The burden of nephrotoxic drug prescriptions in patients with chronic kidney disease: a retrospective population-based study in Southern Italy

Ylenia Ingrasciotta, Janet Sultana, Francesco Giorgianni, Achille Patrizio Caputi, Vincenzo Arcoraci, Daniele Ugo Tari, Claudio Linguiti, Margherita Perrotta, Andrea Nucita, Fabio Pellegrini, Andrea Fontana, Lorenzo Cavagna, Domenico Santoro, Gianluca Trifirò, Ylenia Ingrasciotta, Janet Sultana, Francesco Giorgianni, Achille Patrizio Caputi, Vincenzo Arcoraci, Daniele Ugo Tari, Claudio Linguiti, Margherita Perrotta, Andrea Nucita, Fabio Pellegrini, Andrea Fontana, Lorenzo Cavagna, Domenico Santoro, Gianluca Trifirò

Abstract

Background: The use of nephrotoxic drugs can further worsening renal function in chronic kidney disease (CKD) patients. It is therefore imperative to explore prescribing practices that can negatively affect CKD patients.

Aim: To analyze the use of nephrotoxic drugs in CKD patients in a general population of Southern Italy during the years 2006-2011.

Methods: The general practice "Arianna" database contains data from 158,510 persons, registered with 123 general practitioners (GPs) of Caserta. CKD patients were identified searching: CKD-related ICD-9 CM codes among causes of hospitalization; CKD-relevant procedures undergone in hospital (e.g. dialysis); drug prescriptions issued for a CKD-related indication. A list of nephrotoxic drugs was compiled and validated by pharmacologists and nephrologists. The summary of product characteristics was used to classify drugs as 'contraindicated' or 'to be used with caution' in renal diseases. Frequency of nephrotoxic drug use, overall, by drug class and single compounds, by GPs within one year prior or after first CKD diagnosis and within one year after dialysis entry was calculated.

Results: Overall, 1,989 CKD patients and 112 dialysed patients were identified. Among CKD patients, 49.8% and 45.2% received at least one prescription for a contraindicated nephrotoxic drug within one year prior or after first CKD diagnosis, respectively. In detail, 1,119 CKD patients (56.3%) had at least one nonsteroidal anti-inflammatory drugs (NSAIDs) prescription between CKD diagnosis and end of follow-up. A large proportion of CKD patients (35.6%) were treated with NSAIDs for periods exceeding 90 days. Contraindicated nephrotoxic drugs were used commonly in CKD, with nimesulide (16.6%) and diclofenac (11.0%) being most frequently used.

Conclusions: Contraindicated nephrotoxic drugs were highly prescribed in CKD patients from a general population of Southern Italy. CKD diagnosis did not seem to reduce significantly the prescription of nephrotoxic drugs, which may increase the risk of preventable renal function deterioration.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow chart of CKD patients…
Figure 1. Flow chart of CKD patients included in the study.
Figure 2. Proportion of incident CKD patients…
Figure 2. Proportion of incident CKD patients (N = 1,989) who received at least one prescription of nephrotoxic drug.
Proportion of incident CKD patients (N = 1,989) who received at least one prescription of nephrotoxic drug within one year prior or after first CKD diagnosis, and within one year after dialysis entry (N = 112).
Figure 3. Crude and Cluster-adjusted analysis of…
Figure 3. Crude and Cluster-adjusted analysis of CKD patients’ CND prescription by GP.
Distribution (%) of CKD patients who received at least one prescription of contraindicated nephrotoxic drugs (CND) within the year prior (A) and after (B) first CKD diagnosis, clustered by GP. The distribution was clustered by GP and the was adjusted also by sex and age. CND: contraindicated nephrotoxic drug.
Figure 4. Proportion of CKD patients (N…
Figure 4. Proportion of CKD patients (N = 1,989) who received ≥ 1 prescription of CND, stratified by classes.
Proportion of CKD patients (N = 1,989) who received at least one prescription of contraindicated nephrotoxic drugs, stratified by drug classes, within one year prior or after first CKD diagnosis, and within one year after the entry in dialysis (N = 112) within one year prior or after first CKD diagnosis, and within one year after the entry in dialysis (N = 112). Others: zoledronate, lithium, antineoplastic agents (methotrexate, interferon alfa-2B), gold preparations (auranofin), hydrochlorothiazide. Low dosage acetylsalicylic acid was not included among NSAIDs, but it was analysed in Figure 5, separately. CND: contraindicated nephrotoxic drug.
Figure 5. Proportion of CKD patients (N…
Figure 5. Proportion of CKD patients (N = 1,989) who received ≥ 1 prescription of NSAIDs.
Proportion of CKD patients (N = 1,989) who received at least one prescription of individual NSAIDs within one year prior or after the first CKD diagnosis and within one year after the entry in dialysis (N = 112). Others (

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