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NDT Advance Access published online on December 8, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm858
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Proteinuria in Children with Sickle Cell Disease

Olivera Marsenic1, Kevin G. Couloures2 and Joseph M. Wiley3

1 The Children's Hospital of Philadelphia, PA 2 Alfred I. duPont Hospital for Children, Wilmington, DE 3 The Herman and Walter Samuelson Children's Hospital at Sinai Hospital of Baltimore, Baltimore, MD, USA

Correspondence and offprint requests to: Olivera Marsenic, Children's Hospital of Philadelphia, Nephrology, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. Tel: +1-215-235-0938; E-mail: oljamc{at}mac.com



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. Sickle cell nephropathy is characterized by proteinuria that starts in childhood and may lead to renal failure. Microalbuminuria is used as a marker of glomerular damage. There are no data on the extent and type of proteinuria other than microalbuminuria in children with sickle cell disease (SCD). Our goal was characterization of glomerular permselectivity and tubular proteinuria in children with SCD. The improved characterization will allow earlier recognition and prevention of renal damage.

Methods. Thirty-two stable patients with haemoglobin SS (HbSS) (15 boys and 17 girls, age 9.57 ± 5.45 years, 8 months to 19 years) were investigated. All patients had normal renal function and tested negative for proteinuria with a dipstick method. Markers of glomerular permselectivity used were albumin (marker of charge selectivity and less severe pore-size selectivity) and immunoglobulin G (IgG, marker of more severe pore-size selectivity). The marker of tubular injury used was retinol-binding protein (RBP, marker of proximal tubular dysfunction). These proteins were measured in urine spot samples using nephelometry. We did not include a control group as values in healthy subjects were previously published.

Results. Total protein excretion was elevated in 41% (13/32) of all patients and, of these 13 patients, 38.5% (5/13) had increased microalbuminuria, 15% (2/13) had increased excretion of RBP and 23% (3/13) had increased excretion of IgG. Increased total proteinuria that was not detected by testing for microalbuminuria was found in 61.5% (8/13) of patients. The youngest patient was 3 years old. Increased microalbuminuria was present in 25% (8/32) of all patients and was detected as early as 4 years of age. Of these, 62% (5/8) also had increased total protein excretion and 62% (5/8) also had increased IgG excretion. A total of 62.5% were older than 10 years. RBP excretion was elevated in 16% (5/32) of patients, all of whom were 7–14 years old. None of these patients had increased microalbuminuria or increased excretion of IgG. IgG excretion was elevated in 16% (5/32) of patients and was accompanied by increased microalbuminuria. All patients with increased IgG excretion were ≥13 years old. We found a weak positive correlation between microalbuminuria and age (0.323, P = 0.07). We did not find a significant correlation between any type of proteinuria and disease morbidity. Ten of the thirty-two patients received hydroxyurea treatment and 60% (6/10) had no proteinuria. Twelve of the thirty-two patients received chronic exchange transfusions and 42% (5/12) had no proteinuria.

Conclusion. We found early glomerular selectivity damage in children with SCD, which is secondary to both size-selectivity and charge-selectivity impairment. Microalbuminuria alone does not adequately detect early renal damage in children with SCD. Proximal tubular dysfunction is seen in younger children and is independent of glomerular damage. We suggest that children with SCD be tested for both total protein and IgG excretion in the urine in addition to albumin. Knowing the extent and type of renal damage may allow earlier recognition of renal injury and prompt earlier initiation of preventive therapies.

Keywords: albuminuria; immunoglobulin G; proteinuria; retinol-binding protein; sickle cell nephropathy



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
Sickle cell nephropathy results from recurrent renal vasoocclusion, ischemic injury and loss of nephron mass [1]. Renal failure develops in up to 18% of adult patients with sickle cell disease (SCD) [2]. Glomerular proteinuria occurs as a consequence of intrinsic glomerular capillary injury, increased glomerular filtration rate and increased renal plasma flow [1,3]. A number of studies have addressed the prevalence of microalbuminuria in children with SCD disease [4–8], which has been used as a marker of preclinical glomerular damage. However, adult literature suggests that abnormal albuminuria is accompanied by increased large molecule immunoglobulin G (IgG) excretion [3] and that there is more severe glomerular basement membrane (GBM) damage then initially thought. IgG excretion has not been characterized in children with SCD and there is little data about tubular proteinuria [6].

