Oral purgatives linked with acute kidney injury.

SAN FRANCISCO -- Acute kidney injury may not be as rare a consequence of oral sodium phosphate bowel purgatives as previously thought, researchers said at the annual meeting of the American Society of Nephrology.

In a retrospective study of nearly 10,000 patients, those given oral sodium phosphate purgatives prior to colonoscopy had 2.35 times the chance of developing acute kidney injury as did those given polyethylene glycol purgatives. This result was obtained after adjustment for many potential confounders, and was based on a definition of acute kidney injury as a 50% increase in serum creatinine, said Col. Frank P. Hearst, MC, USA, and his colleagues at the Walter Reed Army Medical Center, Washington.

The study involved 6,432 patients who received oral sodium phosphate and 3,367 who received polyethylene glycol as outpatients prior to colonoscopy. All patients were at least 50 years old, and all had serum creatinine measurements within 365 days before and after the procedure date. The investigators noted in their poster presentation that they excluded patients who used purgatives for reasons other than screening colonoscopy, as well as those who had end-stage renal disease.

The unadjusted absolute risk of acute kidney injury was 1.31% with oral sodium phosphate and 0.92% with polyethylene glycol, for a 0.39% increase in absolute risk. After adjustment for confounders, the relative risk associated with oral sodium phosphate was 2.35. One case of acute kidney injury would be expected to occur for every 81 patients given oral sodium phosphate instead of polyethylene glycol.

With use of a more stringent criterion for acute kidney injury--a doubling in the serum creatinine level--the adjusted relative risk associated with oral sodium phosphate purgatives was 3.81, and the number needed to harm was 288.

Other factors emerged in the multivariate analysis as being independently associated with acute kidney injury: heart failure (relative risk 2.03), contrast exposure (relative risk 1.70), and age (relative risk 1.06 per year). The use of oral sodium phosphate purgatives was thus accompanied by a greater risk of acute kidney injury than were these other risk factors.

Patients who developed acute kidney injury typically did not return to baseline levels of renal function. Their mean preprocedure creatinine level was 0.98 mg/dL. This rose to a mean of 1.78 mg/dL after the procedure. An average of 280 days later, the mean values had declined to 1.38 mg/dL.

In a separate talk, Dr. Glen S. Markowitz of Columbia University, New York, described his earlier study of acute phosphate nephropathy. The pathophysiology appears to involve obstructive calcium phosphate crystalluria and intratubular nephrocalcinosis. Of 7,349 nontransplant renal biopsies, 31 revealed nephrocalcinosis; at least 21 of those were associated with the use of oral sodium phosphate purgatives.

Patients with nephrocalcinosis had a mean baseline serum creatinine of 1.0 mg/dL, which had increased to 3.9 mg/dL at presentation. After a mean follow-up of 17 months, 4 of the 21 patients developed end-stage renal disease. Of the remaining 17 patients, 16 had a decline in serum creatinine to a mean of 2.4 mg/dL, and 4 of the 17 reached 2.0 mg/dL, but none returned to baseline levels.

In response to this report and others, the Food and Drug Administration in May 2006 issued a warning on acute phosphate nephropathy associated with oral sodium phosphate purgatives, stating that individuals at increased risk include those with advanced age and decreased intravascular volume, and people taking certain medications including ACE inhibitors, angiotensin II receptor blockers, and possibly NSAIDs.

Dr. Markowitz said that other probable risk factors are inadequate hydration, excess phosphate dosing, a short interval between oral sodium phosphate doses, and fasting prior to the procedure to decrease the risk of aspiration during sedation. Other possible risk factors are female gender and small body habitus.

Several professional societies--including the American Society of Colon and Rectal Surgeons--have added such warnings to their consensus documents on bowel preparation.

This increased awareness will likely lead to a decline in acute phosphate nephropathy, Dr. Markowitz said. Clinicians will be more careful in selecting purgatives for each patient. Several manufacturers of bowel preparations have decreased their phosphate content by 16%-20%. Also, clinicians are increasingly recommending better hydration, to provide at least 72 ounces before, during, and after the use of oral sodium phosphate purgatives.

BY ROBERT FINN

San Francisco Bureau