Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection

Katja Kotsch, Mir Farzin Mashreghi, Gantuja Bold, Philipp Tretow, Jana Beyer, Mareen Matz, Jan Hoerstrup, Johann Pratschke, Ruchuang Ding, Manikkam Suthanthiran, Hans Dieter Volk, Petra Reinke

Research output: Contribution to journalArticle

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Abstract

Background. Acute rejection (aRx) has a major impact on the long-term outcome of renal allografts, and its diagnosis is contingent on the invasive procedure of allograft biopsy. New immunosuppreasive protocols have reduced the incidence but have not abolished this problem. Moreover, aRx is now more frequently seen several weeks after transplantation in outpatients. A noninvasive diagnostic test for predicting aRx could improve the management and outcome. The recently described measurement of urinary mRNA expression offers a new noninvasive approach. Methods. In this study, the authors monitored the urinary mRNA expression (221 specimens from 26 patients) of various immune molecules by real-time reverse-transcriptase polymerase chain reaction for up to 3 months after kidney transplantation. Most of the patients received anti-interleukin (IL)-2 receptor monoclonal antibody induction and tacrolimus-based maintenance immunosuppression, which resulted in a low incidence of aRx. To verify the "rejection" markers, an additional nine samples of patients with aRx were analyzed. Results. Granulysin mRNA increase (vs. 95% confidence interval of 159 urine samples from nonrejecting patients) was detected during 11 of 14 aRx episodes, and follow-up studies showed its predictive value for delayed aRx episodes, even weeks before enhanced serum creatinine was observed. Granulysin induction was associated with enhanced regulated on activation normal T-cell expressed and secreted (RANTES) mRNA expression in 8 of 11 samples. Other cytotoxic effector molecules (granzyme B, perforin, FasL), cytokines (tumor necrosis factor-α, RANTES, IL-2, IL-10, interferon-γ, transforming growth factor-β), CD3, and CCR1 showed less specificity and sensitivity. Conclusions. The authors' data illustrate that the noninvasive kinetic mRNA expression measurement of defined markers in urinary cells of renal allograft recipients allows the early noninvasive detection of ongoing aRx.

Original languageEnglish
Pages (from-to)1866-1875
Number of pages10
JournalTransplantation
Volume77
Issue number12
DOIs
Publication statusPublished - 27 Jun 2004
Externally publishedYes

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Allografts
Kidney
Messenger RNA
T-Lymphocytes
Interleukin-2 Receptors
Incidence
Transforming Growth Factors
Tacrolimus
Reverse Transcriptase Polymerase Chain Reaction
Routine Diagnostic Tests
Interleukin-10
Kidney Transplantation
Immunosuppression
Interferons
Interleukin-2
Real-Time Polymerase Chain Reaction
Creatinine
Outpatients
Tumor Necrosis Factor-alpha
Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Kotsch, K., Mashreghi, M. F., Bold, G., Tretow, P., Beyer, J., Matz, M., ... Reinke, P. (2004). Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection. Transplantation, 77(12), 1866-1875. https://doi.org/10.1097/01.TP.0000131157.19937.3F

Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection. / Kotsch, Katja; Mashreghi, Mir Farzin; Bold, Gantuja; Tretow, Philipp; Beyer, Jana; Matz, Mareen; Hoerstrup, Jan; Pratschke, Johann; Ding, Ruchuang; Suthanthiran, Manikkam; Volk, Hans Dieter; Reinke, Petra.

In: Transplantation, Vol. 77, No. 12, 27.06.2004, p. 1866-1875.

Research output: Contribution to journalArticle

Kotsch, K, Mashreghi, MF, Bold, G, Tretow, P, Beyer, J, Matz, M, Hoerstrup, J, Pratschke, J, Ding, R, Suthanthiran, M, Volk, HD & Reinke, P 2004, 'Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection', Transplantation, vol. 77, no. 12, pp. 1866-1875. https://doi.org/10.1097/01.TP.0000131157.19937.3F
Kotsch, Katja ; Mashreghi, Mir Farzin ; Bold, Gantuja ; Tretow, Philipp ; Beyer, Jana ; Matz, Mareen ; Hoerstrup, Jan ; Pratschke, Johann ; Ding, Ruchuang ; Suthanthiran, Manikkam ; Volk, Hans Dieter ; Reinke, Petra. / Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection. In: Transplantation. 2004 ; Vol. 77, No. 12. pp. 1866-1875.
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T1 - Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection

