Four prescribed Chinese herbal medicines provide renoprotection and survival benefit without hyperkalemia risk in patients with advanced chronic kidney disease: A nationwide cohort study

Abstract

Background: Chinese herbal medicine (CHM) has been used as adjuvant treatment of chronic kidney disease (CKD) for years. Astragalus membranaceus (A. membranaceus, Huangqi [A]), Angelica sinensis (Oliv.) Diels (Danggui [S]), Rheum palmatum L. (Dahuang [R]), and Salvia miltiorrhiza Bunge (Danshen [D]) are considered as potentially renoprotective CHMs. However, there is limited evidence on whether ASRD use affects outcomes and causes hyperkalemia in patients with stage 4 and stage 5 advanced CKD.

Purpose: To investigate between ASRD use (vs. nonuse) and risks of end-stage renal disease (ESRD), death, and hyperkalemia in patients with advanced CKD.

Study design: Retrospective nationwide cohort study using claims data from the Taiwan's 2005 Longitudinal Generation Tracking Database in 2000-2016.

Methods: A total of 24,572 patients with advanced CKD were identified and 15,729 eligible patients were enrolled in the propensity score matching, with 1,401 incident ASRD users (8.9%) and 14,328 nonusers (91.1%). Finally, 1,076 ASRD users and 4,304 matched nonusers were subjected to analysis. We used Cox proportional hazards regression model to estimate the hazard ratios for ESRD and death and Poisson regression to estimate incidence rate ratio of hyperkalemia. The additive effect of one to four ASRD and the pooling effect of individual ASRD on risks of ESRD and death were also addressed.

Results: In a total follow-up of 15,740 person-years, 2,703 patients (50.2%) developed ESRD and 499 (9.3%) died before progression to ESRD. As compared with nonusers, ASRD users were associated with adjusted hazard ratios of 0.83 (95% confidence interval, 0.76-0.91) for ESRD and 0.78 (0.30-0.93) for death, as well as adjusted incidence rate ratios of 0.54 (0.48-0.60) for inpatient hyperkalemia and 0.44 (0.42-0.46) for total hyperkalemia. The renal and survival benefits of ASRD use were consistent across almost patient subgroups on multivariate stratified analyses. Using all four ASRD provided the lowest risks of ESRD (0.30; 0.71-0.52) and death (0.32; 0.17-0.63). Individual use of ASRD also demonstrated comparable renal and survival benefits.

Conclusion: ASRD use was associated with lower risks of ESRD and death among advanced CKD patients. This benefit did not increase hyperkalemia risk.

Keywords: Advanced CKD; Death; ESRD; Hyperkalemia; Renoprotective Chinese herbal medicine.