Fwd: [SoFlaVegans] Save Your Kidneys � Part 1

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Save Your Kidneys — Part 1

The Hard Way, with Medications

From The McDougall Newsletter

 

http://www.drmcdougall.com/misc/2007nl/jun/kidneys.htm

http://www.drmcdougall.com/misc/2007nl/jun/kidney.pdf

 

(This is a technical article, but very important to anyone with

kidney disease or taking any of the anti-angiotensin

medications—ACE-I or ARB.)

 

The prevalence of chronic kidney disease in the US adult population

is estimated to be 10.8% (approximately 19.2 million people). In 1999

in the USA 357,000 people had end-stage kidney disease and the annual

cost of dialysis and kidney transplant exceeded $15.6 billion. Almost

70% of new cases of end-stage kidney disease are due to hypertension,

diabetes or glomerulonephritis—and these common conditions are in

most cases a direct result of foods consumed on the Western diet.

 

Protein found in the urine in amounts of 30 mg/day or greater, is the

hallmark sign for the beginnings of chronic kidney disease. Over 300

mg/day is considered serious kidney disease. In general, the more

protein in the urine, the worse the kidney disease. Not only does

the protein in the urine reflect the health of the kidneys, but this

is a reliable sign of the health of the rest of the body, including

the blood vessels of the heart, brain, and eyes. Lowering the amount

of protein in the urine in some cases reflects an improvement in the

kidneys and a person’s overall health.

Medications to Prevent Progressive Kidney Disease

 

There are four classes of medications that are believed to slow the

progression of kidney disease: antihypertensive agents, drugs that

have a blockade effect on the renin-angiotensin-aldosterone system,

cholesterol-lowering agents (usually statins), and blood-sugar

lowering medications.

 

Common recommendations are to reduce the blood pressure levels to

130/85 mmHg for people with high blood pressure and kidney disease

from diabetes. However, blood pressures of 140/90 mmHg may be low

enough and lowering the blood pressure too much is considered

detrimental.1 For example, in one recent study of patients with

coronary heart disease treated with sustained-release verapamil (an

ACE-I) or atenolol to lower blood pressure, the risk of death and

heart attack was increased when the diastolic pressure (the lower

number) was reduced below 70 to 80 mm Hg.2 The harmful effects of

lowering blood pressure were greater for people with diabetes and/or

elevated cholesterol. The incidence of heart attacks, death, and/or

stroke was three times higher for patients treated with medications

with a diastolic blood pressure (the lower number) of 60 mmHg

compared to a person with a pressure of 80 to 90 mmHg.2 (A lower

blood pressure for people not on medication is, in contrast,

healthy.)

 

Recommendations are to lower cholesterol levels with statins to below

150 mg/dl and LDL cholesterol below 77 mg/dl.3 Decreases in blood

sugars over the long-term (as measured by Hgb A1c levels) have also

been shown to slow kidney disease in people with type-1 diabetes.

 

Renal Protective Anti-Angiotensin Drugs

 

Medications used to slow the progression of kidney disease are

referred to as “renal-protective” (or renoprotective) and the most

popular of these are a class of blood pressure lowering medications

which inhibit the activity of an adrenal hormone called angiotensin.

(I will refer to these as anti-angiotensin medications.)

 

These medications fall into two general classes: The kinds that block

the production of angiotensin by the adrenal gland are known as

angiotensin-converting enzyme inhibitors (ACE-I) and those that block

the activity of this hormone at the places where it works in the body

(the receptor sites) are called angiotensin receptor blockers (ARB).

Research has found the more severe the kidney damage, as reflected by

a larger amount of protein in the patient’s urine, the greater the

benefits from these medications.

 

 

Two Categories of Anti-angiotensin Medications

 

ACE-I: Accupril (quinapril), Aceon (perindopril), Altace (ramipril),

Capoten (Captopril), Lotensin (benazepril), Mavik (trandolapril),

Monopril (fosinopril), Prinivil (lisinopril), Univasc (moexipril),

Vasotec (enalapril), Zestril (lisinopril)

 

ARB: Cozaar (losartan), Atacand (candesartan), Teveten (eprosartan),

Avapro (irbesartan), Micardis (telmisartan), Benicar (olmesartan),

Hyzaar (losartan) and Diovan (valsartan).

 

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

 

ARB Increase the Risk of Stroke and Heart Disease8

 

The VALUE trial showed the angiotensin receptor blocker valsartan

produced a statistically significant 19% relative increase in

myocardial infarction (fatal and non-fatal) compared with amlodipine

and a 13% increase in the incidence of stroke in patients taking

valsartan.

 

The CHARM-alternative trial showed a significant 36% increase in

myocardial infarction with candesartan (versus placebo) despite a

reduction in blood pressure (4.4 mm Hg systolic and 3.9 mm Hg

diastolic) vs. placebo treatment.

 

The SCOPE study, candesartan was associated with a non-significant

10% increase in fatal plus non-fatal myocardial infarction despite

lower blood pressure (3.2 mm Hg systolic and 1.6 mm Hg diastolic) for

candesartan vs. placebo.

 

 

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.

 

References:

 

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.)

 

8) Verma S, Strauss M. Angiotensin receptor blockers and myocardial

infarction.

BMJ. 2004 Nov 27;329(7477):1248-9.

 

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.

 

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