FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000235440> ?p ?o ?g. }

• W2000235440 endingPage "384" @default.
• W2000235440 startingPage "378" @default.
• W2000235440 abstract "Hypertension occurs commonly in children with chronic kidney disease (CKD) and undoubtedly contributes to the progression of disease. This review summarizes the role of hypertension in the progression of CKD in children and highlights the central role played by the renin-angiotensin system in this relentless process. Strategies for renoprotection are discussed, and treatment recommendations are made for control of hypertension in this patient population. Hypertension occurs commonly in children with chronic kidney disease (CKD) and undoubtedly contributes to the progression of disease. This review summarizes the role of hypertension in the progression of CKD in children and highlights the central role played by the renin-angiotensin system in this relentless process. Strategies for renoprotection are discussed, and treatment recommendations are made for control of hypertension in this patient population. High blood pressure can be both a cause and a complication of chronic kidney disease (CKD). Because of their young age at the onset of either CKD or hypertension, children with CKD have a long period of exposure to these risk factor, and are, therefore, at significantly higher risk for complications.1Kidney Disease Outcomes Quality Initiative (K/DOQI) K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease.Am J Kidney Dis. 2004; 43: S1-S290PubMed Google Scholar Perhaps the most significant effect of hypertension in CKD is its effect on accelerating progression. Fortunately, data from adult studies suggest that aggressive antihypertensive therapy can ameliorate this effect and either delay or prevent the development of end-stage renal disease (ESRD).2Bakris G.L. Williams M. Dworkin L. et al.Preserving renal function in adults with hypertension and diabetes A consensus approach.Am J Kidney Dis. 2000; 36: 646-661Abstract Full Text Full Text PDF PubMed Scopus (1252) Google Scholar Although no similar data exist for children with CKD, recommendations from consensus organizations3National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and AdolescentsThe fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.Pediatrics. 2004; 114: 555-576Crossref PubMed Scopus (5986) Google Scholar support the adoption of this approach. Hypertension in children and adolescents continues to be defined as systolic or diastolic blood pressure (BP) that is, on repeated measurement, 95th percentile or higher for age, gender, and height. BP between the 90th and 95th percentile in childhood is now termed “prehypertensive,” and, as in adults,4Chobanian A.V. Bakris G.L. Black H.R. et al.The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure The JNC 7 report.JAMA. 2003; 289: 2560-2572Crossref PubMed Scopus (16837) Google Scholar adolescents with BP levels higher than 120/80 mm Hg should be considered prehypertensive.3National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and AdolescentsThe fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.Pediatrics. 2004; 114: 555-576Crossref PubMed Scopus (5986) Google Scholar Although these new definitions have not yet been applied to studies of blood pressure in children with CKD, experience from many studies demonstrates that hypertension is a frequent finding in children with CKD of various causes. Data from the 2004 report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reveal that of all children enrolled in the chronic renal insufficiency (CRI) registry, 38% were being treated with antihypertensive medications.5North American Pediatric Renal Transplant Cooperative Study2004 Annual Report. Emmes Corporation, Potomac, MD2005Google Scholar Earlier analyses of the NAPRTCS database have demonstrated that the prevalence of hypertension in children with CKD varies widely by diagnosis (Table 1); up to 70% to 80% of children with glomerulonephritis or polycystic kidney disease receive antihypertensive treatment.6Fivush B.A. Jabs K. Neu A.M. et al.Chronic renal insufficiency in children and adolescents The 1996 annual report of NAPRTCS.Pediatr Nephrol. 