Influence of dialysis duration on outcomes of simultaneous pancreas-kidney transplant.

OBJECTIVE: The objective of this study was to assess how pre-transplant dialysis duration affects transplant outcomes after simultaneous pancreas-kidney transplant (SPK) in patients with type 1 diabetes mellitus (T1DM). METHODS: Data of 6887 T1DM patients who underwent SPK transplantation between 2008 and 2018 were obtained from the Scientific Registry of Transplant Recipients database. According to pre-transplant dialysis duration, the patients were divided into the preemptive SPK, 0-2 years, 2-5 years, and >5 years dialysis groups. Kaplan-Meier survival analysis was performed to compare patient and graft survival among the groups. Univariate and multivariate Cox regression analyses were used to identify predictors of transplant outcomes. RESULTS: The mean follow-up period was 56.7 ± 34.7 months. Compared with no dialysis or preemptive SPK, dialysis for 0-2 years was not significantly associated with patient or kidney graft survival, while long-term dialysis of 2-5 years and >5 years was significantly associated with increased risk of death and kidney graft failure. However, the duration of dialysis was not associated with pancreas graft survival. CONCLUSION: Long-term dialysis duration before SPK transplant is an independent predictor of patient death and kidney graft failure in T1DM patients.

Outcomes of liver-kidney transplantation in patients with primary hyperoxaluria: an analysis of the scientific registry of transplant recipients database.

BACKGROUND: Primary hyperoxaluria (PH) is an inherited disease lacking of hepatic oxalic acid metabolic enzymes which could lead to irreverisible renal damage. Currently, liver-kidney transplantation is a curative but highly invasive therapy used to treat patients with PH. However, limited studies have focused on combined liver-kidney transplantation (CLKT) and sequential liver and kidney transplantation (SLKT) in patients with PH. METHODS: The present study included 201 patients with PH who received both liver and kidney transplants and who were listed on the Scientific Registry of Transplant Recipients from 1987 to 2018. According to the liver-kidney transplant procedure, patients were separated into a CLKT group and a SLKT group. Patient demographics and transplant outcomes were assessed in each group. RESULTS: Compared with the SLKT group, The CLKT group got a worse pretransplant dialysis condition in both the proportion of patients under pretransplant dialysis (p = 0.048) and the duration of the pretransplant dialysis (p < 0.001). The SLKT group got higher human leukocyte antigen mismatch score of kidney donor (p < 0.001) and liver donor (p = 0.003). The CLKT group utilized higher proportion (98.9%) of organs from a single deceased donor, while the SLKT group utilized 75.0% of organs from deceased liver donors and only 35.0% of organs from deceased kidney donors (p < 0.001). Kidney function measured by serum creatinine concentration before liver transplantation (LT) or CLKT was similar (p = 0.305) between groups. Patient survival was not significantly different between the two groups (p = 0.717) and liver (p = 0.685) and kidney (p = 0.464) graft outcomes were comparable between the two groups. CONCLUSIONS: SLKT seems to be an alternative option with strict condition for CLKT, further exploration about the SLKT is still required.

The effect of PINK1/Parkin pathway on glucose homeostasis imbalance induced by tacrolimus in mouse livers.

Treatment using the immunosuppressive drug tacrolimus (TAC) is related to new-onset diabetes after transplantation (NODAT). Previous studies focused mainly on islet ß cells in the diabetogenic effect of TAC. Herein, we revealed that NODAT was probably induced by TAC via hepatic insulin resistance. After daily injection of mice with TAC, a glucose metabolism disorder was induced. In addition, TAC decreased the mRNA and protein levels of insulin receptor substrate 2 (IRS2), glucose transporter type 2 (GLUT2), and the phosphorylation of protein kinase B beta (pAKT2), which indicated impaired hepatic insulin signaling. Furthermore, the PTEN-induced novel kinase 1(PINK1)/Parkin pathway was shown to have a key role in the TAC-induced imbalance of hepatic glucose homeostasis. Mechanistic investigations in human hepatic cell lines revealed that TAC stimulated PINK1/Parkin expression and inhibited the expression of insulin signaling related molecules (e.g., IRS2, GLUT2 and pAKT2). Knockdown of hepatic PINK1 regulated downstream molecules of the PINK1/Parkin pathway (GLUT2 and IRS2), which reversed TAC-induced insulin resistance. Thus, in the liver, PINK1/Parkin signaling plays an important role in the TAC-induced imbalance of glucose homeostasis. TAC-induced diabetes might be prevented using Targeted treatment.

