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Bhattacharya R, Ward T, Kalejaiye TD, Mishra A, Leeman S, Arzaghi H, Seidman JG, Seidman CE, Musah S. Engineered human iPS cell models reveal altered podocytogenesis and glomerular capillary wall in CHD-associated SMAD2 mutations. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.02.606108. [PMID: 39211233 PMCID: PMC11360959 DOI: 10.1101/2024.08.02.606108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Early developmental programming involves extensive cell lineage diversification through shared molecular signaling networks. Clinical observations of congenital heart disease (CHD) patients carrying SMAD2 genetic variants revealed correlations with multi-organ impairments at the developmental and functional levels. For example, many CHD patients present with glomerulosclerosis, periglomerular fibrosis, and albuminuria. Still, it remains largely unknown whether SMAD2 variants associated with CHD can directly alter kidney cell fate, tissue patterning, and organ-level function. To address this question, we engineered human iPS cells (iPSCs) and organ-on-a-chip systems to uncover the role of pathogenic SMAD2 variants in kidney podocytogenesis. Our results show that abrogation of SMAD2 causes altered patterning of the mesoderm and intermediate mesoderm (IM) cell lineages, which give rise to nearly all kidney cell types. Upon further differentiation of IM cells, the mutant podocytes failed to develop arborizations and interdigitations. A reconstituted glomerulus-on-a-chip platform exhibited significant proteinuria as clinically observed in glomerulopathies. This study implicates CHD-associated SMAD2 mutations in kidney tissue malformation and provides opportunities for therapeutic discovery in the future.
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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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Rajpal S, Alshawabkeh L, Almaddah N, Joyce CM, Shafer K, Gurvitz M, Waikar SS, Mc Causland FR, Landzberg MJ, Opotowsky AR. Association of Albuminuria With Major Adverse Outcomes in Adults With Congenital Heart Disease: Results From the Boston Adult Congenital Heart Biobank. JAMA Cardiol 2019. [PMID: 29541749 DOI: 10.1001/jamacardio.2018.0125] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Importance Albuminuria is associated with adverse outcomes in diverse groups of patients, but the importance of albuminuria in the emerging population of increasingly complex adults with congenital heart disease (ACHD) remains unknown. Objective To assess the prevalence, risk factors, and prognostic implications of albuminuria in ACHD. Design, Setting, and Participants This prospective study assessed a cohort of ambulatory patients aged 18 years and older who were examined at an ACHD referral center and enrolled in the Boston ACHD Biobank between May 17, 2012, to August 5, 2016. Albuminuria was defined as an urine albumin-to-creatinine (ACR) ratio of 30 mg/g or more. Main Outcomes and Measures Death or nonelective cardiovascular hospitalization, defined as overnight admission for heart failure, arrhythmia, thromboembolic events, cerebral hemorrhage, and/or disease-specific events. Results We measured the ACR of 612 adult patients with CHD (mean [SD] age, 38.6 [13.4] years; 308 [50.3%] women). Albuminuria was present in 106 people (17.3%) and was associated with older age (patients with ACR <30 mg/g: mean [SD]: 37.5 [13.2] years; vs patients with ACR ≥30 mg/g: 43.8 [13.1] years; P < .001), presence of diabetes mellitus (ACR <30 mg/g: 13 of 506 [2.6%]; vs ≥30 mg/g: 11 of 106 [10.4%]; P < .001), lower estimated glomerular filtration rate (ACR <30 mg/g: median [interquartile range (IQR)]: 103.3 [90.0-116.4] mL/min/1.73 m2; ACR ≥30 mg/g: 99.1 [78.8-108.7] mL/min/1.73 m2; P = .002), and cyanosis (ACR <30 mg/g: 23 of 506 [5.1%]; vs ACR ≥30 mg/g: 21 of 106 [22.6%]; P < .001). After a mean (SD) follow-up time of 270 (288) days, 17 patients (2.5%) died, while 68 (11.1%) either died or experienced overnight inpatient admission. Albuminuria predicted outcome, with 30 of 106 patients with albuminuria (28.3%) affected vs 38 of 506 patients without albuminuria (7.5%; hazard ratio [HR], 3.0; 95% CI, 1.9-4.9; P < .001). Albuminuria was also associated with increased mortality (11 of 106 [10.4%]; vs 6 of 506 [1.2%] in patients with and without albuminuria, respectively; HR, 6.4; 95% CI, 2.4-17.3; P < .001). Albuminuria was associated with the outcomes only in patients with a biventricular circulation (HR, 4.5; 95% CI, 2.5-8.0) and not those with single-ventricle circulation (HR, 1.0; 95% CI, 0.4-2.8; P = 0.01 compared with biventricular circulation group). Among 133 patients (21.7%) in NYHA functional class 2, albuminuria was strongly associated with death or nonelective hospitalization. Conclusions and Relevance Albuminuria is common and is associated with increased risk for adverse outcome in patients with ACHD with biventricular circulation. Albuminuria appears especially useful in stratifying risk in patients categorized as NYHA functional class 2.
