[Show abstract][Hide abstract] ABSTRACT: Patients with acute kidney injury (AKI) on renal replacement therapy (RRT) are at increased risk for bleeding but usually require anticoagulation of the extracorporeal circuit, a key prerequisite for delivery of an adequate RRT dose. To this end, many anti-hemostatic strategies have been proposed, unfractionated heparin-with all of its significant drawbacks and complications-being the most common method used so far. In this clinical context, regional citrate anticoagulation (RCA) could represent the most promising strategy, and it has been endorsed by recent guidelines on AKI. The aim of this position statement is to critically review the current evidence on RCA for the extracorporeal circuit of RRT in patients with AKI, in order to provide suggestions for its application in clinical practice. To this purpose, the most relevant clinical studies and recent guidelines on AKI with special regard to anti-hemostatic strategies for RRT circuit maintenance have been reviewed and commented. Experts from the Working Group "Renal Replacement Therapies in Critically Ill Patients" of the Italian Society of Nephrology have prepared this position paper, which discusses the basic principles, advantages and drawbacks of RCA based on the available safety and efficacy data. Advice is given on how to use and monitor RCA in the different RRT modalities, in order to avoid complications while maximizing the delivery of the prescribed RRT dose.
Full-text · Article · Jan 2015 · Journal of nephrology
[Show abstract][Hide abstract] ABSTRACT: Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process.
No preview · Article · Oct 2014 · Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia
[Show abstract][Hide abstract] ABSTRACT: Chronic inflammation is a complication of conventional hemodialysis that induces progressive cardiovascular damage. An apparently straightforward manipulation to treat this-removal of a large amount of uremic toxins by convection-has proven that the relationships between inflammation and convective techniques such as hemodiafiltration are more complicated than we currently understand. This Commentary addresses all the doubts and questions that lie behind the assertion that convection is the solution to the problem of inflammation in dialysis.
Preview · Article · Aug 2014 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Background:
Central venous catheter (CVC) preparation for a haemodialysis (HD) session is a critical non-standardized manoeuvre.
We compared the procedure in use at our centre (C) versus the use of Haemocatch® (H), a device recently presented for the management of CVC, in 12 patients, with C during 7 dialysis sessions and H during the subsequent 7 sessions.
Out of 75 HD sessions with C and 75 with H, both the number of connections and disconnections of the CVC via a syringe and the amount of blood wasted during the manoeuvres proved significantly lower with H (2.19 ± 0.59 for H vs. 4.23 ± 0.78 for C, p = 0.00093; 5.97 ± 2.77 ml for H vs. 14.57 ± 6.3 ml for C, p = 0.000078, respectively).
The new device could improve the quality of care in the HD patients carrying a CVC: standardization of the procedure, reduced blood wasting and infection risk.
No preview · Article · Jul 2014 · Blood Purification
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Different types of cells have been used for the development of potential bioartificial kidney devices. Recently, the reprogramming of adult cells to embryonic nephron progenitors (C.E.Hendry et al JASN 2013) and human embryonic stem cells differentiated to renal proximal tubular cells (K.Narayan et al KI 2013) have been used as potential building blocks for a bioartificial kidney. Here we propose the combination of adult renal progenitor/stem cells with different microfabrication and nanofabrication technologies to develop miniaturized, bioartificial proximal tubule-like platforms, which are very promising tools for next-generation bio-analytic assays and for studying the nephrotoxicity of drugs. The potentialities of these interdisciplinary, cross-cutting platforms for in-vitro testing of drugs are presented and discussed.Methods: Our class of devices is composed of overlapped elastomeric layers, embedding microfluidic connections, porous and functionalized membranes, and polymeric
Full-text · Article · May 2014 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Intradialytic hypotension (IDH) represents a common hemodialysis (HD) complication. Blood volume tracking (BVT) is a tool regulating the relative blood volume changes and potentially reducing the occurrence of IDH. The aim of this study was to evaluate the ability of BVT to reduce the staff workload associated to IDH.
