Association of Albuminuria With Major Adverse Outcomes in Adults With Congenital Heart Disease

Rajpal, Saurabh; Alshawabkeh, Laith; Almaddah, Nureddin; Joyce, Caroline M.; Shafer, Keri M.; Gurvitz, Michelle; Waikar, Sushrut S.; Causland, Finnian R. Mc; Landzberg, Michael J.; Opotowsky, Alexander R.

doi:10.1001/jamacardio.2018.0125

Cited by 24 publications

(25 citation statements)

References 42 publications

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“…Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events across a range of populations. [1][2][3] It has been suggested that proteinuria not only reflects glomerular damage, but also is a sensitive indicator of generalized endothelial dysfunction and capillary vasculopathy that allows penetration of atherosclerotic lipoproteins into vessel walls. 4 There appears to be a particularly strong association between proteinuria and stroke.…”

Section: Introductionmentioning

confidence: 99%

Proteinuria as an independent predictor of stroke: Systematic review and meta-analysis

Kelly

Rothwell

2020

International Journal of Stroke

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Background Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events including stroke. Hypertension has been proposed as the principal confounder of this relationship but its role has not been systematically examined. Aim We aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure. Summary of review We performed a systematic review, searching MEDLINE and EMBASE (to February 2018) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline proteinuria ± glomerular filtration rate. Study and participant characteristics and relative risks were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by χ 2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure on the association. The quality of cohort studies and post hoc analyses was assessed using the Newcastle–Ottawa Scale. We identified 38 studies comprising 1,735,390 participants with 26,405 stroke events. Overall, the presence of any level of proteinuria was associated with greater stroke risk (18 studies; pooled crude relative risk 2.00, 95%CI 1.63–2.46; p < 0.001) even after adjustment for established cardiovascular risk factors (33 studies; pooled adjusted relative risk 1.72, 1.51–1.95; p < 0.001), albeit with considerable heterogeneity between studies (p < 0.001; I2 = 77.3%). Moreover, the association did not substantially attenuate with more thorough adjustment for hypertension: single baseline blood pressure measure (10 studies; pooled adjusted relative risk = 1.92, 1.39–2.66; p < 0.001); history or treated hypertension (four studies; pooled adjusted relative risk = 1.76, 1.13–2.75, p = 0.013); multiple blood pressure measurements over months to years (four studies; relative risk = 1.68, 1.33–2.14; p < 0.001). Conclusions Even after extensive adjustment for hypertension, proteinuria is strongly and independently associated with incident stroke risk, possibly indicating a shared renal and cerebral susceptibility to vascular injury that is not fully explained by traditional vascular risk factors.

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Section: Introductionmentioning

confidence: 99%

Proteinuria as an independent predictor of stroke: Systematic review and meta-analysis

Kelly

Rothwell

2020

International Journal of Stroke

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“…A study including 1102 adult patients with CHD (mean age 36.0 ± 14.2 years, 9% had eGFR <60 mL/min/1.73 m 2 ) yielded an 8.3 mL/min/1.73 m 2 (7.3–9.4 mL/min/1.73 m 2 ) decrease in eGFR per 10-year increase in age [ 2 ]. Kidney dysfunction in adults with CHD has drawn the attention of physicians because it is associated with increased long-term mortality [ 2 , 3 , 10 ]. However, in our study, CR-CKD was detected in 2-year-old patients with CHD.…”

Section: Discussionmentioning

confidence: 99%

“…Diuretic usage is associated with a decreased eGFR and increased incidence of albuminuria in patients with CHD [ 2 , 3 , 17 ]. Although it is used for controlling congestive heart failure in patients with CHD, loop diuretic usage in patients with non-CR-CKD was higher than in those with CR-CKD in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The survival rate of patients with CHD has improved with advances in surgical and medical care in the last few decades [ 1 ], and because more patients with CHD survive childhood into adulthood, many experience multiple noncardiac complications, with kidney dysfunction being the most prevalent. Nearly 50% of adults with CHD have an abnormal glomerular filtration rate [ 2 ], and 17% have significant albuminuria [ 3 ]. Both kidney dysfunction and albuminuria are closely linked to increased mortality [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nearly 50% of adults with CHD have an abnormal glomerular filtration rate [ 2 ], and 17% have significant albuminuria [ 3 ]. Both kidney dysfunction and albuminuria are closely linked to increased mortality [ 2 , 3 ]. Numerous factors are related to the development of chronic kidney disease (CKD); some are nonmodifiable, such as ischemic insult caused by cardiopulmonary bypass during major surgery, hyperviscosity caused by uncorrected cyanotic heart disease, subsequent glomerular and tubular injuries, and various congenital anomalies of the kidney and urinary tract (CAKUT) related to syndromic CHD.…”

Section: Introductionmentioning

confidence: 99%

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Incidence and risk factors for chronic kidney disease in patients with congenital heart disease

Fang

Chen

et al. 2021

Pediatr Nephrol

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Backgrounds Chronic kidney disease (CKD) is underdiagnosed in children with congenital heart disease (CHD). Our aim was to study the incidence of CKD in CHD children and identify risk factors for CKD. Methods CHD patients were enrolled from the Kaohsiung Veterans General Hospital database between 2010 and 2019. Patient age at enrollment was age at first visit to the hospital. The end of follow-up was marked by the last measurement of serum creatinine, urine protein-to-creatinine ratio (UPCR), or urine microalbumin-to-creatinine ratio (UACR) after enrollment, and only patients who underwent the aforementioned tests in 2 different years were included. Patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were diagnosed as having CKD and were further classified into clinically recognized CKD (CR-CKD, defined as eGFR <60 mL/min/1.73m2, UPCR >0.5, or UACR >30 mg/g) and non-clinically recognized CKD (NCR-CKD). Their demographic data, CHD category, heart surgery types, medications, and contrast-related examinations during follow-up were collected. Results The study included 359 CHD patients, of whom 167 (46.5%) developed CKD (18 patients with CR-CKD and 341 with NCR-CKD). Patients with CR-CKD were significantly older at enrollment than patients with NCR-CKD. Corrective heart surgery may be a protective factor for CKD. Furthermore, cyanotic heart disease, two or more image-related contrast exposures, and diuretic use may be associated with CKD. Conclusion CHD patients have a high incidence of CKD. The early detection of CKD and prompt corrective heart surgery for CHD may be beneficial for kidney function. Graphical abstract

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Association of Albuminuria With Outcomes in Adults With Congenital Heart Disease

Freitas

2018

JAMA Cardiol

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Association of Albuminuria With Major Adverse Outcomes in Adults With Congenital Heart Disease

Abstract: 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.

Cited by 24 publications

References 42 publications

Proteinuria as an independent predictor of stroke: Systematic review and meta-analysis

Proteinuria as an independent predictor of stroke: Systematic review and meta-analysis

Incidence and risk factors for chronic kidney disease in patients with congenital heart disease

Association of Albuminuria With Outcomes in Adults With Congenital Heart Disease

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