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  Table of Contents  
COMMENTARY
Year : 2015  |  Volume : 25  |  Issue : 6  |  Page : 328
 

Dual therapy and diabetic kidney disease


Creator, Nephrology On-Demand, Charlotte, NC, 28075, USA

Date of Web Publication28-Oct-2015

Correspondence Address:
T Desai
1601 Brenner Ave, Salisbury NC 28144
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-4065.168441

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How to cite this article:
Desai T. Dual therapy and diabetic kidney disease. Indian J Nephrol 2015;25:328

How to cite this URL:
Desai T. Dual therapy and diabetic kidney disease. Indian J Nephrol [serial online] 2015 [cited 2020 Jun 3];25:328. Available from: http://www.indianjnephrol.org/text.asp?2015/25/6/328/168441


In this issue of the Indian Journal of Nephrology, Singh et al.[1] present a study that shows dual therapy with an angiotensin-converting enzyme (ACE) inhibitors and a fourth-generation dihydropyridine can reduce the amount of microalbuminuria in patients with diabetic kidney disease. Nephrologists have known for some time that albuminuria is an independent predictor of cardiovascular mortality, and that microalbuminuria (defined as a urine albumin: creatinine ratio of 30–300 mg/g) is an early detector of diabetic kidney disease. The results of this investigation are impressive; a reduction in microalbuminuria by more than 50% in patients administered both ACE inhibitors and dihydropyridine. These results, however, should be cautiously interpreted.

Interventions in the last five (5) years have suggested a disconnect between reductions in albuminuria and the progression of chronic kidney disease. In the BEAM and BEACON trials, an initial enthusiasm surrounding bardoxolone was dampened as reductions in albuminuria did not result in slowing of glomerular filtration rate (GFR) decline or death.[2],[3] Subgroup analyses in the ALTITUDE trial showed a reduction in proteinuria with dual renin-angiotensin-aldosterone blockade; when looked at as a primary outcome in the Veterans Affairs Nephropathy in Diabetes trial, these results were complicated by higher rates of hyperkalemia and acute kidney injury.[4],[5]

Thus far, only intensive glycemic control (glycosylated hemoglobin levels of < 6.5% as in the ADVANCE and ADVANCE-ON trials) has been proven to slow the progression of diabetic kidney disease.[6],[7] Newer therapies, including endothelin receptor antagonists (e.g. atrasentan), have shown promise as anti-fibrotic agents, but their efficacy has been measured by reductions in albuminuria (RADAR trial).[8] The use of ACE inhibitors with dihydropyridines shows reductions in proteinuria similar to that seen with bardoxolone, dual ACE/angiotensin II receptor blockers, and atrasentan. Our hope is that additional studies with these agents show improvements in GFR decline and mortality.

 
  References Top

1.
Singh VK, Mishra A, Gupta KK, Misra R, Patel ML, Shilpa. Reduction of microalbuminuria in type-2 diabetes mellitus with angiotensin-converting enzyme inhibitor alone and with cilnidipine. Indian Journal of Nephrology 2015;25:334-9.  Back to cited text no. 1
    
2.
Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, et al. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 2011;365:327-36.  Back to cited text no. 2
    
3.
de Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med 2013;369:2492-503.  Back to cited text no. 3
    
4.
Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012;367:2204-13.  Back to cited text no. 4
    
5.
Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013;369:1892-903.  Back to cited text no. 5
    
6.
Perkovic V, Heerspink HL, Chalmers J, Woodward M, Jun M, Li Q, et al. Intensive glucose control improves kidney outcomes in patients with type 2 diabetes. Kidney Int 2013;83:517-23.  Back to cited text no. 6
    
7.
Zoungas S, Chalmers J, Neal B, Billot L, Li Q, Hirakawa Y, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med 2014;371:1392-406.  Back to cited text no. 7
    
8.
de Zeeuw D, Coll B, Andress D, Brennan JJ, Tang H, Houser M, et al. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy. J Am Soc Nephrol 2014;25:1083-93.  Back to cited text no. 8
    




 

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