Top

Critical Care

Published in:

Open Access 01-06-2011 | Research

Deceased donor neutrophil gelatinase-associated lipocalin and delayed graft function after kidney transplantation: a prospective study

Authors: Maria E Hollmen, Lauri E Kyllönen, Kaija A Inkinen, Martti LT Lalla, Jussi Merenmies, Kaija T Salmela

Published in: Critical Care | Issue 3/2011

Abstract

Introduction

Expanding the criteria for deceased organ donors increases the risk of delayed graft function (DGF) and complicates kidney transplant outcome. We studied whether donor neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for acute kidney injury, could predict DGF after transplantation.

Methods

We included 99 consecutive, deceased donors and their 176 kidney recipients. For NGAL detection, donor serum and urine samples were collected before the donor operation. The samples were analyzed using a commercial enzyme-linked immunosorbent assay kit (serum) and the ARCHITECT method (urine).

Results

Mean donor serum NGAL (S-NGAL) concentration was 218 ng/mL (range 27 to 658, standard deviation (SD) 145.1) and mean donor urine NGAL (U-NGAL) concentration was 18 ng/mL (range 0 to 177, SD 27.1). Donor S-NGAL and U-NGAL concentrations correlated directly with donor plasma creatinine levels and indirectly with estimated glomerular filtration rate (eGFR) calculated using the modification of diet in renal disease equation for glomerular filtration rate. In transplantations with high (greater than the mean) donor U-NGAL concentrations, prolonged DGF lasting longer than 14 days occurred more often than in transplantations with low (less than the mean) U-NGAL concentration (23% vs. 11%, P = 0.028), and 1-year graft survival was worse (90.3% vs. 97.4%, P = 0.048). High U-NGAL concentration was also associated with significantly more histological changes in the donor kidney biopsies than the low U-NGAL concentration. In a multivariate analysis, U-NGAL, expanded criteria donor status and eGFR emerged as independent risk factors for prolonged DGF. U-NGAL concentration failed to predict DGF on the basis of receiver operating characteristic curve analysis.

Conclusions

This first report on S-NGAL and U-NGAL levels in deceased donors shows that donor U-NGAL, but not donor S-NGAL, measurements give added value when evaluating the suitability of a potential deceased kidney donor.

Available only for authorised users

Giral-Classe M, Hourmant M, Cantarovich D, Dantal J, Blancho G, Daguin P, Ancelet D, Soulillou JP: Delayed graft function of more than six days strongly decreases long-term survival of transplanted kidneys. Kidney Int 1998, 54: 972-978. 10.1046/j.1523-1755.1998.00071.xCrossRefPubMed

Domínguez J, Lira F, Rebolledo R, Troncoso P, Aravena C, Ortiz M, Gonzales R: Duration of delayed graft function is an important predictor of 1-year serum creatinine. Transplant Proc 2009, 41: 131-132. 10.1016/j.transproceed.2008.10.028CrossRefPubMed

Ferrer F, Mota A, Alves R, Bastos C, Macário F, Figueiredo A, Santos L, Roseiro A, Parada Pratas J, Nunes P, Campos M: Renal transplantation with expanded criteria donors: the experience of one Portuguese center. Transplant Proc 2009, 41: 791-793. 10.1016/j.transproceed.2009.02.044CrossRefPubMed

Johnston TD, Thacker LR, Jeon H, Lucas BA, Ranjan D: Sensitivity of expanded-criteria donor kidneys to cold ischaemia time. Clin Transplant 2004,18(Suppl 12):28-32.CrossRefPubMed

Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL: Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 1997, 63: 968-974. 10.1097/00007890-199704150-00011CrossRefPubMed

Moreso F, Serón D, Gil-Vernet S, Riera L, Fulladosa X, Ramos R, Alsina J, Grinyó JM: Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients. Nephrol Dial Transplant 1999, 14: 930-935. 10.1093/ndt/14.4.930CrossRefPubMed

Port FK, Bragg-Gresham JL, Metzger RA, Dykstra DM, Gillespie BW, Young EW, Delmonico FL, Wynn JJ, Merion RM, Wolfe RA, Held PJ: Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. Transplantation 2002, 74: 1281-1286. 10.1097/00007890-200211150-00014CrossRefPubMed

Irish WD, McCollum DA, Tesi RJ, Owen AB, Brennan DC, Bailly JE, Schnitzler MA: Nomogram for predicting the likelihood of delayed graft function in adult cadaveric renal transplant recipients. J Am Soc Nephrol 2003, 14: 2967-2674. 10.1097/01.ASN.0000093254.31868.85CrossRefPubMed

Nyberg SL, Matas AJ, Kremers WK, Thostenson JD, Larson TS, Prieto M, Ishitani MB, Sterioff S, Stegall MD: Improved scoring system to assess adult donors for cadaver renal transplantation. Am J Transplant 2003, 3: 715-721. 10.1034/j.1600-6143.2003.00111.xCrossRefPubMed

10.

