Protein biomarkers associated with acute renal failure and chronic kidney disease

Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently categorized according to serum creatinine concentrations. Serum creatinine, however, has shortcomings because of its low predictive values. The need for novel markers for the early diagnosis and prognosis of renal diseases is imminent, particularly for markers reflecting intrinsic organ injury in stages when glomerular filtration is not impaired. This review summarizes protein markers discussed in the context of ARF as well as CKD, and provides an overview on currently available discovery results following ‘omics’ techniques. The identified set of candidate marker proteins is discussed in their cellular and functional context. The systematic review of proteomics and genomics studies revealed 56 genes to be associated with acute or chronic kidney disease. Context analysis, i.e. correlation of biological processes and molecular functions of reported kidney markers, revealed that 15 genes on the candidate list were assigned to the most significant ontology groups: immunity and defence. Other significantly enriched groups were cell communication (14 genes), signal transduction (22 genes) and apoptosis (seven genes). Among 24 candidate protein markers, nine proteins were also identified by gene expression studies. Next generation candidate marker proteins with improved diagnostic and prognostic values for kidney diseases will be derived from whole genome scans and protemics approaches. Prospective validation still remains elusive for all proposed candidates.

[1]  K. Mori,et al.  Iron, lipocalin, and kidney epithelia. , 2003, American journal of physiology. Renal physiology.

[2]  F. Lai,et al.  Messenger RNA expression of target genes in the urinary sediment of patients with chronic kidney diseases. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  R. Star,et al.  Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses. , 2006, Physiological genomics.

[4]  W. Mauritz,et al.  Serum S 100 B: A Marker of Brain Damage in Traumatic Brain Injury with and without Multiple Trauma , 2003, Shock.

[5]  R. Jensen,et al.  Global analysis of gene expression in renal ischemia-reperfusion in the mouse. , 2002, Biochemical and biophysical research communications.

[6]  M. Nimtz,et al.  Molecular characterization of beta-trace protein in human serum and urine: a potential diagnostic marker for renal diseases. , 1997, Glycobiology.

[7]  A. S. Appel,et al.  ACUTE RENAL FAILURE , 1967, Advances in Experimental Medicine and Biology.

[8]  A. Desmoulière,et al.  Interstitial alpha-smooth muscle actin: a prognostic marker in membranous nephropathy. , 1999, Clinical nephrology.

[9]  A. Desmoulière,et al.  Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[10]  A. Bello,et al.  Chronic kidney disease: the global challenge , 2005, The Lancet.

[11]  A. Kribben,et al.  Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis. , 2004, Clinical chemistry.

[12]  R. D. Marshall,et al.  Excretion of Tamm-Horsfall glycoprotein in renal disease. , 1984, Clinical nephrology.

[13]  T. Meyer,et al.  Genome-wide gene-expression patterns of donor kidney biopsies distinguish primary allograft function , 2004, Laboratory Investigation.

[14]  P. Devarajan,et al.  Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics. , 2003, Molecular genetics and metabolism.

[15]  L. King,et al.  Keratinocyte-derived chemokine is an early biomarker of ischemic acute kidney injury. , 2006, American journal of physiology. Renal physiology.

[16]  D. Fliser,et al.  Increased resistin blood levels are not associated with insulin resistance in patients with renal disease. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[17]  Shun-Fa Yang,et al.  Relationships between circulating matrix metalloproteinase-2 and -9 and renal function in patients with chronic kidney disease. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[18]  Igor Jurisica,et al.  Online Predicted Human Interaction Database , 2005, Bioinform..

[19]  R. Safirstein Acute renal failure: from renal physiology to the renal transcriptome. , 2004, Kidney international. Supplement.

[20]  Anushya Muruganujan,et al.  PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification , 2003, Nucleic Acids Res..

[21]  J. Ochieng,et al.  Extracellular functions of galectin-3 , 2004, Glycoconjugate Journal.

