The importance of early referral for the treatment of chronic kidney disease: a Danish nationwide cohort study

Background: Many patients with advanced chronic kidney disease are referred late to renal units. This is associated with negative aspects. The purpose of the present study was to characterize late versus early referrals for renal replacement therapy including their renal disease, health care contacts and medical treatment before renal replacement therapy (RRT) and the consequences for RRT modality and mortality. Methods: Nationwide cohort study including 4495 RRT patients identified in the Danish Nephrology Registry 1999-2006. The cohort was followed to end 2007 by linkage to other national registries. Late referral: follow-up <= 16 weeks in renal unit before RRT start. Cox proportional hazards models were used to estimate the relative risk of mortality or waiting list status within 365 days in late referrals versus early referrals. Results: A total of 1727 (38%) incident RRT patients were referred late. Among these, 72% were treated in non-nephrology hospital departments and 91% in general practice 2 years to 16 weeks before RRT start. Fewer late referrals received recommended pre-RRT treatment as judged by renin-angiotensin-system blockade: 32% versus 57% or the D-vitamin analogue alfacalcidol: 5% versus 30% (P < .001). Primary RRT modality was peritoneal dialysis: 18% in late versus 32% in early referrals (P < .001), 7% versus 30%, respectively, had an arteriovenous dialysis-fistula (P < .001) and 0.2% versus 6% were on the waiting-list for renal transplantation (P < .001) before RRT start. One-year-mortality was higher in late referrals: hazard ratio 1.55 (CI 95% 1.35-1.78). In a subgroup, 30% (CI 95% 25-35%) late and 9% (CI 95% 6-12%) early referrals had plasma creatinine <= 150% of upper reference limit within 1 to 2 years before RRT start (P < .001). Conclusions: Late nephrology referrals were well-known to the healthcare system before referral for RRT start and more often had near normal plasma creatinine levels within 2 years before RRT start. They infrequently received available treatment or optimal first RRT modality. An increased effort to identify these patients in the healthcare system in time for proper pre-dialysis care including preparation for RRT is needed.