UNASSIGNED: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a \"true\" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies.
UNASSIGNED: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min.
UNASSIGNED: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant.
UNASSIGNED: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease.
UNASSIGNED: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Simultaneous pancreas-kidney transplantation is an effective treatment option for end-stage renal disease with diabetes mellitus. Successful simultaneous pancreas-kidney transplantation allows achieving euglycemia, stabilizing existing microvascular complications and slowing their progression, improving the patient\'s quality of life, lipid and calcium-phosphorus metabolism, reducing the risks of cardiovascular events. Therefore, in view of the patient\'s severe general condition due to prolonged intoxication, hyperglycemia and other complications of chronic kidney disease, the earliest possible surgical treatment with minimization of the patient\'s stay on dialysis therapy is crucial to improve the outcome of transplantation.
Сочетанная трансплантация почки и поджелудочной железы является эффективным методом лечения терминальной стадии почечной недостаточности при сахарном диабете. Успешная трансплантация позволяет достичь эугликемии, стабилизировать имеющиеся микрососудистые осложнения и замедлить их прогрессирование, улучшить качество жизни пациента, показатели липидного, кальций-фосфорного обмена, уменьшить риски сердечно-сосудистых событий. Поэтому из-за тяжелого общего состояния пациента вследствие длительной интоксикации, гипергликемии и других осложнений хронической болезни почек для улучшения исхода трансплантации крайне важным является максимально раннее проведение оперативного лечения с минимизацией периода пребывания пациента на диализной терапии.

BACKGROUND: An increased midnight cortisol (MC) has been described in end-stage kidney disease (ESKD) and type 1 diabetes (T1D). Lower circulating levels of the cytokine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) have been found in T1D and ESKD and associated with cardiovascular (CV) events in the latter. We aimed to study MC and sTWEAK in simultaneous pancreas-kidney transplant (SPKT) recipients, and the association of these markers with CV risk factors and transplant outcomes.
METHODS: This was a retrospective cohort study including subjects with T1D who received a first SPKT between 2008 and 2020. MC and sTWEAK at baseline were correlated with CV risk factors and evolution 1 year after SPKT.
RESULTS: We included 29 subjects (58.6% women, mean age 43.5 ± 7.5 years, diabetes duration 31.9 ± 9.4 years). Systolic blood pressure (SBP) increased directly with MC quartiles, despite similar hypertension prevalence (p < 0.05). At 1 year, antihypertensive treatment was deintensified in those in lower MC quartiles (p < 0.05). Diabetic neuropathy prevalence decreased progressively in higher cortisol quartiles (p for trend = 0.005). Low MC was associated with delayed kidney graft function (p for trend = 0.044), and high sTWEAK with kidney graft rejection (p for trend = 0.018). In multivariate analyses, MC (standardized-β 0.505, p = 0.004) and age (standardized-β - 0.460, p = 0.040) were independently correlated with SBP, and MC was independently associated with the presence of diabetic neuropathy (OR 0.633, 95% CI 0.425-0.944, p = 0.025), adjusted for confounders.
CONCLUSIONS: In this exploratory study, lower MC was associated with a lower baseline SBP, an improvement of antihypertensive treatment 1 year after transplant, and a higher diabetic neuropathy prevalence in SPKT recipients.

Type 1 diabetes mellitus (T1DM) is one of the important causes of chronic kidney disease (CKD) and end-stage renal failure (ESRF). Even with the best available treatment options, management of T1DM poses significant challenges for cli nicians across the world, especially when associated with CKD and ESRF. Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM. Simultaneous pancreas-kidney transplant (SPK) is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications. However, limited availability of the organs for transplantation, the need for long-term immunosuppression to prevent rejection, peri- and post-operative complications of SPK, lack of resources and the expertise for the procedure in many centers, and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe. This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney-pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin-based probe, [18 F]FB(ePEG12)12-exendin-4. Following transplantation, PET imaging with [18 F]FB(ePEG12)12-exendin-4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [18 F]FB(ePEG12)12-exendin-4 whole-body maximum intensity projection and axial PET images. At 1 and 2 h after [18 F]FB(ePEG12)12-exendin-4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [18 F]FB(ePEG12)12-exendin-4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta-cell mass following simultaneous kidney-pancreas transplantation.

