Skip Navigation



NDT Advance Access published online on February 13, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl839
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/5/1332    most recent
gfl839v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Chandar, J.
Right arrow Articles by Zilleruelo, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chandar, J.
Right arrow Articles by Zilleruelo, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Angiotensin blockade as sole treatment for proteinuric kidney disease in children

Jayanthi Chandar, Carolyn Abitbol, Brenda Montané and Gastón Zilleruelo

Department of Paediatrics, Division of Paediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, 33101, Miami, USA

Correspondence and offprint requests to: Jayanthi Chandar, MD, Division of Paediatric Nephrology, University of Miami/Holtz Children's Hospital, P.O. Box 016960 (M-714), Miami, Florida 33101, USA. Email: jchanda2{at}med.miami.edu



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
Background. The traditional management of children with proteinuric kidney disease is treatment with high dose steroids regardless of comorbid conditions such as obesity. This study evaluated the effect of angiotensin blockade (AB) alone as the sole management of children with non-diabetic proteinuric kidney disease.

Methods. Retrospective chart analysis was performed in 146 children. Seventeen were identified to have received angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker exclusively for management of proteinuria. Total proteinuria (Upr/cr), albuminuria (Ualb/cr), estimated glomerular filtration rate (eGFR), serum potassium and blood pressure were assessed at baseline and at 3–month intervals for over 24 months.

Results. Mean age was 11.2 ± 4.8 years with 12 females. Eleven of 17 patients (65%) were overweight or obese. There was a significant decline in total proteinuria and albuminuria after 3–6 months of AB therapy and a further decline with longer duration of treatment (P < 0.001). Although single vs dual AB were similarly effective in lowering total proteinuria, dual therapy was more effective in lowering albuminuria (single 57 ± 23% vs dual 71 ± 15%; P < 0.02). The eGFR decreased from ‘hyperfiltration’ levels prior to initiation of AB to normal at the end of the treatment period (145 ± 41–111 ± 17 ml/min/1.73m2; P = 0.01). Systemic blood pressures remained normal throughout the study period.

Conclusions. Angiotensin blockade alone appears to effectively control proteinuria and stabilize kidney function in children. This may provide an alternative to more toxic therapies, especially corticosteroids, in children with glomerular disorders such as those associated with obesity.

Keywords: albuminuria; angiotensin blockade; hyperfiltration; obesity; proteinuria



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
The renin–angiotensin–aldosterone system (RAAS) has been implicated in the pathophysiology of progressive kidney disease by several mechanisms including induction of systemic and glomerular hypertension, mesangial cell proliferation and matrix synthesis, endothelial injury and direct pro-inflammatory and pro-fibrotic effects [1,2]. Pernicious proteinuria is believed to contribute to and perpetuate renal injury [2,3]. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have been shown to reduce proteinuria and delay progression of kidney disease in adults with diabetic and non-diabetic nephropathies [3–5]. There is substantial experimental evidence that angiotensin blockade results in regression of histological changes including sclerosis in animal studies [6,7]. Therefore, ACEI and/or ARB therapy has potential reno-protective effects beyond decreasing proteinuria [6–8].

Many children with primary glomerular disease are treated with high doses of corticosteroids and other potentially toxic immune modulating agents. The addition of angiotensin blockade (AB) with either ACEI and/or ARB alone or in combination has been shown to further decrease proteinuria in children [9–14]. However, the independent effect of AB needs further elucidation. In a retrospective review, we analysed the effect of AB as the sole management of proteinuria in children with early-stage kidney disease.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 Acknowledgements
 References
 
Between January 2001 and June 2006, a retrospective chart review was performed on 146 children between the ages of 2 and 21 years, referred for evaluation of non-diabetic proteinuric kidney disease to the Division of Paediatric Nephrology, University of Miami Miller School of Medicine, Holtz Children's Hospital. From this cohort, 17 children were identified whose proteinuria was managed solely with angiotensin blockade. The study was approved by the institutional review board. All subjects were assured anonymity in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

Inclusion criteria for the study required a persistent level of proteinuria ≥500 mg/m2/day or a urine protein/creatinine ratio (Upr/cr) ≥0.5 and an estimated eGFR ≥75 ml/min/1.73 m2. The eGFR was calculated as the creatinine clearance (Ccr) by the height index formula of Schwartz [15]. The patients with specific diagnoses could not have concurrent or recent use (within the previous 3 months) of immunosuppressive drugs. No patient was receiving other antihypertensive medications. Infants <2 years of age or patients with human immunodeficiency virus (HIV) nephropathy were excluded.

