Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To explore the impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

This report described one patient of giant polycystic liver and polycystic kidney involving iliac fossa. Preoperative computed tomography (CT) revealed a large polycystic kidney occupying partially iliac fossa space. A decompression of lower pole of original kidney was planned for placing transplanted kidney. During total liver resection plus orthotopic liver transplantation, right polycystic kidney could move up on its own and iliac fossa space was released for placing transplanted kidney smoothly. Polycystic kidney shrunk markedly post-operation. It provided references for surgical planning of combined liver-kidney transplantation for this type of disease.

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Objective:To explore the morbidity features and therapeutic outcomes of rejections in pediatric kidney transplantation (KT) recipients.Methods:Between January 2013 and June 2022, 360 children undergoing KT were recruited.The relevant clinical data were collected for examining the morbidity features and therapeutic outcomes of rejections.The serum levels of creatinine were compared among groups by non-parametric rank test.And Kaplan-Meier and Log-rank methods were employed for examining the incidence of rejection and comparing mortality-censored graft survival rates among patients with different times of rejection.Results:A total of 58 recipients had 82 incidents of rejection with a cumulative incidence of 6.3%, 9.2% and 11.3% at 3/6/12 months respectively.Among 50 incidents of biopsy-proved rejections, the types were T cell-mediated rejection [TCMR, 42.0%(21/50)], antibody-mediated rejection [20.0%(10/50), ABMR] and mixed rejection [38.0%(19/50)].Among 58 incidents of initial rejection, 69% had maintained graft function (MGF) and 31% impaired graft function (IGF) after anti-rejection regimens.Among 80.8%, 85.7% and 75% of recipients with clinical rejection, ABMR or borderline rejection while 36.4% in TCMR patients had MGF.Fifteen kidney allografts lost function in 58 recipients with rejection.Five-year death-censored graft survival was significantly lower in patients with two or more incidents of rejection (30.5%, 95% CI: 12.3%-75.4%) than in those without rejection (92.9%, 95% CI: 89.3%-96.6%) ( P<0.000 1) or with only one rejection (82.9%, 95% CI: 65.9%-100%)( P<0.001). Conclusions:The rejection rate remains high in KT children and it affects graft survival.And TCMR is more likely to cause impaired graft function.Recurrent rejections have a more pronounced impact upon graft survival.

Objective:To explore the diagnosis and treatment of transplanted renal artery stenosis(TRAS)in children.Methods:From January 2016 to August 2021, clinical data of 7 TRAS patients were collected.A definite diagnosis was confirmed by Doppler ultrasound and computed tomography angiography.Results:Patient age was significantly higher than donor age(11.9±3.7 vs 1.0±0.5 years, P<0.001); 5 patients had a widened diameter at stenotic grafted renal artery after intervention(1.98±0.47 vs 4.64±1.19 mm, P=0.002). A reduction in peak systolic flow velocity in stenotic segment of artery(463.3±90.6 vs 183.6±58.9 cm/s, P<0.001)and lower systolic blood pressure(137.2±15.5 vs 129.7±12.3 mmHg, P=0.029)were observed.Resistance index rose(0.38±0.22 vs 0.60±0.03, P=0.063). Significant difference of estimated glomerular filtration rate was observed at Week 4 post-operation as compared with pre-intervention.Two patients developed complications after intervention, including perirenal hematoma and stent-attached thrombus.Two patients were treated conservatively with a gradual increase in blood pressure and three antihypertensive drugs prescribed. Conclusions:Doppler ultrasound should be performed regularly after renal transplantation for detecting TRAS at an early stage in children.Interventional treatment is ideal for severe TRAS to improve perfusion and renal function.Clinicians should pay more attention to complications.