1998; 12: 328-337Crossref PubMed Scopus (107) Google Scholar The NAPRTCS database may actually underestimate the prevalence of hypertension in children with CKD because of the lack of a blood pressure–based definition of hypertension in these reports.Table 1Frequency of Hypertension in Childhood Renal DiseasesRenal DiseasePercent with HypertensionPolycystic kidney disease83Glomerulonephritis71Hemolytic uremic syndrome59Pyelonephritis/interstitial nephritis40Renal infarction23Structural renal disease19Other35Data from Fivush et al.6Fivush B.A. Jabs K. Neu A.M. et al.Chronic renal insufficiency in children and adolescents The 1996 annual report of NAPRTCS.Pediatr Nephrol. 1998; 12: 328-337Crossref PubMed Scopus (107) Google Scholar Open table in a new tab Data from Fivush et al.6Fivush B.A. Jabs K. Neu A.M. et al.Chronic renal insufficiency in children and adolescents The 1996 annual report of NAPRTCS.Pediatr Nephrol. 1998; 12: 328-337Crossref PubMed Scopus (107) Google Scholar The high prevalence of hypertension in children with CKD is indirectly borne out by many recently published studies of antihypertensive agents in children, most of which have enrolled high percentages of children with CKD.7Flynn J.T. Smoyer W.E. Bunchman T.E. Treatment of hypertensive children with amlodipine.Am J Hypertens. 2000; 13: 1061-1066Crossref PubMed Scopus (56) Google Scholar, 8Wells T. Frame V. Soffer B. et al.A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension.J Clin Pharmacol. 2002; 42: 870-880Crossref PubMed Scopus (127) Google Scholar Elevated blood pressure is also common in children after kidney transplantation,9Sorof J.M. Poffenbarger T. Portman R. Abnormal 24-hour blood pressure patterns in children after renal transplantation.Am J Kidney Dis. 2000; 35: 681-686Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar which may be related to graft dysfunction.10Nagasako S.S. Koch Nogueira P.C. et al.Arterial hypertension following renal transplantation in children—a short-term study.Pediatr Nephrol. 2003; 18: 1270-1274Crossref PubMed Scopus (18) Google Scholar Thus, many, if not most, children with CKD ultimately will require treatment for hypertension. In adults, hypertension is one of the most common causes of CKD. According to the 2004 US Renal Data Systems (USRDS) Annual Data Report, hypertension was the second-leading cause of ESRD in adults in 2002. It affected approximately 125,000 individuals, or 24.4% of the entire ESRD population.11US Renal Data System: USRDS 2002 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD2002Google Scholar In children, on the other hand, whether hypertension alone may result in ESRD is not clear. The NAPRTCS dialysis, transplant, and CRI registries do not list hypertension among the causes of CKD/ESRD in children.5North American Pediatric Renal Transplant Cooperative Study2004 Annual Report. Emmes Corporation, Potomac, MD2005Google Scholar However, close analysis of the USRDS data reveals that hypertension was reported as the cause of ESRD in more than 150 children in 2002.11US Renal Data System: USRDS 2002 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD2002Google Scholar As illustrated in Figure 1, hypertension was reported much less often than were other forms of kidney disease in children and was primarily reported as a cause of ESRD in children 10 years of age and older. Reconciling these two databases is difficult, as they are derived from significantly different sources. Because hypertension was reported as a cause of ESRD mostly in older children, perhaps long-standing hypertension may indeed lead to CKD/ESRD in adolescents, which adds further weight to recent recommendations that advocate earlier use of antihypertensive medications in some children and adolescents.3National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and AdolescentsThe fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.Pediatrics. 2004; 114: 555-576Crossref PubMed Scopus (5986) Google Scholar Prospective, long-term studies in adults such as the Multiple Risk Factor Intervention Trial and the Modification of Diet in Renal Disease (MDRD) study have demonstrated that hypertension is one of the major risk factors for the development and progression of CKD.12Klag M.J. Whelton P.K. Randall B.L. et al.Blood pressure and end-stage renal disease in men.N Engl J Med. 1996; 334: 13-18Crossref PubMed Scopus (1464) Google Scholar, 13Peterson J.C. Adler S. Burkart J.M. et al.Blood pressure control, proteinuria, and the progression of renal disease The Modification of Diet in Renal Disease Study.Ann Intern Med. 1995; 123: 754-762Crossref PubMed Scopus (1250) Google Scholar Although similar long-term studies in children are not yet available, a recent analysis of the NAPRTCS CRI database14Mitsnefes M. Ho P.