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.

Clinical outcomes and temporal trends of immunological and non-immunological rare diseases in adult kidney transplant.

BACKGROUND: Rare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs. METHODS: Retrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT). RESULTS: Among 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8-11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups. CONCLUSIONS: Kidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients' and graft survival.

Ultrathin Silicon Nanowires for Optical and Electrical Nitrogen Dioxide Detection.

The ever-stronger attention paid to enhancing safety in the workplace has led to novel sensor development and improvement. Despite the technological progress, nanostructured sensors are not being commercially transferred due to expensive and non-microelectronic compatible materials and processing approaches. In this paper, the realization of a cost-effective sensor based on ultrathin silicon nanowires (Si NWs) for the detection of nitrogen dioxide (NO2) is reported. A modification of the metal-assisted chemical etching method allows light-emitting silicon nanowires to be obtained through a fast, low-cost, and industrially compatible approach. NO2 is a well-known dangerous gas that, even with a small concentration of 3 ppm, represents a serious hazard for human health. We exploit the particular optical and electrical properties of these Si NWs to reveal low NO2 concentrations through their photoluminescence (PL) and resistance variations reaching 2 ppm of NO2. Indeed, these Si NWs offer a fast response and reversibility with both electrical and optical transductions. Despite the macro contacts affecting the electrical transduction, the sensing performances are of high interest for further developments. These promising performances coupled with the scalable Si NW synthesis could unfold opportunities for smaller sized and better performing sensors reaching the market for environmental monitoring.

Assessment of Phasic Changes of Vascular Size by Automated Edge Tracking-State of the Art and Clinical Perspectives.

Assessment of vascular size and of its phasic changes by ultrasound is important for the management of many clinical conditions. For example, a dilated and stiff inferior vena cava reflects increased intravascular volume and identifies patients with heart failure at greater risk of an early death. However, lack of standardization and sub-optimal intra- and inter- operator reproducibility limit the use of these techniques. To overcome these limitations, we developed two image-processing algorithms that quantify phasic vascular deformation by tracking wall movements, either in long or in short axis. Prospective studies will verify the clinical applicability and utility of these methods in different settings, vessels and medical conditions.

Hemodialysis arteriovenous fistula ligation after renal transplantation: Impact on graft resistive index.

BACKGROUND: Kidney allograft resistive index (RI) is prognostic for graft and recipient survivals. Recipient hemodynamics could influence RI. In particular, dialysis arteriovenous fistula (AVF) has been involved in heart function changes, reversible after AVF ligation. Knowledge about AVF and RI is lacking. In this study, we prospectively evaluated RI changes after AVF ligation in kidney transplanted patients. METHODS: We enrolled 22 stable transplanted patients. Mean RI was measured before AVF ligation (T0), 18 to 24 h (T1) and 6 months (T6) after surgery; mean blood pressure (mBP), heart rate (HR), serum creatinine (sCr), estimated glomerular filtration rate (eGFR), 24 h proteinuria (24 h-P), immunosuppressive drug blood levels (IS) and antihypertensive drugs were also recorded. RESULTS: AVF ligation was performed 3.1 years (IQR: 2.1-3.8) after transplantation. Median AVF flow (Qa) was 1868 mL/min (IQR: 1538-2712) and 8 AVF were classified as high flow (Qa ≥ 2 L/min). At baseline, median sCr was 1.32 mg/dL (IQR: 1.04-1.76) and median eGFR was 57.1 mL/min. Median RI was 0.71 at T0, 0.69 at T1, 0.66 at T6. RI reduction at T1 and T6 was statistically significant (p < 0.05 and p < 0.001 respectively); in particular, 90.4% of patients had persistently improved values at T6. Furthermore, mBP increased while HR decreased. These changes were independent from sCr, 24 h-P, IS, antihypertensive drugs number, Qa and AVF type. CONCLUSIONS: AVF ligation improves kidney allograft RI; it may reflect better kidney perfusion.

Implanted blood vessel external support device (VasQ™) for creation of hemodialysis arteriovenous fistula: A single-center experience.

