Pediatric Nephrology

, Volume 28, Issue 7, pp 1049–1058 | Cite as

Proteinuria and progression of glomerular diseases

  • Elif Erkan
Educational Review


One of the major challenges of nephrology is to develop therapeutic strategies to halt the progression of kidney diseases. In clinical settings, nephrotic-range proteinuria correlates with the rate of progression, particularly in glomerular diseases. Hence, the degree of proteinuria has been utilized to monitor the response to treatment as well as to predict outcome. However, the pathophysiology of proteinuria-induced progression remains unknown. Albumin accounts for the majority of the protein in nephrotic urine and as a result of this clinical observation studies have focused on understanding the adverse effects of albumin overload in the kidney. Albumin is internalized by receptor-mediated endocytosis in proximal tubule cells via low density lipoprotein (LDL) type receptor, megalin. Albumin at high concentrations mimicking nephrotic milieu has resulted in the upregulation of pro-inflammatory/fibrogenic genes and apoptosis in proximal tubule cells in in vivo and in vitro models of albumin overload. These properties of albumin on proximal tubule cells may explain extensive tubulointerstitial fibrosis and tubular atrophy observed in end-stage kidney disease. In addition to tubular toxicity, podocytes respond to proteinuric states by cytoskeletal alterations and loss of the differentiation marker synaptopodin. Identifying the molecular network of proteins involved in albumin handling will enable us to manipulate the specific signaling pathways and prevent damage caused by proteinuria.


Proteinuria Progression Kidney disease Microalbuminuria 



  1. 1.
    Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Johansen K, Kasiske B, Kutner N, Liu J, St Peter W, Guo H, Gustafson S, Heubner B, Lamb K, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Thompson B, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Daniels F, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L (2012) United States Renal Data System 2011 Annual Data Report: Atlas of chronic kidney disease & end-stage renal disease in the United States: Pediatric End-Stage Renal Disease. Am J Kidney Dis 59:e257–e266CrossRefGoogle Scholar
  2. 2.
    Ferris ME, Gipson DS, Kimmel PL, Eggers PW (2006) Trends in treatment and outcomes of survival of adolescents initiating end-stage renal disease care in the United States of America. Pediatr Nephrol 21:1020–1026PubMedCrossRefGoogle Scholar
  3. 3.
    Hemmelgarn BR, Manns BJ, Llyod A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M (2010) Relation between kidney function, proteinuria, and adverse outcomes. JAMA 303:423–429PubMedCrossRefGoogle Scholar
  4. 4.
    Agrawal V, Marinescu V, Agarwal M, McCullough PA (2009) Cardiovascular implications of proteinuria: an indicator of chronic kidney disease. Nature Rev Cardiol 6:301–311CrossRefGoogle Scholar
  5. 5.
    Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, Orth SR (2009) Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 20:1069–1077PubMedCrossRefGoogle Scholar
  6. 6.
    Litwin M (2004) Risk factors for renal failure in children with non-glomerular nephropathies. Pediatric Nephrol 19:178–186CrossRefGoogle Scholar
  7. 7.
    Wong CS, Pierce CB, Cole SR, Warady BA, Mak RHK, Benador NM, Kaskel F, Furth SL, Schwartz GJ (2009) Association of Proteinuria with race, cause of chronic kidney disease and glomerular filtration rate in the chronic kidney disease in children study. J Am Soc Nephrol 4:812–819CrossRefGoogle Scholar
  8. 8.
    Christensen EI, Verroust PJ (2008) Interstitial fibrosis: tubular hypothesis versus glomerular hypothesis. Kidney Int 74:1233–1236PubMedCrossRefGoogle Scholar
  9. 9.
    Kriz W, Lehir M (2005) Pathways to nephron loss starting from glomerular diseases-Insights from animal models. Kidney Int 67:404–419PubMedCrossRefGoogle Scholar
  10. 10.
    Holthofer (2007) Molecular architecture of the glomerular slit diaphragm: lessons learnt for a better understanding of disease pathogenesis. Nephrol Dial Transplant 22:2124–2128PubMedCrossRefGoogle Scholar
  11. 11.
