Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation: A Retrospective Study.

OBJECTIVE: Delayed graft function (DGF) and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor. As "non-traditional" risk factors, serum biomarkers of donors, such as lipids and electrolytes, have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts. This study aimed to examine the value of these serum biomarkers for prediction of renal graft function. METHODS: The present study consecutively collected 306 patients who underwent their first single kidney transplantation (KT) from adult deceased donors in our center from January 1, 2018 to December 31, 2019. The correlation between postoperative outcomes [DGF and abnormal serum creatinine (SCr) after 6 and 12 months] and risk factors of donors, including gender, age, body mass index (BMI), past histories, serum lipid biomarkers [cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (DL)], and serum electrolytes (calcium and sodium) were analyzed and evaluated. RESULTS: (1) Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level (≥2 mg/dL) at 6 and 12 months after KT (P<0.05); (2) The donor's BMI was significantly correlated with the incidence rate of DGF after KT (P<0.05); (3) For serum lipids, merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT [P<0.05, OR (95% CI): 0.425 (0.202-0.97)]; (4) The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT [P<0.05, OR (95% CI): 0.184 (0.045-0.747) and P<0.05, OR (95% CI): 0.114 (0.014-0.948), respectively]. CONCLUSION: The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT, in addition to the donor's age, BMI and pre-existing hypertension.

Infective Artery Rupture of Renal Allografts: A Single-Center Retrospective Study in China.

OBJECTIVE: This study investigated the composition of pathogenic microorganisms, clinical features, and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor (DD) kidneys. METHODS: We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital, Wuhan, China from January 1, 2015 to December 31, 2018, related recipients and corresponding donors. We collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and differences. RESULTS: A total of 1440 kidney transplants from DD were performed in our center. The total incidence of infective artery rupture in kidney transplants was about 0.76% (11/1440), and the annual incidence ranged from 0.25% to 1.03%. The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens, including 9 fungal strains (28.1%) and 23 bacterial strains (71.9%). There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients, of which, 10 recipients underwent graft loss, and one died of septic shock. The microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually, and the patients were discharged successfully without significant complications. CONCLUSION: Renal recipients with infections derived from DDs were at high risk of artery rupture, graft loss, or even death. Appropriate anti-infective treatment is essential to reduce the incidence of artery rupture and mortality.

Updated Genetic Testing of Primary Hyperoxaluria Type 1 in a Chinese Population: Results from a Single Center Study and a Systematic Review.

Primary hyperoxaluria type 1 (PH1) is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT. Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian, especially in Chinese. To update the genotypes of PH1 in the Chinese population, we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center, five of whom had delayed diagnosis and failed in kidney transplantation. Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT. Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations. Furthermore, a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees. To the best of our knowledge, 2 novel variants of AGXT, p.Gly41Trp and p.Leu33Met, were first reported. Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT) at a protein level. The systematic review revealed significant population heterogeneity in PH1. In conclusion, new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore, a genotype-phenotype correlation is found in PH1.

Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy.

The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients.In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic Tc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (Tmax), and time for peak activity to decrease by 50% (T1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of Tmax for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed.Quantitative Tc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of Tmax for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, Tmax) were statistically significantly associated with the conventional liver function parameters.Quantitative Tc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and Tmax values obtained from dynamic HBS show good correlation with conventional liver function parameters.

[Histopathologic analysis of 1500 renal allograft biopsies].

