1.Summary of Professor GAO Xiangfu's Experience in Treating Chronic Kidney Disease with Drug Pairs
Zhehao HUANG ; Zhouqi CHEN ; Jiawen QIAN
Journal of Zhejiang Chinese Medical University 2025;49(1):46-53
[Objective]To summarize Professor GAO Xiangfu's experience in treating chronic kidney disease with drug pairs and triangular drugs.[Methods]By following the Professor during clinical consultations,organizing medical cases and reviewing literature,this paper summarized Professor GAO's understanding of the pathogenesis and the characteristics of diagnosis and treatment of chronic kidney disease,and the composition,compatibility principles,clinical applications,common doses,and compatibility significance of Professor GAO's commonly using drug pairs and triangular drugs in treatment chronic kidney disease and a medical case was attached for evidence.[Results]Professor GAO believes that the pathological condition of chronic kidney disease is deficient in origin and excess in superficiality.The core pathogenesis of disease progression is characterized by"vital Qi is deficient and toxins are hiding,essence and blood are leaking,vital Qi is attenuating and toxins are enhancing".The deficiency of vital Qi is mainly manifested as deficiency of the spleen and kidney,while the hidden toxins are mainly turbid toxins,blood stasis toxins and heat toxins.In treatment,the priorities should be put on the origin and the superficiality of the pathogenesis,and a case being acute or chronic should be distinguished first,following the principle of treatment that"treating acute cases as the emerging diseases and treating the chronic cases as the primary disease".For acute progressive cases of this disease,drug pairs for eliminating hidden toxins are commonly combined with classic prescriptions.For chronic protracted cases,drug pairs are often used to formulate prescriptions directly.Particularly,Professor GAO commonly uses"Astragalus membranaceus-Angelica sinensis""Astragalus membranaceus-Atractylodes macrocephala"and"Astragalus membranaceus-Cimicifuga foetida-Bupleurum chinense"are used to tonify spleen Qi and invigorate middle-Jiao;he uses"Radix rehmanniae-Dioscorea opposita-Poria cocos""Herba epimedii-Cistanche deserticola"to nourish kidney Yin and tonify kidney Yang,uses"Herba plantaginis-Rheum officinale""Salvia miltiorrhiza-Centella asiatica"to eliminate turbid and blood stasis,and clear stagnated heat,and uses"Rhizoma imperatae-Agrimonia pilosa""Rosa laevigata-Semen euryales"to calm the blood collaterals and control essence.In the attached medical case,a patient with chronic kidney disease was treated with a main formula consisting of five drug pairs including"Astragalus membranaceus-Angelica sinensis""Radix rehmanniae-Dioscorea opposita-Poria cocos""Herba plantaginis-Rheum officinale""Salvia miltiorrhiza-Centella asiatica"and"Rhizoma imperatae-Agrimonia pilosa",which was adjusted according to the symptoms,and ultimately achieved good results.[Conclusion]Professor GAO's approach to treating chronic kidney disease with drug pairs and triangular drugs is characterized by mild medication,hierarchical compatibility and remarkable efficacy,which is worth summarizing and promoting.
2.Inhibition of interferon regulatory factor 4 orchestrates T cell dysfunction, extending mouse cardiac allograft survival.
Wenjia YUAN ; Hedong ZHANG ; Longkai PENG ; Chao CHEN ; Chen FENG ; Zhouqi TANG ; Pengcheng CUI ; Yaguang LI ; Tengfang LI ; Xia QIU ; Yan CUI ; Yinqi ZENG ; Jiadi LUO ; Xubiao XIE ; Yong GUO ; Xin JIANG ; Helong DAI
Chinese Medical Journal 2025;138(10):1202-1212
BACKGROUND:
T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction.
METHODS:
A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models.
RESULTS:
In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression.
