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Background: Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet., Methods: We performed metabolomic and proteomic analyses on serum samples from 19 patients with advanced CKD (aCKD) and 27 healthy volunteers. The metabolites were quantified using four different approaches, based on their properties. Proteomic analysis was performed after depletion of seven abundant serum proteins (Albumin, IgG, antitrypsin, IgA, transferrin, haptoglobin, and fibrinogen). Integrative analysis was performed using MetaboAnalyst 4.0 and STRING 11.0 software to identify the dysregulated pathways and biomarkers., Results: A total of 135 metabolites and 75 proteins were differentially expressed in aCKD patients, compared to the controls. Pathway enrichment analysis showed significant alterations in the innate immune system pathways, including complement, coagulation, and neutrophil degranulation, along with disrupted linoleic acid and cholesterol metabolism. Additionally, certain key metabolites and proteins were altered in aCKD patients, such as glutathione peroxidase 3, carnitine, homocitrulline, 3-methylhistidine, and several amino acids and derivatives., Conclusions: Our findings reveal significant dysregulation of the serum metabolome and proteome in aCKD, particularly in those pathways associated with endothelial dysfunction and CVD. These results suggest that CVD prevention in CKD may benefit from a multifaceted approach, including dietary interventions such as the Mediterranean diet.

Background: Information about the impact of diabetic neuropathy (DN) on outcomes after pancreas transplantation (PT) is scarce. We assessed the independent relationship between DN markers with both graft survival and incident cardiovascular disease (CVD) after transplantation., Methods: A cohort study in individuals with type 1 diabetes and end-stage kidney disease who underwent PT between 1999 and 2015 was conducted. DN was assessed with vibration perception thresholds (VPTs) and orthostatic hypotension (pre-PT and 6 mo, 2-3, 5-6, and 8-10 y after transplantation). Pretransplantation and posttransplantation DN markers were related with graft failure/dysfunction and incident CVD during follow-up., Results: We included 187 participants (70% men, age 39.9 ± 7.1 y, diabetes duration 27.1 y), with a median follow-up of 11.3 y. Abnormal VPTs (≥25 V) were observed in 53%. After transplantation, VPTs improved (22.4 ± 8.4 pretransplant versus 16.1 ± 6.1 V at 8-10 y post-PT; P < 0.001); additionally, the prevalence of abnormal VPTs decreased (53% pretransplant versus 24.4% at 8-10 y; P < 0.001). After adjusting for age, sex, diabetes duration, blood pressure, body mass index, and previous CVD, pretransplant VPTs ≥25 V were independently associated with pancreas graft failure/dysfunction (hazard ratio [HR], 2.01 [1.01-4.00]) and incident CVD (HR, 2.57 [1.17-5.64]). Furthermore, persistent abnormal VPTs after 6 mo posttransplantation were associated with the worst outcomes (HR, 2.80 [1.25-6.23] and HR, 3.19 [1.14-8.96], for graft failure/dysfunction and incident CVD, respectively)., Conclusions: In individuals with type 1 diabetes and end-stage kidney disease, PT was associated with an improvement of VPTs. This simple and widely available DN study was independently associated with pancreas graft function and CVD posttransplantation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Objectives: Graft outcomes in pancreas transplantation have improved in recent decades, but data are mainly derived from registries or prospective single-centre studies. This large epidemiological study was undertaken to investigate the impact of clinical and demographic factors on graft and patient survival in pancreas transplant recipients in Spain, and to provide robust, country-wide, practice-based data to complement registry findings., Patients and Methods: We conducted a retrospective, longitudinal, epidemiological study to assess risk factors impacting patient and graft survival in pancreas transplant recipients in eight centres in Spain. All patients transplanted between 1 January 2008 and 31 December 2012 were included; data were collected until 31 December 2015. The Kaplan-Meier method was used for all time-to-event analyses, including patient survival, graft survival, acute rejection, and BPAR. For graft survival analysis, in cases of death with functioning graft, patients were censored without any event on the date of death. For acute rejection and BPAR, patients were censored without any event on the date of death or graft loss. Univariable and multivariable