Early Detection of Progressive Chronic Kidney Disease by Monitoring Change in eGFR in CKD Stages 1, 2 & 3
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RATIONALE: Early detection and effective treatment of chronic kidney disease (CKD) is reported to halt or slow progression (pCKD) to end-stage renal disease (ESRD) in many patients. Current guidelines recommend an eGFR upper reporting limit of > 60 mL/min/1.73m2. However, this severely limits the detection of pCKD as the first time a patient is diagnosed with CKD, they are already in Stage 3. OBJECTIVE: To determine if the rate of change in eGFR during early stages of CKD (i.e. 1 - 3) is different in those who progress to ESRD compared to those who are currently not anticipated to progress. METHODS: This retrospective case-control (1:2) study used 5 years of hospital laboratory data (2008 – 2013). All subjects had a maximum eGFR-EPI > 90 mL/min/1.73m2. Cases had a minimum eGFR-EPI < 15 mL/min/1.73m2, while age- and sex-matched controls (± 5 years) had a minimum eGFR-EPI > 45 mL/min/1.73m2. JOINPOINT (JP) regression software was used to identify and estimate the declining “linear” slope for eGFR most reflective of early pCKD. Multi-level modelling (MLM) was used for statistical analysis. RESULTS: There were 30 cases (13 women, 17 men), and 60 controls (26 women, 34 men), for a total of 3,217 observations in 90 subjects. The mean eGFR-EPI slope by MLM was -2.9 mL/min/1.73m2/year (95%CI: -3.3 to -2.4) for controls, and -13.0 mL/min/1.73m2/year (95%CI: -16.6 to -9.4) for cases. The median intra-individual variation for eGFR-EPI was 9.5% (95%CI: 4 - 17%) for controls and 24% (95%CI: 6 - 45%) for cases. The average “reference change value” (RCV) needed between two serial values to detect a significant decrease was -25%. CONCLUSIONS: Although eGFR declined in a linear fashion in some subjects, it may be more accurate to describe pCKD as an event-to-event process overlying progressive deterioration. Thus, analysis assuming linear decline should be undertaken cautiously in CKD. In order to detect pCKD earlier, regression with visual review of eGFR time profiles is optimal. Individuals at high risk need to be monitored at a useful frequency to take full advantage of the testing performed and the potential to significantly modify patient outcomes.