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Patients with end-stage renal disease are 10 to 20 times more at risk of cardiovascular death than the general population. Traditional cardiovascular risk factors are not able to explain the increase in the onset of cardiovascular diseases in dialysis patients. Some of the most important non traditional risk factors in uremic patients are: the inflammatory state of the patients, cytokines and growth factors, hyperhomocysteinemia, the presence of alterations of the calcium phosphorous product which can already be in progress when the glomerular filtration rate decreases to less than 60 mL/min. Clinically, these alterations cause vascular calcifications, calcifications of the heart valves and calcific uremic arteriolopathy or calciphylaxis. The pathogenesis of vascular calcification is complex and cannot be assigned to a simple, passive process: in fact, it includes factors which promote or inhibit calcification. In turn, these pathologic conditions have been found to be highly predictive of general and cardiovascular death. Given the serious clinical consequences that vascular calcifications can cause, it is necessary to carry out an early mapping of the traditional and non traditional risk factors of uremic patients as it seems that therapeutic interventions aimed at reducing or inverting the calcification process can improve the outcome of patients, above all when they are started quickly.

Background: Understanding the level of patients’ satisfaction with treatment and its determinants have the potential to impact therapeutic management and clinical outcome in chronic conditions such as chronic obstructive pulmonary disease (COPD). Methods: A national, multicenter, longitudinal, observational study of COPD from 20 Italian pulmonary centers to explore patients’ satisfaction to treatment [assessed by the Treatment Satisfaction Questionnaire, 9 items (TSQM-9)] and association with clinical parameters [including dyspnea score, COPD Assessment Test (CAT) score, exacerbation rate], adherence to treatment [Morisky Medication-Taking Adherence Scale (MMAS-4)], illness perception [evaluated by Brief Illness Perception Questionnaire (B-IPQ)] in a 1-year follow up. Results: A total of 401 COPD patients were enrolled [69.4% group B Global Initiative for COPD (GOLD), considering 366 patients with available GOLD 2017 classification at enrollment]. At enrollment, satisfaction with treatment was moderate, being TSQM-9 mean scores for effectiveness 64.2 [95% confidence interval (CI) 62.5–65.9], for convenience 75.8 (95% CI 74.2–77.3), and for global satisfaction 65.7 (95% CI 64.0–67.4). Global satisfaction was negatively associated with disease perception (β = −0.4709, p Conclusions: The results of this real-life study showed that the patients’ satisfaction with treatments is only moderate in COPD. A high grade of patients’ satisfaction is associated mainly with a low perception of the disease, high adherence to treatment and lower level of dyspnea. Trial Registration: Clinicaltrials.gov identifier: NCT02689492 The reviews of this paper are available via the supplemental material section.

Background/Aims: Vitamin D deficiency is associated with endothelial dysfunction in uremic patients, possibly by the impairment in the number and function of endothelial progenitor cells (EPCs). In 89 hemodialysis patients, we investigated the factors associated with the number of circulating EPCs (CD34+/CD133+/KDR+ and CD34+/CD133–/KDR+ cells), the presence of VDR and the determinants of VDR expression on EPCs, in particular in calcitriol therapy. Methods: EPC counts, percentages of VDR-positive EPCs and VDR expression were assessed by flow cytometry. Cells isolated from a subgroup of patients were cultured to analyze colony-forming units, specific markers expression and a capillary-like structure formation. Results/Conclusions: Our study demonstrates the presence of VDR on EPCs. In our dialysis patients, the parameters studied on both CD34+/CD133+/KDR+ and CD34+/CD133–/KDR+ cells, in particular VDR expression, seem to be influenced by uremia-related factors, including anemia, inflammation, diabetes, 25(OH)D serum levels and calcitriol therapy.

Background/Aims: DNA fragmentation is one of the typical features of apoptosis, frequently induced by oxidative stress. Increased oxidative stress is known to be related to several pathological processes. In this study, we assessed oxidative damage in the early follow-up period after kidney transplantation measuring DNA oxidation and fragmentation of mononuclear cells and the circulating levels of inflammatory cytokines. Methods: Blood samples from 30 kidney transplant recipients were collected before transplantation and after 2 days, 1 month and 6 months. Oxidative DNA fragmentation was measured by Comet Assay, whereas DNA oxidation was evaluated measuring 8-OHdG leukocyte levels. Serum IL-1β, IL-4, IL-6, IL-8, IL-10, IFN-γ and TNF-α were assayed using a multiplex ELISA analysis. Results: At 6 months after transplantation, a significant reduction in DNA fragmentation and IL-6 plasma levels was observed; DNA oxidation was higher in patients with a worse outcome, with delayed graft function and low nutritional status. We also found a correlation of IL-6 and IL-10 levels with DNA fragmentation and of IL-10 levels with DNA oxidation. Conclusion: Low levels of oxidation and apoptosis at 6 months after transplantation correlate with a better recovery of renal function in kidney allografts. The measurement of cytokine levels confirmed a reduction of inflammatory parameters within 6 months of follow-up.

There is increasing proof that organ preserva- tion by machine perfusion is able to limit ischemia/ reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation.Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion (n = 6) or cold storage (n = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematologi- cal and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5'- triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation. The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation com- pared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys. The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage. Key Words: Renal transplantation—Kidney function—Organ preservation—Machine perfusion—Ischemia/reperfusion injury—Delayed graft function.

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient.

Chronic allograft nephropathy (CAN) is characterized by progressive renal dysfunction leading in many cases to graft loss. The pathogenesis of CAN involves both immune and nonimmune factors. Concerning immune factors, one of the most remarkable predictors of CAN is acute rejection, which is associated with a worse prognosis if there are multiple episodes or when late onset occurs. Delayed graft function is also a major risk factor for CAN because of a correlation between late restoration of renal function after transplantation and long-term decreased graft survival. High creatinine levels at 6 months and 1 year after transplantation, proteinuria, viral infections, and cardiovascular risk factors are additional significant parameters for the development of CAN. Recent findings suggest that a high renal segmental arterial resistance index measured by Doppler ultrasonography in intrarenal vessels is associated with poor allograft function. Moreover, the study of patient genetic profile represents a new approach to identify predictive factors for CAN.

Chronic allograft nephropathy (CAN) is an anatomical and clinical alteration, characterized by proteinuria, hypertension and a progressive decline in kidney function, which begins at variable times (months, years) and can lead to the loss of the transplanted organ. CAN pathogenesis, which remains to be fully clarified, involves both immunological (early acute rejection, hyperimmunization, HLA-mismatches between donor and recipient, suboptimal immunosuppression, etc) and non-immunological factors (ischemia/reperfusion injury, reduced nephron mass, age differences between donor and recipient, dialysis time, hypertension, dislipidemia, proteinuria, etc). The possible prevention strategies for CAN consist of procedures aimed at the reduction of some potential risk factors: optimization of the conditions for organ explantation, diminution of ischemia/reperfusion injury, aggressive pharmacological treatment of acute rejection episodes, routine utilization of anti-hypertensive and hypolipidemic agents, and appropriate and rational immunosuppressive regimen. Moreover, some categories of immunosuppressive drugs, such as calcineurin inhibitors, can have a nephrotoxic effect, often regardless of therapeutic dosage. The introduction in clinical practice of novel immunosuppressive drugs with no nephrotoxicity, like mycophenolate mofetil and rapamycin, makes therapeutical strategies able to reduce the incidence of CAN feasible.