Optimal diagnosis and treatment for renal allograft fibrosis / 器官移植

Renal allograft fibrosis is one of the common and severe complications after kidney transplantation, which seriously affects the function and survival rate of renal allograft, and may even lead to organ failure and patient death. At present, the researches on renal allograft fibrosis are highly complicated, including immunity, ischemia-reperfusion injury, infection and drug toxicity, etc. The diagnosis and treatment of renal allograft fibrosis remain extremely challenging. In this article, the latest research progress was reviewed and the causes, novel diagnosis and treatment strategies for renal allograft fibrosis were investigated. By improving diagnostic accuracy and optimizing treatment regimen, it is expected to enhance clinical prognosis of kidney transplant recipients, aiming to provide reference for clinicians to deliver proper management for kidney transplant recipients.

A novel technique of pure transperitoneal laparoscopic nephroureterectomy at a single position for native upper tract urothelial carcinoma in ipsilateral renal transplant recipients / 中华器官移植杂志

Objective:To explore the techniques and outcomes of pure laparoscopic native nephroureterectomy (LNUT) with ipsilateral allograft at a single position for upper tract urothelial carcinoma (UTUC) in renal transplant (RT) recipients.Methods:Clinical data were retrospectively reviewed for 12 renal transplant children undergoing native UTUC with ipsilateral allograft from January 2016 to December 2021.There were 4 boys and 8 girls.Complete LNUT was performed with bladder cuff resection at a single position via a transperitoneal approach.The interval between UTUC and RT was 12-146 months.There were 6 pelvic UCs and 6 ureter UCs.Results:All laparoscopic procedures were successfully completed without any serious perioperative complication.Postoperative pathological examination confirmed the diagnosis of urothelial carcinoma.And all surgical margins were negative.One patient experienced an elevation of creatinine after one cycle chemotherapy and normalized after withdrawing chemotherapy.The median follow-up period was (4-65) month.Two cases of contralateral native transitional cell carcinoma had radical nephroureterectomy two years later and another two cases underwent transurethral resection of bladder tumor one year later.One case died from tumor metastasis.The remainders had no tumor recurrence or metastasis during follow-ups.Conclusions:Complete single-position LNUT for UTUC with ipsilateral allograft is a safe and effective mini-invasive technique.Effectively avoiding the injury of allograft, it also offers the advantages of standard operation, minimal trauma, simple handling and enhanced recovery after surgery (ERAS).

Efficacy and safety of 3-dimensional laparoscopic pyeloplasty and ultrasound-guided flexible ureteroscopy lithotripsy in the treatment of ureteropelvic junction obstruction and renal calculi / 现代泌尿外科杂志

【Objective】 To evaluate the efficacy and safety of 3-dimensional laparoscopic pyeloplasty and ultrasound-guided flexible ureteroscopy lithotripsy (3DLP-UGFURL) in the treatment of ureteropelvic junction obstruction (UPJO) and renal calculi. 【Methods】 The clinical data of 29 patients of UPJO complicated with renal calculi treated with 3DLP-UGFURL during Dec.2017 and Jul.2022 were retrospectively analyzed. There were 23 males and 6 females with average age of (35.3±13.6) years. The lesions were on the left side in 20 cases, on the right side in 9 cases, and all were unilateral. One case was complicated with horseshoe kidney. The body mass index (BMI) was 23.6±3.9. Multiple calculi of renal pelvis or calyces occurred in 16 cases, and the rest were single calculi. The maximum diameter of calculi was (1.2±0.6)cm. There were 2 cases of mild hydronephrosis, 19 cases of moderate hydronephrosis and 8 cases of severe hydronephrosis. 【Results】 All operations were successful. The operation time of 3DLP was (84.2±15.4)min. Operation time of UGFURL was (42.8±15.7)min. Estimated blood loss was (36.9±13.6)mL. Indwelling time of drainage tube was (3.6±1.6)d. Indwelling time of urinary catheter and postoperative hospital stay was (6.8±1.2)d. One month after operation, the stone removal rate was 97.4%. The retention time of ureteral stent was 2.7 months. During the follow-up of (24.5±10.0)months, there were 45 Clavien Dindo grade 1 complications. 【Conclusion】 3DLP-UGFURL is safe and effective in the treatment of UPJO complicated with renal calculi, but it still needs long-term follow-up data.

Frailty in kidney transplant candidates and recipients: pathogenesis and intervention strategies / 中华医学杂志(英文版)

With the rapid aging of the global population posing a serious problem, frailty, a non-specific state that reflects physiological senescence rather than aging in time, has become more widely addressed by researchers in various medical fields. A high prevalence of frailty is found among kidney transplant (KT) candidates and recipients. Therefore, their frailty has become a research hotspot in the field of transplantation. However, current studies mainly focus on the cross-sectional survey of the incidence of frailty among KT candidates and recipients and the relationship between frailty and transplantation. Research on the pathogenesis and intervention is scattered, and relevant review literature is scarce. Exploring the pathogenesis of frailty in KT candidates and recipients and determining effective intervention measures may reduce waiting list mortality and improve the long-term quality of life of KT recipients. Therefore, this review explains the pathogenesis and intervention measures for frailty in KT candidates and recipients to provide a reference for the formulation of effective intervention strategies.

Clinical application of biomarkers in DCD donor kidney perfusate for predicting delayed graft function after renal transplantation / 器官移植

Objective To explore the feasibility of biomarkers in static cold storage (SCS) perfusate of donor kidney from donation after cardiac death (DCD) for predicting delayed graft function (DGF) after renal transplantation. Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed. All recipients were divided into the DGF group (n=7) and immediate graft function (IGF) group (n=57) according to the incidence of postoperative DGF in the recipients. The levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), interleukin -18(IL-18) and kidney injury molecule-1 (KIM-1) in the SCS perfusate were statistically compared between two groups, and the correlation with DGF was analyzed. The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed. Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11% (7/64). The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group (P=0.009). The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation (r=0.430, P < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation (both P < 0.05). The area under the curve (AUC) of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932 [95% confidence interval (CI) 0.850-1.000]. The sensitivity was calculated as 1.000 and 0.754 for the specificity (P < 0.05). Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation. Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.

