Skip to main content
Top
Published in: International Urology and Nephrology 3/2011

01-09-2011 | Nephrology - Original Paper

Clinical correlation of nitric oxide levels with acute rejection in renal transplantation

Authors: John K. Bellos, Despina N. Perrea, Eleni Theodoropoulou, Ioannis Vlachos, Antonis Papachristodoulou, Alkiviadis I. Kostakis

Published in: International Urology and Nephrology | Issue 3/2011

Login to get access

Abstract

Background

The objective of this study was to examine whether there was an association between acute rejection (AR) and nitric oxide (NO) levels and also to evaluate the clinical impact of NO measurement as a noninvasive marker for early detection of AR.

Methods

Fifty consecutive patients aged 17–62 years old received a living-related kidney graft. Serum levels of total nitrite and nitrate (NOx) were measured 30 min after graft reperfusion (NOx 1) and on days 1 (NOx 2), 5 (NOx 3), and 10 (NOx 4) post-transplantation (Tx). If clinically indicated, graft biopsy was performed.

Results

Acute humoral rejection was diagnosed by biopsy on 3rd post-Tx day in one patient. His serum NOx 2 levels were remarkably higher (380%) compared with his NOx 1 measurement. At the same time, NOx 1–2 measurements in uncomplicated group showed lower levels (−12%). Additionally, during the first month post-Tx, 5 cases of acute cellular rejection (ACR) were diagnosed. The mean percent change of NOx 3–4 levels in ACR group was 180.7 versus 16.1 in uncomplicated patients (P < 0.01). In addition, >70 μmol/L change in NOx levels in consecutive samples had a sensitivity of 100% and a specificity of 97.7% in predicting AR episodes.

