Objective To explore the inhibition of different immunosuppressive drugs or immunosuppressive combination regiments on the development of de novo donor specific antibodies (dnDSA).Methods We used BABL/c mice and C57BL/6 mice alloimmunized using donor splenocytes for establishing model of producing dnDSA.After that,mice were divided into 10 groups,and were administrated with mycophenolate mofetil (MMF,300 mg· kg-1 · d-1);sirolimus (0.3 mg·kg-1 ·d-1);tacrolimus(0.9 mg· kg-1 · d-1);cyclosporine A (45 mg· kg-1 · d-1);MMF (150 mg· kg-1· d-1) + tacrolimus(0.45 mg · kg-1 · d-1);MMF (150 mg · kg-1 · d-1) + cyclosporine A (22.5 mg·kg-1 ·d-1);MMF (150 mg·kg-1 ·d-1) + sirolimus (0.15 mg·kg-1 ·d-1);sirolimus (0.15 mg· kg-1 · d-1) + tacrolimus (0.45 mg· kg-1 · d-1);sirolimus (0.15 mg· kg-1 · d-1) + cyclosporine A (22.5 mg· kg-1 · d-1);and placebo;respectively.Anti-serum was harvested and tested using flow cytometry.Results (1) Four weeks after sensitization,the dnDSA level in BALB/c and C57BL/6 group was 88.86％ and 25.58％.Comparing with control group(25.33％),there was a significant increase in BALB/c group(89.23％ versus 25.33％;P＜0.001),whereas no change was found in C57BL/6 group (25.58％ versus 25.33％;P =0.259),that we chose BABL/c mice as the model for sensitization.(2)After 4 weeks of sensitization and immunosupression,dnDSA level was 29.31％,46.33％,57.10％ and 66.35％ in MMF,sirolimus,cyclosporine A and tacrolimus monotherapy group respectively.In comparison to sensitization group,dnDSA level in all monotherapy arm reduced significantly.Intra-group analysis found MMF monotherapy had the most effective inhibition of dnDSA production,sirolimus came the second,and tacrolimus and cyelosporine A had equivalent effectiveness.dnDSA level was 31.00％,33.12％,45.18％,44.62％ and 61.60％ in MMF+ sirolimus,MMF+ tacrolimus,MMF+ cyclosporine A,sirolimus + cyclosporine A and sirolimus + tacrolimus combination treatment arm,respectively,which was much lower than that of sensitization group (P＜0.001,P＜0.001,P＜0.001,P＜0.001,P =0.015).MMF + tacrolimus and MMF+ sirolimus combination treatment had comparable effectiveness in dnDSA inhibition,which is greater than that of the rest of three combination.Conclusion Our data show that the effects of single immunosuppressive drugs on the level of dnDSA is MMF＞sirolimus＞cyclosporine A =tacrolimus,and that in combination regimens is MMF + tacrolimus =MMF + sirolimus＞MMF + cyclosporine A =sirolimus + cyclosporine A =sirolimus + tacrolimus.In conclusion,this study demonstrates that MMF+ tacrolimus combination treatment arm can minimize the development of dnDSA.But,this conclusion remains to be confirmed by future clinical studies.

Objective To investigate the effect of birth order on outcomes of renal transplantation from siblings.Method We conducted a retrospective study to examine the immune effect exerted by birth order in kidney transplantation between siblings.227 kidney transplants were included and we stratified the cohort by birth order,old to young parings (group A,104 pairs) and young to old pairings (group B,123 pairs),using old to young parings as reference group.Result During the follow-up period,4 recipients suffered graft failure and 2 died.The survival rate of recipients and grafts was 98％ and 95％,respectively.After adjusting the effect of confounding factors in demography,young to old pairings were found at a higher risk of developing death uncensored graft failure (Hazards ratio,HR =2.77,95％ CI..0.23,33.00),which was not significantly different from group A (P =0.42).And group B had a higher risk of developing death censored graft failure (HR =10.79,95％ CI:0.30-389.43),with no statistically significant difference (P＞0.05).Most rejections occurred in two months after transplantation,and the rejection-free rate in 3 years post-transplantation was 86％.Similarly,no significant difference was detected between the two groups in terms of death censored graft failure,and no benefit of birth order was found in rejection protection (HR =1.266,95％ CI:0.391,4.103,P =0.694).Conclusion Birth order may not be taken into consideration in kidney transplantation between siblings.

