Abstract
The standard renoprotection is based on the inhibition of the renin-angiotensin system (RAS) by angiotensin convertase inhibitors (ACEi) or angiotensin II receptor 1 blockers (AT1B). The aim of our study was to analyze the effects of the addition of AT1B to ACEi-based renoprotection in children with chronic kidney disease. We examined 11 children with a mean age of 10.5 years (range, 0.5–18 years) with a mean glomerular filtration rate (GFR) of 61±61 ml/min/1.73 m2. In four patients, the primary renal disease was hemolytic uremic syndrome, in three congenital nephrotic syndrome (CNS), in two reflux nephropathy, prune-belly syndrome in one and acute cortical necrosis in one. All patients were treated with complex hypotensive ACEi-based therapy. AT1B losartan was added in a mean dose of 0.9 mg/kg/day. The change in GFR, proteinuria and blood pressure at two 12-month intervals before and after adding AT1B was compared. The results showed that during the 12 months preceding AT1B therapy, there was no change in blood pressure and proteinuria, but the GFR declined in 7 of 11 patients. After the 12th month of add-on therapy with AT1B, there was a significant decrease in both absolute and indexed blood pressure values. Proteinuria decreased in eight patients, did not change in one and increased in two, including one with CNS. The GFR stabilized or increased in eight patients and decreased in three patients with CNS. In 7 of 11 patients, there was a significant, but not threatening increase in serum potassium. In conclusion, add-on renoprotection with AT1B added to ACEi is safe and significantly improves the renoprotective effects of ACEi treatment in children with progressive nephropathies, including patients with advanced CKD.
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References
Del Vecchio L, Locatelli F (2001) The renoprotective effect of combined antihypertensive drugs. J Nephrol 14:7–14
Lama G, Salsano ME, Pedulla’ M, Grassia C, Ruocco G (1997) Angiotensin converting enzyme inhibitors and reflux nephropathy: a 2-year follow-up. Pediatr Nephrol 11:714–718
Trachtman H, Gauthier B (1988) Effect of angiotensin-converting enzyme inhibitor therapy on proteinuria in children with renal disease. J Pediatr 112:295–298
Ruilope LM, Aldigier JC, Ponticelli C, Oddou-Stock P, Botteri F, Mann JF (2000) Safety of the combination of valsartan and benazepril in patients with chronic renal disease. European Group for the Investigation of Valsartan in Chronic Renal Disease. J Hypertens 18:89–95
Nakao N, Seno H, Kasuga H, Toriyama T, Kawahara H, Fukagawa M (2004) Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: a COOPERATE-ABP substudy. Am J Nephrol 24:543–548
Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T (2003) Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 361:117–124
Shiigai T, Schichiri M (2001) Late escape from the antiproteinuric effect of ACE inhibitors in nondiabetic renal disease. Am J Kid Dis 37:477–483
Kincaid-Smith P, Fairley KF, Packham D (2004) Dual blockade of the renin-angiotensin system compared with a 50% increase in the dose of angiotensin-converting enzyme inhibitor: effects on proteinuria and blood pressure. Nephrol Dial Transplant 19:2272–2274
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576
Wuhl E, Mehls O, Schaefer F; ESCAPE Trial Group (2004) Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. Kidney Int 66:768–776
Van Dyck M, Proesmans W (2004) Renoprotection by ACE inhibitors after severe hemolytic uremic syndrome. Pediatr Nephrol 19:688–690
Litwin M (2004) Risk factors for renal failure in children with non-glomerular nephropathies. Pediatr Nephrol 19:178–186
Adler L, Mathew R, Futterweit S, Frank R, Gauthier BG, Kashtan CE, Trachtman H (2002) Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-beta and nitrite excretion. BMC Nephrol 3:2
Holmberg C, Trygvasson K, Kestila MK, Jalanko HJ (2004) Congenital nephrotic syndrome. In: Avner ED, Harmon WE, Niaudet P (eds) Pediatric nephrology, 5th edn. Lippincot Wiliams & Wilkins, pp 503–516
Hamed RM, Shomaf M (2002) Congenital nephritic syndrome: a clinico-pathological study of 30 children. J Nephrol 14:104–109
Ellis D, Moritz ML, Vats A, Janosky JE (2004) Antihypertensive and renoprotective efficacy and safety of losartan. A long-term study in children with renal disorders. Am J Hypertens 17:928–935
Gartenmann AC, Fossali E, von Vigier RO, Simonetti GD, Schmidtko J, Edefonti A, Bianchetti MG (2003) Better renoprotective effect of angiotensin II antagonist compared to dihydropyridine calcium channel blocker in childhood. Kidney Int 64:1450–1454
Tanaka H, Suzuki K, Nakahata T, Tsugawa K, Konno Y, Tsuruga K, Ito E, Waga S (2004) Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy. Pediatr Int 46:576–579
Yang Y, Ohta K, Shimizu M, Nakai A, Kasahara Y, Yachie A, Koizumi S (2005) Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy. Clin Nephrol 64:35–40
Ihle BU, Whitwirth JA, Shahinfar S, Cnaan A, Kincaid-Smith PS, Becker GJ (1996) Angiotensin-converting enzyme inhibition in non-diabetic progressive renal insufficiency: a controlled double-blind trial. Am J Kidney Dis 27:489–495
Hou FF, Zhang X, Zhang GH, **e D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Gang RW (2006) Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Eng J Med 354:131–140
Shahinfar S, Cano F, Sofffer BA, Ahmed T, Santoro EP, Zhang Z, Gleim G, Miller K, Vogt B, Blumer J, Biezogounov J (2005) A double-blind, dose-response study of losartan in hypertensive children. Am J Hypertens 18:183–190
Rossing K, Schjoedt KJ, Jensen BR, Boomsma F, Parving HH (2005) Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney Int 68:1190–1198
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Litwin, M., Grenda, R., Śladowska, J. et al. Add-on therapy with angiotensin II receptor 1 blocker in children with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors. Pediatr Nephrol 21, 1716–1722 (2006). https://doi.org/10.1007/s00467-006-0223-2
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DOI: https://doi.org/10.1007/s00467-006-0223-2