#5533 DOES AV FISTULA FORMATION DELAY TIMING OF INITIATION OF KIDNEY REPLACEMENT THERAPY IN PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE?

Abstract Background and Aims Several retrospective observational studies have supported kidney protective effects of arteriovenous fistula (AVF) formation. However, these studies were limited by immortal time and selection biases. We investigated whether AVF formation delays the initiation of kidney replacement therapy (KRT) in patients with stage 5 CKD by applying target trial emulation methods, which do not suffer from these biases. Method We included adult patients who had an eGFR ≤15 mL/min/1.73m2, attended the ‘low clearance’ nephrology clinic in the West of Scotland between January 1st 2010 and May 1st 2022, and had no prior AVF or AV graft formation. Available data were obtained from the Strathclyde Electronic Renal Patient Record. The target trial would randomize patients to either receive an AVF immediately or to not receive an AVF. To emulate this trial, we matched each patient who underwent AVF formation to patients who had not undergone AVF formation but remained eligible to participate in the trial, and were matched in sex, age (within 5 years) and eGFR (within 0.5 ml/min/1.73m2). Inverse probability of treatment weighting was used to adjust for baseline confounders, including age, sex, comorbidities, medication use, serum and urine biochemical measurements (eGFR CKD-EPI, eGFR CKD-EPI slope for 6 months preceding trial, haemoglobin, C-reactive protein, albumin, phosphate, adjusted calcium, ferritin, urine protein:creatinine ratio), and blood pressure. The primary outcome was kidney replacement therapy. The eGFR slope closest to the time of AVF creation was estimated as a co-primary endpoint. We estimated hazard ratios using Cox regression and estimated restricted mean survival time (RMST) from the Kaplan-Meier curves. The eGFR slope co-primary endpoint was analysed with a mixed-effects model. Results Among 2,988 included patients (55% men; mean [SD] age 64 [15] years), AVF formation was associated with a higher risk of KRT (HR 1.45; CI 1.20–1.49, p <0.001, Figure 1) and a lower risk of death (HR 0.68; (0.64–0.80, p = 0.001). The AVF group had a lower KRT-free survival with an estimated RMST difference of 265 days (95% CI −331 to −199, p <0.001) and higher overall survival (RMST difference of 191 days; 95% CI 57 to 326, p = 0.005). Finally, we used a mixed-effects model to analyse the association between eGFR CKD-EPI, time, and AVF formation. AVF formation and time were both associated with a negative slope in the model (estimates −1.28; 95% CI −1.36 to −1.19, p<0.001 and −0.01; 95% CI −0.01 to −0.01, p<0.001, respectively, Figure 2). Their interaction was also associated with a negative slope (estimate −0.001; 95% CI −0.0022 to −0.0004, p <0.001), suggesting those undergoing AVF formation had a more rapid eGFR decline compared to the control group. Conclusion Unlike what was observed in previously published work, we did not identify a kidney protective effect of AVF formation. The estimated time of dialysis initiation remains the main determinant for timing of access surgery. These findings illustrate the usefulness of target trial emulation in approaching research questions where randomised controlled trials would be impractical.