Drug-Targeted Alerts for Acute Kidney Injury

In this trial, patients with acute kidney injury who have recently received a drug that may affect kidney function will be randomized to having an alert placed in the electronic health record or usual care.

Acute kidney injury (AKI) carries a significant, independent risk of mortality among hospitalized patients. Recent studies have demonstrated increased mortality among patients with even small increases in serum creatinine concentration. International guidelines for the treatment of AKI focus on appropriate management of drug dosing, avoiding nephrotoxic exposures, and careful attention to fluid and electrolyte balance. Early nephrologist involvement may also improve outcomes in AKI. Without appropriate provider recognition of AKI, however, none of these measures can be taken, and patient outcomes may suffer. AKI is frequently overlooked by clinicians, but carries a substantial cost, morbidity and mortality burden. Our research group recently conducted a large-scale multicenter randomized controlled trial of electronic alerts for AKI throughout the Yale New Haven Health System from 2018 to 2020. The trial, which enrolled 6,030 patients with AKI, randomized patients between usual care and an intervention group whereby providers received a general AKI alert informing them to the presence of AKI and the patient's recent creatinine trends, and provided a link to an AKI-specific order set. Our study showed that, overall, alerting physicians to the presence of AKI did not demonstrate a difference in the rate of our primary outcome of progression of AKI, dialysis, or death, nor were there any differences in process measures accessed (i.e. provider actions) between the two groups, however, there was substantial heterogeneity among the study sites. Given the highly heterogenous nature of AKI, a more personalized approach may be warranted. Further, this study enrolled all patients who developed AKI rather than a targeted subset of patients who may benefit, such as those AKI patients receiving potentially harmful kidney-toxic medications. In the present proposal, we seek to expand upon our prior study to determine if the use of medication targeted electronic alerts will modify provider behavior, particularly in regards to nephrotoxic medication use and cessation, in the care of hospitalized patients with AKI and/or reduce the rates of progression to AKI, dialysis, or mortality in hospitalized patients. The current study is a randomized, controlled trial of a medication-targeted electronic AKI alert system. Using the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria, inpatients at 4 different teaching hospitals of the Yale New Haven Health System that have had at least one dose of a nephrotoxic agent of interest within 24 hours of AKI onset will be randomized to either usual care or a medication-targeted alert that informs the provider of the presence of AKI and the patient's recent exposures to the targeted classes of medications with an option to discontinue. The primary outcome will be a composite of AKI progression, dialysis, or mortality within 14 days of randomization. Secondary outcomes will focus on the rate of cessation of any medication of interest within 24 hours of randomization and various other best practice metrics.

A drug-specific AKI alert, including information about the drug of interest as well as the presence of AKI will be fired.

A drug-specific alert, informing the provider of the presence of AKI as well as recent exposure to a potentially nephrotoxic agent, will be fired.

Progression of AKI is defined by an increase in KDIGO creatinine stage from time of randomization to the present. Dialysis is defined by the receipt of hemodialysis, continuous renal replacement therapy or peritoneal dialysis. Isolated ultrafiltration treatments will not be included. Mortality will be determined from hospital records.

The Percentage of patients for whom the targeted agent was discontinued within 24 hours from randomization. For individuals with active orders for more than one targeted agent, cessation of any will be adequate to meet this endpoint.

Assessed from point of randomization to the date of death from any cause during the end of current index hospitalization, up to 365 days

Receipt of hemodialysis, continuous renal replacement, or peritoneal dialysis within 14 days of randomization

Assessed from point of randomization to date of first documented dialysis order, within 14 days of randomization

Receipt of hemodialysis, continuous renal replacement, or peritoneal dialysis during index hospitalization

Assessed from point of randomization to the date of first documented dialysis order during index hospitalization, up to 365 days

Assessed from date of randomization to date of documented AKI progression, within 14 days of randomization

Assessed from date of randomization to date of documented AKI progression, within 14 days of randomization

Assessed from the point of randomization to the point of AKI cessation during index hospitalization, up to 365 days

Assessed from point of randomization to the date of discharge from index hospitalization, up to 365 days post randomization

Best practices assessed include: Avoidance of nephrotoxins (cessation of order or absence of de novo order of IV constrast agent, aminoglycoside, NSAID, or ACE inhibitor within 24 hours of randomization), fluid administration (administration of fluids within 24 hours of randomization), urinalysis order (with or without microscopy within 24 hours of randomization), documentation of AKI (by ICD-9 and ICD-10 codes during index hospitalization), monitoring of creatinine (at least one serum creatinine measurement occurring within 36 hours of randomization), documentation of urine output (within 24 hours of randomization), renal consult order during index hospitalization. Each metric above is binary. Outcome is reported as a composite best practice outcome representing the proportion of best practices achieved per subject.

Percentage of subjects with chart documentation of AKI by post-discharge ICD-10 codes and by chart adjudication

Assessed from time of randomization through to date of index hospitalization discharge, up to 365 days post randomization

Inclusion Criteria: Acute Kidney Injury based upon the Kidney Disease: Improving Global Outcomes creatinine criteria (a 0.3mg/dl increase over 48 hours or 50% increase over 7 days) and an active order within the past 24 hours to one of the following classes of medications: Non-steroidal anti-inflammatory drug Renin Angiotensin Aldosterone System Antagonists Proton Pump Inhibitors Exclusion Criteria: Dialysis order prior to AKI onset Previous randomization Admission to a hospice service or CMO First hospital creatinine >=4.0 mg/dl ESKD diagnosis code Kidney transplant within six months prior to randomization