Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis

Huang, Rongzhong; Feng, Yuxing; Wang, Ying; Qin, Xiaoxia; Melgiri, Narayan D.; Sun, Ying; Li, Xingsheng

doi:10.1371/journal.pone.0168582

Cited by 11 publications

(12 citation statements)

References 67 publications

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“…However, the proportion of diabetic patients in that systematic review was low. Finally, a recent network meta-analysis comparing the effects of antihypertensive agents in diabetic patients with kidney disease showed that the ACEI-CCB combination therapy of fosinopril and amlodipine appeared to be the most efficacious in reducing proteinuria [28]. While the ACEI-ARB combination was not recommended due to safety concerns [6, 7], based on the results of the network meta-analysis, a combination of ACEIs or ARBs with other antihypertensive agents may deserve further investigation.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria

Hsu¹,

Lin²,

Ou³

et al. 2017

Kidney Blood Press Res

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Background/Aims: Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. Methods: This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. Results: Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50) and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32). Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93) and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55). Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78). Conclusions: Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively.

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Section: Discussionmentioning

confidence: 99%

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria

Hsu¹,

Lin²,

Ou³

et al. 2017

Kidney Blood Press Res

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“…A previous network meta-analysis (Huang et al, 2017) found that the combination therapy of trandolapril plus candesartan was the best one to reduce albuminuria in normotensive diabetic patients. However, Mann et al (2008) also mentioned that the combination therapy of ACEI and ARB reduced proteinuria to a greater extent but had less renal benefit in diabetic patients.…”

Section: Discussionmentioning

confidence: 97%

“…What should be recommended for more proteinuria reduction and less blood pressure reduction in normotensive patients with CKD? A recent network meta-analysis by Huang et al (2017) reported that the ACEI-ARB combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive diabetic patients. The study only included the diabetic patients, which means that the results cannot be generalized to normotensive patients with other kinds of CKD.…”

Section: Introductionmentioning

confidence: 99%

Comparative proteinuria management of different angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for normotensive patients with CKD: a Bayesian network meta-analysis

Huo

et al. 2020

PeerJ

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Background Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are blood pressure-lowering agents, but they are also being used to control proteinuria in early chronic kidney disease (CKD) patients. However, clinically, some patients present merely proteinuria without hypertension. No guidelines pointed out how to select treatments for proteinuria in normotensive patients. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of different kinds of ACEI or ARB or their combination on proteinuria and blood pressure reduction. Methods The protocol was registered in PROSPERO with ID CRD42017073721. A comprehensive literature database query was carried out systematically according to PICOS strategies. The primary outcome was reduction in proteinuria, and the secondary outcomes were eGFR reduction and blood pressure reduction. Random-effects pairwise and Bayesian network meta-analyses were used to estimate the effect of different regimens. Results A total of 14 RCTs with 1,098 patients were included in the analysis. All treatment strategies of ACEI, ARB or their combination had significantly greater efficacy in reducing proteinuria than placebo in normotensive CKD patients. The combination therapy of olmesartan+temocapril had the highest probability (22%) of being the most effective treatment to reduce proteinuria in normotensive CKD patients. Olmesartan and lisinopril ranked second (12%), and temocapril ranked third (15%) but reduced blood pressure less than placebo. For IgA nephropathy, the combination therapy of olmesartan+temocapril also had the highest probability (43%) of being the best antiproteinuric treatment, while enalapril had the highest probability (58%) of being the best antiproteinuric therapy for diabetic nephropathy. Conclusions The combination therapy of olmesartan plus temocapril appeared to be the most efficacious for reducing proteinuria in normotensive CKD patients and IgA nephropathy, but the clinical application should be balanced against potential harms. Temocapril can be an option when practitioners are searching for more proteinuria reduction but less blood pressure variation. In normotensive diabetic nephropathy, monotherapy with the ACEI enalapril seems to be the most efficacious intervention for reducing albuminuria. Future studies are required to give a more definitive recommendation.

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“…In randomized controlled trials (RCTs), treatment with ACE inhibitors can slow down the decline in glomerular filtration rate (GFR) [ 5 ] and the progression to end-stage renal failure [ 6 ], independent of the reduction in blood pressure [ 5 ]. Network meta-analysis of RCTs comparing different classes of antihypertensives suggests that the ACE inhibitor-CCB combination therapy is the most efficacious therapy in reducing albuminuria in patients with diabetes and microalbuminuric kidney disease [ 7 ], while whether the findings can be generalized to people without these comorbidities is unclear. Given the limited number of often small-scale RCTs, current evidence may not be sufficient to support the use of ACE inhibitors as the first-line antihypertensive drug [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Using Mendelian randomization study to assess the renal effects of antihypertensive drugs

Zhao

Schooling

2021

BMC Med

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Background Angiotensin-converting enzyme (ACE) inhibitors and/or in combination with calcium channel blockers (CCBs) are generally recommended as the first-line antihypertensive therapy for people with hypertension and kidney dysfunction. Evidence from large randomized controlled trials comprehensively comparing renal effects of different classes of antihypertensive drugs is lacking. Methods We used a Mendelian randomization study to obtain unconfounded associations of genetic proxies for antihypertensives with kidney function. Specifically, we used published genetic variants in genes regulating target proteins of these drugs and then applied to a meta-analysis of the largest available genome-wide association studies of kidney function (estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria). Inverse variance weighting was used as the main analysis and to combine estimates from different sources. Results Genetically predicted ACE inhibition was associated with higher eGFR (effect size 0.06, 95% confidence interval (CI) 0.008, 0.11), while genetic proxies for beta-blockers were associated with lower eGFR (− 0.02, 95% CI − 0.04, − 0.004) when meta-analyzing the UK Biobank and CKDGen. Genetic proxies for CCBs were associated with lower UACR (− 0.15, 95% CI − 0.28, − 0.02) and lower risk of albuminuria (odds ratio 0.58, 95% CI 0.37, 0.90) in CKDGen. The associations were robust to using different analysis methods and different genetic instruments. Conclusions Our findings suggest the reno-protective associations of genetically proxied ACE inhibitors and CCBs, while genetic proxies for beta-blockers may be related to lower eGFR. Understanding the underlying mechanisms would be valuable, with implications for drug development and repositioning of treatments for kidney disease.

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Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis

Cited by 11 publications

References 67 publications

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria

Comparative proteinuria management of different angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for normotensive patients with CKD: a Bayesian network meta-analysis

Using Mendelian randomization study to assess the renal effects of antihypertensive drugs

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