Effect of Strict Blood Pressure Control and ACE-Inhibition on Progression of Chronic Renal Failure in Pediatric Patients

Summary

In children with chronic kidney disease, progression to end-stage renal failure is associated with high patient morbidity and poor quality of life. In adults, inhibition of the renin angiotensin system (RAS) slows down the rate of renal failure progression. This concept is as yet unproven in children, in whom chronic renal failure (CRF) is more commonly due to hypo/dysplastic malformations than to acquired glomerulopathies as typical for adult chronic kidney disease. The current project aims at assessing the genetic and molecular mechanisms and cardiovascular consequences of progressive CRF and to develop a strategy of pharmacological renoprotection in children.

Timeline

Start

1998-01

Primary completion

2007-07

Completion

2010-01

Publications

• Background ESCAPE Trial Group; Wuhl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Moller K, Wigger M, Peruzzi L, Mehls O, Schaefer F. Strict blood-pressure control and progression of renal failure in children. N Engl J Med. 2009 Oct 22;361(17):1639-50. doi: 10.1056/NEJMoa0902066.
• Background Tabatabaeifar M, Schlingmann KP, Litwin M, Emre S, Bakkaloglu A, Mehls O, Antignac C, Schaefer F, Weber S; ESCAPE Trial Group. Functional analysis of BMP4 mutations identified in pediatric CAKUT patients. Pediatr Nephrol. 2009 Dec;24(12):2361-8. doi: 10.1007/s00467-009-1287-6. Epub 2009 Aug 14.
• Background Gimpel C, Wuhl E, Arbeiter K, Drozdz D, Trivelli A, Charbit M, Gellermann J, Dusek J, Jankauskiene A, Emre S, Schaefer F; ESCAPE Trial Group. Superior consistency of ambulatory blood pressure monitoring in children: implications for clinical trials. J Hypertens. 2009 Aug;27(8):1568-74. doi: 10.1097/HJH.0b013e32832cb2a8.
• Background Grenda R, Wuhl E, Litwin M, Janas R, Sladowska J, Arbeiter K, Berg U, Caldas-Afonso A, Fischbach M, Mehls O, Sallay P, Schaefer F; ESCAPE Trial group. Urinary excretion of endothelin-1 (ET-1), transforming growth factor- beta1 (TGF- beta1) and vascular endothelial growth factor (VEGF165) in paediatric chronic kidney diseases: results of the ESCAPE trial. Nephrol Dial Transplant. 2007 Dec;22(12):3487-94. doi: 10.1093/ndt/gfm300. Epub 2007 Sep 26.
• Background Chinali M, de Simone G, Matteucci MC, Picca S, Mastrostefano A, Anarat A, Caliskan S, Jeck N, Neuhaus TJ, Peco-Antic A, Peruzzi L, Testa S, Mehls O, Wuhl E, Schaefer F; ESCAPE Trial Group. Reduced systolic myocardial function in children with chronic renal insufficiency. J Am Soc Nephrol. 2007 Feb;18(2):593-8. doi: 10.1681/ASN.2006070691. Epub 2007 Jan 10.
• Background Schonfelder EM, Knuppel T, Tasic V, Miljkovic P, Konrad M, Wuhl E, Antignac C, Bakkaloglu A, Schaefer F, Weber S; ESCAPE Trial Group. Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans. Am J Kidney Dis. 2006 Jun;47(6):1004-12. doi: 10.1053/j.ajkd.2006.02.177.
• Background Matteucci MC, Wuhl E, Picca S, Mastrostefano A, Rinelli G, Romano C, Rizzoni G, Mehls O, de Simone G, Schaefer F; ESCAPE Trial Group. Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol. 2006 Jan;17(1):218-26. doi: 10.1681/ASN.2005030276. Epub 2005 Nov 9.
• Results Wuhl E, Mehls O, Schaefer F; ESCAPE Trial Group. Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. Kidney Int. 2004 Aug;66(2):768-76. doi: 10.1111/j.1523-1755.2004.00802.x.
• Results Jourdan C, Wuhl E, Litwin M, Fahr K, Trelewicz J, Jobs K, Schenk JP, Grenda R, Mehls O, Troger J, Schaefer F. Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens. 2005 Sep;23(9):1707-15. doi: 10.1097/01.hjh.0000178834.26353.d5.
• Results Litwin M, Wuhl E, Jourdan C, Trelewicz J, Niemirska A, Fahr K, Jobs K, Grenda R, Wawer ZT, Rajszys P, Troger J, Mehls O, Schaefer F. Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol. 2005 May;16(5):1494-500. doi: 10.1681/ASN.2004110932. Epub 2005 Mar 16.
• Results Wuhl E, Hadtstein C, Mehls O, Schaefer F; ESCAPE Trial Group. Ultradian but not circadian blood pressure rhythms correlate with renal dysfunction in children with chronic renal failure. J Am Soc Nephrol. 2005 Mar;16(3):746-54. doi: 10.1681/ASN.2004070537. Epub 2005 Jan 12.
• Results Hadtstein C, Wuhl E, Soergel M, Witte K, Schaefer F; German Study Group for Pediatric Hypertension. Normative values for circadian and ultradian cardiovascular rhythms in childhood. Hypertension. 2004 Mar;43(3):547-54. doi: 10.1161/01.HYP.0000116754.15808.d8. Epub 2004 Jan 26.
• Results Wuhl E, Hadtstein C, Mehls O, Schaefer F; Escape Trial Group. Home, clinic, and ambulatory blood pressure monitoring in children with chronic renal failure. Pediatr Res. 2004 Mar;55(3):492-7. doi: 10.1203/01.PDR.0000106863.90996.76. Epub 2003 Nov 19.
• Speer T, Schunk SJ, Sarakpi T, Schmit D, Wagner M, Arnold L, Zewinger S, Azukaitis K, Bayazit A, Obrycki L, Kaplan Bulut I, Duzova A, Doyon A, Ranchin B, Caliskan S, Harambat J, Yilmaz A, Alpay H, Lugani F, Balat A, Arbeiter K, Longo G, Melk A, Querfeld U, Wuhl E, Mehls O, Fliser D, Schaefer F; 4C Study Investigators, ESCAPE Trial Investigators. Urinary DKK3 as a biomarker for short-term kidney function decline in children with chronic kidney disease: an observational cohort study. Lancet Child Adolesc Health. 2023 Jun;7(6):405-414. doi: 10.1016/S2352-4642(23)00049-4. Epub 2023 Apr 26.

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Indications