Low urinary levels of angiotensin‐converting enzyme 2 may contribute to albuminuria in children with sickle cell anaemia

Belisário, André Rolim; Vieira, Eliane; Almeida, Jéssica Alves de; Mendes, Fabíola Gomes; Miranda, Aline Silva de; Rezende, Paulo V.; Viana, Marcos Borato; Silva, Ana Cristina Simões e

doi:10.1111/bjh.15439

Cited by 10 publications

(6 citation statements)

References 10 publications

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“…These findings raise the possibility that an upward shift in the intrarenal ACE/ACE2 ratio favoring increased synthesis of Ang II and reduction in Ang-(1-7) might lead to progressive nephron loss in this condition [30]. Our research group recently detected lower urinary levels of ACE2 in children with sickle cell anemia (SCA) presenting persistent proteinuria in comparison to SCA patients with normal albumin excretion in urine, also suggesting a role of reduced ACE2 protein in renal tissue in the emergence of proteinuria and nephropathy [31].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the inclusion of only relatively well controlled INS patients, exhibiting partial or total remission of the proteinuria, may increase the homogeneity of our sample and the results may represent more accurately changes related to disease itself rather than acute alterations due to relapses. Moreover, the utilization of a well-established protocol for molecular measurements may increase the strength of our findings [31,39,40].…”

Section: Discussionmentioning

confidence: 99%

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Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

Filha

Pinheiro²,

Cordeiro

et al. 2019

Bioscience Reports

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Introduction: Renin angiotensin system (RAS) plays a role in idiopathic nephrotic syndrome (INS). Most studies investigated only the classical RAS axis. Therefore, the aims of the present study were to evaluate urinary levels of RAS molecules related to classical and to counter-regulatory axes in pediatric patients with INS, to compare the measurements with levels in healthy controls and to search for associations with inflammatory molecules, proteinuria and disease treatment. Subjects and methods: This cross-sectional study included 31 patients with INS and 19 healthy controls, matched for age and sex. Patients and controls were submitted to urine collection for measurement of RAS molecules [Ang II, Ang-(1-7), ACE and ACE2] by enzyme immunoassay and cytokines by Cytometric Bead Array. Findings in INS patients were compared according to proteinuria: absent (<150 mg/dl, n = 15) and present (≥150 mg/dl, n = 16). Results: In comparison to controls, INS patients had increased Ang II, Ang-(1-7) and ACE, levels while ACE2 was reduced. INS patients with proteinuria had lower levels of ACE2 than those without proteinuria. ACE2 levels were negatively correlated with 24-h-proteinuria. Urinary concentrations of MCP-1/CCL2 were significantly higher in INS patients, positively correlated with Ang II and negatively with Ang-(1-7). ACE2 concentrations were negatively correlated with IP-10/CXCL-10 levels, which, in turn, were positively correlated with 24-h-proteinuria. Conclusion: INS patients exhibited changes in RAS molecules and in chemokines. Proteinuria was associated with low levels of ACE2 and high levels of inflammatory molecules.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

Filha

Pinheiro²,

Cordeiro

et al. 2019

Bioscience Reports

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“…These results differ from those described by Hallab et al (1992) and Burns et al (2017), in which urinary ACE 1 activity was elevated in type 1 diabetic subjects, especially in patients with microalbuminuria, suggesting an early indication of lesions in vascular endothelial cells 27,28 . In addition, Belisario et al (2019) described that SCD children with persistent albuminuria (PA) also presented increased urinary levels of ACE 1 9 . Casarini et al ( 2001) described a correlation between urinary ACE 1 and BP suggesting that the somatic and N-domain urinary ACE 1 are produced locally and released by the tubular cells in normal conditions and in response to ischemic kidney damage 29 .…”

Section: Discussionmentioning

confidence: 99%

“…The imbalance of classical ACE 1/Angiotensin II (Ang II) /AT1 receptor axis and counter-regulatory ACE 2/Ang 1-7/MAS receptor axis was studied by Belisario et al (2018) highlighting that ACE 2 and Ang 1-7 were reduced in pediatric SCD with increase of ACE 1 and Ang II, inducing kidney damage 9 .…”

Section: Introductionmentioning

confidence: 99%

Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease

et al. 2021

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Introduction: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD). Objective: We examined circulating and urinary ACE 1 activity in children with SCD. Methods: This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate. Results: Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05. Conclusion: Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.

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“…Although some studies on ACEI administration showed significant reduction of albuminuria in patients with SCA, none had evaluated RAAS components in these patients. In this regard, Belisário et al [123] performed a cross-sectional study with 72 children and showed lower levels of ACE2 and Ang-(1-7) in SCA children with persistent albuminuria. These results were the first to provide evidence for a role of RAAS molecules in human SCN, suggesting that SCA patients had RAAS imbalance towards the classical axis [123].…”

Section: Systemic Diseases Affecting the Kidneymentioning

confidence: 99%

2020 update on the renin–angiotensin–aldosterone system in pediatric kidney disease and its interactions with coronavirus

et al. 2020

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The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counterregulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor. Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A. In this review, we characterize the two RAAS axes and the role of their components in pediatric kidney diseases, including childhood hypertension (HTN), pediatric glomerular diseases, congenital abnormalities of the kidney and urinary tract (CAKUT), and chronic kidney disease (CKD). We also present recent findings on potential interactions between the novel coronavirus, SARS-CoV-2, and components of the RAAS, as well as potential implications of coronavirus disease 2019 (COVID-19) for pediatric kidney diseases.

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Low urinary levels of angiotensin‐converting enzyme 2 may contribute to albuminuria in children with sickle cell anaemia

Cited by 10 publications

References 10 publications

Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease

2020 update on the renin–angiotensin–aldosterone system in pediatric kidney disease and its interactions with coronavirus

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