The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

BACKGROUND: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. PURPOSE: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). STUDY TYPE: Prospective. SUBJECTS: Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). FIELD STRENGTH/SEQUENCE: 1.5 T/T2-weighted imaging and DTI. ASSESSMENT: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. STATISTICAL TEST: One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. RESULTS: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 µmol/L vs. 82.3 ± 20.9 µmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DATA CONCLUSION: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Prospective quantitative study: Doppler ultrasound in the evaluation of chronic renal allograft disease and correlation with histopathological finding.

Background and Objectives: Renal allograft biopsy is the gold standard for diagnosing chronic allograft nephropathy, but noninvasive methods are needed to avoid unnecessary biopsies. Doppler ultrasonography, particularly the resistive index (RI), correlates with renal allograft dysfunction. This study aims to assess the relationship between renal sonographic parameters and biochemical parameters in diagnosing graft interstitial fibrosis. Methods: The study evaluated 60 renal allograft recipients for sonographic renal morphological features and Doppler indices. The estimated glomerular filtration rate (eGFR) was calculated, and cortical fibrosis after the biopsy was determined using the Banff score. Continuous variables like mean and SD were calculated, and categorical variables were reported using frequencies and proportions. Associations were examined using independent sample t-tests, χ 2tests, and multivariate regression analysis. Results: The mean eGFR was 75.23±25.45 ml/min/1.73 m2. A significant correlation of eGFR with RI (r=0.341, P=0.008) was seen. A significant difference in mean RI (F=10.167; df=2,57; P<0.001) was seen among the histological grades of fibrosis. Among the histological grades of fibrosis, significant differences in RI among mild and moderate (S.E. 0.033, P=0.043), mild and severe (S.E. 0.026, P=0.001) as well as moderate and severe (S.E. 0.036, P=0.029) was seen. Conclusion: Doppler was able to noninvasively predict allograft fibrosis and could be used as a complementary imaging tool during the follow-up of renal allograft patients. Future research is needed to improve evidence, diagnostic criteria, guidelines, and long-term impact.

Non-Traditional Non-Immunological Risk Factors for Kidney Allograft Loss-Opinion.

Rates of late allograft loss have improved slowly in the last decades. Well described traditional risk factors that influence allograft survival include cardiovascular events, rejection, infections and post-transplant neoplasia. Here, we critically evaluate the influence of several non-immunological, non-traditional risk factors and describe their impact on allograft survival and cardiovascular health of kidney transplant recipients. We assessed the following risk factors: arterial stiffness, persistent arteriovenous access, mineral bone disease, immunosuppressive drugs residual levels variability, hypomagnesemia, glomerular pathological alterations not included in Banff criteria, persistent inflammation and metabolic acidosis.

Rationale for the IMAGINE study for chronic active antibody-mediated rejection (caAMR) in kidney transplantation.

Chronic active antibody-mediated rejection (caAMR) in kidney transplantation is a major cause of late graft loss and despite all efforts to date, there is no proven effective therapy. Indeed, the Transplant Society (TTS) consensus opinion called for a conservative approach optimizing baseline immunosuppression and supportive care focused on blood pressure, blood glucose, and lipid control. This review provides the rationale and early evidence in kidney transplant recipients with caAMR that supported the design of the IMAGINE study whose goal is to evaluate the potential impact of targeting the IL6/IL6R pathway.

Vitamin D deficiency may predispose patients to increased risk of kidney transplant rejection.

