Novel aspects regarding mechanisms and consequences of albuminuria

The studies described in this thesis were clustered around three questions. First, what are the echanisms underlying urinary albumin leakage? Second, what causes a rise in albuminuria, and third, why is albuminuria predictive for not only renal but also vascular events?

Microalbuminuria, is not merely a consequence of hypertension or diabetes and a reflection of the severity on these underlying conditions. Even in the absence of hypertension, diabetes and a cardiovascular disease history, microalbuminuria heralds a poor prognosis and warrants medical attention.

Although we cannot exclude that uric acid causes vascular damage, and consequently albuminuria, we provide epidemiological evidence that albuminuria may at least also cause an increase in serum uric acid, by enhancing tubular uric acid reabsorption. Microalbuminuria is associated with an increase in glomerular as well as tubular damage markers, suggesting that albuminuria can have a glomerular as well as a tubular origin. However, if microalbuminuria is associated with glomerular damage, it is often progressive. In contrast, albuminuria associated with tubulointerstitial damage, is in general more stable.

When investigating risk factors for progressive albuminuria, it appears that a high baseline value of albuminuria is by far the most important predictor for progressive albuminuria.

Over time, higher sodium intake is associated with increases in albuminuria. Among individuals with at baseline high albuminuria, a higher sodium intake is furthermore an independent risk factor for developing hypertension, suggesting that especially subjects with higher albuminuria may benefit from dietary salt reduction.

Increased hsTnT or NT-pro-BNP should be taken seriously as a prognostic marker for a worse cardiovascular outcome, even in subjects with mild chronic kidney disease, and not be discarded as merely a reflection of decreased renal clearance.