Ten hypotension-prone HD patients were treated each with 39 conventional HD (HD) sessions and then switched to 39 HD sessions with BVT (HD-BVT). The staff interventions related to IDH were monitored by a trained staff.
Dialysis sessions complicated by IDH and staff interventions were affected by BVT (HD: 102 and 127 vs. HD-BVT: 57 and 59, respectively, for both p<0.001). The time consumed by staff in IDH management was decreased by HD-BVT (1416 vs. 578 min, p<0.001).
The effectiveness of BVT to reduce the frequency of IDH leads to a reduction of the dialysis staff workload with fewer staff interventions, allowing for major work-time saving.
No preview · Article · May 2014 · The International journal of artificial organs
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: The fluid status of hemodialysis patients has been well established as major factor influencing both clinical outcome and
treatment costs. So that headway can be made in defining the thresholds for fluid overload, identifying patients at greater
risk of fluid overload and the design of optimal treatment strategies, an objective measurement of fluid overload (FO) is
necessary. Consequently, a fluid management program (FMP) is being rolled out within NephroCare (Fresenius Medical Care) which
operates dialysis services in over 750 clinics in the regions of Europe, Middle East, Africa and Latin America. A hydration
status score (HSS) has been incorporated within a NephroCare Balanced ScoreCard (BSC) system to assess treatment quality.
Methods: The basis of the FMP is the BCM_Body Composition Monitor. The BCM allows an objective estimation of fluid overload (FO) and
each clinic in the NephroCare network performs a measurement on a monthly basis. A patient card allows data to be transferred
to a clinical information system. The HSS requires a measure of the relative fluid overload (RelFO) which is determined by
dividing the FO by the extracellular water (ECW). This procedure normalises the patient’s fluid status compensating for patients
of different body weight. It has been shown previously that there is a survival improvement in those patients where RelFO
is maintained below 15%. [Wizemann et al. NDT 2009]. Three ranges for the HSS apply namely less than 15% RelFO, 15% to 20%
RelFO and above 15% RelFO. These ranges score the points 1, 0.5 and 0 respectively. We monitored growth of the FMP over the
last 2 years and the assessed the recent distribution of FO in those patients measured in the network. Data were interpreted
in terms of median and 25th to 75th percentiles.
Results: At the time of the August 2013 analysis, with the step rise due to data reported from Latin America the FMP was measuring
32,484 patients with BCM per month, equivalent to >1000 patients/day. See Fig 1. In August 2013, the median, 25th and 75th
percentiles of FO were found to be 1.74 L (0.85 L to 2.71 L) as shown in Fig 2. RelFO were 10.74% (5.44% to 15.95%) respectively.
Regarding the HSS in August 2013, 71% of patients were <15% RelFO.
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Full-text · Article · May 2014 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Background:
Low and high dialysate calcium (Ca²⁺) content may have positive and harmful effects depending on the considered pathological aspect: hemodynamic instability, cardiac arrhythmias, parathormone release, adynamic bone disease, cardio-vascular calcifications. We hypothesized that a time-profiled Ca²⁺ concentration would keep the cardiovascular advantages of high Ca²⁺ but would reduce the risk of calcium overload.
A prospective, multicenter study using a particular hemodiafiltration technique that allows the profiling of electrolytes was designed. Patients (n = 22) underwent randomly a 3-week dialysis session with low and high constant dialysate Ca²⁺ (Ld(Ca,), 1.25 mM and Hd(Ca,), 2 mM) and profiled Ca²⁺ (Pd(Ca)), respectively. Plasma and spent dialysate Ca²⁺, systolic and diastolic arterial pressure (SAP, DAP) and QT interval corrected for heart rate (QTc) were analyzed.
Plasma Ca²⁺ concentration decreased in Ld(Ca), whereas it increased in Hd(Ca) and to a lesser extent, in Pd(Ca). Total amount of Ca²⁺ given to the patient in Pd(Ca) (15.5 ± 1.0 mmol) was higher than in Ld(Ca) (4.3 ± 1.6 mmol) but lower than in Hd(Ca) (21.9 ± 3.3 mmol). SAP and DAP decreased in Ld(Ca), whereas it was almost constant in both Hd(Ca) and Pd(Ca·). QTc significantly increased, up to critical values (>460 msec), only during Ld(Ca·).