BACKGROUND: Vitamin D deficiency occurs in more than 80% of kidney transplant recipients. Its immunomodulatory effects can predispose transplant recipients to rejection and chronic allograft nephropathy (CAN). This study determined the association between serum 25 (OH) vitamin D, biopsy-proven allograft rejection, and CAN rates. AIM: To determine the relationship between serum 25 (OH) vitamin D level and biopsy-proven allograft rejection and CAN rate in renal transplant recipients. METHODS: Adult renal transplant recipients followed at the clinic between January 2013 and 2018 were included. Recipients requiring graft biopsy due to declined function, hematuria, and proteinuria were reviewed. The two groups were compared regarding collected data, including the biopsy results, immunologic parameters, vitamin D, parathyroid hormone (PTH), phosphorus, albumin levels, and graft function tests. RESULTS: Fifty-two recipients who underwent graft biopsy met the inclusion criteria. In all, 14 recipients had a vitamin D level > 15 ng/mL (group 1) vs ≤ 15 ng/mL (group 2) in 38. In total, 27 patients had biopsy-proven rejection, and 19 had CAN. There was only 1 recipient with biopsy-proven rejection in group 1, whereas there were 24 patients with rejection in group 2. The rejection rate was significantly higher in group 2 than in group 1 (P < 0.001). Four patients were diagnosed with CAN in group 1 vs fifteen in group 2. There was no significant difference in the CAN rate between the two groups. PTH was higher at the time of graft biopsy (P = 0.009, P = 0.022) in group 1 with a mean of 268 pg/mL. Donor-specific antibodies were detected in 14 (56.0%) of the recipients with rejection. Vitamin D level was 9.7 ± 3.4 ng/mL in the rejection group vs 14.7 ± 7.2 in the non-rejection group; this difference was statistically significant (P = 0.003). The albumin levels were significantly lower in patients with rejection than in those without rejection (P = 0.001). In univariate regression analysis of risk factors affecting rejection, sex, serum vitamin D, phosphorus and albumin were found to have an impact (P = 0.027, P = 0.007, P = 0.023, P = 0.008). In multivariate regression analysis, the same factors did not affect rejection. CONCLUSION: The serum 25 (OH) vitamin D level in kidney transplant recipients remained low. Although low serum vitamin D level emerged as a risk factor for rejection in univariate analysis, this finding was not confirmed by multivariate analysis. Prospective studies are required to determine the effect of serum vitamin D levels on allograft rejection.

Identification of Hub Gene and Transcription Factor Related to Chronic Allograft Nephropathy Based on WGCNA Analysis.

INTRODUCTION: Kidney transplantation (KT) has surpassed dialysis as the optimal therapy for end-stage kidney disease. Yet, most patients could suffer from a slow but continuous deterioration of kidney function leading to graft loss mostly due to chronic allograft nephropathy (CAN) after KT. The dysregulated gene expression for CAN is still poorly understood. METHODS: To explore the pathogenesis of genomics in CAN, we analyzed the differentially expressed genes (DEGs) of kidney transcriptome between CAN and nonrejecting patients by downloading gene expression microarrays from the Gene Expression Omnibus database. Then, we used weighted gene coexpression network analysis (WGCNA) to analyze the coexpression of DEGs to explore key modules, hub genes, and transcription factors in CAN. Functional enrichment analysis of key modules was performed to explore pathogenesis. ROC curve analysis was used to validate hub genes. RESULTS: As a result, 3 key modules and 15 hub genes were identified by WGCNA analysis. Three key modules had 21 mutual Gene Ontology term enrichment functions. Extracellular structure organization, extracellular matrix organization, and extracellular region were identified as significant functions in CAN. Furthermore, transcription factor 12 was identified as the key transcription factor regulating key modules. All 15 hub genes, Yip1 interacting factor homolog B, membrane trafficking protein, toll like receptor 8, neutrophil cytosolic factor 4, glutathione peroxidase 8, mesenteric estrogen dependent adipogenesis, decorin, serpin family F member 1, integrin subunit beta like 1, SRY-box transcription factor 15, trophinin associated protein, SRY-box transcription factor 1, metallothionein 3, lysosomal protein transmembrane, FERM domain containing kindlin 3, and cathepsin S, had a great diagnostic performance (AUC > 0.7). CONCLUSION: This study updates information and provides a new perspective for understanding the pathogenesis of CAN by bioinformatics means. More research is needed to validate and explore the results we have found to reveal the mechanisms underlying CAN.

The phenotype of HLA-binding B cells from sensitized kidney transplant recipients correlates with clinically prognostic patterns of interferon-γ production against purified HLA proteins.