OBJECTIVE: To summarize the histopathological features of posttransplant complications for renal allografts and evaluate the biopsy values. METHODS: Between January 1997 and May 2010, a total of 1712 percutaneous renal allograft biopsies were performed in 1500 kidney transplants and diagnostic procedures for staining, classification and staging had been performed according to the Banff 1997 and 2005 Schema. RESULTS: There were 213 (14.2%) cases of acute T cell-mediated rejection post transplantation in 1500 kidney transplants. Meanwhile there were 36 (2.4%) cases of acute antibody-mediated rejection. Chronic T cell-mediated rejection and chronic antibody-mediated rejection were 251 (16.7%) cases and 45 (3.0%) cases, respectively. Acute CNI-nephrotoxicity and chronic CNI-nephrotoxicity were 106 (7.1%)cases and 251 (16.7%) cases, respectively. Relapsed or new nephropathy were 6 (0.4%) cases. Chronic CNI-nephrotoxicity is the most common cause of allograft dysfunction in the long survival recipients. CONCLUSION: Percutaneous renal allograft biopsy is valuable for the diagnosis of various posttransplantation complications.

[Histopathological study of 268 hepatic allograft biopsies].

OBJECTIVE: To observe the histopathological features of posttransplant complications for hepatic allografts and evaluate their biopsy values. METHODS: From January 1999 to May 2011, a total of 268 percutaneous hepatic allograft biopsies were conducted in 207 recipients and the diagnostic procedures for staining, classification and staging performed according to the Banff schema and Chinese Schema on hepatic allograft rejection. RESULTS: Among them, there were ischemia/reperfusion injury (n = 26, 9.7%), acute T cell-mediated rejection (n = 83, 31.0%), acute antibody-mediated rejection (n = 12, 4.5%), chronic posttransplantation rejection (n = 31, 11.6%), immunosuppressive-induced liver injury (n = 70, 26.1%) and recurrent diseases (n = 18, 6.7%). Acute T cell-mediated rejection and drug-induced liver injury were two most common causes of allograft dysfunctions. CONCLUSION: Percutaneous hepatic allograft biopsy is valuable for the diagnosis and evaluation of various posttransplantation complications.

Combined en bloc liver/pancreas transplantation in two different patients.

Combined en bloc liver/pancreas transplantation (CLPT) was used primarily in the treatment of otherwise non-resectable upper abdominal malignancy. In fact, a more appropriate indication is in patients with liver disease and insulin-dependent diabetes mellitus (IDDM). Here, we report on two successful cases of CLPT at our hospital. One was a patient with non-resectable advanced liver cancer. The recipient survived for 23 mo and finally died of recurrent tumor. The other was a patient with severe biliary complication after orthotopic liver transplantation and preoperative IDDM. We performed CLPT with a modified surgical technique of preserving the native pancreas. He is currently liver-disease- and insulin-free more than 27 mo post-transplant. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of CLPT and a modification of the surgical procedure.

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma.

AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced-stage hepatocellular carcinoma. METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups. RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 +/- 1.4 vs 7.1 +/- 1.1 microg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 +/- 183 vs 617 +/- 217 nka/L, P > 0.05; creatinine: 66 +/- 18 vs 71 +/- 19 micromol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 +/- 1.8 vs 5.9 +/- 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 +/- 2.1 vs 8.9 +/- 3.6 mmol/L, P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroid-maintenance group. CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an increase in long-term survival rate.

[The protective effects on allografts of adeno-associated heme-oxygenase-1 gene therapy against chronic rejection injury].

OBJECTIVE: To investigate the protective effects on allografts and the possible mechanism of adeno-associated heme-oxygenase-1 (AdHO-1) gene therapy against chronic rejection injury. METHODS: Ex vivo AdHO-1 gene therapy was performed in vascular and renal transplantation models. The structure and function, the expression of therapeutic genes and proteins, and the immune modulation were analyzed. RESULTS: AdHO-1 gene therapy protected renal transplant against chronic rejection, but the effect was not as remarkable as that in vascular transplant. The transfected empty vehicle aggravated chronic rejection damage in renal transplantation. AdHO-1 decreased the infiltration of macrophages and CD4(+) T cells. CONCLUSIONS: AdHO-1 gene therapy can lessen damage of chronic rejection in allografts. It plays roles by protecting transplants, down-regulating immune response and inducing immune deviation.

Impact of early biliary complications in liver transplantation in the presence or absence of a T-tube: a Chinese transplant centre experience.

