Renin‐angiotensin system blockade promotes a cardio‐renal protection in albuminuric homozygous sickle cell patients

Abstract

The management of sickle cell nephropathy (SCN) at an early stage is an important issue to prevent renal and cardiovascular morbidity and mortality. This study aimed to evaluate in this population, whether angiotensin converting enzyme inhibitors (ACEIs) treatment could exert a cardio-renal protection in a SCN cohort. Forty-two SCN patients (urine albumin:creatinine ratio (ACR) > 10 mg/mmol) were treated with ACEIs for 6 months, then evaluated for ACR, measured glomerular filtration rate (mGFR) together with haematological and cardiovascular parameters. A 1-month washout was also performed in order to differentiate short- and long-term ACEIs effects. A decrease in ACR baseline value (>30%) was detected in 62% of cases (mean ACR: 46·4 ± 7·6 and 26·4 ± 3·9 mg/mmol at baseline and 6 months respectively; P = 0·002), whereas mGFR values were unchanged. ACR decrease was detected at 1 month following ACEI initiation (32·9 ± 6·9, P = 0·02) with a persistent trend after withdrawal (P = 0·08). ACEIs also decreased diastolic blood pressure (P = 0·007), pulse wave velocity (P = 0·01), tricuspid regurgitation velocity (TRV; P = 0·04), asymmetric dimethyl arginine (ADMA: P = 0·001) and haemoglobin (P = 0·01) while conventional haemolytic biomarkers were unchanged. Our data suggest that ACEIs are safe and effective at decreasing albuminuria in sickle cell patients with a beneficial effect on specific mortality risk factors, such as TRV and asymmetric dimethyl arginine.

American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease

“…Urine albumin was reported in 1 RCT (n 5 22) 85 and 7 observational studies (total n 5 114). [86][87][88][89][90][91][92] In the 6 studies that examined ACEi therapy, 53 of 84 patients (63%) who received ACEi therapy showed improvement in urine albumin. [86][87][88][90][91][92] Of those who improved while receiving ACEi therapy, 18 (34%) had severe albuminuria (macroalbuminuria), 6 (11%) had moderate albuminuria (microalbuminuria), and the rest did not have their degree of albuminuria specified.…”

“…A total of 6 observational studies reported the treatment effect on blood pressure. [85][86][87]89,91,92 In 4 studies, 8 of 72 patients (11%)…”

“…No hypotension was reported with either ACEi or ARB therapy. In 1 RCT and 4 observational studies that reported potassium levels with either ACEi or ARB treatment (total n 5 92), 85,86,89,91,92 potassium was elevated in 12 of 92 patients (13%). In 3 observational studies that examined changes in renal function after treatment (total n 5 140), 89,92,93 2 studies did not identify a significant change in renal function, but 1 study demonstrated a slower decline in estimated GFR, although the effect was lost after adjusting for hydroxyurea use.…”

Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study

“…45 Although we did not screen for these genetic modifiers in our study, incorporating these modifiers may further enhance the screening accuracy for early detection of renal disease. Although new therapies have recently shown promising results in small studies in halting the progression of albuminuria and sickle nephropathy, 16,24,46,47 powered, controlled, randomized trials are still needed to evaluate the safety and efficacy of these therapies. Our study provides new insight into the natural progression of albuminuria in SCA that is needed for the successful design of such studies.…”

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

“…However, the exact mechanism remains unclear. Our data also suggest that, despite the successful use of ACEi in patients with SCA (Haymann et al, 2017), angiotensin receptor blockers might provide better renal protection. Theoretically, in addition to blocked Ang II formation, patients would benefit from enhanced formation of Ang-(1-7), converted from Ang II by ACE2.…”