B cells play crucial roles in cell-mediated alloimmune responses. In vitro, B cells can support or regulate indirect T-cell alloreactivity in response to donor antigens on ELISpot and these patterns associate with clinical outcome. Previous reports of associations between B-cell phenotype and function have examined global phenotypes and responses to polyclonal stimuli. We hypothesized that studying antigen-specific B cells, using samples from sensitized patients, would inform further study to identify novel targets for intervention. Using biotinylated HLA proteins, which bind HLA-specific B cells via the B-cell receptor in a dose-dependent fashion, we report the specific phenotype of HLA-binding B cells and define how they associated with patterns of anti-HLA response in interferon-γ ELISpot. HLA-binding class-switched and IgM+CD27+ memory cells associated strongly with B-dependent interferon-γ production and appeared not suppressible by endogenous Tregs. When the predominant HLA-binding phenotype was naïve B cells, the associated functional ELISpot phenotype was determined by other cells present. High numbers of non-HLA-binding transitional cells associated with B-suppressed interferon-γ production, especially if Tregs were present. However, high frequencies of HLA-binding marginal-zone precursors associated with B-dependent interferon-γ production that appeared suppressible by Tregs. Finally, non-HLA-binding marginal zone precursors may also suppress interferon-γ production, though this association only emerged when Tregs were absent from the ELISpot. Thus, our novel data provide a foundation on which to further define the complexities of interactions between HLA-specific T and B cells and identify new targets for intervention in new therapies for chronic rejection.

RtNet: a deep hybrid neural network for the identification of acute rejection and chronic allograft nephropathy after renal transplantation using multiparametric MRI.

BACKGROUND: Reliable diagnosis of the cause of renal allograft dysfunction is of clinical importance. The aim of this study is to develop a hybrid deep-learning approach for determining acute rejection (AR), chronic allograft nephropathy (CAN) and renal function in kidney-allografted patients by multimodality integration. METHODS: Clinical and magnetic resonance imaging (MRI) data of 252 kidney-allografted patients who underwent post-transplantation MRI between December 2014 and November 2019 were retrospectively collected. An end-to-end convolutional neural network, namely RtNet, was designed to discriminate between AR, CAN and stable renal allograft recipient (SR), and secondarily, to predict the impaired renal graft function [estimated glomerular filtration rate (eGFR) ≤50 mL/min/1.73 m2]. Specially, clinical variables and MRI radiomics features were integrated into the RtNet, resulting in a hybrid network (RtNet+). The performance of the conventional radiomics model RtRad, RtNet and RtNet+ was compared to test the effect of multimodality interaction. RESULTS: Out of 252 patients, AR, CAN and SR was diagnosed in 20/252 (7.9%), 92/252 (36.5%) and 140/252 (55.6%) patients, respectively. Of all MRI sequences, T2-weighted imaging and diffusion-weighted imaging with stretched exponential analysis showed better performance than other sequences. On pairwise comparison of resulting prediction models, RtNet+ produced significantly higher macro-area-under-curve (macro-AUC) (0.733 versus 0.745; P = 0.047) than RtNet in discriminating between AR, CAN and SR. RtNet+ performed similarly to the RtNet (macro-AUC, 0.762 versus 0.756; P > 0.05) in discriminating between eGFR ≤50 mL/min/1.73 m2 and >50 mL/min/1.73 m2. With decision curve analysis, adding RtRad and RtNet to clinical variables resulted in more net benefits in diagnostic performance. CONCLUSIONS: Our study revealed that the proposed RtNet+ model owned a stable performance in revealing the cause of renal allograft dysfunction, and thus might offer important references for individualized diagnostics and treatment strategy.

Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in kidney disease.

Matrix metalloproteinases (MMPs) are a group of zinc and calcium endopeptidases which cleave extracellular matrix (ECM) proteins. They are also involved in the degradation of cell surface components and regulate multiple cellular processes, cell to cell interactions, cell proliferation, and cell signaling pathways. MMPs function in close interaction with the endogenous tissue inhibitors of matrix metalloproteinases (TIMPs), both of which regulate cell turnover, modulate various growth factors, and participate in the progression of tissue fibrosis and apoptosis. The multiple roles of MMPs and TIMPs are continuously elucidated in kidney development and repair, as well as in a number of kidney diseases. This chapter focuses on the current findings of the significance of MMPs and TIMPs in a wide range of kidney diseases, whether they result from kidney tissue changes, hemodynamic alterations, tubular epithelial cell apoptosis, inflammation, or fibrosis. In addition, the potential use of these endopeptidases as biomarkers of renal dysfunction and as targets for therapeutic interventions to attenuate kidney disease are also explored in this review.

Autologous bone marrow-derived mesenchymal stem cells for interstitial fibrosis and tubular atrophy: a pilot study.

BACKGROUND: Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated. METHODS: From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson's trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor ß1 (TGF-ß1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment. RESULTS: At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-ß1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed. CONCLUSION: Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-ß1: transforming growth factor ß1; CTGF: connective tissue growth factor.

Urinary Proteomics in Kidney Transplantation.

