Online Hemodiafiltration Inhibits Inflammation-Related Endothelial Dysfunction and Vascular Calcification of Uremic Patients Modulating miR-223 Expression in Plasma Extracellular Vesicles.

Decreased inflammation and cardiovascular mortality are evident in patients with end-stage chronic kidney disease treated by online hemodiafiltration. Extracellular vesicles (EV) are mediators of cell-to-cell communication and contain different RNA types. This study investigated whether mixed online hemodiafiltration (mOL-HDF) beneficial effects associate with changes in the RNA content of plasma EV in chronic kidney disease patients. Thirty bicarbonate hemodialysis (BHD) patients were randomized 1:1 to continue BHD or switch to mOL-HDF. Concentration, size, and microRNA content of plasma EV were evaluated for 9 mo; we then studied EV effects on inflammation, angiogenesis, and apoptosis of endothelial cells (HUVEC) and on osteoblast mineralization of vascular smooth muscle cells (VSMC). mOL-HDF treatment reduced different inflammatory markers, including circulating CRP, IL-6, and NGAL. All hemodialysis patients showed higher plasma levels of endothelial-derived EV than healthy subjects, with no significant differences between BHD and mOL-HDF. However, BHD-derived EV had an increased expression of the proatherogenic miR-223 with respect to healthy subjects or mOL-HDF. Compared with EV from healthy subjects, those from hemodialysis patients reduced angiogenesis and increased HUVEC apoptosis and VSMC calcification; however, all these detrimental effects were reduced with mOL-HDF with respect to BHD. Cell transfection with miR-223 mimic or antagomiR proved the role of this microRNA in EV-induced HUVEC and VSMC dysfunction. The switch from BHD to mOL-HDF significantly reduced systemic inflammation and miR-223 expression in plasma EV, thus improving HUVEC angiogenesis and reducing VSMC calcification.

Acute Kidney Injury and Chronic Kidney Disease in the Elderly and Polypharmacy.

BACKGROUND: Acute kidney injury (AKI) incidence is reported to be 10 times higher in aged people. Related to their higher prevalence of chronic kidney disease (CKD), older patients are at high risk of toxic effects driven by drugs. METHODS: The demographics, hospitalizations, visits to the Emergency Department, pharmacological therapy, and lab tests were analyzed in 71,588 individuals. RESULTS: Data showed a higher prevalence of AKI as well as CKD in the elderly as compared to the younger group, with an associated very high mortality. A broad number of drugs was prescribed, ranging from 1 to 35, the majority being between 5 and 9 drugs. CONCLUSION: Elderly patients who developed AKI had a higher number of hospitalizations (underlying frailty), were more likely to progress to more severe stages of CKD and to be affected by other non-renal pathologies (associated comorbidities) and to be given heavier pharmacological prescriptions (polypharmacy).

[Part I. End-stage chronic organ failures: a position paper on shared care planning. The Integrated Care Pathway]. / Parte I. Il percorso clinico e assistenziale nelle insufficienze croniche d'organo "end-stage".Documento di consenso per una pianificazione condivisa delle scelte di cura.

In Italy the birth rate decrease together with the continuous improvement of living conditions on one hand, and the health care progress on the other hand, led in recent years to an increasing number of patients with chronic mono- or multi-organ failures and in an extension of their life expectancy. However, the natural history of chronic failures has not changed and the inescapable disease's worsening at the end makes more rare remissions, increasing hospital admissions rate and length of stay. Thus, when the "end-stage" get close clinicians have to engage the patient and his relatives in an advance care planning aimed to share a decision making process regarding all future treatments and related ethical choices such as patient's best interests, rights, values, and priorities. A right approach to the chronic organ failures end-stage patients consists therefore of a careful balance between the new powers of intervention provided by the biotechnology and pharmacology (intensive care), both with the quality of remaining life supplied by physicians to these patients (proportionality and beneficence) and the effective resources rationing and allocation (distributive justice). However, uncertainty still marks the criteria used by doctors to assess prognosis of these patients in order to make decisions concerning intensive or palliative care. The integrated care pathway suggested in this position paper shared by nine Italian medical societies, has to be intended as a guide focused to identify end-stage patients and choosing for them the best care option between intensive treatments and palliative care.

