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JAMA Mar 2023Guidelines recommend that all children and adolescents with hypertension undergo evaluation for secondary causes. Identifying clinical factors associated with secondary... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Guidelines recommend that all children and adolescents with hypertension undergo evaluation for secondary causes. Identifying clinical factors associated with secondary hypertension may decrease unnecessary testing for those with primary hypertension.
OBJECTIVE
To determine the utility of the clinical history, physical examination, and 24-hour ambulatory blood pressure monitoring for differentiating primary hypertension from secondary hypertension in children and adolescents (aged ≤21 years).
DATA SOURCES AND STUDY SELECTION
The databases of MEDLINE, PubMed Central, Embase, Web of Science, and Cochrane Library were searched from inception to January 2022 without language limits. Two authors identified studies describing clinical characteristics in children and adolescents with primary and secondary hypertension.
DATA EXTRACTION AND SYNTHESIS
For each clinical finding in each study, a 2 × 2 table was created that included the number of patients with and without the finding who had primary vs secondary hypertension. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool.
MAIN OUTCOMES AND MEASURES
Random-effects modeling was used to calculate sensitivity, specificity, and likelihood ratios (LRs).
RESULTS
Of 3254 unique titles and abstracts screened, 30 studies met inclusion criteria for the meta-analysis and 23 (N = 4210 children and adolescents) were used for pooling in the meta-analysis. In the 3 studies conducted at primary care clinics or school-based screening clinics, the prevalence of secondary hypertension was 9.0% (95% CI, 4.5%-15.0%). In the 20 studies conducted at subspecialty clinics, the prevalence of secondary hypertension was 44% (95% CI, 36%-53%). The demographic findings most strongly associated with secondary hypertension were family history of secondary hypertension (sensitivity, 0.46; specificity, 0.90; LR, 4.7 [95% CI, 2.9-7.6]), weight in the 10th percentile or lower for age and sex (sensitivity, 0.27; specificity, 0.94; LR, 4.5 [95% CI, 1.2-18]), history of prematurity (sensitivity range, 0.17-0.33; specificity range, 0.86-0.94; LR range, 2.3-2.8), and age of 6 years or younger (sensitivity range, 0.25-0.36; specificity range, 0.86-0.88; LR range, 2.2-2.6). Laboratory studies most associated with secondary hypertension were microalbuminuria (sensitivity, 0.13; specificity, 0.99; LR, 13 [95% CI, 3.1-53]) and serum uric acid concentration of 5.5 mg/dL or lower (sensitivity range, 0.70-0.73; specificity range, 0.65-0.89; LR range, 2.1-6.3). Increased daytime diastolic blood pressure load combined with increased nocturnal systolic blood pressure load on 24-hour ambulatory blood pressure monitoring was associated with secondary hypertension (sensitivity, 0.40; specificity, 0.82; LR, 4.8 [95% CI, 1.2-20]). Findings associated with a decreased likelihood of secondary hypertension were asymptomatic presentation (LR range, 0.19-0.36), obesity (LR, 0.34 [95% CI, 0.13-0.90]), and family history of any hypertension (LR, 0.42 [95% CI, 0.30-0.57]). Hypertension stage, headache, and left ventricular hypertrophy did not distinguish secondary from primary hypertension.
CONCLUSIONS AND RELEVANCE
Family history of secondary hypertension, younger age, lower body weight, and increased blood pressure load using 24-hour ambulatory blood pressure monitoring were associated with a higher likelihood of secondary hypertension. No individual sign or symptom definitively differentiates secondary hypertension from primary hypertension.
Topics: Adolescent; Child; Humans; Blood Pressure Monitoring, Ambulatory; Essential Hypertension; Hypertension; Sensitivity and Specificity; Uric Acid; Vital Signs
PubMed: 36976276
DOI: 10.1001/jama.2023.3184 -
Expert Review of Endocrinology &... Jan 2023The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D.
METHODS
We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbAlevels. Subgroup analysis was also performed to account for the inclusion of glucose only versus multi-factorial intervention trials. Results are reported as risk ratio (RR) and 95% confidence interval (CI).
RESULTS
Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5--0.87), microalbuminuria (0.67, 0.52-0.85), major amputation (0.6, 0.38-0.96), retinopathy (0.75 ,0.63-0.9), and nephropathy (0.78, 0.63-0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34-3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57-0.95).
