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Kidney Disease and Kidney Failure

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Diet for Prevention of Kidney Stones
To prevent the recurrence of kidney stones, doctors often recommend changes in diet. For instance, reducing calcium intake seems to make sense. Kidney stones frequently occur from a build up of calcium oxalate (calcium combined with the mineral oxalate). Or doctors may prescribe a diet that maintains a normal calcium intake but limits the amount of salt and animal protein. Research shows both salt and animal protein influence the amount of calcium excreted by the body, and a high level of calcium excretion is a risk factor for the formation of stones. But which of the diets is more effective over the long-term was unknown.

Recently, researchers conducted a study to compare the benefits of the two diets on the recurrence of kidney stones and calcium levels in the urine. Sixty men with histories of kidney stones and high calcium levels in their urine were randomly assigned to each diet for five years. Men on both diets drank plenty of water — a mainstay of kidney stone prevention. The study participants were evaluated annually for signs of kidney stone formation and urine calcium and oxalate levels.

Over the five years of the study, the risk of recurrence of stones was 50% less for men on the normal calcium, low salt, and low animal protein diet compared to men on the low-calcium diet. Both diets significantly reduced the amount of calcium excreted. But the low calcium diet actually increased the amount of oxalate passed through the kidney into the urine.

If you suffer from recurrent kidney stones and a high urinary calcium level, you should talk with your doctor about beginning a normal calcium, low salt, and low animal protein diet. This diet appears to be the most effective at preventing the condition.
February 2002 Update

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Angiotensin-II-receptor Antagonists for Diabetic Nephropathy
Anyone with type 2 diabetes knows about the host of complications that can result if blood sugar is not kept under tight control. One complication is diabetic nephropathy, or kidney damage. When functioning normally, our kidneys keep proteins and other beneficial substances in the blood and filter out waste products, which the body excretes as urine. Diabetes can interfere with this process. As a result, waste products remain in the blood and protein is excreted into the urine (proteinuria).

Angiotensin-converting-enzyme (ACE) inhibitors have been shown to slow the progression of renal, or kidney, disease in patients with type 1 diabetes. ACE inhibitors are widely given to patients with type 2 diabetes for the same purpose, even though there's less evidence they are effective. A set of studies published in the September 20, 2001 New England Journal of Medicine examined the effects of a different class of drugs, called angiotensin-II-receptor antagonists on nephropathy caused by type 2 diabetes.

The first study involved 1,715 patients with type 2 diabetes, above-normal blood pressure, urinary protein excretion of at least 900 mg per day, and serum creatinine levels (a marker of kidney damage) between 1-3 mg/dL. Each day, the patients took either 300 mg of the angiotensin-II-receptor antagonist irbesartan, 10 mg of the calcium-channel blocker amlodipine, or a placebo. After an average of 2.6 years, significantly fewer patients receiving irbesartan experienced a doubling of serum creatinine, end-stage renal disease, or death than patients taking either amlodipine or placebo (33% vs. 41% vs. 39%).

In another study, which involved a similar patient group, investigators studied the effects of the angiotensin II-receptor antagonist losartan versus the effects of a placebo. At the end of 3.4 years, patients taking losartan had a 25% risk reduction in the incidence of serum creatinine doubling and a 28% risk reduction of end-stage renal disease compared to patients taking a placebo. However, losartan did not have any effect on the rate of death.

An editorial accompanying the NEJM articles suggests that although angiotensin-II-receptor antagonists performed well in these trials, they are still far from effective in all patients. In addition, this study did not compare the performance of angiotension-II-receptor antagonists to that of the widely used ACE inhibitors.
October 2001 Update

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Caution Always Key in Using Herbal Medicines
A recent study published in the New England Journal of Medicine offers another important reminder on careful use of herbal remedies. This caution is rooted in the absence of strict pharmaceutical controls in the manufacture of such products and how the lack of these requirements can leave room for tragic errors.

In the mid-1990s, doctors at a clinic in Belgium treated 43 patients with end-stage kidney failure, requiring dialysis or transplant. Not surprisingly, these individuals had something in common in their medical histories. Between 1990 and 1992, each had used a Chinese herbal remedy in combination with two other drugs for weight loss. The herbal preparation supposedly contained Stephania tetrandra and Magnolia officinalis. But the sudden appearance of kidney failure in these patients, caused their doctors to suspect that the herb Aristolochia fangchi, which is poisonous to the kidneys, had unintentionally been substituted for S. tetrandra. The Chinese names for A. fangchi and S. tetrandra sound similar and the two are often confused. Analysis showed that the herbal remedy did, in fact, contain aristolochic acids, which are derived from A. fangchi. Aristolochic acids cause cancer in rats and mutations in bacteria and mammals.