Clinical application of new donor blood biomarker in the evaluations of delayed graft function after donor-after-cardiac-death kidney transplantation / 中华器官移植杂志

Objective:To explore the relationship between new biomarkers in donor blood and delayed graft function after kidney transplantation and evaluate the clinical value of new biomarkers in the diagnosis of DGF (delayed graft function).Methods:For recipients of donor kidney transplantation from August 2016 to December 2017, blood samples were collected from operations of donor organ resection within 12 hours of the day. Enzyme-linked immunosorbent assay (ELISA) was employed for detecting neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1) and interleukin-18(IL-18). They were divided into DGF and EGF (early graft function) groups according to the diagnosis of DGF. The inter-group differences of four new biomarkers were calculated. Receiver operating characteristic curve (ROC curve) was plotted for finding the best positive cutoff value and the sensitivity and specificity of new donor blood marker for diagnosing delayed graft function were calculated.Results:Among them, 8 had postoperative DGF and 62 had none. The overall incidence of DGF was 11.43%. The serum concentration of NGAL was 521.01±132.84 ng/ml in DGF group versus (299.99±100.03) ng/ml in EGF group ( P<0.001). The ROC curve was plotted. With a NGAL concentration >425.15 ng/ml, the sensitivity and specificity for diagnosing DGF were 87.5% and 90.3% respectively. The area under the curve (AUC) was 0.891. The serum concentration of IL-18 was (14.10±12.36) ng/ml in DGF group and (4.61±1.83) ng/ml in EGF group ( P=0.047). With a IL-18 concentration of >5.345 ng/ml, the sensitivity and specificity for diagnosing DGF were 100% and 64.5% respectively. The AUC was 0.914. No significant inter-group difference existed in serum L-FABP/KIM-1. The sensitivity of donor creatinine in the diagnosis of DGF was 62.5%, specificity 75.8% and AUC 0.692. Conclusions:With an excellent level of sensitivity and specificity, an elevated concentration of NGAL/IL-18 in donor blood is superior to traditional creatinine in the diagnosis of DGF after renal transplantation.

De novo donor specific antibody affect the prognosis of kidney transplant recipients:retrospective study / 中华器官移植杂志

Objective To explore the relationship between positive rate of de novo donor specific antibody (dnDSA ) and human leukocyte antigen (HLA ) mismatch after kidney transplantation and explore the impact of dnDSA upon long-term graft survival and rejection .Methods Retrospective analysis was conducted for clinical data of 101 kidney transplant recipients .Based upon HLA antibody and dnDSA ,they were divided into three groups of HLA-(n=70) ,dnDSA- (n=23) and dnDSA+(n=8) .Rejection and graft survival were recorded for evaluating the impact of dnDSA on rejection and graft survival and observing the differences among all groups .Results The mismatchs of HLA-A/B and HLA-DR were more frequent than HLA-and dnDSA-groups(P=0 .047 , P=0 .010)and graft survival was lower in dnDSA+ group than HLA-and dnDSA-groups (P=0 .001) .The rejection rate was higher in dnDSA+ group (62 .5％ ) than HLA- group (8 .57％ ) and dnDSA-group (8 .69％ ) . The difference was statistically significant (P=0 .013) . Pathological examination indicated microcirculatory inflammation (glomerulonephritis & trichodangiitis ) and damage (multilayer change of capillary basement membrane) occurred frequently in dnDSA + group and C4d remained positive . However ,scar ,arterial fibrosis or tubulointerstitial inflammation was not correlated with dnDSA . Conclusions HLA mismatch is correlated with dnDSA positivity . And dnDSA may reduce graft survival and enhance rejection rate . Rejection mediated by dnDSA is often accompanied by microcirculatory inflammation and C4d positivity .

Desensitization treatment with bortezomib in a highly-sensitized patient before secondary renal transplantation: report of one case and literature review / 器官移植

Objective To summarize the clinical experience of the application of bortezomib desensitization regime prior to secondary renal transplantation in a highly-sensitized recipient. Methods At 13, 10 and 6 d prior to secondary renal transplantation, one patient positive for donor specific antibody (DSA) was subcutaneously administered with bortezomib at a dose of 1.3 mg/m2 combined with a low dose of immunoglobulin. Postoperatively, immunosuppressive regime of tacrolimus (FK506), mycophenolat sodium and methylprednisolone was adopted. The serum creatinine (Scr), blood urea nitrogen (BUN) levels, FK506 concentration, DSA titre, C3d binding DSA (C3d-DSA) titre, pathological biopsy of the renal graft and adverse reactions were observed. Results During 12-month follow-up after administration of bortezomib, the Scr level was declined and maintained at 130 μmol/L, and the BUN level was remained at 3.9 mmol/L. The DSA level was significantly decreased and the C3d-DSA was negative. At postoperative 4 and 9 months, pathological biopsy of the renal graft revealed that the patient was positive for C4d, prompting the chronic active antibody mediated rejection (AMR). The patient presented with grade Ⅲ peripheral neuropathy. Conclusions Application of preoperative bortezomib desensitization regime can effectively down-regulate the DSA level in the recipient and avert the incidence of acute rejection in highly-sensitized patients undergoing secondary renal transplantation. Comprehensive treatment using bortezomib is recommended for preoperative desensitization in the highly-sensitized transplant recipients.