiliation(s)
- Bernard Canaud
- Nephrology, Dialysis and Intensive Care Unit, Montpellier, France
- Corresponding author: Bernard Canaud, Nephrology, Dialysis and Intensive Care Unit, Lapeyronie University Hospital & Institut de Recherche et Formation en Dialyse, 375, Avenue du Doyen Giraud, 34295 Montpellier, France. Tel.: +334-67338495, Fax: +334-67603783, E-mail:
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Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:237482. [PMID: 22675377 PMCID: PMC3362917 DOI: 10.1155/2012/237482] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Revised: 03/03/2012] [Accepted: 03/19/2012] [Indexed: 11/18/2022]
Abstract
Cyprinus carpio decoction (CCD) is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR) in rats. 70 eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal group received 6.5 mg/kg·bw of ADR injection into the vena caudalis once. Different doses of CCD (11.3 and 22.5 g kg(-1)) were lavaged to rats in YD and YG groups, respectively. Then the serum biochemical values of the total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), electrolyte levels, and the urinary protein (UP) content in 12 hr urine were measured. Interleukin-4 (IL-4) and interferon (INF-γ) were measured by enzyme-like immunosorbent assay (ELISA). The pathomorphological analysis was observed using light and electron microscopy, and the expressions of nephrin and CD2-associated protein (CD2AP) in renal tissues were determined by immunohistochemical assay. The results indicated that CCD can relieve ADR-induced nephropathy (ADN) by improving the nutrition status, regulating the immunity, and inhibiting proteinuria by increasing nephrin and CD2AP expressions.
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Ghoti H, Rachmilewitz EA, Simon-Lopez R, Gaber R, Katzir Z, Konen E, Kushnir T, Girelli D, Campostrini N, Fibach E, Goitein O. Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron. Eur J Haematol 2012; 89:87-93. [PMID: 22435497 DOI: 10.1111/j.1600-0609.2012.01783.x] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/13/2012] [Indexed: 11/29/2022]
Abstract
BACKGROUND/AIMS Erythropoiesis in long-term hemodialyzed (LTH) patients is supported by erythropoietin (rHuEpo) and intravenous (IV) iron. This treatment may end up in iron overload (IO) in major organs. We studied such patients for the parameters of IO in the serum and in major organs. METHODS Patients were treated with rHuEpo (6-8 x 10(3) units × 1-3/wk) and IV 100 mg ferric saccharate. RESULTS Of 115 patients, 21 had serum ferritin (SF) > 1000 ng/mL. This group was further analyzed. Their SF and transferrin saturation (TSAT) were 2688 ± 1489 ng/mL and 54.2 ± 32.7%, respectively (vs. 125-360 ng/mL and 20-50% in normal controls). Serum hepcidin was 60.1 ± 29.5 nm (vs. 10.61 ± 6.44 nm in controls) (P < 0.001). Nineteen patients had increased malonyldialdehyde, a product of lipid peroxidation, indicating oxidative stress. T2* MRI disclosed in 19 of 21 patients moderate to severe IO in the liver and spleen, in three of eight patients in the pancreas, but in no patient in the heart. After stopping IV iron for a mean of 12 months, while continuing rHuEpo, the mean SF decreased in 11 patients to 1682 ng/mL and the mean TSAT decreased to 28%, whereas hemoglobin did not change indicating that tissue iron was utilized. CONCLUSION High SF correlates with IO in the liver and spleen, but not in the heart.
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Affiliation(s)
- Hussam Ghoti
- Department of Hematology, E Wolfson Medical Center, Holon, Israel
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Engineer DR, Garcia JM. Leptin in anorexia and cachexia syndrome. INTERNATIONAL JOURNAL OF PEPTIDES 2012; 2012:287457. [PMID: 22518191 PMCID: PMC3303568 DOI: 10.1155/2012/287457] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Revised: 10/25/2011] [Accepted: 10/28/2011] [Indexed: 12/31/2022]
Abstract
Leptin is a product of the obese (OB) gene secreted by adipocytes in proportion to fat mass. It decreases food intake and increases energy expenditure by affecting the balance between orexigenic and anorexigenic hypothalamic pathways. Low leptin levels are responsible for the compensatory increase in appetite and body weight and decreased energy expenditure (EE) following caloric deprivation. The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic obstructive pulmonary disease, congestive heart failure, chronic kidney disease, and aging, where the decrease in body weight and food intake is not followed by a compensatory increase in appetite or decreased EE. Crosstalk between leptin and inflammatory signaling known to be activated in these conditions may be responsible for this paradox. This manuscript will review the evidence and potential mechanisms mediating changes in the leptin pathway in the setting of anorexia and cachexia associated with chronic diseases.