    Friden V, Oveland E, Tenstad O, Ebefors K, Nystrom J, Nilsson UA, Haraldsson B (2011) The glomerular endothelial cell coat is essential for glomerular filtration. Kidney Int 79:1322–1330PubMedCrossRefGoogle Scholar
  12. 12.
    Eddy AA, McCulloch L, Liu E, Adams J (1991) A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. Am J Pathol 138:1111–1123PubMedGoogle Scholar
  13. 13.
    Eddy AA (1994) Protein restriction reduces transforming growth factor-β and interstitial fibrosis in nephrotic syndrome. Am J Physiol 266:F884–893PubMedGoogle Scholar
  14. 14.
    Eddy AA, Giachelli CM (1995) Renal expression of genes that promote interstitial inflammation and fibrosis in rats with protein-overload proteinuria. Kidney Int 47:1546–1557PubMedCrossRefGoogle Scholar
  15. 15.
    Eddy AA (1989) Interstitial nephritis induced by protein-overload proteinuria. Am J Pathol 135:719–733PubMedGoogle Scholar
  16. 16.
    Hsu SI, Couser WG (2003) Chronic progression of glomerular damage is mediated by complement activation: a therapeutic role for complement inhibitors. J Am Soc Nephrol 14:S186–191PubMedCrossRefGoogle Scholar
  17. 17.
    Zoja C, Donadelli R, Colleoni S, Figliuzzi M, Bonazzola S, Morigi M, Remuzzi G (1998) Protein overload stimulates RANTES production by proximal tubular cells depending on NF-κB activation. Kidney Int 53:1608–1615PubMedCrossRefGoogle Scholar
  18. 18.
    Donadelli R, Zanchi C, Morigi M, Buelli S, Batani C, Tomasoni S, Corna D, Rottoli D, Benigni A, Abbate M, Remuzzi G, Zoja C (2003) Protein overload induces fractalkine upregulation in proximal tubule cells through nuclear factor kappa B and p38 mitogen-activated protein kinase-dependent pathways. J Am Soc Nephrol 14:2436–2446PubMedCrossRefGoogle Scholar
  19. 19.
    Tang S, Leung JC, Chan KW, Chan LY, Lai KN (2003) Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. J Clin Invest 111:515–527PubMedGoogle Scholar
  20. 20.
    Wolf G, Schroeder R, Ziyadeh FN, Stahl RA (2004) Albumin up-regulates the type II transforming growth factor-beta receptor in cultured proximal tubule cells. Kidney Int 66:1849–1858PubMedCrossRefGoogle Scholar
  21. 21.
    Wang Y, Chen J, Chen L, Tay YC, Rangan GK, Harris DC (1997) Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein. J Am Soc Nephrol 8:1537–1545PubMedGoogle Scholar
  22. 22.
    Zoja C, Morigi M, Figliuzzi M, Bruzzi I, Oldroyd S, Benigni A, Ronco P, Remuzzi G (1995) Proximal tubule cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins. Am J Kidney Dis 26:934–941PubMedCrossRefGoogle Scholar
  23. 23.
    Arimura A, Li M, Batuman V (2006) Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury. Blood 107:661–668PubMedCrossRefGoogle Scholar
  24. 24.
    Ying WZ, Wang PX, Aaron KJ, Basnayake K, Sanders PW (2011) Immunoglobulin light chains activate nuclear factor-κB in renal epithelial cells through a Src-dependent mechanism. Blood 117:1301–1307PubMedCrossRefGoogle Scholar
  25. 25.
    Hutchison CA, Bridoux F (2011) Renal impairment in multiple myeloma: time is of the essence. J Clin Oncol 29:e312–313PubMedCrossRefGoogle Scholar
  26. 26.
    Kees-Folts D, Sadow JL, Schreiner GF (1994) Tubular catabolism of albumin is associated with the release of an inflammatory lipid. Kidney Int 45:1697–1709PubMedCrossRefGoogle Scholar
  27. 27.