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Affiliation(s)
- Saurabh Rajpal
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.,Department of Cardiology, Nationwide Children's Hospital, Columbus, Ohio.,Department of Medicine, Ohio State University, Columbus
| | - Laith Alshawabkeh
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.,Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego
| | - Nureddin Almaddah
- Department of Medicine, North Shore Medical Center, Salem, Massachusetts
| | - Caroline M Joyce
- Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts
| | - Keri Shafer
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts
| | - Michelle Gurvitz
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts
| | - Sushrut S Waikar
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | | | - Michael J Landzberg
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts
| | - Alexander R Opotowsky
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts
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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: 17] [Impact Index Per Article: 2.4] [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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Morgan C, Al-Aklabi M, Garcia Guerra G. Chronic kidney disease in congenital heart disease patients: a narrative review of evidence. Can J Kidney Health Dis 2015; 2:27. [PMID: 26266042 PMCID: PMC4531493 DOI: 10.1186/s40697-015-0063-8] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 07/09/2015] [Indexed: 11/10/2022] Open
Abstract
Purpose of review Patients with congenital heart disease have a number of risk factors for the development of chronic kidney disease (CKD). It is well known that CKD has a large negative impact on health outcomes. It is important therefore to consider that patients with congenital heart disease represent a population in whom long-term primary and secondary prevention strategies to reduce CKD occurrence and progression could be instituted and significantly change outcomes. There are currently no clear guidelines for clinicians in terms of renal assessment in the long-term follow up of patients with congenital heart disease. Consolidation of knowledge is critical for generating such guidelines, and hence is the purpose of this view. This review will summarize current knowledge related to CKD in patients with congenital heart disease, to highlight important work that has been done to date and set the stage for further investigation, development of prevention strategies, and re-evaluation of appropriate renal follow-up in patients with congenital heart disease. Sources of information The literature search was conducted using PubMed and Google Scholar. Findings Current epidemiological evidence suggests that CKD occurs in patients with congenital heart disease at a higher frequency than the general population and is detectable early in follow-up (i.e. during childhood). Best evidence suggests that approximately 30 to 50 % of adult patients with congenital heart disease have significantly impaired renal function. The risk of CKD is higher with cyanotic congenital heart disease but it is also present with non-cyanotic congenital heart disease. Although significant knowledge gaps exist, the sum of the data suggests that patients with congenital heart disease should be followed from an early age for the development of CKD. Implications There is an opportunity to mitigate CKD progression and negative renal outcomes by instituting interventions such as stringent blood pressure control and reduction of proteinuria. There is a need to invest time, thought and money to fill existing knowledge gaps to improve health outcomes in this population. This review should serve as an impetus for generation of follow-up guidelines of kidney health evaluation in patients with congenital heart disease.