Objective:To conduct a retrospective analysis of efficacy and safety of different conversion schemes of tacrolimus to slow-release dosage forms for recipients in stable phase after renal transplantation to provide rationales for the conversion strategy of tacrolimus.Methods:From January 2020 to June 2020, clinical data were reviewed for 101 kidney transplant recipients converting from common tacrolimus dosage form to tacrolimus sustained-release dosage form during postoperative stable period.There were 62 males and 49 females with an age range of 19 to 69 years.They were divided into two groups according to iso-dose and incremental-dose switching schemes.The common dosage form of tacrolimus was converted into a sustained-release dosage form with different conversion doses, They were divided into two groups of 1∶1 conversion( n=55)and >1∶1 conversion( n=46). The clinical parameters of serum creatinine(Scr), blood urea nitrogen(BUN), alanine aminotransferase(ALT)and aspartate aminotransferase(AST), alkaline phosphatase(ALP), serum albumin(ALB), white blood cell count(WBC), urinary white blood cell(UWBC), hemoglobin(Hb)and fasting blood glucose(Glu)were compared between two groups after conversion. Results:Regarding numerical change trend after switching to tacrolimus sustained-release dosage form, drug dose/variation trend was smaller and blood drug concentration more stabilized.In two subgroups converted by 1∶1 and 1>1 initial dose, change trend of dose/blood concentration in 1∶1 conversion group appeared to be more stable.However, no inter-group difference existed in long-term parameters.Scr was lower at 1 week and 3 months after switching to extended-release dosage form( P<0.05)and BUN was lower at 2 weeks( P<0.05). In addition, at 5 months after conversion, ALT and AST significantly improved as compared with common dosage form( P<0.05). Significant differences existed in urinary WBC(UWBC)at 2/3 weeks( P<0.05). After switching for 2 weeks, hemoglobin significantly improved compared with common dosage form( P<0.05). No significant differences existed in ALP, ALB or Glu at other timepoints and pre-conversion( P>0.05). In 1∶1 switch group, renal function tended to improve.At 2 weeks, BUN was lower than pre-conversion; at 1/3 weeks, Scr was lower than pre-conversion( P<0.05). In addition, there was also a trend of improvement in liver function in 1∶1 conversion group.At 1 week and 5 months, ALT was lower than pre-conversion( P<0.05). However, no significant differences existed in AST, ALB, ALP, Glu, UWBC and serum WBC count at each timepoint between two different dose conversion groups( P>0.05). After conversion, intra-individual variability of tacrolimus trough concentration significantly improved( P<0.05). Conclusions:With the same safety and efficacy as common dosage form, sustained-release dosage form of tacrolimus may improve drug variability of individuals.When converting common dosage form into sustained-release dosage form, individual differences should be considered.While monitoring trough concentrations, proper doses should be adjusted on the basis of various clinical parameters.

Objective:To explore the clinical efficacy of dual-kidney transplantation from infant donors to adult recipients.Methods:From December 2012 to November 2020 in Organ Transplant Center First Affiliated Hospital Sun Yat-sen University, rertrospective reviews were conducted for clinical data of 25 pairs of infant donors and adult recipients. The survival rates were calculated for both recipients and transplanted kidneys at Year 1/3/5 post-transplantation. And the postoperative recovery status and the postoperative incidence of adverse events of recipients were observed.Results:The survival rates of recipients were all 95.8% at Year 1/3/5 and those of transplanted kidney and dealth-cancelling transplanted kidney all 87.2%. One case died due to acute inferior-wall cardiac infarction while three others lost renal functions for vascular thrombosis, ureteral stenosis and urinary fistula. Except for loss of renal function and death, the postoperative estimated golmerular fitration rate was (99.35±21.78), (103.11±29.20) and (114.99±28.55) ml/(min·1.73 m 2) at Year 1/2/3 respectively. Conclusions:Selecting proper recipients, standardizing donor acquisition and surgical procedures and strengthening perioperative managements may expand the donor pool. The overall outcomes are excellent for adult recipients with dual-kidney transplantation from donations after infants' death.

Objective:To explore the application value of modified technique of ureter implantation in murine renal transplantation.Methods:Thirty left donor kidneys from BALB/c mice was transplanted into syngeneic mice. Cuff technique was applied for anastomosing kidney artery and vein. The procedure of ureter-bladder anastomoses shifted from implication-fixation-embedding to fixation-implication-embedding. Operative duration, recipient survival rate and complications were recorded.Results:Time for separating vessels, perfusion and excision of donor graft was (25±3) min, (10±6) s for warm ischemia and (25±5) min for cold ischemia. Time for separating recipient vessels was (12±5) min, (7±1) min for arterial anastomosis, (7±1) min for venous anastomosis, (13±2) min for ureter-bladder anastomosis, (5±1) min for right kidney excision and (5±1) min for abdominal closure. Operative duration was(77±3)min. Twenty-six recipients survived over 3 months. The successful operative rate was 86.7%.Conclusions:With a shorter learning curve, modified technique of ureter implantation is easier and faster so as to reduce the postoperative incidence of urinary tract complications during murine renal transplantation.