Objective To reduce the perioperative complications of simultaneous pancreas and kidney transplantation (SPK ) and boost the clinical efficacy by exploring its perioperative management in diabetics with end-stage renal disease .Methods Retrospective analysis was performed for the clinical data of 5 diabetics with end-stage renal disease undergoing SPK since 2017 .Results The cold ischemic time of all allografts was under 8 hours .No surgical complications occurred in recipients post-transplantation .Two patients were complicated with hyperkalemia and their serum potassium levels normalized after treatment .One case of bleeding in abdominal cavity was cured conservatively . Renal functions of two patients with delayed renal function post-transplantation gradually recovered after hematodialysis . One case of peritransplant fluid collection recovered after debridement and drainage .Another case of acute left heart failure and cardiac arrest at 45 days post-transplantation resumed normal heart rhythm after rescue .However ,his consciousness could not be restored and his families gave up subsequent treatments . Transplanted kidneys and pancreases of these 4 patients normalized .Follow-up was conducted until March 20 , 2019 . They became insulin and dialysis independent and serum creatinine and blood glucose normalized .Diabetic complications were relieved and their quality-of-life also improved significantly .Conclusions SPK is an effective treatment for diabetics with end-stage renal disease .While maintaining normal serum creatinine and blood glucose , it may liberate patients from insulin dosing and dialytic maintenance ,lower diabetic complications and improve quality-of-life .

Objective:To explore the safety and efficacy of retrograde machine perfusion of kidneys from deceased donors.Methods:From January 1, 2020 to July 1, 24 renal transplant recipients underwent organ donation.All grafts were preserved by Kidney Transporter machines(LifePort). Through a random number table, they were divided into two groups of retrograde perfusion(RP group, 12 cases)and anterograde perfusion group(AP group, 12cases). The incidence of delayed recovery of kidney/graft function was compared between two groups.Results:During a follow-up period of 1 month, kidney resistance remained stable in RP group during perfusion.No primary non-function occurred in neither groups.No inter-group difference existed in the incidence of delayed graft function (3 in RP and 2 in AP, P=0.62). At all timepoints within 30 days, both groups had comparable values of urine output, serum creatinine, estimated glomerular filtration rate, cystatin c and blood urea nitrogen.RP group with a resistance index of <0.4 had numerically better kidney function than those with a resistance index of ≥0.4. Conclusions:This novel technique may be an effective and safe alternative for kidney preservation.

Objective To investigate the changes of short chain fatty acids (SCFA) induced by tacrolimus (FK506) in rats and evaluate its effect on blood glucose levels. Methods Ten SD rats were divided into the FK506 group and control group (n=5 in each group). In the FK506 group, the rats were received a subcutaneous injection of FK506 (3 mg/kg) +sunflower oil solution containing 10% ethanol daily for consecutive 4 weeks. In the control group, the rats were received a subcutaneous injection of an equivalent amount of sunflower oil solution containing 10% ethanol for consecutive 4 weeks. During the drug injection period, the body mass of rats was measured every week in two groups. After the drug injection period, blood glucose level, SCFA content in the blood and feces samples were measured in two groups. Results Compared with the control group, the relative body mass of rats in the FK506 group was significantly lower at the 2nd, 3rd and 4thweeks (all P<0.01). Compared with the control group, the blood glucose levels of rats in the FK506 group were significantly increased at 0, 30, and 60 min after giving glucose (P<0.01-0.05). Compared with the control group, the contents of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid and valeric acid in the feces sample were significantly lower in the FK506 group (P<0.01-0.05). Conclusions FK506 can upregulate the blood glucose level in rats, which is probably induced by the decrease of SCFA content in rat feces.

