Noninvasive Diagnosis of Renal-Allograft Rejection by Measurement of Messenger RNA for Perforin and Granzyme B in Urine

Li, Baogui; Hartono, Choli; Ding, Ruchuang; Sharma, Vijay Kumar; Ravi, R.; Qian, Biao; Serur, David; Mouradian, Janet; Schwartz, Joseph E.; Suthanthiran, Manikkam

doi:10.1056/nejm200103293441301

Cited by 543 publications

(420 citation statements)

References 36 publications

Supporting

Mentioning

383

Contrasting

Unclassified

Order By: Relevance

“…Although a number of clinical investigations focused on other putative indicators of alloreaction like IL-2, MCP-1, or granzyme B (27)(28)(29), more recently transplantation studies in animals (8,24,30) and measurements of chemokine mRNA in biopsy specimens (11,12,31,32) have stressed the prominent role of IFN-␥-dependent chemokines, especially MIG, for the acute phase of allograft rejection. Urinary measurements of MIG in a small number of pediatric patients (33) and in adult renal allograft patients support our data (34,35).…”

Section: Discussionmentioning

confidence: 99%

Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG)

Hauser¹,

Spiegler²,

Kiss³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Early diagnosis of acute allograft rejection (AR) is still decisive for long-term renal allograft survival. The aim of this study was to define the role of the chemokine monokine induced by IFN-␥ (MIG) (CXCL9) and IFN-␥-inducible protein 10 (IP-10) (CXCL10) as early markers of AR in renal transplantation (NTX). In a prospective study, 69 de novo renal transplant recipients were monitored and urine samples were collected after NTX for a median of 29 d. In pH-adjusted urine, MIG and IP-10 were determined by modified ELISA. AR was clinically diagnosed in 15 of 69 recipients and confirmed by biopsy in 14 of 15 AR patients (Banff classification). Corresponding to CXCR3-positive infiltrates in renal tissue, urinary MIG was elevated in 14 of 15 AR patients with a median of 2809 pg/ml (quartile 25% and 75% ‫؍‬ 870 and 13,000; n ‫؍‬ 15), being significantly (P < 0.0001) different from both nonrejecting allograft patients (NO-AR) (median, 25%, and 75%: 96, 1.0, and 161, n ‫؍‬ 54) and healthy controls (median, 25%, and 75%: 144, 19, and 208, n ‫؍‬ 13). Urinary MIG predicted AR with a sensitivity of 93% and a specificity of 89%. In AR and NO-AR groups, MIG values correlated well with IP-10 (P < 0.001). MIG values indicated both imminent rejection and response to successful antirejection therapy. MIG was not related to intercurrent infections or other causes for impairment of renal function. In a multivariate analysis, MIG correlated best (P < 0.001) with AR from all AR-associated parameters. In conclusion, urinary MIG serves as a very sensitive and specific predictor for AR, mirrors response to antirejection therapy, and thus may contribute to improved long-term renal allograft survival.

show abstract

Section: Discussionmentioning

confidence: 99%

Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG)

Hauser¹,

Spiegler²,

Kiss³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Therefore, a renal biopsy is necessary to determine the appropriate treatment. In an attempt to find molecular markers for acute rejection in a minimally invasive manner, Li et al showed that granzyme B and perforin mRNA levels measured in urine can be used as powerful tools to discriminate acute rejection from other causes of acute graft failure [100]. A recent report contains speculations about the application of microarray technology on peripheral blood lymphocytes (PBSL) in finding more sensitive markers for acute rejection [101].…”

Section: Potential Of Molecular Diagnostics In Nephrological Practicementioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

View full text Add to dashboard Cite

Chronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor-beta, platelet-derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large-scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention.

show abstract

“…Past studies on pancreatic islet allograft rejection have shown increased cytokine gene expression levels, which reached a high steady-state before significant graft damage occurred (9). Li et al used conventional competitive polymerase chain reaction (PCR) in 17 samples from 8 renal allograft recipients rejecting their graft and 83 samples from 29 non-rejecting patients, to show that perforin and granzyme B expression is higher in the urine of rejecting patients during the first 9 days post transplantation (10). Thus, molecular correlates may not only be a more sensitive tool for detecting acute rejection, they may also predict an impending rejection before extensive damage has been done to the graft.…”

Section: Introductionmentioning

confidence: 99%

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

Simon

Opelz

Wiesel

et al. 2003

American Journal of Transplantation

101

View full text Add to dashboard Cite

In the present study we investigated whether peripheral blood gene expression measurements may serve as an early and non-invasive tool to predict renal allograft rejection. Peripheral blood was collected twice weekly after transplantation and gene expression was measured using real-time polymerase chain reaction (PCR). Recipients with acute rejection (n = 17) had higher levels of perforin and granzyme B transcript on days 5-7, 8-10, 11-13, 17-19, 20-22, and 26-29, as compared to patients without rejection (n = 50, p < 0.05 in all cases). Rejection diagnosis using gene expression criteria, determined with receiver operating characteristic (ROC) curves, was possible 2-30 days before traditional diagnosis (median 11 days). The best diagnostic result was obtained from samples taken on days 8-10, with a specificity of 90% and a sensitivity of 82% for perforin, and a specificity of 87% and sensitivity of 72% for granzyme B. Decreases in perforin (p < 0.01) and granzyme B expression (p < 0.05) were observed after initiation of anti-rejection therapy. Our data indicate that gene expression measurement is a useful tool for the recognition of graft rejection in its earliest stages. Serial measurements could be implemented as a monitoring system to highlight patients at higher risk of rejection, making them candidates for biopsy or pre-emptive anti-rejection therapy.

show abstract

Noninvasive Diagnosis of Renal-Allograft Rejection by Measurement of Messenger RNA for Perforin and Granzyme B in Urine

Abstract: Measurement of mRNA encoding cytotoxic proteins in urinary cells offers a noninvasive means of diagnosing acute rejection of renal allografts.

Cited by 543 publications

References 36 publications

Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG)

Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG)

ECM homeostasis in renal diseases: a genomic approach

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

Contact Info

Product

Resources

About