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Affiliation(s)
- Catherine Morgan
- Division of Nephrology, Department of Pediatrics, 4-557 Edmonton Clinic Health Academy, 11405 - 87 Avenue, Edmonton, AB T6G 1C9 Canada
| | - Mohammed Al-Aklabi
- Division of Cardiac Surgery, Department of Medicine, 4A7.C Mazankowski Heart Institute, 8440 - 112 Street, Edmonton, AB T6G 2B7 Canada
| | - Gonzalo Garcia Guerra
- Division of Pediatric Critical Care, Department of Pediatrics, 4-548 Edmonton Clinic Health Academy, 11405 - 87 Avenue, Edmonton, AB T6G 1C9 Canada
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Amoozgar H, Basiratnia M, Ghasemi F. Renal function in children with cyanotic congenital heart disease: pre- and post-cardiac surgery evaluation. IRANIAN JOURNAL OF PEDIATRICS 2014; 24:81-6. [PMID: 25793050 PMCID: PMC4359609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2013] [Accepted: 01/11/2014] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Cyanotic congenital heart diseases (CCHDs) are a series of cardiac anomalies that have long been recognized as a potential cause of nephropathy. There have been few reports on renal impairment in patients with CCHD before and after corrective cardiac surgery. The aim of this study was to evaluate the prevalence of renal dysfunction before and after cardiac surgery and the impact of some risk factors on final renal outcome. METHODS Thirty children with CCHD who had done corrective cardiac surgery in the previous 6 months were enrolled in this study. All data prior to surgery were collected from the charts. Post-operation data including blood and spot urine samples were taken simultaneously for CBC, Cr, and uric acid and 24 hour urine was collected for microalbumin and Cr during the follow up visits. Pre- and post-operation parameters were compared to study the impact of cardiac surgery on renal function. Findings : Pre- and post-operative GFRs were not significantly different. Final GFR was significantly and inversely associated with pre- and post-operation age (P=0.008 r=-0.48, P=0.03 r=-0.38). Three (10%) patients had microalbuminuria. The prevalence of microalbuminuria in children older than 10 years was 30%. There was no link between microalbuminuria and age, GFR, and hematocrit (P=0.1, P=0.3, P=0.3, respectively). Patients with preoperation hematocrit >45 had a significantly lower final GFR compared to children with HCT <45 (83.7±6.5 vs 111.10.2, P=0.001). The mean uric acid fraction (FEua) excretion was 8.21±4.75. Pre-operative HCT was inversely associated to FEua (P=0.01, r=-0.44). There was no relationship between FEua and age, serum uric acid, and GFR (P=0.7, P=0.4, P=0.2). CONCLUSION Children with CCHD are at increased risk of renal injury which is related more to the duration of cyanosis and higher degree of hematocrit level. To lower the risk, corrective cardiac surgery is recommended to be done as soon as possible to improve renal function and stop more renal impairment.
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Affiliation(s)
| | - Mitra Basiratnia
- Shiraz Nephrology and Urology Research Center,Corresponding Author: Address: Pediatric Nephrology Ward, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz-Iran
| | - Fatemeh Ghasemi
- Department of Pediatrics, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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Gupte PA, Vaideeswar P, Kandalkar BM. Cyanotic nephropathy--a morphometric analysis. CONGENIT HEART DIS 2013; 9:280-5. [PMID: 23834022 DOI: 10.1111/chd.12121] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/12/2013] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Nephropathy is a known complication in cyanotic congenital heart disease (CCHD). This study was undertaken for an objective analysis of histopathological changes of cyanotic nephropathy at autopsy. DESIGN Retrospective case records studied. SETTING Tertiary care teaching hospital affiliated to medical college in Mumbai, India. PATIENTS AND METHODS The renal histopathological findings of 50 consecutive autopsies in patients with CCHD were compared with 25 age-matched controls. The Bowman's capsular, glomerular tuft, and hilar arteriolar diameters were measured morphometrically. Statistical analysis was performed using unpaired t-test. A P value equal to or less than .05 was considered significant. RESULTS Among the 50 autopsied cases of CCHD, there were 35 males and 15 females, with a mean age of 4.64 years. The renal changes observed were glomerulomegaly, glomerulosclerosis, periglomerular fibrosis, hyperplastic arteriolosclerosis, and interstitial fibrosis. The objectively measured parameters were higher in cases as compared with controls in all age groups, and further these were also found to be higher in patients having decreased pulmonary arterial blood flow than those having normal to increased pulmonary arterial blood flow. The difference in Bowman's capsular and glomerular tuft diameters was statistically significant in the neonates and children in the age groups, 1-5 years and above 10 years. The difference in hilar arteriolar diameter was statistically significant for all age groups except neonates. CONCLUSION Patients with CCHD show significant changes in the kidneys as assessed morphometrically, leading to renal dysfunction, and the age of the patients plays a role in their development.
