Optimal blood pressure control and antihypertensive regimens in hypertensive renal disease: the potential of exploring the mechanisms of response variability

In renal patients rigorous blood pressure control is crucial to prevent renal and cardiovascular target organ damage. For renoprotection target blood pressure depends on the severity of proteinuria before treatment. For proteinuria of 1--3g/day a mean arterial pressure of 98 mmHg provides additional benefit, whereas the target should be as low as 92 mmHg if proteinuria exceeds 3g/day. The antiproteinuric effect of antihypertensive intervention predicts renoprotection; it is therefore recommended that therapy should be titrated not only on blood pressure, but also on reduction of proteinuria. All currently available classes of antihypertensives can be used to reduce blood pressure in renal patients. Interventions based on blockade of the renin-angiotensin-aldosterone system have additional antiproteinuric, and thus renoprotective, potential. Large individual differences in therapeutic benefit are common, even for interventions of proven efficacy at group level. Studies applying different classes of drugs in the same patient (rotation schedules) demonstrate that individual factors are main determinants of therapy response. Exploration of the mechanisms underlying these patient factors is important to improve treatment outcome. Analysis of genetic determinants of therapy response has great potential in this respect. However, therapy response is a complex phenotype. Thus, careful study of gene-gene and gene-environment interactions will be needed in order to turn this type of knowledge into benefit for the patient.