Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes in the Irbesartan Diabetic Nephropathy Trial

Background. It is important to know the reliability of early changes in proteinuria in predicting late renal outcomes. The IDNT was a trial in which treatment assignment, baseline and follow-up blood pressure determinations, and albumin/creatinine ratios (ACR), and renal outcomes were recorded. Methods. Risk of renal outcomes in the IDNT was assessed by proportional hazards modeling as a function of treatment assignment, and achieved systolic blood pressure (SBP) both without. and then with, inclusion of values for baseline proteinuria and early changes in proteinuria. Results. In models without ACR variables, both treatment with irbesartan and achieved SBP during follow-up were significantly predictive of the risk of renal outcomes. Addition of ACR variables to the models reduced the apparent impact of assignment to irbesartan by 52% to 81%, and irbesartan was no longer a significant predictor of renal outcomes. Conversely, addition of ACR variables to the models attenuated the effect of achieved follow-up SBP by only 32% to 46%, and follow-up BP remained a highly significant predictor of renal outcomes. Conclusion. The ability of early changes in proteinuria to predict the impact of treatment on renal outcomes is a function of the specific treatment. One must use caution in using early changes in proteinuria as a surrogate for longer-term renal outcomes.