Pd(Ca) seems to retain the advantages of high Ca²⁺ in terms of hemodynamic stability and modification of QTc while reducing the excessive positive calcium balance typical of dialysis with high Ca²⁺ content.
Full-text · Article · Apr 2014 · The International journal of artificial organs
[Show abstract][Hide abstract] ABSTRACT: Background:
Malnutrition in dialysis patients could be offset by intradialytic parenteral nutrition (IDPN), provided it is possible to demonstrate that this technique improves the aminoacid (AA) pool, despite clearance during dialysis.
A kinetic study was conducted in 10 malnourished patients, undergoing thrice- weekly low-flux HD, 240 mins/session (Bologna Malpighi and Trento Hospitals, Italy). After an HD session without IDPN (baseline), the patients received an IDPN solution with 16 AAs (all-in-one bag,NutriSpecialipid: 625 ml, Prot 35.9 gr) over a one-month period. At baseline, after 2 and 4 weeks, pre- and post-HD plasma and dialysate AA concentrations were measured.
Even with a low-flux dialyzer and in the absence of IDPN infusion, AA loss in the dialysate occurred, increasing with the addition of IDPN infusion (3.9+0.3 gr/session with no IDPN compared to 7.7+0.5 with IDPN, p=0.00043), accounting foralmost 26% of the infused AA mass. Nevertheless, the AA mass balance was positive in the patients studied (+21.06+0.95 gr AA/session). After a one-month period with IDPN, the pre-dialysis concentration of each AA infused had indeed increased when compared with baseline concentrations, with a mean overall increase of 36.8%. No severe glucose imbalance was reported.
After a one-month period, overall increase in the plasma concentration of all the infused AAs was observed, supporting the hypothesis that the use of IDPN for longer periods may result in increased protein synthesis.
No preview · Article · Jul 2013 · Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia
[Show abstract][Hide abstract] ABSTRACT: Background:
Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested.
We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).
Full-text · Article · Jul 2013 · Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia
[Show abstract][Hide abstract] ABSTRACT: Multiple myeloma (MM) is still one of the most common haematological diseases and is associated with a poor prognosis. It is frequently worsened by acute kidney failure that, in turn, aggravates the risk of death. In the past few years, the idea has made headway that the removal of free light chains (FLC) by means of extracorporeal blood purification systems may facilitate the recovery of renal function. Up to now, many different extracorporeal techniques have been put forward in FLC removal, such as plasma exchange, dialysis with super-flux filters, and adsorption by means of cartridge of resins. In this paper, we illustrate the use of polymethylmethacrylate (PMMA) dialysis membranes with a high adsorptive capacity (Toray BK-F; Toray Industries, Inc., Tokyo, Japan). We have evaluated light chain removal by means of an original dialysis procedure using a double-filter circuit made of PMMA working in sequential dialysis (DELETE system). The system provides satisfactory results in terms of FLC removal and, at the same time, ensures an adequate dialysis treatment (Kt/V >1.5) with significant reduction in urea, creatinine, and β2-microglobulin. The dual PMMA filter system combines an acceptable cost/efficiency ratio when compared with other methods and constitutes a concrete prospect in FLC removal. Its preferential setting of use is in patients with MM or with monoclonal gammopathies, who are on chronic dialysis and maintain high circulating levels of FLC.