CONCLUSIONS
Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Interferon Regulatory Factors/metabolism*
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Heart Transplantation/methods*
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T-Lymphocytes/immunology*
;
Sirolimus/therapeutic use*
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Pyridones/therapeutic use*
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Graft Survival/drug effects*
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Pyrimidinones/therapeutic use*
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Cell Proliferation/drug effects*
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Apoptosis/drug effects*
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Male
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Signal Transduction/drug effects*
3.Summary of Professor GAO Xiangfu's Experience in Treating Chronic Kidney Disease with Drug Pairs
Zhehao HUANG ; Zhouqi CHEN ; Jiawen QIAN
Journal of Zhejiang Chinese Medical University 2025;49(1):46-53
[Objective]To summarize Professor GAO Xiangfu's experience in treating chronic kidney disease with drug pairs and triangular drugs.[Methods]By following the Professor during clinical consultations,organizing medical cases and reviewing literature,this paper summarized Professor GAO's understanding of the pathogenesis and the characteristics of diagnosis and treatment of chronic kidney disease,and the composition,compatibility principles,clinical applications,common doses,and compatibility significance of Professor GAO's commonly using drug pairs and triangular drugs in treatment chronic kidney disease and a medical case was attached for evidence.[Results]Professor GAO believes that the pathological condition of chronic kidney disease is deficient in origin and excess in superficiality.The core pathogenesis of disease progression is characterized by"vital Qi is deficient and toxins are hiding,essence and blood are leaking,vital Qi is attenuating and toxins are enhancing".The deficiency of vital Qi is mainly manifested as deficiency of the spleen and kidney,while the hidden toxins are mainly turbid toxins,blood stasis toxins and heat toxins.In treatment,the priorities should be put on the origin and the superficiality of the pathogenesis,and a case being acute or chronic should be distinguished first,following the principle of treatment that"treating acute cases as the emerging diseases and treating the chronic cases as the primary disease".For acute progressive cases of this disease,drug pairs for eliminating hidden toxins are commonly combined with classic prescriptions.For chronic protracted cases,drug pairs are often used to formulate prescriptions directly.Particularly,Professor GAO commonly uses"Astragalus membranaceus-Angelica sinensis""Astragalus membranaceus-Atractylodes macrocephala"and"Astragalus membranaceus-Cimicifuga foetida-Bupleurum chinense"are used to tonify spleen Qi and invigorate middle-Jiao;he uses"Radix rehmanniae-Dioscorea opposita-Poria cocos""Herba epimedii-Cistanche deserticola"to nourish kidney Yin and tonify kidney Yang,uses"Herba plantaginis-Rheum officinale""Salvia miltiorrhiza-Centella asiatica"to eliminate turbid and blood stasis,and clear stagnated heat,and uses"Rhizoma imperatae-Agrimonia pilosa""Rosa laevigata-Semen euryales"to calm the blood collaterals and control essence.In the attached medical case,a patient with chronic kidney disease was treated with a main formula consisting of five drug pairs including"Astragalus membranaceus-Angelica sinensis""Radix rehmanniae-Dioscorea opposita-Poria cocos""Herba plantaginis-Rheum officinale""Salvia miltiorrhiza-Centella asiatica"and"Rhizoma imperatae-Agrimonia pilosa",which was adjusted according to the symptoms,and ultimately achieved good results.[Conclusion]Professor GAO's approach to treating chronic kidney disease with drug pairs and triangular drugs is characterized by mild medication,hierarchical compatibility and remarkable efficacy,which is worth summarizing and promoting.
4.Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model
Xia QIU ; Hedong ZHANG ; Zhouqi TANG ; Yuxi FAN ; Wenjia YUAN ; Chen FENG ; Chao CHEN ; Pengcheng CUI ; Yan CUI ; Zhongquan QI ; Tengfang LI ; Yuexing ZHU ; Liming XIE ; Fenghua PENG ; Tuo DENG ; Xin JIANG ; Longkai PENG ; Helong DAI
Chinese Medical Journal 2024;137(12):1453-1464
Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.