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Affiliation(s)
- Diana R. Engineer
- Division of Diabetes, Endocrinology and Metabolism, Michael E DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA
- Baylor College of Medicine, 2002 Holcombe Boulevored, Building 109, Room 210, Houston, TX 77030, USA
- Division of Diabetes, Department of Medicine, Endocrinology and Metabolism, St Luke's Episcopal Hospital, Houston, TX 77030, USA
| | - Jose M. Garcia
- Division of Diabetes, Endocrinology and Metabolism, Michael E DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA
- Baylor College of Medicine, 2002 Holcombe Boulevored, Building 109, Room 210, Houston, TX 77030, USA
- Huffington Center of Aging, Baylor College of Medicine, Houston, TX 77030, USA
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Chung S, Koh ES, Shin SJ, Park CW. Malnutrition in patients with chronic kidney disease. ACTA ACUST UNITED AC 2012. [DOI: 10.4236/ojim.2012.22018] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Sztanek F, Seres I, Harangi M, Locsey L, Koncsos P, Paragh G. Effect of Nutritional Status on Human Paraoxonase-1 Activity in Patients with Chronic Kidney Disease. ACTA ACUST UNITED AC 2012; 36:310-9. [DOI: 10.1159/000343383] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2012] [Indexed: 11/19/2022]
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Caliskan Y, Yelken B, Gorgulu N, Ozkok A, Yazici H, Telci A, Turkmen A, Yildiz A, Sever MS. Comparison of markers of appetite and inflammation between hemodialysis patients with and without failed renal transplants. J Ren Nutr 2011; 22:258-267. [PMID: 22056149 DOI: 10.1053/j.jrn.2011.07.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2011] [Revised: 07/16/2011] [Accepted: 07/19/2011] [Indexed: 11/11/2022] Open
Abstract
OBJECTIVE The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation. METHODS Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 ± 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 ± 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed. RESULTS There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed-transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF-α levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group. CONCLUSIONS Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts.
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Affiliation(s)
- Yasar Caliskan
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
| | - Berna Yelken
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Numan Gorgulu
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Abdullah Ozkok
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Halil Yazici
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Aysegul Telci
- Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Aydin Turkmen
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Alaattin Yildiz
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehmet S Sever
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Drechsler C, Grootendorst DC, Pilz S, Tomaschitz A, Krane V, Dekker F, März W, Ritz E, Wanner C. Wasting and sudden cardiac death in hemodialysis patients: a post hoc analysis of 4D (Die Deutsche Diabetes Dialyse Studie). Am J Kidney Dis 2011; 58:599-607. [PMID: 21820222 DOI: 10.1053/j.ajkd.2011.05.026] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2010] [Accepted: 05/26/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Wasting is common in hemodialysis patients and often is accompanied by cardiovascular disease and inflammation. The cardiovascular risk profile meaningfully changes with the progression of kidney disease, and little is known about the impact of wasting on specific clinical outcomes. This study examined the effects of wasting on the various components of cardiovascular outcome and deaths caused by infection in hemodialysis patients. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 1,255 hemodialysis patients from 178 centers participating in Die Deutsche Diabetes Dialyse Studie (4D) in 1998-2004. PREDICTOR Moderate wasting was defined as body mass index, albumin, and creatinine values less than the median (26.7 kg/m(2), 3.8 g/dL, and 6.8 mg/dL, respectively) and C-reactive protein level less than the median (5 mg/L) at baseline. Severe wasting was defined as body mass index, albumin, and creatinine levels less than the median and C-reactive protein level greater than the median at baseline. OUTCOMES & MEASUREMENTS Risks of sudden cardiac death (SCD), myocardial infarction (MI), stroke, combined cardiovascular events, deaths due to infection, and all-cause mortality were determined using Cox regression analyses during a median of 4 years of follow-up. RESULTS 196 patients had wasting (severe, n = 109; and moderate, n = 87). Overall, 617 patients died (160 of SCD and 128 of infectious deaths). Furthermore, 469 patients experienced a cardiovascular event, with MI and stroke occurring in 200 and 103 patients, respectively. Compared with patients without wasting (n = 1,059), patients with severe wasting had significantly increased risks of SCD (adjusted HR, 1.8; 95% CI, 1.1-3.1), all-cause mortality (adjusted HR, 1.8; 95% CI, 1.4-2.4), and deaths due to infection (adjusted HR, 2.3; 95% CI, 1.2-4.3). In contrast, MI was not affected. The increased risk of cardiovascular events (adjusted HR, 1.5; 95% CI, 1.0-2.1) was explained mainly by the effect of wasting on SCD. LIMITATIONS Selective patient cohort. CONCLUSIONS Wasting was associated strongly with SCD, but not MI, in diabetic hemodialysis patients. Nonatherosclerotic cardiac disease potentially has a major role to account for the increased cardiovascular events in patients with wasting, suggesting the need for novel treatment strategies.
