Medication reconciliation (MR) is defined as the systematic process of comparing a current medication regimen of a patient with prescribed orders to ensure consistency (1,2). Through MR, clinical pharmacists can identify actual or potential drug-related problems (DRPs), supervise and intervene in the medication-taking behaviors of patients, and promptly negotiate and adjust therapeutic plans with the multidisciplinary team to safeguard the safety and efficacy of pharmacotherapy. Over the years, the incidence of DRPs has been gradually increasing among various diseases and populations, leading to adverse effects on the therapeutic outcomes of diseases and individual health. For example, Venugopal et al (3) conducted a systematic analysis of 11 prospective studies and six retrospective studies, and revealed that the incidence of DRPs in patients with cancer ranged from 9.6-92.8%. Lau et al (4) performed a meta-analysis of the incidence of DRPs in patients with dementia by collecting data from six public datasets, and the results indicated that the incidence of DRPs in patients with dementia was 19%. In another study targeting home-dwelling patients, it was revealed that the average number of DRPs per individual could reach 4.16(5). Regarding pediatric patients, Rashed et al (6) conducted a statistical analysis of DRPs in children from the Hong Kong region and found that the incidence of DRPs in pediatric patients was 21%, which was higher than that in adult patients overall (6,7). Clinical pharmacists, as patient-centered pharmaceutical care professionals, are responsible for identifying, analyzing and resolving DRPs (8-10). Since the 1990s, pharmacists have employed classification systems to achieve comprehensive and standardized qualitative management of DRPs. At present, no universally accepted classification system exists, but the most widely used schemes are the Pharmaceutical Care Network Europe (PCNE) taxonomy (11) and the Strand classification system (12). Research on DRPs in China is still in its infancy. Nevertheless, in 2022, the Shanghai Hospital Association released the first national classification system, the Chinese Drug-Related Problem Classification System (version 1.0) (13). However, previous domestic studies have predominantly focused on adult populations and have largely adopted foreign DRP classification systems (14-18). Investigations specifically addressing pediatric patients remain limited.

The prevalence of chronic kidney disease (CKD) in children globally is estimated to range from 14.9-118.8 per million (19). Epidemiological research on CKD in China is still developing; however, given the large population base and the uneven distribution of medical resources across different regions in China, CKD is characterized by high prevalence, high mortality rates and low levels of awareness among the general population (20). In addition, patients with early-stage CKD often exhibit no notable clinical symptoms, which renders them prone to being overlooked or misdiagnosed during medical visits. This is particularly true for pediatric patients, who are more likely to experience the occurrence of DRPs (21). Ibrahim et al (22) reported that, in pediatric nephrology units, the incidence of DRPs among children with CKD is substantial and markedly higher in inpatients than in outpatients (51.2 vs. 32.0%, respectively). The treatment of pediatric CKD is a prolonged, continuous process; complete recovery during hospitalization is rare, necessitating sustained post-discharge therapy (23,24). Following discharge, the absence of a supervised environment often leads to declining adherence over time. Moreover, omissions or administration errors are common since young patients mainly depend on caregivers for medication administration, further predisposing them to DRPs. Additionally, patients referred from external hospitals may have incomplete medication histories, resulting in DRPs, such as therapeutic duplication or drug-drug interactions (25,26). For pediatric patients with CKD, the occurrence of DRPs can have adverse effects on their prognosis and quality of life, such as disease progression, a decreased quality of life, increased hospitalization rates, prolonged periods of hospitalization and increased treatment costs (27-32). Therefore, there is an urgent need to conduct research on DRPs in pediatric patients with CKD, to identify common types and causes of DRPs, and to provide references for the treatment and management of CKD. At present, to the best of our knowledge, no studies have systematically investigated DRPs in Chinese children with CKD.

The present study prospectively collected clinical data on pediatric patients with CKD from the Guiyang Maternal and Child Health Care Hospital (Guiyang, China) to determine the incidence of DRPs in this population and to characterize their types and underlying causes. Furthermore, the impact of clinical-pharmacist interventions on DRPs was evaluated to inform the development of evidence-based pharmaceutical care models for chronic disease management in children.

Pediatric patients often have difficulty adhering accurately to prescribed regimens due to limited swallowing capacity and under-developed autonomy; consequently, medication administration typically depends on a caregiver. In a previous study, Zhang et al (33) applied the PCNE taxonomy to 914 patients with CKD and reported that ‘Treatment safety’ was the predominant DRP domain, followed by ‘Treatment effectiveness’. This hierarchy diverges from the findings of the present study and is probably attributable to the distinct demographic profile of their study cohort. In the present study, MR identified DRPs that were predominantly attributable to drug selection, patient-related factors and dose selection; specifically, 66 DRPs arose from untreated or incompletely treated indications, 23 from sub-optimal dosing frequency and 21 from under-dosing or non-administration of prescribed doses. In a previous study, Zafar et al (34), employing the PCNE framework in patients from Pakistan with CKD, identified ‘inappropriate drug selection’ as the most common root cause of DRPs; an identical pattern was also reported in a separate cohort that consisted of 269 pre-dialysis patients recruited from the nephrology ward of Ibni Sina Hospital, Ankara University School of Medicine (Ankara, Turkey) between October 2019 and March 2020(35). These findings suggest that lapses in caregiver or self-supervision serve a key role; compared with adults, children exhibit a poorer comprehension of medication use and, in the event that the caregiver lacks adequate medication literacy or no consistent caregiver is available, safety and effectiveness cannot be assured (36,37).

