Predicting and improving individual long-term outcome in patients with diabetes and nephropathy: determinants of response to RAAS inhibition

PhD ceremony: Mr. F.A. Holtkamp, 14.30 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Predicting and improving individual long-term outcome in patients with diabetes and nephropathy: determinants of response to RAAS inhibition

Promotor(s): prof. P.A. de Graeff, prof. D. de Zeeuw

Faculty: Medical Sciences

This thesis deals with long-term renal and cardiovascular outcomes of patients with diabetes type 2 and nephropathy that were treated with angiotensin receptor blockers (ARBs). The predictive value of some important biomarkers and the value in predicting the response of ARBs and associated long-term effects in this patient group with a high mortality rate were evaluated. For this purpose the individual patient data of the RENAAL and the IDNT trials were used. First, the value of albuminuria (protein level in urine) and GFR (measure of renal function) for prediction of long-term outcome were described. We demonstrated that albuminuria is an important biomarker that should be reduced together with high blood pressure to achieve optimal cardiovascular protection during ARB treatment. Also, we showed that a reduction in eGFR (a measure of renal function) after initiation of ARB treatment could be predictive for long-term renal protection. Renal and cardiovascular protection may be enhanced by a lower sodium intake during ARB treatment. However, we also showed that altered potassium levels caused by this treatment, may increase cardiovascular risk and should therefore be maintained within normal levels by means of sufficient monitoring and management for optimal protection. In addition to providing more insight in individual treatment with ARBs, these analyses also provide valuable information on how to conduct and interpret clinical trials in patients with diabetes and nephropathy.