Acute kidney injury and infections in patients taking antihypertensive drugs: a self-controlled case series analysis

Abstract

Background: The relative risk of acute kidney injury (AKI) following different infections, and whether angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) modify the risk, is unclear. We aimed to determine the risks of hospital admission with AKI following infections (urinary tract infection [UTI], lower respiratory tract infection [LRTI], and gastroenteritis) among users of antihypertensive drugs.

Methods: We used UK electronic health records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database. We identified adults initiating ACEIs/ARBs or alternative antihypertensive therapy (β-blockers, calcium channel blockers, or thiazide diuretics) between April 1997 and March 2014 with at least 1 year of primary care registration prior to first prescription, who had a hospital admission for AKI, and who had a primary care record for incident UTI, LRTI, or gastroenteritis. We used a self-controlled case series design to calculate age-adjusted incidence rate ratios (IRRs) for AKI during risk periods following acute infection relative to noninfected periods (baseline).

Results: We identified 10,219 eligible new users of ACEIs/ARBs or other antihypertensives with an AKI record. Among these, 2,012 had at least one record for a UTI during follow-up, 2,831 had a record for LRTI, and 651 had a record for gastroenteritis. AKI risk was higher following infection than in baseline noninfectious periods. The rate ratio was highest following gastroenteritis: for the period 1-7 days postinfection, the IRR for AKI following gastroenteritis was 43.4 (95% CI=34.0-55.5), compared with 6.0 following LRTI (95% CI=5.0-7.3), and 9.3 following UTI (95% CI=7.8-11.2). Increased risks were similar for different antihypertensives.

Conclusion: Acute infections are associated with substantially increased transient AKI risk among antihypertensive users, with the highest risk after gastroenteritis. The increase in relative risk is not greater among users of ACEIs/ARBs compared with users of other antihypertensives.

Keywords: acute kidney injury; angiotensin receptor antagonists; angiotensin-converting enzyme inhibitors; infection; self-controlled case series.

Figure 1

Graphical representation of self-controlled case series study design. Notes: Figure illustrates a single individual with an acute infection (UTI, LRTI, or gastroenteritis) during their observation period. All participants included in the analyses had at least one acute infection and at least one episode of AKI requiring hospital admission (analyses used first episode of AKI as the outcome and ignored subsequent AKI records). Rate ratios presented are pooled estimates derived from the rate of AKI events during risk (exposed) periods divided by the rate of events during baseline periods; age is adjusted for at all stages of analysis. Incident AKI can occur during any one of six exposure periods: baseline, 7 days prior to infection, day of infection, 1–7 days postinfection, 8–14 days postinfection, or 15–28 days postinfection. *Follow-up ends at the earliest of death, the end of registration, last collection date from GP, or 30/60/90 days after the end of first break in ACEI/ARB or CCB treatment of 30/60/90 days or more. Abbreviations: ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; AKI, acute kidney injury; CCB, calcium channel blocker; GP, general practitioner; LRTI, lower respiratory tract infection; UTI, urinary tract infection.

Figure 2

Identification of study participants. Note: UTI, LRTI, and gastroenteritis are analyzed as separate outcomes. Abbreviations: ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; AKI, acute kidney injury; BB, β-blocker; CCB, calcium channel blocker; CPRD, Clinical Research Practice Datalink; ESRD, end-stage renal disease; HES, Hospital Episode Statistics; LRTI, lower respiratory tract infection; UTI, urinary tract infection.

Figure 3

Main analysis: age-adjusted incidence rate ratios (95% CI) for AKI in risk periods after acute community-acquired infections (gastroenteritis, urinary tract infection, and lower respiratory tract infection). Notes: The numbers of participants exposed to each type of infection are shown in parentheses for each exposure. These include a small number who had a recorded AKI event on the day of infection exposure that was not included in the analysis, because the events may have been recorded retrospectively. Incidence during the baseline period served as the reference category. IRR denotes age-adjusted incidence ratio; age-adjusted in the following age bands: 18–44, 45–54, 55–59, 60–64, 65–69, 70–74, 75–84, 85–89, and 90+ years. Participants may appear within more than one category. Abbreviations: AKI, acute kidney injury; IRR, incidence rate ratio.