Slowing progression of chronic kidney disease – time to reconsider treatment choice?
Associate Professor Sunil Badve, staff specialist nephrologist at St George Hospital is also Conjoint Associate Professor at UNSW Medicine and Senior Research Fellow at The George Institute for Global Health.
His research interests are interventions to slow the progression of chronic kidney disease, treatment of cardiovascular diseases and anticoagulation treatment in patients with chronic kidney disease.
He co-led a landmark CKD-FIX Study, looking at a commonly used treatment for CKD progression has just been published in the New England Journal of Medicine. We asked him to tell us a bit more about this important study.
How big a problem is chronic kidney disease?
As many as 1.7 million Australians have chronic kidney disease (CKD) and each year around 3,000 progress to end-stage kidney disease requiring dialysis or kidney transplantation. More than 13,000 Australians are currently receiving dialysis and over 12,000 Australians are living with a kidney transplant.
What are the causes of chronic kidney disease and how it is treated?
The most common causes of kidney disease are diabetes and high blood pressure. Treatments currently used to prevent worsening of or slowing the progression of CKD are limited to certain types of blood pressure-lowering and glucose-lowering medications. These are, however, only partially effective and many patients continue to experience further worsening of kidney disease to the point that they need dialysis or kidney transplantation. Researchers are constantly looking for new effective treatments to help people with chronic kidney disease.
What was the purpose of the CKD-FIX Study?
Research studies show that elevated blood levels of uric acid (also known as urate) are associated with worsening of kidney disease. But it is not known whether lowering blood urate levels slows CKD progression. We wanted to find out whether urate-lowering therapy with allopurinol reduced the decline in kidney function.
What is uric acid?
Uric acid is a waste product created during the normal breakdown of purines, which are substances normally produced in the body and also found in some foods. Most urate dissolves in the blood and is eliminated in the urine, but blood levels rise when kidneys don't eliminate it efficiently - as many as three quarters of people with CKD have elevated blood urate levels. A medication called allopurinol is commonly given to lower blood urate levels.
How was the CKD-FIX Study conducted?
Allopurinol was originally developed to treat gout, but for nearly 20 years, doctors have also used it to slow the progression of chronic kidney disease. But whether lowering blood urate levels slows CKD progression is not yet known.
We conducted a two-year trial – the CKD-FIX Study - across 31 hospitals in Australia and New Zealand involving 369 patients with chronic kidney disease at increased risk of further progression. These patients were randomly assigned to receive allopurinol or placebo (identical looking dummy tablets).
What did your research find?
Treatment with allopurinol reduced blood urate levels by 35 percent and this was maintained throughout the study period. However, we found that kidney function declined at a similar rate in patients receiving allopurinol and those receiving placebo. The results suggest the widely held view that high blood urate levels were responsible for a rapid decline in kidney function was probably wrong.
What does this mean for people with chronic kidney disease?
Our findings have major implications – one in five people with chronic kidney disease are on medication like allopurinol to lower blood urate levels. Now we know that they are likely taking medication that is of no benefit to them, unless they have other conditions that allopurinol is effective against, like gout.
Allopurinol can also have side effects, like severe allergic reactions and skin rashes. But it is important that people taking allopurinol to lower blood urate levels do not abruptly stop treatment – they should first discuss this with their doctor.
What are the clinical implications of this study?
The CKD-FIX Study has helped settle the two decade-long question of whether urate-lowering treatment prevents further progression of chronic kidney disease. Our results do not appear to support the view that high blood urate levels lead to progression of chronic kidney disease. Evidence from observational studies shows only an association between urate levels and progression of chronic kidney disease, not a cause-and-effect relationship. Urate-lowering treatment in patients with chronic kidney disease should be reserved only for specific clinical indications, such as gout.
The CKD-FIX study was sponsored by The University of Queensland and coordinated by the Australasian Kidney Trials Network. Professor David Johnson, Queensland Kidney Transplant Service Medical Director was the Chair of the Trial Steering Committee and in New Zealand, the trial was led by Dr Janak de Zoysa from the University of Auckland and Waitemata District Health Board.