-L. McEnery P.T. Hypertension and progression of chronic renal insufficiency in children A report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTICS).J Am Soc Nephrol. 2003; 14: 2618-2622Crossref PubMed Scopus (151) Google Scholar suggests that hypertension does play a similar role in children with CKD. In the study, Mitsnefes and coworkers14Mitsnefes M. Ho P.-L. McEnery P.T. Hypertension and progression of chronic renal insufficiency in children A report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTICS).J Am Soc Nephrol. 2003; 14: 2618-2622Crossref PubMed Scopus (151) Google Scholar compared the rate of progression of CKD in hypertensive children with that in normotensive children. Forty-eight percent of those enrolled in the CRI registry had hypertension at baseline. The time to endpoint was defined as the time between registry enrollment and progression to initiation of renal replacement therapy or a 10 mL/min/1.73 m2 decline in estimated glomerular filtration rate (eGFR) from baseline, whichever came first. A significant difference occurred in reaching endpoints between hypertensive and normotensive children; hypertensive children reached one of the defined endpoints sooner. Rate of progression of CKD was significantly greater for those with higher systolic BP (Fig 2), older age, and eGFR less than 50 mL/min/1.73m2. The authors concluded that hypertension is a highly significant and independent predictor for progression of CRI in children.14Mitsnefes M. Ho P.-L. McEnery P.T. Hypertension and progression of chronic renal insufficiency in children A report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTICS).J Am Soc Nephrol. 2003; 14: 2618-2622Crossref PubMed Scopus (151) Google Scholar One pediatric study provides additional support to the concept that hypertension is probably related to progression of CKD in children. In a prospective multicenter study that assessed the effects of a low-protein diet on the kidney function and growth in children with chronic kidney failure, Wingen et al15Wingen A.-M. Fabian-Bach C. Schaefer F. et al.Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children.Lancet. 1997; 349: 1117-1123Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar found that although a low-protein diet for 3 years did not effect the rate of decline in creatinine clearance, systolic BP greater than 120 mm Hg and urinary protein excretion greater than 50 mg/kg body weight/day were both independent predictors of an increased rate of decline in creatinine clearance. In their conclusions, the authors stated that their findings support the adoption of lower BP treatment goals in children as a means of slowing the progression of CKD, a recommendation that has, in fact, recently been made by consensus organizations in the United States.3National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and AdolescentsThe fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.Pediatrics. 2004; 114: 555-576Crossref PubMed Scopus (5986) Google Scholar Progression of CKD in hypertensive patients has been attributed to many interrelated mechanisms. The renin-angiotensin system (RAS) is believed to play a central role in the chain of events that lead to deterioration of kidney function (Fig 3). 16Soergel M. Schaefer F. Effect of hypertension on the progression of chronic renal failure in children.Am J Hypertens. 2002; 15: 53S-56SCrossref PubMed Google Scholar Systemic or local angiotensin II induces constriction, especially of the efferent arteriole, and thereby increases the intraglomerular pressure, which leads to elevated fluid shear stress,17Riser B.L. Cortes P. Zhao X. et al.Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formationin the rat.J Clin Invest. 1992; 90: 1932-1943Crossref PubMed Scopus (248) Google Scholar hyperfiltration, and proteinuria.18Johnsson E. Rippe B. Haraldsson B. Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure.Acta Physiol Scand. 1994; 150: 201-209Crossref PubMed Scopus (20) Google Scholar, 19Lewington A.J. Arici M. Harris K.P. et al.Modulation of the rennin-angiotensin system in proteinuric renal disease Are these added benefits?.Nephrol Dial Transplant. 