The Contribution of Muscle Innate Immunity to Uremic Cachexia.

Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, "sterile" muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering "sterile" tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1ß and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.

[Dialysis withdrawal and shared end-of-life management between nephrology and palliative care: our three-year experience].

Most dialysis patients with end-stage kidney disease (ESKD) lack access to palliative care services. According to the data of the Dialysis Outcomes and Practice Study (DOPPS), Italy when compared to other countries included in the study, had the lowest rates of dialysis discontinuation. Indeed, there is a growing interest in the implementation of international and national programs for the co-management between nephrology and palliative care in end-of-life decision-making for patients with ESKD. On behalf of this, since 2017, we started in the nephrology outpatient clinic and hemodialysis facilities of the Provincia Autonoma of Trento a shared program between Nephrology and Palliative Care Units to improve the end-of-life quality of care in ESKD patients in conservative and dialytic therapy. Methods:A retrospective analysis, from the 1st of January 2019 to 31st December 2021, of dialysis withdrawal in a cohort of patients undergoing hemodialysis and peritoneal dialysis. Results:Dialysis withdrawal and subsequent death, according to the integrated protocol with the Palliative Care resources, were 24 in 2019, 20 in 2020, and 28 in 2021. The mean age was 75 years in 2019, 78 years in 2020, and in 2021. Most of the patients were male. Dialysis discontinuation was higher in chronic dialysis patients (80% in 2019 and 2020, and 79% in 2021), and considering the annual rates of death of all the dialysis patients, those who died because of dialysis withdrawal were 38% in 2019, 31% in 2020 and 40% in 2021. Survival after dialysis withdrawal was in most of the cases less than 7 days; only few patients lived more than 30 days. Furthermore, the data, in the 3 years considered, showed a reduction of hospitalization and an increase of the rate of death at home. Conclusions:As described in the present study, strategies to expand palliative care by a shared protocol among nephrology and palliative care staff improved the quality of care in the end of life and reduced the hospitalization rates of admission of patients after dialysis withdrawal.

How to Overcome Anabolic Resistance in Dialysis-Treated Patients?

A current hypothesis is that dialysis-treated patients are "anabolic resistant" i. e., their muscle protein synthesis (MPS) response to anabolic stimuli is blunted, an effect which leads to muscle wasting and poor physical performance in aging and in several chronic diseases. The importance of maintaining muscle mass and MPS is often neglected in dialysis-treated patients; better than to describe mechanisms leading to energy-protein wasting, the aim of this narrative review is to suggest possible strategies to overcome anabolic resistance in this patient's category. Food intake, in particular dietary protein, and physical activity, are the two major anabolic stimuli. Unfortunately, dialysis patients are often aged and have a sedentary behavior, all conditions which per se may induce a state of "anabolic resistance." In addition, patients on dialysis are exposed to amino acid or protein deprivation during the dialysis sessions. Unfortunately, the optimal amount and formula of protein/amino acid composition in supplements to maximixe MPS is still unknown in dialysis patients. In young healthy subjects, 20 g whey protein maximally stimulate MPS. However, recent observations suggest that dialysis patients need greater amounts of proteins than healthy subjects to maximally stimulate MPS. Since unneccesary amounts of amino acids could stimulate ureagenesis, toxins and acid production, it is urgent to obtain information on the optimal dose of proteins or amino acids/ketoacids to maximize MPS in this patients' population. In the meantime, the issue of maintaining muscle mass and function in dialysis-treated CKD patients needs not to be overlooked by the kidney community.

[PD in Italy: the 5th GSDP-SIN Census 2014].

