Background Proton pump inhibitors (PPIs) cause interstitial nephritis and are an underappreciated cause of acute kidney injury. We examined the risk of acute kidney injury and acute interstitial nephritis in a large population of older patients receiving PPIs. Methods We conducted a population-based study involving Ontario residents aged 66 years and older who initiated PPI therapy between Apr. 1, 2002, and Nov. 30, 2011. We used propensity score matching to establish a highly comparable reference group of control patients. The primary outcome was hospital admission with acute kidney injury within 120 days, and a secondary analysis examined acute interstitial nephritis. We used Cox proportional hazards regression to adjust for differences between groups. Results We studied 290 592 individuals who commenced PPI therapy and an equal number of matched controls. The rates of acute kidney injury (13.49 v. 5.46 per 1000 person-years, respectively; hazard ratio [HR] 2.52, 95% CI 2.27 to 2.79) and acute interstitial nephritis (0.32 vs. 0.11 per 1000 person-years; HR 3.00, 95% CI 1.47 to 6.14) were higher among patients given PPIs than among controls. Interpretation In our study population of older adults, those who started PPI therapy had an increased risk of acute kidney injury and acute interstitial nephritis. These are potentially reversible conditions that may not be readily attributed to drug treatment. Clinicians should appreciate the risk of acute interstitial nephritis during treatment with PPIs, monitor patients appropriately and discourage the indiscriminate use of these drugs.

We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV) infection using administrative health databases in Ontario, Canada. We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%–97.9%) and 99.6% (95% CI 99.1%–99.8%), respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple “3 claims in 3 years” definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.

Research from JAMA Internal Medicine — Trimethoprim-Sulfamethoxazole–Induced Hyperkalemia in Patients Receiving Inhibitors of the Renin-Angiotensin System — A Population-Based Study

Objectives: Despite the recent publication of case reports describing various manifestations of tenofovir‐related nephrotoxicity, data regarding the incidence of and risk factors for this adverse effect are currently lacking.Methods: A retrospective cohort study of patients from four centres in Toronto, Canada, enrolled in the tenofovir expanded access programme with a minimum of 3 months follow up, was carried out.Results: A total of 172 patients receiving tenofovir disoproxil fumarate (TDF) for a median of 16 months (range 3–25 months) were included in the study. Seven (4%) patients developed grade 1 (>44 μmol/L from baseline) increases in serum creatinine (SCr) during follow up; no patient developed grade 2 or higher nephrotoxicity. Fifteen (8.7%) patients had an increase in SCr of greater than 1.5 times baseline values during follow up. Four (2.3%) patients discontinued TDF because of an increase in SCr and/or abnormal urinalysis. Of 62 patients with a urinalysis, grade 1 or higher proteinuria (< 3 g/L) was observed in 27 (43%) patients. Only baseline SCr [odds ratio (OR)=0.51 per 10 μmol/L increase; P=0.0005] and baseline creatinine clearance (1.26 per 10 mL/min increase; P=0.01) were significantly associated with ever having a 1.5‐fold increase in serum creatinine. Twenty‐eight (16%) and 11 (6%) patients developed grade 1 (serum phosphorus≤0.71 mmol/L) and grade 2 (serum phosphorus≤0.61 mmol/L) hypophosphataemia during follow‐up, respectively.Conclusions: Although slight increases in SCr did occur after starting TDF, clinically significant nephrotoxicity was rare. The clinical significance of TDF‐related hypophosphataemia and proteinuria requires further study.

Cannabidiol inhibits CYP2C19, increasing levels of the active metabolite of clobazam threefold.1^,3 Interactions with other drugs metabolized by CYP2C19 (Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.191097/-/DC1) should be anticipated. Very high international normalized ratio levels and bleeding have been reported with combined used of warfarin and marijuana.1 A case reporting a threefold increase in tacrolimus levels following the addition of cannabidiol shows that CYP3A4/5 inhibition can also occur.4