[Part II. Scientific evidence in end-stage chronic organ failure. A position paper on shared care planning]. / Parte II. Evidenze scientifiche nelle insufficienze croniche d'organo "end-stage". Documento di consenso per una pianificazione condivisa delle scelte di cura.

The therapeutic options related to chronic organ failure are interconnected to the variability of human biological responses and the personal history and choices of the chronically ill patient on one hand, and with the variable human answers to therapies on the other hand. All these aspects may explain the small number and low quality of studies aimed to define the clinical criteria useful in identifying end-stage chronically ill patients, as highlighted through the 2012-2013 Medline survey performed by the task force. These results prevented the grading of scientific evidence. However, taking into account the evidence based medicine definition, the task force believes the clinical reasoning and the individual experience of clinicians as well as the patients and families preferences cannot be replaced "tout court" with a strict methodological research. Accordingly, the working method selected by the task force members was to draw up a set of clinical parameters based on the available scientific literature, submitting it to a peer review process carried out by an expert panel. This paper discusses a set of clinical parameters included in the clinical decision-making algorithm and shared by nine medical societies. For each chronic organ failure these clinical parameters should be intended not as a rigid cutoff system to make a choice between two selected care options (intensive vs palliative), rather as the starting point for a joint and careful consideration regarding the opportunity to adopt the clinical decision-making algorithm care proposed in Part I.

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.

The prevalence of peripheral neuropathy in hemodialysis patients.

BACKGROUND/AIMS: 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. METHODS: 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. 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. CONCLUSIONS: 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.

[Renal biopsy practice in Piedmont and Valle d'Aosta]. / Indagine sulle modalità di esecuzione delle biopsia renale in Piemonte e Valle d'Aosta.

In 2010 a questionnaire was administered to the renal units of Piedmont and Valle d'Aosta to analyze their procedures for renal biopsy (RB). Seventy-eight percent of units performed RBs, 57% for more than 20 years, but only 43% performed at least 20 BRs per year. 20/21 units performed RB in an inpatient setting and 1/21 in day hospital with the patient remaining under observation the night after. Thirty-two percent did not consider a single kidney as a contraindication to RB, 59% considered it a relative contraindication and 9% considered it an absolute contraindication. In 90.5% of units there was a specific protocol for patient preparation for RB and 86% used a specific informed consent form. Ninety-five percent of units performed ultrasound-guided RB, 60% of them using needle guides attached to the probe. In 81% of units the left side was preferred; 71% put a pillow under the patient's abdomen. All units used disposable, automated or semi-automated needles. Needle size was 16G in 29%, 18G in 58%, and both 16G and 18G in 14% of units; 1 to 3 samples were drawn. One third of units had a microscope available for immediate evaluation of specimen adequacy. After RB, 86% of units kept patients in the prone position for 2-6 hours and all prescribed a period of bed rest (at least 24 hours in 90.5%). 90.5% of units followed a specific postbiopsy observation protocol consisting of blood pressure, heart rate and red blood cell measurements at different times, and urine monitoring and ultrasound control within 12-24 hours (only half of them also employing color Doppler). One third of all units discharged patients after 1 day and two thirds after 2-3 days; all prescribed abstention from effort and from antiplatelet drugs for 7-15 days. In 9 units both RB and tissue processing and examination were done in the same hospital, while 12 units sent the samples elsewhere. 76% obtained results in 2-4 days, 19% in 6-7 days, and 5% in 10-15 days. Less than 20% of the interviewed operators were fully familiar with the clauses of hospital insurance securing their activity. Use of RB is widespread in Piedmont and Valle d'Aosta but its practice shows variation between centers.