The study objective was to investigate the extent and type of proteinuria that occurs in children with a spectrum of haemoglobin SS (HbSS) disease. We aimed to characterize glomerular permselectivity (which can be damaged by impaired size selectivity, or impaired charge selectivity) and investigate for tubular proteinuria by using various markers of glomerular and tubular injury. The enhanced characterization of the location and severity of renal damage will allow better understanding of the renoprotective role of therapies such as angiotensin-converting enzyme inhibitors (ACEi), hydroxyurea and blood transfusions [7,10,11].



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
Albumin and IgG were used as markers of glomerular permselectivity. Albumin, a molecule with a radius of 36 Å, and a weight of 69 kDa, is a small, negatively charged protein and its increased excretion indicates damage of charge selectivity and less severe pore-size selectivity [12,13]. IgG is a larger uncharged molecule with a radius of 55 Å and a weight of 150 kDa, and its increased excretion indicates size-selectivity damage and disruption of the glomerular capillary wall [12,13]. Retinol-binding protein (RBP) was used as a marker of tubular injury. It is a molecule with a radius of 10 Å and a weight of 21 kDa. It passes freely through the GBM and is reabsorbed by the proximal tubule, and therefore its increased excretion suggests proximal tubular dysfunction. It is a preferred low-molecular-weight (LMW) protein for the study of proximal tubular dysfunction since it remains stable in acidic urine and, hence, does not require urine alkalinization for accurate quantification [14,15].

This study was performed at Children’s Hospital at Sinai Hospital of Baltimore during the year 2005–2006. Stable patients with SCD, with HbSS, presenting for routine visits every 6 months were screened for the study. Stable patients were defined as those who were not having an acute illness and a crisis of SCD, and those without other chronic illness. Other exclusion criteria were known hypertension, fever and pregnancy. Hypertension was defined as systolic and diastolic blood pressure >90th percentile for age, height and gender [16]. Haemoglobin levels and frequency of sickle cell crisis were not part of the exclusion criteria. None of the patients were treated with angiotensin receptor blockers or ACEi. Patients were not started on any new medications for at least 6 months prior to the study. Indications for treatment with hydroxyurea or exchange transfusions were history of stroke, abnormal transcranial Doppler ultrasound, acute chest syndrome, history of severe chronic pain, frequent vasoocclusive episodes and priapism.

Specialty Laboratories (Santa Monica, CA, USA) performed the laboratory studies. Creatinine, RBP, albumin, IgG and total protein were measured in urine spot samples. Results were expressed as urinary protein tested/urinary Cr. Urine dipstick testing, urinalysis and serum creatinine were done as part of the routine patient visit. Medical records review and patient interviews were used to obtain SCD course and management history including use of exchange transfusions and hydroxyurea. Morbidity was expressed as the number of hospital admissions per year of life (Table 1).


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  		Table 1. Patient characteristics and elevated urinary proteins

 
Albumin, IgG and RBP in urine were determined by nephelometry, based on the formation of specific antigen-antibody complexes. Total protein was determined by spectrophotometry. Minimal amounts detected were 2.3 mcg/ml for albumin, 10 mcg/ml for IgG, 6 mcg/ml for RBP and 40 mcg/ml for total protein. Urine creatinine testing was performed using a Jaffe reaction.

Previously published normal values for RBP [17], IgG [17,18] and total protein [19] excretion for age were used to determine if excretion of these proteins was increased. Increased microalbuminuria was defined as albumin/creatinine > 20 mg/g, as previously used in other studies [4]. Data analysis was done using descriptive statistics and correlation analysis.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Thirty-two children with HbSS disease aged 8 months to 19 years (9.57 ± 5.45 years, median 10.25 years) were enrolled in the study (15 males and 17 females). Patients were divided into three age groups: 0–6 years (12 patients), 7–13 years (12 patients) and 14–19 years (8 patients). All patients had normal renal function (normal serum creatinine (0.31 ± 0.15 mg/dl, min 0.1, max 0.7) and normal GFR for age calculated using the Schwartz formula) and tested negative for proteinuria with the dipstick method. Results are presented in Table 1 and Figures 1–4. Three of thirty-two patients tested positive for increased excretion of total protein, albumin and IgG, while none were positive for all proteins tested.


