Patient in the five long-term, randomized, controlled trials (RCTs) who received allopurinol experienced a small but significant improvement in their estimated glomerular filtration rates (eGFRs) compared with those who were on placebo or usual treatment. The researchers also identified trends toward reduction of blood pressure and proteinuria favoring allopurinol.
“These results raise some interesting questions,” lead author Tahir Kanji told Renal & Urology News at the Canadian Society of Nephrology’s 2013 annual meeting, where he and his co-investigators presented the results in poster form. “Are these drugs actually renoprotective or is the eGFR improvement due to alternative explanations such as hemodynamic mechanisms?”
Kanji, a medical student at McMaster University, Hamilton, Ontario, noted this is a “hot” area of research right now, and a large trial will be presented by Takeda researchers at Kidney Week 2013 meeting this November.
He conducted the systematic review with Mandark Gandhi, another medical student, under the supervision of nephrology professor Robert Yang, MD. They used Medline, Embase, Central and Web of Science to find RCTs published up to September 2012.
Twelve RCTs published in peer-reviewed journals fit their criteria of focusing on patients with stages 3-5 CKD and comparing a form of ULT to placebo, usual care, or another ULT. The most commonly used therapy in the treatment arms was allopurinol; benzbromarone, losartan, amlodipine, and rasburicase were also studied. The comparators were placebo, usual therapy, no treatment, and in some cases enalapril or tertatolol.
The team found a potential for bias in many of the studies. “This makes our results somewhat less reliable,” Kanji noted.
They used Forest plots to visually display the effects of ULT in the RCTs individually and collectively. The plot of eGFR revealed that ULT significantly enhanced eGFR, by 3.17 mL/min/1.73 m2. As expected, they found a significant reduction in serum uric acid favoring allopurinol.
“The implication of our research is that a larger RCT needs to be conducted,” Kanji said. “Our meta-analysis is suggestive of a possible pathogenic role of uric acid and benefits from uric-acid lowering, but more evidence is definitely needed.”