2001; 16: 885-888Crossref PubMed Scopus (11) Google Scholar The proteinuria becomes part of a vicious circle by further activating the local RAS. Angiotensin II, apart from its vasoconstricting effects, induces local proinflammatory signaling molecules such as transforming growth factor–β (TGF-β), tissue necrosis factor–α (TNF-α), RANTES, and monocyte chemoattractant protein–1 (MCP-1) at the tubulointerstitial level and ultimately leads to increased matrix deposition, interstitial scarring, and glomerulosclerosis.19Lewington A.J. Arici M. Harris K.P. et al.Modulation of the rennin-angiotensin system in proteinuric renal disease Are these added benefits?.Nephrol Dial Transplant. 2001; 16: 885-888Crossref PubMed Scopus (11) Google Scholar, 20Zucchelli P. Zuccala A. Progression of renal failure and hypertensive nephrosclerosis.Kidney Int. 1998; 68: S55-S59Crossref Scopus (27) Google Scholar Angiotensin II and TGF-β1 have also been shown to up-regulate the expression of GLUT-1, the predominant glucose transporter for glomerular mesangial cells, and thereby are potentially involved in the development of diabetic glomerulosclerosis by promotion of excessive mesangial cell matrix production.21Weigert C. Brodbeck K. Brosius 3rd, F.C. et al.Evidence for a novel TGF-β1-independent mechanism of fibronectin production in mesangial cells overexpressing glucose transporters.Diabetes. 2003; 52: 527-535Crossref PubMed Scopus (62) Google Scholar Given the importance of the RAS in the progression of kidney disease, McLaughlin et al22McLaughlin K.J. Harden P.N. Ueda S. et al.The role of genetic polymorphisms of angiotensin-converting enzyme in the progression of renal diseases.Hypertension. 1996; 28: 912-915Crossref PubMed Scopus (60) Google Scholar studied the effect of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene on the rate of kidney function deterioration in 822 patients with a variety of kidney diseases and found that patients with the DD genotype, which is associated with increased transcription of the gene and leads to higher circulating levels of ACE, had more rapid deterioration of their kidney function.22McLaughlin K.J. Harden P.N. Ueda S. et al.The role of genetic polymorphisms of angiotensin-converting enzyme in the progression of renal diseases.Hypertension. 1996; 28: 912-915Crossref PubMed Scopus (60) Google Scholar Finally, exposure to systemic hypertension and progressive loss of kidney mass as a result of the natural history of the underlying kidney disease or as a result of hypertensive glomerulosclerosis also contributes to the progression of kidney disease via increased work and hyperfiltration in the remaining nephrons, a process that leads to glomerulosclerosis and, ultimately, to ESRD. Many studies in adults have demonstrated a slower progression rate of CRD and a renoprotective effect by aggressive BP control. In the MDRD study, for example, subjects randomized to the lower BP goal (defined as mean arterial pressure [MAP] of 92 mm Hg or less for patients 60 years of age or younger or 98 mm Hg or less for patients 61 years of age or older) had slower rates of progression of CKD than did subjects randomized to the “usual” BP goal (15 mm Hg higher than the lower BP goal). The effect of strict BP control was greatest in the subjects with higher levels of proteinuria.13Peterson J.C. Adler S. Burkart J.M. et al.Blood pressure control, proteinuria, and the progression of renal disease The Modification of Diet in Renal Disease Study.Ann Intern Med. 1995; 123: 754-762Crossref PubMed Scopus (1250) Google Scholar On the basis of the findings in the MDRD study, among others, recent consensus guidelines have recommended strict BP control in adults with proteinuric kidney disease as a method of slowing the progression of CKD.1Kidney Disease Outcomes Quality Initiative (K/DOQI) K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease.Am J Kidney Dis. 2004; 43: S1-S290PubMed Google Scholar, 2Bakris G.L. Williams M. Dworkin L. et al.Preserving renal function in adults with hypertension and diabetes A consensus approach.Am J Kidney Dis. 2000; 36: 646-661Abstract Full Text Full Text PDF PubMed Scopus (1252) Google Scholar, 4Chobanian A.V. Bakris G.L. Black H.R. et al.The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure The JNC 7 report.JAMA. 2003; 289: 2560-2572Crossref PubMed Scopus (16837) Google Scholar Given the central role of the RAS in progression of CKD as discussed above, many studies have examined whether interruption of the RAS would have a more specific effect on slowing progression. In the Ramipril Efficacy in Nephropathy (REIN) study,23Ruggenenti P. Perna A. Gherardi G. et al.Randomized placebo-controlled trial of effect of remipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia).Lancet. 