Skip to main content
Erschienen in: International Urology and Nephrology 4/2013

01.08.2013 | Nephrology - Original Paper

Neutrophil gelatinase-associated lipocalin is a sensitive biomarker for the early diagnosis of acute rejection after living-donor kidney transplantation

verfasst von: Junko Kohei, Hideki Ishida, Tanabe Kazunari, Ken Tsuchiya, Kosaku Nitta

Erschienen in: International Urology and Nephrology | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

Early diagnosis of kidney allograft dysfunction is crucial for the management and long-term survival of transplanted kidneys. We investigated whether neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) are capable of being used as novel biomarkers of acute kidney allograft dysfunction.

Methods

We measured serum and urine NGAL, urine IL-18, and urine L-FABP levels on the first 3 days after transplantation. To assess the diagnostic sensitivity of these biomarkers, a receiver-operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to quantify the accuracy of the parameter. Sections from paraffin-embedded biopsy specimens were examined by immunohistochemistry for NGAL expression.

Results

Twelve cases were clinically diagnosed as acute rejection (AR) by renal biopsy. Urine NGAL was the most sensitive of these markers for detection of acute kidney allograft dysfunction. The cutoff value of urine NGAL was 66.0 ng/ml, with an AUC of 0.79 (95 % CI 0.68–0.88). Sensitivity of serum NGAL was about the same as urine NGAL with an AUC of 0.75 (0.64–0.85). IL-18 and L-FABP were 0.584 (95 % CI 0.433–0.725) and 0.612 (95 % CI 0.460–0.749), respectively. NGAL was more useful than other biomarkers to detect AR of kidney allograft dysfunction. NGAL staining intensity was significantly increased in the proximal tubules of the transplants with AR than in transplants that were not acutely rejected.

