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 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: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 clinical efficacy and safety of individualized preconditioning in ABO-incompatible living donor kidney transplantation.Methods A series of 36 living donor kidney transplants across a wide range of ABO blood group incompatibilities using individualized preconditioning protocols were performed from September 2014 to June 2017.Preconditioning included oral immunosuppressants with or without the administration of rituximab,PE or DFPP.Medical records and electronic databases were reviewed for isoagglutinin titers,patient and graft survivals,graft function,rejections,infections as well as surgical complications.Results Of 30 ABO blood group incompatibilities,there were 6 cases of AB to A,2 cases of AB to B,4 cases of A to B,3 cases of B to A,13 cases of A to O (13),and 8 cases of B to O.Median initial ABO antibody titers were 1∶32 (1∶2-1∶256) (IgM) and 1 ∶ 8 (0-1∶64) (IgG),respectively.Individualized preconditioning included oral immunosuppressants alone (10 cases),oral immunosuppressants + PE (4 cases),oral immunosuppressants + PE + DFPP (1 case),oral immunosuppressants + rituximab + PE (16 cases),oral immunosuppressants + rituximab + DFPP (2 cases),and oral immunosuppressants + rituximab + PE+ DFPP (3 cases).After individualized preconditioning,an acceptable ABO antibody titer (≤1 ∶ 16) was obtained on the day of transplantation.Median follow-up duration was 12 months (1-33).Graft and patient survival rate was 94.4％ (34/36) and 100％ (36/36) respectively.Median value of serum creatinine at one year posttransplantation was 89 μmol/L,and eGFR was (81.07 mL/min/1.73 m2).In total,there was one episode of urinary tract infection and upper gastrointestinal tract hemorrhage,two cases of hyperacute rejection (leading to graft loss),acutecelluar-mediated rejection,delayed graft function,bone marrow suppression and pneumonia,and 3 cases of acute antibody-mediated rejection and wound fat liquefaction,respectively.Conclusion Our initial experience indicates that individualized preconditioning protocol based on initial ABO antibody titers is safe and technically feasible,and leads to excellent short-term survival of ABOi living donor kidney transplantation.

Objective To investigate the safety and efficacy of conversion from calcineurin inhibitors (CNI) to mammalian target of rapamycin (mTORi) in liver transplant recipients.Methods Such databases as MEDLINE (PUBMED),EMBASE,Cochrane Library and clinical trial registries (ClinicalTrials.gov,WHO International Trial Registry Network,Australian & New Zealand Clinical Trials Registry) were searched from the inception of each resource up to April 2015 for collecting the randomized controlled trials (RCTs) about liver transplant recipients after conversion from CNIs to mTORi,and the references of those trials were also searched by hand.After study selection,assessment and data extraction conducted by two reviewers independently,meta-analyses were performed by using the RevMan5.3 software.The quality of those trials was assessed by using the Jadad Score.Then,the safety and efficacy of conversion from CNI to mTORi were systematically assessed as a strategy for eliminating CNI exposure in liver transplant recipients.Results Ten RCTs (1917 patients) were included in this meta-analysis.The follow-up duration post-randomization was 6 to 36 months.The mean mTORi conversion time after transplantation was ≤6 months in 4 trials,and ＞6 months in 6.The meta-analysis revealed that the estimated glomerular filtration rate was significantly increased,and the incidence of renal failure and hyperglycemia was significantly reduced in mTORi conversion group as compared with those in CNI treatment group (P＜0.05 for all).The incidence of acute rejection in mRORi conversion group and CNI treatment group was 11.3％ and 6.3％ respectively (P＜0.01),and that confirmed by biopsy was 14.0％ and 8.4％ respectively (P＜0.01).The percentage of recipients discontinuing the medication in mRORi conversion group and CNI treatment group was 41.6％ and 21.5％ respectively (P＜0.01).The main reasons for drug withdrawal were drug-related adverse events (Aes),including acute rejection,bone marrow depression,anemia,leucopenia,thrombocytopenia,mouth sores/stomatitis,hyperlipidemia,hypercholesterolemia,rash,edema,and pyrexia.There was no significant difference between the two groups with regard to death,graft loss,loss to follow-up,infection,gastrointestinal symptoms,malignancy,and hypertension.Conclusion Conversion from CNI to mTORi therapy results in a significant improvement in renal function.However,this conversion strategy may lead to the high discontinuation rate due to mTORi-associated Aes,indicating that conversion may only be a treatment option in selected patients.

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 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.