BACKGROUND: Biliary complications continue to be an important determinant of the recipient's survival rate after orthotopic liver transplantation (OLT). The objective of this study was to evaluate the incidence of early biliary complications in OLT in the presence or absence of a T-tube. METHODS: This retrospective study, based on inpatient data, focused on the relationship between T-tube placement and early biliary complications of 84 patients after OLT, from November 2002 to June 2005. Patients were divided into two groups based on whether or not a T-tube was used following bile duct reconstruction: T-tube group (group I, n = 33); non-T-tube group (group II, n = 51). RESULTS: 45.2% of OLT recipients had a malignant neoplasm. There were no significant differences in the demographic characteristics or operation data between the two groups. Overall, early biliary tract complications developed in 19.0% (16/84) of patients. The rate of early biliary complications was 30.3% (10/33) and 11.8% (6/51) in groups I II, respectively (p = 0.035). Biliary complications which were directly caused by T-tube placement occurred in 12.1% (4/33) of patients in group I. Overall, the percentage of malignant neoplasms, chronic viral cirrhosis, fulminant liver failure and other primary disease recipients with early biliary complications were 6.2%, 37.5%, 43.8% and 12.5%, respectively. CONCLUSION: This study suggests that the use of a T-tube in Chinese patients undergoing OLT causes a higher incidence of early biliary complications. Most of the early biliary complications occurred in chronic viral cirrhosis and fulminant liver failure recipients.

[Expression of survivin in activated T cells and its significance].

AIM: To investigate the expression of survivin in activated T cells in vitro and in vivo. METHODS: Expressions of survivin and proliferating cell nuclear antigen (PCNA) in splenocytes stimulated with ConA or alloantigen were detected by immunohistochemical straining. Flow cytometry was used to analyze CD3, CD25 and survivin expressions and apoptosis of cultured splenocytes. Splenocytes from C57BL/6(H-2b) mice were infused into BALB/c(H-2d) nude mice to observe the survivin expression in vivo after alloantigen stimulation. RESULTS: Expressions of survivin and PCNA were detected in stimulated cells. Survivin+ cells were CD3+ T cells, and lymphoblasts could simultaneously express CD3, CD25 and survivin. However, not all survivin+ cells expressed CD25. Five days after culture, apoptotic rate of ConA-stimulated splenocytes increased markedly (P<0.001). From day 4 to 7 after infusion, the alloantigen-activated T cell infiltrating in livers of nude mice expressed survivin. CONCLUSION: Survivin can be detected in T cells after in vivo and in vitro stimulation, and thus may be used as a marker of activated T cells. Continuous expression of survivin in T cells needs continuous stimulation with alloantigen in vivo.

Eukaryotic expression vector of heme oxygenase-1 and its expression in endothelial cell.

BACKGROUND: Heme oxygenase-1 (HO-1)-mediated cytoprotection may inhibit or postpone the formation of graft arteriosclerosis. The aim of this study was to construct eukaryotic expression vector of HO-1 gene and express recombinant HO-1 in human endothelial cells of the umbilical vein to provide an important clue for chronic rejection study. METHODS: HO-1 gene was amplified from rat spleen with reverse transcription-polymerase chain reaction, and then cloned into eukaryotic expression vector pcDNA3 by means of recombinant gene technology. The recombinant plasmid pcDNA3-HO-1 was transfected into endothelial cells, and recombinant HO-1 was expressed in the endothelial cells under G418 selection. The expressed products were detected using indirect fluorescent staining and Western blot analysis. RESULTS: Restriction analysis indicated that the HO-1 gene was successfully inserted into the expression vector, and DNA sequencing verified that the reading frame of the recombinant vector was correct. Recombinant HO-1 was successfully expressed in endothelial cells and its molecular weight was about 32 kD. CONCLUSION: The successful construction of eukaryotic expression vector containing the HO-1 gene and the effective expression of recombinant HO-1 in endothelial cells has laid a foundation for further study on its biological functions.