Effectiveness of tolvaptan on renal replacement therapy in patients with autosomal dominant polycystic kidney disease: a retrospective cohort study from the TriNetX global collaborative network

Abstract

Background and hypothesis: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major genetic contributor to end-stage kidney disease (ESKD). Current evidence on tolvaptan primarily focuses on slowing estimated glomerular filtration rate (eGFR) decline and kidney volume growth. However, direct confirmation of its effectiveness in reducing the need for hemodialysis in ESKD remains limited.

Methods: We included ADPKD patients aged ≥18 years using TriNetx data from Sep 2, 2018, to Sep 3, 2023. Propensity score matching (PSM) ensured baseline comparability (standardized mean difference (SMD) <0.1). Hazard ratios (HRs) with 95% confidence intervals (CIs) evaluated outcomes, and subgroup analyses were performed.

Results: After 1:1 PSM, both groups comprised 673 patients. The average age was 45, with generally good health (3-5% diabetes, 2-3% ischemic heart disease). Baseline eGFR averaged ∼55 ml/min/1.732m². Post-matching, all SMDs were <0.1, indicating successful matching. Tolvaptan users exhibited lower eGFR (51.45 ± 30.09 vs. 57.37 ± 33.65, p < 0.001) and higher risk of stage 4-CKD (HR: 2.436, 95% CI:1.649, 3.599) compared to non-users. However, tolvaptan users showed significantly reduced chances of initiating hemodialysis (HR:0.362, 95%CI:0.176, 0.745), experiencing urinary tract infections (HR:0.581, 95%CI:0.354, 0.956), and all-cause mortality (HR:0.355, 95% CI:0.180, 0.700). Kaplan-Meier curves for hemodialysis initiation indicated higher survival rates among tolvaptan users across age and number of medication refill subgroups.

Conclusions: This real-world study, employing precise matching, reveals tolvaptan's role in reducing hemodialysis initiation risk in ADPKD, despite initial hemodynamic-induced lower eGFR.

Keywords: Tolvaptan; autosomal dominant polycystic kidney disease (ADPKD); end-stage kidney disease (ESKD); hemodialysis; mortality.

Figure 1.

Flowchart of cohort construction and study designs for tolvaptan and non-tolvaptan groups. (A) Algorithm for participants recruitment. (B) Study design for tolvaptan group. (C) Study design for non-tolvaptan group.

Figure 1.

Flowchart of cohort construction and study designs for tolvaptan and non-tolvaptan groups. (A) Algorithm for participants recruitment. (B) Study design for tolvaptan group. (C) Study design for non-tolvaptan group.

Figure 2.

Kaplan-Meier survival curves (Two Kaplan-Meier curves were presented per outcome with different scales to highlight the differences) (outcome: 1 month after the index event). (A) CKD stage 4 (log-rank test p < 0.0001). (B) CKD stage 5 (log-rank test p < 0.0001). (C) Initiation of hemodialysis (log-rank test p = 0.028) (refill time ≥ 1). (D) All-cause mortality (log-rank test p = 0.016).

Figure 2.

Kaplan-Meier survival curves (Two Kaplan-Meier curves were presented per outcome with different scales to highlight the differences) (outcome: 1 month after the index event). (A) CKD stage 4 (log-rank test p < 0.0001). (B) CKD stage 5 (log-rank test p < 0.0001). (C) Initiation of hemodialysis (log-rank test p = 0.028) (refill time ≥ 1). (D) All-cause mortality (log-rank test p = 0.016).

Figure 3.

Kaplan-Meier survival curves for the initiation of hemodialysis according to different tolvaptan refill time (Two Kaplan-Meier curves were presented per outcome with different scales to highlight the differences) (outcome: 1 month after the index event). (A) Refill time ≥3 (log-rank test p = 0.004). (B) Refill time ≥6 (log-rank test p = 0.021). (C) Refill time ≥9 (log-rank test p = 0.002).

Figure 3.

Kaplan-Meier survival curves for the initiation of hemodialysis according to different tolvaptan refill time (Two Kaplan-Meier curves were presented per outcome with different scales to highlight the differences) (outcome: 1 month after the index event). (A) Refill time ≥3 (log-rank test p = 0.004). (B) Refill time ≥6 (log-rank test p = 0.021). (C) Refill time ≥9 (log-rank test p = 0.002).