Simultaneous pancreas-kidney transplantation (SPK) is an option for patients with type 1 diabetes (T1D) and kidney failure but can be associated with a high complication rate. Here we describe our 10-year experience since the launch of the SPK program.
This retrospective study included consecutive patients with T1D receiving SPK from March 14, 2010 to March 14, 2020 at Helsinki University Hospital. Portocaval anastomosis (i.e., systemic venous drainage) and enteric exocrine drainage were used. A specific team was trained for both pancreas retrieval and transplantation, postoperative care was standardized to include somatostatin analogues, antimicrobial treatment, and preoperatively initiated chemothrombopropylaxis. During program maturation donor criteria were expanded and logistical processes improved to minimize cold ischemia time. Clinical data were collected from a nationwide transplantation registry and patient records.
A total of 166 SPKs were performed (median 2 per year in the first 3 years, 17.5 per year for the following 4 years, and 23 per year for the past 3 years). Seven patients (4.1%) died with a functioning graft with a median 43 months follow-up. One-year pancreas graft survival was 97.0%, 3-year pancreas graft survival was 96.1% and 5-year was 96.1%. Mean HbA1c was 36 mmol/mol (SD 5.57) and creatinine was 107 μmol/L (SD 34.69) at 1-year after transplantation. All kidney grafts were functioning at the end of follow-up. Complications required re-laparotomy in 39 (23%) patients, mostly due to a pancreas graft related problem (N = 28). No pancreas or kidney graft failure from thrombosis occurred.
A planned, step-wise development of an SPK program offers a safe and effective treatment for patients with T1D and kidney failure.

Pancreas transplant alone (PTA) recipients are more affected by pancreas graft thrombosis, and graft loss compared to simultaneous pancreas-kidney (SPK) recipients. The pathophysiology is unknown, but an increased immune response has been suggested in the PTA recipients. In this observational study, we compared perioperative thromboinflammation between PTA (n=32) and SPK (n=35) recipients, and between PTA recipients with (n=14) versus without (n=18) early graft thrombosis.
We measured C-reactive protein (CRP), plasma markers of activated coagulation and complement, and cytokines preoperatively and daily during the first postoperative week.
Preoperatively, coagulation and complement activation markers were comparable between PTA and SPK recipients, while cytokine concentrations were higher in SPK recipients (TNF, IL-8, IP-10, MCP-1, MIP-1α; all p<0.05). On the first postoperative day, PTA recipients had higher coagulation activation, measured as thrombin-antithrombin complex (TAT), than SPK recipients (p=0.008). In the first postoperative week, PTA recipients showed higher relative cytokine release (IL-6, IL-8, G-CSF, IP-10, MCP-1, and MIP-1α; all p<0.05) while SPK recipients showed higher absolute cytokine concentrations (TNF, IL-1ra, IL-8, MIP-1α, and IL-4; all p<0.05). PTA and SPK recipients showed similar terminal complement complex (TCC, sC5b-9) activation. On the first postoperative day, TCC (OR 1.2 [95% CI 1.0-1.5] for 0.1 CAU/ml increase, p=0.02) and CRP (OR 1.2 [95% CI 1.0-1.3] for 10 mg/L increase, p=0.04) were associated with an increased risk of early graft thrombosis. TCC was specific for graft thrombosis, while CRP increased with several complications. PTA recipients with compared to those without graft thrombosis had higher TCC pre- (p=0.04) and postoperatively (p=0.03).
The relative increase in postoperative thromboinflammatory response was more pronounced in PTA recipients. Complement activation was associated with an increased risk of graft thrombosis. This study indicates that innate immune activation rather than elevated levels may affect early postoperative pancreas graft thrombosis.
https://clinicaltrials.gov/ct2/show/NCT01957696, identifier NCT01957696.