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Affiliation(s)
- Christiane Drechsler
- Department of Medicine, Division of Nephrology, University Hospital Würzburg, Germany.
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Lestz RM, Atkinson M, Fivush B, Furth SL. No difference in meeting hemoglobin and albumin targets for dialyzed children with urologic disorders. Pediatr Nephrol 2011; 26:1129-36. [PMID: 21424524 PMCID: PMC5739035 DOI: 10.1007/s00467-011-1850-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2010] [Revised: 03/01/2011] [Accepted: 03/01/2011] [Indexed: 11/25/2022]
Abstract
Urologic disorders are the most common cause of chronic kidney disease in children. To determine whether children with urologic etiology of end-stage renal disease (ESRD) fare better than children with ESRD from other causes while on dialysis, we conducted a cross-sectional study of children <18 years receiving peritoneal and hemodialysis in the United States using data from the Centers for Medicare & Medicaid Services 2005 ESRD CPM Project. We compared baseline demographics and the study groups. In multivariate logistic regression analysis of 1,286 subjects, we assessed whether children with urologic disorders had a higher odds of meeting adult KDOQI targets for hemoglobin levels ≥11 g/dl and albumin ≥3.5 BCG/3.2 BCP g/dl. We conducted a subset analysis of 1,136 patients to examine the impact of erythropoietin on hemoglobin targets. Our results did not reveal differences in achievement of adult hemoglobin targets (adjusted OR: 1.27; p value 0.09; CI: 0.97-1.66) or in the subset analysis with erythropoietin (adjusted OR: 1.32; p value 0.06; CI: 0.98-1.78) or albumin targets (adjusted OR: 1.22; p value 0.21; CI: 0.90-1.65) in adjusted analyses. Due to our study's limitations, it is difficult to determine whether this may result from treatment prior to dialysis initiation or treatment effect of dialysis rather than underlying diagnosis.
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Affiliation(s)
- Rachel M Lestz
- Division of Pediatric Nephrology, Johns Hopkins University, 200 N. Wolfe St., Baltimore, MD 21287, USA.
