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Huang C, Yang Y, Li C, Guo L, Liu M, Xiong G. Benazepril Promotes the Proliferation and Differentiation of Urine-Derived Stem Cells from Children with Nephrotic Syndrome During the Chronic Kidney Disease Stage. Biochem Genet 2025:10.1007/s10528-025-11056-9. [PMID: 39969653 DOI: 10.1007/s10528-025-11056-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 02/07/2025] [Indexed: 02/20/2025]
Abstract
Nephrotic Syndrome (NS), especially in the Chronic Kidney Disease (CKD) stage, poses significant challenges in pediatric nephrology. Urine-derived stem cells (USCs) show promise for renal repair and regeneration. While benazepril is commonly used to treat CKD, its impact on USCs from children with NS during the CKD stage is unclear. USCs were isolated from the urine of 6 healthy children and 6 with NS (CKD stage), cultured through passages, and their morphology and cell surface markers were assessed microscopically and by flow cytometry, respectively. USCs were treated with benazepril at concentrations of 1, 10, 20, 40 μmol/L, and proliferation was evaluated using the CCK-8 assay. ROS levels were measured using DCFH-DA probe, and the expression levels of IL-1β, Connexin 43, AEC, ACE2, Ang2, AQP-1 and E-cadherin were analyzed by Western Blot. Tubular epithelial cell differentiation was also examined. USCs could be cultured from both healthy and NS (CKD stage) children, but USCs from NS children only reached passage 5 and exhibited weaker proliferation and differentiation abilities compared to those from healthy children. IL-1β, Connexin 43, ROS,ACE and Ang2 levels were higher in USCs from NS children than in those from healthy children, while ACE2 showed the opposite trend. Treatment with 1 μmol/L benazepril enhanced the proliferation and differentiation ability of USCs from NS children, inhibiting the level of inflammation factors, ROS, ACE and Ang2 while promoting ACE2 expression in these cells. This study offers valuable insights for future USCs applications.
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Affiliation(s)
- Chengqiang Huang
- Department of Pediatric Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361101, People's Republic of China
- Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, People's Republic of China
| | - Yuan Yang
- Department of Pediatric Surgery, The People's Hospital of Leshan, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, People's Republic of China
| | - Cheng Li
- Department of Child Health Care, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People's Republic of China
| | - Ling Guo
- Department of Pediatric hematologic Oncology and Respiratory, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, Sichuan, People's Republic of China
| | - Ming Liu
- Department of Pediatric Surgery, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, Sichuan, People's Republic of China
| | - Geng Xiong
- Department of Pediatric Surgery, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, Sichuan, People's Republic of China.
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Adeva-Andany MM, Adeva-Contreras L, Carneiro-Freire N, Ameneiros-Rodríguez E, Vila-Altesor M, Calvo-Castro I. The impact of high altitude (hypobaric hypoxia) on insulin resistance in humans. J Physiol Biochem 2025; 81:35-55. [PMID: 40019670 DOI: 10.1007/s13105-025-01069-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 01/30/2025] [Indexed: 03/01/2025]
Abstract
Exposure to hypobaric hypoxia (high altitude) diminishes systemic tissue oxygenation. Tissue hypoxia induces insulin resistance and a metabolic switch that reduces oxidative phosphorylation and glucose storage while enhancing glycolysis. Similarly to hypobaric hypoxia, insulin resistance develops in normal humans undergoing normobaric hypoxia and in patients with obstructive sleep apnea. Following acute exposure to high altitude, insulin resistance returns to baseline values upon returning to sea level or when compensatory mechanisms restore tissue oxygenation. However, insulin resistance persists in subjects unable to achieve sufficient oxygen delivery to tissues. Likewise, long-term residents at high altitude develop persistent insulin resistance when compensatory mechanisms do not attain adequate tissue oxygenation. Among these subjects, insulin resistance may cause clinical complications, such as hypertriglyceridemia, reduced HDL-c, visceral obesity, metabolic dysfunction-associated steatotic liver disease, essential hypertension, type 2 diabetes, subclinical vascular injury, cardiovascular disease, and kidney disease. Impaired tissue oxygenation allows the stabilization of hypoxia-inducible factor-1 (HIF-1), a transcription factor that modulates the transcriptional activity of a number of genes to coordinate the physiological responses to tissue hypoxia. Among them, HIF-1 downregulates PPARG, that codes peroxisome proliferator-activated receptor-gamma (PPAR-γ) and PPARGCA, that codes PPAR-γ coactivator-1α, in order to enable insulin resistance and the metabolic switch from oxidative phosphorylation toward glycolysis.