No preview · Article · May 2013 · Blood Purification
[Show abstract][Hide abstract] ABSTRACT: Hemodialysis sessions are often complicated by the occurrence of intradialytic hypotension (IDH), mainly due to the decrease of central blood volume. Blood oxygen content may play a role in hypotension onset and can reflect changes in cardiac output and tissue perfusion. Currently, there is an increasing interest in intradialytic monitoring, through the development of biofeedback based technologies aimed to IDH prevention. Blood Oxygen saturation (SO2) is a patient parameter easy to monitor during hemodialysis thanks to optical noninvasive sensors placed on blood line. The aim of this study was to analyze SO2 variations in relationship with IDH in ten hypotension prone patients with central venous vascular access. A higher decrease of SO2 was found in sessions complicated by hypotension, in comparison with stable sessions (p
[Show abstract][Hide abstract] ABSTRACT: The traditional control of the dialysis session comes about by means of an open-loop system. At the beginning of the session some parameters are set, such as the kind of dialyzer, the blood flow, the ultrafiltration rate, the dialysate conductivity and the dialysate temperature. Generally speaking, these parameters are not modified unless there occur complications in the patient that call for adjustments to be made. The biofeedback concept, which is synonymous with a closed-loop control of biological variables, presupposes, on the other hand: the continuous measurement of a variable thanks to a specific sensor its evaluation by a sort of expert system - the so-called controller and a series of means - the actuators - that allow the behavior of the variable to be directly or indirectly influenced. In clinical practice, different biofeedback systems are emerging, addressed to the control of blood volume, body temperature, and blood pressure. Each one of these systems has been successfully utilized, especially in the management of “difficult” patients unstable from the hemodynamic point of view. However, the future will be an integrated system that sees a complex adaptive, multi-input, multi-output controller which, with a great simplicity of use and low costs, will allow renal replacement therapy to be increasingly physiological and more efficient.
[Show abstract][Hide abstract] ABSTRACT: Uremic Neuropathy (UN) highly limits the individual self-sufficiency causing near-continuous pain. An estimation of the actual UN prevalence among hemodialysis patients was the aim of the present work.
We studied 225 prevalent dialysis patients from two Italian Centers. The Michigan Neuropathy Score Instrument (MNSI), already validated in diabetic neuropathy, was used for the diagnosis of UN. It consisted of a questionnaire (MNSI_Q) and a physical-clinical evaluation (MNSI_P). Patients without any disease possibly inducing secondary neuropathy and with MNSI score ≥ 3 have been diagnosed as affected by UN. Electroneurographic (ENG) lower limbs examination was performed in these patients to compare sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) with the MNSI results.
37 patients (16.4%) were identified as being affected by UN, while 9 (4%) presented a score < 3 in spite of neuropathic symptoms. In the 37 UN patients a significant correlation was found between MNSI_P and SCV (r2 = 0.1959; p < 0.034) as well as SNAP (r2 = 0.3454; p = 0.027) both measured by ENG.
UN is an underestimated disease among the dialysis population even though it represents a huge problem in terms of pain and quality of life. MNSI could represent a valid and simple clinical-instrumental screening test for the early diagnosis of UN in view of an early therapeutic approach.
No preview · Article · Jun 2012 · Clinical nephrology
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Blood uremic toxin measurements are presumed to reflect extracellular fluid, on the assumption of a uniform distribution
between its two compartments, plasma and interstitial fluid (ISF). ISF is however separated from plasma by microvascular pores;
toxins may not necessarily circulate “freely”. Interstitial uremic composition may be particularly important due to proximity
to cell metabolism, and a much larger, often expanded ISF volume in CKD. Little is known about ISF composition in CKD, owing
to the difficulty of sampling the compartment. This study aimed to extract ISF and study its uremic composition in CKD patients,
in steady states and during dialysis, in comparison to plasma.
Methods: A flow-variation microdialysis technique was modified and adapted to simultaneously sample subcutaneous ISF of urea, creatinine,
phosphate and urate in CKD patients during, and off haemodialysis (HD). ISF concentrations of these toxins were compared to
their plasma levels. Metabolomic and proteomic analyses of were performed on contemporaneous ISF and plasma samples, to characterise
their uremic profiles. A novel microneedle was also developed and tested as a new means of sampling ISF in CKD patients.
