Medication Holds in CKD During Acute Volume-Depleting Illnesses: A Randomized Controlled Trial of a "Sick-Day" Protocol.

RATIONALE & OBJECTIVE: Some drugs prescribed for chronic kidney disease (CKD) may become hazardous on sick days with volume depletion by increasing the risk of acute kidney injury (AKI) and kidney function loss; however, the risks and benefits of their use during intercurrent illness is unknown.

STUDY DESIGN

6-month pragmatic trial examining a sick-day protocol to determine if withholding prespecified drugs during a volume-depleting illness reduces the incidence AKI or kidney function loss in CKD.

SETTING & PARTICIPANTS: 315 veterans with stage 3-5 CKD, treated with a renin-angiotensin-aldosterone inhibitor blocker, diuretic, nonsteroidal anti-inflammatory drug, or metformin were randomized into the study with n = 159 and n = 156 in sick-day protocol and usual care groups, respectively.

INTERVENTION

Sick-day protocol administered via interactive voice response system (IVRS) or usual care with 6-month follow-up.

OUTCOMES

The outcomes of the study are as follows: (1) Change in kidney function, (2) incidence of AKI based on codes and ambulatory laboratory testing, (3) urgent service utilizations, and (4) sick days.

RESULTS

The mean age was 70.1 ± 7.4 and 69.2 ± 8.1 years, with a mean baseline glomerular filtration rate (GFR) of 43.1 ± 13.1 and 43.8 ± 13.0 mL/min/1.73 m, and 112 (70%) and 100 (64%) of participants with diabetes in the sick-day protocol and usual care groups, respectively. The mean change in GFR in the sick-day protocol and usual care groups from baseline to 6-month follow-up, adjusting for baseline GFR, was -0.71 (95% CI, -2.11 to 0.69) and -0.72 (95% CI, -2.12 to 0.68), respectively, with no significant difference,  = 0.99. Hospitalizations in the sick-day protocol and usual care groups were 11.5/100 and 8.4/100 events per person-months, respectively, with the adjusted rate ratio not significantly increased (prevalence ratio, 1.30; 95% CI, 0.96-1.76). Participants interacted with the IVRS in 81% of expected weeks and 19 had one or more qualifying events. In 33 true sick days, participants correctly followed the protocol in only 14.

LIMITATIONS

Low incidence of sick days over the 6-month period of the study.

CONCLUSIONS

The sick-day protocol was not associated with a significant reduction in AKI episodes or kidney function loss in a high-risk CKD population. Engagement with the IVRS was high, but successful implementation of the sick-day protocol was not optimal.

TRIAL REGISTRATION

ClinicalTrials.gov; NCT03141905.