Twenty-Three-Year Trends in the Use of Potentially Nephrotoxic Drugs in Denmark

Abstract

Background

The occurrence of acute and chronic kidney diseases has been rising in the last decades. Although drug use is a common risk factor for impaired kidney function, changes in utilization of potential nephrotoxic drugs have received little attention.

Purpose

To describe temporal trends in the utilization of potentially nephrotoxic drugs in Denmark between 1999 and 2021.

Methods

Specific drugs known or suspected to be nephrotoxic were identified in the literature. Data on the sold defined daily doses (DDDs) of potentially nephrotoxic drugs between 1999 and 2021 were retrieved using the Danish Register of Medical Product Statistics. Trends in sales of DDDs per 1000 inhabitants per day were tabulated and illustrated graphically.

Results

From 1999 to 2021, the total sale of all selected drugs increased from 286 to 457 DDDs per 1000 inhabitants per day. The overall sale reached a preliminary peak in 2012 with 449 DDDs per 1000 inhabitants per day and remained relatively stable thereafter until reaching an all-time high in 2021 with 457 DDDs per 1000 inhabitants per day. Contributing with the majority in volume, sales of drugs inhibiting the renin-angiotensin-aldosterone system (RAAS) increased dramatically throughout the period. The same was observed for acetaminophen, methotrexate, tacrolimus, and iodinated contrast dye. In contrast, the sales of diuretics, acetylsalicylic acid, and ciclosporin decreased during the last decade of the study period.

Conclusion

From 1999–2021 considerable changes in sales of potentially nephrotoxic drugs were observed. In general, the sales increased, in volume predominated by RAAS inhibiting drugs. This increase in sales of potential nephrotoxins could contribute to an increasing occurrence of kidney diseases.

Keywords:

• adverse events
• nephrotoxins
• drug utilization
• acute kidney injury
• kidney disease

Abbreviations

ACE-I, Angiotensin converting enzyme inhibitor; AKI, Acute kidney injury; ARB, Angiotensin receptor blocker; ATC, Anatomical therapeutical chemical classification; CKD, Chronic kidney disease; COX-2, Cyclooxygenase-2; DDD, Defined daily dose; MTX, Methotrexate; NSAID, Non-steroid anti-inflammatory drug; RAAS, Renin-angiotensin-aldosterone system.

Data Sharing Statement

The data reported in this article are publicly available through the online database Medical Statistics.³⁰

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to disclose in this work.

Additional information

Funding

The study was funded by the Independent Research Fund Denmark (grant number: 0134-00407B).