Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the transcripts that are increased by stress and injury in mouse kidney transplants, focusing on transcripts increased in parenchymal cells-injury and repair-induced transcripts (IRITs). We compared four types of stressed kidneys: isografts, allografts, host kidneys of mice with isografts and nontransplant kidneys with ischemic acute tubular necrosis (ATN). After excluding transcripts associated with infiltrating cells and interferon-gamma-induced transcripts, we defined 790 IRITs in isografts. IRITs were remarkably heterogeneous in timing and mechanisms. Some were increased in host as well as donor kidneys, reflecting systemic influences (wounding, anesthetic). Most reflected local stress, resembling changes in ATN despite the lack of ATN histopathology. Mathematical decomposition of IRIT expression patterns confirmed heterogeneity, separating IRIT changes into component subsets, with an early peak (day 1) showing systemic effects and late peaks that resembled ATN, manifested Tgf-ss1 effects and recapitulated embryonic development. In allografts IRITs were initially similar to isografts but diverged due to allogeneic injury. The allospecific induction of IRITs was T-cell-dependent but perforin-granzyme-independent, compatible with delayed type hypersensitivity. The alloresponse strikingly and selectively increased the late IRITs but not the IRITs that peak early, indicating that rejection triggers parenchymal responses similar to those in ATN.
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PMID:Transcriptome analysis reveals heterogeneity in the injury response of kidney transplants. 1790 79

Delayed graft function (DGF) often occurs in kidney transplants from deceased donors. We wanted to provide studies giving more accurate non-invasive tests for acute rejection (AR). Using real-time PCR, we examined the expression of cytolytic molecules such as perforin, granzyme B, and fas-ligand along with serpin proteinase inhibitor-9. We also measured the expression of FOXP3, a characteristic gene of T-regulatory cells known to be involved in AR. These studies were conducted on peripheral blood monocytes, urinary cells, and 48 surveillance kidney biopsies taken from a total of 35 patients with DGF. Of these patients, 20 had a histopathological diagnosis of AR, whereas other 28 had characteristics of acute tubular necrosis (ATN). Expression of cytolytic and apoptotic-associated genes in the biopsy tissue, peripheral blood leukocytes, and urinary cells was significantly higher in patients with AR than that in patients with ATN. Diagnostic parameters associated with FOXP3 gene expression were most accurate in peripheral blood leukocytes and urine cells with sensitivity, specificity, positive and negative predictive values, and accuracy between 94 and 100%. Our study shows that quantification of selected genes in peripheral blood leukocytes and urinary cells from renal transplant patients with DGF may provide a useful and accurate non-invasive diagnosis of AR.
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PMID:Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function. 1821 81

Chemokines and their receptors play an important role in the development of allograft rejection through directing mononuclear cell invasion of the graft. To study whether chemokine assays in the urine could prove to be predictive of acute rejection, we measured the urinary excretion of several chemokines, including fractalkine, chemokine monokine induced by interferon-gamma, interferon-gamma-inducible protein 10, macrophage inflammatory protein-3 alpha, granzyme B, and perforin in 215 allograft recipients and in 80 healthy control subjects. The 67 patients with acute rejection had significantly higher levels of all urinary chemokines compared to the healthy controls or patients having chronic allograft nephropathy but with stable renal function. Only changes in urinary fractalkine differentiated patients with acute rejection from those with acute tubular necrosis. The 7 patients who lost their grafts had greater urinary fractalkine, interferon-gamma, and macrophage inflammatory protein-3 alpha concentrations than those patients with reversible acute rejection. The area under the receiver operating characteristic curve for fractalkine was the best indicator among all of the markers differentiating 39 patients diagnosed with steroid-resistant from the 28 patients with steroid-sensitive acute rejection and in predicting graft loss. Our study shows that measuring urinary fractalkine levels is a noninvasive approach for detecting acute rejection where high levels were associated with steroid-resistance and poor outcome.
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PMID:Urinary fractalkine is a marker of acute rejection. 1880 27

The distinction between T-cell-mediated rejection (TCMR) and other causes of kidney transplant dysfunction such as tubular necrosis requires biopsy. Subclinical rejection (SCR), an established risk factor for chronic allograft dysfunction, can only be diagnosed by protocol biopsy. A specific non-invasive biomarker to monitor immunological graft status would facilitate diagnosis and treatment of common transplantation-related complications. To identify possible markers, we measured urinary mRNA levels of several cytolytic proteins by quantitative PCR. Our cohort of 70 renal transplant recipients had biopsy proven type I and type II TCMR, acute tubular necrosis, SCR, calcineurin inhibitor-toxicity, cytomegalovirus infection, and stable graft function with normal histology. Granzyme A (GzmA) mRNA was significantly higher in subclinical and acute cellular rejection compared to patients with stable grafts or those with tubular necrosis with 80% sensitivity and up to 100% specificity. Granzyme B and perforin mRNA levels could significantly discriminate acute rejection from stable or tubular necrosis, but were not significantly elevated during SCR. Importantly, only GzmA mRNA remained below detection limits from grafts that were stable and most with tubular necrosis. Hence, the presented data indicate that urinary GzmA mRNA levels may entail a diagnostic non-invasive biomarker to distinguish patients with subclinical and acute cellular rejection from those with tubular necrosis or stable grafts.
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PMID:Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients. 2072 May 22