CONCLUSION
Targeting HbA levels should be individualized based on the clinical status, balancing risks and benefits and potential risk for developing these complications among people with T2D.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucose; Blood Glucose; Hypoglycemia
PubMed: 36718676
DOI: 10.1080/17446651.2023.2166489 -
Frontiers in Pharmacology 2022Keluoxin capsule (KLXC) has been widely used in diabetic kidney disease (DKD), but its efficacy and safety have not yet been clarified. A systematic review and...
Keluoxin capsule (KLXC) has been widely used in diabetic kidney disease (DKD), but its efficacy and safety have not yet been clarified. A systematic review and meta-analysis were performed to assess the efficacy and safety of KLXC for DKD. The randomized control trials (RCTs) included KLXC searched from seven major English and Chinese databases up until 3 June 2022. The methodological quality and risk of bias were assessed by version 2 of the Cochrane risk-of-bias tool (RoB 2) for the RCTs from the Cochrane Handbook. The analyses were conducted by RevMan 5.4 and Stata 17.0. A total of 20 trials with 1,500 participants were identified. The meta-analysis showed that KLXC combined with Western medicine was superior to the use of Western medicine alone for DKD which included improvements in the estimated glomerular filtration rate (eGFR) [MD = 3.04, 95% CI (0.30, 5.78), = 0.03], reduction in microalbuminuria (mALB) [MD = -25.83, 95% CI (-41.20, -10.47), = 0.001], urinary albumin excretion rate (UAER) [SMD = -0.97, 95% CI (-1.50, -0.44), = 0.0003], 24-h urine protein (24hUpro) [SMD = -1.31, 95% CI (-1.82, -0.80), < 0.00001], serum creatinine (Scr) [MD = -11.39, 95% CI (-18.76, -4.02), = 0.002], blood urea nitrogen (BUN) [MD = -1.28, 95% CI (-1.67, -0.88), < 0.00001], fasting blood glucose (FBG) [MD = -0.51, 95% CI (-0.90, -0.11), = 0.01], total cholesterol (TC) [MD = -1.04, 95% CI (-1.40, -0.68), < 0.00001], triglycerides (TG) [MD = -0.36, 95% CI (-0.50, -0.23), < 0.00001], and low-density lipoprotein cholesterol (LDL) [MD = -0.39, 95% CI (-0.71, -0.07), = 0.02]. Results showed no statistically significant difference in glycated hemoglobin (HbA1c) ( = 0.14) or adverse events ( = 0.81) between the two groups. The combination of KLXC and Western medicine had a positive effect on DKD. However, due to the high clinical heterogeneity and low quality of included studies, further standardized, large-scale, rigorously designed RCTs for DKD in the definitive stage are still necessary to achieve more accurate results. https://inplasy.com/inplasy-2021-11-0067/, identifier INPLASY 2021110067.
PubMed: 36686708
DOI: 10.3389/fphar.2022.1052852 -
The Cochrane Database of Systematic... Jan 2023There is strong evidence that our current consumption of salt is a major factor in the development of increased blood pressure (BP) and that a reduction in our salt... (Review)
Review
BACKGROUND
There is strong evidence that our current consumption of salt is a major factor in the development of increased blood pressure (BP) and that a reduction in our salt intake lowers BP, whether BP levels are normal or raised initially. Effective control of BP in people with diabetes lowers the risk of strokes, heart attacks and heart failure and slows the progression of chronic kidney disease (CKD) in people with diabetes. This is an update of a review first published in 2010.