Conclusion

Our study reports significant increase in serum NOx levels in episodes of AR. NOx might be an useful noninvasive marker for early diagnosis of AR.
Literature
1.
go back to reference Gjertson DW (2000) Impact of delayed graft function and acute rejection on kidney graft survival. Clin Transpl: 467–80 Gjertson DW (2000) Impact of delayed graft function and acute rejection on kidney graft survival. Clin Transpl: 467–80
2.
go back to reference Pallardó Mateu LM, Sancho Calabuig A, Capdevila Plaza L, Franco Esteve A (2004) Acute rejection and late renal transplant failure: risk factors and prognosis. Nephrol Dial Transpl 19(Suppl 3):iii38–iii42 Pallardó Mateu LM, Sancho Calabuig A, Capdevila Plaza L, Franco Esteve A (2004) Acute rejection and late renal transplant failure: risk factors and prognosis. Nephrol Dial Transpl 19(Suppl 3):iii38–iii42
3.
go back to reference Shin GT, Kim SJ, Lee TS, Oh CK, Kim H (2005) Gene expression of perforin by peripheral blood lymphocytes as a marker of acute rejection. Nephron Clin Pract 100:c63–c70PubMedCrossRef Shin GT, Kim SJ, Lee TS, Oh CK, Kim H (2005) Gene expression of perforin by peripheral blood lymphocytes as a marker of acute rejection. Nephron Clin Pract 100:c63–c70PubMedCrossRef
4.
go back to reference Erickson LM, Pan F, Ebbs A, Kobayashi M, Jiang H (2003) Microarray-based gene expression profiles of allograft rejection and immunosuppression in the rat heart transplantation model. Transplantation 76:582–588PubMedCrossRef Erickson LM, Pan F, Ebbs A, Kobayashi M, Jiang H (2003) Microarray-based gene expression profiles of allograft rejection and immunosuppression in the rat heart transplantation model. Transplantation 76:582–588PubMedCrossRef
5.
go back to reference Kurian SM, Heilman R, Mondala TS et al (2009) Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood. PLoS One 4(7):e6212PubMedCrossRef Kurian SM, Heilman R, Mondala TS et al (2009) Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood. PLoS One 4(7):e6212PubMedCrossRef
6.
go back to reference Reeve J, Einecke G, Mengel M et al (2009) Diagnosing rejection in renal transplants: a comparison of molecular- and histopathology-based approaches. Am J Transpl 9(8):1802–1810CrossRef Reeve J, Einecke G, Mengel M et al (2009) Diagnosing rejection in renal transplants: a comparison of molecular- and histopathology-based approaches. Am J Transpl 9(8):1802–1810CrossRef
7.
go back to reference Gross SS, Wolin MS (1995) Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 57:737–769PubMedCrossRef Gross SS, Wolin MS (1995) Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 57:737–769PubMedCrossRef
8.
go back to reference Kuo PC, Alfrey EJ, Abe KY, Huie P, Sibley RK, Dafoe DC (1996) Cellular localization and effect of nitric oxide synthesis in a rat model of orthotopic liver transplantation. Transplantation 61:305–312PubMedCrossRef Kuo PC, Alfrey EJ, Abe KY, Huie P, Sibley RK, Dafoe DC (1996) Cellular localization and effect of nitric oxide synthesis in a rat model of orthotopic liver transplantation. Transplantation 61:305–312PubMedCrossRef
9.
go back to reference Stoica SC, Satchithananda DK, Atkinson C, Charman S, Goddard M, Large SR (2003) Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the acute phase of human cardiac transplantation. Eur J Cardiothorac Surg 24(6):932–939PubMedCrossRef Stoica SC, Satchithananda DK, Atkinson C, Charman S, Goddard M, Large SR (2003) Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the acute phase of human cardiac transplantation. Eur J Cardiothorac Surg 24(6):932–939PubMedCrossRef
10.
go back to reference Stevens RB, Ansite JD, Mills CD et al (1996) Nitric oxide mediates early dysfunction of rat and mouse islets after transplantation. Transplantation 61:1740–1749PubMedCrossRef Stevens RB, Ansite JD, Mills CD et al (1996) Nitric oxide mediates early dysfunction of rat and mouse islets after transplantation. Transplantation 61:1740–1749PubMedCrossRef
11.
go back to reference Dedeoglu IO, Feld LG (1996) Decreased urinary excretion of nitric oxide in acute rejection episodes in pediatric renal allograft recipients. Transplantation 62:1936–1938PubMedCrossRef Dedeoglu IO, Feld LG (1996) Decreased urinary excretion of nitric oxide in acute rejection episodes in pediatric renal allograft recipients. Transplantation 62:1936–1938PubMedCrossRef
12.
go back to reference Albrecht EW, van Goor H, Tiebosch AT, Moshage H, Tegzess AM, Stegeman CA (2000) Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection. Transplantation 70:1610–1616PubMedCrossRef Albrecht EW, van Goor H, Tiebosch AT, Moshage H, Tegzess AM, Stegeman CA (2000) Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection. Transplantation 70:1610–1616PubMedCrossRef
13.
go back to reference Khanafer A, Ilham MA, Namagondlu GS et al (2007) Increased nitric oxide production during acute rejection in kidney transplantation: a useful marker to aid in the diagnosis of rejection. Transplantation 84:580–586PubMedCrossRef Khanafer A, Ilham MA, Namagondlu GS et al (2007) Increased nitric oxide production during acute rejection in kidney transplantation: a useful marker to aid in the diagnosis of rejection. Transplantation 84:580–586PubMedCrossRef
