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Commonly Prescribed Drug Found to Be Ineffective in Slowing Kidney Disease

  • Researchers say a clinical trial has shown the commonly prescribed drug allopurinol isn’t effective in slowing kidney disease.
  • Experts say the trial results may make them rethink their strategy of trying to lower uric acid levels to treat kidney disease.
  • About 37 million people in the United States have chronic kidney disease, but many are not aware they have the condition.

A drug commonly prescribed for people with kidney disease doesn’t prevent decline in kidney function.

That’s the conclusion from a clinical trial in Australia that found the drug allopurinol (Zyloprim, Aloprim) doesn’t prevent worsening of kidney disease.

“We compared the use of allopurinol to a placebo and found, to our surprise, that it made no difference to the rate of kidney function decline,” David Johnson, PhD, researcher on the study and medical director at the Queensland Kidney Transplant Service, said in a press release.

“Based on these results, we believe there is no benefit in prescribing this medication, unless there is an additional specific medical reason, such as gout,” Johnson said. “This much awaited, high-quality evidence will inform global clinical guidelines for patient treatment.”

The study by the numbers

The trial, known as CKD-FIX, followed 363 people with stage 3 or 4 chronic kidney disease who were at increased risk for worsening of the disease.

The study ran for 2 years across 31 hospitals in Australia and New Zealand.

One group was given the drug allopurinol and one group was given a placebo.

Allopurinol is a drug that helps reduce urate (uric acid) levels in the blood. High urate levels are common in people with chronic kidney disease, as the kidneys fail to adequately remove uric acid from the blood.

High urate levels are associated with a greater risk of developing chronic kidney disease and associated with a higher risk of disease progression.

The researchers found the participants prescribed allopurinol experienced a 35 percent reduction in their blood urate levels, but kidney function declined at similar rates between participants prescribed allopurinol and those who were given a placebo.

Given this, the researchers concluded that allopurinol is ineffective at treating kidney disease and preventing its progression.

Reaction from expert

Dr. Anjay Rastogi, director of the CORE Kidney Program at the University of California, Los Angeles, says the findings of the trial are somewhat surprising.

“It’s a bit of a surprise, as observational data suggested otherwise. I won’t necessarily call it bad news, but definitely disappointing,” he told Healthline.

“Allopurinol has been prescribed for patients with kidney disease in the hope of slowing the progression. This is in addition to the use in treating gout, which is a significant associated comorbidity. This study will definitely make us rethink our approach of targeting uric acid to slow down progression of kidney disease,” he said.

Rastogi argues the study had some limitations, including patients of older age, moderate to advanced kidney failure in the people studied, and increased levels of protein in the urine.

But he says the study will cause doctors to re-examine their approach in focusing on uric acid levels.

“Whenever we prescribe a medication, we always weigh the benefits versus risks. This study will definitely make us rethink our approach of targeting uric acid to slow down progression of kidney disease,” he said.

A deadly disease

In the United States, 37 million people, or more than 1 in 7 adults, have chronic kidney disease.

It’s estimated that 90 percent of people with chronic kidney disease are unaware they have it.

Chronic kidney disease is responsible for more deaths than breast cancer or prostate cancer.

“There are many causes of kidney disease. The majority of kidney disease occurs as damage over time from other risk factors,” Dr. Jeffrey Klein, a transplant nephrologist at the University of Kansas Health System, told Healthline. “Traditionally, these risk factors include hypertension, diabetes, and metabolic syndrome (obesity). Other risk factors like heart disease and smoking can contribute to loss of kidney function over time.”

According to the National Kidney Foundation, detecting chronic kidney disease early is essential for the best treatment. That’s when the disease can be stopped or slowed.

Early treatment options include management of risk factors such as diabetes and hypertension, as well as modifications to diet and lifestyle, exercise, and medications.

Kidney disease can cause a number of complications, such as bone disease, anemia, heart disease, high potassium, and, most commonly, gout.

“The buildup of blood urate levels can lead to crystals depositing in tissues in the body. These deposits can lead to gout, kidney stones, and other problems. Patients with symptoms from elevated blood urate levels should be treated with urate lowering medications. Although rare, kidney disease can occur from gout,” Klein said.

“As suggested by the results of the recent study, most patients do not need to be on allopurinol or drugs like it for kidney disease alone. Patients with symptoms from elevated blood urate levels are likely to benefit from these medications,” he added.

A possible change in strategy

The researchers of the trial say that elevated urate levels in the blood are likely to be indicative of reduction in kidney function, rather than a cause of reduced kidney function.

Given this, Rastogi says the findings of the study could result in a shift away from the view that lowering uric acid will, in turn, slow progression of kidney disease.

“The thought was that allopurinol, by inhibiting urate levels, slows down progression of kidney disease, as uric acid can be toxic to the kidneys. These trials indicate that might not be the case. Similar results were seen with another uric acid lowering drug, febuxostat,” he said.

“So the question is whether uric acid is still a viable target to slow down progression of kidney disease,” he added. “The [Australian] trials… have some limitations before we can finally call the hunt off completely.”

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  • Posted on June 30, 2020