Conclusion

Urine NGAL level was found to be the most sensitive biomarker of acute kidney allograft dysfunction after living-donor kidney transplantation.
Literatur
1.
Zurück zum Zitat Alachkar N, Rabb H, Jaar BG (2011) Urinary biomarkers in acute kidney transplant dysfunction. Nephron Clin Pract 118:c173–c181PubMedCrossRef Alachkar N, Rabb H, Jaar BG (2011) Urinary biomarkers in acute kidney transplant dysfunction. Nephron Clin Pract 118:c173–c181PubMedCrossRef
2.
Zurück zum Zitat Ojo AO, Wolfe RA, Held PJ et al (1997) Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 63:968–974PubMedCrossRef Ojo AO, Wolfe RA, Held PJ et al (1997) Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 63:968–974PubMedCrossRef
3.
Zurück zum Zitat Halawa A (2011) The early diagnosis of acute renal graft dysfunction: a challenge we face. The role of novel biomarkers. Ann Transplant 16:90–98PubMed Halawa A (2011) The early diagnosis of acute renal graft dysfunction: a challenge we face. The role of novel biomarkers. Ann Transplant 16:90–98PubMed
4.
Zurück zum Zitat Perrone RD, Madias NE, Levey AS (1992) Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 38:1933–1953PubMed Perrone RD, Madias NE, Levey AS (1992) Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 38:1933–1953PubMed
5.
Zurück zum Zitat Kee TY, Chapman JR, O’Connell PJ et al (2006) Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants. Transplantation 82:36–42PubMedCrossRef Kee TY, Chapman JR, O’Connell PJ et al (2006) Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants. Transplantation 82:36–42PubMedCrossRef
6.
Zurück zum Zitat Kurtkoti J, Sakhuja V, Sud K et al (2008) The utility of 1- and 3-month protocol biopsies on renal allograft function: a randomized controlled study. Am J Tansplant 8:317–323CrossRef Kurtkoti J, Sakhuja V, Sud K et al (2008) The utility of 1- and 3-month protocol biopsies on renal allograft function: a randomized controlled study. Am J Tansplant 8:317–323CrossRef
7.
Zurück zum Zitat Coca SG, Yalavarthy R, Concato J et al (2008) Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int 73:1008–1016PubMedCrossRef Coca SG, Yalavarthy R, Concato J et al (2008) Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int 73:1008–1016PubMedCrossRef
8.
Zurück zum Zitat Hall IE, Yarlagadda SG, Coca SG et al (2010) IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 21:189–197PubMedCrossRef Hall IE, Yarlagadda SG, Coca SG et al (2010) IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 21:189–197PubMedCrossRef
9.
Zurück zum Zitat Yamamoto T, Noiri E, Ono Y et al (2007) Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol 18:2894–2902PubMedCrossRef Yamamoto T, Noiri E, Ono Y et al (2007) Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol 18:2894–2902PubMedCrossRef
10.
Zurück zum Zitat Imai E, Matsuo S, Makino H et al (2010) Chronic Kidney Disease Japan Cohort study: baseline characteristics and factors associated with causative diseases and renal function. Clin Exp Nephrol 14:558–570PubMedCrossRef Imai E, Matsuo S, Makino H et al (2010) Chronic Kidney Disease Japan Cohort study: baseline characteristics and factors associated with causative diseases and renal function. Clin Exp Nephrol 14:558–570PubMedCrossRef
11.
Zurück zum Zitat Parikh CR, Devarajan P, Zappitelli M et al (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747PubMedCrossRef Parikh CR, Devarajan P, Zappitelli M et al (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747PubMedCrossRef
12.
Zurück zum Zitat Solez K, Colvin RB, Racusen LC et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 8:753–760PubMedCrossRef Solez K, Colvin RB, Racusen LC et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 8:753–760PubMedCrossRef
13.
Zurück zum Zitat Nitta K, Horita S, Honda K et al (1999) Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis. Virchows Arch 435:422–427PubMedCrossRef Nitta K, Horita S, Honda K et al (1999) Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis. Virchows Arch 435:422–427PubMedCrossRef
14.
Zurück zum Zitat DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristics curves: a nonparametric approach. Biometrics 44:837–845PubMedCrossRef DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristics curves: a nonparametric approach. Biometrics 44:837–845PubMedCrossRef
15.
Zurück zum Zitat Kusaka M, Kuroyanagi Y, Mori T et al (2008) 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 17:129–134PubMedCrossRef Kusaka M, Kuroyanagi Y, Mori T et al (2008) 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 17:129–134PubMedCrossRef
16.
Zurück zum Zitat Parikh CR, Jani A, Mishra J et al (2006) Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 6:1639–1645PubMedCrossRef Parikh CR, Jani A, Mishra J et al (2006) Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 6:1639–1645PubMedCrossRef
17.
Zurück zum Zitat Xu S, Venge P (2000) Lipocalins as biochemical markers of disease. Biochim Biophys Acta 1482:298–307PubMedCrossRef Xu S, Venge P (2000) Lipocalins as biochemical markers of disease. Biochim Biophys Acta 1482:298–307PubMedCrossRef
18.
Zurück zum Zitat Haase M, Bellomo R, Devarajan P et al (2009) 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 54:1012–1024PubMedCrossRef Haase M, Bellomo R, Devarajan P et al (2009) 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 54:1012–1024PubMedCrossRef
19.
Zurück zum Zitat Soni SS, Cruz D, Bobek I et al (2010) NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 42:141–150PubMedCrossRef Soni SS, Cruz D, Bobek I et al (2010) NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 42:141–150PubMedCrossRef
20.
Zurück zum Zitat Hollmen ME, Kyllonen LE, Inkinen KA et al (2011) Urine neutrophil gelatinase-associated lipocalin is a marker of graft recovery after kidney transplantation. Kidney Int 79:89–98PubMedCrossRef Hollmen ME, Kyllonen LE, Inkinen KA et al (2011) Urine neutrophil gelatinase-associated lipocalin is a marker of graft recovery after kidney transplantation. Kidney Int 79:89–98PubMedCrossRef
21.
Zurück zum Zitat Mishra J, Ma Q, Kelly C et al (2006) Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 21:856–863PubMedCrossRef Mishra J, Ma Q, Kelly C et al (2006) Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 21:856–863PubMedCrossRef
22.
Zurück zum Zitat Schmidt-Ott KM, Mori K, Kalandadze A et al (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18:407–413PubMedCrossRef Schmidt-Ott KM, Mori K, Kalandadze A et al (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18:407–413PubMedCrossRef
23.
Zurück zum Zitat Schmidt-Ott KM, Mori K, Kalandadze A et al (2006) Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 15:442–449PubMedCrossRef Schmidt-Ott KM, Mori K, Kalandadze A et al (2006) Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 15:442–449PubMedCrossRef
24.
Metadaten
Titel
Neutrophil gelatinase-associated lipocalin is a sensitive biomarker for the early diagnosis of acute rejection after living-donor kidney transplantation
verfasst von
Junko Kohei
Hideki Ishida
Tanabe Kazunari
Ken Tsuchiya
Kosaku Nitta
Publikationsdatum
01.08.2013
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 4/2013
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-012-0321-y

Weitere Artikel der Ausgabe 4/2013

International Urology and Nephrology 4/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.