Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimer's dementia

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.

Automated summary

Preclinical evidence suggests that the use of Cholinesterase inhibitors (ChEIs) may have beneficial effects on the kidney. This study examined the risk of chronic kidney disease (CKD) progression among newly diagnosed Alzheimer's disease (AD) patients who either used or did not use ChEIs. The results showed that ChEI use was associated with a lower risk of CKD progression.