INTRODUCTION: the external support device VasQ is intended to promote arteriovenous fistula (AVF) maturation by maintaining the optimal anastomotic angle in order to minimize blood flow disturbances around the anastomotic area. The aim of the study is to assess efficacy and safety of the VasQ device both in brachiocephalic and radiocephalic fistulae. METHODS: a single institution prospective study was conducted with implantation of the VasQ device during AVF creation. Clinical and Doppler ultrasounds evaluations were performed at day-1, 1, 6, and 12 months for assessment of device-related adverse events, AVF maturation and patency. Moreover, volume flow rate and diameter of outflow vein were measured. A total of 16 patients were enrolled. Ten brachiocephalic and 6 radiocephalic AVFs were created with VasQ. Preoperatively cephalic vein diameter was 3.6 ± 0.9 mm. RESULTS: our population included 13 male and 3 females patients, 9 end stage kidney disease in conservative therapy, 4 dialysis treated patients, and 3 transplanted patients; mean age was 74.0 ± 8.1 years; no severe device-related adverse events were observed. Primary patency at 1, 6, and 12 months was 100%, 87.5%, and 67.7%, respectively, while secondary patency was 100%, 100%, and 78.3%, respectively. Comparing brachiocephalic to radiocephalic AVFs no significant differences in patency rates were seen. Overall maturation rate was 94% (15/16). Mean vein diameter measured with Doppler ultrasound at postoperative day-1 and at 1, 6, and 12 months was 5.0 ± 1.0, 5.9 ± 0.9, 7.2 ± 1.6, and 7.9 ± 1.4 mm, respectively, with a mean flow rate at the brachial artery of 841 ± 176, 1052 ± 224, 1261 ± 490, and 1348 ± 477 ml/min, respectively. CONCLUSIONS: in our limited experience VasQ was safe, with high maturation and patency rates. Positive results suggest a potential benefit for VasQ in AVF.

Citrate anion improves chronic dialysis efficacy, reduces systemic inflammation and prevents Chemerin-mediated microvascular injury.

Systemic inflammation and uremic toxins (UT) determine the increased cardiovascular mortality observed in chronic hemodialysis (HD) patients. Among UT, the adipokine Chemerin induces vascular dysfunction by targeting both endothelial and vascular smooth muscular cells (EC and VSMC). As Citrate anion modulates oxidative metabolism, systemic inflammation and vascular function, we evaluated whether citrate-buffered dialysis improves HD efficiency, inflammatory parameters and chemerin-mediated microvascular injury. 45 patients were treated in sequence with acetate, citrate and, again, acetate-buffered dialysis solution (3 months per interval). At study admission and after each treatment switch, we evaluated dialysis efficacy and circulating levels of chemerin and different inflammatory biomarkers. In vitro, we stimulated EC and VSMC with patients' plasma and we investigated the role of chemerin as UT. Citrate dialysis increased HD efficacy and reduced plasma levels of CRP, fibrinogen, IL6 and chemerin. In vitro, patients' plasma induced EC and VSMC dysfunction. These effects were reduced by citrate-buffered solutions and paralleled by the decrease of chemerin levels. Consistently, chemerin receptor knockdown reduced EC and VSMC dysfunction. In conclusion, Switching from acetate to citrate improved dialysis efficacy and inflammatory parameters; in vitro, chemerin-induced EC and VSMC injury were decreased by using citrate as dialysis buffer.

[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.

["Getting to zero infections" in hemodialysis]. / "Getting to zero infections" in emodialisi: un obiettivo raggiungibile. Ruolo della formazione del personale sanitario e dell'impiego di nuovi presidi nella prevenzione delle infezioni cvc correlate.

INTRODUCTION: We describe two measures adopted in hemodialysis outpatient population in order to reduce Central Venous Catheter (CVC) related infections. The first is a nurse staff training in the field project and the second deals with the employment of chlorhexidine-impregnated dressing devices. These actions were performed after high infection rates were observed through a dedicated register. MATERIALS AND METHODS: In the limited assistance dialysis center, direct observation (12/2012-02/2013) quantified the gap between the observed and expected health care behaviour. Training needs were defined and a 40 hours nurse staff training in the field was performed on two occasions. In the hospital dialysis center, we introduced alcoholic 2% chlorhexidine solution and chlorhexidine-impregnated dressing devices to the exit site (CHG-Tegaderm and BioPatch). Infections (cumulatively bacteremia/sepsis/skin exit/subcutaneous tunnel) were monitored continuously. RESULTS: Infection rates at the two locations were progressively reduced, reaching a value of zero at the limited assistance center. Nurse staff training in the field produced: two patient reports and three CVC management protocols, Italian language translation of the "The 5 moments of dialysis" WHO poster, alcoholic 2% chlorhexidine adoption to exit-site medication and improvement of environment cleaning/sanitation actions. CONCLUSIONS: Our experience shows that continuously monitoring infection rates represents the first step for timely corrective action. The continuous updating of health personnel, codified prevention measures and an ongoing commitment to raise awareness in a routine practice, allows us to obtain the goal of "getting to zero infections". The staff training produced equal or superior results compared to the isolated use of new chlorhexidine-impregnated dressing devices.

Glycemic pattern in diabetic patients on hemodialysis: continuous glucose monitoring (CGM) analysis.

BACKGROUND/AIMS: Recent evidences suggest that hemodialysis (HD) induces glycemic variations in diabetic patients. Continuous glucose monitoring (CGM) devices measure interstitial glucose in a 'Holter-like' manner thereby improving the glycemic control assessment method. METHODS: A CGM device (Medtronic iPRO) was used on 12 diabetic patients with chronic HD for 6 days to assess intra- and extra-dialytic interstitial glucose. RESULTS: In all enrolled patients, HD was associated with a decrease of interstitial glucose values. Intradialytic glucose nadir was 79 mg/dl and it was reached at the third hour after the beginning of the session. At the end of HD, interstitial glucose increased in all patients and a glycemic peak (187 mg/dl) occurred after an average time of 2.5 h. No episodes of nocturnal hypoglycemia occurred. CONCLUSION: HD is associated with significant intradialytic reduction of glycemia and postdialytic hyperglycemia. CGM devices result in better monitoring of glycemic trends in diabetic patients on chronic HD and could improve insulin management.