    Kamijo A, Sugaya T, Kimura K, Sugaya T, Yamanouchi M, Hase H, Kaneko T, Hirata Y, Goto A, Fujita T, Omata M (2002) Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage. Kidney Int 62:1628–1637PubMedCrossRefGoogle Scholar
  28. 28.
    Ghiggeri GM, Ginevri F, Candiano OR, Perfumo F, Queirolo C, Gusmano R (1987) Characterization of cationic albumin in minimal change nephropathy. Kidney Int 32:547–553PubMedCrossRefGoogle Scholar
  29. 29.
    Arici M, Brown J, Williams M, Harris KPG, Walls J, Brunskill NJ (2002) Fatty acid carried on albumin modulate proximal tubule cell fibronectin production: a role for protein kinase C. Nephrol Dial Transplant 17:1751–1757PubMedCrossRefGoogle Scholar
  30. 30.
    Arici M, Chana R, Lewington A, Brown J, Brunskill NJ, Williams M (2003) Stimulation of proximal tubule cell apoptosis by albumin-bound fatty acids mediated by peroxisome proliferator activated receptor-γ. J Am Soc Nephrol 14:17–27PubMedCrossRefGoogle Scholar
  31. 31.
    Saland JM, Ginsberg HN (2007) Lipoprotein metabolism in chronic renal insufficiency. Pediatr Nephrol 22:1095–1112PubMedCrossRefGoogle Scholar
  32. 32.
    Fink HA, Ishani A, Taylor BC, Greer NL, MacDonald R, Rossini D, Sadiq S, Lankireddy S, Kane RL, Wilt TJ (2012) Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: A Systematic Review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline. Ann Intern Med 156:570–581PubMedCrossRefGoogle Scholar
  33. 33.
    Wingen AM, Fabian-Bach C, Schaefer F, Mehls O (1997) Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood. Lancet 349:1117–1123PubMedCrossRefGoogle Scholar
  34. 34.
    Fouque D, Laville M (2009) Low protein diets for chronic kidney disease in non diabetic adults. Cochrane Database Syst Rev 8:CD001892Google Scholar
  35. 35.
    Levey AS, Adler S, Caggiula AW, England BK, Greene T, Hunsicker LG, Kusek JW, Rogers NL, Teschan PE (1996) Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis 27:652–663PubMedCrossRefGoogle Scholar
  36. 36.
    Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Möller K, Wigger M, Peruzzi L, Mehls O, Schaefer F (2009) Strict blood-pressure control and progression of renal failure in children. ESCAPE Trial Group. N Engl J Med 361:1639–1650PubMedCrossRefGoogle Scholar
  37. 37.
    Dixon R, Brunskill NJ (1999) Activation of mitogenic pathways by albumin in kidney proximal tubule epithelial cells: implications for the pathophysiology of proteinuric states. J Am Soc Nephrol 10:1487–1497PubMedGoogle Scholar
  38. 38.
    Thomas ME, Brunskill NJ, Harris KPG, Bailey E, Pringle JH, Furness PN, Walls J (1999) Proteinuria induces cell turnover: a potential mechanism for tubular atrophy. Kidney Int 55:890–898PubMedCrossRefGoogle Scholar
  39. 39.
    Erkan E, Garcia CD, Patterson LT, Mishra J, Mitsnefes MM, Kaskel FJ, Devarajan P (2005) Induction of renal tubular cell apoptosis in focal segmental glomerulosclerosis: roles of proteinuria and Fas-dependent pathways. J Am Soc Nephrol 16:398–340PubMedCrossRefGoogle Scholar
  40. 40.
    Erkan E, De Leon M, Devarajan P (2001) Albumin overload induces apoptosis in LLC-PK(1) cells. Am J Physiol Renal Physiol 280:F1107–1114PubMedGoogle Scholar
  41. 41.
    Erkan E, Devarajan P, Schwartz GJ (2007) Mitochondria are the major targets in albumin-induced apoptosis in proximal tubule cells. J Am Soc Nephrol 18:1199–1208PubMedCrossRefGoogle Scholar
  42. 42.