AU - Kotsch, Katja

AU - Mashreghi, Mir Farzin

AU - Bold, Gantuja

AU - Tretow, Philipp

AU - Beyer, Jana

AU - Matz, Mareen

AU - Hoerstrup, Jan

AU - Pratschke, Johann

AU - Ding, Ruchuang

AU - Suthanthiran, Manikkam

AU - Volk, Hans Dieter

AU - Reinke, Petra

PY - 2004/6/27

Y1 - 2004/6/27

N2 - Background. Acute rejection (aRx) has a major impact on the long-term outcome of renal allografts, and its diagnosis is contingent on the invasive procedure of allograft biopsy. New immunosuppreasive protocols have reduced the incidence but have not abolished this problem. Moreover, aRx is now more frequently seen several weeks after transplantation in outpatients. A noninvasive diagnostic test for predicting aRx could improve the management and outcome. The recently described measurement of urinary mRNA expression offers a new noninvasive approach. Methods. In this study, the authors monitored the urinary mRNA expression (221 specimens from 26 patients) of various immune molecules by real-time reverse-transcriptase polymerase chain reaction for up to 3 months after kidney transplantation. Most of the patients received anti-interleukin (IL)-2 receptor monoclonal antibody induction and tacrolimus-based maintenance immunosuppression, which resulted in a low incidence of aRx. To verify the "rejection" markers, an additional nine samples of patients with aRx were analyzed. Results. Granulysin mRNA increase (vs. 95% confidence interval of 159 urine samples from nonrejecting patients) was detected during 11 of 14 aRx episodes, and follow-up studies showed its predictive value for delayed aRx episodes, even weeks before enhanced serum creatinine was observed. Granulysin induction was associated with enhanced regulated on activation normal T-cell expressed and secreted (RANTES) mRNA expression in 8 of 11 samples. Other cytotoxic effector molecules (granzyme B, perforin, FasL), cytokines (tumor necrosis factor-α, RANTES, IL-2, IL-10, interferon-γ, transforming growth factor-β), CD3, and CCR1 showed less specificity and sensitivity. Conclusions. The authors' data illustrate that the noninvasive kinetic mRNA expression measurement of defined markers in urinary cells of renal allograft recipients allows the early noninvasive detection of ongoing aRx.

AB - Background. Acute rejection (aRx) has a major impact on the long-term outcome of renal allografts, and its diagnosis is contingent on the invasive procedure of allograft biopsy. New immunosuppreasive protocols have reduced the incidence but have not abolished this problem. Moreover, aRx is now more frequently seen several weeks after transplantation in outpatients. A noninvasive diagnostic test for predicting aRx could improve the management and outcome. The recently described measurement of urinary mRNA expression offers a new noninvasive approach. Methods. In this study, the authors monitored the urinary mRNA expression (221 specimens from 26 patients) of various immune molecules by real-time reverse-transcriptase polymerase chain reaction for up to 3 months after kidney transplantation. Most of the patients received anti-interleukin (IL)-2 receptor monoclonal antibody induction and tacrolimus-based maintenance immunosuppression, which resulted in a low incidence of aRx. To verify the "rejection" markers, an additional nine samples of patients with aRx were analyzed. Results. Granulysin mRNA increase (vs. 95% confidence interval of 159 urine samples from nonrejecting patients) was detected during 11 of 14 aRx episodes, and follow-up studies showed its predictive value for delayed aRx episodes, even weeks before enhanced serum creatinine was observed. Granulysin induction was associated with enhanced regulated on activation normal T-cell expressed and secreted (RANTES) mRNA expression in 8 of 11 samples. Other cytotoxic effector molecules (granzyme B, perforin, FasL), cytokines (tumor necrosis factor-α, RANTES, IL-2, IL-10, interferon-γ, transforming growth factor-β), CD3, and CCR1 showed less specificity and sensitivity. Conclusions. The authors' data illustrate that the noninvasive kinetic mRNA expression measurement of defined markers in urinary cells of renal allograft recipients allows the early noninvasive detection of ongoing aRx.

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