Seminars in Nephrology
Volume 27, Issue 6 , Pages 637-651 , November 2007

Proteomics for Biomarker Discovery in Acute Kidney Injury

  • Prasad Devarajan, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Prasad Devarajan, MD, Director of Nephrology and Hypertension, MLC 7022, 3333 Burnet Ave, Cincinnati, OH 45229-3039.

References 

  1. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31
  2. Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet. 2005;365:417–430
  3. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–818
  4. Palevsky PM. Epidemiology of acute renal failure: the tip of the iceberg. Clin J Am Soc Nephrol. 2006;1:6–7
  5. Liangos O, Wald R, O’Bell JW, et al. Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol. 2006;1:43–51
  6. Xue JL, Daniels F, Star RA, et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol. 2006;17:1135–1142
  7. Ympa YP, Sakr Y, Reinhart K, et al. Has mortality from acute renal failure decreased? (A systematic review of the literature). Am J Med. 2005;118:827–832
  8. Waikar SS, Curhan GC, Wald R, et al. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006;17:1143–1150
  9. Metnitz PG, Krenn CG, Steltzer H, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med. 2002;30:2051–2058
  10. Clermont G, Acker CG, Angus DC, et al. Renal failure in the ICU: comparison of the impact of acute renal failure and end-stage renal disease on ICU outcomes. Kidney Int. 2002;62:986–996
  11. Lassning A, Schmidlin D, Mouhieddine M, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol. 2004;15:1597–1605
  12. Levy MM, Macias WL, Vincent JL, et al. Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med. 2005;33:2194–2201
  13. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365–3370
  14. Hoste EAJ, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury is associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73–R82
  15. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17:1503–1520
  16. Schrier RW. Need to intervene in established acute renal failure. J Am Soc Nephrol. 2004;15:2756–2758
  17. Hewitt SM, Dear J, Star RA. Discovery of protein biomarkers for renal diseases. J Am Soc Nephrol. 2004;15:1677–1689
  18. Herget-Rosenthal S, Marggraf G, Hüsing J, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004;66:1115–1122
  19. Bellomo R, Kellum JA, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med. 2004;30:33–37
  20. Allgren RL, Marbury TC, Rahman SN, et al. Anaritide in acute tubule necrosis (Auriculin Anaritide Acute Renal Failure Study Group). N Engl J Med. 1997;336:828–834
  21. Hirschberg R, Kopple J, Lipsett P, et al. Multicenter clinical trial of recombinant human insulin-like growth factor 1 in patients with acute renal failure. Kidney Int. 1999;55:2423–2432
  22. Devarajan P, Mishra J, Supavekin S, et al. Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics. Mol Genet Metab. 2003;80:365–376
  23. Han WK, Bonventre JV. Biologic markers for the early detection of acute kidney injury. Curr Op Crit Care. 2004;10:476–482
  24. Zhou H, Hewitt SM, Yuen PST, et al. Acute kidney injury biomarkers—needs, present status, and future promise. NephSAP. 2006;5:63–71
  25. Perco P, Pleban C, Kainz A, et al. Protein biomarkers associated with acute renal failure and chronic kidney disease. Eur J Clin Invest. 2006;36:753–763
  26. Devarajan P. Emerging biomarkers of acute kidney injury. Contrib Nephrol. 2007;156:203–212
  27. Bonventre JV. Diagnosis of acute kidney injury: from classic parameters to new biomarkers. Contrib Nephrol. 2007;156:213–219
  28. Nguyen MT, Devarajan P. Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol. Epub 2007 Mar 30, PMID:17394022.
  29. American Society of Nephrology. Renal research report. J Am Soc Nephrol. 2005;16:1886–1893