    Erkan E, Devarajan P, Schwartz GJ (2005) Apoptotic response to albumin overload: proximal vs. distal/collecting tubule cells. Am J Nephrol 25:121–131PubMedCrossRefGoogle Scholar
  43. 43.
    Takase O, Minto AWM, Puri TS, Cunningham PN, Jacob A, Hayashi M, Quigg RJ (2008) Inhibition of NF-κB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis. Kidney Int 73:567–577PubMedCrossRefGoogle Scholar
  44. 44.
    Li X, Pabla N, Wei Q, Dong G, Messing RO, Wang CY, Dong Z (2010) PKC-delta promotes renal tubular cell apoptosis associated with proteinuria. J Am Soc Nephrol 21:1115–1124PubMedCrossRefGoogle Scholar
  45. 45.
    Patrakka J, Tryggvason K (2009) New insights into the role of podocytes in proteinuria. Nat Rev Nephrol 5:463–468PubMedCrossRefGoogle Scholar
  46. 46.
    Davies DJ, Messina A, Thumwood CM, Ryan GB (1985) Glomerular podocytic injury in protein overload proteinuria. Pathology 17:412–419PubMedCrossRefGoogle Scholar
  47. 47.
    Morigi M, Buelli S, Angioletti S, Zanchi C, Longaretti L, Zoja C, Galbusera M, Gastoldi S, Mundel P, Remuzzi G, Benigni A (2005) In response to protein load podocytes reorganize cytoskeleton and modulate endothelin-1 gene. Am J Pathol 106:1309–1320CrossRefGoogle Scholar
  48. 48.
    Abbate M, Zoja C, Morigi M, Rottoli D, Angioletti S, Tomasoni S, Zanchi C, Longaretti L, Donadelli R, Remuzzi G (2002) Transforming growth factor-β1 is up-regulation by podocytes in response to excess intraglomerular passage of proteins. Am J Pathol 161:2179–2193PubMedCrossRefGoogle Scholar
  49. 49.
    Chang AM, Ohse T, Krofft RD, Wu JS, Eddy AA, Pippin JW, Shankland SJ (2012) Albumin-induced apoptosis of glomerular parietal epithelial cells is modulated by extracellular signal-regulated kinase 1/2. Nephrol Dial Transplant 27:1330–1343PubMedCrossRefGoogle Scholar
  50. 50.
    Yoshida S, Nagase M, Shibata S, Fujita T (2008) Podocyte injury induced by albumin overload in vivo and in vitro: involvement of TGF-beta and p38 MAPK. Nephron Exp Nephrol 108:e57–68PubMedCrossRefGoogle Scholar
  51. 51.
    Chen S, He FF, Wang H, Fang Z, Shao N, Tian XJ, Liu JS, Zhu ZH, Wang YM, Wang S, Huang K, Zhang C (2011) Calcium entry via TRPC6 mediates albumin overload induced endoplasmic reticulum stress and apoptosis in podocytes. Cell Calcium 50:523–529PubMedCrossRefGoogle Scholar
  52. 52.
    He F, Chen S, Wang H, Shao N, Tian X, Jiang H, Liu J, Zhu Z, Meng X, Zhang C (2011) Regulation of CD2-associated protein influences podocyte endoplasmic reticulum stress-mediated apoptosis induced by albumin overload. Gene 484:18–25PubMedCrossRefGoogle Scholar
  53. 53.
    Guo JK, Marlier A, Shi H, Shan A, Ardito TA, Du ZP, Kashgarian M, Krause DS, Biemesderfer D, Cantley LG (2011) Increased tubular proliferation as an adaptive response to glomerular albuminuria. J Am Soc Nephrol 23:429–437PubMedCrossRefGoogle Scholar
  54. 54.
    Park CH, Maack T (1984) Albumin absorption and catabolism by isolated perfused proximal convoluted tubules of the rabbit. J Clin Invest 73:767–777PubMedCrossRefGoogle Scholar
  55. 55.