OBJECTIVES
To evaluate the effect of altered salt intake on BP and markers of cardiovascular disease and of CKD in people with diabetes.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 31 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of altered salt intake in individuals with type 1 and type 2 diabetes. Studies were included when there was a difference between low and high sodium intakes of at least 34 mmol/day.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies and resolved differences by discussion. We calculated mean effect sizes as mean difference (MD) and 95% confidence intervals (CI) using the random-effects model. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Thirteen RCTs (313 participants), including 21 comparisons (studies), met our inclusion criteria. One RCT (two studies) was added to this review update. Participants included 99 individuals with type 1 diabetes and 214 individuals with type 2 diabetes. Two RCTs (four studies) included some participants with reduced overall kidney function. The remaining studies either reported that participants with reduced glomerular filtration rate (GFR) were excluded from the study or only included participants with microalbuminuria and normal GFR. Five studies used a parallel study design, and 16 used a cross-over design. Studies were at high risk of bias for most criteria. Random sequence generation and allocation concealment were adequate in only three and two studies, respectively. One study was at low risk of bias for blinding of participants and outcome assessment, but no studies were at low risk for selective reporting. Twelve studies reported non-commercial funding sources, three reported conflicts of interest, and eight reported adequate washout between interventions in cross-over studies. The median net reduction in 24-hour urine sodium excretion (24-hour UNa) in seven long-term studies (treatment duration four to 12 weeks) was 76 mmol (range 51 to 124 mmol), and in 10 short-term studies (treatment duration five to seven days) was 187 mmol (range 86 to 337 mmol). Data were only available graphically in four studies. In long-term studies, reduced sodium intake may lower systolic BP (SBP) by 6.15 mm Hg (7 studies: 95% CI -9.27 to -3.03; I² = 12%), diastolic BP (DBP) by 3.41 mm Hg (7 studies: 95% CI -5.56 to -1.27; I² = 41%) and mean arterial pressure (MAP) by 4.60 mm Hg (4 studies: 95% CI -7.26 to -1.94; I² = 28%). In short-term studies, low sodium intake may reduce SBP by 8.43 mm Hg (5 studies: 95% CI -14.37 to -2.48; I² = 88%), DBP by 2.95 mm Hg (5 studies: 95% CI -4.96 to -0.94; I² = 70%) and MAP by 2.37 mm Hg (9 studies: 95% CI -4.75 to -0.01; I² = 65%). There was considerable heterogeneity in most analyses but particularly among short-term studies. All analyses were considered to be of low certainty evidence. SBP, DBP and MAP reductions may not differ between hypertensive and normotensive participants or between individuals with type 1 or type 2 diabetes. In hypertensive participants, SBP, DBP and MAP may be reduced by 6.45, 3.15 and 4.88 mm Hg, respectively, while in normotensive participants, they may be reduced by 8.43, 2.95 and 2.15 mm Hg, respectively (all low certainty evidence). SBP, DBP and MAP may be reduced by 7.35, 3.04 and 4.30 mm Hg, respectively, in participants with type 2 diabetes and by 7.35, 3.20, and 0.08 mm Hg, respectively, in participants with type 1 diabetes (all low certainty evidence). Eight studies provided measures of urinary protein excretion before and after salt restriction; four reported a reduction in urinary albumin excretion with salt restriction. Pooled analyses showed no changes in GFR (12 studies: MD -1.87 mL/min/1.73 m², 95% CI -5.05 to 1.31; I² = 32%) or HbA1c (6 studies: MD -0.62, 95% CI -1.49 to 0.26; I² = 95%) with salt restriction (low certainty evidence). Body weight was reduced in studies lasting one to two weeks but not in studies lasting for longer periods (low certainty evidence). Adverse effects were reported in only one study; 11% and 21% developed postural hypotension on the low-salt diet and the low-salt diet combined with hydrochlorothiazide, respectively.
AUTHORS' CONCLUSIONS
This systematic review shows an important reduction in SBP and DBP in people with diabetes with normal GFR during short periods of salt restriction, similar to that obtained with single drug therapy for hypertension. These data support the international recommendations that people with diabetes with or without hypertension or evidence of kidney disease should reduce salt intake to less than 5 g/day (2 g sodium).
Topics: Humans; Diabetic Nephropathies; Sodium Chloride, Dietary; Diabetes Mellitus, Type 1; Hypertension; Renal Insufficiency, Chronic; Sodium; Diabetes Mellitus, Type 2
PubMed: 36645291
DOI: 10.1002/14651858.CD006763.pub3 -
Frontiers in Pharmacology 2022Cardiovascular and renal impairment are the most common complications of type 2 diabetes mellitus (T2DM). As an emerging class of glucose-lowing agents sodium glucose...