OBJECTIVES: To know PD modalities and results in Italy. METHODS: The Census was carried out by means of an on-line questionnaire in ALL the 225 non-pediatric public centers which PERFORMED PD in 2014. The results were compared with those of previous Censuses (2005:Cs-05; 2008:Cs-08; 2010:Cs-10; 2012:Cs-12). RESULTS: Incidence. In 2014 PD was begun (first treatment for ESRD) by 1,652 pts (CAPD: 57.2%) and HD by 4,442 pts (%PD-incidence= Cs-14: 27,1%; Cs-12: 23.4%; Cs-10: 23.3%; Cs-08: 22.8%; Cs-05: 24.2%). For the first time Incremental PD does not increase (Cs-14: 27,5%; Cs-12: 28,8%; Cs-10: 22,8%; Cs-08: 18,3%; Cs-05: 11,9%). Prevalence. At 31/12/2014 there were 4,480 patients on PD (CAPD: 46.9%) (%PD-prevalence= Cs-14: Cs-12: 17.1%; Cs-10: 16.6%; Cs-08: 16.7%; Cs-05:16.8%; p=NS), 24.3% of whom were on assisted PD (family members: 83.6%; paid caregivers: 11.5%; nurses: 1.1%; NH: 2.8%). Out. In 2014 there was no change in the PD drop-out rate (32.0 ep/100yrs-pt) (death: 502; transplant: 329; switch to HD: 528 pts). The main reason for transferring to HD remained peritonitis (24.8%). Choice (9.3%) and impossibility to continue PD (15.2%) are increasing. Peritonitis. The peritonitis rate (953 episodes) was 0.224 ep/yrs-pt. The incidence of new cases of EPS in 2013-14 (39 cases=0.444 ep/100yrs-pt) is decreasing (2011-12= 0.505; 2009-10= 0.529; 2004-08= 0.701 ep/100-yrs-pt). Other results. Compared to 2012, in 2014 the number of Centers using 3.86% for PET increased (41.3%) (Cs-12: 30.8%; Cs-10: 15.6%; p <0.001), while the number carrying out home visits (59.6%) remained unchanged (56.3% in 2012, 59.4% in 2010). CONCLUSION: Cs-14 confirms the extensive use, stability and good results of PD in Italy. Incremental PD and assisted PD are unchanged, peritonitis are decreased and EPS remains a rare event. PET-3.86% is increasingly used.

[Peritoneal Dialysis in Italy: the fourth GSDP-SIN census 2012].

OBJECTIVE: To know PD modalities and results in Italy. METHODS: The Census was carried out by means of an on-line questionnaire in all the 224 non-pediatric public centers which performed PD in 2012. The results were compared with those of previous Censuses. RESULTS: Incidence. In 2012 PD was begun (first treatment for ESRD) by 1,433 pts (CAPD: 54.3%) and HD by 4,700 pts (%PD-incidence= Cs-12: 23.4%; Cs-10: 23.3%; Cs-08: 22.8%; Cs-05: 24.2%; p=NS), with a further increase in incremental PD (Cs-12: 28.8%; Cs-10: 22.8%; Cs-08: 18.3%; Cs-05: 11.9%; p-0.001). Prevalence. At 31/12/12 there were 4,299 patients on PD (CAPD: 46.1%) (%PD-prevalence= Cs-12: 17.1%; Cs-10: 16.6%; Cs-08: 16.7%; Cs-05:16.8%; p=NS), 24.5% of whom were on assisted PD (family members: 82.3%; paid caregivers: 12.4%; nurses: 0.7%; NH: 3.0%). Out. In 2012 there was no change in the PD drop-out rate (30.9 ep/100yrs-pt) (death: 481; transplant: 290; switch to HD: 511 pts). The main reason for transferring to HD remained peritonitis (28.2%). Peritonitis. The peritonitis rate (1,179 episodes) was 0.284 ep/yrs-pt. EPS. The incidence of new cases of EPS in 2011-12 (43 cases=0.505 ep/100yrs-pt) remained unchanged (2009-10= 0.529; 2004-08= 0.701 ep/100-yrs-pt). Other results. Compared to 2010, in 2012 the number of Centers using 3.86% for PET increased (30.8% vs 15.6%-p-0.001), while the number carrying out home visits remained unchanged (56.3 vs 59.4%). CONCLUSIONS: Cs-12 confirms the extensive use, stability and good results of PD in Italy. Incremental PD is on the increase. EPS remains a rare event.

Incremental start to PD as experienced in Italy: results of censuses carried out from 2005 to 2014.

BACKGROUND: It is not known how widely used in Italy an incremental start to in peritoneal dialysis (Incr-PD) is. METHODS: By analyzing the peritoneal dialysis (PD) censuses conducted by the PD Study Group (GSDP-SIN) for the years 2005, 2008, 2010, 2012 and 2014 in all the Centers performing PD in Italy, the use of Incr-PD, i.e. continuous ambulatory peritoneal dialysis (CAPD) with 1 or 2 exchanges/day or automated peritoneal dialysis (APD) with 3-4 sessions/week, was examined among incident PD patients. RESULTS: In 2014 PD was started in Italy by 1,652 patients, 455 (27.5%) of whom incrementally (Incr-CAPD 82.2% vs. Incr-APD 17.8%). Incr-PD was used in 53.5% of the 225 Centers. The number of patients and of Centers using Incr-DP increased constantly over the years up to 2012 (in 2005 Incr-PD was used in 33.4% of Centers, and in 11.9% of patients). The use of Incr-PD was greater in Centers with a more extensive PD program and greater use of PD in general. The most widely-used modality in Incr-PD was CAPD. CONCLUSIONS: Incr-PD is used in Italy in a large number of incident PD patients. The reasons for this increase need to be clarified, as current adequacy targets are based on full-dose studies with a very low glomerular filtration rate (GFR).

