Our analysis of a dataset from the population-based NHIRD revealed a positive association between the duration of polypharmacy and the occurrence of ARF. Even after controlling for other factors, a longer duration of polypharmacy was associated with a higher risk of ARF.
The adoption of managed care systems by more countries has made research focusing on polypharmacy [17
], especially duration of polypharmacy, more difficult to perform. Usually the medications prescribed to enrollees in managed care programs are highly controlled, whereas non-prescription medications are not. The lack of information about non-prescription medications makes it very difficult to trace polypharmacy under managed care environments. The actual occurrence of polypharmacy may be higher than that reported, since many people do not inform their doctors about taking non-prescription drugs regularly. This situation, however, is rare in Taiwan, because the NHI pays for most drugs for acute and chronic diseases, and enrollees seldom spend their own money to buy nonprescription drugs regularly. It has made it easier to assess polypharmacy in Taiwan than in other countries. Moreover, since we defined polypharmacy as the concomitant use of more than five medications and we assessed the cumulative days of polypharmacy, we were better able to assess the duration of polypharmacy and the association of duration with ARF (or adverse drug events leading to ARF) than previous studies, which assessed only the correlation between polypharmacy and ARF [1
]. Indeed, we found that patients with a longer duration of polypharmacy were at higher risk for ARF hospitalization, consistent with previous findings reporting that excessive medication intake can cause renal damage and ARF [32
]. Although we did not observe any significant differences between our case and control groups in the reasons for medication, we found that the average duration of polypharmacy was longer in the case than in the control group (191
days vs. 146
days). Therefore, the main cause of ARF may not be the medication itself, but rather the cumulative effects of polypharmacy. After controlling for confounding factors, including comorbidities, stay in the ICU during ARF hospitalization or site of operation within one month prior to ARF hospitalization, we still found that the risk of ARF was associated with duration of polypharmacy.
Consistent with previous reports, we found that polypharmacy was more likely to occur in elderly people [3
]. The cumulative duration of polypharmacy in elderly people was likely higher because many of these individuals may take more than 5 medications per day due to multiple chronic diseases, including gastrointestinal bleeding, diabetes, chronic obstructive pulmonary disease and atherosclerotic heart disease. The optimal strategy to prevent ARF in elderly people may be to encourage doctors to avoid prescribing multiple medications or medications with renal toxicity to elderly people, or to prescribe medications at minimal doses [35
]. This, however, may become more unrealistic since the elderly population in many countries is growing rapidly. Therefore, more research is necessary to reduce inappropriate medications in elderly patients requiring long duration of polypharmacy.
We also found that comorbidities, ICU stay during hospitalization for ARF and site of operation within one month prior to ARF hospitalization were associated with higher risks of ARF, findings consistent with previous reports [36
]. Our finding, however, that dysrhythmia was not associated with a risk of ARF, differed from those showing associations between cardiac diseases and ARF [38
]. Our result may have been because of the inclusion of too many cardiac comorbidities in our logistic regression analysis. Although the number of days taking NSAID or Triamterene drugs was found significantly different between two groups, it was not selected in stepwise logistic regression model. It was probably because the number of days taking NSAID or triamterene drug was highly correlated with the duration of polyphamacy.
This study had two main limitations. First, we relied on medication claims in the NHIRD database to define polypharmacy. In reality, some patients may have purchased or taken medications on their own, thus underestimating the actual occurrence and duration of polypharmacy. However, due to the high accessibility of Taiwan’s universal health insurance and the wide coverage for medications, few people would purchase medications on their own. Therefore, the influence of this underestimation on our results were likely minimal. Second, this study was limited by the use of this database, in that our case group included patients without a history of ARF for the previous three years, minimizing the effects of previous ARF on current ARF.