Cardiovascular and renal impairment are the most common complications of type 2 diabetes mellitus (T2DM). As an emerging class of glucose-lowing agents sodium glucose co-transporter 2 (SGLT2), possesses beneficial effects on cardiovascular and renal outcomes in patients with T2DM. The aim of this study is to assess the efficacy of different SGLT2 inhibitors for cardiovascular and renal outcomes for patients with T2DM when compared with placebo. We performed a systematic search of PubMed, Embase, and the Cochrane library from inception through November 2021. Randomized clinical trials enrolling participants with T2DM were included, in which SGLT2 inhibitors were compared with each other or placebo. The primary outcomes including all-caused mortality, Cardiovascular outcomes (cardiovascular mortality, hospitalization for heart failure), and the renal composite outcomes (worsening persistent microalbuminuria or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death). The data for the outcomes were pooled and recorded as Hazard rations (HRs) with 95% confidence intervals (CLs). Two researcher independently screened the trials and drawn the data. Ten trials enrolling 68,723 patients were included. Compared with placebo groups, Canagliflozin [HR, 0.85 (95%CI, 0.75-0.98)], ertugliflozin [HR, 0.93 (95%CI, 0.78-1.11)], and sotagliflozin [HR, 0.94 (95%CI, 0.79-1.12)] were associated with a reduction in all-cause mortality. Canagliflozin [HR, 0.84 (95%CI, 0.72-0.97)], dapagliflozin [HR, 0.88 (95%CI, 0.79-0.99)], empagliflozin [HR, 0.62 (95%CI, 0.49-0.78)], ertugliflozin [HR, 0.92 (95%CI, 0.77-1.10)], and sotagliflozin [HR, 0.88 (95%CI, 0.73-1.06)] were associated with a reduction in cardiovascular mortality; Canagliflozin [HR, 0.64 (95%CI, 0.53-0.77)], dapagliflozin [HR, 0.71 (95%CI, 0.63-0.81)], empagliflozin [HR, 0.65 (95%CI, 0.50-0.85)], ertugliflozin [HR, 0.70 (95%CI, 0.54-0.90)], and sotagliflozin [HR, 0.66 (95%CI, 0.56-0.77)] were associated with a reduction in hospitalization for heart failure. Dapagliflozin [HR, 0.55 (95%CI, 0.47-0.63)], Empagliflozin [HR, 0.54 (95%CI, 0.39-0.74)], canagliflozin [HR, 0.64 (95%CI, 0.54-0.75)], sotagliflozin [HR, 0.71 (95%CI, 0.46-1.09)], and ertugliflozin [HR, 0.81 (95%CI, 0.63-1.04)] were associated with a reduction in the renal composite outcome. All SGLT2 inhibitors showed a reduction in cardiovascular mortality, hospitalization for heart failure, renal composite outcomes and all-cause mortality. Canagliflozin and empagliflozin seemed to have the same efficacy in reducing hospitalization for heart failure, but empagliflozin had advantage in reducing cardiovascular mortality, whereas dapagliflozin most likely showed the best renal composite outcomes.
PubMed: 36506550
DOI: 10.3389/fphar.2022.986186 -
Frontiers in Medicine 2022Diabetic nephropathy (DN) is one of the main causes of chronic kidney disease (CKD), which increases the risk of cardiovascular diseases and progresses to end-stage...
AIMS
Diabetic nephropathy (DN) is one of the main causes of chronic kidney disease (CKD), which increases the risk of cardiovascular diseases and progresses to end-stage renal failure. Thus, early diagnostic markers for diabetic patients are urgently needed to improve the prognosis of DN and predict DN progression.
MATERIALS AND METHODS
PubMed, MEDLINE, EMBASE, and Scopus were searched for publications until February 24, 2021. Review Manager 5.4 software was used for meta-analysis. We performed the heterogeneity test using the I statistic: < 0.1 and I> 50% meant statistical significance.
RESULTS
We included 13 studies. The urinary liver-type fatty acid-binding protein (uL-FABP) concentrations in the normal albuminuria group were significantly higher than those in the normal control group without diabetes mellitus (DM) [ = 0.009, SMD 1.72, 95% CI (0.44, 2.99)]. Urinary F-LABP levels were elevated in the macroalbuminuria group compared with those in the microalbuminuria group with DM [ = 0.002, SMD 2.82, 95% CI (1.03, 4.61)]. Urinary L-FABP levels were also significantly increased in the progression and CKD groups compared with non-progression and CKD subjects with DM [ = 0.02, < 0.00001, respectively]. Furthermore, uL-FABP concentrations were positively correlated with the albumin-to-creatinine ratio and systolic blood pressure in patients with DM [Summary Fisher's = 0.58 < 0.00001; Summary Fisher's = 0.24 < 0.0001, respectively] and negatively correlated with estimated glomerular filtration rate in patients with DM [Summary Fisher's = -0.36, < 0.0001].
