Effects of interventions in the RAAS and sodium status on classical and non-classical outcome parameters in chronic kidney disease

PhD ceremony: Mr. M.C.J. Slagman, 14.30 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Effects of interventions in the RAAS and sodium status on classical and non-classical outcome parameters in chronic kidney disease

Promotor(s): prof. G.J. Navis

Faculty: Medical Sciences

Chronic renal disease is prevalent in approx. 13% of the population. It is accompanied by renal function decline which can render patients dependent on dialysis or renal transplantation. Furthermore, chronic renal disease is associated with cardiovascular disease, in particular hypertension and proteinuria. Hypertension and proteinuria are maintained by over-activation of the RAAS hormone system (Renin Angiotensin Aldosterone System) and by excess retention of sodium chloride. Key elements of current treatment are reduction of proteinuria and hypertension by RAAS blocking medication, i.e., ACEi (Angiotensin Converting Enzyme inhibitors) or ARB (Angiotensin Receptor Blockers). Unfortunately this treatment is often insufficiently effective. In this thesis we investigated whether standard treatment can be improved by correcting sodium retention with dietary sodium restriction, and sodium-reducing medication (diuretics), and/or by intensified RAAS blockade. We found that dietary sodium restriction, with or without diuretics, highly improves the effects of standard treatment with ACEi or ARB. Combining sodium restriction (and diuretics) with ACEi or ARB better reduces proteinuria and hypertension, and lowers markers of injury, scarring, or a possible lack of oxygen in the kidneys. Combining ACEi with ARB (dual RAAS blockade) is less effective than sodium restriction, but may be a supplementary measure in some patients. Our research shows that a relatively modest reduction in sodium intake allows considerable health gains. This justifies efforts to support patients in accomplishing a healthy lifestyle, in order to prevent progressive renal and cardiovascular injury. Less sodium, less medication, less dialysis!