Although kidney transplantation is the best treatment option for end stage kidney disease, it is still associated with long-term graft failure. One of the greater challenges for transplant professionals is the ability to identify grafts with a high risk of failure before initial decline of eGFR with irreversible graft changes. Transplantation medicine is facing an emerging need for novel disease end point-specific biomarkers, with practical application in preventive screening, early diagnostic, and improved prognostic and therapeutic utility. The aim of our review was to evaluate the clinical application of urinary proteomics in kidney transplant recipients at risk for any type of future graft failure.

Prevention of Chronic Rejection of Marginal Kidney Graft by Using a Hydrogen Gas-Containing Preservation Solution and Adequate Immunosuppression in a Miniature Pig Model.

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney.

Expression and role of matrix metalloproteinase in injury related renal transplantation / 器官移植

Matrix metalloproteinase (MMP) is a large class of proteases which can cut or reshape extracellular matrix (ECM) and cell surface proteins. The activity of MMP is regulated by a variety of cytokines, including tissue inhibitor of metalloprotease (TIMP), signal transduction molecules and cell adhesion molecules. The latest research shows that MMP has a role in the pathophysiology process of many acute and chronic kidney diseases. In this article, the classification, expression and distribution in the kidney of MMP and its role in injury related renal transplantation was reviewed.

Neutrophil gelatinase-associated lipocalin (NGAL) is localised to the primary cilium in renal tubular epithelial cells - A novel source of urinary biomarkers of renal injury.

BACKGROUND: Primary cilia have been shown to play a central role in regulating epithelial cell differentiation during injury and repair. Growing evidence implicates structural and functional abnormalities of primary cilia in kidney epithelial cells in the onset and development of various kidney diseases including polycystic kidney disease (PKD). Neutrophil-gelatinase associated lipocalin (NGAL) has been identified as a reliable urinary biomarker of kidney injury. However, the mechanism by which this protein accumulates in patient urine samples has not been fully elucidated. METHODS: Human renal tubular epithelial cells (RPTECs) were exposed to previously characterized deciliating agents to assess mechanisms of primary cilium loss. Confocal immunofluorescent imaging was employed to visualise the effects on cilia. Western blot analysis was utilised to quantify the ciliary protein Arl13b in both RPTEC whole cell lysates and supernatants. Co-immunoprecipitation was used to demonstrate co-localisation of Arl13b and NGAL in urinary samples from a clinical Chronic Allograft Nephropathy (CAN) cohort. RESULTS: Immunofluorescent analysis revealed that NGAL was localised to the primary cilium in RPTECs, co-localizing with a ciliary specific protein, Arl13b. Deciliation experiments showed that loss of the cilia coincided with loss of NGAL from the cells. CONCLUSION: The accumulation of NGAL in supernatants in vitro and in the urine of CAN patients was concurrent with loss of Arl13b, a specific ciliary protein. The findings of this study propose that increased NGAL urinary concentrations are directly linked to deciliation of the renal epithelial cells as a result of injury.

Anti-vimentin antibodies in transplant and disease.

Non-HLA antibodies are recognized as a potential source of antibody mediated rejection following transplantation. The epitopes which lead to production of these antibodies are a result of tissue disruption, specifically endothelium, secondary to inflammation and injury. Vimentin is a cytoskeletal protein involved in many aspects of cellular organization, signaling, and proliferation. Recently, antivimentin antibodies have been shown to be important not only for rheumatological autoimmune diseases, but also cardiac and renal transplant dysfunction. In cardiac transplant recipients, antivimentin antibodies are associated with coronary artery vasculopathy and chronic graft loss. In renal transplantation, antivimentin antibodies are detected prior to transplantation and are also correlated with chronic graft dysfunction. In renal transplant recipients, antivimentin antibodies seen prior to transplantation are thought to be secondary to chronic endothelial injury during hemodialysis and therefore more prevalent prior to renal transplant than cardiac transplantation. In this review, we will examine the generation and pathogenesis of antivimentin antibodies. Given that these antibodies appear to be associated with both post-cardiac and -renal transplant dysfunction, developing standard detection paradigms may be important for risk stratification prior to transplantation. Finally, understanding the pathogenesis of antivimentin antibodies may lead to the development potential therapies in order to improve long-term survival.

Deceased-donor acute kidney injury is not associated with kidney allograft failure.

Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate ≤ 20 mL/min/1.73 m2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI.