ACEI or ARB were used as the AB agents. The ACEI was enalapril at a dose of 0.25–0.5 mg/kg/day. The ARB was either candesartan (dose 0.2–0.4 mg/kg/day) or losartan (0.4–1 mg/kg/day). The patients were started on a low dose of the medication with increments in dosing every 4–12 weeks based on the patient's tolerance to the drug and the response in proteinuria. The goal was to achieve the maximum anti-proteinuric effect at the lowest possible dose of medication. Combination (dual) therapy allowed lower dosing of each drug with one being given in the morning and the other at bedtime.

Patients were initially assessed for systemic signs and symptoms of their kidney disease. Body mass index (BMI = weight(kg)/height(m2)) was recorded at the initial encounter and results reported as percentile values for age [16]. Overweight was considered >85th percentile and obesity >95th percentile. ‘Casual’ sitting systolic and diastolic blood pressures were measured by the Dinamap® oscillometric technique at each clinic visit. Normal values were taken from the Fourth Report of the Working Group on Paediatric Hypertension [17]. Hypertension in casual measurements was defined as ≥95th percentile for age, height and gender.

Appropriate serological tests and kidney biopsy were performed in all patients to help determine diagnosis and management. Twenty-four hour and/or random urine for protein/creatinine and microalbumin, serum electrolytes, creatinine, albumin and blood pressures were obtained at baseline, 3–6 months, 12–18 months and at 24–30 months of treatment.

All urine product measurements were reported or converted into metric units [milligrams/deciliter (mg/dl)]. Degree of proteinuria was determined by the random urine protein to creatinine ratio (Upr/cr) in milligrams/milligrams with normal <0.2 and nephrotic range >2.0 [18]. Albuminuria was determined by the urine albumin to creatinine ratio (Ualb/cr) converted to milligrams per milligram creatinine (mg Alb/mg Cr) for ease of comparison with the Upr/cr. The calculation was as follows:


Formula

with normal considered ≤0.030 mg Alb/mg Cr or ≤30 mg/g Cr.

Urine and serum assays were performed in the central hospital clinical laboratory on the multi-channel analyser or the Quest® referral laboratories. Total protein was analysed by a standard modification of the Lowry technique using a dye-binding automated spectrophotometric method. The coefficient of variation is <5%. Creatinine was performed by the alkaline picrate method, a modification of the kinetic Jaffé reaction [Dade Paramax® (Dade Corp. Miami, FL, USA)]. The coefficient of variation is <2%. Microalbumin was determined by rate nephelometry with the Beckman Coulter Array®. The coefficient of variation is <4%.

Statistical methods
All data sets were analysed for Gaussian distribution using the D’Agostino-Pearson omnibus test for normality. Differences in proteinuria over time and percentage decline in urine protein fractions were analysed by one way analysis of variance (ANOVA) using the Kruskal–Wallis test for non-parametric data with Dunn's multiple comparisons post-test. The final GFR was compared with that at each time interval using repeated measures ANOVA with Bonferroni's multiple comparisons test. Correlation coefficients between two variables were calculated using Spearman rank order correlation. P-values of <0.05 were considered significant. All results are expressed as the mean ± SD). All graphs and statistical analyses were determined using GraphPad Prism® version 4.00 for Windows, GraphPad Software (San Diego, California USA, www.graphpad.com).



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 Acknowledgements
 References
 
Demographics (Table 1)
Average age of the 17 children with proteinuria was 11.2 ± 4.8 years. Twelve of them were females. The racial distribution was nine African-American, seven Hispanics and one Caucasian. Nine of them received monotherapy with ARB and one with ACEI. Seven children received a combination of both ACEI and ARB. The average dose of candesartan was 0.2 ± 0.08 mg/kg/day, losartan 0.42 ± 0.1 mg/kg/day, and enalapril 0.1 ± 0.04 mg/kg/day. The maximum doses were 0.38, 0.57 and 0.16 mg/kg/day, respectively. All patients had a renal biopsy after they were noted to have persistent and/or progressive proteinuria.