  30. Zerhouni E. The NIH roadmap. Science. 2003;302:63–65
  31. Thongboonkerd V. Proteomics in nephrology: current status and future directions. Am J Nephrol. 2004;24:360–378
  32. Thongboonkerd V. Proteomic analysis of renal diseases: unraveling the pathophysiology and biomarker discovery. Expert Rev Proteomics. 2005;2:349–366
  33. Vidal BC, Bonventre JV, Hsu SI-H. Towards the application of proteomics in renal disease diagnosis. Clin Sci. 2005;109:421–430
  34. Pisitkun T, Johnstone R, Knepper MA. Discovery of urinary biomarkers. Mol Cell Proteomics. 2006;5:1760–1771
  35. O’Riordan E, Gross SS, Goligorsky MS. Technology insight: renal proteomics—at the crossroads between promise and problems. Nat Clin Pract Nephrol. 2006;2:445–458
  36. Witzmann FA, Li J. Proteomics and nephrotoxicity. Contrib Nephrol. 2004;141:104–123
  37. Gibbs A. Comparison of the specificity and sensitivity of traditional methods for assessment of nephrotoxicity in the rat with metabolomic and proteomic methodologies. J Appl Toxicol. 2005;25:277–295
  38. Schaub S, Wilkins JA, Rush D, Nickerson P. Developing a tool for noninvasive monitoring of renal allografts. Expert Rev Proteomics. 2006;3:497–509
  39. Wishart DS. Metabolomics in monitoring kidney transplants. Curr Opin Nephrol Hypertens. 2006;15:637–642
  40. Thongboonkerd V, Klein JB, Jevans AW, McLeish KR. Urinary proteomics and biomarker discovery for glomerular diseases. Contrib Nephrol. 2004;141:292–307
  41. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39:561–577
  42. In:  Pepe MS editors. The statistical evaluation of medical tests for classification and prediction. Cary, NC: Oxford University Press; 2003;
  43. Pepe MS, Etzioni R, Feng Z, et al. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst. 2001;93:1054–1061
  44. Nguyen M, Ross G, Dent C, et al. Early prediction of acute renal injury using urinary proteomics. Am J Nephrol. 2005;25:318–326
  45. Supavekin S, Zhang W, Kucherlapati R, et al. Differential gene expression following early renal ischemia-reperfusion. Kidney Int. 2003;63:1714–1724
  46. Cheng C-W, Rifai A, Ka S-M, et al. Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure. Kidney Int. 2005;68:2694–2703
  47. Thakar CV, Zahedi K, Revelo MP, et al. Identification of thrombospondin 1 (TSP-1) as a novel mediator of cell injury in kidney ischemia. J Clin Invest. 2005;115:3451–3459
  48. Yuen PST, Jo S-K, Holly MK, et al. Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses. Physiol Genomics. 2006;25:375–386
  49. Ichimura T, Bonventre JC, Bailly V, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998;273:4135–4142
  50. Muramatsu Y, Tsujie M, Kohda Y, et al. Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury. Kidney Int. 2002;62:1601–1610
  51. Zahedi K, Wang Z, Barone S, et al. Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury. Am J Physiol. 2003;284:F1046–F1055
  52. Saikumar P, Venkatachalam MA. Role of apoptosis in hypoxic/ischemic damage in the kidney. Semin Nephrol. 2003;6:512–521
  53. Kaushal GP, Basnakian AG, Shah SV. Apoptotic pathways in ischemic acute renal failure. Kidney Int. 2004;66:500–505
  54. Dagher PC. Apoptosis in ischemic renal injury: roles of GTP depletion and p53. Kidney Int. 2004;66:506–509
  55. Del Rio M, Imam A, DeLeon M, et al. The death domain of kidney ankyrin interacts with Fas and promotes Fas-mediated cell death in renal epithelia. J Am Soc Nephrol. 2004;15:41–51
  56. Burns AT, Davies DR, McLaren AJ, et al. Apoptosis in ischemia/reperfusion injury of human renal allografts. Transplantation. 1998;66:872–876
  57. Oberbauer R, Rohrmoser M, Regele H, et al. Apoptosis of tubular epithelial cells in donor kidney biopsies predicts early renal allograft function. J Am Soc Nephrol. 1999;10:2006–2013
