Diagnosis Of Acute Renal Rejection Research Articles

Performance of Polymerase Chain Reaction Techniques Detecting Granzyme B in the Diagnosis of Acute Renal Rejection

Studies have shown that granzyme B expression was up-regulated during acute renal rejection, which provides hopes for a noninvasive and reliable diagnostic method. However, the diagnostic performance has not been assessed systematically so far. Relevant materials were searched from electronic databases before February 1, 2012. Clinical studies that reported the diagnostic performance of detecting granzyme B mRNA using polymerase chain reaction techniques in acute renal rejection patients were included. The data of true-positive, true-negative, false-positive, and false-negative cases identified by granzyme B detection were extracted from each data set of the relevant materials. The publication year, sample origin, mRNA quantification method, and housekeeping gene were extracted as potential confounding variables. Fourteen studies with a total of 514 cases were included. The overall diagnostic performance of granzyme B was pooled sensitivity of 0.76 (95% confidence interval [CI], 0.69-0.81), pooled specificity of 0.87 (95% CI, 0.83-0.90), diagnostic odds ratio of 19.27 (95% CI, 1.20-195.00), and area under the summary receiver operating characteristic curve value of 0.8900±0.0270. The univariate analysis of potential variables showed no statistically significant variations. Despite interstudy variability, granzyme B mRNA demonstrated both sensitivity and specificity in the diagnosis of acute rejection and showed consistency under circumstances of methodologic changes. However, the clinical practice requires careful consideration and other supplementary tests.

Performance of Polymerase Chain Reaction Techniques Detecting Perforin in the Diagnosis of Acute Renal Rejection: A Meta-Analysis

BackgroundStudies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance.Methodology/Principal FindingsRelevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88); pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90); diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97); and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance.Conclusions/SignificanceDespite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal rejection. These results suggest a great diagnostic potential for perforin mRNA detection as a reliable marker of acute rejection in renal allograft recipients.

Detection of urinary biomarkers for early diagnosis of acute renal allograft rejection by proteomic analysis

Acute allograft rejection has been recognized as a major impediment to improved success in renal transplantation. Timely detection and control of rejection are very important for the improvement in long-term renal allograft survival. Thus, biomarkers for early diagnosis of acute rejection are required urgently to clinical medication. This study seeks to search for such biomarker candidates by comparing patients' pre-treatment urinary protein profiling with their post-treatment urinary protein profiling. A total of 15 significantly and consistently down-regulated protein candidates were identified. Among them, alpha-1-antichymotrypsin precursor (AACT), tumor rejection antigen gp96 (GP96) and Zn-Alpha-2-Glycoprotein (ZAG) were selected for further analysis. The results indicated that Western Blot assay of AACT, GP96 and ZAG had advanced the diagnosis time of acute renal rejection by 3 days, compared with current standard clinical observation and laboratory examination. Furthermore, the double-blind detection revealed that the accuracy, sensitivity and specificity of the diagnosis of acute renal rejection of AACT, GP96 and ZAG were 66.67%/100%/60%, 83.33%/100%/80% and 66.67%/100%/60%, respectively, and 100%/100%/100% in combination. In conclusion, urinary protein AACT, GP96 and ZAG could be a set of potential biomarkers for early non-invasive diagnosis of the acute rejection after renal transplantation.

Renal expression of CD44 correlates with acute renal allograft rejection

As CD44 is involved in the activation, proliferation, adhesion, and extravasation of lymphocytes, we hypothesized that CD44 could be involved in the pathogenesis of acute renal allograft rejection. Renal biopsies and plasma were collected from patients suffering an episode of acute renal allograft rejection. CD44 and its ligands, hyaluronic acid (HA) and osteopontin, were analyzed retrospectively by immunohistochemistry and, computer-aided, morphometric analysis. Soluble CD44 (sCD44) and osteopontin in the plasma were determined by enzyme-linked immunosorbent assay. During acute rejection episodes, CD44 and its ligands, HA and osteopontin, were upregulated in the renal allograft. Also, increased sCD44 plasma levels were observed, which correlated with both tubular expression of CD44 and the extent of infiltrate. No differences could be detected between the different pathologic grades of rejection. Upregulation of tubular CD44 and increased levels of circulating sCD44 may reflect a common pathogenic mechanism during acute renal rejection and could be useful markers in the diagnosis of acute renal rejection.

Usefulness of Thromboxane B2 in Diagnosis of Renal Transplant Rejection

Abstract Morelet et al. (1) assessed the usefulness of sequential urinary albumin measurements in 16 renal allograft recipients, eight with and eight without acute graft-rejection episodes. They concludedthat the urinary albumin/creatinine ratio is poorly specific in the diagnosis of acute renal rejection, as shown by a high proportion of false-positive results. In addition, they commented on similar findings-poor specificity and poor positive predictive value-for other urinary components, e.g., β2-microglobulin, neopterin, renal tubular enzymes, thromboxane B2 (TxB2), interleukin-2, and solubleIL-2 receptor.

The Importance of Urinary Thromboxane B<sub>2</sub> Excretion in the Diagnosis of Acute Renal Rejection

To establish whether or not urinary excretion TxB2 is a useful parameter in the diagnosis of acute renal rejection, 45 renal transplant patients were studied and classified in four groups: Group A. Ten observations of satisfactory clinical outcome (without either acute rejection or tubular necrosis). Urinary TxB2 was initially increased but had settled to normal by the 3rd postoperative day. Two patients had subsequent increases. Group B. Twenty-five episodes of acute rejection on a previously satisfactorily functioning graft. Nineteen had increases in TxB2 values before serum creatinine increased. Group C. Five episodes of tubular necrosis without acute rejection. The evolution was similar to Group A. Group D. Nine acute episodes of rejection on kidneys with tubular necrosis. The urinary output of TxB2 was increased from the beginning. This increase was maintained until the rejection was treated. This group had the highest values of urine TxB2. The principal significance of this parameter lies in its precocity and in its utility for diagnosis of acute rejection in the graft with tubular necrosis, as the persistence of raised values of TxB2 in the urine beyond the 3rd postoperative day is highly suggestive of an acute rejection.