BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Renal autotransplantation (RA) offers significant technical advantages for the management of certain complex renal vascular diseases, such as complex renal aneurysms and renal artery malformations. This report describes a case of a 5-year-old child with a complex left renal artery aneurysm combined with multiple aneurysms. The child was admitted to Peking University People's Hospital in December 2023 due to a one-year history of intermittent abdominal pain, with an abdominal mass detected in the past month. Computed tomography angiography(CTA) revealed multiple vascular anomalies, including: (1) a left renal artery aneurysm, (2) an abdominal aortic aneurysm, and (3) a right iliac artery aneurysm. After a comprehensive evaluation of these findings, the surgical team developed a treatment plan that involved the excision of the left renal artery aneurysm, autotransplantation of the left kidney, and resection of the abdominal aortic aneurysm with an artificial vascular catheterization. During surgery, it was discovered that the left renal artery anatomy was highly complex. The artery had two primary branches, along with an additional polar artery located at the lower pole. The aneurysm was identified at the distal end of the renal artery trunk, with a pronounced bulging at the intersection between the main renal artery trunk and its secondary branches. Due to these structural complexities, the team decided to use an ex vivo surgical approach to repair the aneurysm. Ex vivo repair involves temporarily removing the kidney from the body to repair the renal artery aneurysm with enhanced precision, enabling the surgical team to meticulously reconstruct the complex vascular architecture without the constraints of in vivo manipulation. The ex vivo repair of the renal artery aneurysm was successful, allowing for accurate vascular reconstruction and avoiding potential intraoperative complications. Following the reconstruction, the kidney was autotransplanted back into the child's body, and blood flow was effectively restored to the organ. The therapeutic outcome was excellent, with the child experiencing no postoperative complications. The patient recovered well and was discharged from the hospital in stable condition. This case underscores the value of renal autotransplantation combined with ex vivo repair for pediatric patients with complicated renal artery aneurysms. Through this report, we aim to provide insights and considerations for the surgical treatment of similar cases in children with complex renal vascular anatomy.
Child, Preschool ; Humans ; Aneurysm/surgery* ; Aortic Aneurysm, Abdominal/diagnostic imaging* ; Computed Tomography Angiography ; Iliac Aneurysm/surgery* ; Kidney Transplantation/methods* ; Renal Artery/abnormalities* ; Transplantation, Autologous

To summarize the clinicopathological features and prognosis of kidney injury after hematopoietic stem cell transplantation (HSCT), to provide basis for preventing its occurrence and development. By using a retrospective cohort study method, we collected the clinical and renal biopsy pathological data of all the patients who hospitalized in the Department of Nephrology of Peking University First Hospital from June 2011 to June 2021 with renal injury after HSCT and underwent renal biopsy, and prognosis was followed up by telephone. The clinical laboratory characteristics, renal pathology and prognosis, and their association were analyzed. The results showed that the most common clinical phenotype was chronic kidney disease (CKD,69.2%, 18/26), in this term 13/18 patients received stem cells from haploidentical donors, and 11/18 patients experienced with extrarenal graft-versus-host disease (GVHD). The most common pathologic phenotype was thrombotic microangiopathy (TMA, 61.5%, 16/26). Renal function returned to baseline level in 6 patients, and the kidney survival at 2 years and 5 years were 95.7% (22/23) and 87.5% (14/16), respectively. In conclusion, the clinical phenotype of renal injury after HSCT were mainly CKD, and the most common pathologic phenotype was TMA, the long-term prognosis was favourable.
Humans ; Retrospective Studies ; Kidney/pathology* ; Hematopoietic Stem Cell Transplantation/methods* ; Thrombotic Microangiopathies/pathology* ; Renal Insufficiency, Chronic/pathology*

