1. In advanced-stage chronic kidney disease (CKD), there was no significant difference in long-term glomerular filtration rate (eGFR) between those who used and who discontinued renin-angiotensin system (RAS) inhibitors.

2. There was no significant difference in long-term clinical endpoints, such as hospitalization rate and quality of life, between the discontinuation and continuation groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: RAS inhibitors have been a cornerstone in managing CKD both due to their benefits in controlling blood pressure and reducing the rate of decline of eGFR. This is particularly true for patients with mild to moderate CKD, as RAS inhibitors have slow progression into advanced-stage CKD. Recent studies have demonstrated that RAS inhibitors may have limited benefits for patients with advanced-stage CKD and may actually be associated with decreases in eGFR for this group. This study evaluated the effect of discontinuing RAS inhibitor use in patients with advanced CKD. The primary outcome of interest was the effect on eGFR after three years. The secondary outcomes of interest were clinical metrics of CKD progression, quality of life, and incidence of adverse events experienced. The study found no statistically significant differences between the two groups in eGFR, hospitalization, and quality of life measures. However, this study is limited by generalizability, including predominantly White patients. Additionally, contamination bias was noted as adherence to treatment reduced over the three years of follow-up.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: This study was a multicenter, randomized, open-label trial evaluating the effect of RAS inhibitor discontinuation on the eGFR of patients with stage four or five CKD. A total of 411 patients were randomized in a 1:1 ratio to either continue RAS inhibitors (n=205) or discontinue RAS inhibitors (n=206) with balanced baseline characteristics for age, eGFR, diabetes, mean arterial pressure, and proteinuria. The primary outcomes of interest were eGFR at three years. Secondary outcomes included survival-free time of end-stage kidney disease, whether participants developed end-stage kidney disease, hospitalization, quality of life, exercise capacity, reduction >50% of eGFR, cardiovascular events, and blood pressure increase. The primary analysis found no significant difference in the eGFR between the two groups (difference, -0.7; 95% Confidence Interval [CI], -2.5 to 1.0; p=0.42). Results of the secondary outcome analysis found that there were also no significant differences between the two groups concerning any of the secondary outcomes of interest except for increased blood pressure in the discontinuation group more than the continuation group within the first 15 months. Overall, this study provided evidence that discontinuation of RAS inhibitors did not cause significantly different clinical outcomes with respect to eGFR or progression of advanced-stage CKD.

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