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Affiliation(s)
- María M Adeva-Andany
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, Ferrol, 15406, Spain.
| | - Lucia Adeva-Contreras
- School of Medicine, Santiago de Compostela University, Santiago de Compostela, Galicia, Spain
| | - Natalia Carneiro-Freire
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, Ferrol, 15406, Spain
| | - Eva Ameneiros-Rodríguez
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, Ferrol, 15406, Spain
| | - Matilde Vila-Altesor
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, Ferrol, 15406, Spain
| | - Isabel Calvo-Castro
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, Ferrol, 15406, Spain
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Juarez-Villa JD, Zepeda-Quiroz I, Toledo-Ramírez S, Gomez-Johnson VH, Pérez-Allende F, Garibay-Vega BR, Rodríguez Castellanos FE, Moguel-González B, Garcia-Cruz E, Lopez-Gil S. Exploring kidney biopsy findings in congenital heart diseases: Insights beyond cyanotic nephropathy. World J Nephrol 2024; 13:88972. [PMID: 38596269 PMCID: PMC11000040 DOI: 10.5527/wjn.v13.i1.88972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 12/20/2023] [Accepted: 01/15/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND The association between congenital heart disease and chronic kidney disease is well known. Various mechanisms of kidney damage associated with congenital heart disease have been established. The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis (FSGS), however, this has only been demonstrated in case reports and not in observational or clinical trials. AIM To identify baseline and clinical characteristics, as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital. METHODS This is a retrospective observational study conducted at the Nephrology Department of the National Institute of Cardiology "Ignacio Chávez". All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study. RESULTS Ten patients with congenital heart disease and kidney biopsy were found. The average age was 29.00 years ± 15.87 years with pre-biopsy proteinuria of 6193 mg/24 h ± 6165 mg/24 h. The most common congenital heart disease was Fallot's tetralogy with 2 cases (20%) and ventricular septal defect with 2 (20%) cases. Among the 10 cases, one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found, receiving specific treatment after histopathological diagnosis, delaying the initiation of kidney replacement therapy. Among remaining 8 cases (80%), one case of FSGS with perihilar variety was found, while the other 7 cases were non-specific FSGS. CONCLUSION Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy. In 2 out of 10 patients in our study, interventions were performed, and initiation of kidney replacement therapy was delayed. Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.
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Affiliation(s)
- Jose Daniel Juarez-Villa
- Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
| | - Iván Zepeda-Quiroz
- Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
| | - Sebastián Toledo-Ramírez
- Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
| | - Victor Hugo Gomez-Johnson
- Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
| | - Francisco Pérez-Allende
- Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
| | | | | | - Bernardo Moguel-González
- Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
| | - Edgar Garcia-Cruz
- Congenital Heart Disease, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
| | - Salvador Lopez-Gil
- Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City 14080, Mexico
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Sharma M, Singh V, Sharma R, Koul A, McCarthy ET, Savin VJ, Joshi T, Srivastava T. Glomerular Biomechanical Stress and Lipid Mediators during Cellular Changes Leading to Chronic Kidney Disease. Biomedicines 2022; 10:407. [PMID: 35203616 PMCID: PMC8962328 DOI: 10.3390/biomedicines10020407] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 02/04/2023] Open
Abstract
Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their metabolites are potent transducers of biomechanical stress from the cell surface to intracellular compartments. Omega-6 and ω-3 long-chain PUFA from membrane phospholipids generate many versatile and autacoid oxylipins that modulate pro-inflammatory as well as anti-inflammatory autocrine and paracrine signaling. We advance the idea that lipid signaling molecules, related enzymes, metabolites and receptors are not just mediators of cellular stress but also potential targets for developing novel interventions. With the growing emphasis on lifestyle changes for wellness, dietary fatty acids are potential adjunct-therapeutics to minimize/treat hyperfiltration-induced progressive glomerular damage and CKD.
