Disease Mongering with Proteinuria
The bulk of the research on the medications that modify the effects of angiotensin is funded by the pharmaceutical companies, so the real truths about the benefits of these drugs are hard to know for certain. The amount of protein in the patient’s urine (proteinuria) is the “end point” most often measured to determine a drug’s benefit. However, the “end points” most meaningful to the patient are staying alive, healthy, and off a dialysis machine. Research has clearly established that these medications will decrease the amount of protein in the urine, but their benefits for improved health are seriously questioned.
An example of the lack of a direct connection between reducing proteinuria with medication and a patient’s improved health is the diabetic medication Avandia. (Avandia is also known as rosiglitazone.) Rosiglitazone combined with metformin has been proven to provide a greater reduction in proteinuria than other oral antidiabetic combinations.4 Yet, the New England Journal of Medicine on June 2007 published the results of diabetics taking rosiglitazone—they found a 43% increased risk of a heart attack and a 64% increased risk of death from all cardiovascular causes.5 Thus, diabetic patients using Avandia will be more likely to die, but they will die with less protein in their urine.
Renal-protective Effects of Anti-Angiotensin Drugs Questioned
A study recently published in the Lancet concluded, “…claims that ACE inhibitors and ARBs are renoprotective in diabetes seem to derive from small placebo-controlled trials that provide uncertain evidence of the existence of any true advantage over and above blood-pressure control… There seems to be little justification for ACE inhibitors or ARBs to be first-line choices for renoprotection in diabetes on the basis of efficacy, and residual uncertainty still exists about the inherent value of these drugs in other renal disorders. In view of the present analysis, treatment decisions for hypertension in renal disease should be based on the blood-pressure-lowering effect, comparative tolerability, and cost of antihypertensive treatment.”6
Not only may these two categories of anti-angiotensin medications (ACE-I and ARB) have no special benefits, they may actually be more harmful than other antihypertensive medications. There is good evidence from one very large study that ACE-I drugs result in a higher risk of stroke and cardiovascular disease (like heart failure and heart surgery) when compared to the use of inexpensive diuretics (chlorthalidone) for the treatment of hypertension.7
Patients with Diabetes without Proteinuria
A common practice by almost all doctors these days is to treat all diabetics, with or without hypertension, with ACE-I and/or ARB drugs, even when they have no protein in their urine. The highly respected Cochrane review of diabetic patients, many with hypertension, but no protein in their urine, found the future development of protein in the urine was reduced by ACE-I medications, but this had no effect on progression of kidney disease or risk of death.9 Another recent review of the current evidence concluded: “Until more evidence accumulates on the alleged renoprotection associated with RAS inhibition (inhibition of the renin-angiotensin system), it seems reasonable for clinicians to not use pharmacologic intervention with ACE inhibitors or ARBs in normotensive patients with diabetes. For hypertensive patients with diabetes, prescribing a thiazide diuretic would also seem to represent the practice of evidence-based medicine.”10 In addition, patients with kidney disease from causes other than diabetes with low levels of protein in their urine (500 mg/day or less) have not been shown to benefit from ACE-I or ARB medications.11
What To Do?
Kidney disease is a serious problem and people with diabetes are at especially high risk of losing the function of their kidneys. Treating high blood pressure, cholesterol, and blood sugar with medications will be of some benefit. However, these medications are associated with serious side effects and financial costs. ACE-I and ARB medications are highly profitable for the pharmaceutical industry and as a result they have spent billions of dollars for research that favors their products and marketing to their sales division, the medical doctors. As discussed above, the real benefits for the patient of using these medications, over less expensive ones, are in doubt. Based on available research, a diuretic, such as chlorthalidone, would be the drug of first choice for treating hypertension in patients with kidney disease. People with diabetes and no protein in their urine should not routinely receive so-called “renal-protective” medications in the form of ACE-I or ARB. In addition, people with kidney disease from non-diabetic causes and no protein in their urine should not take these medications for “renal-protection.” For people with diabetes and significant kidney disease, given a choice between use of an ACE-I and ARB, the ACE-I are more effective with fewer risks that the ARB.12
Hypertension, elevated cholesterol, and type-2 diabetes are due to the Western diet. Likewise, the health of the heart, kidneys, arteries, and the rest of the body is dependent on a healthy diet. What is missing in the current treatment of people with kidney disease is diet-therapy. For almost seventy years doctors have been aware of the profound effect that a healthy diet has on preserving kidney function, and even reversing some of the kidney damage. Next month’s newsletter will continue with a discussion of the most effective form of renal-protection: a healthy, cost-free, low-protein vegan diet.
1) Garcia-Donaire JA, Segura J, Ruilope LM. Clinical trials in nephrology: success or failure. Curr Opin Nephrol Hypertens. 2007 Mar;16(2):59-63.
2) Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, Kolloch R, Benetos A, Pepine CJ. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006 Jun 20;144(12):884-93.
3) Crespin SR. What does the future hold for diabetic dyslipidaemia? Acta Diabetol. 2001;38 Suppl 1:S21-6.)
4) Bakris G, Ruilope LM, McMorn S, et al. Rosiglitazone reduces microalbuminuria and blood pressure independently of glycemia in type 2 diabetes patients with microalbuminuria. J Hypertens 2006; 24:2047–2055.
5) Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71.)
6) Casas JP, Chua W, Loukogeorgakis S, et al. Effect of inhibitors of the reninangiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366:2026-33.
7) The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-97.)
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Strauss M. Angiotensin receptor blockers and myocardial
9) Strippoli GF, Craig M, Craig JC. Antihypertensive agents for preventing diabetic kidney disease. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004136.
10) Curtiss FR. What evidence supports guidelines for use of ACE inhibitors and ARBs in diabetes? J Manag Care Pharm. 2006 Oct;12(8):690-1.
11) Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, Maschio G, Brenner BM, Kamper A, Zucchelli P, Becker G, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med. 2001 Jul 17;135(2):73-87.
12) Strippoli GF, Craig MC, Schena FP, Craig JC. Role of blood pressure targets and specific antihypertensive agents used to prevent diabetic nephropathy and delay its progression. J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S153-5.