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Affiliation(s)
- Prajakta A Gupte
- Department of Pathology (Cardiovascular & Thoracic Division), Seth GS Medical College, Mumbai, India
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Ohuchi H, Ikado H, Noritake K, Miyazaki A, Yasuda K, Yamada O. Impact of Central Venous Pressure on Cardiorenal Interactions in Adult Patients with Congenital Heart Disease after Biventricular Repair. CONGENIT HEART DIS 2012; 8:103-10. [DOI: 10.1111/j.1747-0803.2012.00717.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/19/2012] [Indexed: 11/26/2022]
Affiliation(s)
- Hideo Ohuchi
- Department of Pediatric Cardiology; National Cerebral and Cardiovascular Center; Osaka; Japan
| | - Hiromi Ikado
- Department of Laboratory of Clinical Physiology; National Cerebral and Cardiovascular Center; Osaka; Japan
| | - Kanae Noritake
- Department of Pediatric Cardiology; National Cerebral and Cardiovascular Center; Osaka; Japan
| | - Aya Miyazaki
- Department of Pediatric Cardiology; National Cerebral and Cardiovascular Center; Osaka; Japan
| | - Kenji Yasuda
- Department of Pediatric Cardiology; National Cerebral and Cardiovascular Center; Osaka; Japan
| | - Osamu Yamada
- Department of Pediatric Cardiology; National Cerebral and Cardiovascular Center; Osaka; Japan
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Dimopoulos K, Diller GP, Koltsida E, Pijuan-Domenech A, Papadopoulou SA, Babu-Narayan SV, Salukhe TV, Piepoli MF, Poole-Wilson PA, Best N, Francis DP, Gatzoulis MA. Prevalence, Predictors, and Prognostic Value of Renal Dysfunction in Adults With Congenital Heart Disease. Circulation 2008; 117:2320-8. [PMID: 18443238 DOI: 10.1161/circulationaha.107.734921] [Citation(s) in RCA: 274] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
- Konstantinos Dimopoulos
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Gerhard-Paul Diller
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Evdokia Koltsida
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Antonia Pijuan-Domenech
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Sofia A. Papadopoulou
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Sonya V. Babu-Narayan
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Tushar V. Salukhe
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Massimo F. Piepoli
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Philip A. Poole-Wilson
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Nicky Best
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Darrel P. Francis
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
| | - Michael A. Gatzoulis
- From the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension (K.D., G.-P.D., E.K., A.P.-D., S.A.P., S.V.B.-N., M.A.G.), Royal Brompton Hospital & National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Department of Clinical Cardiology, National Heart and Lung Institute (T.V.S., M.F.P., P.A.P.-W.) and Department of Epidemiology and Public Health (N.B.), Imperial College, London, United Kingdom; and International Centre of Circulatory Health
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Sakazaki H, Niwa K, Echigo S, Akagi T, Nakazawa M. Predictive factors for long-term prognosis in adults with cyanotic congenital heart disease — Japanese multi-center study. Int J Cardiol 2007; 120:72-8. [PMID: 17140681 DOI: 10.1016/j.ijcard.2006.08.081] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2006] [Revised: 08/02/2006] [Accepted: 08/10/2006] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Adults with cyanotic congenital heart disease (CCHD) are associated with a significant incidence of morbid events and premature deaths that may be predicted during childhood. We aimed to identify predictive factors related to long-term prognosis through a Japanese multi-center cross-sectional study. METHODS Data were collected from 253 adults with CCHD (126 men; age 28 (18 to 56) years) from 15 participating centers between 1998 and 2003. Laboratory data such as cardiothoracic ratio (CTR), percutaneous oxygen saturation (SpO2), hematocrit levels (Ht) and platelet counts (Pl-c) at the age of 15 years were collected for predictive factor analysis for death and cardiovascular and systematic events. Predictive factors were determined by multivariate Cox regression analysis. RESULTS After a mean follow-up of 21 (0-42) years, 23 patients died with a median age of 29 (18-54) years (heart failure in 8, sudden in 6 and systematic complications in 9). Survival since 18 years of age was 91% and 84% at 10 and 20 years, respectively. Significant predictive factor for death was Pl-c<130x10(9)/l and for renal failure (n=7) was Ht>65%. 