Preventive use of low molecular weight heparin in portal vein system thrombosis after splenectomy without portal hypertension.

Background/aim: Portal vein system thrombosis (PVST) is a serious complication after splenectomy, and many researches focus on how to prevent PVST these years. The current study aimed to explore an effectively method to prevent PVST occur after splenectomy. Methods: Records of patients performed with splenectomy from January 2018 to December 2020 were reviewed. Clinical parameters, including patient history, physical examination, and the results of laboratory investigations, were analyzed. Results: One hundred and eighty patients (127 females) were included. Twenty-four patients were confirmed PVST by Color Doppler ultrasonography and CTA (thrombus group) and the others were not (non-thrombus group). One hundred and twenty patients were performed with laparoscopic splenectomy (LS) and 53 were open splenectomy (OS). Seventeen PVST were found in LS patients and 7 PVST were found in OS patients (P = 0.974). The average time of thrombosis was 4.48 ± 2.9 days after operation. The proportion of postoperative preventive use of low molecular weight heparin (LMWH) in non-thrombus group was higher than that in thrombus group (27.6% vs. 8.3%, P = 0.045). Compared with the non-thrombus group, the thrombus group showed significantly higher serum alanine transaminase (ALT) and aspartate transaminase (AST) 7 days after splenectomy (79.67 ± 39.1 U/L vs. 29.34 ± 2.5 U/L, P = 0.001; 192.4 ± 145.8 U/L vs. 30.54 ± 3.0 U/L, P < 0.001). Conclusion: Laparoscopic splenectomy does not seem to increase the occurrence of PVST in patients without portal hypertension. Early postoperative preventive use of LMWH after splenectomy may prevent the formation of PVST.

Pancreas preservation time as a predictor of prolonged hospital stay after pancreas transplantation.

OBJECTIVE: Length of hospital stay is a sensitive indicator of short-term prognosis. In this retrospective study, we investigated how pancreas preservation time affects length of hospital stay after pancreas transplantation. METHODS: Patients receiving pancreas transplantation (1998.7-2018.6) were identified from the Scientific Registry of Transplant Recipients database and grouped according to pancreas preservation time. We analyzed the relationship of pancreas preservation time with graft and patient survival and prolonged length of stay (PLOS; i.e., hospital stay ≥20 days). RESULTS: We included 18,099 pancreas transplants in the survival analysis. Pancreas preservation time >20 hours had a significantly higher risk of graft failure than 8 to 12 hours. Pancreas preservation time was not significantly associated with patient survival. We included 17,567 pancreas transplants in the analysis for PLOS. Compared with 8 to 12 hours, pancreas preservation time >12 hours had a significantly higher PLOS risk, which increased with increased pancreas preservation time. In simultaneous pancreas-kidney transplantation, we also found that pancreas preservation time was positively associated with PLOS risk with pancreas preservation time >12 hours. CONCLUSION: Pancreas preservation time is a sensitive predictor of PLOS. Transplant centers should minimize pancreas preservation time to optimize patient outcomes.

Influence of duration of type 1 diabetes on long-term pancreatic transplant outcomes.