  58. Schwarz C, Hauser P, Steininger R, et al. Failure of Bcl-2 up-regulation in proximal tubular epithelial cells of donor kidney biopsy specimens is associated with apoptosis and delayed graft function. Lab Invest. 2002;82:941–948
  59. Hoffman SC, Kampen RL, Amur S, et al. Molecular and immunohistochemical characterization of the onset and resolution of human renal allograft ischemia-reperfusion injury. Transplantation. 2002;74:916–923
  60. Castaneda MP, Swiatecka-Urban A, Mitsnefes MM, et al. Activation of mitochondrial apoptotic pathways in human renal allografts following ischemia-reperfusion. Transplantation. 2003;76:50–54
  61. Hauser P, Schwarz C, Mitterbauer C, et al. Genome-wide gene-expression patterns of donor kidney biopsies distinguish primary allograft function. Lab Invest. 2004;84:353–361
  62. Ortiz A, Justo P, Sanz A, et al. Targeting apoptosis in acute tubular injury. Biochem Pharmacol. 2003;66:1589–1594
  63. Fleischer A, Ghadiri A, Dessauge F, et al. Modulating apoptosis as a target for effective therapy. Mol Immunol. 2006;43:1065–1079
  64. Faubel S, Edelstein CL. Caspases as drug targets in ischemic organ injury. Curr Drug Targets Immune Endocr Metabol Disord. 2005;5:269–287
  65. Green DR, Kroemer G. Pharmacologic manipulation of cell death: clinical applications insight?. J Clin Invest. 2005;115:2610–2617
  66. Bouchier-Hayes L, Lartigue L, Newmeyer DD. Mitochondria: pharmacological manipulation of cell death. J Clin Invest. 2005;115:2640–2647
  67. Letai A. Pharmacologic manipulation of Bcl-2 family members to control cell death. J Clin Invest. 2005;115:2648–2655
  68. Lavrik IN, Golks A, Krammer PH. Caspases: pharmacological manipulation of cell death. J Clin Invest. 2005;115:2665–2672
  69. Jani A, Ljubanivic D, Faubel SG, et al. Caspase inhibition prevents the increase in caspase-3, -2, -8 and -9 activity and apoptosis in the cold ischemic mouse kidney. Am J Transplant. 2004;8:1246–1254
  70. Hoglen NC, Chen LS, Fisher CD, et al. Characterization of IDN-6556 (3-[2-(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid): a liver-targeted caspase inhibitor. J Pharmacol Exp Ther. 2004;309:634–640
  71. Quadri SM, Segall L, de Perrot M, et al. Caspase inhibition improves ischemia-reperfusion injury after lung transplantation. Am J Transplant. 2005;5:292–299
  72. Mishra J, Ma Q, Prada A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel urinary biomarker for ischemic injury. J Am Soc Nephrol. 2003;4:2534–2543
  73. Mishra J, Mori K, Ma Q, et al. Neutrophil gelatinase-associated lipocalin (NGAL): a novel urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol. 2004;24:307–315
  74. Mori K, Lee HT, Rapoport D, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest. 2005;115:610–621
  75. Schmitt-Ott KM, Mori K, Kalandadze A, et al. Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens. 2005;15:442–449
  76. Mishra J, Dent C, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury following cardiac surgery. Lancet. 2005;365:1231–1238
  77. Parikh CR, Mishra J, Thiessen-Philbrook H, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2006;70:199–203
  78. Wagener G, Jan M, Kim M, et al. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006;105:485–491
  79. Mishra J, Ma Q, Kelly C, et al. Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol. 2006;21:856–863
  80. Parikh CR, Jani A, Mishra J, et al. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant. 2006;6:1639–1645
  81. Trachtman H, Christen E, Cnaan A, et al. Urinary neutrophil gelatinase-associated lipocalin in D+HUS: a novel marker of renal injury. Pediatr Nephrol. 2005;21:989–994
  82. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, et al. Neutrophil gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol. 2006;26:287–292