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Affiliation(s)
- Mukut Sharma
- Research and Development Service, Kansas City VA Medical Center, Kansas City, MO 64128, USA;
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
- Department of Internal Medicine, The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, MO 66160, USA;
| | - Vikas Singh
- Neurology, Kansas City VA Medical Center, Kansas City, MO 64128, USA;
| | - Ram Sharma
- Research and Development Service, Kansas City VA Medical Center, Kansas City, MO 64128, USA;
| | - Arnav Koul
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
| | - Ellen T. McCarthy
- Department of Internal Medicine, The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, MO 66160, USA;
| | - Virginia J. Savin
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
| | - Trupti Joshi
- Department of Health Management and Informatics, University of Missouri, Columbia, MO 65201, USA;
| | - Tarak Srivastava
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
- Section of Nephrology, Children’s Mercy Hospital and University of Missouri, Kansas City, MO 64108, USA
- Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri, Kansas City, MO 64108, USA
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Kuppe C, Rohlfs W, Grepl M, Schulte K, Veron D, Elger M, Sanden SK, Saritas T, Andrae J, Betsholtz C, Trautwein C, Hausmann R, Quaggin S, Bachmann S, Kriz W, Tufro A, Floege J, Moeller MJ. Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures. Nephrol Dial Transplant 2019; 33:1514-1525. [PMID: 29635428 DOI: 10.1093/ndt/gfy057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 02/08/2018] [Indexed: 12/17/2022] Open
Abstract
Background Vascular endothelial growth factor A (VEGF) is an essential growth factor during glomerular development and postnatal homeostasis. VEGF is secreted in high amounts by podocytes into the primary urine, back-filtered across the glomerular capillary wall to act on endothelial cells. So far it has been assumed that VEGF back-filtration is driven at a constant rate exclusively by diffusion. Methods In the present work, glomerular VEGF back-filtration was investigated in vivo using a novel extended model based on endothelial fenestrations as surrogate marker for local VEGF concentrations. Single nephron glomerular filtration rate (SNGFR) and/or local filtration flux were manipulated by partial renal mass ablation, tubular ablation, and in transgenic mouse models of systemic or podocytic VEGF overexpression or reduction. Results Our study shows positive correlations between VEGF back-filtration and SNGFR as well as effective filtration rate under physiological conditions along individual glomerular capillaries in rodents and humans. Conclusion Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.
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Affiliation(s)
- Christoph Kuppe
- Division of Nephrology and Immunology, RWTH Aachen University, Aachen, Germany
| | - Wilko Rohlfs
- Institute of Heat and Mass Transfer, RWTH Aachen University, Aachen, Germany
| | - Martin Grepl
- Numerical Mathematics, Faculty for Mathematics, Informatics and Natural Sciences, RWTH Aachen University, Aachen, Germany
| | - Kevin Schulte
- Division of Nephrology and Immunology, RWTH Aachen University, Aachen, Germany.,Department of Nephrology, University of Kiel, Kiel, Germany
| | - Delma Veron
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
| | - Marlies Elger
- Department of Anatomy and Developmental Biology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | | | - Turgay Saritas
- Division of Nephrology and Immunology, RWTH Aachen University, Aachen, Germany
| | - Johanna Andrae
- Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden
| | - Christer Betsholtz
- Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden
| | - Christian Trautwein
- Division of Gastroenterology and Endocrinology, RWTH Aachen University Hospital, Aachen, Germany
| | - Ralf Hausmann
- Institute of Molecular Pharmacology, RWTH Aachen University Hospital, Aachen, Germany
| | - Susan Quaggin
- Division of Medicine-Nephrology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | - Wilhelm Kriz
- Department of Anatomy and Developmental Biology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Alda Tufro
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
| | - Jürgen Floege
- Division of Nephrology and Immunology, RWTH Aachen University, Aachen, Germany
| | - Marcus J Moeller
- Division of Nephrology and Immunology, RWTH Aachen University, Aachen, Germany.,Interdisciplinary Centre for Clinical Research (IZKF Aachen), RWTH Aachen University Hospital, Aachen, Germany.,Heisenberg Chair for Preventive and Translational Nephrology, Division of Nephrology, RWTH Aachen University, Aachen, Germany
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Rajani H, Narayanappa D, Shetty M. Renal impairment in a child with cyanotic congenital heart disease. PROGRESS IN PEDIATRIC CARDIOLOGY 2018; 48:105-106. [DOI: 10.1016/j.ppedcard.2018.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Hongsawong N, Khamdee P, Silvilairat S, Chartapisak W. Prevalence and associated factors of renal dysfunction and proteinuria in cyanotic congenital heart disease. Pediatr Nephrol 2018; 33:493-501. [PMID: 28971258 DOI: 10.1007/s00467-017-3804-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 09/02/2017] [Accepted: 09/04/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Cyanotic nephropathy (CN), seen in 30-50% of patients with congenital cyanotic heart disease (CCHD), affects both tubular and glomerular function, resulting in proteinuria and azotemia. Microalbuminuria is an early marker for glomerular damage and an independent predictor of progressive renal disease. METHODS A cross-sectional study was conducted. A total of 116 patients aged 1 month to 15 years with CCHD at Chiang Mai University Hospital between 2015 and 2016 were assessed and 94 patients were enrolled. To determine the prevalence and associated factors of significant albuminuria in CCHD patients, baseline