CONCLUSION
Urinary L-FABP may be a potential marker for the detection of all stages of DN and for the prediction of the progression and severity of DN in patients with type 1 and 2 DM.
PubMed: 36117980
DOI: 10.3389/fmed.2022.914587 -
Frontiers in Medicine 2022Huangqi injection (HQI) is the extract of Astragalus membranaceus (Fisch.) Bunge, which is widely used in the treatment of a variety of diseases in China. It is supposed...
BACKGROUND
Huangqi injection (HQI) is the extract of Astragalus membranaceus (Fisch.) Bunge, which is widely used in the treatment of a variety of diseases in China. It is supposed to be an important adjuvant therapy for hypertensive nephropathy.
OBJECTIVE
To evaluate the efficacy of HQI combined with antihypertensive drugs in the treatment of hypertensive nephropathy.
MATERIALS AND METHODS
We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang Knowledge Service Platform (WanfangData), Chinese Biomedical Database (CBM), EMBASE, PubMed and Cochrane Library from their inception to April 23st, 2021. All studies were independently screened by two auditors according to the inclusion and exclusion criteria. Randomized controlled trials comparing HQI in combination with antihypertensive drugs vs. antihypertensive drugs alone were extracted.
RESULTS
The meta-analysis included 15 studies involving 1,483 participants.The effect of HQI combined with antihypertensive drugs is better than that of antihypertensive drugs alone in regulating hypertensive nephropathy for reducing 24-h urinary total protein (24 h UTP) [WMD=-0.29, 95% CI (-0.40, -0.18), = 0.000], microalbuminuria (mALB) [WMD = -17.04, 95% CI (-23.14, -10.94), = 0.000], serum creatinine (SCr) [WMD = -40.39, 95% CI (-70.39, -10.39), = 0.008], systolic blood pressure (SBP) [WMD = -9.50, 95% CI (-14.64, -4.37), = 0.000], diastolic blood pressure (DBP) [WMD = -4.588, 95% CI (-6.036, -3.140), = 0.000], cystatin-C (Cys-c) [WMD = -0.854, 95% CI (-0.99, -0.72), = 0.000], blood urea nitrogen (BUN) [WMD = -4.155, 95% CI (-6.152, -2.157), = 0.000].
CONCLUSION
The combination of HQI and antihypertensive drugs is more efficient in improving the related indexes of patients with hypertensive nephropathy than using antihypertensive drugs alone, and a moderate dose of HQI (no more than 30 mL) may benefit more. However, the quality of the methodology is low and the number of samples is small, the results need to be confirmed by more stringent randomized controlled trials.
PubMed: 35547210
DOI: 10.3389/fmed.2022.838256 -
Oxidative Medicine and Cellular... 2022Artemisinin and its derivatives have potential antidiabetic effects. There is no evaluation of reported studies in the literature on the treatment of diabetic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Artemisinin and its derivatives have potential antidiabetic effects. There is no evaluation of reported studies in the literature on the treatment of diabetic nephropathy (DN), one of the commonest diabetic microangiopathies, with artemisinins. Here, we aimed to evaluate preclinical evidence for the efficacy and possible mechanisms of artemisinins in reducing diabetic renal injury.
METHODS
We conducted an electronic literature search in fourteen databases from their inception to November 2021. All animal studies assessing the efficacy and safety of artemisinins in DN were included, regardless of publication or language. Overall, 178 articles were screened according to predefined inclusion and exclusion criteria. Finally, 18 eligible articles were included in this systematic review. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool was used to assess the risk of bias in the included studies. The primary outcomes were kidney function, proteinuria, and renal pathology. Secondary endpoints included changes in fasting plasma glucose (FPG) levels, body weight, and relevant mechanisms.