  83. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, et al. Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and eGFR in patients with normal serum creatinine undergoing coronary angiography. Nephrol Dial Transplant. 2007;22:295–296
  84. Hirsch R, Dent C, Pfriem H, et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol. 2007;Epub ahead of print, PMID: 17874137
  85. Zapitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care. 2007;11:R84 Epub ahead of print, PMID: 17678545
  86. Mitsnefes M, Kathman T, Mishra J, et al. Serum NGAL as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol. 2007;22:101–108
  87. Xu S, Venge P. Lipocalins as biochemical markers of disease. Biochim Biophys Acta. 2000;482:298–307
  88. Han WK, Bailly V, Abichandani R, et al. Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2006;62:237–244
  89. Ichimura T, Hung CC, Yang SA, et al. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol. 2004;286:F552–F563
  90. Vaidya VS, Ramirez V, Ichimura T, et al. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol. 2006;290:F517–F529
  91. Liangos O, Han WK, Wald R, et al. Urinary kidney injury molecule-1 level is an early and sensitive marker of acute kidney injury following cardiopulmonary bypass. [abstract] J Am Soc Nephrol. 2006;17:403A
  92. Han WK, Waikar SS, Johnson A, et al. Urinary biomarkers for early detection of acute kidney injury. [abstract] J Am Soc Nephrol. 2006;17:403A
  93. Liangos O, Perianayagam MC, Vaidya VS, et al. Urinary N-Acetyl-β-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007;18:904–912
  94. Wang Z, Zahedi K, Barone S, et al. Overexpression of SSAT in kidney cells recapitulates various phenotypic aspects of kidney ischemia-reperfusion injury. J Am Soc Nephrol. 2004;15:1844–1852
  95. Tarabishi R, Zahedi K, Mishra J, et al. Induction of Zf9 in the kidney following early ischemia/reperfusion. Kidney Int. 2005;68:1511–1519
  96. Hochegger K, Koppelstatter C, Tagwerker A, et al. p21 and mTERT are novel markers for determining different ischemic time periods in renal ischemia reperfusion injury. Am J Physiol Renal Physiol. 2007;292:F762-8.
  97. Nath KA, Dvergsten J, Correa-Rotter R, et al. Induction of clusterin and chronic oxidative renal disease in the rat and its dissociation from cell injury. Lab Invest. 2004;71:209–218
  98. Caron A, Desrosiers RR, Beliveau R. Kidney ischemia-reperfusion regulates expression and distribution of tubulin subunits, β-actin and rho GTPases in proximal tubules. Arch Biochem Biophys. 2004;431:31–46
  99. Akagi R, Takahashi T, Sassa S. Cytoprotective effects of heme oxygenase in acute renal failure. Contrib Nephrol. 2005;148:70–85
  100. Takahashi T, Itano Y, Noji S, et al. Induction of renal metallothionein in rats with ischemic renal failure. Res Commun Mol Pathol Pharmacol. 2001;110:147–160
  101. Nishiyama J, Kobayashi S, Ishida A, et al. Up-regulation of Galectin-3 in acute renal failure of the rat. Am J Pathol. 2000;157:815–823
  102. Bonventre JV, Sukhatme VP, Bamberger M, et al. Localization of the protein product of the immediate early growth response gene, Egr-1, in the kidney after ischemia and reperfusion. Cell Regul. 1991;2:251–260
  103. Briscoe DM, Pober JS, Harmon WE, et al. Expression of vascular cell adhesion molecule-1 in human renal allografts. J Am Soc Nephrol. 1992;3:1180–1185
  104. Witzgall R, Brown D, Schwarz C, et al. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney (Evidence for a heterogeneous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells). J Clin Invest. 1994;93:2175–2188
  105. Aufricht C. Heat-shock protein 70: molecular supertool?. Ped Nephrol. 2005;20:707–713
  106. Kielar ML, John R, Bennett M, et al. Maladaptive role of IL-6 in ischemic acute renal failure. J Am Soc Nephrol. 2005;16:3315–3325
  107. Gobe G, Zhang ZJ, Wollgoss DA, et al. Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat. J Am Soc Nephrol. 2000;11:454–467