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Li ZI, Chung ACK, Zhou L, Huang XR, Liu F, Fu P, Fan JM, Szalai AJ, Lan HY. C-reactive protein promotes acute renal inflammation and fibrosis in unilateral ureteral obstructive nephropathy in mice. J Transl Med 2011; 91:837-51. [PMID: 21383672 DOI: 10.1038/labinvest.2011.42] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Elevated blood level of C-reactive protein (CRP) is associated with increased risk of chronic kidney disease. However, whether this association reflects functional importance of CRP in the pathogenesis of kidney disease remains unclear. In this study, we examined the biological role of CRP in a well-characterized model of progressive kidney disease, unilateral ureteral obstruction (UUO), in mice that express the human CRP gene (CRPtg). Compared with wild-type (Wt) mice at 3 days after UUO, CRPtg mice developed more severe renal inflammation with a significant increase in tubulointerstitial T cells and macrophages, upregulation of proinflammatory cytokines (IL-1β and TNF-α), chemokines (MCP-1), and adhesion molecules (ICAM-1). Renal fibrosis was also significantly enhanced in CRPtg mice as demonstrated by increased expression of tubulointerstitial α-smooth muscle actin and collagen types I and III compared with Wt mice. Interestingly, on days 7 and 14 after UUO, an equal severity of renal inflammation and fibrosis were observed in CRPtg and Wt mice. These findings suggested that CRP may have a role in the initiation of renal inflammation and fibrosis. Further study revealed that enhanced early renal inflammation and fibrosis on day 3 in CRPtg mice was associated with a significant upregulation of endogenous mouse CRP and FcγRI mRNA and increased activation of both NF-κB/p65 and TGF-β/Smad2/3 signaling, while equal severity of progressive renal injury at day 7 and day 14 between CRPtg and Wt mice were attributed to equivalent levels of CRP, FcγRI, phospho-NF-κB/p65, and TGF-β/Smad2/3 signaling. Based on these findings, we conclude that CRP may not only be a biomarker, but also a mediator in the early development of renal inflammation and fibrosis in a mouse model of UUO. Enhanced activation of both NF-κB and TGF-β/Smad signaling pathways may be mechanisms by which CRP promotes early renal inflammation and fibrosis.
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Affiliation(s)
- Z I Li
- Department of Medicine-Nephrology, West China Hospital of Sichuan University, Chengdu, China
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Abstract
PURPOSE OF REVIEW Cachexia is a progressive deterioration of body habitus associated with chronic diseases. The finding that only a proportion of patients with chronic disease develop cachexia has prompted studies looking for genetic polymorphisms that may underlie differential susceptibility. The aim of this review is to explore how inflammation and gene polymorphisms influence susceptibility to cachexia. RECENT FINDINGS There has been evidence that certain cytokine gene polymorphisms are associated with cachexia. However, only the IL10 -1082 G allele, which is associated with an increased risk of developing cachexia has been replicated in more than one study. Variation in genes outwith inflammation pathways (e.g. genes involved in protein metabolism) is also likely to contribute the susceptibility of developing cachexia. The insertion/deletion angiotensin converting enzyme (ACE) gene polymorphism has recently been linked with lower lean body mass in cancer patients with cachexia. SUMMARY Although there is an increasing body of evidence of genetic susceptibility to cachexia, most studies so far have only focussed on a small number of polymorphisms and have small sample sizes. Large-scale candidate gene studies or genome-wide association studies are required to further elucidate the link between genotype and cachexia.
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Plasma albumin levels correlate with decreased microcirculation and the development of skin defects in hemodialyzed patients. Nutrition 2011; 26:880-5. [PMID: 20692601 DOI: 10.1016/j.nut.2010.05.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2010] [Revised: 05/12/2010] [Accepted: 05/12/2010] [Indexed: 11/22/2022]
Abstract
OBJECTIVES Difficulty healing wounds and skin defects is a frequent problem in patients on chronic hemodialysis (HD) because of malnutrition, inflammation, and atherosclerosis (MIA) syndrome. The aim of the present study was to estimate the influence of peripheral blood flow changes during HD on the development of foot defects and its relationship to plasma albumin levels. METHODS Peripheral skin blood flow was measured using a laser Doppler line scanner in 10 different areas of the dorsal part of the instep and the toes of each foot before and during HD with ultrafiltration (897 +/- 465 mL/procedure) in 31 HD patients (10 female, 21 male; age 36-79 y, body mass index = 28 +/- 5.0). No skin defects or apparent acute disease or infection were detected in any patient at the time of laser Doppler line scanner measurement. The feet of the patients were clinically re-examined carefully over the next 18 mo. RESULTS We found a significant and constant decrease of skin blood flow during the HD procedure (P < 0.001). Skin blood flow was significantly correlated with serum albumin level both before HD (r = 0.36, P = 0.05) and during HD (r = 0.47, P = 0.007). Skin defects developed in 11 patients, with significantly lower skin blood flow during the 18-mo follow-up period. A significantly larger number of patients who had normal perfusion remained defect-free in comparison to patients with critical perfusion (93% versus 38%, P = 0.002, Kaplan-Meier analysis). CONCLUSION Skin blood flow may be impaired in HD patients. The apparent malnutrition and inflammation in HD patients are likely responsible for the decreased skin blood flow and the development of the difficulty to heal skin defects and wounds.
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