1998; 352: 1252-1256Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar 352 subjects with nondiabetic CKD were randomized to ramipril or placebo (in addition to conventional antihypertensive therapy). Whereas achieved BP control was similar in the two groups, subjects with proteinuria of 3 g/day or higher at baseline who were assigned to ramipril had a significantly lower rate of decline in glomerular filtration rate (GFR) than did the placebo group.23Ruggenenti P. Perna A. Gherardi G. et al.Randomized placebo-controlled trial of effect of remipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia).Lancet. 1998; 352: 1252-1256Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar A similar beneficial effect of ACE inhibition on slowing progression has been demonstrated for benazepril. Maschio et al,24Maschio G. Alberti D. Janin G. et al.Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency.N Engl J Med. 1996; 334: 939-945Crossref PubMed Scopus (1721) Google Scholar in the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group, randomized 583 adult patients with various underlying renal diseases and diastolic blood pressure less than 90 mm Hg to treatment with either benazepril or placebo in addition to their other antihypertensive medications. Those patients randomized to benazepril had a decreased risk of reaching a study endpoint (doubling of the baseline serum creatinine concentration or the need for dialysis). Greatest benefit was seen in male patients, patients with glomerular disease, and patients with more than 1 g of proteinuria per 24 hours. The protective effect of benazepril was associated with decreases in both blood pressure and urinary protein excretion, which suggests that the renoprotective effect of benazepril was attributable to mechanisms other than blood pressure reduction.24Maschio G. Alberti D. Janin G. et al.Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency.N Engl J Med. 1996; 334: 939-945Crossref PubMed Scopus (1721) Google Scholar Many other trials of ACE inhibition have come to similar conclusions and have been pooled in recent meta-analyses. In their examination of the efficacy of ACE inhibitors for treatment of nondiabetic kidney disease, Jafar et al 25Jafar T.H. Schmid C.H. Landa M. et al.Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease A meta-analysis of patient-level data.Ann Intern Med. 2001; 135: 73-87Crossref PubMed Scopus (915) Google Scholar found that ACE inhibition significantly reduced the risk of progression of CKD, and the effect was dependent on multiple factors, including, but not limited to, blood pressure reduction and decreased proteinuria. They concluded that antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic kidney disease, and they recommended that ACE inhibitors be incorporated into the antihypertensive regimens of patients with CKD. Similar conclusions have been reached in other meta-analyses and systematic literature reviews.26Giatras I. Lau J. Levey A.S. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease A meta-analysis of randomized trials.Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group. Ann Intern Med. 1997; 127: 337-345Google Scholar, 27Kshirsagar A.V. Joy M.S. Hogan S.L. Falk R.J. Colindres R.E. Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease A systematic overview of randomized placebo-controlled trials.Am J Kidney Dis. 2000; 35: 695-707Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar On the basis of early evidence that angiotensin-receptor blockers (ARBs) are well tolerated in hypertensive patients with kidney disease,28Gansevoort R.T. de Zeeuw D. Shahinfar S. et al.Effects of the angiotensin II antagonist losartan in hypertensive patients with renal disease.J Hypertens. 1994; 12: S37-S42Google Scholar and more recent studies that demonstrate their benefit in patients with diabetic nephropathy,29Lewis E.J. Hunsicker L.G. Clarke W.R. et al.Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.N Engl J Med. 2001; 345: 851-860Crossref PubMed Scopus (5182) Google Scholar investigators have begun to examine their potential benefits when used in combination with ACE inhibitors. In the COOPERATE study,30Nakao N. Yoshimura A. Morita H. et al.Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE) A randomized controlled trial.Lancet. 2003; 361: 117-124Abstract Full Text Full Text PDF PubMed Scopus (984) Google Scholar subjects with nondiabetic CKD were randomized to receive either the ACE inhibitor trandolapril, the ARB losartan, or both agents in combination and followed for up to 36 months. Subjects who received the combined ACE/ARB treatment were significantly less likely to reach the combined primary endpoint of time to doubling of serum creatinine concentration or development of ESRD than were those who received either therapy alone.30Nakao N. Yoshimura A. Morita H. et al.Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE) A randomized controlled trial.Lancet. 2003; 361: 117-124Abstract Full Text Full Text PDF PubMed Scopus (984) Google Scholar Pediatric investigators have also examined whether interruption of the RAS can affect progression. Seeman et al31Seeman T. Dusek J. Vondrak K. et al.Ramipril in the treatment of hypertension and proteinuria in children with chronic kidney diseases.Am J Hypertens. 2004; 17: 415-420Crossref PubMed Scopus (38) Google Scholar treated 31 children with various forms of CKD and hypertension or proteinuria with ramipril for 6 months. They found that ramipril treatment effectively lowered ambulatory BP and normalized hypertension in 55% of their study population. In addition, proteinuria was reduced in 84% of subjects; greater reduction of proteinuria seen in subjects with higher levels of proteinuria at study entry. GFR was unchanged through the duration of the study, and ramipril treatment was well tolerated.31Seeman T. Dusek J. Vondrak K. et al.Ramipril in the treatment of hypertension and proteinuria in children with chronic kidney diseases.Am J Hypertens. 2004; 17: 415-420Crossref PubMed Scopus (38) Google Scholar Although these findings are intriguing, the duration of follow-up was too short to draw any conclusions about the potential effect of ramipril on progression of CKD in children. However, the question of whether ACE inhibition may slow the progression of CKD in children may soon be answered by the ongoing prospective multicenter trial, Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE).32Wühl E. Mehls O. Schaefer F. ESCAPE Trial Group Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure.Kidney Int. 2004; 66: 768-776Crossref PubMed Scopus (160) Google Scholar The ESCAPE investigators have treated 397 children with ramipril at a dose of 6 mg/m2/day. Subjects were randomized to either “conventional” (50th to 95th percentile mean 24-hour MAP) or “intensified” (less than 50th percentile mean 24-hour MAP) BP targets. Initial results have demonstrated that ramipril safely and effectively reduces BP and that it also reduces proteinuria; the magnitude of proteinuria reduction depended on the degree of baseline proteinuria. The antiproteinuric effect of ramipril was also significantly correlated with the antihypertensive efficacy of the drug.32Wühl E. Mehls O. Schaefer F. ESCAPE Trial Group Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure.Kidney Int. 2004; 66: 768-776Crossref PubMed Scopus (160) Google Scholar Long-term follow-up of this cohort should demonstrate whether ramipril (and ACE inhibition in general) has similar renoprotective effects in children with CKD as in adults. Angiotensin-receptor blockers have also been examined in children with CKD, although the experience is more limited than with ACE inhibitors. In one retrospective study, the use of losartan in children with proteinuria was found to be well tolerated and to significantly reduce proteinuria while preserving GFR.33Ellis D. Vats A. Moritz M.L. et al.Long-term antiproteinuric and renoprotective efficacy and safety of losartan in children with proteinuria.J Pediatr. 2003; 143: 89-97Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar However, to our knowledge, no studies have yet examined the combination of angiotensin-receptor blockers and ACE inhibitors in children with CKD. At present, therefore, no specific evidence from pediatric studies indicates that interruption of the RAS will be beneficial in slowing progression in children with CKD. Despite this lack of evidence, many pediatric nephrologists seem to have incorporated the results of trials conducted in adults into their treatment of children with CKD and hypertension. We surveyed more than 400 North American pediatric nephrologists on their antihypertensive medication choices for treatment of children with proteinuric kidney disease.34Woroniecki R.P. Flynn J.T. How are hypertensive children evaluated and managed?.A survey of North American pediatric nephrologists. Pediatr Nephrol. 