BACKGROUND: Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. METHODS: From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. RESULTS: After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P  = 0.787, P  = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P  = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P  = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P  = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P  = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P  = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. CONCLUSIONS An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.
Humans ; Kidney Transplantation/adverse effects* ; Living Donors ; Kidney ; Immunosuppressive Agents/therapeutic use* ; Rituximab/therapeutic use* ; ABO Blood-Group System ; Graft Rejection ; Graft Survival

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 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 summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

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 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 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 evaluate the clinical efficacy and safety of immunosuppression of calcineurin inhibitor monotherapy (AiCNIm)after alemtuzumab induction following renal transplantation.Methods Randomized control clinical trials related to application of AiCNIm (AiCNIm group ) and conventional triple regimes (Triple group ) for immunosupression after renal transplantation,published from 1 980 to December 31 201 4,were searched online from PubMed,Embase,Web of Science,Cochrance library and China National Knowledge Infrastructure (CNKI) databases.Meta-analysis was performed by Rev Man 5.2 software.Results Five randomized control studies consisting of 421 renal transplant recipients were included.The results of follow up for 6-1 2 months revealed that compared with the Triple group, the incidence of rejection response confirmed by acute rejection or aspiration biopsy in the AiCNIm group was significantly lower [relative risk (RR) =0.59,95% confidence interval (CI):0.40-0.89 ].However,there was no significant difference in the risk of renal allograft dysfunction (RR =0.85,95%CI:0.38-1 .87),death of recipient (RR =0.89,95%CI:0.30-2.67),infection (RR =1 .03,95%CI:0.91 -1 .1 7)and new-onset diabetes after transplantation (RR =0.62, 95%CI:0.29-1 .30)between two groups (all in P >0.05).Conclusions According to the existing evidence,application of calcineurin inhibitor monotherapy after renal transplantation exerts short-term immunosuppressive effect and high safety after alemtuzumab induction.

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.