Figure 1
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  		Fig. 1. Total urinary protein. The line represents high-normal values for age.

 

Figure 4
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  		Fig. 4. Urinary immunoglobulin G (IgG). The line represents high-normal values.

 
Total protein excretion was elevated in 41% (13/32) of patients. The increased total protein excretion was accompanied by increased microalbuminuria in 38.5% (5/13), increased RBP excretion in 15% (2/13) and increased IgG excretion in 23% (3/13). However, 46% (6/13) had increased total protein excretion without increased excretion of any of the tested proteins. A total of 61.5% (8/13) of patients with increased total protein excretion had increased proteinuria that was not detected either by dipstick testing or by testing for microalbuminuria. Increased total protein excretion was evenly distributed among age groups, 38.5% (5/13) were 0–6 years old (youngest patient was 3 years old), 38.5% (5/13) were 7–13 years old and 23% (3/13) were 14–19 years old.

Increased microalbuminuria was present in 25% (8/32) of all patients, and it was accompanied by increased total protein excretion in 62% (5/8) and increased IgG excretion in 62% (5/8) of patients. None of the patients with increased microalbuminuria had increased excretion of RBP. Of all patients with increased microalbuminuria 25% (2/8) were in the age group 0–6 years (youngest patient was 4 years old), 37.5% (3/8) were in the age group 7–13 years and 37.5% (3/8) were in the age group 14–19 years.

RBP excretion was elevated in 16% (5/32) of patients. Of these, two patients had increased total protein excretion and none had increased microalbuminuria or increased excretion of IgG. All patients with increased RBP excretion were 7–14 years old.

IgG excretion was elevated in 16% (5/32) of patients. All of these also had increased microalbuminuria, and only 60% (3/5) tested positive for increased excretion of total protein as well. None had increased excretion of RBP. All patients with increased IgG excretion were older (2/5 were 13 years old and 3/5 were in the age group of 14–19 years).

Ten of the thirty-two patients received hydroxyurea treatment and 60% (6/10) had no proteinuria (4 of these 6 patients also received treatment with exchange transfusions). Twelve of the thirty-two patients received chronic exchange transfusions and 42% (5/12) had no proteinuria (4 of these 5 patients also received hydroxyurea). We correlated different types of proteinuria with use of exchange transfusions and hydroxyurea treatments, age and SCD morbidity. We found high positive correlations between IgG excretion and treatment with hydroxyurea (r = 1.000) and exchange transfusions (0.998). We found a weak positive correlation between microalbuminuria and age (0.323, P = 0.07). We did not find a significant correlation between any type of proteinuria and disease morbidity.



   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
Only a small number of studies address proteinuria and tubular function in the paediatric patients with SCD [4–8]. Increased microalbuminuria has been found in 6.2–26.5% of patients with HbSS disease [4,5,7,8]. Bayazit et al. found distal tubular dysfunction without tubular proteinuria [6].

We found elevated total protein excretion in 41% of all patients, while the urine dipstick test was negative in all patients and, therefore, unreliable. A total of 61.5% of the patients with elevated total protein excretion did not have microalbuminuria. Renal disease would have remained undetected if only albumin was used as a screening test. Also, 46% of patients with elevated total protein excretion had normal levels of urinary albumin, IgG and RBP, suggesting that other proteins are responsible for proteinuria in these patients. Total proteinuria was increased in a large portion of the very young patients, starting at age 3 years, suggesting that renal damage occurs very early.

We found that increased microalbuminuria was present in 25% of all patients [4,5,7,8], but that the onset of increased microalbuminuria is 4 years, which is 3 years earlier than the previously reported 7 years of age [4,8]. Increased microalbuminuria indicates damage of less severe pore-size selectivity and charge selectivity [12,13]. A large portion (62%) of patients with increased microalbuminuria also had increased IgG excretion, suggesting that greater renal injury was present that would not have been recognized based on microalbuminuria testing alone. We found that microalbuminuria increased in prevalence in older children (62.5% were older than 10 years) [4,5,7,8], but its severity did not correlate with age (r = 0.323, P = 0.07).