Schold JD, Kaplan B, Baliga RS, Meier-Kriesche HU: The broad spectrum of quality in deceased donor kidneys. Am J Transplant 2005, 5: 757-765. 10.1111/j.1600-6143.2005.00770.xCrossRefPubMed

11.

Mishra J, Dent C, Tarabishi R, Mitsnefes M, Ma Q, Kelly C, Ruff S, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury following cardiac surgery. Lancet 2005, 365: 1231-1238. 10.1016/S0140-6736(05)74811-XCrossRefPubMed

12.

Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT: Association between increases with urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 2006, 105: 485-491. 10.1097/00000542-200609000-00011CrossRefPubMed

13.

Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, Haase M: Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery: a prospective cohort study. Crit Care Med 2009, 37: 553-560. 10.1097/CCM.0b013e318195846eCrossRefPubMed

14.

Niemann CU, Walia A, Waldman J, Davio M, Roberts JP, Hirose R, Feiner J: Acute kidney injury during liver transplantation as determined by neutrophil gelatinase-associated lipocalin. Liver Transpl 2009, 15: 1852-1860. 10.1002/lt.21938CrossRefPubMed

15.

Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki A: 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.CrossRefPubMed

16.

Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A, NGAL Meta-Analysis Investigator Group: Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 2009, 54: 1012-1024. 10.1053/j.ajkd.2009.07.020CrossRefPubMed

17.

Siew ED, Ware LB, Gebretsadik T, Shintani A, Moons KG, Wickersham N, Bossert F, Ikizler TA: Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. J Am Soc Nephrol 2009, 20: 1823-1832. 10.1681/ASN.2008070673PubMedCentralCrossRefPubMed

18.

Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Piccinni P, Ronco C: Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in adult ICU population. Intensive Care Med 2010, 36: 444-451. 10.1007/s00134-009-1711-1PubMedCentralCrossRefPubMed

19.

Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, D'amico G, Goldsmith D, Devarajan P, Bellomo R: Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med 2010, 36: 452-461. 10.1007/s00134-009-1724-9CrossRefPubMed

20.

Kümpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K, Fliser D, Faulhaber-Walter R, Kielstein JT: Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury. Crit Care 2010, 14: R9. 10.1186/cc8861PubMedCentralCrossRefPubMed

21.

Nickolas TL, O'Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J: Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 2008, 148: 810-819.PubMedCentralCrossRefPubMed

22.

Makris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K, Rizos D, Baltopoulos G, Haliassos A: Urinary neutrophil gelatinase-associated lipocalin as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med 2009, 47: 79-82. 10.1515/CCLM.2009.004CrossRefPubMed

23.

Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P: Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 2006, 6: 1639-1645. 10.1111/j.1600-6143.2006.01352.xCrossRefPubMed

24.

Hall IE, Yarlagadda SG, Coca SG, Wang Z, Doshi M, Devarajan P, Han WK, Marcus RJ, Parikh CR: IL-18 and urinary NGAL predict dialysis and raft recovery after kidney transplantation. J Am Soc Nephrol 2010, 21: 189-197. 10.1681/ASN.2009030264PubMedCentralCrossRefPubMed

25.

Kusaka M, Kuroyanagi Y, Mori T, Nagaoka K, Sasaki H, Maruyama T, Hayakawa K, Shiroki R, Kurahashi H, Hoshinaga K: Serum neutrophil gelatinase-associated lipocalin as a predictor of organ recovery from delayed graft function after kidney transplantation from donors after cardiac death. Cell Transplant 2008, 17: 129-134. 10.3727/000000008783907116CrossRefPubMed

26.

Lebkowska U, Malyszko J, Lebkowska A, Koc-Zorawska A, Lebkowski W, Malyszko JS, Kowalewski R, Gacko M: Neutrophil gelatinase-associated lipocalin and cystatin C could predict renal outcome in patients undergoing kidney allograft transplantation: a prospective study. Transplant Proc 2009, 41: 154-157. 10.1016/j.transproceed.2008.10.092CrossRefPubMed

27.