    Tojo A, Endou H (1992) Intrarenal handling of proteins in rats using fractional micropuncture technique. Am J Physiol 263:F601–606PubMedGoogle Scholar
  56. 56.
    Tojo A, Kinugasa S (2012) Mechanisms of glomerular albumin filtration and tubular reabsorption. Int J Nephrol 2012:481520PubMedGoogle Scholar
  57. 57.
    Russo LM, Sandoval RM, McKee M, Osicka TM, Collins AB, Brown D, Molitoris BA, Comper WD (2007) The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states. Kidney Int 71:504–513PubMedCrossRefGoogle Scholar
  58. 58.
    Leheste JR, Rolinski B, Vorum H, Hilpert J, Nykjaer A, Jacobsen C, Aucouturier P, Moskaug JO, Otto A, Christensen EI, Willnow TE (1999) Megalin knockout mice as an animal model of low molecular weight proteinuria. Am J Pathol 155:1361–1370PubMedCrossRefGoogle Scholar
  59. 59.
    Takeda T, Yamazaki H, Farquhar MG (2003) Identification of an apical sorting determinant in the cytoplasmic tail of megalin. Am J Physiol Cell Physiol 284:C1105–1113PubMedCrossRefGoogle Scholar
  60. 60.
    Ahuja R, Yammani R, Bauer JA, Kalra S, Seetharam S, Seetharam B (2008) Interactions of cubilin with megalin and the product of the amnionless gene (AMN): effect on its stability. Biochem J 410:301–308PubMedCrossRefGoogle Scholar
  61. 61.
    Hauck FH, Tanner SM, Henker J, Laass MW (2008) Imerslund-Gräsbeck syndrome in a 15-year-old German girl caused by compound heterozygous mutations in CUBN. Eur J Pediatr 167:671–675PubMedCrossRefGoogle Scholar
  62. 62.
    He Q, Fyfe JC, Schaffer AA, Kilkenney A, Werner P, Kirkness EF, Henthorn PS (2003) Canine Imerslund-Gräsbeck syndrome maps to a region orthologous to HSA14q. Mamm Genome 14:758–764PubMedCrossRefGoogle Scholar
  63. 63.
    Broch H, Imerslund O, Monn E, Hovig T, Seip M (1984) Imerslund-Gräsbeck anemia. A long-term follow-up study. Acta Paediatr Scand 73:248–253PubMedCrossRefGoogle Scholar
  64. 64.
    Keyel PA, Mishra SK, Roth R, Heuser JE, Watkins SC, Traub LM (2006) A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. Mol Biol Cell 17:4300–4317PubMedCrossRefGoogle Scholar
  65. 65.
    Nagai M, Meerloo T, Takeda T, Farquhar MG (2003) The adaptor protein ARH escorts megalin to and through endosomes. Mol Biol Cell 14:4984–4996PubMedCrossRefGoogle Scholar
  66. 66.
    Gallagher H, Oleinikov AV, Fenske C, Newman DJ (2004) The adaptor disabled-2 binds to the third psi xNPxY sequence on the cytoplasmic tail of megalin. Biochimie 86:179–182PubMedCrossRefGoogle Scholar
  67. 67.
    Pedersen GA, Chakraborty S, Steinhauser AL, Traub LM, Madsen M (2010) AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. Traffic 11:706–720PubMedCrossRefGoogle Scholar
  68. 68.
    Nagai J, Christensen EI, Morris SM, Willnow TE, Cooper JA, Nielsen R (2005) Mutually dependent localization of megalin and Dab2 in the renal proximal tubule. Am J Physiol Renal Physiol 289:F569–576PubMedCrossRefGoogle Scholar
  69. 69.
    Maurer ME, Cooper JA (2005) Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein. J Cell Sci 118:5345–5355PubMedCrossRefGoogle Scholar
  70. 70.
    Morris SM, Tallquist MD, Rock CO, Cooper JA (2002) Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport. EMBO J 21:1555–1564PubMedCrossRefGoogle Scholar
  71. 71.