2005; 20: 791-797PubMed Google Scholar The overwhelming first-line antihypertensive class choice was ACE inhibitors; more than 80% of respondents selected this therapy over other classes of antihypertensives (Fig 4). However, less than 50% of respondents utilized a lower BP goal in the management of hypertensive children with CKD than in those without CKD, probably because of the lack of consensus and clear clinical guidelines at the time that the survey was conducted.34Woroniecki R.P. Flynn J.T. How are hypertensive children evaluated and managed?.A survey of North American pediatric nephrologists. Pediatr Nephrol. 2005; 20: 791-797PubMed Google Scholar In 2005, however, pediatric consensus organizations have weighed in on the treatment of hypertensive children with CKD. In the “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents has recommended that hypertensive children with CKD should be treated to below the 90th percentile BP for age, gender and height—as opposed to children with primary hypertension, whose BP should only be lowered to below the 95th percentile.3National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and AdolescentsThe fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.Pediatrics. 2004; 114: 555-576Crossref PubMed Scopus (5986) Google Scholar The group, furthermore, recommended that consideration should be given to use of either ACE inhibitors or ARBs as first-line choices in this patient population; drugs from other classes with complementary mechanisms of action may be added as needed to achieve goal BP. The recently released K/DOQI practice guidelines for management of hypertension in patients with CKD1Kidney Disease Outcomes Quality Initiative (K/DOQI) K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease.Am J Kidney Dis. 2004; 43: S1-S290PubMed Google Scholar also state that children with CKD should be treated to below the 90th percentile. However, although specific recommendations were made in that document for preferential use of ACE inhibitors and angiotensin receptor blockers in adults with CKD, the evidence was considered too weak to make a similar recommendation in children. This reinforces the need for further study of renoprotection in children with CKD. Hypertension is extremely common in children with CKD and may even be a cause of CKD in some older children. Progression of CKD in children is likely to be exacerbated by hypertension; the RAS likely plays a central role among the many mechanisms of CKD progression. Given the beneficial effects of interruption of the RAS in hypertensive adults with CKD and the safety and efficacy of ACE inhibitors in short-term pediatric studies, antihypertensive regimens for children with CKD should be based upon ACE inhibition. Following the stepped-care approach,3National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and AdolescentsThe fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.Pediatrics. 2004; 114: 555-576Crossref PubMed Scopus (5986) Google Scholar an ACE inhibitor should be the initial agent chosen; other classes of antihypertensive agents may be added as needed until the child’s BP is below the 90th percentile for age, gender, and height. Addition of an ARB may provide additional benefit, although no pediatric data support this combination at present. Future interventional studies should be conducted to determine whether even lower levels of BP may provide additional benefit in slowing the progression of CKD in children." @default.
• W2000235440 created "2016-06-24" @default.
• W2000235440 creator A5010459902 @default.
• W2000235440 creator A5031877476 @default.
• W2000235440 date "2005-10-01" @default.
• W2000235440 modified "2023-10-12" @default.
• W2000235440 title "Hypertension in Children with Chronic Kidney Disease" @default.
• W2000235440 cites W1969950498 @default.
• W2000235440 cites W1970400657 @default.
• W2000235440 cites W1984778284 @default.
• W2000235440 cites W1993039788 @default.
• W2000235440 cites W1999730408 @default.
• W2000235440 cites W2008036896 @default.
• W2000235440 cites W2014855569 @default.