5.Mouse kidney transplantation model:Three novel methods
Zhouqi TANG ; Chen FENG ; Yaguang LI ; Tengfang LI ; Hedong ZHANG ; Yingqi ZENG ; Longkai PENG ; Xubiao XIE ; Fenghua PENG ; Helong DAI
Journal of Central South University(Medical Sciences) 2024;49(2):220-235
Objective:The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate,making it difficult to master.This study aims to provide a crucial model for transplantation immunology research by modifying and developing novel techniques for mouse kidney transplantation. Methods:A total of 57 pairs of mice were used to establish and compare the modified and innovative surgical techniques for mouse kidney transplantation.Three different surgical models were established,including the abdominal suture technique for orthotopic kidney transplantation,the abdominal cuff technique for orthotopic kidney transplantation,and the cervical cuff technique for ectopic kidney transplantation.BALB/c or C57BL/6 male mice,aged 8 to 12 weeks and weighed 20 to 25 g with specified pathogen free-grade were served as the donor mice or the recipient mice.The surgical technique characteristics,key surgical times,complications,and pathological examination in the early postoperative period were summarized and compared. Results:Three different surgical models of mouse kidney transplantation were successfully established.The comparison of warm ischemic time for the 3 groups of mice showed no statistical significance(P=0.510 4).The abdominal suture group had the shortest total operation time of the donor compared with the abdominal cuff group and the cervical cuff group[(18.3±3.6)min vs(26.2±4.7)min and(22.8±2.5)min;both P<0.000 1].There was a significant difference in cold ischemia time among the 3 groups(all P<0.000 1),with(60.8±4.1)min in the cervical cuff group,(43.3±5.0)min in the abdominal suture group,and(88.8±6.7)min in the abdominal cuff group.Due to different anastomosis methods,the cervical cuff group had the shortest time[(17.6±2.7)min],whereas the abdominal cuff group had the longest time[(38.8±5.4)min].The total operation time for the recipients showed significant differences(P<0.000 1),with the abdominal suture group having the shortest time[(44.0±6.9)min],followed by the cervical cuff group[(64.1±5.2)min],and the abdominal cuff group[(80.0±6.0)min]being the longest.In the 32 mice of the abdominal suture group,there were 6 with intraoperative bleeding,including 1 arterial intimal injury bleeding and 5 with bleeding after vessel opening.Six mice had ureteral complications,including ureteral bladder anastomotic stenosis,necrosis,and renal pelvis dilation.Two mice had postoperative abdominal infections.In the abdominal cuff group,there was no intraoperative bleeding,but 6 mice showed mild arterial stenosis and 5 showed venous stenosis,4 arterial injury,4 arterial thrombosis,and 2 ureteral complications.No postoperative infections occurred in the mice.In the cervical cuff group,no intraoperative bleeding,arterial intimal injury,arterial/venous stenosis,or thrombosis were found in 13 mice.Five mice had ureteral complications,including ureteral necrosis and infection,which were the main complications in the cervical cuff group.The renal function in mice of the 3 groups remained stable 7 days after surgery.Hematoxylin and eosin staining and periodic acid-Schiff staining showed no significant differences in terms of acute rejection among the 3 surgical methods(all P>0.05). Conclusion:All 3 surgical methods are able to successfully establish mouse kidney transplantation models,with no significant differences observed in the short-term graft survival and acute rejection.The modified abdominal suture technique and abdominal cuff technique have their respective advantages in research applications.The novel cervical cuff technique for ectopic kidney transplantation model is relatively simple to be prepared and causes less trauma to the mice,providing more options for studies involving xenotransplantation,secondary transplantation,and local lymphatic drainage.However,the difficulty in harvesting the donor kidney and the high incidence of ureteral infections need further validation in long-term survival.This study holds important reference value for choosing the type of mouse kidney transplantation model for different research needs.