    He J, Xu J, Xu XX, Hall RA (2003) Cell cycle-dependent phosphorylation of Disabled-2 by cdc2. Oncogene 22:4524–4530PubMedCrossRefGoogle Scholar
  72. 72.
    Yang DH, Smith ER, Roland IH, Sheng Z, He J, Martin WD, Hamilton TC, Lambeth JD, Xu XX (2002) Disabled-2 is essential for endodermal cell positioning and structure formation during mouse embryogenesis. Dev Biol 251:27–44PubMedCrossRefGoogle Scholar
  73. 73.
    Petersen HH, Hilpert J, Militz D, Zandler V, Jacobsen C, Roebroek AJ, Willnow TE (2003) Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule. J Cell Sci 116:453–461PubMedCrossRefGoogle Scholar
  74. 74.
    Zou Z, Chung B, Nguyen T, Mentone S, Thomson B, Biemesderfer D (2004) Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule. J Biol Chem 279:34302–34310PubMedCrossRefGoogle Scholar
  75. 75.
    Caruso-Neves C, Pinheiro AA, Cai H, Souza-Menezes J, Guggino WB (2006) PKB and megalin determine the survival or death of renal proximal tubule cells. Proc Natl Acad Sci USA 103:18810–18815PubMedCrossRefGoogle Scholar
  76. 76.
    Koral K, Erkan E (2012) PKB/Akt partners with Dab2 in albumin endocytosis. Am J Physiol Renal Physiol 302:F1013–1024PubMedCrossRefGoogle Scholar
  77. 77.
    Tilton RG, Chang K, Pugliese G, Eades DM, Province MA, Sherman WR, Kilo C, Williamson JR (1898) Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes 38:1258–1270CrossRefGoogle Scholar
  78. 78.
    Tojo A, Onozato ML, Ha H, Kurihara H, Sakai T, Goto A, Fujita T, Endou H (2001) Reduced albumin reabsorption in the proximal tubule of early-stage diabetic rats. Histochem Cell Biol 116:269–276PubMedGoogle Scholar
  79. 79.
    Bacchetta J, Harambat J, Guy B, Putet G, Cochat P, Dubourg L (2009) Long term renal outcome of children born preterm: a regular follow-up is needed. Arch Pediatr 16:S42–48PubMedCrossRefGoogle Scholar
  80. 80.
    Schreuder MF, Langemeijer ME, Bokenkamp A, Dekemarre-Van de Waal HA, Van Wijk JA (2008) Hypertension and microalbuminuria in children with congenital solitary kidneys. J Paediatr Child Health 44:363–368PubMedCrossRefGoogle Scholar
  81. 81.
    Westland R, Schreuder MF, Bökenkamp A, Spreeuwenberg MD, van Wijk JA (2011) Renal injury in children with a solitary functioning kidney–the KIMONO study. Nephrol Dial Transplant 26:1533–1541PubMedCrossRefGoogle Scholar
  82. 82.
    Azurmendi PJ, Fraga AR, Galan FM, Kotliar C, Arrizurieta EE, Valdez MG, Forcada PJ, Stefan JSS, Martin RS (2009) Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function. Nephrol Dial Transplant 24:2458–2463PubMedCrossRefGoogle Scholar
  83. 83.
    Lou-Meda R, Oakes RS, Gilstrap JN, Williams CG, Siegler RL (2007) Prognostic significance of microalbuminuria in postdiarrheal hemolytic uremic syndrome. Pediatr Nephrol 22:117–120PubMedCrossRefGoogle Scholar
  84. 84.
    Alvarez O, Lopez-Mitnik G, Zilleruelo G (2008) Short-term follow-up of patients with sickle cell disease and albuminuria. Pediatr Blood Cancer 50:1236–1239PubMedCrossRefGoogle Scholar

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© IPNA 2012

Authors and Affiliations

  1. 1.Division of Pediatric NephrologyChildren’s Hospital of PittsburghPittsburghUSA

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