View this table:
[in this window]
[in a new window]

  		Table 1. Patient Demographics

 
Three patients had a history of receiving immunosuppressive drugs 6–12 months prior to the study. These patients presented with oedema and had the biopsy diagnosis of mesangial proliferative nephritis (MesGN), focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN), respectively. All three had received treatment with steroids and one received ciclosporin followed by mycophenolate mofetil. All three persisted with significant proteinuria despite treatment with immunosuppressive agents. Therefore, immunosuppression was stopped and they were maintained on angiotensin blockade therapy alone.

A majority of the patients (11/17;65%) were either overweight or obese. These patients had lesions of FSGS (4), MN (2), MesGN (4) by biopsy. The remainder of the patients had FSGS (3), MesGN (2), membranoproliferative glomerulonephritis (MPGN) (1), and Alport's syndrome (1).

Treatment course (Table 2)
Fourteen patients completed >24 months of treatment while three completed >12 months of treatment. Blood pressures remained within normal parameters for age, gender and height throughout the observation period. Serum potassium also remained within normal limits. One patient complained of dizziness on candesartan when the dose was increased to >0.2 mg/kg body weight without a documented change in heart rate or blood pressure. No patient experienced cough.


View this table:
[in this window]
[in a new window]

  		Table 2. Treatment parameters over time

 
Fractional response of proteinuria
Ten of 17 (59%) children had nephrotic range proteinuria. Figure 1 demonstrates the progressive decrease in total proteinuria (Upr/cr) and the albumin fraction (Ualb/cr) during the 2-year treatment observation period. The fall in Upr/cr was significant after 3 months of therapy. By 24 months, the fall from baseline was maintained at near normal levels (mean Upr/cr = 0.4 ± 0.3; P < 0.001). The decline in the albumin fraction was proportionate to that of total proteinuria but failed to reach significance from baseline until after 24 months of treatment (final Ualb/cr = 0.2 ± 0.3; P < 0.05). Therefore, the decline in the ‘non-albumin’ fraction of proteinuria was proportionately greater than in the ‘albumin’ fraction. Due to the small size of the cohort, it was difficult to correlate response to histopathological diagnosis. Three of 17 patients (1- FSGS and sickle cell disease, 1-mesangial proliferative glomerulonephritis and obesity, 1-membranous nephropathy and obesity) with an initial mean Upr/cr of 2.5 ± 1.0 (mg/mg), had total resolution of proteinuria at 24–30 months and maintained stable renal function. There was no difference in initial proteinuria or response to AB between African-American and Hispanic children. Serum albumin was 3.4 ± 0.9 gm/dl at the initiation of AB and increased to 4.0 ± 0.4 gm/dl after 24–30 months. However, the difference was not statistically significant.


Figure 1
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1. Relative decline in proteinuria over time with angiotensin blockade is shown by urine total protein (Upr/cr) (solid line) and albumin (Ualb/cr) (dashed line) to creatinine ratios expressed as milligram per milligram (mg/mg). *P < 0.05 Baseline versus 3–6 months, 12–18 months; **P < 0.001 Baseline versus 24–30 months for Upr/cr only.

 
Dual vs single drug angiotensin blockade
Although the numbers were small, patients receiving a single AB blocker (n = 10) were compared with those receiving dual therapy with both ACEI and ARB (N = 7). Figure 2 demonstrates the difference in percent decline in Upr/cr and Ualb/cr by single vs dual AB. The decrease in the total protein component was similar with both single and dual therapy (single 84.6 ± 11% vs dual 84.1 ± 12%; P = NS). However, in patients treated with a single drug, the percent decline in albuminuria was significantly less than that of total proteinuria (Upr/cr 84.6 ± 11% vs Ualb/cr 57 ± 23%; P < 0.05). Whereas, combination therapy was equally effective in decreasing both the total and albumin components of proteinuria (Upr/cr 84.1 ± 121% vs Ualb/cr 71 ± 15%; P = NS).


