The impact of pre-intervention rate of kidney function change on the assessment of CKD progression

Background Without a run in phase, chronic kidney disease (CKD) patients enrolled in clinical trials may not be identified as having progressive disease. The aim of this analysis was to quantify the effects of a run-in phase on a kidney function outcome in CKD patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial. Methods The LORD trial assessed the effects of atorvastatin on the rate change of eGFR and included patients with serum creatinine >120 μmol/l. In this post-hoc analysis, we assessed rate of eGFR change during the, 12-months prior to enrolment, three-month run-in phase and first 12-months of the trial. Eighty of the original 132-patients were included where retrospective data was available. The rate of eGFR change during each period was compared. Results Overall kidney function decreased during the 12-months prior to enrollment by 0.39±(SD) 0.98 ml/min/1.73m2/month, improved during the three-month run-in phase by 0.48±2.90 ml/min/1.73m2/month and decreased during the first 12-months of the trial by 0.15± 0.57ml/min/1.73m2/month. However, only 39% of patients had declining eGFR during the 12-months prior, 19% in the three-month run-in and 42% during the first 12-months. Conclusion Most patients (>60%) entering this clinical trial had stable or improving kidney function. Enrolment was associated with further improved kidney function, which may have been due to regression to the mean or the Hawthorne effect. Investigators should include a run-in period to establish the presence of eGFR decline to use as an inclusion criterion in clinical trials assessing this measure of CKD progression.