[Dialysis adequacy and Kt/V]. / Dialysis adequacy and Kt/V.

Fractional clearance of urea to quantify the adequacy of dialysis was introduced in the late 1980s to allow nephrologists to personalize hemodialysis treatment, assess its effectiveness (dose), and create an index that would represent the concept of adequate dialysis. Since then, the number of nephrologists really involved in this novelty has been rather small, while the majority have been using the new instrument more or less uncritically. At the same time, the dialysis technology has evolved: the extracorporeal techniques have become more diversified, dialyzers have been transformed in terms of materials, hydraulic permeability and purification efficiency, and treatment schedules have been modified in terms of duration and frequency. The purpose of this paper is to evaluate, at a distance of about 30 years, the validity of the control parameter of dialysis - Kt/V - in 2010. In essence, the authors claim that Kt/V is of marginal utility in the quantification of traditional dialysis, while it is wholly inappropriate for frequent or long-term treatment schemes. We maintain that the calculation of Kt/V is still a tool to be used - also recommended by international guidelines - at least until the validation of new and more efficacious solutions, in order to avoid ineffective dialysis sessions (in terms of dose for small molecules), although it does not provide any certainty of a fully adequate performance in terms of reduced morbidity and mortality.

[Quality of life assessment in dialyzed patients in the Cuneo area]. / Valutazione della qualita' di vita dei dializzati del cuneese.

The concept of quality of life includes several aspects of physical and psychological status. In a medical setting the evaluation of quality of life comprises physiopathological and clinical aspects as well as patient well-being and functioning. The aims of this study were to carry out an updated evaluation of the health status and quality of life of chronic dialysis patients in a defined geographic area; to obtain data comparable with other studies or other populations; and to identify possible action or interventions. The tool chosen to achieve these aims was the Italian version of SF36. The SF36 survey was filled in and returned by 78% of patients; the mean rate of missing data was 5%. The results showed that physical aspects were the most compromised, whereas the dialyzed patients' mental status was reasonably intact. Peritoneal dialysis patients had better scores than hemodialysis patients. Age and time on dialysis were closely related to quality of life. The obtained data confirm that end-stage renal disease provokes physical invalidity and disability, severely compromising the health and quality of life of patients and their caregivers. The resulting picture describes a dialysis patient mainly affected by physical problems and difficult management of treatment but with a good mental endurance, who is seeking to regain the autonomy lost due to the disease but also the possibility to socialize and exchange experiences with fellow patients.

Nephrogenic systemic fibrosis: an unusual scleroderma-like fibrosing disorder.

Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder, recently described in patients with advanced chronic kidney disease, usually after exposure to gadolinium (Gd)-based contrast agents, characterized by progressive fibrotic involvement mainly of the skin. At clinical examination, the cutaneous findings of NSF may partly resemble those of systemic sclerosis. However, the different topographic distribution of the skin thickening and hardening, usually involving the limbs and trunk, whilst sparing the face, the lack of serologic abnormalities and the distinctive histopathological findings allow this new disease entity to be distinguished from systemic sclerosis and other scleroderma-like fibrosing disorders (scleromyxedema, scleredema, eosinophilic fasciitis, etc.). Herein, we describe what, to best of our knowledge, is the first, biopsy proven, Italian case of NSF, which highlights the issue of the differential diagnosis between NSF and scleroderma-like fibrosing disorders.

Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury.