14.
go back to reference Mattson DL, Wu F (2000) Nitric oxide synthase activity and isoforms in rat renal vasculature. Hypertension 35:337–341PubMed Mattson DL, Wu F (2000) Nitric oxide synthase activity and isoforms in rat renal vasculature. Hypertension 35:337–341PubMed
15.
go back to reference Saura M, López S, Rodríguez Puyol M, Rodríguez Puyol D, Lamas S (1995) Regulation of inducible nitric oxide synthase expression in rat mesangial cells and isolated glomeruli. Kidney Int 47(2):500–509PubMedCrossRef Saura M, López S, Rodríguez Puyol M, Rodríguez Puyol D, Lamas S (1995) Regulation of inducible nitric oxide synthase expression in rat mesangial cells and isolated glomeruli. Kidney Int 47(2):500–509PubMedCrossRef
16.
go back to reference Chatterjee PK, Hawksworth GM, McLay JS (1999) Cytokine-stimulated nitric oxide production in the human renal proximal tubule and its modulation by natriuretic peptides: a novel immunomodulatory mechanism? Exp Nephrol 7(5–6):438–448PubMedCrossRef Chatterjee PK, Hawksworth GM, McLay JS (1999) Cytokine-stimulated nitric oxide production in the human renal proximal tubule and its modulation by natriuretic peptides: a novel immunomodulatory mechanism? Exp Nephrol 7(5–6):438–448PubMedCrossRef
17.
go back to reference Joles JA, Vos IH, Gröne HJ, Rabelink TJ (2002) Inducible nitric oxide synthase in renal transplantation. Kidney Int 61:872–875PubMedCrossRef Joles JA, Vos IH, Gröne HJ, Rabelink TJ (2002) Inducible nitric oxide synthase in renal transplantation. Kidney Int 61:872–875PubMedCrossRef
18.
go back to reference Green LC, Ruiz de Luzuriaga K, Wagner DA et al (1981) Nitrate biosynthesis in man. Proc Natl Acad Sci USA 78:7764–7768PubMedCrossRef Green LC, Ruiz de Luzuriaga K, Wagner DA et al (1981) Nitrate biosynthesis in man. Proc Natl Acad Sci USA 78:7764–7768PubMedCrossRef
19.
go back to reference Tsikas D (2005) Methods of quantitative analysis of the nitric oxide metabolites nitrite and nitrate in human biological fluids. Free Radic Res 39(8):797–815PubMedCrossRef Tsikas D (2005) Methods of quantitative analysis of the nitric oxide metabolites nitrite and nitrate in human biological fluids. Free Radic Res 39(8):797–815PubMedCrossRef
20.
go back to reference Solez K, Colvin RB, Racusen LC et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transpl 8:753–760CrossRef Solez K, Colvin RB, Racusen LC et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transpl 8:753–760CrossRef
21.
go back to reference Shoskes DA, Xie Y, Gonzalez-Cadavid NF (1997) Nitric oxide synthase activity in renal ischemia-reperfusion injury in the rat: implications for renal transplantation. Transplantation 63:495–500PubMedCrossRef Shoskes DA, Xie Y, Gonzalez-Cadavid NF (1997) Nitric oxide synthase activity in renal ischemia-reperfusion injury in the rat: implications for renal transplantation. Transplantation 63:495–500PubMedCrossRef
22.
go back to reference Castillo J, Berrazueta JR, Herrera L et al (1996) Nitric oxide production during the hyperacute vascular rejection. J Surg Res 63:375–380PubMedCrossRef Castillo J, Berrazueta JR, Herrera L et al (1996) Nitric oxide production during the hyperacute vascular rejection. J Surg Res 63:375–380PubMedCrossRef
23.
go back to reference Tullius SG, Nieminen M, Bechstein WO et al (1998) Prompt treatment of initial acute rejection episodes may improve long-term graft outcome. Transpl Int 11:S3–S4PubMed Tullius SG, Nieminen M, Bechstein WO et al (1998) Prompt treatment of initial acute rejection episodes may improve long-term graft outcome. Transpl Int 11:S3–S4PubMed
24.
go back to reference Bellos JK, Perrea DN, Vlachakos D, Kostakis AI (2005) Chronic allograft nephropathy: the major problem in long-term survival: review of etiology and interpretation. Transpl Rev (Orlando) 19:138–144 Bellos JK, Perrea DN, Vlachakos D, Kostakis AI (2005) Chronic allograft nephropathy: the major problem in long-term survival: review of etiology and interpretation. Transpl Rev (Orlando) 19:138–144
25.
go back to reference Hirt SW, You XM, Möller F et al (1998) Early treatment of acute rejection prevents chronic rejection in a rat model of allogenic left lung transplantation. Transpl Proc 30:1005–1006CrossRef Hirt SW, You XM, Möller F et al (1998) Early treatment of acute rejection prevents chronic rejection in a rat model of allogenic left lung transplantation. Transpl Proc 30:1005–1006CrossRef
Metadata
Title
Clinical correlation of nitric oxide levels with acute rejection in renal transplantation
Authors
John K. Bellos
Despina N. Perrea
Eleni Theodoropoulou
Ioannis Vlachos
Antonis Papachristodoulou
Alkiviadis I. Kostakis
Publication date
01-09-2011
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 3/2011
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-010-9858-9

Other articles of this Issue 3/2011

International Urology and Nephrology 3/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine