Dick de Zeeuw

The Antiproteinuric Effect of Angiotensin-Converting-Enzyme Inhibitors in Human Renal Disease

Many renal diseases are accompanied by an excess loss of plasma proteins in the urinary space. As such proteinuria has been successfully used as a tool both to detect the presence of renal disease and to evaluate the success of therapeutic interventions on disease activity. The quantity and quality of the urinary protein leakage may in some cases distinguish between the different underlying causes of renal disease. In case of minimalchange disease, protein is usually excreted in considerable quantities, largely confined to albumin, whereas in case of specific renal tubular diseases proteinuria is rather small consisting mainly of low-molecular-weight proteins. However, in general, proteinuria does not differentiate between the multiple causes of renal insults, suggesting a more or less common cause and pathway of urinary protein loss. Indeed, such a common cause may be a loss of the discriminating properties of the glomerular filtration barrier for different macromolecules. In health, this barrier prevents the leakage of plasma proteins to the urinary space by at least two selective mechanisms. Firstly, the filtration pores are of limited size, hindering passage of macromolecules larger than ≈55 Angstrom (size selectivity). Secondly, negative charges embedded in the filtration barrier prevent leakage of the main negatively-charged plasma protein, albumin (charge selectivity). Furthermore, proximal tubular protein reabsorption prevents urinary protein leakage of those proteins that escape these restrictive filtration properties.

NT-PROBNP AND HSTNT IMPROVE CARDIOVASCULAR RISK PREDICTION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS, CHRONIC KIDNEY OR CARDIOVASCULAR DISEASE OR BOTH

Although patients with type 2 diabetes (T2DM) are at high risk of cardiovascular (CV) events, the factors associated with risk are unclear. We examined the predictors of CV mortality and morbidity in a high risk population with T2DM (history of chronic kidney or CV disease or both) in the Aliskiren

How to Attain Optimal Antiproteinuric Dose of Losartan in Non-Diabetic Patients with Nephrotic Range Proteinuria

Although the antiproteinuric response to antihypertensive treatment is the main predictor of renoprotective efficacy in long-term renal disease, dose finding studies of antihypertensives have only been based on blood pressure so far. The present study aimed to find the optimal antiproteinuric dose of the angiotensin II antagonist losartan. An open-label dose-response study using subsequent six-week treatment periods was performed in ten non-diabetic patients with proteinuria (Uprot) of 5.8 ± 0.8 g/d and a mean arterial pressure (MAP) of 103 ± 3.7 mmHg without antihypertensive medication. All patients had a normal to moderately impaired renal function. After the baseline period, five periods followed with respectively a daily losartan dose of 50 mg, 100 mg, 150 mg, again 50 mg, and a recovery without losartan. At the end of each period, Uprot and MAP were measured. The consecutive doses of losartan had a similar antihypertensive response (−11.3 f 2.8% at the 100 mg dose). The optimal antiproteinuric response was reached at 100 mg losartan (−30 ± 8%). The 50 mg dose (−13 ± 7%) was less effective and the 150 mg dose (−28 ± 8%) was not more effective. We conclude that 100 mg losartan is the optimal dose for reduction of proteinuria in non-diabetic patients with nephroticrange proteinuria.