characteristics, oxygen saturation, surgery, hemoglobin (Hb), hematocrit (Hct), spot urine albumin, urine protein, and creatinine were obtained. Binary logistic-regression modeling was used to identify associated factors. RESULTS Prevalence of CN in children with CCHD was 58.51% and 92.55% according to albuminuria and proteinuria staging respectively. Prevalence of significant proteinuria, significant albuminuria, and decreased GFR was 88.30%, 41.49% and 31.91% respectively. Participants with significant albuminuria had fewer previous surgeries (p = 0.05), a longer waiting time for surgery (p = 0.02), enalapril usage (p = 0.04), pulmonary hypertension (p = 0.03), higher Hct z-score (p = 0.03) and lower platelet count (p = 0.001) compared with those without significant albuminuria. Using multivariate logistic regression analysis, waiting duration for surgery (p = 0.04), Hct >40% (p = 0.02), and platelet count <290,000/mm3 (p = 0.04) were predictive of microalbuminuria. CONCLUSIONS Cyanotic nephropathy can be detected in the first decade of life with the presentation of microalbuminuria. High Hct level and low platelet count were identified as a predictor of microalbuminuria, whereas early cardiac surgery decreased the risk of developing significant albuminuria.
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Affiliation(s)
- Nattaphorn Hongsawong
- Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
| | - Prapimdaw Khamdee
- Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Suchaya Silvilairat
- Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Wattana Chartapisak
- Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
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Yamada S, Yotsueda H, Taniguchi M, Tsuruya K, Hirakata H, Iida M. Successful initiation and maintenance of hemodialysis in an adult patient with complete transposition of the great arteries. Clin Exp Nephrol 2010; 14:511-5. [PMID: 20607578 DOI: 10.1007/s10157-010-0315-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2009] [Accepted: 06/14/2010] [Indexed: 10/19/2022]
Abstract
Cyanotic congenital heart disease (CCHD) is a life-threatening cardiac defect that requires palliative or corrective surgery in early life. Major advances in medical and surgical management have resulted in the survival of CCHD patients to adulthood with or without corrective surgery, though some are at risk of development of end-stage renal disease (ESRD) due to cyanotic nephropathy (CN). There is little or no information on the initiation and maintenance of hemodialysis (HD) in such patients. We present here a case of a 44-year-old man with complete transposition of the great arteries and CN-related ESRD. He had only received a bi-directional Glenn's operation and still suffered persistent severe hypoxemia and impaired cardiac function. ESRD was successfully treated with HD over more than 4 years. The case emphasizes the need for special attention in the selection and initiation of renal replacement therapy.
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Affiliation(s)
- Shunsuke Yamada
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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9
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Chronic cyanosis and vascular function: implications for patients with cyanotic congenital heart disease. Cardiol Young 2010; 20:242-53. [PMID: 20416139 DOI: 10.1017/s1047951110000466] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
In patients with cyanotic congenital heart disease, chronic hypoxaemia leads to important changes in blood vessel function and structure. Some of these alterations are maladaptive and probably contribute to impaired cardiopulmonary performance and an increased incidence of thrombotic and embolic events. Recent evidence suggests that deranged endothelial function, a sequel of chronic cyanosis, could be an important factor in the pathogenesis of cyanosis-associated cardiovascular risk. In this article, we discuss the physiological and mechanical consequences of compensatory erythrocytosis and possible pathophysiological mechanisms of vascular dysfunction in chronic cyanosis.
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Inatomi J, Matsuoka K, Fujimaru R, Nakagawa A, Iijima K. Mechanisms of development and progression of cyanotic nephropathy. Pediatr Nephrol 2006; 21:1440-5. [PMID: 16902784 DOI: 10.1007/s00467-006-0220-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2006] [Revised: 05/09/2006] [Accepted: 05/09/2006] [Indexed: 10/24/2022]
Abstract
Cyanotic nephropathy (CN) is often accompanied by congenital cyanotic heart diseases (CCHD). The purpose of this study was to clarify the risk factors and the mechanisms of involved in the development and progression of CN. Thirty patients with CCHD were examined. We analyzed the risk factors for the development of CN on the basis of the clinical and laboratory findings. We also examined ten renal biopsy specimens obtained from patients with CN. Patients with CN showed significantly higher hematocrit levels than those without CN (P=0.025), although there was no difference between the two groups in terms of oxygen saturation. The renal plasma flow (RPF) in patients both with and without CN was low. However, the filtration fraction (FF) was significantly lower in patients with CN than in those without CN (P=0.001). The glomeruli of biopsy specimens with significant proteinuria (n=7) were larger than those of biopsy specimens without significant proteinuria, and there were more capillaries per glomerulus in the former than in the latter (n=3) and the control specimens (n=6) (glomerular size: P<0.01; number of glomerular capillaries: P<0.01). In conclusion, hyperviscosity by polycythemia may be responsible for the development of CN. This pathological condition may induce an angiogenic increase in the glomerular capillary beds, in turn leading to glomerulomegaly. In addition, the failure of a compensatory mechanism to respond to reduced RPF by hyperfiltration may be accompanied by the development and progression of CN.
