Effects of Rheopheresis in dialysis patients with peripheral artery disease and diabetic foot ulcers: A multicentric Italian study.

BACKGROUND: Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment. MATERIALS AND METHODS: Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks. Improvements in pain symptoms using Numerical Rating Scale (NRS), healing ulcers and laboratory hemorheological parameters have been evaluated. RESULTS: A clinically and statistically significant mean value reduction and of relative percentage differences between estimated marginal means (Δ), calculated at each visits, of NRS was observed, with a maximum value (-48.5%) between the first and last visit. At the end of the treatment period 14.3% of ulcers were completely healed, 46.4% downgraded, 53.6% were stable. Overall, no ulcers upgraded. A statistically significant reduction of the Δ, between the first and last visit, for fibrinogen (-16%) was also observed. CONCLUSION: Rheopheresis reduced overall painful symptoms; data suggest that it could heal or improve ulcers and hemorheological laboratory parameters in HD patients with PAD and ischemic ulcers resistant to standard therapies.

Increase of continuous treatments and regional citrate anticoagulation during renal replacement therapy in the ICUs of the North-West of Italy from 2007 to 2015.

BACKGROUND: Few reports have addressed the change in renal replacement therapy (RRT) management in the Intensive care Units (ICUs) over the years in western countries. This study aims to assess the trend of dialytic practice in a 4.5-million population-based study of the northwest of Italy. METHODS: A nine-year survey covering all the RRT provided in the ICUs. Consultant nephrologists of the 26 Nephrology and Dialysis centers reported their activities in the years 2007, 2009, 2012, and 2015. RESULTS: From 2007 to 2015 the patients treated increased from 1042 to 1139, and the incidence of RRT from 254 to 263 cases/10^6 inhabitants. The workload for dialysis center was higher in the larger hub hospitals. RRT for acute kidney injury (AKI), continuation of treatment in chronically dialyzed patients, or extrarenal indications accounted for about the stable rate of 70, 25 and 5% of all RRT sessions, respectively. Continuous modality days increased from 2731 days (39.5%) in 2007 to 5076 (70.6%) in 2015, when the continuous+prolonged treatment days were 6880/7196 (95.6% of total days). As to RRT timing, in 2015 only the classical clinical criteria, and no K-DIGO stage were adopted by most Centers. As to RRT interruption, in 2015 urine volume was the first criterion. Implementation of citrate anticoagulation (RCA) for RRT patients significantly increased from 2.8% in 2007 to 30.9% in 2015, when it was applied in all 26 Centers. CONCLUSIONS: From 2007 to 2015, current practice has changed towards shared protocols, with increasing continuous modality and RCA implementation.

Does Mediterranean Adequacy Index Correlate with Cardiovascular Events in Patients with Advanced Chronic Kidney Disease? An Exploratory Study.

The Mediterranean Diet (MD) is a healthy dietary pattern, demonstrated to reduce the risk of cancer, diabetes, cardiovascular and neurodegenerative diseases, and early death. The Mediterranean Adequacy Index (MAI) is used to measure adherence to the MD in perspective studies in the general population and correlates with cardiovascular events. The aim of this study was to calculate the MAI among patients with advanced chronic kidney disease (CKD) and correlate it with traditional uremic, microbiota-derived, and proatherogenic toxins as well as nutritional status, quality of life, and cardiovascular events. A total of 60 adult patients with advanced CKD were enrolled and their MAI was calculated. According to the median value, patients were divided into lower (l-MAI, <1.80) and higher (h-MAI, ≥1.80) MAI groups. Biochemical parameters, microbiota-derived and proatherogenic toxins (p-Cresyl sulphate, Indoxyl-sulphate, and Lipoprotein-associated phospholipase A2), nutritional status, quality of life, and cardiovascular events that occurred in the previous three years were recorded. The mean value of the MAI was 2.78 ± 2.86. The MAI was significantly higher in foreigners (median (IQR) 6.38 (8.98) vs. 1.74 (1.67), p < 0.001) and diabetic patients. The l-MAI and h-MAI groups had similar routinary blood, p-Cresyl-sulphate, Indoxyl-sulphate, and Lp-PLA2 as well as nutritional status and quality of life parameters. The MAI was not associated with previous cardiovascular events and did not correlate with cardiovascular events in CKD patients. New and nephro-tailored indexes are warranted to evaluate nutritional therapy in CKD patients.

Probiotics-Supplemented Low-Protein Diet for Microbiota Modulation in Patients with Advanced Chronic Kidney Disease (ProLowCKD): Results from a Placebo-Controlled Randomized Trial.

