Association between Acute Declines in eGFR during Renin-Angiotensin System Inhibition and Risk of Adverse Outcomes

Elaine Ku, Hocine Tighiouart, Charles E. Mcculloch, Lesley A. Inker, Ogechi M. Adingwupu, Tom Greene, Raymond O. Estacio, Mark Woodward, Dick De Zeeuw, Julia B. Lewis, Thierry Hannedouche, Fan Fan Hou, Tazeen H. Jafar, Enyu Imai, Giuseppe Remuzzi, Hiddo J.L. Heerspink, Robert D. Toto, Mark J. Sarnak*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

2 Citaten (Scopus)

Samenvatting

Background
Declines in GFR occur commonly when renin-angiotensin system (RAS) inhibitors are started. Our objective was to determine the relation between declines in eGFR during trials of RAS inhibition and kidney outcomes.

Methods
We included participants with CKD (eGFR <60 ml/min per 1.73 m2) from 17 trials of RAS inhibition. The exposure was subacute declines in eGFR expressed as % change between randomization and month 3, and in the subset of trials with data available, we also examined % change in eGFR between randomization and month 1. The primary outcome was kidney failure with replacement therapy. Cox proportional hazards models were used to examine the association between subacute declines in eGFR and risk of kidney failure. We used spline models to identify the threshold of change in eGFR below which RAS inhibition was favorable (conservatively comparing a given decline in eGFR with RAS inhibition to no decline in the comparator).

Results
A total of 11,800 individuals with mean eGFR 43 (SD 11) ml/min per 1.73 m2 and median urine albumin-to-creatinine ratio of 362 mg/g (interquartile range, 50-1367) were included, and 1162 (10%) developed kidney failure. The threshold of decline in eGFR that favored the use of RAS inhibitors for kidney failure was estimated to be up to 13% (95% confidence interval, 8% to 17%) over a 3-month interval and up to 21% (95% confidence interval, 15% to 27%) over a 1-month interval after starting RAS inhibitors.

Conclusions
In patients treated with RAS inhibitors, ≤13% decline in eGFR over a 3-month period or ≤21% decline over a 1-month period was associated with lower risk of kidney failure compared with no decline in those assigned to placebo or other agents.

Originele taal-2English
Aantal pagina's10
TijdschriftJournal of the American Society of Nephrology
DOI's
StatusAccepted/In press - 2024

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