In disease states involving the proximal tubule, there is reduced reabsorption of LMW proteins and consequently increased spillage of these proteins into the urine. This increase in the urinary concentration of LMW proteins is a sensitive marker of proximal tubular dysfunction, and therefore of tubulointerstitial damage, and has been found to have predictive value in disease progression [12,14]. LMW proteins have pointed to tubular dysfunction in diseases such as IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, Fanconi syndrome, interstitial nephritis, acute tubular necrosis, drug toxicity, SCD and diabetes mellitus [14,20,21]. Most commonly used LMW proteins for the assessment of renal tubular abnormalities are RBP, Alpha-1-microglobulin and Beta-2-microglobulin. We chose RBP for our study since it was recommended as a preferred marker of tubular dysfunction because of its tubular specificity and its stability profile. Also, it had not been studied in children with SCD before. Alpha-1-microglobulin is less specific for tubular injury as it is also elevated in glomerular proteinuria. Beta-2-microglobulin is degraded in urine with a pH of <6.0 and therefore requires monitoring and alkalinization of urine for accurate measurements [14,15]. We found that it was elevated in 16% of patients, suggesting proximal tubular dysfunction and was mostly present in the younger patients. Tubular proteinuria is not as frequent a finding as glomerular proteinuria, and since it is only found in younger patients, this tubular dysfunction may be transient and independent of age. Increased RBP excretion was not associated with either increased microalbuminuria or IgG excretion, suggesting that tubular dysfunction is independent of glomerular damage. Bayazit et al. studied N-acetyl-b-D-glucosaminidase (NAG; a lysosomal enzyme originating directly from the tubule) excretion and tubular resorption of phosphate to assess proximal tubular dysfunction in 55 children with HbSS and did not find that these were different from normal controls [6]. Alvarez et al. found increased β-2-microglobulin excretion in 14.6% of their patients, which was not associated with increased microalbuminuria [11].

IgG excretion in children with SCD has also not been studied before. Under physiologic conditions proteins of the size of IgG are almost completely restricted from filtration because their radius is higher than that of small restrictive pores, and the contribution of the shunt pores or large selective pores is quantitatively irrelevant [12]. Therefore, IgG has been used as a marker of proteins of high molecular weight, and its increased excretion in the urine points to the loss of barrier size-selectivity [12,13]. IgG has been used as a marker of glomerular damage and was found to have a predictive value in various renal diseases such as membranous nephropathy, IgA nephropathy, focal segmental sclerosis, pyelonephritis, diabetes mellitus and SCD [9,12,18,21,22]. It was elevated in 16% of our patients, all of whom were older than 13 years and had increased microalbuminuria. Greater glomerular permeability occurs as early as 13 years of age, and is accompanied with microalbuminuria. Patients with microalbuminuria also had increased IgG excretion (62%) suggesting that there is greater size-selectivity damage and a greater severity of the disruption of the structural integrity of the glomerular capillary walls. As the severity of glomerular lesions escalates, the amount of IgG in the urine increases progressively [12] and GBM damage may be more severe than initially thought on the basis of microalbuminuria studies alone [9]. Even though we found increased large molecule excretion (IgG), this was not always reflected in total protein excretion, as 40% of patients with increased IgG and albumin excretion still had normal total protein excretion. Testing for either albumin or total protein alone may miss greater glomerular damage. Increased IgG excretion occurred only in older patients who had also required exchange transfusions or hydroxyurea treatment for other complications of SCD, suggesting that greater glomerular damage may only happen after a longer and more severe disease course.

We found that although proteinuria and larger molecule excretion occurred more frequently as HbSS patients got older, we did not find that the degree of proteinuria correlated with disease morbidity. Reports conflict about microalbuminuria and SCD morbidity, showing either no association [4,8] or positive association with chest syndrome [5,11], stroke, cholelithiasis and hospitalization rate [5]. Recent studies have shown that the early use of angiotensin-converting enzyme inhibitor, hydroxyurea and blood transfusions is beneficial in preventing the progression of renal disease in children with SCD [7,10,11]. Our study supports these findings as 60% of our patients treated with hydroxyurea and 42% treated with exchange transfusions had no proteinuria.