The probiotics-supplemented low-protein diet in chronic kidney disease (ProLowCKD) was a single-centre, double-blind, placebo-controlled, randomised trial that was conducted to investigate whether the association between a low protein diet (LPD) and a new formulation of probiotics (Bifidobacterium longum and Lactobacillus reuteri) was effective at reducing traditional uremic, microbiota-derived, and proatherogenic toxins in sixty patients affected by advanced CKD. After 2 months of a LPD-a reduction in blood urea nitrogen (52 ± 17 vs. 46 ± 15 mg/dL, p = 0.003), total cholesterol (185 ± 41 vs. 171 ± 34 mg/dL, p = 0.001), and triglycerides (194 ± 148 vs. 161 ± 70 mg/dL, p = 0.03) was observed; 57 subjects were then randomized to receive probiotics or a placebo for the subsequent 3 months. A total of 27 patients in the placebo group showed increased serum values of total cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.01), LDL cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.02), lipoprotein-associated phospholipase A2 (155.4 ± 39.3 vs. 167.5 ± 51.4 nmol/mL/min, p = 0.006), and indoxyl-sulphate (30.1 ± 17.6 vs. 34.5 ± 20.2 µM, p = 0.026), while the 24 subjects in the probiotics group showed a trend in the reduction of microbiota toxins. A reduction of antihypertensive and diuretic medications was possible in the probiotics group. This study shows that associating probiotics to LPD may have an additional beneficial effect on the control and modulation of microbiota-derived and proatherogenic toxins in CKD patients.

Compliance, Adherence and Concordance Differently Predict the Improvement of Uremic and Microbial Toxins in Chronic Kidney Disease on Low Protein Diet.

BACKGROUND: In medicine, "compliance" indicates that the patient complies with the prescriber's recommendations, "adherence" means that "the patient matches the recommendations" and "concordance" means "therapeutic alliance" between patient and clinician. While a low protein diet (LPD) is a cornerstone treatment of chronic kidney disease (CKD), monitoring the actual performance of LPD is a challenge. PATIENTS: Fifty-seven advanced CKD adult patients were enrolled and LPD prescribed. Compliance was evaluated through the normalized protein catabolic rate (nPCR), adherence by the dietitian by means of a 24-h dietary recall and concordance by the nephrologist during consultations. Traditional parameters as well as total p-Cresyl Sulphate (t-PCS), total Indoxyl Sulphate (t-IS) and Lipoprotein-associated phspholipase A2 (Lp-PLA2) were compared between adherent/not adherent and concordant/not concordant subjects at enrolment and after two months. RESULTS: nPCR, blood urea nitrogen, cholesterol and triglycerides significantly decreased in all patients. t-PCS and t-IS decreased among adherent subjects. Lp-PLA2, t-PCS, free-PCS and t-IS decreased among concordant subjects, while these increased in non-concordant ones. CONCLUSION: This study demonstrates that LPD may improve the control of traditional uremic toxins and atherogenic toxins in "adherent" and "concordant" patients. A comprehensive and multidisciplinary approach is needed to evaluate the compliance/adherence/concordance to LPD for optimizing nutritional interventions.

Ionizing radiation exposure from dialysis tunneled catheters procedures: European directive and legal implications.

BACKGROUND: Advances in medical imaging and interventional procedures have been associated with increased exposure to ionizing radiation. Thus, the International Commission on Radiological Protection (ICRP) established uniform safety standards to protect the general public against the dangers arising from ionizing radiations. In Europe, the ICRP standards are listed in the European Directive 2013/59/EURATOM, which should be transposed into national legislation by member states. They require that the administered dose must be part of the radiological report and identify the practitioners' responsibilities in justifying and optimizing the dose and correctly informing the patient.Despite these indications, the literature lacks information about the dose from fluoroscopically inserted dialysis tunneled central venous catheters (td-CVC). This study aimed to quantify the effective dose and organ dose to relevant organs in td-CVC to comply with the EU statements. METHODS: We revised fluoroscopically-guided procedures of td-CVC insertion, considering dose per area product, fluoroscopic time, effective dose, organ dose, and anatomical district. We also compared these parameters with those of fluoroscopically inserted oncological central venous devices (Port-a-cath). RESULTS: The dose-area product, fluoroscopic time, and organ dose for td-CVC were 13 ± 22.2 Gy*cm2, 81 ± 129 s, and 1.9 ± 3.3 mSv. The radiological parameters for the left internal jugular, subclavian and femoral veins were similar but higher than for the right internal jugular vein. The radiological parameters were significantly higher for td-CVC than for Port-a-cath. CONCLUSIONS: Fluoroscopically inserted td-CVC are associated with a relatively low dose of ionizing radiation, with considerable variability due to the anatomical puncture site and previous accesses' history. In light of the European Directive, it is a concern for nephrologists to be aware of the administered ionizing dose to comply with their legal responsibilities.

Lipoprotein-associated phospholipase A2 predicts lower limb ischemia in hemodialysis subjects.