OBJECTIVES: The results of elastic imaging in evaluating the function and histopathological changes of allogeneic renal transplantation are contradictory, one of the important reasons may be that there are differences in human parameters related to kidney transplantation among individuals. The purpose of this study is to explore the related human body parameters on shear-wave elastography (SWE) effects on quantitative stiffness of graft cortex. METHODS: From March 2021 to November 2021, a total of 63 patients with allogeneic kidney transplantation in the Department of Ultrasonography, Third Xiangya Hospital, Central South University, were selected to collect the parameters of two-dimensional, color Doppler and SWE. The subjects were divided into a <20% group and a 20%-30% group according to the variation of cortical hardness measurement. Mann Whitney U test was used to compare the differences in relevant human parameters, and Spearman rank correlation was used to analyze the correlation between relevant human parameters and cortical hardness of transplanted kidney. RESULTS: There was no significant difference between the 2 groups in age, sex, postoperative time, resistance index of interlobar artery, SCr, blood uric acid, ratio of fat layer to muscle layer, and BMI (all P>0.05). Compared with the <20% group, the patients in the 20%-30% group had smaller cortical hardness of the transplanted kidney, greater total distance between the transplanted kidney and the skin surface, and thicker fat layer or muscle layer in front of the transplanted kidney (all P<0.05). The age of patients, the total distance from the transplanted kidney to the skin surface, the thickness of fat layer and muscle layer, the ratio of fat layer to muscle layer, BMI, and the variation of cortical hardness were significantly negatively correlated with the cortical hardness of the transplanted kidney (all P<0.05). CONCLUSIONS Human parameters relevant to kidney transplantation affect the accuracy of SWE in measuring the cortical hardness of the transplanted kidney. It is very important to obtain the highly stabile elastic measurement value and interpret the elastic measurement results according to different levels of human body related parameters in combination with individual conditions.
Humans ; Kidney Transplantation ; Elasticity Imaging Techniques/methods* ; Kidney ; Ultrasonography/methods* ; Transplantation, Homologous

PURPOSE: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis. METHODS: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis. RESULTS: Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures. CONCLUSION: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.
Allografts ; Atrophy ; Biomarkers ; Biopsy ; Extracellular Matrix ; Fibrosis ; Humans ; Inflammation ; Kidney Transplantation ; Kidney ; Methods ; Prospective Studies ; Proteoglycans ; Syndecan-4 ; Tissue Donors ; Transplant Recipients

BackgroundImmunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR.

MethodsWe performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC) and Tac Cwere measured at the 1 week and the 1 month posttransplant, respectively. The correlation was assessed by multivariate logistic regression.

ResultsThe occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC at the 1 week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUClevel was <30 mg·h·L at the 1 week (15.0% vs. 44.4%) or the Tac Cwas <4 ng/ml at the 1 month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC at the 1 week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac Cat the 1 month (OR: 0.904, 95% CI: 0.822-0.986) had significant inverse correlation with BPAR (P < 0.05).

ConclusionsLow-level exposure of MPA and Tac Cin the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC <30 mg·h·L and Tac C <4 ng/ml should be avoided in the first few weeks after transplantation.

Adult ; Female ; Graft Rejection ; immunology ; prevention & control ; Humans ; Immunosuppressive Agents ; chemistry ; therapeutic use ; Kidney Transplantation ; adverse effects ; methods ; Male ; Middle Aged ; Mycophenolic Acid ; chemistry ; therapeutic use ; Retrospective Studies ; Tacrolimus ; chemistry ; therapeutic use ; Time Factors

Background: Vascular resistance and flow rate during hypothermic machine perfusion (HMP) of kidneys is correlated with graft function. We aimed to determine the effects of increasing HMP pressure versus maintaining the initial pressure on kidney transplantation outcomes. Methods: We retrospectively reviewed the data of 76 primary transplantation patients who received HMP-preserved kidneys from 48 donors after cardiac death between September 1, 2013, and August 31, 2015. HMP pressure was increased from 30 to 40 mmHg (1 mmHg = 0.133 kPa) in kidneys with poor flow and/or vascular resistance (increased pressure [IP] group; 36 patients); otherwise, the initial pressure was maintained (constant pressure group; 40 patients). Finally, the clinical characteristics and transplantation outcomes in both groups were assessed. Results: Delayed graft function (DGF) incidence, 1-year allograft, patient survival, kidney function recovery time, and serum creatinine level on day 30 were similar in both groups, with improved flow and resistance in the IP group. Among patients with DGF, kidney function recovery time and DGF duration were ameliorated in the IP group. Multivariate logistic regression analysis revealed that donor hypertension (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.02-2.06, P = 0.035), donor terminal serum creatinine (OR: 1.27, 95% CI: 1.06-1.62, P = 0.023), warm ischemic time (OR: 3.45, 95% CI: 1.97-6.37, P = 0.002), and terminal resistance (OR: 3.12, 95% CI: 1.76-6.09, P = 0.012) were independent predictors of DGF. Cox proportional hazards analysis showed that terminal resistance (hazard ratio: 2.06, 95% CI: 1.32-5.16, P = 0.032) significantly affected graft survival. Conclusion Increased HMP pressure improves graft perfusion but does not affect DGF incidence or 1-year graft survival.
Adult ; Allografts ; Delayed Graft Function ; Female ; Humans ; Hypertension ; physiopathology ; Kidney Function Tests ; Kidney Transplantation ; methods ; Logistic Models ; Male ; Middle Aged ; Organ Preservation ; Retrospective Studies ; Tissue Donors