6.EGR3 reduces podocyte inflammatory damage in obesity related glomerulopathy by inhibiting the PRMT1/p-STAT3 pathway
Lin PENG ; Xiaoying SUN ; Xuan YI ; Zhouqi WANG ; Ke CHEN
Journal of Central South University(Medical Sciences) 2024;49(3):349-358
Objective:Obesity related glomerulopathy(ORG)is induced by obesity,but the pathogenesis remains unclear.This study aims to investigate the expression of early growth response protein 3(EGR3)in the renal cortex tissues of ORG patients and high-fat diet-induced obese mice,and to further explore the molecular mechanism of EGR3 in inhibiting palmitic acid(PA)induced human podocyte inflammatory damage. Methods:Renal cortex tissues were collected from ORG patients(n=6)who have been excluded from kidney damage caused by other diseases and confirmed by histopathology,and from obese mice induced by high-fat diet(n=10).Human and mouse podocytes were intervened with 150 μmol/L PA for 48 hours.EGR3 was overexpressed or silenced in human podocytes.Enzyme linked immunosorbent assay(ELISA)was used to detcet the levels of interleukin-6(IL-6)and interleukin-1β(IL-1β).Real-time RT-PCR was used to detect the mRNA expressions of EGR3,podocytes molecular markers nephrosis 1(NPHS1),nephrosis 2(NPHS2),podocalyxin(PODXL),and podoplanin(PDPN).RNA-seq was performed to detect differentially expressed genes(DEGs)after human podocytes overexpressing EGR3 and treated with 150 μmol/L PA compared with the control group.Co-immunoprecipitation(Co-IP)combined with liquid chromatography tandem mass spectrometry(LC-MS)was used to detect potential interacting proteins of EGR3 and the intersected with the RNA-seq results.Co-IP confirmed the interaction between EGR3 and protein arginine methyltransferases 1(PRMT1),after silencing EGR3 and PRMT1 inhibitor intervention,the secretion of IL-6 and IL-1β in PA-induced podocytes was detected.Western blotting was used to detect the expression of phosphorylated signal transducer and activator of transcription 3(p-STAT3)after overexpression or silencing of EGR3. Results:EGR3 was significantly upregulated in renal cortex tissues of ORG patients and high-fat diet-induced obese mice(both P<0.01).In addition,after treating with 150 μmol/L PA for 48 hours,the expression of EGR3 in human and mouse podocytes was significantly upregulated(both P<0.05).Overexpression or silencing of EGR3 in human podocytes inhibited or promoted the secretion of IL-6 and IL-1β in the cell culture supernatant after PA intervention,respectively,and upregulated or downregulated the expression of NPHS1,PODXL,NPHS2,and PDPN(all P<0.05).RNA-seq showed a total of 988 DEGs,and Co-IP+LC-MS identified a total of 238 proteins that may interact with EGR3.Co-IP confirmed that PRMT1 was an interacting protein with EGR3.Furthermore,PRMT1 inhibitors could partially reduce PA-induced IL-6 and IL-1β secretion after EGR3 silencing in human podocytes(both P<0.05).Overexpression or silencing of EGR3 negatively regulated the expression of PRMT1 and p-STAT3. Conclusion:EGR3 may reduce ORG podocyte inflammatory damage by inhibiting the PRMT1/p-STAT3 pathway.
7.Single cell sequencing reveals the antigen presentation characteristics of dendritic cells and B cells in cardiac grafts
Yuexing ZHU ; Chao CHEN ; Ye XU ; Yuxi FAN ; Xinguo ZHENG ; Qiulin LUO ; Zhouqi TANG ; Hedong ZHANG ; Tengfang LI ; Longkai PENG ; Helong DAI
Organ Transplantation 2024;15(5):789-798
Objective To investigate the antigen presentation characteristics of dendritic cells(DC)and B cells in cardiac grafts.Methods The heart of BALB/c mice was transplanted into the abdominal cavity of C57BL/6J mice.CD45+cells in the heart graft were extracted and sorted by flow cytometry at postoperative 5 d,and single cell RNA sequencing was performed.Taking DC and B cell subsets in cardiac grafts as the main study cells,the changing trend,antigen presenting ability and intercellular communication with T cells after heart transplantation were analyzed by bioinformatics analysis and flow cytometry.Gene ontology(GO)function enrichment difference analysis was adopted to prove the specific function and the reliability annotation of cell subsets.Results Germinal center-like B cell(GC-L B)was the B cell subset with the largest increase in quantity during the acute rejection phase,accounting for 87%.Classical DC(cDC)2 was the only DC subset with a significant increase in quantity during acute rejection of heart transplantation,accounting for 44%of DC subset,and it occupied the highest communication intensity with T cells after heart transplantation.Mononucleated DC(moDC)and memory B cell(MBC)were the main transmitters of T cell input signals in non-transplanted hearts,whereas transformed into cDC2 and GC-L B during the acute rejection phase.Among them,MBC and GC-L B were the main sources of T cell input signals in non-transplanted hearts and heart grafts.Conclusions Compared with DC,B cells occupy a higher number and weight in the intercellular communication with T cells in non-transplanted hearts and heart grafts,prompting that the antigen presenting activity of B cells is more active and stronger than DC in the early stage of acute rejection of heart transplantation.