Objective:Exploring the surgical method and safety of robot assisted kidney transplantation (RAKT) with a kidney implanted through the vagina, currently there is no such surgery in China.Method:Retrospective analysis of the data of a 44-year-old postpartum woman with stage 5 chronic kidney disease admitted to the kidney transplantation ward of West China Hospital, Sichuan University on June 28, 2021. RAKT with a kidney inserted through the vagina was performed on the recipient. The transplanted kidney was cooled using continuous surface cooling technology (CSCT) using ice physiological saline. The recipient was followed up for 3 months after surgery. In addition, we searched the Wanfang database, China National Knowledge Infrastructure, VIP database, China Biomedical Literature Service System, PubMed, Embase, and Central databases. The Chinese search keywords were "robot kidney transplantation" and "vagina", while the English search keywords were "kidney transplantation" and "robot" and "vacuum". The literature was published from June 1990 to June 2022, and a detailed summary of all published cases was provided.Result:a perineal approach was used to open the posterior fornix of the vagina and the graft was successfully implanted. The surgery was successfully completed, with a total duration of 250 minutes, vascular anastomosis time of 45 minutes, and warm ischemia time of 63 minutes. The recipient recovered smoothly without vaginal pain and postoperative pain relief; There was also no abdominal infection. Using CSCT, the surface temperature of the graft was maintained at 10~16 ℃ during anastomosis. After literature review, a total of 12 cases of renal RAKT implantation through vagina have been reported. All cases were successful, except for one case where the graft was poorly positioned and converted to open surgery. The average surgical time reported in the literature is (210 ± 37) minutes, vascular anastomosis time is (41 ± 8) minutes, and warm ischemia time is (50 ± 10) minutes. There were no surgical complications.Conclusion:Transvaginal insertion of RAKT into the kidney is safe and feasible, but special types of recipients should be selected for this surgical method and evaluated before surgery.

Objective:To explore the efficacy and safety of pretreating with oral immunosuppressants alone for ABO-incompatible (ABOi) renal transplant recipients with an initial isoagglutinin titer <1: 8.Methods:From September 2014 to October 2019, 16 cases of ABOi renal transplantation pretreated with oral immunosuppressants alone and 32 cases of ABO-compatible (ABOc) renal transplantation were recruited for comparing the inter-group incidence of graft function, acute rejection, infection and recipient and allograft survival.Results:The 16 ABOi renal transplantations were AB-to-A(n=4), AB-to-B(n=3), A-to-B(n=1), B-to-A(n=4), A-to-O(n=2) and B-to-O(n=2). The initial isoagglutinin titer (IgM & IgG) and that on the date of transplantation were both ≤1∶8. The median follow-up period was 495(90-1696) days. One patient in ABOi group underwent allograft nephrectomy due to hyperacute rejection. The graft survival rates were 93.75%(15/16) and 100%(32/32) in ABOi and ABOc groups respectively. No recipient died. No significant inter-group difference existed in postoperative renal function after 6 months (serum creatinine μmol/L: 114.30±28.13 vs. 106.08±23.80, P=0.38; eGFR ml/min/1.73 m 2: 64.93±19.60 vs. 82.34±22.58, P=0.13). In ABOi group, there were 3 episodes of postoperative infection, 2 episodes of acute rejection within 2 weeks (including 1 episode of hyperacute rejection) and 1 episode of acute rejection after 2 weeks; 5 episodes of postoperative infection, no acute rejection within 2 weeks and 5 episodes of acute rejection after 2 weeks in ABOc group. No significant inter-group difference existed in the incidence of infection or rejection ( P>0.05). Conclusions:Using oral immunosuppressant alone is both safe and feasible for ABOi renal transplantation recipients with an initial isoagglutinin titer ≤1∶8. It may greatly simplify the pretreatment scheme for those with a low initial isoagglutinin titer and lower the incidence of complications.