Background: Hypothermic machine perfusion (HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function (DGF) by HMP parameters is still controversial. Therefore, we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment. Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios (ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model. Results: HMP duration (OR = 1.165, 95% confidence interval [CI]: 1.008-1.360, P = 0.043), resistance (OR = 2.190, 95% CI: 1.032-10.20, P < 0.001), and flow rate (OR = 0.931, 95% CI: 0.894-0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories (scores 0-3, 4-7, 8-11, and 12-14) according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c-statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow (P = 0.012) and resistance (P = 0.006). Conclusion The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.
Adult ; Delayed Graft Function ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; adverse effects ; methods ; Logistic Models ; Male ; Multivariate Analysis ; Odds Ratio ; Organ Preservation

Transplantation of the horseshoe kidney can be performed en bloc or split into 2 grafts according to the vascular anomaly and the existence of the urinary collecting system in isthmus. From 2011 to 2014, there were 3 horseshoe kidney transplantations in Korea and transplantations were performed at 2 different centers. The transplantations were carried out successfully for all recipients without complications. All recipients have shown good graft kidney function after transplantation. No severe complication was revealed during follow-up period. We described the surgical technique used in the en bloc method to overcome various vascular anomalies and difficulties in choosing cannulation site and postoperative complications. En bloc transplantation of a horseshoe kidney is a useful strategy for patients with end-stage renal disease, and can provide favorable outcomes compared to the transplantation of a normal kidney.
Catheterization ; Follow-Up Studies ; Fused Kidney* ; Humans ; Kidney ; Kidney Failure, Chronic ; Kidney Transplantation ; Korea* ; Methods ; Postoperative Complications ; Transplants

PURPOSE: This study was conducted to develop an Empowerment Education Program (EEP) for kidney transplant patients and to test the program's effects on uncertainty, self-care ability, and compliance. METHODS: The research was conducted using a nonequivalent control group with a pretest-posttest design. The participants were 53 outpatients (experimental group: 25, control group: 28) who were receiving hospital treatment after kidney transplants. After the pre-test, patients in the experimental group underwent a weekly EEP for six weeks. The post-test was conducted immediately after, and four weeks after the program's completion in the same manner as the pre-test. For the control group, we conducted a post-test six and ten weeks after the pre-test, without and program intervention. A repeated measure ANOVA was performed to compare the change scores on main outcomes. RESULTS: Uncertainty was significantly lower in the experimental group than in the control group, both immediately after (t=-3.84, p=<.001) and 4 weeks after (t=-4.51 p=<.001) the program, whereas self-care ability (t=5.81, p=<.001), (t=5.84, p=<.001) and compliance (t=5.07, p=<.001), (t=5.45, p=<.001) were significantly higher. CONCLUSION: Kidney transplant patients who underwent an EEP showed a decrease in uncertainty and an improvement in self-care ability and compliance. Thus, our findings confirmed that an EEP can be an independent intervention method for improving and maintaining the health of kidney transplant patients.
Compliance ; Education* ; Humans ; Kidney Transplantation* ; Kidney* ; Methods ; Outpatients ; Patient Compliance ; Power (Psychology)* ; Self Care ; Uncertainty