8.Clinical effect of adult donor dual kidney transplantation
Jianfei HOU ; Longkai PENG ; Xubiao XIE ; Zhouqi TANG ; Jiawei PENG ; Hedong ZHANG ; Tengfang LI ; Kankan SHUI ; Chen GAO ; Gongbin LAN ; Fenghua PENG ; Shaojie YU ; Yu WANG ; Xiaotian TANG ; Helong DAI
Chinese Journal of Urology 2023;44(4):282-286
Objective:To explore the clinical efficacy of adult donor dual kidney transplantation.Methods:Retrospective analysis of case data of 13 adult donor kidney dual kidney transplantation (DKT) performed in the The Second Xiangya Hospital of Central South University from September 2016 to December 2020. For 13 donors, the average age and BMI were (53.5±12.4)years and (24.3±2.8) kg/m 2, respectively. Their mean Serum creatinine (SCr) at admission and before procurement was (132.9±54.1)and (228.7±112.4)μmol/L, respectively. 3 of them had diabetes mellitus history, and 8 had hypertension history. 11 met the United Network for Organ Sharing (UNOS) DKT criteria and 6 met Remuzzi score DKT criteria. For 13 recipients, the average age and BMI were (39.3±8.9)years and (20.2±2.4)kg/m 2, respectively. All of them received ABO blood type-matched kidney transplants. 2 of them had their grafts transplanted in the bilateral iliac. In 12 cases, the grafts filled rapidly and urinated immediately when opening blood flow. In 1 case, the grafts were dark in color and vascular showed weak pulsation after opening blood flow. The time to recovery of perioperative graft function (from the day of surgery to the natural reduction of SCr to the normal range 44-133μmol/L), the occurrence of delayed graft function (DGF), acute rejection (AR), ureteral and surgical incision complications, as well as the recipients’ final follow-up SCr, eGFR, urinary protein, and grafts outcome were observed. Risk factors affecting outcomes were assessed by univariate logistic regression analysis. Results:The SCr dropped to the normal range at discharge in 10 recipients, and the average recovery time was (13.8±13.0) days. In other 3 cases SCr at discharge were 300.0, 149.0, 152.5μmol/L. 4 cases had DGF, 4 had AR, 1 experienced urinary fistula, and 1 experienced incisional dehiscence, which were treated with anti-rejection, J-tube implantation, continuous catheterization to maintain bladder void, secondary suturing, respectively. The follow-up time ranged from 4 to 54 months, with a median of 28(15.5, 31.0) months. At the final follow-up time, 10 cases had good graft function, 2 suffered impaired kidney function, and 1 experienced graft failure. The average SCr and eGFR except for graft failure patient were (144.2±101.3)μmol/L and (52.9±21.2)ml/min, respectively. 4 had positive urine protein. Univariate logistic regression analysis showed that donor age, BMI, history of diabetes mellitus and hypertension, and SCr were not significantly correlated with recipients’ DGF and graft impairment ( P>0.05), and due to the small sample size, multifactorial logistic regression analysis was not performed. Conclusion:The short to medium-term effects of adult donor DKT coule be safe and feasible.