[22]  T. Meyer,et al.  Alterations in Gene Expression in Cadaveric vs. Live Donor Kidneys Suggest Impaired Tubular Counterbalance of Oxidative Stress at Implantation , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[23]  H. Nogami,et al.  Up-regulation of galectin-3 in acute renal failure of the rat. , 2000, The American journal of pathology.

[24]  S. Gullans,et al.  Monitoring changes in gene expression in renal ischemia-reperfusion in the rat. , 2002, Kidney international.

[25]  P. Ronco,et al.  Do matrix metalloproteinases MMP-2 and MMP-9 (gelatinases) play a role in renal development, physiology and glomerular diseases? , 2001, Current opinion in nephrology and hypertension.

[26]  Joseph V Bonventre,et al.  Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. , 2006, American journal of physiology. Renal physiology.

[27]  Stephen M Hewitt,et al.  Discovery of protein biomarkers for renal diseases. , 2004, Journal of the American Society of Nephrology : JASN.

[28]  Timothy A Bertram,et al.  Identification of putative gene based markers of renal toxicity. , 2004, Environmental health perspectives.

[29]  M. Mitsnefes,et al.  Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. , 2003, Journal of the American Society of Nephrology : JASN.

[30]  M S Pepe,et al.  Phases of biomarker development for early detection of cancer. , 2001, Journal of the National Cancer Institute.

[31]  A. Kribben,et al.  Early detection of acute renal failure by serum cystatin C. , 2004, Kidney international.

[32]  M. Yamanouchi,et al.  Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: a multicenter trial. , 2005, The Journal of laboratory and clinical medicine.

[33]  R. Star,et al.  Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury. , 2002, Kidney international.

[34]  Qing Ma,et al.  Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery , 2005, The Lancet.

[35]  Youhua Liu,et al.  Renal fibrosis: new insights into the pathogenesis and therapeutics. , 2006, Kidney international.

[36]  J. Morrow,et al.  Effect of Renal Transplantation on Biomarkers of Inflammation and Oxidative Stress in End-Stage Renal Disease Patients , 2005, Transplantation.

[37]  Hiroaki Kitano,et al.  The PANTHER database of protein families, subfamilies, functions and pathways , 2004, Nucleic Acids Res..

[38]  R E Stoll,et al.  Assessment of cisplatin-induced nephrotoxicity by microarray technology. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[39]  T. Larson,et al.  Glomerular filtration rate estimated by cystatin C among different clinical presentations. , 2006, Kidney international.

[40]  Lynn Kl,et al.  Excretion of Tamm-Horsfall glycoprotein in renal disease. , 1984 .

[41]  F. Lönnqvist,et al.  Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. , 2006, Kidney international.

[42]  R. Poveda,et al.  Goodpasture syndrome during the course of a Schönlein-Henoch purpura. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[43]  H. Rabb,et al.  Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury. , 2003, American journal of physiology. Renal physiology.

[44]  K E Hammermeister,et al.  Independent association between acute renal failure and mortality following cardiac surgery. , 1998, The American journal of medicine.

[45]  M. Gladwin,et al.  Biomarker and drug-target discovery using proteomics in a new rat model of sepsis-induced acute renal failure. , 2006, Kidney international.

[46]  Changyu Shen,et al.  Mining Alzheimer Disease Relevant Proteins from Integrated Protein Interactome Data , 2005, Pacific Symposium on Biocomputing.

[47]  V. Thongboonkerd Proteomic analysis of renal diseases: unraveling the pathophysiology and biomarker discovery , 2005, Expert review of proteomics.

[48]  A. Lentsch,et al.  Distinct and sequential upregulation of genes regulating cell growth and cell cycle progression during hepatic ischemia-reperfusion injury. , 2005, American journal of physiology. Cell physiology.

[49]  A. Desmoulière,et al.  Interstitial expression of α‐SMA: an early marker of chronic renal allograft dysfunction , 2002 .

[50]  M. Yamanouchi,et al.  Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease. , 2003, The Journal of laboratory and clinical medicine.

[51]  H. Jüppner,et al.  New PTH assays and renal osteodystrophy , 2004, Pediatric Nephrology.