There are no studies of overt proteinuria and renal failure in children with SCD for comparison with our results. One report describes three teenagers with SCD, overt proteinuria and normal renal function [10], and the other describes a 15-year-old patient with SCD, nephrotic syndrome, renal failure and collapsing FSGS [23]. Proteinuria in the four patients described was reported as total urinary protein only. Published studies of the type of proteinuria in children with SCD focused only on children with minimal proteinuria and normal renal function. Sickle cell nephropathy rarely progresses to end-stage renal disease in children [24]. However, reports in adults have shown that asymptomatic proteinuria progresses to overt proteinuria and ultimately to renal failure [3,25–27]. Therefore, earlier detection and treatment of SCD nephropathy may be important for preventing or slowing the progression to renal failure.

In conclusion, we found that there is early glomerular selectivity damage in children with SCD, which is secondary to both size-selectivity and charge-selectivity impairment. Therefore, microalbuminuria alone is not a good measure of early renal damage in this patient population and will underestimate the degree of renal damage. We suggest that children with SCD be tested for both total protein and IgG excretion in the urine in addition to albumin. Knowing the extent and type of renal damage may allow earlier recognition of renal injury and prompt earlier initiation of preventive therapies.


Figure 2
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  		Fig. 2. Urinary albumin. The line represents high-normal values.

 


Figure 3
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  		Fig. 3. Urinary retinol-binding protein (RBP). The line represents high-normal values for age.

 



   Acknowledgments
 
We are grateful to Dr Joseph M. Wiley MD, Chief of Division of Pediatric Hematology–Oncology and Chairman of Department of Pediatrics at Children's Hospital at Sinai Hospital of Baltimore, for his continuous support that has enabled us to perform this study. The Thomas Wilson Sanitarium for Children of Baltimore City provided funding to O.M.

