Prevention of nephrolithiasis: Holes in the evidence

Istanbul, Turkey-While clinicians have been combating kidney stones for centuries, their  knowledge about the best ways to prevent nephrolithiasis recurrence remains limited, a new review of existing research reveals.

“Much work remains to be done,” said co-author Manoj Monga, MD, director of the Stevan B. Streem Center for Endourology & Stone Disease at Cleveland Clinic’s Glickman Urological & Kidney Institute.

There’s only low-strength evidence, for example, to support the old standby advice of advising patients to drink more fluid. There’s higher quality evidence, however, to support the use of thiazide diuretics, citrates, and allopurinol (Zyloprim) for patients with calcium stones.

Dr. Monga and his co-authors reached their conclusions after examining 28 English-language studies regarding the benefits and harms of dietary and pharmacologic interventions to prevent recurrences of kidney stones. They presented their findings at the 2012 World Congress of Endourology and SWL in Istanbul, Turkey.

The low-strength evidence in favor of increased liquid intake suggested it reduced the risk of recurrence by 55% compared to no treatment (relative risk=0.45 [95% confidence interval=0.24–0.84]). And the low-strength evidence in favor of reduced soft-drink intake in men who consume a lot suggested a reduced risk of 17% (RR=0.83 [CI=0.71–0.98]).

“While patients should understand that up to 80% of their stone risk may be related to their genetic predisposition, diet may be an effective means of ameliorating this risk, and should not be thrown out the window yet,” Dr. Monga told Urology Times.

For now, though, “What is needed first is a standardization of a definition of success for stone prevention: At what time point should it be measured, and how should it be defined-clinical recurrence versus radiographic recurrence,” Dr. Monga said. “Are 24-hour urine parameters a good surrogate measure for success? For example, does a decrease in urinary calcium after 1 year of treatment translate into a lower clinical stone recurrence rate after 5 years of follow-up?”

Thiazides, citrates appear efficacious

In patients with recurrent calcium stones, most of whom drank more liquid as a co-intervention, the authors found moderate-strength evidence that thiazides, citrates, and allopurinol reduced the risk of recurrence by 47% (RR=0.53 [CI=0.41–0.68]), 74% (RR=0.26 [CI=0.14–0.48]), and 41% (RR=0.59 [CI=0.42–0.84]), respectively.

“Thiazides and citrates are effective means of decreasing the risk of stone recurrence,” Dr. Monga said. “Who should get these medications deserves further study. This effect was obtained by treating patients empirically. We need to determine if there is value to tailoring treatment based on 24-hour urine parameters or if it is better to use this empiric approach.”

The evidence supporting other approaches, both dietary and medical, was poor. So was reporting of adverse events.

As for other issues, Dr. Monga said, “To date, no randomized controlled trials have evaluated the impact of stone prevention measures on the recurrence of uric acid stones, despite the common utilization of allopurinol and urine alkalization to achieve this goal. This should be a priority.”

The study was funded by the Agency for Healthcare Research and Quality. Dr. Monga is a speaker for Mission Pharmacal.