BACKGROUND: There are no multicenter studies on the influence of diabetes duration on pancreatic transplant outcomes. Our study aimed to determine how type 1 diabetes duration influenced survival of pancreatic grafts. METHODS: The data of 8,139 patients who received pancreas transplants during 2006-2015 were extracted from the Scientific Registry of Transplant Recipients database. Patients were separated into two groups according to duration of diabetes: S group (diabetes ≤20 years) and L group (>20 years). RESULTS: Compared to S group, L group were older and prone to be male, to have higher body mass index, to receive pancreas after kidney transplantation (PAK), and to be White. Patient survival was not significantly different between the two groups, but pancreatic survival was better in the L group (hazard ratio 0.88; P = 0.012). Pancreatic survival of L group was better than S group in pancreas transplant alone and simultaneous pancreas-kidney transplantation (SPK). Graft survival was not significant different between the two groups in PAK. Diabetes duration was an independent predictor of graft survival in SPK patients (hazard ratio 0.86; P = 0.012). CONCLUSIONS: Diabetes duration has no influence on patient survival. However, long duration of type 1 diabetes mellitus appears to be protective against pancreatic graft loss.

Survival rates after liver transplantation using hypertensive donor grafts: an analysis of the Scientific Registry of Transplant Recipients database.

BACKGROUND: The use of grafts from donors with hypertension (HTN) in liver transplantation has grown rapidly recently, but whether HTN donors affect post-liver transplantation survival is unclear. METHODS: We used data from the Scientific Registry of Transplant Recipients database (2004-2008), and evaluated differences in baseline characteristics and outcomes between recipients of grafts from HTN and non-HTN donors. Kaplan-Meier and multivariate Cox regression models were used in assessing patient survival. RESULTS: We identified 8,411 recipients of HTN donor grafts (33.2%) and 16,891 (66.8%) recipients of non-HTN donor grafts. Graft and patient survival rates were significantly lower in recipients of HTN donor grafts versus non-HTN donor grafts (1-year, 3-year, and 5-year graft survival rates of 75%, 64%, 50% vs. 80%, 72%, 62% [P < 0.001], respectively, and patient survival rates of 79%, 69%, 56% vs. 83%, 75%, 65% [P < 0.001], respectively). A history of HTN >5 years was also associated with lower rates of graft and patient survival (P < 0.001). A HTN donor was independently associated with a higher risk of graft loss (hazard ratio 1.10, 95% confidence interval 1.01-1.18). CONCLUSION: The present study shows that graft and patient survivals were lower in recipients of hypertensive donor grafts, and highlights the importance of appropriately screening donors for HTN.

Influence of donor-recipient sex mismatch on long-term survival of pancreatic grafts.

To assess the role of sex mismatch on graft survival after pancreas transplantation. We evaluated 24,195 pancreas-transplant recipients reported in the Scientific Registry of Transplant Recipients over a 25-year period. Pancreatic graft survival (PGS) was analyzed according to donor-recipient sex pairing using Kaplan-Meier estimations. Hazard ratios were estimated using Cox proportional hazard models. A total of 14,187 male and 10,008 female recipients were included in final analyses. Mean follow-up was 8.3 ± 5.7 years. In multivariate analyses, neither recipient sex nor donor sex was associated with pancreatic graft failure (PGF), but donor-recipient sex mismatch (regardless of recipient sex) was an independent predictor of PGS (HR, 1.09; 95% CI, 1.04-1.14; p < 0.001). Compared with M → M sex-matched recipients in univariate analyses, M → F and F → M sex mismatches were associated with an increased risk of PGF. Adjustment for significant recipient and donor factors eliminated the association between F → M sex mismatch and PGF (HR, 1.02; 95% CI, 0.93-1.10; p = 0.752), but not M → F (1.09; 1.02-1.17; 0.020). Stratified analyses suggested that the negative effect of donor-recipient sex mismatch could be neutralized in older patients. These findings suggest that donor-recipient sex pairing should be taken into consideration in organ-allocation strategies.