162 patients were hospitalized and predictors for hospitalization due to heart failure (n=45) were common atrioventricular canal CTR>60% and Pl-c<100x10(9)/l and that due to arrhythmias (n=44) were systematic right ventricle and CTR>60%. CONCLUSIONS This multi-center study provides an objective basis of assessing the long-term prognosis in patients with CCHD. These data are useful in making decisions regarding medical management and in favorably altering the non-operative course of the disease.
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Affiliation(s)
- Hisanori Sakazaki
- Department of Pediatric Cardiology in the Heart Center, Amagasaki Hospital, 1-1-1 Higashidaimotsu, Amagasaki, Hyogo 660-0828, Japan.
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Hayabuchi Y, Matsuoka S, Takahashi Y, Akita H, Kitagawa T, Kato I, Kuroda Y. Hyperuricemia in an infant with Taussig-Bing anomaly and interruption of the aortic arch. Pediatr Cardiol 1994; 15:249-51. [PMID: 7997431 DOI: 10.1007/bf00795737] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Hyperuricemia is commonly recognized in adolescents and adults with cyanotic congenital heart disease. We report a case of a male infant with hyperuricemia, Taussig-Bing anomaly, and interruption of the aortic arch. The patient underwent correction of interrupted aortic arch and pulmonary arterial banding at the age of 7 days. Hyperuricemia appeared when he was 2 months old (max 17.7 mg/dl) and persisted until he underwent a Jatene operation at the age of 10 months. The hyperuricemia improved gradually after the disappearance of hypoxia and polycythemia. The laboratory findings suggest that hyperuricemia can result from uric acid overproduction due to secondary polycythemia, impairment of uric acid excretion by the kidney, or the acceleration of anaerobic metabolism. Allopurinol and benzbromarone together were partially effective treatments for hyperuricemia in this patient with cyanotic congenital heart disease.
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Affiliation(s)
- Y Hayabuchi
- Department of Pediatrics, University of Tokushima School of Medicine, Japan
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Pridjian AK, Bove EL, Beekman RH, Lupinetti FM. Comparison of a low osmolarity nonionic radiographic contrast agent with a standard medium on renal function in cyanotic and normal dogs. CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS 1994; 31:90-3. [PMID: 8118866 DOI: 10.1002/ccd.1810310118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Renal dysfunction may follow administration of iodinated radiographic contrast agents. This complication may be less common when low osmolarity nonionic agents are used. Although potential benefits from the use of low osmolarity nonionic contrast may be minimal in individuals with normal physiology, a greater benefit has been postulated in the presence of chronic cyanosis. To test this hypothesis, six adult mongrel dogs underwent anastomosis of the inferior vena cava to the left atrium. This produced chronic cyanosis with a mean pO2 of 48 +/- 4 mm Hg and polycythemia with a mean hematocrit of 56 +/- 2 gm%. Three to 5 months after preparation, these cyanotic dogs and five control dogs each received diatrizoate (a high osmolarity ionic agent) or ioversol (a low osmolarity nonionic agent), 465 mg iodine/kg body weight, by intravenous bolus injection. One month later, each animal received the other agent. The order of administration was randomized. Renal function studies, including serum creatinine and creatinine clearance, were performed precontrast, after 60 min, and 24 hr postcontrast. Neither agent adversely affected renal function in either the cyanotic or the normal group. We conclude that at the doses that are commonly used in clinical practice, high osmolarity ionic contrast agents do not create a greater risk of renal injury than do low osmolarity nonionic agents in this model of cyanosis.