Objective:To explore the safety and early prognosis of robot assisted living donor kidney transplantation(KT)and plot the learning curve of mastering the operation.Methods:From July 2020 to March 2021, 30 cases of living robot assisted KT were completed.The follow-up period was 3 months.Cumulative sum analysis was performed for plotting the learning curve.According to the learning curve, they were divided into two groups of practice period(the first 17 cases)and proficiency period(the last 13 cases). Time of each operative stage and early prognosis were compared.Kidney function and perioperative complications of two groups were compared for evaluating the safety and effectiveness of robot assisted KT.Results:The average operative duration was (221.4±36.1)min.No intestinal obstruction, delayed graft function, urinary leakage and incision infection occurred during perioperative period.The average anal exhaust time was(1.9±0.2)days.During follow-ups, both pulmonary infection(2 cases)and acute rejection(1 case)improved after treatment.According to the learning curve, venous anastomosis(10 cases), arterial anastomosis(12 cases), warm ischemic time(12 cases)and ureteral anastomosis(17 cases)should be performed for reaching a proficiency level.An average of 15 operations was required for achieving proficiency throughout operations.Significant inter-group differences existed in operative duration [(235.5±31.6)vs(203.0±34.3)min, P=0.012] and warm ischemic time [(63.7±24.9)vs(47.0±11.3)min, P=0.033]. At some postoperative timepoints, creatinine of proficiency group was lower than that of practice group, such as Day 7 post-operation [(192.7±135.2)vs(107.8±27.9)μmol/L, P=0.022] and Day 30 post-operation [(147.8±46.3)vs(112.3±28.0)μmol/L, P=0.021]. However, no significant difference existed in estimated glomerular filtration rate at Day 7 post-operation [(56.1±34.1)ml/(min·1.73m 2)vs(72.0±18.5)ml/(min·1.73m 2), P=0.14] and Day 30 post-operation [(56.2±18.9)ml/(min·1.73m 2)vs(68.7±15.3)ml/(min·1.73m 2), P=0.14]. Conclusions:Robot assisted KT is both safe and feasible.And the learning curve requires 17 cases for reaching a proficiency level.

Objective To evaluate the safety of super-minimal incision kidney transplantation (SMIKT).Methods We included the clinical data and outcomes of 40 cases of SMIKT and 56 cases of conventional Gibson incision kidney transplantation (CIKT),and compared the operation time,post operative pain,analgesic requirements,1 month renal function and 1 month Vancouver scar scale between the two groups.Results As compared with CIKT,operation time was significantly shortened (100 ± 10 versus 127.5 ± 34.3 min,P =0.044),incision length was significantly shortened (5.2 ± 0.2 versus 13.0 ± 2.0 cm,P＜0.001),and post-operative pain at day 1 was significantly reduced in SMIKT (1.31 ± 1.15 versus 4.02 ± 1.83,P =0.004).However,there was no significant difference in post-operative pain at day 2 and day 3 between CIKT and SMIKT.SMIKT required less analgesic medications than CIKT (3.13 ± 1.74 versus 11.69 ± 2.89,P =0.002).No significant difference in 1 month renal function was observed between two groups.SMIKT had fewer Vancouver scar scale score than CIKT (6.50 ± 0.58 versus 8.67 ± 0.58,P =0.004).Conclusion SMIKT is a safe novel surgery,which can significantly reduce operation time,post-operative pain,had fewer analgesic requirements and better 1-month cosmetic effect.

Objective:To evaluate the safety of pregnancy after kidney transplantation and summarize the optimal timing of pregnancy and the experience in the management during pregnancy and peripartum.Methods:A total of 25 kidney transplant recipients were pregnant during March 2013 to February 2020. A matched cohort of 75 general pregnant women wasincluded as control.Results:Twenty-five women successfully delivered healthy babies in the transplant group. The mean age at kidney transplantationwas (25.6 ±3.2) years old, and the mean interval between transplantation and conception was (54.0±23.1) months. 92% (23 / 25) of recipients had cesarean surgery and all infants were singletons.During pregnancy, the incidence of preeclampsia was significantly higher in the transplant group(20.0%VS. 1.3%, P=0.001)compared with matched control. Compared with pre-pregnancy, the serum creatinine levels of the recipients decreased in the second trimester( P<0.001)and increased in the third trimester( P=0.019), which was similar with the control group. In the third trimester, 40%(10/25)of recipients in the transplant group had proteinuria, which decreased to negative(5/10) or 1+ (4/10) within 6 months after delivery. No rejection occurred in all patients during pregnancy and 6 months after delivery. A higher dose of tacrolimus was needed to maintain the normal trough level after pregnancy, which returned to routine dose postpartum. Conclusions:Although the risk of pregnancy was higher in kidney transplant recipients than that in non-transplant women, the overall risk was acceptable. Strict screening of patients preparing for pregnancy, adjustment of immunosuppressive drugs, and multi-disciplinary collaboration are important for safe pregnancy and delivery.