Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction

Badid, Chérif; Desmoulière, Alexis; Babici, Daniela; Hadj‐Aïssa, Aoumeur; McGregor, Brigitte; Lefrançois, N; Touraine, Jean Louis; Laville, Maurice

doi:10.1093/ndt/17.11.1993

Cited by 83 publications

(59 citation statements)

References 21 publications

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“…Indeed, kidneys preserved in IGL-1 solution presented a degree of fibrosis similar to that of control kidneys while kidneys preserved in K-UW solution showed early appearance of fibrosis, which is specific for pig models [16]. Interstitial expression of alpha-SMA is considered an early marker of chronic renal allograft dysfunction and its evaluation in timezero biopsies can predict this event [24]. IGL-1 solution was found to be able to significantly limit the fibrosis, which is considered to be the lesion leading to chronic renal injury and progressive loss of renal function [25].…”

Section: Discussionmentioning

confidence: 96%

Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

et al. 2004

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Ischemia-reperfusion injury conditions short-term and longterm graft function. The effects of the inversion of K + and N a + concentrations and substitution with polyethylene glycol for hydroxyethyl starch in University of Wisconsin (K-UW) solution were evaluated in isolated perfused rat kidneys and in autotransplanted pig kidneys. In the rat model kidneys were cold-stored for 24 h in K-UW or Na-UW or Na-PEG UW solutions (IGL-I solution). Fractional sodium reabsorption and glomerular filtration rate was better in kidneys preserved in Na-UW and IGL-1 solution than those preserved in K-UW solution. In the pig model the left kidney was harvested and preserved in K-UW or IGL-1 solution for 24 h and then transplanted. In the autotransplanted pig model, kidneys preserved in IGL-1 solution showed a better function and a significant reduction of MHC class I1 expression, cellular apoptosis and interstitial fibrosis.In conclusion, kidneys preserved in IGL-I solution tolerated ischemia/ reperfusion injury better than those preserved in K-UW solution.

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Section: Discussionmentioning

confidence: 96%

Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

et al. 2004

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“…However, very little is known about the role of interstitial myofibroblast in the pathogenesis and progression of renal allograft fibrosis. Badid et al (33) suggested that interstitial ␣-SMA expression in pretransplant biopsies can strongly predict chronic renal allograft dysfunction. Recently, the presence of ␣-SMA-expressing interstitial myofibroblast in the development of chronic allograft nephropathy was suggested by Djamali et al (34) in an experimental model of chronic allograft dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin for Treatment of Chronic Allograft Nephropathy in Renal Transplant Patients

Stallone

Infante

Schena³

et al. 2005

Journal of the American Society of Nephrology

113

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Chronic allograft nephropathy (CAN) represents the main cause of renal allograft loss after 1 yr of transplantation. Calcineurin inhibitor (CNI) use is associated with increased graft expression of profibrotic cytokines, whereas rapamycin inhibits fibroblast proliferation. The aim of this randomized, prospective, open-label, single-center study was to evaluate the histologic and clinical effect of rapamycin on biopsy-proven CAN. Eighty-four consecutive patients who had biopsy-proven CAN and received a transplant were randomized to receive either a 40% CNI reduction plus mycophenolate mofetil (group 1; 50 patients) or immediate CNI withdrawal and rapamycin introduction with a loading dose of 0.1 mg/kg per d and a maintaining dose aiming at through levels of 6 to 10 ng/ml (group 2; 34 patients). The follow-up period was 24 mo. At the end of follow-up, 25 patients (group 1, 10 patients; group 2, 15 patients) underwent a second biopsy. CAN lesions were graded according to Banff criteria. ␣-Smooth muscle actin (␣-SMA) protein expression was evaluated in all biopsies as a marker of fibroblast activation. Graft function and Banff grading were superimposable at randomization. Graft survival was significantly better in group 2 (P ‫؍‬ 0.0376, 2 ‫؍‬ 4.323). CAN grading worsened significantly in group 1, whereas it remained stable in group 2. After 24 mo, all group 1 biopsies showed an increase of ␣-SMA expression at the interstitial and vascular levels (P < 0.001); on the contrary, ␣-SMA expression was dramatically reduced in group 2 biopsies (P ‫؍‬ 0.005). This study demonstrates that rapamycin introduction/CNI withdrawal improves graft survival and reduces interstitial and vascular ␣-SMA expression, slowing down the progression of allograft injury in patients with CAN.

