Renal epithelial cells retain primary cilia during human acute renal allograft rejection injury

Abstract Objectives Primary cilia are sensory organelles which co-ordinate several developmental/repair pathways including hedgehog signalling. Studies of human renal allografts suffering acute tubular necrosis have shown that length of primary cilia borne by epithelial cells doubles throughout the nephron and collecting duct, and then normalises as renal function returns. Conversely the loss of primary cilia has been reported in chronic allograft rejection and linked to defective hedgehog signalling. We investigated the fate of primary cilia in renal allografts suffering acute rejection. Results Here we observed that in renal allografts undergoing acute rejection, primary cilia were retained, with their length increasing 1 week after transplantation and remaining elevated. We used a mouse model of acute renal injury to demonstrate that elongated renal primary cilia in the injured renal tubule show evidence of smoothened accumulation, a biomarker for activation of hedgehog signalling. We conclude that primary cilium-mediated activation of hedgehog signalling is still possible during the acute phase of renal allograft rejection.

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The value of urine cytologic examination findings in the diagnosis of the acute renal allograft rejection

Vojnosanitetski pregled ◽

10.2298/vsp0301035t ◽

2003 ◽

Vol 60 (1) ◽

pp. 35-41 ◽

Cited By ~ 3

Author(s):

Zeljka Tatomirovic ◽

Radojka Bokun ◽

Jovan Dimitrijevic ◽

Ljiljana Ignjatovic ◽

Anastasija Aleksic ◽

...

Keyword(s):

Acute Rejection ◽

Allograft Rejection ◽

Renal Allograft ◽

Urine Cytology ◽

Acute Allograft Rejection ◽

Histological Findings ◽

Renal Allograft Rejection ◽

Renal Tubular Cells ◽

Allograft Dysfunction ◽

Acute Renal Allograft Rejection

Background. Acute rejection of allograft is one of the most serious complications of renal transplantation that requires fast and precise diagnostic approach. In this paper our experience in cytologic urinalysis as a diagnostic method of the acute renal allograft rejection was reviewed. Methods. The study group included 20 of 56 patients with transplanted kidneys who were assumed for the acute allograft rejection according to allograft dysfunction and/or urine cytology findings. Histological findings confirmed allograft rejection in 4 patients. Urine sediment obtained in cytocentrifuge was air-dried and stained with May-Grunwald-Giemsa. Acute allograft rejection was suspected if in 10 fields under high magnification 15 or more lymphocytes with renal tubular cells were found. Results. Acute transplant rejection occured in 32.1% patients. In 15 patients clinical findings of the acute renal allograft rejection corresponded with cytological and histological findings (in the cases in which it was performed). Three patients with clinical signs of the acute allograft rejection were without cytological confirmation, and in 2 patients cytological findings pointed to the acute rejection, but allograft dysfunction was of different etiology (acute tubular necrosis, cyclosporine nephrotoxicity). In patients with clinical, cytological and histological findings of the acute allograft rejection urine finding consisted of 58% lymphocytes, 34% neutrophilic leucocytes and 8% monocytes/macrophages on the average. The accuracy of cytologic urinalysis related to clinical and histological finding was 75%. Conclusion. Urine cytology as the reliable noninvasive, fast and simple method is appropriate as the a first diagnostic line of renal allograft dysfunction, as well as for monitoring of the graft function.

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Longitudinal Analysis of Whole Blood Transcriptomes to Explore Molecular Signatures Associated with Acute Renal Allograft Rejection

Bioinformatics and Biology Insights ◽

10.4137/bbi.s13376 ◽

2014 ◽

Vol 8 ◽

pp. BBI.S13376 ◽

Cited By ~ 7

Author(s):

Heesun Shin ◽

Oliver GÜnther ◽

Zsuzsanna Hollander ◽

Janet E. Wilson-Mcmanus ◽

Raymond T. Ng ◽

...

Keyword(s):

Gene Expression ◽

Acute Rejection ◽

Whole Blood ◽

Allograft Rejection ◽

Time Course ◽

Renal Allograft ◽

Acute Rejection Episode ◽

Renal Allograft Rejection ◽

Expression Signature ◽

Acute Renal Allograft Rejection

In this study, we explored a time course of peripheral whole blood transcriptomes from kidney transplantation patients who either experienced an acute rejection episode or did not in order to better delineate the immunological and biological processes measureable in blood leukocytes that are associated with acute renal allograft rejection. Using microarrays, we generated gene expression data from 24 acute rejectors and 24 nonrejectors. We filtered the data to obtain the most unambiguous and robustly expressing probe sets and selected a subset of patients with the clearest phenotype. We then performed a data-driven exploratory analysis using data reduction and differential gene expression analysis tools in order to reveal gene expression signatures associated with acute allograft rejection. Using a template-matching algorithm, we then expanded our analysis to include time course data, identifying genes whose expression is modulated leading up to acute rejection. We have identified molecular phenotypes associated with acute renal allograft rejection, including a significantly upregulated signature of neutrophil activation and accumulation following transplant surgery that is common to both acute rejectors and nonrejectors. Our analysis shows that this expression signature appears to stabilize over time in nonrejectors but persists in patients who go on to reject the transplanted organ. In addition, we describe an expression signature characteristic of lymphocyte activity and proliferation. This lymphocyte signature is significantly downregulated in both acute rejectors and nonrejectors following surgery; however, patients who go on to reject the organ show a persistent downregulation of this signature relative to the neutrophil signature.

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Determinants of Hypofiltration during Acute Renal Allograft Rejection

Journal of the American Society of Nephrology ◽

10.1681/asn.v133773 ◽

2002 ◽

Vol 13 (3) ◽

pp. 773-778

Author(s):

Alkesh Jani ◽

Catherine Polhemus ◽

Geraldine Corrigan ◽

Osun Kwon ◽

Bryan D. Myers ◽

...

Keyword(s):

Acute Rejection ◽

Morphometric Analysis ◽

Allograft Rejection ◽

Renal Allograft ◽

Control Group ◽

Hydraulic Pressure ◽

Acid Extraction ◽

Oncotic Pressure ◽

Renal Allograft Rejection ◽

Acute Renal Allograft Rejection

ABSTRACT. This study sought to determine the extent to which GFR is decreased during acute renal allograft rejection in human subjects and to determine the mechanism of the decrease in GFR. Eight patients with biopsy-proven acute rejection were compared with 18 recipients of optimally functioning renal allografts. GFR and renal plasma flow (RPF) were measured as the clearance of inulin and para-aminohippuric acid, respectively. Arterial BP was determined, blood was sampled, and plasma oncotic pressure (πA) was measured. Glomeruli obtained by biopsy during rejection were subjected to morphometric analysis, for determination of Kf. Control morphometric values for healthy glomeruli were provided by 10 living donors from whom biopsies were obtained at the time of organ donation. The subjects in the acute rejection group exhibited a significantly reduced GFR of 17 ± 4 ml/min per 1.73 m2, compared with 72 ± 4 ml/min per 1.73 m2 for control subjects (P < 0.001). With the use of a sensitivity analysis to take into account the unknown para-aminohippuric acid extraction ratio, the RPF rate was calculated to have likely been significantly decreased, by 45 to 70%, in the acute rejection group. Neither the plasma oncotic pressure nor the mean arterial pressure differed between the two groups. Morphometric analysis revealed no difference in the single-nephron Kf values for the acute rejection group, compared with the control group. These results indicate that acute renal allograft rejection causes a profound decrease in GFR, which is attributable to a decrease in RPF alone or in combination with a decrease in the glomerular transcapillary hydraulic pressure gradient (ΔP).

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