The Impact of Nephrology Referral on Chronic Kidney Disease Outcomes in Israel

Timely nephrology referral is critical in managing chronic kidney disease (CKD), yet referral practices and their impact on outcomes remain poorly characterized at the population level. We examined the landscape of CKD in Israel, focusing on referral rates, timing, and associations with mortality. We conducted a retrospective cohort study using electronic health records (EHRs) from Clalit Health Services, covering 4.7 million individuals between 2005 and 2017. Adults (≥18 years) with confirmed CKD, defined by two estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 or albumin-to-creatinine ratio (ACR) levels ≥30 mg/g 3-12 months apart, were included. Patients on dialysis or post-transplant at baseline were excluded. The exposure was the first nephrology consultation. To mitigate confounding and immortal time bias, a sequential time-dependent propensity-score (PS) matching approach generated 19,417 matched pairs of referred and unreferred patients. The primary outcome was all-cause mortality; end-stage kidney disease (ESKD) was secondary. Follow-up began at exposure, excluding events within three months. Among 288,263 individuals with CKD, only 15.3% had a nephrology consultation during follow-up. Median time to referral was lower with advancing CKD: 6.8 years (interquartile range [IQR] 4.2-9.8) for G3a, 4.66 (2.4-7.6) for G4, and 4.09 (2.1-7.1) for G5. Referral was associated with lower 10-year mortality (25.0% vs. 32.7%; hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.74-0.81). The association with lower mortality was strongest in early stages – G2 (HR 0.59; 95% CI 0.50-0.68), G3a (HR 0.65; 95% CI 0.61-0.71), G3b (HR 0.75; 95% CI 0.71-0.79) – and smaller in G4 (HR 0.85; 95% CI 0.80-0.91). Progression to ESKD was similar (7.4% vs. 7.6%). In this nationwide cohort, nephrology referral was infrequent and delayed but was associated with higher long-term survival, especially when initiated early. Referral did not alter ESKD progression, suggesting potential benefits stemming from cardiovascular and metabolic management. Findings support systematic CKD risk stratification and earlier referral in primary care.