BACKGROUND: Knowledge about the nature of long-term changes in kidney function in the general population is sparse. We aim to identify whether primary care electronic healthcare records capture sufficient information to study the natural history of kidney disease. METHODS: The National Chronic Kidney Disease Audit database covers ∼14% of the population of England and Wales. Availability of repeat serum creatinine tests was evaluated by risk factors for chronic kidney disease (CKD) and individual changes over time in estimated glomerular filtration rate (eGFR) were estimated using linear regression. Sensitivity of estimation to method of evaluation of eGFR compared laboratory-reported eGFR and recalculated eGFR (using laboratory-reported creatinine), to uncover any impact of historical creatinine calibration issues on slope estimation. RESULTS: Twenty-five per cent of all adults, 92% of diabetics and 96% of those with confirmed CKD had at least three creatinine tests, spanning a median of 5.7 years, 6.2 years and 6.1 years, respectively. Median changes in laboratory-reported eGFR (mL/min/1.73 m2/year) were -1.32 (CKD) and -0.60 (diabetes). Median changes in recalculated eGFR were -0.98 (CKD) and -0.11 (diabetes), underestimating decline. Magnitude of underestimation (and between-patient variation in magnitude) decreased with deteriorating eGFR. For CKD Stages 3, 4 and 5 (at latest eGFR), median slopes were -1.27, -2.49 and -3.87 for laboratory-reported eGFR and -0.89, -2.26 and -3.75 for recalculated eGFR. CONCLUSIONS: Evaluation of long-term changes in renal function will be possible in those at greatest risk if methods are identified to overcome creatinine calibration problems. Bias will be reduced by focussing on patients with confirmed CKD.