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“…39,40 Furthermore, early myofibroblast infiltration predicts chronic renal allograft dysfunction in renal transplant recipients. 42 Additional studies to determine whether the degree of myofibroblast infiltration in the bronchial tissue correlates with clinical course of the disease would be useful in making clinical predictions. Our studies used two different murine models of BO to evaluate the role of IL-13 in the pathogenesis of this disease.…”

Section: Discussionmentioning

confidence: 99%

Obligatory Role for Interleukin-13 in Obstructive Lesion Development in Airway Allografts

Lama

Harada

Badri

et al. 2006

The American Journal of Pathology

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The pathogenesis of bronchiolitis obliterans (BO), a common and devastating obliterative disorder of small airways following lung transplantation, remains poorly understood. Lesions are characterized in their early stages by lymphocyte influx that evolves into dense fibrotic infiltrates. Airway specimens taken from patients with histological BO revealed infiltrating myofibroblasts, which strongly expressed the signaling chain of the high affinity interleukin-13 (IL-13) receptor IL-13R␣1. Because IL-13 has proinflammatory and profibrotic actions, a contributory role for IL-13 in BO development was examined using murine models of orthotopic and heterotopic tracheal transplantation. Compared with airway isografts, allografts exhibited a significant increase in relative IL-13 mRNA and protein levels. Allogeneic tracheas transplanted into IL-13-deficient mice were protected from BO in both transplant models. Flow cytometric analysis of orthotopic transplant tissue digests revealed markedly fewer infiltrating mononuclear phagocytes and CD3؉ T lymphocytes in IL-13-deficient recipients. Furthermore, protection from luminal obliteration, collagen deposition, and myofibroblast infiltration was observed in heterotopic airways transplanted into the IL-13 ؊/؊ recipients. Transforming growth factor-␤1 expression was significantly decreased in tracheal allografts into IL-13 ؊/؊ recipients, compared to wild-type counterparts. These human and murine data implicate IL-13 as a critical effector cytokine driving cellular recruitment and subsequent fibrosis in clinical and ex- Bronchiolitis obliterans syndrome (BOS) is the major factor limiting quality of life as well as long-term survival after lung transplantation. BO is a histological diagnosis, characterized by fibrosis and obliteration of the small airways.1 BOS, the clinical correlate of BO, is diagnosed by irreversible deterioration of pulmonary function in the absence of other causes.2 BOS is seen in up to 60% of lung transplant recipients by 5 years after transplantation. There are currently no meaningful therapeutic interventions, providing a compelling rationale to understand fully BOS pathogenesis as this may lead to development of new therapeutic approaches.Data from human as well as animal studies suggest associations between inflammatory cells/mediators and BOS. Lymphocytic bronchitis is considered a risk factor for development of BOS in humans, 3 and lymphocytic infiltration precedes development of luminal obliteration in animal models of tracheal transplantation. 4,5 Similarly, several markers of inflammation (eg, neutrophilia,(6)(7)(8)7 and monocyte chemoattractant protein-1 (MCP-1/ CCL2) 8,9 ) are predictive of development of BO in humans. However, the failure of immunosuppressive therapy and anti-inflammatory agents to demonstrate efficacy in preventing or treating this disease has focused attention on BOS as a fibroproliferative response to airway epithelial injury. Evidence for this is provided by studies suggesting a role for transforming growth factor-␤ (TGF-...

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Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction

Abstract: This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.

Cited by 83 publications

References 21 publications

Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

Rapamycin for Treatment of Chronic Allograft Nephropathy in Renal Transplant Patients

Obligatory Role for Interleukin-13 in Obstructive Lesion Development in Airway Allografts

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