Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease

Abstract 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.

Download Full-text

Enalapril Therapy Prevents Cardiac Remodelling of Sickle Cell Disease Patients.

Blood ◽

10.1182/blood.v108.11.3792.3792 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3792-3792

Author(s):

Sara T. Saad ◽

Carmen S. Passos Lima ◽

Osvaldo M. Ueti ◽

Adriana A. Ueti ◽

Kleber G. Franchini ◽

...

Keyword(s):

Blood Pressure ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Ace Inhibitors ◽

Aortic Root ◽

Fetal Hemoglobin ◽

Treated Group ◽

Left Ventricular ◽

Cell Disease

Abstract Angiotensin-converting enzyme (ACE) inhibitors are capable of decreasing cardiac remodelling in patients with cardiac dysfunction, however their effects on sickle cell disease (SCD) are unknown. Thus, this study aimed to investigate the cardiac effects of enalapril on SCD patients. Thirteen adult patients with sickle cell disease (SCD) and microalbuminuria (3M/10F); 11 sickle cell anemia patients (SCA), 1 Sβ thalassemia patient (Sβ) and 1 patient with hemoglobin SC (SC) were treated with enalapril. Thirteen other SCD patients (4M/9F) without microalbuminuria, matched according to age, diagnosis (11 SCA, 1 Sβ and 1 SC), and levels of hemoglobin, hematocrit and fetal hemoglobin, did not receive enalapril and were followed up as the control group in the same period of study. In the treated group, enalapril (5mg) was administered to 9 SCD patients during the entire study period. One patient did not complete follow-up, and higher doses (7.5mg to 20mg) were administered to 3 patients who developed systolic BP over 120 mmHg during the study period. Median age (28.5 vs 29.0; P= 0.580), baseline values of hemoglobin (8.5 vs 8.4g/dL, P= 0.600), hematocrit (25.0 vs 23.5%, P= 0.500), fetal hemoglobin (4.4 vs 4.1%, P=0.720) and mean blood pressure (MBP; 80 vs 93mmHg, P= 0.13) were similar in treated and untreated patients Echocardiograms were performed before the study entry and once a year in patients and controls. Comparisons of groups were performed at the beginning of the study and after 36 months of follow-up using the Wilcoxon-signed rank test and Spearman coefficient. At 36 months of follow-up, MBP was lower than the baseline value (93 mmHg vs 87 mmHg, P= 0.018) in the treated group. Significant increases in left ventricular mass (192 vs 231g, P= 0.005), posterior left ventricular wall thickness in end-diastole (8.5 vs 10.0mm, P= 0.013), left ventricular mass index (114.4 vs 131g/m2, P= 0.043), interventricular septal wall thickness in end-diastole (9.0 vs 9.5mm, P= 0.036) and aortic root dimension (28 vs 32mm, P= 0.009) values were seen in untreated, but not in enalapril treated patients. No major changes were seen in left ventricular ejection fraction, left ventricular systolic diameter, left ventricular diastolic dimension and left atrial diameter, in both groups, along the observational period. No significant correlation was detected between the data here presented. At the end of the study, no symptoms or signals related to cardiac failure were found in any of the enrolled patients. These results indicate a trend toward cardiac and aortic root remodeling in untreated SCD patients and suggest that long-term treatment with ACE inhibitors has beneficial effects on the cardiac remodeling of SCD patients and could be indicated for adult patients, if an increase in baseline blood pressure occurs.

Download Full-text

Prevalence Of Nocurnal Enuresis and Proteinuria In Children With Sickle Cell Disease and Its Relation To Severity Of Painful Crises

Blood ◽

10.1182/blood.v122.21.4693.4693 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4693-4693 ◽

Cited By ~ 1

Author(s):

Chakravorty Subarna ◽

Josu de la Fuente ◽

Ali Mohammed

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Nocturnal Enuresis ◽

Converting Enzyme ◽

Cell Disease ◽

Emergency Admissions ◽

Statistical Manual ◽

Diagnostic And Statistical Manual ◽

Dsm Iv ◽

Age Category

Nocturnal enuresis and albuminuria or proteinuria are markers of renal damage in sickle cell disease (SCD) and commonly develop early on in life. Proteinuria progresses with age, leading to chronic kidney disease in adulthood. The aims of this study were to identify the prevalence of enuresis and albuminuria/proteinuria in paediatric patients with SCD in London and to determine the relationship between these and various demographic and clinical variables. Methods A cross sectional, single centre study was conducted. Questionnaire-based interviews themed on nocturnal enuresis were undertaken for patients between the ages of 6 and 17. Urinalysis was performed for the presence of albuminuria or proteinuria. Hospital patient records were accessed for clinical data. Results A total of 56 patients were recruited to the study, of which 27 (51.8%) were female. Twenty patients (35.7%) had a history of enuresis and met the DSM IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria for nocturnal enuresis compared to 5% prevalence in children in the general population1. There was a statistically significant association between enuresis and age, overactive bladder (OAB) symptoms, sleep-disordered breathing (SDB), painful crises and regular transfusions (Table 1). Fourteen out of 29 patients (48.3%) with OAB symptoms reported nocturnal enuresis compared to six out of 27 patients (22.2%) who did not (p<0.05). Of the patients reporting SDB, 48.6% were enuretic compared to 14.3% who did not (p<0.01). Incidence of painful crises per month was higher for the enuretic group (2.29 vs. 0.88, p<0.05) but the mean number of emergency admissions in the preceding 18 months was similar. Of the 14 regular blood transfusion patients, only one (7.1%) was currently enuretic compared to 14 out of 32 (40.6%) who were not receiving any treatment (p<0.05). Seven patients (13.4%) had albuminuria/proteinuria. (Table 2) There was no difference in albuminuria/proteinuria prevalence between the hydroxycarbamide or blood transfusion group compared to the non-treatment group. There was no difference in HbF percentage, systolic BP, frequency of emergency admissions, painful crises per month, haemoglobin levels and estimated glomerular filtration rates (eGFR) in patients with albuminuria/proteinuria and those without. The prevalence of haematuria increased with age; 6.7% in the 6-9 age category compared to 36.4% in the 16 to 17 age category (p=<0.05). Conclusions Nocturnal enuresis and albuminuria or proteinuria is prevalent at an early age in many children with SCD. Early identification and initiation of treatment such as Angiotensin Converting Enzyme inhibitors2 may delay onset of complications especially alongside beneficial sickle cell treatments such as hydroxycarbamide and regular blood transfusions. Questioning parents on enuresis, OAB and SDB sumptoms and undertaking regular urinalysis on younger age groups is a practical and cost-effective surveillance method. References 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Publishing, Inc.; 2000. Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease Cochrane Database of Systematic Reviews, 2013. Disclosures: No relevant conflicts of interest to declare.

Download Full-text