Divided dosing reduces prednisolone-induced hyperglycaemia and glycaemic variability: a randomized trial after kidney transplantation.
Yates CJ, Fourlanos S, et al.Nephrology Dialysis Transplantation 2014; 29(3):698-705
Aims
To compare the glycaemic effects of divided twice daily (BD) and once daily (QD) prednisolone, in addition to determining whether BD reduces hyperglycaemia and glycaemic variability compared with QD in kidney transplant recipients.
Interventions
Patients received either twice daily or once daily doses of prednisolone. Maintenance immunosuppression consisted of tacrolimus, mycophenolate and prednisolone.
Participants
22 renal transplant recipients without diabetes.
Outcomes
The outcomes included mean interstitial fluid glucose, the time and magnitude of peak and nadir interstitial fluid glucose, glycaemic variability and exposure to hyperglycaemia.
Follow-up
3 weeks
CET Conclusions
This interesting study looks at the glycaemic variability in kidney transplant recipients on either once-daily or twice-daily prednisolone, tacrolimus and MMF. It utilises a randomised crossover design, and the authors demonstrate less glycaemic variability early post-transplant with twice daily dosing. Such a reduction in variability may help to reduce beta-cell dysfunction based on the result of previous studies. There are a few issues that may hamper interpretation of the results of this study. First of all, the number of patients is small (22) and the dropout rate from the 34 originally randomised patients is quite high (35%) with no intention-to-treat analysis presented. Secondly, the actual magnitude of the results is small, with a difference in mean glucose of just 0.2 mmol/L between QD and BD dosing. In their sample size calculation, the authors themselves define a clinically important difference in mean blood glucose as 1.4mmol/L, so the clinical significance of these results is unclear. The differences in exposure to hyperglycaemia and peak glucose were slightly larger (although peak glucose only differed by 1mmol/L). It should also be noted that the prednisolone doses used were relatively high by modern standards (20-25mg/day), and the variability resulting from a lower dose early withdrawal protocol is less certain. There is also the issue of compliance that is not addressed – the pill-burden of the typical transplant patient in the early post-transplant period is high, and splitting doses in this way may have an effect on compliance.
Data analysis
Modified intention-to-treat analysis
Trial registration
Australian New Zealand Clinical Trials Registry: ACTRN12612001302842