Horm Metab Res 2020; 52(05): 289-297
DOI: 10.1055/a-1138-0959
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Effects of ACE Inhibitors and Angiotensin Receptor Blockers in Normotensive Patients with Diabetic Kidney Disease

Dandan He
1   Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China
,
Yaru Zhang
1   Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China
,
Wei Zhang
2   Department of Cardiac Surgery, Tianjin Chest Hospital, China
,
Yue Xing
1   Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China
,
Yipeng Guo
3   Department of Epidemiology, Tianjin Public Health Bureau, Tianjin, China
,
Fuzhen Wang
4   Department of Statistics, Fenyang Hospital of Shanxi Province, Fenyang, China
,
Junya Jia
1   Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China
,
Tiekun Yan
1   Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China
,
Youxia Liu
1   Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China
,
Shan Lin
1   Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China
› Author Affiliations
Funding This work was supported by grants from the National Natural Science Foundation (81600553, 81270791, and 30800529), Tianjin Municipal Science and Technology Commission Foundation (14JCYBJC27900) and Tianjin Public Health Bureau Foundation (2014KR16), The 12th Five-Year Plan National Science and Technology Support Program (No. 2011BAI10B02) and Shanxi Public Health Bureau Foundation (201302051), the General Hospital of Tianjin Medical University Youth Incubation Foundation (ZYYFY2015001).
Further Information

Publication History

received 19 December 2018

accepted 10 March 2020

Publication Date:
27 March 2020 (online)

Abstract

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing the progression of albuminuria and risk of cardiovascular events in hypertensive patients with diabetic kidney disease (DKD) is well-documented. However, the efficacy and safety of these agents in normotensive patients with DKD are still controversial. MEDLINE, Embase, and Cochrane Library were searched for relevant random controlled trials. The odd risk (OR) reductions were calculated with a random-effects model. Decrease in albuminuria, changes in eGFR, major cardiovascular events, and drug-related adverse events were analyzed. Thirteen RCTs including 1282 patients were retrieved. Compared with placebo or other active agent groups, ACEIs or ARBs significantly decreased albuminuria (MD –80.28 mg/d, 95% CI –104.79 mg/d to –55.77 mg/d), and the efficacy is independent of changes in blood pressure and systolic blood pressure at baseline. The result of subanalysis showed the declining of albuminuria was more significantly in normotensive DKD patients with 2DM (p=0.005). No significant differences were found with regard to the declining of evaluated glomerular filtration rate (eGFR) (MD –0.29 ml/min/1.73 m2, 95% CI –2.99 to 2.41 ml/min/1.73 m2). There were no significant differences in the side effect of the drugs such as hypotension and hyperkalemia. This meta-analysis demonstrated that ACEIs or ARBs can decrease albuminuria to varying degree in normotensive patients with DKD, and better response occurred in patients with 2DM.

Supplementary Material

 
  • References

  • 1 Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med 1999; 341: 1127-1133
  • 2 Zhang L, Long J, Jiang W. et al. Trends in Chronic Kidney Disease in China. N Engl J Med 2016; 375: 905-906
  • 3 Basi S, Fesler P, Mimran A. et al. Microalbuminuria in type 2 diabetes and hypertension: a marker, treatment target, or innocent bystander?. Diabetes Care 2008; 31 (Suppl 2) S194-S201
  • 4 Marfella R, Esposito K, Giugliano D. Increase in nocturnal blood pressure and progression to microalbuminuria in diabetes. N Engl J Med 2003; 348: 260-264 author reply 260–264
  • 5 Becker GJ, Wheeler D, De Zeeuw D. et al. Kidney Disease: Improving Global Outcomes KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl 2012; 37-414
  • 6 O’Hare P, Bilbous R, Mitchell T. et al. Low-dose ramipril reduces microalbuminuria in type 1 diabetic patients without hypertension: results of a randomized controlled trial. Diabetes Care 2000; 23: 1823-1829
  • 7 Makino H, Haneda M, Babazono T. et al. Microalbuminuria reduction with telmisartan in normotensive and hypertensive Japanese patients with type 2 diabetes: a post-hoc analysis of The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) study. Hypertens Res 2008; 31: 657-664
  • 8 Bojestig M, Karlberg BE, Lindström T. et al. Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes. Diabetes Care 2001; 24: 919-924
  • 9 Laffel LM, Mcgill JB, Gans DJ. The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med 1995; 99: 497-504
  • 10 Parving HH, Hommel E, Damkjaer Nielsen M. et al. Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy. BMJ 1989; 299: 533-6
  • 11 Viberti G, Mogensen CE, Groop LC. et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group. JAMA 1994; 271: 275-279
  • 12 Ahmad J, Siddiqui MA, Ahmad H. Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care 1997; 20: 1576-1581
  • 13 Crepaldi G, Carta Q, Deferrari G. et al. Effects of lisinopril and nifedipine on the progression to overt albuminuria in IDDM patients with incipient nephropathy and normal blood pressure. The Italian Microalbuminuria Study Group in IDDM. Diabetes Care 1998; 21: 104-110
  • 14 Jerums G, Allen TJ, Campbell DJ. et al. Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria. Am J Kidney Dis 2001; 37: 890-899
  • 15 Jerums G, Allen TJ, Campbell DJ. et al. Long-term renoprotection by perindopril or nifedipine in non-hypertensive patients with type 2 diabetes and microalbuminuria. Diabet Med 2004; 21: 1192-1199
  • 16 Ravid M, Savin H, Jutrin I. et al. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 1993; 118: 577-581
  • 17 O'Donnell MJ, Rowe BR, Lawson N. et al. Placebo-controlled trial of lisinopril in normotensive diabetic patients with incipient nephropathy. J Hum Hypertens 1993; 7: 327-332
  • 18 Diabetologia Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. The Microalbuminuria Captopril Study Group. Diabetologia 1996; 39: 587-593
  • 19 Futrakul N, Chaisuriya P, Ratanabanangkoon K. et al. Microvascular dysfunction in normotensive, normoalbuminuric, normo- or hyperfiltrate type 2 diabetes. Ren Fail 2013; 35: 1191-1192
  • 20 Ustündağ B, Canatan H, Cinkilinç N. et al. Angiotensin converting enzyme (ACE) activity levels in insulin-independent diabetes mellitus and effect of ACE levels on diabetic patients with nephropathy. Cell Biochem Func 2000; 18: 23-28
  • 21 Lozano-Maneiro L, Puente-García A. Renin-angiotensin-aldosterone system blockade in diabetic nephropathy. Present Evidences. J Clin Med 2015; 4: 1908-1937