Results: Microdialysis was performed on 24 subjects (4 controls, 13 CKD non HD, 7 HD). Although a good correlation was seen between
plasma and ISF urea (r=0.98), creatinine (r=0.94), phosphate (r=0.74) and urate (r=0.82), paired analysis of the whole group
showed significant differences between ISF and plasma for urea (p=0.01), creatinine (p=0.02) and urate (p=0.03), with slightly
lower individual ISF levels. During HD, the ISF toxin decay curves lagged behind their plasma counterparts in most patients,
indicating a disharmony between plasma and ISF toxin clearances. Metabolomics revealed over 6000 metabolites in ISF, with
33 peaks consistent with known small and protein-bound uremic toxins, and several unidentified peaks occurring more in ISF
than plasma, and vice-versa. Larger hydrophobic metabolites like sphingolipids did not seem to circulate freely between the
two compartments. Proteomics identified 354 proteins in ISF, with the uremic toxins beta-2 microglobulin, cystatin C and complement
factor D seen in ISF, but not in plasma of some patients, and several others exhibiting a compartmental behaviour. The novel
microneedles were successful in painlessly extracting ISF in 68.8% of oedematous CKD patients.
Conclusions: ISF is toxin rich, ideal for metabolomic and proteomic research in uremia, and may reveal earlier accumulation of toxins
and possibly a sequestration of some larger toxins within the compartment. Even small toxins may show a differential compartmental
distribution, enhanced by dialysis. Microneedles show great promise in minimally invasively sampling ISF, and may bridge the
gap to better understanding of ISF uremic composition, with a likely significant impact on treatment delivery in CKD, and
the assessment of its efficacy.
Full-text · Article · May 2012 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Blood purification by means of plasmapheresis has been known since the 1950s. Plasmapheresis first separates plasma from the blood's cell component; in the classical plasma exchange modality, the patient's plasma is then replaced with fresh frozen plasma from a donor. This procedure is still current in different fields of medicine, as there are hematological (thrombotic thrombocytopenic purpura, Waldenström's disease), neurological (Guillain-Barre' syndrome, myasthenia gravis) and toxicological indications (several forms of mushroom poisoning, tricyclic antidepressants, transfusional reactions), as well as nephrological indications (Goodpasture's syndrome, ANCA-associated vasculitis, myeloma) for its use. Many of these diseases are encountered in the intensive care setting due to the organ dysfunction they may cause. In recent years, purification procedures have been developed that avoid the replacement of plasma by purifying plasma directly. Once treated, the plasma can be returned to the patient, thereby avoiding the loss of factors like vitamins, coagulation proteins, and antibodies and at the same time reducing the possible risk of infection. The technological prerequisite is the use of cartridges containing absorbent material (resins) on which the plasma obtained from the plasma separation is perfused. The physicochemical characteristics of the resins allow them to trap large-sized or protein-bound solutes. Such procedures have found particular application in two fields typically related to intensive care: liver failure and sepsis. The future of plasmapheresis seems oriented towards increasingly selective treatments capable of removing only those molecules that are the cause or associated cause of the damage.
No preview · Article · Jan 2012 · Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia
[Show abstract][Hide abstract] ABSTRACT: It is commonly accepted that the longer the time on extracorporeal cardiopulmonary bypass (CPB), the higher is the likelihood of developing acute renal failure requiring dialysis (ARF-D). Nonetheless, previous works elicited conflicting evidence. We investigated the relationship between CPB duration and ARF-D occurrence. Data were extracted from a large observational study. All factors independently associated with ARF-D were detected. Overall, 11,092 case record forms were analyzed. At the univariate analyses, time on CBP was associated with an increase in the ARF-D risk (odds ratio of fifth vs. first quintile of CBP time: 3.84; 95% confidence interval: 2.58-5.7; P < 0.001). However, after adjusting for confounders, the association between time on CBP and ARF-D lost its statistical significance. In this large dataset, CBP time did not predict ARF-D occurrence. These results might suggest that an accurate risk assessment might be more important than time on CPB in determining ARF-D occurrence.
Full-text · Article · Nov 2011 · Hemodialysis International