1. Use of ACE inhibitors for children with CKD Retrospective studies have suggested ACE inhibitors decrease proteinuria and slow the progression of renal insufficiency.
The ESCAPE Trial reported that strict blood pressure control using ramipril slowed the progression of renal insufficiency. However, the ACE inhibitors are not approved as renoprotective agents. The dose of ACE inhibitors (enalapril and ramipril) approved as antihypertensive agents for children in Japan should serve as the reference dose. 2. Use of ARBs for children with CKD Retrospective studies have suggested that ARBs decrease proteinuria Bortezomib order and inhibit the progression of renal insufficiency. A double-blind multinational study of 306 children with CKD reported that losartan significantly lowered BMS-354825 mw proteinuria and was well tolerated after 12 weeks in children with proteinuria with or without hypertension. ARBs are not approved as renoprotective agents. The dose of ARBs (valsartan) approved as antihypertensive agents of children in Japan should serve as the reference dose. 3. Combination therapy with ACE inhibitors and ARBs
for children with CKD The efficacy of combination therapy with ACE inhibitors and ARBs compared with single agent therapy (ACE inhibitor or ARB) has not been investigated in any RCTs. Therefore, we cannot
recommend combination therapy for the treatment of children with CKD with hypertension or proteinuria. Both ACE inhibitors and ARBs should be used cautiously if the GFR is less than 60 mL/min per 1.73 m2. Since the decline in GFR and hyperkalemia induced by RAS inhibition typically occurs within the first few days after the onset of therapy, the serum creatinine and potassium concentrations should be monitored. Bibliography 1. Soergel M, et al. Pediatr Nephrol. 2000;15:113–8. (Level 4) 2. Wühl E, et al. Kidney Int. 2004;66:768–76. (Level 4) 3. Ardissino G, et al. Nephrol Dial Transplant. 2007;22:2525–30. (Level 4) 4. ESCAPE Trial Group, et al. N Engl J Med. 2009;361:1639–50. (Level 2) 5. von Vigier RO, et al. Eur J Pediatr. Rebamipide 2000;159:590–3. (Level 4) 6. Ellis D, et al. J Pediatr. 2003;143:89–97. (Level 4) 7. Ellis D, et al. Am J Hypertens. 2004;17:928–35. (Level 4) 8. Simonetti GD, et al. Pediatr Nephrol. 2006;21:1480–2. (Level 4) 9. Franscini LM, et al. Am J Hypertens. 2002;15:1057–63. (Level 4) 10. White CT, et al. Pediatr Nephrol. 2003;18:1038–43. (Level 3) 11. Webb NJ, et al. Clin J Am Soc Nephrol. 2010;5:417–24. (Level 2) 12. Seeman T, et al. Kidney Blood Press Res. 2009;32:440–4. (Level 4) 13. Litwin M, et al. Pediatr Nephrol. 2006;21(11):1716–22.