RESULTS
Of the 18 included articles involving 418 animal models of DN, 1, 2, 6, and 9 used dihydroartemisinin, artemether, artesunate, and artemisinin, respectively. Overall, artemisinins reduced indicators of renal function, including blood urea nitrogen ( < 0.00001), serum creatinine ( < 0.00001), and kidney index ( = 0.0001) compared with control group treatment. Measurements of proteinuria ( < 0.00001), microalbuminuria ( < 0.05), and protein excretion ( = 0.0002) suggested that treatment with artemisinins reduced protein loss in animals with DN. Artemisinins may lower blood glucose levels ( = 0.01), but there is a risk of weight gain ( < 0.00001). Possible mechanisms of action of artemisinins include delaying renal fibrosis, reducing oxidative stress, and exerting antiapoptotic and anti-inflammatory effects.
CONCLUSION
Available evidence suggests that artemisinins may be protective against renal injury secondary to diabetes in preclinical studies; however, high-quality and long-term trials are needed to reliably determine the balance of benefits and harms.
Topics: Animals; Artemisinins; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Male; Models, Animal; Proteinuria
PubMed: 35528521
DOI: 10.1155/2022/5401760 -
The Cochrane Database of Systematic... Dec 2021Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of... (Review)
Review
BACKGROUND
Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013 and 2015.
OBJECTIVES
To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.
SEARCH METHODS
The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 18 October 2021. We also searched clinical trial registries. Date of the most recent search: 22 August 2021.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.
DATA COLLECTION AND ANALYSIS
Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.
MAIN RESULTS
Seven studies were identified through the searches. Six studies were excluded. The included study randomized 22 participants (7 males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. Overall, the certainty of the evidence provided in this review was very low, since most risk of bias domains were judged to have either an unclear or a high risk of bias. Because of this, we are uncertain whether captopril makes any difference, in total urinary albumin excretion (at six months) as compared to the placebo group, although it yielded a mean difference of -49.00 (95% confidence interval (CI) -124.10 to 26.10) or in the absolute change score, although it yielded a mean difference of -63.00 (95% CI -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean (standard deviation) of 45 (23) mg/day and the placebo group was noted to increase by 18 (45) mg/day. Serum creatinine and potassium levels were reported constant throughout the study (very low-certainty evidence). The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Overall, we judged the certainty of the evidence to be very low. The included study selectively reported its results, was not powered to detect a group difference, should it exist, and otherwise did not offer enough information to allow us to judge the bias inherent in the study. Indirectness (in relation to the limited age and type of population included) and imprecision (wide confidence intervals around the effect estimate) were observed. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. Overall, we judged the certainty of this evidence to be very low.
Topics: Albuminuria; Anemia, Sickle Cell; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Humans; Proteinuria; Randomized Controlled Trials as Topic
PubMed: 34932828
DOI: 10.1002/14651858.CD009191.pub4 -
Frontiers in Pharmacology 2021We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on... (Review)
Review
We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in comparison with the renin-angiotensin-aldosterone system inhibitor (RAASi). Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. We pooled relative risks (RRs) with 95% confidence intervals (CIs) or the mean difference with 95% CIs for the variables. Our search yielded 10 randomized controlled trials with a total of 18,362 patients. Compared with RAASi treatment, patients treated with sacubitril/valsartan had lower incidence of composite renal impairment (10 studies, 18,362 patients, RR 0.84; 95% CI 0.72-0.96, = 0.01; = 22%), ESRD development (3 studies, 13,609 patients, RR 0.53; 95% CI 0.30-0.96, = 0.03; = 0%), drug discontinuation due to renal events (4 studies, 9,995 patients, RR 0.58; 95% CI 0.40-0.83, = 0.003; = 47%), severe hyperkalemia (6 studies, 16,653 patients, RR 0.80; 95% CI 0.68-0.93, = 0.01; = 25%) and a slower eGFR decline (4 studies, 13,608 patients, WMD 0.56; 95% CI 0.36-0.76, < 0.00001; = 65%). Subgroup analysis demonstrated that sacubitril/valsartan was associated with a lower incidence of renal impairment in patients with heart failure and preserved ejection fraction (HFpEF), but not in those with heart failure and reduced ejection fraction (HFrEF). The superior renal function preservation of sacubitril/valsartan treatment was not associated with different baseline eGFR levels and follow-up duration. There was a smaller increase in the change in the urine albumin-to-creatinine ratio (UACR) (3 studies, 9,114 patients, SMD 0.06; 95% CI 0.02-0.10, = 0.003; = 14%) with sacubitril/valsartan treatment. However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF ( = 0.80 for interaction). Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.
PubMed: 34867310
DOI: 10.3389/fphar.2021.604017