UNASSIGNED: Biopsy of a transplanted pancreas is sometimes necessary in patients who have undergone simultaneous pancreas-kidney (SPK) transplantation and have elevated serum lipase and amylase concentrations. However, the risks associated with pancreatic graft biopsy are high, and the best biopsy technique for different location of pancreatic graft remains unclear.
UNASSIGNED: Depending on the anatomical location of the transplanted pancreas, percutaneous computed tomography (CT) combined with color Doppler-guided puncture biopsy or laparoscopic biopsy was used to obtain samples of transplanted pancreatic tissue that were shallow and deep, respectively.
UNASSIGNED: After SPK transplantation, 4 patients developed abnormal serum lipase and amylase concentrations and underwent pancreas graft biopsy, 1 patient underwent percutaneous CT combined with color Doppler-guided puncture biopsy, 2 patients underwent laparoscopic wedge biopsy, and 1 patient underwent laparoscopic and puncture biopsy. All biopsies were performed successfully, with no intra- or postoperative complications (e.g., bleeding, pancreatic leakage, intestinal leakage). Biopsy sampling was effective in 3 patients, including 1 case of acute pancreatic rejection, 1 case of pancreatitis, and 1 case of pancreatic plasmablastic lymphoma. Biopsy failed to retrieve samples in 1 patient with a deep pancreatic graft who underwent laparoscopic wedge biopsy.
UNASSIGNED: Pancreas graft biopsy is safe and feasible after SPK transplantation. In addition to the two biopsy methods mentioned, other methods can also be used. Different biopsy strategies should be formulated according to the anatomical location of the transplanted pancreas.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) has demonstrated favorable impact on the progression of chronic complications in type-1 diabetes (T1D) and terminal chronic kidney disease (CKD). However, some CKD mineral and bone disorders (CKD-MBD) may persist, even after transplantation. There are only a few studies addressing the long-term progression of bone mineral density (BMD) in these patients. Our aim was to assess baseline BMD and long-term progression and consequences in patients with T1D undergoing SPKT.
METHODS: A retrospective cohort included patients undergoing SPKT in our tertiary center between 2000 and 2017. BMD progression was assessed on dual X-ray absorptiometry (DXA). Only patients with baseline data and a minimum follow-up of 2 years were included.
RESULTS: Seventy-three patients were included, 53.4% male, with a median age at SPKT of 35 years (interquartile range [IQR] 31; 39). At transplantation, the median T-scores for the lumbar spine (LS) and femoral neck (FN) were -1.6 (IQR -2.6; -1.1) and --2.1 (IQR -2.7; -1.6), respectively. Seventy-five percent of patients presented low BMD (osteopenia or osteoporosis) in the LS and 90% in the FN, with 33% osteoporosis in the LS and 36% in the FN. On multivariate analysis, male gender (odds ratio [OR] 10.82, 95% confidence interval (CI) 2.88-40.70) and low body-mass index (BMI) (OR 0.73, 95% CI 0.55-0.97) were significantly associated with lumbar but not femoral osteoporosis. At long-term follow-up, BMD significantly improved in the LS (ΔT-score +0.41, P<0.001) and FN (ΔT-score +0.29, P=0.01), at a median 4 years after SPKT. Twelve (16.4%) and 9 (12.3%) patients showed persistent FN and LS osteoporosis, respectively. Multivariate linear regression showed that high BMI was predictive of improvement in BMD.
CONCLUSIONS: This study demonstrated severe skeletal fragility in T1D patients with terminal CKD undergoing SPKT, more than a quarter of whom showed osteoporosis. The significant improvement in BMD may result from metabolic correction by SPKT and from physiological skeleton mineralization, which continues in this age group. BMD progression was positively associated with BMI, due to improved nutritional balance after transplantation.