**1. Introduction**

As specified by the Kidney Disease Improving Global Outcomes (NKF KDIGO) guidelines [1], chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for more than three months, with implications for health. CKD is a general term for various heterogeneous disorders a ffecting kidney structure and function with variable clinical presentations; in part, related to the cause, severity, and rate of progression. The glomerular filtration rate (GFR) is generally accepted as the best overall index of kidney function, and is classified into di fferent stages (G1, G2, G3a, G3b, G4, and G5). The diagnostic criteria of CKD are those denominated as kidney damage markers or a threshold of GFR < 60 mL/min/1.73 m<sup>2</sup> (GFR categories G3a–G5), or both, for more than three months.

CKD is a major health problem worldwide; in 2017, 1.2 million people died from CKD. Furthermore, between 1990 and 2017, the global all-age mortality rate from CKD increased by 41.5% [2]. In Spain, CKD is present in 15.1% of individuals and this prevalence is more than three times higher in men than in women (23.1% vs. 7.3%) and increases with age [3]. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries and in many low-income countries [4]. Among other reasons, the prevalence of CKD is increasing worldwide due to the fact that the prevalence of both hypertension and diabetes is also rising. Diabetes is expected to increase by 69% in high-income countries and 20% in low-income and middle-income countries from 2010 to 2030 [5]. Regarding hypertension, it is predicted to increase by 60% from 2000 to 2025 [6]. Additionally, CKD is also associated with other comorbidities such as dyslipidemia, hyperuricemia, or cardiovascular disease [7], and patients need to be prescribed multiple medications.

Polypharmacy is usually defined as the concomitant prescription of five or more medications [8] and it is a major risk factor of drug–drug interactions, which increases with the number of prescribed drugs leading to 100% with eight or more medications [9]. The elderly are at risk for polypharmacy, and this fact increases the risk of adverse drug reactions (ADRs) from 13 to 58% with two and five medications, respectively. Seven or more medications increase the risk of ADRs to 82% [9].

Previous studies have evaluated the prevalence and severity of potential drug–drug interactions (pDDIs) using di fferent drug–drug interaction programs among CKD patients from Brazil [10,11], India [12,13], Pakistan [14], Palestine [15], and Nigeria [16–19]; however, there are no published studies evaluating the prevalence of pDDIs among CKD patients in any European country.

Lexicomp ® (Wolters Kluwer Clinical Drug Information) is considered one of the best performing drug–drug interaction programs and it was reported to be highly sensitive and specific (around 90–100%). It focuses on the depth and duplication of information and it is a resource of choices for locating the mechanism of a drug–drug interaction [20–22].

This study was aimed to determine the prevalence, pattern, and factors associated with potential drug–drug interaction among CKD patients attending a hospital nephrology department using the drug interaction program Lexicomp ®.

#### **2. Materials and Methods**