9.Clinical outcomes for kidney transplantation in 81 adults with IgA nephropathy
Zhouqi TANG ; Tengfang LI ; Chen FENG ; Longkai PENG ; Xubiao XIE ; Fenghua PENG ; Gongbin LAN ; Shaojie YU ; Yu WANG ; Helong DAI
Journal of Central South University(Medical Sciences) 2023;48(7):1017-1025
Objective: Immunoglobulin A nephropathy (IgAN) is one of the most common types of kidney disease, and kidney transplantation is the most effective treatment for end-stage renal disease. This study aims to analyze the clinical curative effect of renal transplantation for adults with IgAN and to discuss the efficacy and safety of kidney transplantation for IgAN at the perioperative period and medium- and long-term follow-up. Methods: This retrospective study included the clinical and follow-up data of 81 adult patients with IgAN who underwent kidney transplantation at the Second Xiangya Hospital, Central South University from January 2018 to January 2022. Of the 81 patients whose age at (34.1±9.9) years old, 47 (58.0%) were male. The body mass index was (20.8±3.2) kg/m2, and the human leukocyte antigen (HLA) mismatch number was 3.5±1.2. The estimated glomerular filtration rate (eGFR) and daily 24-hour urine output for the recipients on the 1st, 5th, and 7th day after kidney transplantation and when they were discharged were analyzed. The recovery of the transplanted kidney and occurrence of complications were comprehensively evaluated. The eGFR, urinary protein, and occult blood were evaluated at the 6th, 12th, 24th, 36th, and 48th month and at the last follow-up. Results: The follow-up time was (25.7±15.8) months. No primary non-function occurred in any patient during the perioperative period time. Fifty-one (63.0%) patients had immediate graft function recovery, and 16 (19.8%) patients had slow graft function recovery. Delayed recovery of graft function was observed in 14 (17.3%) patients. A total of 19 perioperative complications occurred, including 9 patients with acute rejection, 5 patients with urinary fistula, 1 thrombosis in both lower limbs, and 4 lymphatic fistula. The eGFR at 6th, 12th, 24th, 36th, and 48th month of follow-up were (65.3±22.9), (67.6±23.0), (64.3±21.8), (65.9± 24.7), and (68.7±31.2) mL/(min·1.73 m2), respectively. The eGFR remained high during the medium- and long-term follow-ups. At the longest follow-up of 56 months, eGFR fluctuation was still mild, and the positive rate of urine protein and occult blood was low. IgAN recurred in 4 transplanted kidneys, accounting for 4.94% of the total patients, without severe renal insufficiency. Three patients had kidney dysfunction due to severe pneumonia, rejection, and stone in the transplanted kidney. The overall survival rate of the transplanted kidney was higher than 95%, and the survival rate of all patients was 100% till Januray 2022. Conclusion: Renal transplantation for adults with IgAN had a remarkable short-term effect. The recipients can be beneficial significantly to favorable midium- and long-term outcomes. IgAN recurrence is infrequent and rarely causes severe renal function damage.
10.Dual kidney transplantation from infant donors to adult recipients: a report of 42 cases
Zhouqi TANG ; Huicong LIU ; Longkai PENG ; Xubiao XIE ; Helong DAI ; Jingliang CHEN ; Ni WU ; Shanshan GUI ; Shanbiao HU ; Shaojie YU
Chinese Journal of Organ Transplantation 2021;42(1):14-19
Objective:To explore the clinical efficacy of single-center infant kidney donor adult dual kidney transplantation to explore the difference of different operation methods and the operation options of different donor kidney conditions so as to improve the success rate of children kidney donor adult dual kidney transplantation and reduce complications.Methods:A total of 42 cases of infant and adult dual kidney transplantations at Department of Kidney Transplantation in The Second Xiangya Hospital of Central South University from December 2012 to May 2019 were divided into two groups according to whether or not donor kidney fulfilled the criteria of three " 5" . According to different surgical approaches, they were divided into three groups of A (classical En-Bloc operation), B (separated dual kidney transplantation) and C (modified operation). The clinical data and prognoses were analyzed.Results:The median follow-up period was 55(11-92) months. The estimated glomerular filtration rate was 123.4(92.2-156.6) ml/min for operation A, 97.2(81.3-116.6) ml/min for operation B and 133.9(133.9-133.9) ml/min for operation C. In donor group not fulfilling the " 5" principle, no thrombotic event occurred for operation A/C and 3 cases of transplantation for operation B. There were single renal embolism ( n=2) and dual renal embolism ( n=1)(3/5, 60%)( P<0.05). Urinary protein was positive in the last follow-up: operation A (1/2, 50%) and operation B (3/5, 60%) ( P<0.05). The estimated glomerular filtration rate at the last follow-up was 82.4(80.9-83.9) ml/min for operation A, 71.8(46.1-114.2) ml/min for operation B and 122(83.3-142.4) ml/min for operation C. The 1-year graft survival rate was 100% and 89.5% in three " 5" donor group and 3-year graft survival rate was 100% and 84.2% respectively. Conclusions:Satisfactory outcomes might be obtained during dual kidney transplantation for infants and adults. The incidence of thrombosis, urine leakage and urinary protein is lower in improved kidney transplantation group than that in previously operated group. The problem of graft hyperperfusion injury is well solved. And the long-term follow-up outcome is excellent.

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