ABSTRACT
Kidney is a highly vascularized organ and peritubular capillary network constitutes the critical component of its microvascular system. Peritubular capillaries, as the main vessels for blood supply in renal tubules and renal interstitium, involve in important physiological processes in renal tubules such as energy metabolism, substance secretion and reabsorption. In recent years, it has been demonstrated that ischemia-reperfusion injury, rejection and renal fibrosis during kidney transplantation would result in compromised structural integrity and decreased number in peritubular capillaries, thus leading to interstitial fibrosis in renal allograft, which would seriously affect the long-term stability of renal function in the renal allograft. Therefore, we reviewed the structure and function of peritubular capillary, peritubular capillary and ischemia-reperfusion injury, rejection and renal allograft fibrosis, focusing on the mechanism for peritubular capillary injury in kidney transplantation and the specific changes manifested, with the aim of providing a reference for preventing and treating perioperative complications in kidney transplantation and improving the long-term prognosis of grafts.
ABSTRACT
With the development of organ transplantation in clinical practice, allograft pathology has been constantly developing and advancing. The convening of Banff conference on allograft pathology and the establishment of Banff classification on allograft pathology (Banff classification) are pivotal milestones in the development of international allograft pathology. Since then, Banff classification on pathological diagnosis of various transplant organs have been continually updated and improved. Ultrastructural pathological observation by electron microscope plays an irreplaceable role in the early diagnosis of antibody-mediated rejection, recurrent disease and de novo disease of renal allograft. Early detection and rational treatment help to maintain the long-term survival of renal allograft and reduce the failure of renal allograft. In this article, the basic definition of electron microscope and the ultrastructural pathological diagnosis, the research history and main progress on electron microscope diagnosis on Banff classification for renal allograft pathology were introduced, and typical pathological changes, specific terminology and diagnostic criteria of electron microscope diagnosis on renal allograft biopsy were summarized, aiming to provide reference for clinical and basic research of organ transplantation.
ABSTRACT
Objective To investigate the role of eNOS/NO signaling pathway in peritubular capillary lesions of mouse renal interstitial fibrosis with unilateral ureteral obstruction ( UUC) and the potential mechanism .Methods Sixty-four healthy male KM mice were randomly divided into sham operated group ( n=32 ) and unilateral ureteral obstruction group (n =32).At each week, serum BUN, Scr and NO were determined and the percentages of CD 133 +/VEGFR+en-dothelial progenitor cells in peripheral blood mononuclear cells were detected by flow cytometry .Morphological changes of the renal tissue were observed using Masson staining .The expression of CD34 +cells in the renal interstitium was analyzed by immunohistochemistry to calculate the peritubular capillary density .The expressions of eNos and VEGF mRNA were de-termined by real-time PCR.Results The expression of blood NO , the percentages of endothelial progenitor cells , peritu-bular capillaries, eNOS mRNA, and VEGF mRNA in the UUO group were significantly decreased compared with those of the sham group at 2, 3, and 4 weeks (P<0.05).NO was positively correlated with peritubular capillaries (r =0.715, P<0.05), eNOS mRNA was positively correlated with peritubular capillaries (r =0.624, P<0.05), endothelial progeni-tor cells (r =0.375, P<0.05), and VEGF mRNA (r =0.351, P<0.05).Conclusions eNOS/NO signaling path-way participates in regulation of peritubular capillary lesions in renal interstitial fibrosis of UUO mice .The mechanism may be partly related to the regulation of vasomotor reflex , the expression of VEGF mRNA and mobilization of endothelial pro-genitor cells.
ABSTRACT
Objective To study the pathogenesis of anemia in chronic aristolochic acid nephmpathy(CAAN) rats. Methods The hemoglobin(Hb)values of sixty-two male SD rats were assayed to determine its normal range.Among them,24 rats with normal Hb value were randomly divided into 2 groups:model group (MG)in which rats received the extract of Aristololochia manshuriensis Kom (AmK) by gavage,and control group (CG) received tap water only by gavage.Body weisht(BW),Hb,24 h urinary protein excretion(UP)and creatinine clearance (Ccr)of 6 rats in each group were measured before administration and at the end of the 8th week, respeetively.then these rats were sacrificed.The relative area of renal interstitial fibrosis was measured by microscopy.The mRNA expression of erythropoietin (EPO)in kidney tissue Was determined by real-time RT-PCR;protein expression of type I collagen(Coll),aminopeptidase P (APP),hypoxia indHeible factor let and 2α(HIF-1α and HIF-2α)in kidney tissue Was examined by immunohistochemistry staining. Results Hb values of normal rats presented normal distribution. The normal Hb was (155.9±16.5) g/L. Rat anemia was diagnosed when Hb was below 123.6 g/L. There was no difference in all the examination results between CG and MG before administration (P>0.05). Compared with CG, the Hb and Cer in MG were significantly decreased [(121.66±15.68) g/L vs (169.00±12.89) g/L, (0.63±0.13) ml/min vs (1.27±0.18) ml/min, P< 0.01], and the UP in MG was significantly increased at the end of the 8th week [(27.04±9.40) mg/d vs (6.11±0.84) mg/d, P<0.01]; the relative areas of fibrosis and Col l in renal interstitium of MG were significantly enlarged [(12.89±2.33)% vs (0.55±0.10)%, (13.92±2.92)% vs (1.32±0.84)%, P<0.01]; the protein expression of APP and the mRNA expression of EPO in the kidney tissue of MG were significantly down-regulated [(0.55±0.23)% vs (3.77±1.06)%, 0.005±0.001 vs 0.032±0.013, P<0.01]; the protein expression of HIF-lα and HIF-2α in the kidney tissue of MG was significantly up-regulated (2.55±0.16 vs 1.12±0.46, 2.33±0.33 vs 1.15±0.27, P<0.01), at the end of the 8th week. Conclusions The pathogenesis of anemia in CAAN may be due to the decreased production of EPO caused by the destruction of peritubular capillary. The compensatory up-regulation of HIF-lα and HIF-2α expression can not prevent the anemia development.
ABSTRACT
Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.