  108. Yoshino J, Monkawa T, Tsuji M, Hayashi M, Saruta T. Leukemia inhibitory factor is involved in tubular regeneration after experimental acute renal failure. J Am Soc Nephrol. 2003;14:3090–3101
  109. du Cheyron D, Daubin C, Poggioli J, et al. Urinary measurement of Na+/H+ exchanger isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF. Am J Kidney Dis. 2003;42:497–506
  110. Nadasdy T, Laszik Z, Blick KE, et al. Human acute tubular necrosis: a lectin and immunohistochemical study. Hum Pathol. 1995;26:230–239
  111. Hortin GL, Sviridov D. Diagnostic potential for urinary proteomics. Pharmacogenomics. 2007;8:237–255
  112. Gonzalez-Buitrago JM, Ferreira L, Lorenzo I. Urinary proteomics. Clin Chim Acta. 2007;375:49–56
  113. Fliser D, Novak J, Thongboonkerd V, et al. Advances in urinary proteome analysis and biomarker discovery. J Am Soc Nephrol. 2007;18:1057–1071
  114. Clarke W, Silverman BC, Zhang Z, et al. Characterization of renal allograft rejection by urinary proteomic analysis. Anal Surg. 2003;237:660–664
  115. Schaub S, Rush D, Wilkins J, et al. Proteome-based detection of urine proteins associated with acute renal allograft rejection. J Am Soc Nephrol. 2004;15:219–227
  116. Schaub S, Wilkins J, Weiler T, et al. Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry. Kidney Int. 2004;65:323–332
  117. Nguyen MT, Ross GF, Dent CL, et al. Early prediction of acute renal injury using urinary proteomics. Am J Nephrol. 2005;25:318–326
  118. Lefler DM, Pafford RG, Black NA, et al. Identification of proteins in slow continuous ultrafiltrate by reversed-phase chromatography and proteomics. J Proteome Res. 2004;3:1254–1260
  119. Zhou H, Pisitkun T, Aponte A, et al. Exosomal fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury. Kidney Int. 2006;70:1847–1857
  120. Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004;101:13368–13373
  121. Zhou H, Yuen PS, Pisitkun T, et al. Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. Kidney Int. 2006;69:1471–1476
  122. Molls RM, Savransky V, Liu M, et al. Keratinocyte-derived chemokine is an early biomarker of ischemic acute kidney injury. Am J Physiol. 2006;290:F1187–F1193
  123. Holly MK, Dear JW, Hu X, et al. Biomarker and drug-target discovery using proteomics in a new rat model of sepsis-induced acute renal failure. Kidney Int. 2006;70:496–506
  124. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351:159–169
  125. Melnikov VY, Ecder T, Fantuzzi G, et al. Impaired IL-18 processing protects caspase-1 deficient mice from ischemic acute renal failure. J Clin Invest. 2001;107:1145–1152
  126. Parikh CR, Jani A, Melnikov VY, Faubel S, Edelstein CL. Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis. 2004;43:405–414
  127. Parikh CR, Abraham E, Ancukiewicz M, et al. Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol. 2005;16:3046–3052
  128. Herget-Rosenthal S, Poppen D, Husing J, et al. Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis. Clin Chem. 2004;50:552–558
  129. VandeVoorde RG, Katman TI, Ma Q, et al. Serum NGAL and cystatin C as predictive biomarkers for acute kidney injury. [abstract] J Am Soc Nephrol. 2006;17:404A

 Studies cited in this review that were performed in the author’s laboratory were supported by grants from the National Institutes of Health/National Institute for Diabetes and Digestive and Kidney Diseases (R01 DK53289 and R21 DK070163), a Grant-in-Aid from the American Heart Association Ohio Valley Affiliate, and a Translational Research Initiative Grant from the Cincinnati Children’s Hospital Medical Center.

PII: S0270-9295(07)00129-5

doi: 10.1016/j.semnephrol.2007.09.005

Seminars in Nephrology
Volume 27, Issue 6 , Pages 637-651 , November 2007

Article Tools

* Image Usage & Resolution