Conflict of interest statement. We have had no involvements that might raise the question of bias in the work reported or in the conclusions, implications or opinions stated. The results presented in this paper have not been published previously in whole or part.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Pham PTT, Pham PCT, Wilkinson AH, et al. Renal abnormalities in sickle cell disease. Kidney Int (2000) 57:1-a–8.[Web of Science][Medline]
  2. Wesson DE. The initiation and progression of sickle cell nephropathy. Kidney Int (2002) 61:2277–2286.[CrossRef][Web of Science][Medline]
  3. Schmitt F, Martinez F, Brillet G, et al. Early glomerular dysfunction in patients with sickle cell anemia. Am J Kidney Dis (1998) 32:208–214.[Web of Science][Medline]
  4. Dharnidharka VR, Dabbagh S, Atiyeh B, et al. Prevalence of microalbuminuria in children with sickle cell disease. Pediatr Nephrol (1998) 12:475–478.[CrossRef][Web of Science][Medline]
  5. Wigfall DR, Ware RE, Burchinal MR, et al. Prevalence and clinical correlates of glomerulopathy in children with sickle cell disease. J Pediatr (2000) 136:749–753.[CrossRef][Web of Science][Medline]
  6. Bayazit AK, Noyan A, Aldudak B, et al. Renal function in children with sickle cell anemia. Clin Nephrol (2002) 57:127–130.[Web of Science][Medline]
  7. McKie KT, Hanevold CD, Hernandez C, et al. Prevalence, prevention and treatment of microalbuminuria and proteiunuria in children with sickle cell disease. J Pediatr Hematol Oncol (2007) 29(3):140–144.[CrossRef][Web of Science][Medline]
  8. McBurney PG, Hanevold CD, Hernandez CM, et al. Risk factors for microalbuminuria in children with sickle cell anemia. J Pediatr Hematol Oncol (2002) 24:473–477.[CrossRef][Web of Science][Medline]
  9. Guasch A, Cua M, Mitch WE. Early detection and the course of glomerular injury in patients with sickle cell anemia. Kidney Int (1996) 49:786–791.[Web of Science][Medline]
  10. Fitzhugh CD, Wigfall DR, Ware RE. Enalapril and hydroxyurea therapy for children with sickle nephropathy. Pediatr Blood Cancer (2005) 45:982–985.[CrossRef][Web of Science][Medline]
  11. Alvarez O, Montane B, Lopez G, et al. Early blood transfusions protect against microalbuminuria in children with sickle cell disease. Pediatr Blood Cancer (2006) 47:71–76.[CrossRef][Web of Science][Medline]
  12. D’Amico G, Bazzi C. Pathophysiology of proteinuria. Kidney Int (2003) 63:809–825.[CrossRef][Web of Science][Medline]
  13. Anderson S, Tank JE, Brenner BM. Renal and systemic manifestations of glomerular disease: proteinuria. In: The Kidney—Brenner MB, ed. (2000) Philadelphia, PA: WB Saunders. 1871–1878.
  14. Tomlinson PA. Low molecular weight proteins in children with renal disease. Pediatr Nephrol (1992) 6:565–571.[CrossRef][Web of Science][Medline]
  15. Tomlinson PA, Dalton RN, Hartley B, et al. Low molecular weight protein excretion in glomerular disease: a comparative analysis. Pediatr Nephrol (1997) 11:285–290.[CrossRef][Web of Science][Medline]
  16. National high blood pressure education program working group on high blood pressure in children and adolescents: the fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics (2004) 114:555–576.[Free Full Text]
  17. Lehrnbecher T, Gressinger S, Navid F, et al. Albumin, IgG, retinol-binding protein, and Alpha-1-microglobulin excretion in childhood. Pediatr Nephrol (1998) 12:290–292.[CrossRef][Web of Science][Medline]
  18. Narita T, Hosoba M, Kakei M, et al. Increased urinary excretions of immunoglobulin G, ceruloplasmin and tranferrin predict development of microalbuminuria in patients with type 2 diabetes. Diabetes Care (2006) 29(1):142–144.[Free Full Text]
  19. Guignard JP, Santos F. Laboratory investigations: Proteinuria. In: Pediatric Nephrology—Avner ED, Harmon WE, Niaudet P, eds. (2004) Philadelphia, PA: Lippincott Williams & Wilkins. 399–401.
  20. Voskaridou E, Terpos E, Michail S, et al. Early markers of renal dysfunction in patients with sickle cell/β-thalassemia. Kidney Int (2006) 69:2037–2042.[CrossRef][Web of Science][Medline]
  21. Du Buf-Vereijken PWG, Wetzels JFM. Treatment-related changes in urinary excretion of high and low molecular weight proteins in patients with idiopathic membranous nephropathy and renal insufficiency. Nephrol Dial Transplant (2006) 21:389–396.[Abstract/Free Full Text]
  22. Horcajada JP, Velasco M, Filella X, et al. Evaluation of inflammatory and renal-injury markers in women treated with antibiotics for acute pyelonephritis caused by Escherichia coli. (2004) 11:142–146.
  23. Nasr SH, Markowitz GS, Sentman RL, et al. Sickle cell disease, nephrotic syndrome, and renal failure. Kidney Int (2006) 69:1276–1280.[CrossRef][Web of Science][Medline]
  24. NAPRTCS. (2006) Annual Report. https://web.emmes.com/study/ped/ annlrept/annlrept2006.pdf.
  25. Guasch A, Navarrete J, Nass K, et al. Glomerular involvement in adults with sickle cell hemoglobinopathies: prevalence and clinical correlates of progressive renal failure. J Am Soc Nephrol (2006) 17:2228–2235.[Abstract/Free Full Text]
  26. Bakir AA, Hathiwala SC, Ainis H, et al. Prognosis of the nephrotic syndrome in sickle glomerulopathy. A retrospective study. Am J Nephrol (1987) 7:110–115.[Web of Science][Medline]
  27. Falk RJ, Scheinman J, Phillips G, et al. Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme. N Engl J Med (1992) 326:910–915.[Abstract]
Received for publication: 9. 8.07
Accepted in revised form: 12.11.07


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