PLoS One. 2026 Aug 26;21(8):e0338001. doi: 10.1371/journal.pone.0338001. eCollection 2026.
ABSTRACT
BACKGROUND: Timely nephrology referral is considered important in chronic kidney disease (CKD), however, definitions of "late referral" vary, and may not accurately reflect patient risk or predict outcomes.
STUDY AIM: To evaluate referral patterns among Chronic Kidney Disease Queensland Registry (CKD.QLD) participants, focusing on the timing and appropriateness of referrals and their association with clinical outcomes.
METHODS: We conducted a retrospective cohort study of adults (≥18 years) in the CKD.QLD Registry from seven public nephrology clinics (May 2011-June 2018). Participants were followed from referral to kidney replacement therapy (KRT), death, or study end. Late referral was defined as initiation of KRT within 12 months of referral among those who progressed to KRT. Comorbidity burden was assessed using an unweighted count. A primary Cox proportional hazards model was performed in KRT starters. To address selection bias, a multivariable Fine-Gray competing risks model with left truncation was applied to the full cohort, incorporating pre-KRT mortality.
RESULTS: Among 3,775 participants, 775 (20.5%) developed end-stage kidney disease and 513 of these (66.2%) initiated KRT. Overall, 722 (19.1%) died, including 598 before KRT. Late referral occurred in 60 (11.7%) KRT patients. In a fully adjusted Cox proportional hazards model restricted to the 513 participants who progressed to KRT, late referral was not associated with post-KRT mortality (hazard ratio [HR] 0.91; 95% CI 0.52-1.59; p = 0.74). On the other hand, in a fully adjusted Fine-Gray model, longer pre-KRT care showed a statistically significant but clinically small increase in post-KRT mortality (sub-distribution hazard ratio [SHR]1.004 per additional month; 95% CI 1.001-1.006; p = 0.004). This minimal effect was supported by near-overlapping cumulative incidence curves across 1-, 3-, 6-, and 12-month referral thresholds. In contrast, baseline clinical factors were strongly associated with post-KRT mortality: higher comorbidity score (SHR 2.113; 95% CI 1.792-2.493; p < 0.001), pre-existing cardiovascular disease (SHR 1.910; 95% CI 1.232-2.961; p = 0.004), and Indigenous status (SHR 1.931; 95% CI 1.193-3.127; p = 0.007).
CONCLUSION: After accounting for pre-dialysis deaths, longer pre-KRT care had minimal impact on post-dialysis survival. Outcomes were instead driven mainly by baseline comorbidity and cardiovascular disease rather than referral timing. These findings support a shift from primarily using time-based referral criteria toward risk-stratified approaches in CKD management.
PMID:42647570 | DOI:10.1371/journal.pone.0338001