Vascular access for hemodialysis in Italy: What a national survey reveals.

BACKGROUND: Since in Italy there are no official data on vascular access (VA) for hemodialysis the Vascular Access Project Group (VAPG) of the Italian Society of Nephrology (SIN) designed a national survey. METHODS: A 35-question survey was designed and sent it to the Italian facilities through the SIN website. The basic questions were the prevalence, the location, and the surveillance of VA, the bedside use of ultrasound, the use of fluoroscopy for central venous catheter (CVC) placement, and of buttonhole technique, the role of nephrologist in the access creation. RESULT: The questionnaire was completed in June 2022 by 161 facilities. The survey registered 15,499 patients, approximately one-third of the Italian dialysis population. The prevalence of arteriovenous fistula (AVF), arteriovenous Graft (AVG), and CVC were 61.8%, 3.7%, and 34.5% respectively. The AVF location was 50% in distal forearm, 20% in meanproximal forearm, 30% in upper arm. For AVF creation, nephrologists were involved in 72% of facilities while for CVC placement in 62%. As regards VA monitoring, 21% of the facilities did not have a surveillance protocol; 60% did not register AVF thrombosis and 53% did not register CVC infections. Most of facilities use the fluoroscope during CVC placement, 37% when needed, and 22% never. Ultrasound-guided puncture of complex AVFs was used by 80% of facilities. Buttonhole puncture was used in 5% of patients. CONCLUSIONS: Some considerations emerge from the survey data: (1) The increasing CVC prevalence compared to DOPPS 5 study. (2) The low rate of AVG prevalence. (3) The nephrologist is the operator in many VA procedures. (4) The fluoroscopy for CVC placement and the US-guide puncture of the complex AVF are widely used in most facilities. (5) The practice of the buttonhole is not widespread. (6) When the operator is the nephrologist more distal fistulas are performed.

Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.

BACKGROUND: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI). METHODS: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU. RESULTS: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints. CONCLUSIONS: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.

[Utility of computerized vascular access monitoring: a pilot study].

The surveillance of a vascular access (VA) is of primary importance for its outcome and for the patients' survival. However, there is still confusion about its usefulness, who should make it (physician or nurse) and when, and what is the best functional test to use. This retrospective analysis reports our experience of VA monitoring; it is based on the collaboration between concept doctors and nurses and on parameters integration, realized with the help of a software for vascular access monitoring (SMAV) designed by us. The analysis confronts the data gathered on a group of 100 patients, 13 months before the adoption of the SMAV, and another 100 patients, 19 months after. Of these patients, 13 belonged to both groups and were "controls of themselves". The number of thrombosis and angioplasties (PTA) plummeted in the 19 months in which the SMAV was used, from 10 (10%; 0.008 thrombosis/patient month) to 1 (1%; 0.0005 thrombosis/patient month) (p <0.01) and from 49 (49%; 0.037 PTA/patient month) to 27 (27%; 0.014PTA/patient month) (p <0.05) respectively. In the 13 control patients, a reduction of 70% in the number of PTA (from 26 to 8) was observed. SMAV allowed us to integrate the many functional parameters, making it easy to share information, encouraging teamwork, strengthening professional skills, and favouring the best management of AVs. The result was a reduction in thrombotic events and, surprisingly, a reduction of the need for PTA, most likely thanks to the higher level of attention in the evaluation and puncture of AV.

The low-protein diet for chronic kidney disease: 8 years of clinical experience in a nephrology ward.