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Affiliation(s)
- A K Pridjian
- Department of Pediatric Cardiology, University of Michigan Medical Center, Ann Arbor
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Abstract
This study examines the exacerbating factors of hyperuricaemia in patients with cyanotic congenital heart disease (CCHD). We studied 59 CCHD patients aged 1 month-30 years. The following variables were assessed: serum uric acid levels, red blood cell count, haemoglobin, hematocrit, partial oxygen pressure and arterial oxygen saturation. Uric acid excretion and renal function were also measured in ten patients with serum levels of uric acid greater than 8 mg/dl (hyperuricaemia group). Serum uric acid level correlated significantly with age and severity of polycythaemia. However, it did not correlate with partial oxygen pressure or arterial oxygen saturation. Uric acid excretion was measured in hyperuricaemia group. Urinary uric acid excretion (24 h) was within normal limits in infants but markedly lower in patients over 15 years of age. The aetiology of hyperuricaemia and decreased uric acid fractional excretion and clearance in infants appears to be secondary to diminished excretion of uric acid in concert with uric acid overproduction. Hyperuricaemia in adolescents and adults with CCHD, however, results mainly from age-related impairment of uric acid excretion.
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Affiliation(s)
- Y Hayabuchi
- Department of Paediatrics, University of Tukoshima School of Medicine, Japan
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Flanagan MF, Hourihan M, Keane JF. Incidence of renal dysfunction in adults with cyanotic congenital heart disease. Am J Cardiol 1991; 68:403-6. [PMID: 1858686 DOI: 10.1016/0002-9149(91)90842-9] [Citation(s) in RCA: 54] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- M F Flanagan
- Department of Cardiology, Children's Hospital, Boston, Massachusetts
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Ross EA, Perloff JK, Danovitch GM, Child JS, Canobbio MM. Renal function and urate metabolism in late survivors with cyanotic congenital heart disease. Circulation 1986; 73:396-400. [PMID: 3948350 DOI: 10.1161/01.cir.73.3.396] [Citation(s) in RCA: 55] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Diminished glomerular filtration rate, proteinuria, and large hypercellular congested glomeruli with segmental sclerosis are found in late survivors with cyanotic congenital heart disease (CCHD). Hyperuricemia is common, acute gouty arthritis is less common than uric acid levels would predict, and overt tophaceous deposits of uric acid are exceptional. The role of the kidney in causing the basic biochemical disturbances, and the relative importance of impaired urate excretion vs urate overproduction have not been established. Accordingly, we reviewed the courses of two index patients and prospectively studied eight additional CCHD patients from 28 years to 46 years old with mean hematocrits of (62 +/- 10%). Plasma creatinine concentration was normal (0.9 +/- 0.1 mg/dl) yet glomerular filtration rate was mildly reduced to 93 +/- 14 ml/min as measured by creatinine clearance and to 81 +/- 6 ml/min as measured by 111In DTPA. Three patients had significant proteinuria and one was nephrotic. Plasma uric acid concentration was high in all but one (8.2 +/- 2.1 mg/dl), mean 24 hr uric acid excretion was normal (564 +/- 221 mg), and fractional uric acid excretion was relatively low (6.3 +/- 2.6%). The two patients with highest plasma uric acid levels (12.0 and 10.2 mg/dl) had the lowest fractional excretions (2.8% and 4.0%). Both of these patients had diminished capacity to excrete a water load (38% and 27%/4 hr) and to maximally concentrate urine (520 and 635 mOsm/kg after water deprivation and vasopressin). In conclusion, high plasma uric acid levels in late survivors with CCHD are secondary to inappropriately low fractional uric acid excretion, not to urate overproduction.(ABSTRACT TRUNCATED AT 250 WORDS)
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