Survival and time-to-transplantation of peritoneal dialysis versus hemodialysis for end-stage renal disease patients: competing-risks regression model in a single Italian center experience.

AIMS: Despite several studies reporting similar outcomes for peritoneal dialysis (PD) and hemodialysis (HD), the former is underused worldwide, with a PD prevalence of 15% in Italy. In 2008, the Unit of Nephrology and Dialysis of the Healthcare Trust of the Autonomous Province of Trento implemented a successful PD program which has increased the proportion of PD incident patients from 7 to 47%. We aimed to assess the effect of this extensive use of PD by comparing HD and PD in terms of survival and time-to-transplantation. METHODS: A total of 334 HD and 153 PD incident patients were enrolled between January 2008 and December 2014. After screening for exclusion criteria and propensity score matching, 279 HD and 132 PD patients were analyzed. Survival and time-to-transplantation were assessed by competing-risks regression models, using death and transplantation as primary and competing events. RESULTS: Crude and adjusted regression models for survival revealed the absence of significant differences between HD and PD cumulative incidence functions (subhazard ratio: 1.09, p = 0.62 and 1.34, p = 0.10, respectively). Differently, crude and adjusted regression models for transplantation revealed a lower time-to-transplantation for PD versus HD patients (subhazard ratio: 2.34, p < 0.01, and 2.57, p < 0.01, respectively). The waiting time for placement in the transplant waiting list was longer in HD than PD patients (330 vs. 224 days, p < 0.01). CONCLUSIONS: The extensive use of PD did not lead to any statistically significant difference in mortality. Furthermore, PD was associated with lower time to transplantation. PD may be a viable option for large-scale dialytic treatment in the advanced chronic kidney disease population.

[Identikit of the patient who chooses the PD. Experience of the Autonomous Province of Trento]. / Caratterizzazione dei pazienti con questionario strutturato per la scelta della terapia renale sostitutiva. L'esperienza della provincia autonoma di Trento (PAT).

Peritoneal dialysis is a method still underused in Italy. In the Autonomous Province of Trento (PAT) since 2008 has been implemented, with excellent results, a program for the enhancement of the use of this therapy. The most important innovation was the introduction of a questionnaire proposed by nurses to patients in pre-dialysis colloquia. The questionnaire aimed to outline the patient personal and family profile in relation to the chosen dialysis methods. We analyzed 174 questionnaires collected from 1/04/2008 to 01/12/2015. Among these 84 patients had opted for the peritoneal dialysis (PD) and 90 had chosen the Hemodialysis (HD). The questionnaire comparison shown that the patient who opted for the PD have a more positive attitude towards this method. PD patient had more often a job, lived far away from the center of HD, had more frequently the support of a family and had a psychological profile more "sad" or "emotional" than the HD patient, who was more "insecure". On the other hand, factors like age, type of family, degree of autonomy and nationality do not affect the choice about dialysis.

A prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae survival.

Balloon angioplasty (PTA) is an established treatment modality for stenosis in dysfunctional arteriovenous fistulae (AVF), although most studies showing efficacy have been retrospective, uncontrolled, and nonrandomized. In addition, it is unknown whether correction of stenosis not associated with significant hemodynamic, functional, and clinical abnormality may improve survival in AVF. This study was a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access dysfunction improves survival in native, virgin, radiocephalic forearm AVF. Sixty-two stenotic, functioning AVF, i.e., able to provide adequate dialysis, were enrolled in the study: 30 were allocated to control and 32 to PTA. End points of the study were either AVF thrombosis or surgical revision due to reduction in delivered dialysis dose. Kaplan-Meier analysis showed that PTA improved AVF functional failure-free survival rates (P = 0.012) with a fourfold increase in median survival and a 2.87-fold decrease in risk of failure. Cox proportional hazard model identified PTA as the only variable associated with outcome (P = 0.012). PTA induced an increase in access blood flow rate (Qa) by 323 (236 to 445) ml/min (P < 0.001), suggesting that improved AVF survival is the result of increased Qa. PTA was also associated with a significant decrease in access-related morbidity by approximately halving the risk of hospitalization, central venous catheterization, and thrombectomy (P < 0.05). This study shows that prophylactic PTA of stenosis in functioning forearm AVF improves access survival and decreases access-related morbidity, supporting the usefulness of preventive correction of stenosis before the development of access dysfunction. It also strongly supports surveillance program for early detection of stenosis.