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Affiliation(s)
- Jun Inatomi
- Department of Nephrology, National Children's Medical Center, National Center for Child Health and Development, 10-1, Okura 2-chome, Setagaya-ku, Tokyo 157-8535, Japan
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Vonder Muhll I, Liu P, Webb G. Applying standard therapies to new targets: the use of ACE inhibitors and B-blockers for heart failure in adults with congenital heart disease. Int J Cardiol 2004; 97 Suppl 1:25-33. [PMID: 15590076 DOI: 10.1016/j.ijcard.2004.08.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Increasingly, patients and clinicians are being confronted with congestive heart failure (CHF) as a late complication of congenital heart disease. However, medical management of heart failure in this patient group represents a challenge because of complex hemodynamics and a lack of evidence from large randomized controlled trials to guide therapy. This article will review the evidence of the use angiotensin converting enzyme inhibitors (ACEIs) and beta-blockers (BBs) in left heart failure, discuss the mechanisms of heart failure as they pertain to congenital heart disease and review the limited literature of the use of neurohormonal antagonists in congenital heart disease. Some recommendations for use of angiotensin converting enzyme inhibitors and beta-blockers in heart failure due various congenital heart lesions are offered. Well-designed clinical trials are urgently needed to extend the impressive reductions in morbidity and mortality achieved with neurohormonal blockade in left ventricular (LV) heart failure to adults with congenital heart disease.
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Affiliation(s)
- Isabelle Vonder Muhll
- Joint Fellow in Adult Congenital Heart Disease, Royal Brompton Hospital/Toronto General Hospital, Canada.
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12
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Pölzl G, Lhotta K, Tiefenthaler M, Smekal A, Müller S. Bilateral perirenal fluid accumulation associated with Eisenmenger's syndrome. Nephrol Dial Transplant 2004; 19:1928-9. [PMID: 15199204 DOI: 10.1093/ndt/gfh162] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Gerhard Pölzl
- Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, Austria.
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13
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Vats AN, Ishwad C, Vats KR, Moritz M, Ellis D, Mueller C, Surti U, Parizhskaya MZ, Meza MP, Burke L, Schneck FX, Saxena M, Ferrell R. Steroid-resistant nephrotic syndrome and congenital anomalies of kidneys: evidence of locus on chromosome 13q. Kidney Int 2003; 64:17-24. [PMID: 12787391 DOI: 10.1046/j.1523-1755.2003.00066.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Steroid-resistant nephrotic syndrome (SRNS) and congenital anomalies of kidney and urinary tract (CAKUT) are major causes of renal dysfunction in children. Although a few patients with 13q deletion have been previously reported with renal anomalies, the association of SRNS with 13q has not been reported and critical regions associated with CAKUT have not been identified. We present the results of deletion mapping studies to identify the critical regions. METHODS Cytogenetic and deletion mapping studies were performed on DNA obtained from peripheral blood of two children with renal anomalies and interstitial deletion of 13q as well as their parents. Twenty eight microsatellite markers with a spacing of 1-8 Mb (1-3 cM) were utilized. RESULTS The patients (both males, 5 and 10 years old) had varying severity of developmental delay and other neurologic disorders. The renal involvement included hydronephrosis, ureterocele, renal dysplasia, and mesangioproliferative SRNS. Our studies imply existence of at least two critical regions in the 13q area that are linked to CAKUT. The first is a 7 Mb region defined by markers D13S776 and D13S891 shared by both patients. The second is a much larger region extending at least 33 Mb above D13S776 seen in one patient with severe renal malformations and SRNS. CONCLUSION We report an association of chromosome 13q with CAKUT as well as SRNS. Our studies suggest the presence of more than one gene in this region that is likely to be involved in renal development and function.
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Affiliation(s)
- Abhay N Vats
- Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
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