• W2000235440 cites W2021472878 @default.
• W2000235440 cites W2036719186 @default.
• W2000235440 cites W2037859712 @default.
• W2000235440 cites W2044773944 @default.
• W2000235440 cites W2049397775 @default.
• W2000235440 cites W2049587432 @default.
• W2000235440 cites W2057469615 @default.
• W2000235440 cites W2075391935 @default.
• W2000235440 cites W2091031177 @default.
• W2000235440 cites W2091496740 @default.
• W2000235440 cites W2096587435 @default.
• W2000235440 cites W2098011461 @default.
• W2000235440 cites W2108807575 @default.
• W2000235440 cites W2110046158 @default.
• W2000235440 cites W2120041834 @default.
• W2000235440 cites W2143144750 @default.
• W2000235440 cites W2156121263 @default.
• W2000235440 cites W2157734027 @default.
• W2000235440 cites W2170453602 @default.
• W2000235440 cites W2288605373 @default.
• W2000235440 cites W2312400976 @default.
• W2000235440 doi "https://doi.org/10.1053/j.ackd.2005.07.002" @default.
• W2000235440 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16198277" @default.
• W2000235440 hasPublicationYear "2005" @default.
• W2000235440 type Work @default.
• W2000235440 sameAs 2000235440 @default.
• W2000235440 citedByCount "28" @default.
• W2000235440 countsByYear W20002354402012 @default.
• W2000235440 countsByYear W20002354402013 @default.
• W2000235440 countsByYear W20002354402014 @default.
• W2000235440 countsByYear W20002354402017 @default.
• W2000235440 countsByYear W20002354402018 @default.
• W2000235440 countsByYear W20002354402019 @default.
• W2000235440 countsByYear W20002354402020 @default.
• W2000235440 countsByYear W20002354402021 @default.
• W2000235440 countsByYear W20002354402022 @default.
• W2000235440 crossrefType "journal-article" @default.
• W2000235440 hasAuthorship W2000235440A5010459902 @default.
• W2000235440 hasAuthorship W2000235440A5031877476 @default.
• W2000235440 hasBestOaLocation W20002354401 @default.
• W2000235440 hasConcept C126322002 @default.
• W2000235440 hasConcept C177713679 @default.
• W2000235440 hasConcept C2778653478 @default.
• W2000235440 hasConcept C2779134260 @default.
• W2000235440 hasConcept C71924100 @default.
• W2000235440 hasConceptScore W2000235440C126322002 @default.
• W2000235440 hasConceptScore W2000235440C177713679 @default.
• W2000235440 hasConceptScore W2000235440C2778653478 @default.
• W2000235440 hasConceptScore W2000235440C2779134260 @default.
• W2000235440 hasConceptScore W2000235440C71924100 @default.
• W2000235440 hasIssue "4" @default.
• W2000235440 hasLocation W20002354401 @default.
• W2000235440 hasLocation W20002354402 @default.
• W2000235440 hasOpenAccess W2000235440 @default.
• W2000235440 hasPrimaryLocation W20002354401 @default.
• W2000235440 hasRelatedWork W1995515455 @default.
• W2000235440 hasRelatedWork W2012225890 @default.
• W2000235440 hasRelatedWork W2060897516 @default.
• W2000235440 hasRelatedWork W2080531066 @default.
• W2000235440 hasRelatedWork W2748952813 @default.
• W2000235440 hasRelatedWork W2899084033 @default.
• W2000235440 hasRelatedWork W3031052312 @default.
• W2000235440 hasRelatedWork W3032375762 @default.
• W2000235440 hasRelatedWork W3108674512 @default.
• W2000235440 hasRelatedWork W3143792321 @default.
• W2000235440 hasVolume "12" @default.
• W2000235440 isParatext "false" @default.
• W2000235440 isRetracted "false" @default.
• W2000235440 magId "2000235440" @default.
• W2000235440 workType "article" @default.