Patients with chronic diseases are frequently re-hospitalized and among the 383 children enrolled in the present study, 292 were repeat patients, of which 136 experienced DRPs; conversely, no DRPs were observed in first-time patients. Additionally, the ‘hospital readmission’ variable displayed a significant association with the occurrence of DRPs, indicating that repeated admissions may introduce gaps in medication histories, particularly in pediatric patients, leading to incomplete information at admission and subsequent DRPs. Moreover, patients who experienced DRPs were significantly older, had more comorbidities and were exposed to more concomitant medications. By contrast, the duration of hospitalization and CKD stage did not exert significant effects on the risks of developing DRPs. Unexpectedly, a non-significant trend toward a higher DRP rate was observed among children with a shorter duration of hospitalization. Pehlivanli et al (35) reported that DRPs were associated with a prolonged duration of hospitalization, which may reflect age-specific care dynamics: Extended periods of hospitalization in pediatric units may facilitate intensive pharmaceutical stewardship, thereby attenuating the occurrence of DRPs. Nevertheless, the absence of a statistically significant duration of hospitalization between groups in the present study may stem from limited statistical power; the multi-center enlargement of the cohort is warranted to clarify the true association between the duration of hospitalization and DRPs in children with CKD. Notably, patients with CKD in the early stages (particularly stage 1) face disproportionate medication-management challenges. The present study hypothesized that these patients often perceive their illness as trivial, resulting in an inadequate appreciation of treatment complexity and the critical importance of adherence. Frequent therapeutic adjustments, repeated admissions and inter-facility transfer further magnify the probability of prescribing errors, duplication or omissions. Thus, clinical pharmacists could compare physician orders with patient-reported use, perform MR, identify potential issues, rationalize dosing schedules, revise medication lists, and thereby mitigate medication-related risks and enhance the safety of patients with CKD.

In 2022, the Shanghai Hospital Association and the Shanghai Pharmaceutical Association released the Chinese Drug-Related Problem Classification System (version 1.0). Compared with the PCNE taxonomy, this system adds a ‘DRP evaluation’ domain requiring explicit coding of ‘E1 primary subject’ and ‘E2 DRP severity’ and introduces ‘C7 information systems and devices’ under causes, while adjusting several other items; however, its target population is adults. As the cohort in the present study comprised children, certain categories in the Chinese system were not applicable. During the pilot phase of the present project, the original PCNE classification system was first applied to 100 pediatric in-patients and it was revealed that several root causes of DRPs could not be adequately coded. On the basis of these preliminary data, a revised version of the PCNE system was developed that could provide exhaustive categories for the present study population. Accordingly, in the present study, the PCNE (v9.1) was adapted to reflect local pediatric practice, focusing on the causal domain and adding 10 new codes. Multicenter validation of the modified PCNE system is nevertheless required in future work to confirm its reliability and generalizability for detecting DRP causes in Chinese children.

During the present MR study, several deficiencies and misconceptions among medication caregivers were identified. Typical examples included the following: i) the omission or incorrect administration of drugs due to polypharmacy and the absence of a dedicated caregiver (such as a patient prescribed nine concurrent medications failed to take hydroxychloroquine and mycophenolate mofetil); ii) the substitution of prescribed therapy with nutraceuticals of uncertain composition (for example, caregivers purchased unlabeled calcium supplements instead of the prescribed calcium preparation, resulting in persistent hypocalcemia); iii) dose discrepancies arising from transitions of care (such as an outpatient instruction to taper prednisone according to weekly urinalysis was misinterpreted; thus, the dose on readmission differed from the intended regimen); iv) the intentional omission of chronic therapy at admission (for example, enalapril was withheld without justification); v) the administration of doses exceeding the manufacturer's labeled maximum; and vi) the continuation of therapy after the indication had resolved. Consequently, clinical pharmacists could use the study-specific, pediatric-adapted PCNE (v9.1) to rapidly classify DRPs and their causes, and to design targeted interventions, such as regimen simplification, caregiver education, written action plans and psychological support, which could enhance both the efficacy and the safety of pharmacotherapy.

The present MR initiative successfully identified and addressed DRPs in children with CKD, providing a replicable model for pediatric chronic disease management. Nevertheless, several limitations should be acknowledged. First, the modifications to the PCNE v9.1 were derived solely from a single-center cohort, and external validity across institutions and pediatric chronic conditions remains to be established through multicenter studies. Second, long-term outcomes, particularly sustained adherence and disease control, were not evaluated. Future research is thus warranted to expand the research to diverse geographic regions and hospital tiers to enhance generalizability and incorporate prospective follow-up to assess the impact of pharmaceutical care on long-term prognosis, including disease progression and quality of life.

In conclusion, the implementation of comprehensive pharmaceutical care throughout the continuum of chronic disease management represents an inevitable trajectory for the advancement of pharmacy practice. The present study explored a MR model tailored to pediatric patients with CKD and further refined the PCNE v9.1 taxonomy to enable more accurate classification of DRPs in this population. These enhancements facilitate the development of individualized interventions.