London, ON - Residents of Walkerton, ON, who developed acute bacterial gastroenteritis from drinking contaminated water five years ago are more likely to have newly diagnosed hypertension and reduced renal function now than those who were not affected at the time of the outbreak.
"We observed a relative increase of 33%, or an absolute increase of 9%, in the rate of newly diagnosed hypertension among participants who had experienced severe gastroenteritis during the outbreak," Walkerton Health Study investigators report. Increased rates of hypertension after bacterial gastroenteritis were also accompanied by evidence of reduced kidney function.
This is the first time that acute bacterial gastroenteritis from toxogenic Escherichia coli has been associated with an increased risk of long-term hypertension and renal impairment. "I think we need to see these findings replicated first," lead author Dr Amit X Garg (University of Western Ontario, London) told heart wire . "But clearly, they do suggest that there may be a role here for following people who develop these kinds of infections and to screen them for reduced kidney function."
The study was published May 27, 2005 online in the Canadian Medical Association Journal.
Previously healthy adults
In May 2000, more than 2300 individuals developed acute gastroenteritis due to contamination of the regional drinking water supply in Walkerton with E coli 0157:H7 and Campylobacter species. Among these, there were 27 episodes of hemolytic uremic syndrome (HUS) and six deaths. A review of the literature undertaken by these investigators suggested that approximately 25% of patients who experience HUS go on to develop hypertension, reduced kidney function, and proteinuria.
"That's the extreme example," Garg noted, "but that was the rationale for wanting to look at people who developed [only] acute gastroenteritis [during the outbreak] . . . to see if it, too, might be associated with hypertension and reduced kidney function."
The Walkerton Health Study investigators followed the long-term risk of developing hypertension and reduced kidney function among 1958 previously healthy adults following the outbreak. "Of the participants, 675 had been asymptomatic during the outbreak, 909 had had moderate symptoms of acute self-limited gastroenteritis, and 374 had had severe symptoms that necessitated medical attention," the authors write. Each participant visited a clinic two, three, and four years after the initial outbreak, where they underwent a physical examination, completed a standardized questionnaire, and provided blood and urine specimens. The primary end point of the study was newly diagnosed hypertension (140/90 mm Hg), while secondary outcomes included the presence of reduced kidney function, microalbuminuria, or macroalbuminuria.
At a mean follow-up of 3.7 years, 27% of participants who remained asymptomatic during the outbreak had been diagnosed with hypertension. Among those who developed moderate gastroenteritis during the outbreak, 32.3% developed hypertension, as did 35.9% of those who had severe gastroenteritis (trend p=0.009). "Those who had had acute gastroenteritis had systolic and diastolic blood pressures that were 2 to 4 mm Hg higher than the measurements of participants who had remained asymptomatic during the outbreak," investigators add.
Adjusted risk for new hypertension at follow-up in those with and without acute gastroenteritis
| Group | Hazard ratio | 95% CI |
| Asymptomatic during outbreak | Ref | - |
| Moderate gastroenteritis | 1.15 | 0.97-1.35 |
| Severe gastroenteritis | 1.28 | 1.04-1.56 |
None of the previously healthy participants developed end-stage renal failure by study end. However, 6.9% of participants who developed severe gastroenteritis during the outbreak had a glomerular filtration rate (GFR) below 60 mL/min per 1.73 m at follow-up, compared with 3.9% of those with moderate gastroenteritis and 2.2% of those who remained asymptomatic.
Potential explanations
There are several potential explanations for how an episode of acute bacterial gastroenteritis from toxogenic E coli might precipitate hypertension and renal impairment. First, in the setting of acute infection, "you can develop enough of a toxin load that you can get some silent kidney impairment," Garg told heartwire . With some nephron loss, remaining nephrons must work "overtime" to make up for those that were lost. "Over time, this can lead to hypertension and reduced kidney function," he added.
Alternatively, bacterial infections can lead to a state of chronic inflammation, and this may also reduce kidney function. The situation in Walkerton also precipitated considerable psychosocial stress during and even after the outbreak. "We know that psychosocial stress is associated with hypertension, so those most severely affected may have been under severe psychosocial stress as well," Garg said.
Garg did not feel that additional screening for hypertension is called for in patients who develop acute bacterial gastroenteritis, "as people should have their blood pressure monitored every year anyway." But screening for reduced kidney functionnot normally recommendedmight be considered for patients who develop infections similar to those experienced by Walkerton residents.
"More important, maintaining safe drinking water remains essential to human health, as transient bacterial contaminations may have implications well beyond a period of acute self-limited illness," investigators add.