Therapeutic strategies to slow chronic kidney disease progression

Abstract

Childhood chronic kidney disease commonly progresses toward end-stage renal failure, largely independent of the underlying disorder, once a critical impairment of renal function has occurred. Hypertension and proteinuria are the most important independent risk factors for renal disease progression. Therefore, current therapeutic strategies to prevent progression aim at controlling blood pressure and reducing urinary protein excretion. Renin-angiotensin-system (RAS) antagonists preserve kidney function not only by lowering blood pressure but also by their antiproteinuric, antifibrotic, and anti-inflammatory properties. Intensified blood pressure control, probably aiming for a target blood pressure below the 75th percentile, may exert additional renoprotective effects. Other factors contributing in a multifactorial manner to renal disease progression include dyslipidemia, anemia, and disorders of mineral metabolism. Measures to preserve renal function should therefore also comprise the maintenance of hemoglobin, serum lipid, and calcium-phosphorus ion product levels in the normal range.

Fig. 1

Pathophysiology, consequences, and treatment options of hypertension and proteinuria in chronic kidney disease. EPO erythropoietin, P reduction serum phosphate reduction, RAS renin angiotensin system, Non-DHP CCP non dihydropyridine calcium channel blockers, TGFβ transforming growth factor β, TIMP tissue inhibitors of metalloproteinases, ET1 endothelin 1, PAI plasminogen activator inhibitor, ⊥ inhibitory effect