BACKGROUND: Guidelines indicate that a low-protein diet (LPD) delays dialysis in severe chronic kidney disease (CKD). We assessed the value of these guidelines by performing a retrospective analysis in our renal clinical practice. METHODS: The analysis was performed from 1 January 2010 to 31 March 2018 in 299 CKD Stage 4 patients followed for 70 months in collaboration with a skilled nutritionist. The patients included 43 patients on a controlled protein diet (CPD) of 0.8 g/kg/day [estimated glomerular filtration rate (eGFR) 20-30 mL/min/1.73 m2 body surface (b.s.)], 171 patients on an LPD of 0.6 g/kg/day and 85 patients on an unrestricted protein diet (UPD) who were not followed by our nutritionist (LPD and UPD, eGFR <20 mL/min/1.73 m2 b.s.). RESULTS: eGFR was higher in CPD patients than in UPD and LPD patients (21.9 ± 7.4 mL/min/1.73 m2 versus 17.6 ± 8.00 mL/min/1.73 m2 and 17.1 ± 7.5 mL/min/1.73 m2; P = 0.008). The real daily protein intake was higher in UPD patients than in LPD and CDP patients (0.80 ± 0.1 g/kg/day versus 0.6 ± 0.2 and 0.63 ± 0.2 g/kg/day; P = 0.01). Body mass index (BMI) was stable in the LPD and CPD groups but decreased from 28.5 ± 4.52 to 25.4 ± 3.94 kg/m2 in the UPD group (P < 0.001). The renal survival of UPD, LPD and CPD patients was 47.1, 84.3 and 90.7%, respectively, at 30 months (P < 0.001), 42.4, 72.0 and 79.1%, respectively, at 50 months (P < 0.001) and 42.4, 64.1 and 74.4%, respectively, at 70 months (P < 0.001). The LPD patients started dialysis nearly 24 months later than the UPD patients. Diet was an independent predictor of dialysis [-67% of RR reduction (hazard ratio = 0.33; confidence interval 0.22-0.48)] together with a reduction in BMI. CONCLUSIONS: An LPD recommended by nephrologists in conjunction with skilled dietitians delays dialysis and preserves nutritional status in severe CKD.

Sodium removal and plasma tonicity balance are not different in hemodialysis and hemodiafiltration using high-flux membranes.

BACKGROUND: The clinical benefits of on-line hemodiafiltration (HDF) versus high-flux membranes hemodialysis (hf-HD) are still debated. In fact, although a superiority of one treatment over the other, especially in terms of mortality, did not emerge from the analysis of clinical trials, improved intradialytic vascular stability and cardiovascular mortality have been observed in patients undergoing HDF rather than hf-HD; the lower removal of sodium (Na+) during HDF seems to play a major role. The plasma concentration of Na+ is the major determinant of plasma tonicity, which, by determining the flow of water between the intracellular and the extracellular compartment, contributes to the vascular refilling process and the maintenance of blood pressure during the hemodialysis treatment. Plasma tonicity also depends on plasma glucose concentration, especially in patients with diabetes mellitus with hyperglycaemia at the start of hemodialysis treatment. MATERIALS AND METHODS: We evaluated the removal of Na+ and plasma tonicity balance during a 2-week period by performing 2-3 consecutive sessions of hf-HD followed by 2-3 consecutive sessions of HDF, or vice versa, in 47 patients (40% diabetics) on chronic hemodialysis. Identical parameters were used in all dialytic sessions. RESULTS: Na+ removal per session was - 224 ± 144 mmol and - 219 ± 152 mmol, respectively, in hf-HD and in HDF (p = 0.79). The plasma tonicity balance per session was - 575 ± 310 mOsm and - 563 ± 328 mOsm, respectively, in hf-HD and in HDF (p = 0.75). CONCLUSIONS: The removal of Na+ and plasma tonicity balance did not differ between hf-HD and HDF. This observation suggests that factors other than those assessed in our study might explain the improved cardiovascular stability reported in HDF.

Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy.

BACKGROUND AND OBJECTIVE: Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp<1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months). RESULTS: In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp<1 g/d was 30.2% in the NT, 67.3% in the CS, and 66.6% in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4%) in the CS, and 23 (20.7%) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3% to 15.4%). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8% versus 5.7% in study 2 and 30.0% versus 15.4% in study 3; overall P<0.001). CONCLUSIONS: In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp<1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.

[Assisted peritoneal dialysis]. / La Dialisi Peritoneale Assistita con l'impiego degli OSS come caregiver.