Figure 2
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2. Percentage decline in urine protein fractions with single drug angiotensin blockade (Single AB) vs combination ACEI + ARB (Dual AB). Solid columns represent percent decline in total proteinuria (Upr/cr) while open columns are percent decline in albuminuria (Ualb/cr). *P < 0.05 compared with Upr/cr.

 
eGFR and hyperfiltration
All patients in this cohort had early stage kidney disease with eGFR averaging within the; ‘normal filtration’ (eGFR ≤ 125 ml/min/1.73 m2; n = 6) or the ‘hyperfiltration’ (eGFR > 125 ml/min/1.73 m2; n = 11) range. Overall, there was a significant decline in the average eGFR from 145 ± 41 ml/min/1.73 m2 prior to initiation of AB to 111 ± 17 ml/min/1.73 m2 at 24–30 months (P = 0.03). When the 11 patients with hyperfiltration were considered separately, only these showed a significant decline in their eGFR from an initial average of 172 ± 35 ml/min/1.73 m2 to a normal range of 121 ± 17ml/min/1.73 m2 after 24–30 months (P ≤ 0.02). Whereas, the six patients who began with normal filtration (average eGFR = 101.5 ± 15 ml/min/1.73 m2) showed no significant change in eGFR at 24–30 months (Figure 3). The initial and final Upr/cr of patients with eGFR in the hyperfiltration range was comparable to those with normal filtration. In all patients, the change in eGFR was independent of systemic blood pressures since initial and subsequent blood pressures throughout the treatment period were ≤95th percentile for age, gender, and height.


Figure 3
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3. Change in eGFR over time during treatment with angiotensin blockade. There was a significant decline in eGFR in those children with hyperfiltration (eGFR > 125 ml/min/1.73 m2) (solid line) at 24–30 months after initiation of angiotensin blockade (P < 0.001). Those with normal initial filtration (eGFR ≤ 125 ml/min/1.73 m2) (dashed line) maintained similar eGFR throughout treatment. **Indicates significant difference between normal eGFR group and hyperfiltration eGFR group, P < 0.001. *Indicates significant difference between initial and final eGFR in the hyperfiltration group at 24–30 months, P < 0.02.

 


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
Acknowledgements
 References
 
This study demonstrates the individual effectiveness of blockade of the RAAS axis in the treatment of proteinuric kidney disease in children. Steroids and cytotoxic drugs have been used in the treatment of glomerular disease with the aim of decreasing inflammation and suppressing the immune responses believed to be responsible for the progressive nature of proteinuric kidney disease. Although these drugs have proven benefits in some glomerular disorders, they are fraught with significant toxicity. In recent years, efforts have been directed towards alternative and disease-specific therapies [9–10,12]. Our observations in children treated with angiotensin blockade alone suggest that this may provide an effective alternative to aggressive steroid and immune modulating therapies in some glomerular diseases.

This small cohort of young patients provided a unique opportunity to analyse the independent effect of angiotensin blockade on proteinuria in the clinical setting of early stage chronic kidney disease with normal systemic blood pressures. The long-term effect of angiotensin blockade was impressive with a continual decline in total proteinuria, albuminuria and hyperfiltration through the course of treatment. Although this study involved children with various types of glomerular disease, it demonstrates that decline in albuminuria is associated with a decline in total proteinuria suggesting that there is a beneficial effect on non-albumin proteinuria. The decrease in non-albumin proteinuria may have the potential to improve glomerular size-selectivity and stabilize progression of kidney disease in young children as suggested in studies done on adults [19]. There are scant anecdotal reports in the literature about treatment of chronic glomerulonephritis with angiotensin blockade in children with normal renal function [10]. Most studies involve patients who are on concurrent immunosuppressive treatment, or have hypertension and renal insufficiency [9,11,14]. There is substantial clinical and experimental evidence regarding the beneficial effect of angiotensin blockade on preservation of renal function [3–6]. Many of these studies have been short-term observations.

The retrospective nature of this study is a pitfall as GFR was estimated and not measured. However, the observations in this study support the hypothesis that hyperfiltration is an early event in the pathogenesis of progressive kidney disease. Although estimated creatinine clearance is a crude measure of GFR, this series suggests that glomerular hypertension may occur in the absence of systemic hypertension. An interesting observation in this study was that, while all patients showed a significant decline in proteinuria, only those patients with hyperfiltration demonstrated a decline to normal range eGFR. Clearly, more accurate measures of GFR in the ‘hyperfiltration’ ranges relative to systemic blood pressures are warranted.