[52]  C. Gleason Prostaglandins and the developing kidney. , 1987, Seminars in perinatology.

[53]  S. Stepkowski,et al.  Correlation between cyclosporine-induced nephrotoxicity in reduced nephron mass and expression of kidney injury molecule-1 and aquaporin-2 gene. , 2005, Transplantation proceedings.

[54]  D. Powell,et al.  Powell, D. W. et al. Myofibroblasts. I. Paracrine cells important in health and disease. Am. J. Physiol. 277, C1-C9 , 1999 .

[55]  D. Lovett,et al.  Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. , 2003, The American journal of pathology.

[56]  M. Pfeffer,et al.  Biomarkers of inflammation and progression of chronic kidney disease. , 2005, Kidney international.

[57]  L. Zimmerhackl Evaluation of nephrotoxicity with renal antigens in children: Role of Tamm-Horsfall protein , 2005, European Journal of Clinical Pharmacology.

[58]  W. Stetler-Stevenson,et al.  Matrix metalloproteinases in renal development and disease. , 2000, Journal of the American Society of Nephrology : JASN.

[59]  D R Flower,et al.  Beyond the superfamily: the lipocalin receptors. , 2000, Biochimica et biophysica acta.

[60]  J. Bonventre,et al.  Kidney Injury Molecule-1 ( Kim-1 ) : A Tissue and Urinary Biomarker for Nephrotoxicant-Induced Renal Injury . , 2003 .

[61]  J. Bonventre,et al.  Towards the application of proteomics in renal disease diagnosis. , 2005, Clinical science.

[62]  J. Bonventre,et al.  Recent advances in the pathophysiology of ischemic acute renal failure. , 2003, Journal of the American Society of Nephrology : JASN.

[63]  Christine A. White,et al.  Estimating glomerular filtration rate in kidney transplantation: a comparison between serum creatinine and cystatin C-based methods. , 2005, Journal of the American Society of Nephrology : JASN.

[64]  C. Brown,et al.  Urinary and serum type III collagen: markers of renal fibrosis. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[65]  R. Bellomo,et al.  Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group , 2004, Critical care.

[66]  D. Powell Water transport revisited , 1999, The Journal of physiology.

[67]  Wei-Hwa Lee,et al.  Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure. , 2005, Kidney international.

[68]  J. Rhim,et al.  Role of interleukin 10 and transforming growth factor beta1 in the angiogenesis and metastasis of human prostate primary tumor lines from orthotopic implants in severe combined immunodeficiency mice. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[69]  F. Scolari,et al.  Uromodulin storage diseases: clinical aspects and mechanisms. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[70]  R. Kucherlapati,et al.  Differential gene expression following early renal ischemia/reperfusion. , 2003, Kidney international.

[71]  John A Kellum,et al.  Acute renal failure in critically ill patients: a multinational, multicenter study. , 2005, JAMA.

[72]  D. Fliser,et al.  Renal function in the elderly: impact of hypertension and cardiac function. , 1997, Kidney international.

[73]  B. Molitoris,et al.  Urinary actin, interleukin-6, and interleukin-8 may predict sustained ARF after ischemic injury in renal allografts. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[74]  Kdoqi Disclaimer K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[75]  G. Eknoyan,et al.  National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification , 2003, Annals of Internal Medicine.

[76]  V. Thongboonkerd Proteomics in Nephrology: Current Status and Future Directions , 2004, American Journal of Nephrology.

[77]  H. Redl,et al.  Release of S100B Differs During Ischemia and Reperfusion of the Liver, the Gut, and the Kidney in Rats , 2004, Shock.

[78]  D. Brigstock The CCN family: a new stimulus package. , 2003, The Journal of endocrinology.

[79]  W. Clarke Proteomic Research in Renal Transplantation , 2006, Therapeutic drug monitoring.

[80]  M. Kretzler,et al.  Modification of the transcriptomic response to renal ischemia/reperfusion injury by lipoxin analog. , 2003, Kidney international.

[81]  D. Lovett,et al.  Proteinases and glomerular matrix turnover. , 1992, Kidney international.