B cell positive cross-match not due to anti-HLA Class I antibodies and first kidney graft outcome.

The effect of B cell cross-match (XM) was investigated in 680 first deceased-donor kidney transplants in a single centre from 1990 to 1999: 74 transplants presented a B-positive XM (Group 1) 606 had a B-negative XM (Group 2). The absence in Group 1 of weak/low-titre anti-HLA Class I antibodies was assured blocking anti-Class I reactivity by treating B cells with non-cytotoxic anti-beta2 microglobulin (alphabeta2 M) serum before XM. Graft survivals up to 5 years were not significantly different; some differences were nevertheless observed: HLA-A,B,DR mismatches influenced graft outcome in Group 1: patients with 0-2 mismatches had better survival than patients with 3-4. When analysed according DR mismatch, patients with 1 mismatch had worse graft survival than well matched patients (p<0.05). No significant difference depending on HLA match was observed in Group 2. Early acute rejection rate was similar in the Groups except the rejection episodes after one year: Group 1 had significantly more. 61/74 patients of Group 1 were retrospectively analysed for anti-HLA-DR,DQ reactivity: only 11/61 had anti-HLA-DR or DQ antibodies (3/11 were donor specific); graft survival and rejections were not significantly different in the patients with and without anti-HLA Class II antibodies. Anti-donor B cell reactivity, at XM, once excluded the presence of weak/low-titre anti-HLA Class I antibodies, did not influence first kidney graft survival.

Preferential allocation of marginal kidney allografts to elderly recipients combined with modified immunosuppression gives good results.

BACKGROUND: There is an increasing tendency to allocate kidneys from marginal donors in older recipients. This combination optimizes the uses of an expanded donor pool but demands attention for the higher nephrotoxic sensitivity of the kidney and the increased immunosuppression vulnerability of the elderly recipients. We aimed to reduce these hazards by means of a calcineurin-free induction therapy followed by a maintenance regimen targeted to minimize/withdraw steroid. METHODS: Eighty-eight single (43%) or double (57%) transplant recipients (58.4+/-5.7 years) from 88 marginal donors (67+/-8.3 years) received monoclonal anti-IL-2 receptor antibodies, mycophenolate mofetil (MMF), and steroid. When serum creatinine was less than 2.6 mg/dL, tacrolimus was started and MMF was withdrawn when the tacrolimus trough level was above 15 ng/ml. Steroid was tapered to 5 mg at day 45 and then progressively reduced. RESULTS: Overall patient and graft survival at the first and fourth year were respectively 100 and 96%, and 98 and 79%. Acute rejection rate was 13.6% (12/88), creatinine clearance remained stable (48.2 ml/min at the sixth month, 50.9 ml/min at 48th month). At the first, second, third, and fourth years, 23, 69, 80, and 100% of recipients were off steroids. For those on steroids, mean dose was respectively 2.6 mg/day from month 12. No recipient re-assumed steroids CONCLUSIONS: In the "old-for-old" allocation, the calcineurin-inhibitor avoidance at induction and the steroid withdrawal/minimization during the tacrolimus-based maintenance regimen allow a low acute rejection rate, a stable renal function, and favorable recipient and graft outcomes.

Basiliximab in association with tacrolimus and steroids in caucasian cadaveric renal transplanted patients: significant decrease in early acute rejection rate and hospitalization time.

Safety and tolerability of basiliximab in renal transplantation have been proven in different immunosuppressive regimens. Few informations are available about the association of basiliximab with tacrolimus and steroids. We present a retrospective analysis performed in Caucasian cadaveric renal transplant recipients, comparing a basiliximab, tacrolimus and steroids induction protocol (GrA: 51 patients) with a tacrolimus and steroids protocol (GrB: 46 patients). A significant decrease in acute rejection rate in the first 3 months (2.0% vs. 17.4%; p < 0.01) was noted. Interestingly, the recipients in GrA were at major immunologic risk for the younger age of recipients, the greater number of mismatches and the higher rate of second transplants. The hospitalization times resulted reduced of 5.3 d in GrA vs. GrB (20.8 d vs. 26.1 d; p < 0.05). The adverse events patterns and profiles were similar in the two treatments groups. One patient in each group had a post-transplant lymphoprolipherative disorder. No significant difference was found in patient and graft survival. According to the results of this study, in a Caucasian adult population, basiliximab in association with tacrolimus and steroids is a safe and efficacious tool for acute rejection prevention and it is cost saving by reducing the hospitalization times.