Does eGFR calculated by creatinine or cystatin C predict future decline in kidney function? Results of the FORM-2C observational study of primary care patients with reduced eGFR.

Conference:

SAPC ASM 2019 - Exeter

Talk Code:

P2.56

Presenter:

Susannah Fleming

Twitter:

@SusannahFleming

Co-authors:

Richard Stevens, Louise Jones, Kathryn Taylor, Richard Hobbs, Daniel Lasserson, Chris O’ Callaghan, Rafael Perera, Clare Bankhead

Author institutions:

University of Oxford, University of Birmingham (Daniel Lasserson)

Problem

The FORM-2C (Frequency Of Renal Monitoring – Cystatin C and Creatinine) Study is an observational study of patients with reduced eGFR (30-89 ml/min/1.73²) recruited from primary care. The primary objective of the study is to investigate whether baseline renal function measured by cystatin C or plasma creatinine is better at predicting future change in renal function over time. Cystatin C may provide primary care physicians with a better estimate of current renal function than serum creatinine, according to cross-sectional studies, but there is a lack of prospective data on which better predicts future renal function.

Approach

We recruited 749 participants to FORM-2C. Each participant attended an initial visit, with follow-up visits at 2 weeks, 12 weeks, 6 months, 12 months, 18 months and 24 months. At each visit, participants provided blood and urine samples for measurement of various biochemical markers, including plasma creatinine and cystatin-C. CKD-EPI equations using either creatinine or cystatin-C were used for eGFR calculations. Baseline renal function was calculated as the mean eGFR using either creatinine or cystatin-C collected at the initial, 2-week, and 12-week visits. Change in renal function over time was calculated by fitting a linear slope to the eGFRs calculated using either creatinine or cystatin-C collected at the 6, 12, 18, and 24-month visits. We used complete case analysis for all patients with at least one baseline result for both creatinine and cystatin-C, and at least 2 results for both creatinine and cystatin-C from visits between 6 and 24 months.The generalised c-statistic was used to quantify the predictive value of baseline eGFR to predict future change in eGFR. Confidence intervals were calculated using the non-parametric bootstrap method.

Findings

There was sufficient data to include 594 patients in this analysis. We anticipate that the completeness of the data will continue to increase. Mean ±SD rate of decline in eGFR between 6 and 24 months was -0.04 ±10.7 ml/min/1.73²/year when calculated from creatinine, and 2.16 ±6.1 ml/min/1.73²/year when calculated from cystatin-C.The c-statistic for the predictive value of baseline eGFR derived from creatinine for predicting future change in kidney function was 0.491 (95% CI 0.465 to 0.518). The equivalent c-statistic for eGFR derived from cystatin-C was 0.499 (95% CI 0.472 to 0.527). There was no statistically significant difference in the predictive value of the two methods for calculating eGFR.

Consequences

As both c-statistics are very close to 0.5, it can be seen that neither method of calculating baseline eGFR has value for predicting future change in kidney function, and so may not be of benefit to identify patients who are at risk of further renal decline. In particular, we have shown that the more expensive cystatin-C biomarker does not appear to provide any prognostic benefit over plasma creatinine.

Submitted by:

Susannah Fleming

Funding acknowledgement:

This research was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme (Reference: RP-PG-1210-12003) and supported by the NIHR Biomedical Research Centre, Oxford. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.