Advancements in renal protection

Chronic kidney disease is a rising worldwide public health problem. The prevention of progressive renal function loss of both native and transplanted kidneys is therefore the main challenge in current clinical nephrology. Blockade of the renin-angiotensin aldosterone system (RAAS) with blood pressure and proteinuria lowering medication is standard treatment for patients with chronic kidney disease. However, as many patients still suffer ongoing renal function loss apparently the renoprotective effect of the current RAAS-blockade based regimens remains incomplete. This prompts for optimization of RAAS-blockade based therapy to provide better renoprotection. This thesis shows advancements in the efficacy of renoprotective intervention of RAAS blockade by combined intervention in sodium status by sodium restriction and diuretic treatment. We also show that aldosterone receptor blockade is a promising tool to improve renoprotective intervention in native and transplanted kidney disease. Additional modes of intervention that directly target other pathophysiological pathways involved in kidney disease might be useful. In this thesis we investigated whether intervention in advanced glycation end products (AGEs; glycated proteins) can exert renoprotective effects. Whether the AGE formation inhibitor pyridoxamine exerted renoprotective or nephrotoxic effects, depended on the studied animal model of renal damage. Based on the results of this thesis, we caution to study pyridoxamine in renal patients, especially when combining pyridoxamine with blockade of the RAAS. At present, RAAS blockade remains the cornerstone of renoprotective therapy; control of sodium status is important to optimize its effects.