Long-term follow-up of the DeKAF cross-sectional cohort study.

The DeKAF study was developed to better understand the causes of late allograft loss. Preliminary findings from the DeKAF cross-sectional cohort (with follow-up < 20 months) have been published. Herein, we present long-term outcomes in those recipients (mean follow-up ± SD, 6.6 ± 0.7 years). Eligibility included being transplanted prior to October 1, 2005; serum creatinine ≤ 2.0 mg/dL on January 1, 2006; and subsequently developing new-onset graft dysfunction leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Histologic findings and DSA were studied in relation to postbiopsy outcomes. Long-term follow-up confirms and expands the preliminary results of each of 3 studies: (1) increasing inflammation in area of atrophy (irrespective of inflammation in nonscarred areas [Banff i]) was associated with increasingly worse postbiopsy death-censored graft survival; (2) hierarchical analysis based on Banff scores defined clusters (entities) that differed in long-term death-censored graft survival; and (3) C4d-/DSA- recipients had significantly better (and C4d+/DSA+ worse) death-censored graft survival than other groups. C4d+/DSA- and C4d-/DSA+ had similar intermediate death-censored graft survival. Clinical and histologic findings at the time of new-onset graft dysfunction define high- vs low-risk groups for long-term death-censored graft survival, even years posttransplant. These findings can help differentiate groups for potential intervention studies.

Clinical efficacy of Shuxuening injection combined with compound coenzyme in treatment of chronic allograft nephropathy / 实用医学杂志

Objective To observe the clinical efficacy of Shuxuening injection combined with compound coenzyme in the treatment of chronic allograft nephropathy (CAN). Methods A retrospective analysis of 108 patients with chronic allograft nephropathy (CAN) admitted to our hospital from June 2014 to May 2018 were divided into two groups according to different treatments. The 43 cases in the experimental group were given Shuxuening injection combined with compound coenzyme, and the 65 cases in control group were given non-Shu Xuening + compound coenzyme. The original immunization protocol was maintained in both groups. After 4 weeks of treatment, the changes of hemodynamic parameters, clinical efficacy, biochemical parameters, coagulation function and adverse reactions were observed before and after treatment. Results There was no significant difference in baseline data between the two groups before treatment (P> 0.05). After treatment, the peak systolic velocity of the intersegmental artery and cortical arteriole in the experimental group were significantly higher than that the control group (P < 0.05) , and the resistance index was lower than that in the control group (P < 0.05). After treatment, serum creatinine, 24 h urine protein quantitation, urinary microalbumin, total cholesterol and triglycerides were lower than that before treatment (P < 0.05) , and estimated glomerular filtration rate (eGFR) and serum. Albumin increased significantly (P < 0.05) , but the 24 h urine protein quantitation and urinary albumin decreased significantly in the experimental group compared with the control group (P < 0.05). After treatment, the total amount of cholesterol, triglycerides showed no significant difference (P> 0.05). After treatment, the platelet count, fibrinogen and D-dimer of the experimental group were significantly lower than those before treatment (P < 0.05) , and the activated partial thrombin time (APT) was significantly higher than that before treatment (P < 0.05). Significant difference in platelet count, fibrinogen, D-dimer and APTT was found after treatment (P < 0.05). After 4 weeks of treatment, the values of urea nitrogen and serum creatinine were significantly lower than those of the control group (P < 0.05). The recovery of transplanted kidney function in the experimental group was higher than that in the control group (P < 0.05). The experimental group reported 2 cases of fatigue complain and 1 case of dizziness, but no special treatment was given to them and their condition improved after symptomatic treatment; 1 case of mild phlebitis which was cured after given slowed drip rate and local hot compress therapy. The incidence of adverse events was 9.3％ (4/43). The control group reported 2 cases of fatigue complain, 1 case of nausea, 1 case of facial flushing, and all cured with no special treatment was given; 1 case of mild phlebitis, and cured after slowed the i.v. drip rate and ocal hot compress; The adverse events rate was 7.7％ (5/65). No serious adverse reactions occurred during the entire clinical trial. There was no significant difference in the incidence of adverse events between the experimental group and the control group (χ2=0.054, P=0.732). Conclusion Combined with Shuxuening injection and compound coenzyme can improve blood flow of transplanted kidney, reduce proteinuria, reduce blood urea nitrogen and creatinine in patients with CAN after renal transplantation and effectively improve patient's hemodynamic parameters and safety.