More on Angiotensin Blockade and Diabetic Nephropathy

I recently reviewed a paper that indicated that angiotensin blockade with an angiotensin receptor blocker (ARB) did not protect against the development of diabetic nephropathy in diabetic patients with normal renal function. Despite what that paper concluded angiotensin blockade with and an angiotensin converting enzyme (ACE) inhibitor offered protection.

Two papers in the July 7 Annals of Internal Medicine looked at the effect of ARBs in patients with renal disease. The first study included patients with high vascular risk but who did not have microalbuminuria; about a third were diabetic. In these patients the ARB telmisartan had no effect on major renal outcomes.

The second study was of normotensive diabetic patients. Candesartan (another ARB given at a maximum dose of 32 mg daily) did not prevent microalbuminuria in patients with either type 1 or type 2 diabetes. This makes three studies which indicate no salutary renal effect of ARBs.

The clinician is left wondering if ACE inhibitors are better for the kidney than ARBs or other anti-hypertensive medicines. This question may remain unresolved because ACE inhibitors are available in generic form while ARBs are still on patent. Thus there is little incentive for drug companies to fund long and expensive research projects which are not likely to help them market their product. The NIH should be encouraged to mount additional studies of ACE inhibitors on patients at great risk for serious renal disease who are at an early stage of their disease.

The best practice in the absence of such studies would be to continue to prescribe ACE inhibition in diabetic patients and other at increased renal risk and to do so early in their disease. The worst that will happen from this treatment is that blood pressure will be reduced and the retina will be protected; there is no down side. I think that ARBs should be avoided  unless the patients cannot tolerate ACE inhibition, usually because of cough and rarely because of angioedema.

If there turns out to be a different effect on clinical outcomes between the two types of angiotensin blockers the explanation for the difference will be of intense interest. One possible explanation for a difference between ACE inhibitors and ARBs is that the former decreases angiotensin levels while the latter increases them. ARBs block the AT-1 receptor. If angiotensin exerts a harmful effect mediated by a mechanism other the via the AT-1 receptor then ARBs would make things worse while ACE inhibitors would be beneficial.

I suspect when the fog lifts that ACE inhibition will be shown to have a beneficial effect on patients at high risk for progressive renal disease. But well designed research will have the final word.

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2 Responses to More on Angiotensin Blockade and Diabetic Nephropathy

  1. Osmotic says:

    The questions below are not related to ARB and DN. If you could open a small space in your blog for random questions will be great.

    Questions:

    If you infuse Mannitol to a young healthy man(let’s say 26 years old at a dose sufficient enough to cause osmotic diuresis), what happens in the thin descending and ascending loop of Henle, what would be the osmolarity in the inner medullary intesrtitium, what happens to the 2Na+Cl-KATPase in the T.A.L, what happens to urea reabsortion in the medullary collecting duct and lastly, what happens to ADH levels in the serum

    Thank you in advance for your response

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