analyses (Cox proportional hazards model) were conducted to assess the association between baseline clinical and demographic characteristics and patient/graft survival., Results: Data were included for 241 (80.1%) simultaneous pancreas-kidney transplants, 56 (18.6%) pancreas-after-kidney transplants and 4 (1.3%) pancreas transplants alone. Mean±standard deviation time from diagnosis until transplantation was 26.1±7.5 years. Nineteen patients died, mainly due to infections (n=10); the remaining 282 patients (93.7%) survived from transplantation until the end of the study. Among 55 patients (18.3%) with pancreas graft loss, the main reasons were vascular thrombosis (n=19), chronic rejection (n=10), acute rejection (n=6) and death with a functioning graft (n=5). The overall rate of vascular-related death was 1.3% at 5 years post transplant. Univariable analysis showed that patient age and weight, donor age, previous kidney transplantation, previous cardiovascular events and need for insulin more than 48h post transplantation were significantly associated with pancreas graft survival. Of these, in multivariable analyses pancreas graft survival was inferior in patients who had received a previous kidney transplant prior to pancreas transplantation (log-rank test, p=0.0002). Glucose metabolism, renal function and cardiovascular risk factors were generally stable following transplantation., Conclusions: The results of this multicentre study highlight the excellent patient and graft outcomes following pancreas transplantation, with a notably low incidence of cardiovascular events., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Of the available risk predictors for this population, the Steno Type 1 Risk Engine (STENO T1) is the only one that includes kidney function as a risk factor, which is a well-described independent risk factor for cardiovascular disease., Methods: We explore how simultaneous pancreas-kidney transplantation (SPKT) modifies the predicted cardiovascular risk by the STENO T1 through a retrospective study including recipients of a first SPKT between 2000 and 2016., Results: Two hundred sixty-eight SPKT recipients with a mean age of 40 y old and a median follow-up of 10 y were included. Before transplantation, the expected incidence of cardiovascular events (CVEs) at 5 and 10 y according to STENO T1 would have been 31% and 50%, respectively, contrasting with an actual incidence of 9.3% and 16% for the same timepoints, respectively (P < 0.05). These differences were attenuated when STENO T1 was recalculated assuming 12th-mo glomerular filtration rate (at 5 and 10 y predicted CVE incidence was 10.5% and 19.4%, respectively). Early pancreas graft failure (hazard ratio [HR] 3.00, 95% confidence interval [CI], 1.14-7.88; P = 0.02) was an independent risk factor for post-SPKT CVE, alongside kidney graft failure (HR 2.90, 95% CI, 1.53-5.48; P = 0.001), and diabetes duration (HR 1.04, 95% CI, 1.00-1.09, P = 0.04)., Conclusions: SPKT decreases in more than two-thirds of the predicted cardiovascular risk by the STENO T1. A functioning pancreas graft further reduces CVE risk, independently of kidney graft function., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To evaluate the changes in cardiovascular risk factors (CVRFs) and cardiovascular disease (CVD) in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD) who were candidates for kidney-pancreas transplantation (KPTx) from 1999 to 2017., Methods: Patients with T1D referred for KPTx evaluation were included. The cohort was divided into five groups according to the year of evaluation (1999-2002, 2003-2006, 2007-2010, 2011-2014 and 2015-2017). The control of CVRFs and the prevalence of prior CVD were evaluated., Results: We evaluated 360 patients (64.4% men, age 38.9 ± 7.1 years). LDL-cholesterol <100 mg/dl increased from 22.7% to 76.9% (1999-2002 vs. 2015-2017; p < 0.001), as did the use of statins (from 24.7% to 74.5%; p < 0.001). Systolic blood pressure decreased from 138.8 ± 27.6 to 125.1 ± 27.9 mmHg (p = 0.001) and current smokers from 48% to 25% (p = 0.018). Intensive insulin treatment increased from 34.4% to 93.6% (p < 0.001). Diabetes duration before the initiation of renal replacement therapy increased from 23 ± 5.5 to 26.9 ± 8.9 years (p = 0.001). Overall, 30.3% had previous CVD, without significant changes over time (p = 0.699), albeit patients were older and had longer diabetes duration., Conclusions: Patients with T1D and ESRD referred for KPTx have better control of CVRFs over time, which might lead to a decrease in cardiovascular events., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)