Implication of Trends in Timing of Dialysis Initiation for Incidence of End-stage Kidney Disease

“Because ESKD [end-stage kidney disease] is operationally defined as receiving long-term dialysis or a kidney transplant, we hypothesized that the number of patients with incident ESKD can vary considerably depending on decisions between patients and physicians about the choice and timing of kidney replacement therapy, and particularly of initiating dialysis. Consistent with this, after publication of the Initiating Dialysis Early and Late (IDEAL) trial—a randomized clinical trial showing no significant difference in death or other outcomes with earlier (eGFR of 9.0 mL/min/1.73 m2) vs later (eGFR of 7.2 mL/min/1.73 m2) initiation of dialysis—a rapid drop in early dialysis initiation was observed in Canada. Although early dialysis initiation was defined in that study as dialysis initiation at eGFR higher than 10.5 mL/min/1.73 m2, there was no information regarding how the number of patients with chronic kidney disease (CKD) in the underlying population with eGFR higher than 10.5 mL/min/1.73 m2 may have changed during the relevant period.

[..] Kaiser Permanente Northern California (KPNC) is a large, integrated health care delivery system currently providing comprehensive care for more than 4.5 million members. Its membership is sociodemographically diverse and highly representative of the local and statewide population. Nearly all aspects of care are captured through KPNC’s integrated electronic health record system, with access to clinical data elements from all practice settings (eg, laboratory test results and vital signs) as well as previously validated algorithms that incorporate relevant diagnostic or procedure codes and pharmacy dispenses.

[..] Our primary outcome was initiation of long-term dialysis within the first eligible year in each 3-year interval, ascertained through a comprehensive, manually validated health plan ESKD treatment registry. Patients are entered into the registry after manual review to confirm that receipt of dialysis was not temporary or only for acute kidney injury. We removed cases of preemptive kidney transplant (3% of ESKD cases). Initial dialysis modality (hemodialysis vs peritoneal dialysis) was ascertained from registry files. We defined urgent dialysis starts as being preceded by an episode of dialysis-requiring acute kidney injury within 28 days before long-term dialysis initiation. All cases not meeting this definition were considered elective starts.

[..] Mean (SD) eGFR at dialysis initiation for patients starting long-term dialysis was 12.4 (13.1) mL/min/1.73 m2 in 2001 to 2003, rose to 16.3 (17.7) mL/min/1.73 m2 in 2010 to 2012, and did not further increase through 2016 to 2018. These temporal trends were similar for elective starts and for all patients undergoing peritoneal dialysis or hemodialysis.

[..] After adjustment for age, sex, race, and diabetes, statistically significant temporal increases in 1-year odds of initiating dialysis persisted among eGFR categories of 20 to 24, 16 to 17, and 10 to 13 mL/min/1.73 m2. Among patients with an index eGFR of 20 to 24 mL/min/1.73 m2, the 1-year odds of initiating dialysis increased for every 3-year interval by 5.2% (adjusted odds ratio, 1.052; 95% CI, 1.004-1.102); among patients with an eGFR 16 to 17 mL/min/1.73 m2, the 1-year odds of initiating dialysis increased by 6.6% (adjusted odds ratio, 1.066; 95% CI, 1.007-1.130); and among patients with an eGFR of 10 to 13 mL/min/1.73 m2, the 1-year odds of initiating dialysis increased by 5.3% (adjusted odds ratio, 1.053; 95% CI, 1.008-1.100). By contrast, among patients with very low index eGFR (≤9 mL/min/1.73 m2), we observed stable or decreased unadjusted and adjusted odds of initiating dialysis over time. These patterns were similar among the subset of patients with elective dialysis starts.

Overall, we estimated that incidence of ESKD could have potentially been 16% (95% CI, 13%-18%) lower if there were no changes in system-level practice patterns or other factors besides timing of initiation of long-term dialysis from the initial 3-year interval (2001-2003) to the final 3-year interval (2016-2018) assessed in this study.

[..] Given the lack of strong evidence that earlier initiation of long-term dialysis has net clinical benefit, careful evaluation of contemporary dialysis initiation practices is needed, along with ongoing improved shared decision-making efforts to personalize the approach with patients. Dialysis is currently recommended when kidney function is “low” and a patient has symptoms or signs consistent with kidney failure. However, some symptoms and signs (eg, fatigue or pruritus) may be nonspecific and caused by comorbid conditions, whereas others (eg, anorexia or hypoalbuminemia) can change over time and may improve spontaneously without dialysis therapy. In most cases, long-term dialysis is initiated not to treat an immediately life-threatening condition (eg, uremic pericarditis or refractory hyperkalemia). As noted previously, the aggressive promotion of earlier arteriovenous fistula placement in patients with CKD may also affect patient and physician expectations about the timing of initiating dialysis. Thus, decisions about when to start dialysis are not always fully objective, and policy decisions that have encouraged systematic earlier dialysis initiation can be adjusted. [..] The United Kingdom National Institute for Health and Care Excellence now recommends waiting until an eGFR of 5 to 7 mL/min/1.73 m2 or the presence of symptoms affecting daily life before starting dialysis. Furthermore, the Japanese Society of Nephrology guidelines recommend patients “endure under conservative treatment until the GFR is <8 mL/min/1.73 m2 even when the symptoms of renal failure are observed.”

[..] incidence of ESKD (as currently defined) in a population may not be an entirely optimal quality metric to reflect the success or failure of renoprotective efforts, and policy makers and public health officials should consider other metrics as well.”

Full article, Hsu C, Parikh RV, Pravoverov LN et al. JAMA Internal Medicine 2020.10.12