BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for ...BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results.AIM To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results.METHODS This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February 2023.All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this study.SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility.RESULTS The mean age of all patients was 35.32±11.08 years.Among these,126(81.8%)were males and 28(18.2%)were females.The mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 m2.Kidney allograft biopsy results showed chronic changes in 55(37.66%)biopsies.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage.It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.展开更多
BACKGROUND Diabetic nephropathy(DN)is frequently seen in the development of diabetes mellitus,and its pathogenic factors are complicated.Its current treatment is controversial,and there is a lack of a relevant efficac...BACKGROUND Diabetic nephropathy(DN)is frequently seen in the development of diabetes mellitus,and its pathogenic factors are complicated.Its current treatment is controversial,and there is a lack of a relevant efficacy prediction model.AIM To determine the effects of paricalcitol combined with hemodiafiltration on bonemetabolism-related indexes in patients with DN and chronic renal failure(CRF),and to construct an efficacy prediction model.METHODS We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022.We selected 94 patients who met the inclusion and exclusion criteria.Patients were assigned to a dialysis group(n=45)and a joint group(n=49)in relation to therapeutic regimen.The clinical efficacy of the two groups was compared after treatment.The changes in laboratory indexes after treatment were evaluated,and the two groups were compared for the incidence of adverse reactions.The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed.RESULTS The dialysis group showed a notably worse improvement in clinical efficacy than the joint group(P=0.017).After treatment,the joint group showed notably lower serum levels of serum creatinine,uric acid(UA)and blood urea nitrogen(BUN)than the dialysis group(P<0.05).After treatment,the joint group had lower serum levels of phosphorus,procollagen type I amino-terminal propeptide(PINP)and intact parathyroid hormone than the dialysis group,but a higher calcium level(P<0.001).Both groups had a similar incidence of adverse reactions(P>0.05).According to least absolute shrinkage and selection operator regression analysis,UA,BUN,phosphorus and PINP were related to treatment efficacy.According to further comparison,the non-improvement group had higher risk scores than the improvement group(P<0.0001),and the area under the curve of the risk score in efficacy prediction was 0.945.CONCLUSION For treatment of CRF and DN,combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients,with good safety.展开更多
Objective To investigate the expression of OPN, α - SMA,E - cadherin and their correlation in chronic allograft nephropathy ( CAN) rat model,and to explore the possible role of OPN in CAN. Methods Orthotopic renal - ...Objective To investigate the expression of OPN, α - SMA,E - cadherin and their correlation in chronic allograft nephropathy ( CAN) rat model,and to explore the possible role of OPN in CAN. Methods Orthotopic renal - transplantation using Fisher rats as donors and Lewis rats as recipients was done to establish展开更多
Objective To investigate role and mechanism of phosphate myosin light chain ( pMLC) in rat kidney of chronic allograft nephropathy ( CAN) model. Methods Left donor kidneys from Fisher ( F344) rats were ortho-topically...Objective To investigate role and mechanism of phosphate myosin light chain ( pMLC) in rat kidney of chronic allograft nephropathy ( CAN) model. Methods Left donor kidneys from Fisher ( F344) rats were ortho-topically transplanted into Lewis recipients,Meanwhile, F344 rats and LEW rats with resection of right展开更多
Objective To summarize experience of establishing stable rat model ot chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients. After left kidney of donor perfused in situ unde...Objective To summarize experience of establishing stable rat model ot chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients. After left kidney of donor perfused in situ under hypothermic condition,left renal vein,abdominal aorta and bladder flap of donor was anastomosed with展开更多
Objective To investigate the effect of conversion from cyelosporine A ( CsA ) to tacrolimus ( Tac) on chronic allograft nephropathy ( CAN) . Methods 153 CAN patients undergoing kidney transplantation received CsA,myco...Objective To investigate the effect of conversion from cyelosporine A ( CsA ) to tacrolimus ( Tac) on chronic allograft nephropathy ( CAN) . Methods 153 CAN patients undergoing kidney transplantation received CsA,mycophenolate mofetil ( MMF) and展开更多
AIM: To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS: AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft d...AIM: To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS: AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day (POD) 5. Hepatic overexpression of A20 was achieved by recom- binant adenovirus (rAd.)-mediated gene transfer ad- ministered intravenously every 10 d starting from POD 10. The recipient rats were injected with physiologi- cal saline, rAdEasy-A20 (1 × 109 pfu/30 g weight) or rAdEasy (1 × 109 pfu/30 g weight) every 10 d through the tail vein for 3 mo starting from POD 10. Liver tissue samples were harvested on POD 30 and POD 60. RESULTS: Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis. A20 overexpression ameliorated the effects on liver function, attenuated liver allograft fibrosis and prolonged the survival of the recipient rats. Treatment with A20 suppressed hepatic protein pro- duction of tumor growth factor (TGF)-β1, interleukin- 113, caspase-8, CD40, CD40L, intercellular adhesion molecule-i, vascular cell adhesion molecule-1 and E-selectin. A20 treatment suppressed liver cell apopto- sis and inhibited nuclear factor-KB activation of Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs. CONCLUSION: A20 might prevent chronic liver allogra- ft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.展开更多
BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To invest...BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.展开更多
Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and im...Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.展开更多
Dear Editor,I am Dr.Elias F Jarade from the Beirut Eye and ENT Specialist Hospital, Beirut, Lebanon. I write to describe a novel surgical technique in the management of chronic ocular graft-versus-host disease(GVHD).
Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound ...Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.展开更多
Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment ...Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:Bronchiolitis obliterans syndrome and restrictive allograft syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.展开更多
文摘BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results.AIM To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results.METHODS This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February 2023.All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this study.SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility.RESULTS The mean age of all patients was 35.32±11.08 years.Among these,126(81.8%)were males and 28(18.2%)were females.The mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 m2.Kidney allograft biopsy results showed chronic changes in 55(37.66%)biopsies.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage.It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.
文摘BACKGROUND Diabetic nephropathy(DN)is frequently seen in the development of diabetes mellitus,and its pathogenic factors are complicated.Its current treatment is controversial,and there is a lack of a relevant efficacy prediction model.AIM To determine the effects of paricalcitol combined with hemodiafiltration on bonemetabolism-related indexes in patients with DN and chronic renal failure(CRF),and to construct an efficacy prediction model.METHODS We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022.We selected 94 patients who met the inclusion and exclusion criteria.Patients were assigned to a dialysis group(n=45)and a joint group(n=49)in relation to therapeutic regimen.The clinical efficacy of the two groups was compared after treatment.The changes in laboratory indexes after treatment were evaluated,and the two groups were compared for the incidence of adverse reactions.The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed.RESULTS The dialysis group showed a notably worse improvement in clinical efficacy than the joint group(P=0.017).After treatment,the joint group showed notably lower serum levels of serum creatinine,uric acid(UA)and blood urea nitrogen(BUN)than the dialysis group(P<0.05).After treatment,the joint group had lower serum levels of phosphorus,procollagen type I amino-terminal propeptide(PINP)and intact parathyroid hormone than the dialysis group,but a higher calcium level(P<0.001).Both groups had a similar incidence of adverse reactions(P>0.05).According to least absolute shrinkage and selection operator regression analysis,UA,BUN,phosphorus and PINP were related to treatment efficacy.According to further comparison,the non-improvement group had higher risk scores than the improvement group(P<0.0001),and the area under the curve of the risk score in efficacy prediction was 0.945.CONCLUSION For treatment of CRF and DN,combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients,with good safety.
文摘Objective To investigate the expression of OPN, α - SMA,E - cadherin and their correlation in chronic allograft nephropathy ( CAN) rat model,and to explore the possible role of OPN in CAN. Methods Orthotopic renal - transplantation using Fisher rats as donors and Lewis rats as recipients was done to establish
文摘Objective To investigate role and mechanism of phosphate myosin light chain ( pMLC) in rat kidney of chronic allograft nephropathy ( CAN) model. Methods Left donor kidneys from Fisher ( F344) rats were ortho-topically transplanted into Lewis recipients,Meanwhile, F344 rats and LEW rats with resection of right
文摘Objective To summarize experience of establishing stable rat model ot chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients. After left kidney of donor perfused in situ under hypothermic condition,left renal vein,abdominal aorta and bladder flap of donor was anastomosed with
文摘Objective To investigate the effect of conversion from cyelosporine A ( CsA ) to tacrolimus ( Tac) on chronic allograft nephropathy ( CAN) . Methods 153 CAN patients undergoing kidney transplantation received CsA,mycophenolate mofetil ( MMF) and
基金Supported by The National Natural Science Foundation of China,No.30872529the PhD Program Fund of the Ministry of Education of China,No.20030610078the Chinese Postdoctoral Science Foundation,No.2003033531
文摘AIM: To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS: AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day (POD) 5. Hepatic overexpression of A20 was achieved by recom- binant adenovirus (rAd.)-mediated gene transfer ad- ministered intravenously every 10 d starting from POD 10. The recipient rats were injected with physiologi- cal saline, rAdEasy-A20 (1 × 109 pfu/30 g weight) or rAdEasy (1 × 109 pfu/30 g weight) every 10 d through the tail vein for 3 mo starting from POD 10. Liver tissue samples were harvested on POD 30 and POD 60. RESULTS: Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis. A20 overexpression ameliorated the effects on liver function, attenuated liver allograft fibrosis and prolonged the survival of the recipient rats. Treatment with A20 suppressed hepatic protein pro- duction of tumor growth factor (TGF)-β1, interleukin- 113, caspase-8, CD40, CD40L, intercellular adhesion molecule-i, vascular cell adhesion molecule-1 and E-selectin. A20 treatment suppressed liver cell apopto- sis and inhibited nuclear factor-KB activation of Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs. CONCLUSION: A20 might prevent chronic liver allogra- ft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.
基金Supported by National Natural Science Foundation of China,No.8187150391 and No.81904126Science and Technology Commission of Shanghai Municipality,No.20Y21901800.
文摘BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.
文摘Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.
文摘Dear Editor,I am Dr.Elias F Jarade from the Beirut Eye and ENT Specialist Hospital, Beirut, Lebanon. I write to describe a novel surgical technique in the management of chronic ocular graft-versus-host disease(GVHD).
文摘Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.
文摘Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:Bronchiolitis obliterans syndrome and restrictive allograft syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.