Peritoneal dialysis (PD) has a prevalence in Italy that does not exceed 10% of patients in substitution treatment. Among the barriers, which hinder access to DP, the lack of patient autonomy or family support has great importance. In 2012 in Lombardy, the lack of support has prevented 155 new patients to use DP and has forced 17 to stop it. According to the Italian Census of 2012, made by the Peritoneal Dialysis Study Group, Assisted DP involved the 24.5% of patients in 2010. In these cases, the caregiver was a family member in 80.8% of cases, a carer in 12.4%, a homecare nurse in 2.5% and the retirement home staff in 3.9%. In Italy, several regional Governments have sought to encourage home dialysis with economic contributions to the patient or the family. However, so far, none of these interventions has managed to increase the use of DP. In January 2004, we started a program of Assisted PD, using health worker as caregiver, in agreement with ASL Milano and ICP Milano Hospital. In the first 6 months of activity we treated 4 patients, 3 of them had been treated with hemodialysis. We had no critical cases and patients have welcomed this solution. In addition, the costs related to the Assisted PD are lower in comparison with the costs of the hospital hemodialysis. Considering the reliability of the first results, ASL has decided to raise the economic contribution for this activity, allowing us to increase the number of patients to include in Assisted PD.

-374 T/A RAGE polymorphism is associated with chronic kidney disease progression in subjects affected by nephrocardiovascular disease.

BACKGROUND: Chronic kidney disease (CKD) patients present elevated advanced glycation end products (AGEs) blood levels. AGEs promote inflammation through binding to their receptor (RAGE), located on the membrane of mesangial cells, endothelial cells and macrophages. Several genetic polymorphisms influence RAGE transcription, expression and activity, including the substitution of a thymine with an adenine (T/A) in the position -374 of the gene promoter of RAGE. Our study investigates the role of -374 T/A RAGE polymorphism in CKD progression in subjects affected by nephrocardiovascular disease. METHODS: 174 patients (119 males (68.4%) mean age 67.2±0.88 years; 55 females (31.6%): mean age 65.4±1.50 years) affected by mild to moderate nephrocardiovascular CKD were studied. Each subject was prospectively followed for 84 months, every 6-9 months. The primary endpoint of the study was a rise of serum creatinine concentrations above 50% of basal values or end stage renal disease. RESULTS: Carriers of the A/A and T/A genotype presented higher plasma levels of interleukin 6 (A/A 29.5±15.83; T/A 30.0±7.89, vs T/T 12.3±5.04 p = 0.01 for both) and Macrophages chemoattractant protein 1 (A/A 347.1±39.87; T/A 411.8±48.41, vs T/T 293.5±36.20, p = 0.04 for both) than T/T subjects. Carriers of the A allele presented a faster CKD progression than wild type patients (Log-Rank test: Chi square = 6.84, p = 0,03). Cox regression showed that -374 T/A RAGE polymorphism (p = 0.037), albuminuria (p = 0.01) and LDL cholesterol (p = 0.038) were directly associated with CKD progression. HDL cholesterol (p = 0.022) and BMI (p = 0.04) were inversely related to it. No relationship was found between circulating RAGE and renal function decline. CONCLUSIONS: -374 T/A RAGE polymorphism could be associated with CKD progression and inflammation. Further studies should confirm this finding and address whether inhibiting RAGE downstream signalling would be beneficial for CKD progression.

[The ambiguous concept of predialysis: proposal for a model]. / L'ambiguita' del concetto di predialisi: proposta di un modello.

In 2009, 90% of nephrology centers in Lombardy declared to have a ''predialysis'' outpatient department, without, however, specifying its meaning. Research carried out in 2008 among nephrology centers in Piemonte showed how ambiguous this term was. According to the 2007 EDTA-ERA Registry, about 68% of European nephrology centers stated that they had an outpatient department for stage 4-5 CKD patients, but no information was available about the role of patients in the choice of dialysis. It is known that when the predialysis phase is poorly managed, the patient's rehabilitation will be more difficult. Dissatisfaction with dialysis often leads to withdrawal from dialysis, as several registries have shown. For this reason, we created a predialysis course at our center, involving a nephrologist, a nurse, and a dietician. The nephrologist helps the patient choose the most suitable therapeutic strategy, which means that doctor and patient share the responsibility for the treatment choice. The offered options are hemodialysis, peritoneal dialysis, preemptive kidney transplant, and a conservative dietary-pharmacological program. The nurse plans at least 4 meetings: 1) to talk with the patient in order to get to know him or her and his/her family; 2) to provide information about the dialysis procedure and establish the patient's preferences; 3) to clear any doubts about the treatment and deliver a booklet with information about the chosen dialysis procedure; 4) to explain the chosen dialysis procedure; 5) to meet the patient after their preparation for dialysis (vascular access or peritoneal catheter). The dietician manages the dietary programs both for patients who are close to starting dialysis and those on a longlasting conservative program. The predialysis course includes a meeting among all those involved with the patient (nephrologists, nurses, dieticians) to exchange information with the purpose of shared evaluation and decision-making.