Hemodialyzed patients (HD) have high prevalence of peripheral arterial disease. In the general population, lipoprotein-associated phospholipase A2 (Lp-PLA2 ) is associated with peripheral arterial disease but no data are available for renal subjects. The aim of this study was to evaluate the relationship between Lp-PLA2 and lower limb ischemia among dialyzed patients. One hundred and two dialyzed subjects, with median (IQR) age of 71 (59-78) years, enrolled in June 2013 and followed until June 2018, were investigated for Lp-PLA2 activity and the occurrence of peripheral arterial disease and lower limb ischemia. The median (IQR) levels of Lp-PLA2 were 184 nmol/min/mL (156.5-214.5). The 43 HD patients with abnormal Lp-PLA2 activity (>194 nmol/min/mL) had higher levels of total and LDL-cholesterol, ApoB/A1 ratio, and higher occurrence of lower limb ischemia during the follow up (44% vs 17%, P = .003). In multivariate analysis, Lp-PLA2 activity (P = .018) and diabetes (P < .001) were independently associated with time to lower limb ischemia, and when the presence of previous PAD was added to the multivariate model, only presence of previous PAD (P < .001) and Lp-PLA2 (P = .003) remained associated. Lp-PLA2 is an independent predictor of lower limb ischemia in dialyzed patients.

Lipoprotein-associated phospholipase A2 predicts cardiovascular events in dialyzed patients.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a serine lipase that enhances the instability of the atherosclerotic plaques. While in the general and cardiac population Lp-PLA2 is recognized as an important determinant of cardiovascular (CV) accidents, no data are available for the renal population. The aim of this study was to evaluate the relationship between Lp-PLA2 and acute CV events in hemodialyzed patients. METHODS: We enrolled 102 dialyzed patients, 63% male, age 71 years (59-78), 35% with diabetes, 54% hypertension, 40% coronary artery disease and 31% peripheral vascular disease. They were investigated for Lp-PLA2 (cut-off < 194 nmol/min/ml), lipoprotein profile and the occurrence of acute CV events and death in the subsequent 3 years of follow-up. RESULTS: The median (interquartile ranges) levels of Lp-PLA2, total-, HDL-, LDL-cholesterol and ApoB/ApoA lipoprotein ratio were 184.5 (156.5-214.5) nmol/min/ml, 158 (127-191) mg/dl, 41 (33-51) mg/dl, 79 (63-102) mg/dl and 0.72 (0.58-0.89), respectively. In 42% of patients, Lp-PLA2 was > 194 nmol/min/ml and total- and LDL-cholesterol were higher, as well as CV morbidity and mortality. During follow-up, 51% of patients developed at least one CV event; the median survival time was 36 months, with a total and CV mortality of 42 and 29%, respectively. At multivariate Cox regression, Lp-PLA2 > 194 nmol/min/ml (HR = 2.98, p = 0.005), age (HR = 1.03, p = 0.029), diabetes (HR = 2.86, p = 0.002) and hypertension (HR = 2.93, p = 0.002) were independently associated with time to CV events. CONCLUSIONS: Lp-PLA2 activity is elevated among dialyzed patients and is an independent risk factor for acute CV events in a mean follow-up of 3 years.

[Efficacy of SUPRA HFR in the treatment of acute renal damage during multiple myeloma].

Acute Kidney Injury (AKI) is a frequent complication of multiple myeloma (MM) with unfavorable prognostic significance. Light chains removal, combined with hematological therapy (CT) seems to offer significant benefits to renal function recovery (RFR). The SUPRA HFR, through the combination of high cut-off membrane without albumin loss and adsorbent cartridge, represents one of the "emerging" light chain removal methods. We report our multicentric retrospective experience with SUPRA HFR in 7 MM patients. At the end of the treatment with SUPRA HFR a significant reduction in serum free light chains compared to baseline was observed (min 24%; max 90%; median 74%). Despite a not always early start of the treatment, all patients recovered renal function with withdrawal from dialysis in 6/7 cases. Our preliminary experience of a combination of SUPRA HFR treatment with CT in 7 MM patients with AKI showed a significative renale functional recovery, with favourable cost/benefit ratio and a simple treatment schedule. These encouraging data suggest to further extend such treatment option, waiting for larger studies in this field.

Vitamin K Antagonist Therapy Is a Risk Factor for Ulcer Development and Death Among Dialyzed Patients.

Peripheral artery disease is a common complication among dialyzed patients. Since Vitamin K antagonists promote metastatic calcifications and these are the main determinants of vascular damage, we investigated their role in the development of lower limb ulcers in dialyzed patients. We retrospectively enrolled 316 dialyzed patients, aged 68 ± 15 years, 65% male, 32% diabetic, 43% with ischemic heart disease and followed them for 36 ± 25 months. 60 patients assumed Vitamin K antagonists: they were older, with a higher prevalence of heart disease, at greater risk of death and they developed more ulcers and underwent more lower limb amputations compared to the rest of our cohort. Peripheral artery disease, Vitamin K antagonists and diabetes were independent risk factors for foot lesions. In addition, Vitamin K antagonists were also an independent risk factor for death. Vitamin K antagonists are a potent independent risk factor for the development of the uremic foot syndrome and death.