Hollmen M, Kyllönen L, Inkinen K, Lalla M, Salmela K: Urine neutrophil gelatinase-associated lipocalin: a marker for graft recovery after kidney transplantation. Kidney Int 2011, 79: 89-98. 10.1038/ki.2010.351CrossRefPubMed

28.

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth T: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999, 130: 461-470.CrossRefPubMed

29.

Schwartz GF, Haycock GB, Edelmann CM Jr, Spitzer A: A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976, 58: 259-263.PubMed

30.

Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Marcussen N, Mihatsch MJ, Nadasdy T, Nickerson P, Olsen TS, Papadimitriou JC, et al.: The Banff 97 working classification of renal allograft pathology. Kidney Int 1999, 55: 713-723. 10.1046/j.1523-1755.1999.00299.xCrossRefPubMed

31.

Isoniemi HM, Krogerus L, von Willebrand E, Taskinen E, Ahonen J, Häyry P: Histopathological findings in well-functioning, long-term renal allografts. Kidney Int 1992, 41: 155-160. 10.1038/ki.1992.21CrossRefPubMed

32.

Halloran PF, Aprile MA, Farewell V, Ludwin D, Smith EK, Tsai SY, Bear RA, Cole EH, Fenton SS, Cattran DC: Early function as the principal correlate of graft survival: a multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine. Transplantation 1988, 46: 223-228. 10.1097/00007890-198808000-00007CrossRefPubMed

33.

Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 2008, 3: 665-673. 10.2215/CJN.04010907PubMedCentralCrossRefPubMed

34.

Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, Wong HR: Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 2008, 36: 1297-1303. 10.1097/CCM.0b013e318169245aPubMedCentralCrossRefPubMed

35.

Liu Q, Nielsen-Hamilton M: Identification of a new acute phase protein. J Biol Chem 1995, 270: 22565-22570. 10.1074/jbc.270.38.22565CrossRefPubMed

36.

Cowland JN, Borregaard N: Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 1997, 45: 17-23. 10.1006/geno.1997.4896CrossRefPubMed

37.

Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P: Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003, 14: 2534-2543. 10.1097/01.ASN.0000088027.54400.C6CrossRefPubMed

38.

Meheus LA, Fransen LM, Raymackers JG, Blockx HA, Van Beeumen JJ, Van Bun SM, Van de Voorde A: Identification by microsequencing of lipopolysaccharide-induced proteins secreted by mouse macrophages. J Immunol 1993, 151: 1535-1547.PubMed

39.

Cowland JB, Sørensen OE, Sehested M, Borregaard N: Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1β, but not by TNF-α. J Immunol 2003, 171: 6630-6639.CrossRefPubMed

40.

Grenier FC, Ali S, Syed H, Workman R, Martens F, Liao M, Wang Y, Wong PY: Evaluation of the ARCHITECT urine NGAL assay: assay performance, specimen handling requirements and biological variability. Clin Biochem 2010, 43: 625-620.CrossRef

41.

Mori K, Lee HT, Rapaport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D'Agati V, Devarajan P, Barasch J: Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 2005, 115: 610-621.PubMedCentralCrossRefPubMed

42.

Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, Devarajan P, Barasch J: Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 2006, 15: 442-449. 10.1097/01.mnh.0000232886.81142.58CrossRefPubMed

43.

Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J: Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2007, 18: 407-413. 10.1681/ASN.2006080882CrossRefPubMed

Title: Deceased donor neutrophil gelatinase-associated lipocalin and delayed graft function after kidney transplantation: a prospective study
Authors: Maria E Hollmen
Lauri E Kyllönen
Kaija A Inkinen
Martti LT Lalla
Jussi Merenmies
Kaija T Salmela
Publication date: 01-06-2011
Publisher: BioMed Central
Published in: Critical Care / Issue 3/2011
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc10220

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Deceased donor neutrophil gelatinase-associated lipocalin and delayed graft function after kidney transplantation: a prospective study

Abstract

Introduction

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2011

Health-related quality of life and physical recovery after a critical illness: a multi-centre randomised controlled trial of a home-based physical rehabilitation program

Soluble CD40 ligand, a mediator of sepsis or of transfusion-related adverse effects?

In memoriam: Herbert Benzer

Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study

Ability of respiratory pulse pressure variation to predict fluid responsiveness in ARDS: still an unanswered question?

Emergency overcrowding: an incurable disease?