The emergence of obesity as a contributing factor to the progression of proteinuric kidney disease in children is pertinent to our observations since the majority of our patients were either overweight or obese with heavy proteinuria, but without hypoalbuminaemia or edema. This phenomenon has been described previously and may be associated with hyperfiltration [20]. Obesity contributes to the pathogenesis of renal disease in the absence of systemic hypertension by eliciting local and systemic cytokines [2,6–8]. Hyperfiltration may also occur as a phenomenon of actual or relative decrease in nephron mass by virtue of mass ratios. A human study in which total nephron number and glomerular volume were quantitated and compared to BMI showed that body mass correlated independently with increasing glomerular volume [21]. This suggests that hyperfiltration occurs with obesity when total nephron number is normal. However, in the clinical setting of congenital or acquired decrease in total nephron mass as in the preterm infant [22] or by nephrectomy [23], additional vulnerability to obesity and hyperfiltration is apparent.

An intriguing issue raised with this small observational study relates to the choice of monotherapy vs dual therapy against the various limbs of the RAAS axis. Our observations show a distinct advantage with dual therapy in maximizing the lowering of the albumin component of proteinuria. This difference would not have been perceived without differentiating the proteinuria into the albumin and ‘non-albumin’ fractions [24]. Because angiotensin II is also generated from angiotensin I by enzymes other than ACE, ARB would provide a more effective blockade of angiotensin II; however, ACE inhibition increases plasma levels of substances such as bradykinin which have strong antifibrotic properties. These differential effects of ACEI and ARB are the rationale for combined administration of both agents [25,26]. The potential advantage of combination therapy over monotherapy is that a lower dose of each drug can be used which may improve patient tolerance, particularly in children with normal systemic blood pressures. In the current study there were no significant side effects to ACEI and/or ARB since lower dosing was used in both single and dual therapy.

In conclusion, angiotensin blockade alone appears to effectively control proteinuria and stabilize kidney function in children. AB may provide an alternative to more toxic therapies in glomerular disorders in which immunosuppressive drugs have no proven benefit or in those that failed immunosuppressive regimens. Long-term observations are needed to determine if angiotensin blockade truly arrests progression of kidney disease. More vigilance regarding early ‘hyperfiltration’ and unperceived proteinuria in the "non-albumin" fraction is warranted.



   Acknowledgements
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
References
 
This study was supported in part by a grant from the Kidney Foundation of South Florida and from Florida's Department of Health, Children's Medical Services.