Reports of patients who had developed urothelial carcinoma (cancer of the tissues lining the bladder, ureter, and part of the kidney), as well as kidney failure related to the Chinese herbs, drew concern among the Belgian doctors. When one of their patients also developed this cancer, the doctors decided that all patients with end-stage kidney failure related to the use of Chinese herbs should be checked for cancer of these organs. By removing these organs, the doctors hoped to prevent cancer from developing in their patients. Thirty-nine of the 43 patients agreed to undergo the preventive surgery. Of these patients, 46% of them already had cancerous growths in the removed tissues. In addition, 19 of the remaining 21 patients had abnormal growths in the urinary system. The investigators also analyzed DNA samples taken from the kidneys and ureters of each patient. The DNA samples for every patient showed changes typically found after exposure to aristolochic acid. The researchers compared these results to analysis of DNA samples taken from eight patients with end-stage kidney failure unrelated to Chinese herbs. None of these control samples showed DNA changes formed by aristolochic acid.

The doctors calculated the cumulative dose of the implicated herb and other treatments for each patient. They found that the risk of cancer was related to the cumulative dose of A. fangchi. Because many of the patients had also taken appetite suppressants as well as a diuretic, the doctors noted that these drugs might enhance the toxicity of aristolochic acid.

This case study provides strong evidence suggesting a relationship between the Chinese herb A. fangchi and urothelial carcinoma. While a manufacturing mistake led to the introduction of this herb into an herbal preparation for weight loss, this study highlights the risks involved in taking herbal remedies. There is little control over the quality of herbal medicines. This means that the label on an herbal medicine may not accurately represent what is actually in the container, as was the case with S. tetrandra. Several countries have banned the use of herbs that contain aristolochic acid, yet Aristolochia is readily available in the United States in capsule form.

In the United States, the FDA does not have the authority to assess the safety and efficacy of a dietary supplement before it reaches the shelves of stores. The agency is allowed to restrict a supplement only after it proves the substance is harmful as commonly consumed, but there is no adequate system for reporting serious side effects associated with these products. Furthermore, the FDA does not have any way of knowing which herbal remedies contain harmful substances such as aristolochic acid. The case of the Chinese herbal diet pill and its association with urothelial cancer is just one of a number of cases that demonstrate the need for greater oversight of dietary supplements and caution in the use of supplements on the part of consumers.

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Renal Artery Stenosis-Related High Blood Pressure: Angioplasty vs. Medication

For many people with difficult to control high blood pressure, the problem really begins with (or is made worse by) narrowing of the arteries that supply the kidneys (renal stenosis). One way to manage the resulting elevations in blood pressure is with antihypertensive medications. Another way is balloon angioplasty — the same procedure used to clear narrowed or blocked coronary arteries, but applied to the renal arteries. A study conducted in the Netherlands compared the effects of balloon angioplasty with that of medical therapy (medication) on high blood pressure caused by renal stenosis.

Patients in this study had similar blood pressure levels and took similar doses of high blood pressure drugs at the beginning of the trial. Researchers then randomly assigned these volunteers to two groups. One group continued the two-drug regimen they had been taking, but could take a higher dose of a drug or add a drug, as needed; the other group continued to take a two-drug regimen and was also assigned to undergo balloon angioplasty.

The blood pressure of study participants was measured at three months and at 12 months. At three months, there was no significant difference in blood pressure between the two groups of patients. Also at three months, nearly half of the patients in the drug-therapy group had received balloon angioplasty either because drug therapy failed to adequately reduce blood pressure or because they showed signs of worsening kidney function. Nevertheless, the patients who only received drug therapy did not have higher blood pressure than those who underwent balloon angioplasty did.

Researchers concluded that, compared with antihypertensive drugs, balloon angioplasty does not always result in better blood pressure control for patients with renal stenosis. In patients whose high blood pressure cannot be controlled even when they take three or more medications or those for whom the renal artery blockages worsen, balloon angioplasty serves only to lower blood pressure to the level that can be achieved by drug therapy in other patients. In only a very few cases did balloon angioplasty cure hypertension.
October 2000 Update

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©2000–2006 President & Fellows of Harvard College

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