**4. Discussion**

#### *4.1. Frequency and Severity of Potential Drug–Drug Interactions*

Table 8 shows previous reports in which the prevalence and severity of pDDIs has been evaluated on CKD patients. It is remarkable that there are two studies published in 2017 that were carried out in di fferent hospitals in Nigeria, with di fferent numbers of individuals, but their results are practically identical despite using di fferent analysis tools [17,18].


*Pharmaceutics* **2020**,

 *12*, 713


**Table 8.** Previous studies in which prevalence and severity of potential drug–drug interactions has been evaluated on CKD patients.

As mentioned, most of the pDDIs were Type C (moderate severity), and 12.5% were Type D (major severity) and Type X (avoid drug combination). These data are similar to those observed in a previous study in Palestinian patients [15]. Other studies highlighted di fferences in the frequency of pDDIs types (Table 8). Among other causes, the variability in the reported pDDIs could also be a consequence of using di fferent screening platforms to analyze potential drug interactions. In our case, we used Lexicomp ®, which classifies pDDIs in di fferent levels of severity. However, other software (Micromedex Drug-Reax, Medscape Drug interaction checker, etc.) for similar drug combinations perform dissimilar categorizations, or find di fferent pDDIs.

Even though the majority of pDDIs reported in this study were Type C, it is necessary to closely monitor patients in order to identify adverse events. Moreover, major severity drug interactions and avoided drug combinations present a high risk to the health of patients and, consequently, physicians or clinical pharmacists must analyze, detect, and early prevent pDDIs.

In the present study, the majority of the patients were in CKD stage 3, and only 4.5% of the total were in CKD stage 5 or hemodialysis. This result is comparable with another study from Brazil [10] in which patients in CKD stage 5 represented 6.6% of the total sample. However, in the remaining previous studies, most of the patients were in stage 5 or hemodialysis (Table 8). This could a ffect the number and type of prescribed treatment and, therefore, the pDDI. The present study did not only focus on patients on hemodialysis, but on all patients with CKD.

#### *4.2. Factors Associated with Potential Drug–Drug Interactions*

Regarding comorbid conditions, these appeared in 91 patients (81.2%), and the most frequent were hypertension (44.6%), dyslipidemia/hypercholesterolemia (28.6%), and diabetes mellitus (22.3%).

The prevalence of hypertension and diabetes in previous studies [10,13–15] were higher than those found in the present study. In addition, each country could have implemented di fferent clinical guidelines for similar disease conditions, which results in the prescription of di fferent drugs and thereby other pDDIs. The selected hospital is a reference hospital with a nephrology unit similar and representative of most hospitals in the country. The percentage of patients with chronic kidney disease is also similar to those other nephrology units in Spain.

In the present study, the mean age of patients was higher (77.1 ± 10.4 years) than in the rest of the studies, which reported mean age data from 38.3 ± 16.8 to 59.1 ± 14.7 years (Table 8). Polypharmacy prevalence increases with advancing age [23], and hence also pDDIs. Furthermore, people aged 80 and over are still much more likely to have DDIs [24]. Therefore, the main reasons for the di fferences found in the present study, comparing to most of the previous studies, could be the di fferent CKD stages, age, or the country of patients. These factors could a ffect the number and type of prescribed drug treatment and, therefore, the number and severity of pDDIs. On the other hand, the use of di fferent software to evaluate the pDDIs in the reported studies (Table 8) could lead to di fferences of the severity of pDDIs. Furthermore, many of the analyzed drugs that appear in Lexicomp ® do not appear in some other databases.

This could be one of the reasons for variability in the pattern of frequency and severity of pDDIs observed in the present study compared to previous studies.