Improvement of endothelial function in uraemic patients on peritoneal dialysis: a possible role for 5-MTHF administration.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. METHODS: We examined the effect of oral treatment with 15 mg/daily of 5-methyltetrahydrofolate (5-MTHF) for 12 weeks, on homocysteinaemia and endothelial function in 19 patients undergoing peritoneal dialysis and compared them, for the same period of time, to a control group of patients on peritoneal dialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by the inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after sublingual administration of glyceryl trinitrate. Finally, oxidative stress was assessed by evaluating the conjugated dienes plasma levels. RESULTS: Plasma homocysteine concentrations fell by 30% after oral treatment with 5-MTHF. Endothelial function improved significantly after oral 5-MTHF treatment (13.8 +/- 1.2% vs 11.4 +/- 1.4%; P < 0.02) while in the control group we observed a worsening of basal values from 12.1 +/- 2.66% to 8.7 +/- 2.90% (P < 0.02). The conjugated dienes plasma levels did not change either. CONCLUSIONS: Our study demonstrated that 5-MTHF administration improves endothelial dysfunction in patients undergoing peritoneal dialysis. This effect appears to be independent of the reduction in homocysteine plasma levels.

Home peritoneal ultrafiltration in patients with severe congestive heart failure without end-stage renal disease.

Congestive heart failure (CHF), mainly because of ischemic heart disease, is becoming a common medical problem. As CHF worsens and reaches New York Heart Association (NYHA) class IV, many patients can become refractory to medical therapy, especially those who are elderly or who have pre-existing non uremic chronic renal failure. For such patients, quality of life, morbidity, and mortality are expected to be bad. Our objective in the present study was to make a preliminary assessment of the usefulness of icodextrin administered in a single nocturnal peritoneal exchange to patients nonrespondent to the maximal conventional medical therapy. We studied two patients (aged 80 and 87 years), who were affected by severe dilatative cardiomyopathy and moderate-to-severe chronic renal failure. After at least 12 months of treatment, we observed a significant improvement in quality of life and a reduction in morbidity and hospitalization in both patients. Both patients also significantly increased their creatinine clearance. One patient maintained ejection fraction stability (22%-->27%); the other experienced an increase in ejection fraction to 50%from 25%. These preliminary observations suggest that a single nocturnal exchange with icodextrin can be an effective treatment in patients affected by refractory CHF and moderate-to-severe chronic renal failure.

Morpho-functional study of peritoneum in peritoneal dialysis patients.

BACKGROUND: Structure and function of the peritoneal membrane (PM) are impaired on peritoneal dialysis (PD). The aim of this study was to examine the relationship between dialytic parameters and histological and functional characteristics of the peritoneum of PD patients. METHODS: A peritoneal biopsy (PB) was performed on 31 PD patients during catheter removal due to malfunction or after drop-out from treatment. PB was performed at least 5 cm from the catheter insertion. For each patient PM transport was evaluated by the last peritoneal equilibration test (PET) before PB. Each daily glucose load was calculated. Tissue was formalin-embedded and stained for histological and immunohistochemical studies. RESULTS: (1) Duration of treatment was longer in patients with mesothelial impairment. (2) Patients showing sub-mesothelial sclerosis (SS) and those with impairment of submesothelial basement membrane and subendothelial vascular membrane (SVM) were submitted to a larger daily glucose load. (3) SS exceeding 50 mm was more frequent among high transporters, who were exposed to larger daily glucose load compared to medium-high transporters. (4) Mesothelial loss correlated to SS and vascular alterations. (5) SS was related to vascular injuries but not to inflammatory infiltrate. CONCLUSIONS: SS is not constant in PD patients and is not a prominent factor in treatment drop-out. Mesothelial impairment seems to be mainly related to duration of PD treatment. Glucose load seems to mainly damage the sub-mesothelial layer.