Conflict of interest statement: The authors report that the Division of Paediatric Nephrology is currently participating in a multicenter trial funded by AstraZeneca to study the use of candesartan in hypertensive children.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Brewster UC and Perazella MA. (2004) Renin-Angiotensin-Aldosterone System and the kidney: Effects on Kidney Disease. Am J Med 116:263–272.[CrossRef][Web of Science][Medline]
  2. Wolf G. (2000) Angiotensin as a mediator of tubulointerstitial injury. Nephrol Dial Transplant 15:61–63.[Free Full Text]
  3. Ruggenenti P, Pagano E, Tammuzzo L, Benini R, Garattini L, Remuzzi G. (2001) Ramipril prolongs life and is cost effective in chronic proteinuric nephropathies. Kidney Int 59:286–294.[Web of Science][Medline]
  4. Tylicki L, Rutkowski P, Renke M, Rutkowski B. (202) Renoprotective effect of small doses of losartan and enalapril in patients with primary glomerulonephritis. Short-term observation. Am J Nephrol 22:356–362.
  5. Noda M, Matsuo T, Fukuda R. (1999) Effect of candesartan cilexitil in rats with chronic renal failure. Kidney Int 56:898–909.[CrossRef][Web of Science][Medline]
  6. Fogo A. (2006) Progression versus regression of chronic kidney disease. Nephrol Dial Transplant 21:281–284.[Free Full Text]
  7. Remuzzi A, Gagliardini E, Sangalli F, et al. (2006) ACE inhibition reduces glomerulosclerosis and regenerates glomerular tissue in a model of progressive renal disease. Kidney Int 69:1124–1130.[CrossRef][Web of Science][Medline]
  8. Nakao N, Sakai M, Fujimori A, Fukagawa M. (2005) Combination therapy with ACE inhibitors and angiotensin II receptor blockers in chronic renal disease: new therapeutic world beyond blood pressure reduction. Kidney Int 67:799–812.[CrossRef][Web of Science][Medline]
  9. Montane B, Abitbol C, Chandar J, Strauss J, Zilleruelo G. (2003) Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 18:772–777.[CrossRef][Web of Science][Medline]
  10. Butani L. (2005) Angiotensin blockade in children with chronic glomerulonephritis and heavy proteinuria. Pediatr Nephrol 20:1651–1654.[CrossRef][Web of Science][Medline]
  11. Ellis D, Moritz ML, 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.[Web of Science][Medline]
  12. Proesmans W, Wambeke IV, Dyck MV. (1996) Long-term therapy with enalapril in patients with nephrotic range proteinuria. Pediatr Nephrol 10:587–589.[CrossRef][Web of Science][Medline]
  13. White CT, Macpherson CF, Hurley RM, Matsell DG. (2003) Antiproteinuric effects of enalapril and losartan: a pilot study. Pediatr Nephrol 18:1038–1043.[CrossRef][Web of Science][Medline]
  14. Simonetti GD, von Vigier RO, Konrad M, Rizzi M, Fossali E, Bianchetti MG. (2006) Child Project Candesartan Cilexitil in children with hypertension or proteinuria: a preliminary study. Pediatr Nephrol 21:1480–1482.[CrossRef][Web of Science][Medline]
  15. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263.[Abstract/Free Full Text]
  16. Ogden CL, Kuczmarski RJ, Flegal KM, et al. (2002) Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109:45–60.[Abstract/Free Full Text]
  17. 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.[Free Full Text]
  18. Hogg RJ, Portman RJ, Milliner D, et al. (2000) Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation Conference on Proteinuria, Albuminuria, Risk Assessment, Detection and Elimination (PARADE). Pediatrics 105:1242–1249.[Abstract/Free Full Text]
  19. Remuzzi A, Pertucucci S, Battaglia C, Remuzzi G. (1991) Angiotensin converting enzyme inhibition improves glomerular size selectivity in IgA nephropathy. Kidney Int 39:1267–1273.[Web of Science][Medline]
  20. Praga M, Morales E, Herrero JC, et al. (1999) Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am J Kidney Dis 33:52–58.[Web of Science][Medline]
  21. Hughson MD, Douglas-Denton R, Bertram JF, Hoy WE. (2006) Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int 69:671–678.[CrossRef][Web of Science][Medline]
  22. Abitbol CL, Bauer CR, Montane B, Chandar J, Duara S, Zilleruelo G. (2003) Long-term follow-up of extremely low birth weight infants with neonatal renal failure. Pediatr Nephrol 18:887–893.[CrossRef][Web of Science][Medline]
  23. Praga M. (2005) Synergy of low nephron number and obesity: a new focus on hyperfiltration nephropathy. Nephrol Dial Transplant 20:2594–2597.[Free Full Text]
  24. Abitbol CL, Chandar J, Onder AM, Nwobi O, Montane B, Zilleruelo G. (2006) Profiling proteinuria in pediatric patients. Pediatr Nephrol 21:995–1002.[CrossRef][Web of Science][Medline]
  25. Russo D, Minutolo R, Pisani A, et al. (2001) Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 38:18–25.[Web of Science][Medline]
  26. Mogensen CE, Neldam S, Tikkanen I, et al. (2000) Randomized controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microabluminuria (CALM) study. Br Med J 321:1440–1444.[Abstract/Free Full Text]
Received for publication: 3.10.06
Accepted in revised form: 26.12.06


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. M. Bivol, R. K. Berge, and B. M. Iversen
Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R438 - R447.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/5/1332    most recent
gfl839v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Chandar, J.
Right arrow Articles by Zilleruelo, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chandar, J.
Right arrow Articles by Zilleruelo, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?