INTRODUCTION: The optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. We sought to evaluate the relationship between renal replacement therapy (RRT) dose and outcome. METHODS: We performed a prospective multicentre observational study in 30 intensive care units (ICUs) in eight countries from June 2005 to December 2007. Delivered RRT dose was calculated in patients treated exclusively with either continuous RRT (CRRT) or intermittent RRT (IRRT) during their ICU stay. Dose was categorised into more-intensive (CRRT >or= 35 ml/kg/hour, IRRT >or= 6 sessions/week) or less-intensive (CRRT < 35 ml/kg/hour, IRRT < 6 sessions/week). The main outcome measures were ICU mortality, ICU length of stay and duration of mechanical ventilation. RESULTS: Of 15,200 critically ill patients admitted during the study period, 553 AKI patients were treated with RRT, including 338 who received CRRT only and 87 who received IRRT only. For CRRT, the median delivered dose was 27.1 ml/kg/hour (interquartile range (IQR) = 22.1 to 33.9). For IRRT, the median dose was 7 sessions/week (IQR = 5 to 7). Only 22% of CRRT patients and 64% of IRRT patients received a more-intensive dose. Crude ICU mortality among CRRT patients were 60.8% vs. 52.5% (more-intensive vs. less-intensive groups, respectively). In IRRT, this was 23.6 vs. 19.4%, respectively. On multivariable analysis, there was no significant association between RRT dose and ICU mortality (Odds ratio (OR) more-intensive vs. less-intensive: CRRT OR = 1.21, 95% confidence interval (CI) = 0.66 to 2.21; IRRT OR = 1.50, 95% CI = 0.48 to 4.67). Among survivors, shorter ICU stay and duration of mechanical ventilation were observed in the more-intensive RRT groups (more-intensive vs. less-intensive for all: CRRT (median): 15 (IQR = 8 to 26) vs. 19.5 (IQR = 12 to 33.5) ICU days, P = 0.063; 7 (IQR = 4 to 17) vs. 14 (IQR = 5 to 24) ventilation days, P = 0.031; IRRT: 8 (IQR = 5.5 to 14) vs. 18 (IQR = 13 to 35) ICU days, P = 0.008; 2.5 (IQR = 0 to 10) vs. 12 (IQR = 3 to 24) ventilation days, P = 0.026). CONCLUSIONS: After adjustment for multiple variables, these data provide no evidence for a survival benefit afforded by higher dose RRT. However, more-intensive RRT was associated with a favourable effect on ICU stay and duration of mechanical ventilation among survivors. This result warrants further exploration. TRIAL REGISTRATION: Cochrane Renal Group (CRG110600093).

Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients.

BACKGROUND: Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. METHODS: This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. RESULTS: Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (p< 0.001). The adjusted difference in mean hemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. CONCLUSIONS: This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.

[Bardet-Biedl syndrome and Kidney failure: a case report].

Bardet-Biedl Syndrome (BBS) is a rare multi-systemic disease with autosomal recessive transmission. BBS was at first considered to be homogeneous as for its genetics, but subsequent studies have shown an extensive gene variability. Currently, 21 genes (BBS1-21) present on different chromosomes have been mapped: these genes are responsible for BBS phenotypes and they show a great heterogeneity of mutations.The most common genes are BBS1 (locus 11q13) and BBS10.We show here the case of a 50 year old patient with BBS. Medical History: retinitis pigmentosa at 4 years of age evolved to complete blindness, generalized epilepsy crises, poly-syndactyly, left-hand malformation. In April 1986 developed an epileptic episode: on that occasion Chronic Kidney Failure (CKF) diagnosis and starting of haemodialysis. In 1989, hospitalization for epileptic seizures. In 2009 the patient underwent kidney transplantation from deceased donor. Immunosuppressive initial protocol: Basiliximab, Azathioprine, Tacrolimus, Steroid, and Tacrolimus, Azathioprine, Steroid at hospital discharge. Post-operative care complicated by respiratory failure with mechanical ventilation assistance. During hospitalization, the neurological picture remained stable. At hospital discharge Creatinine 1.8 mg/dl. Subsequently, immunosuppressant were gradually tapered until monotherapy with Tacrolimus. At present the patient's conditions appear to be good, renal function has remained substantially stable with Creatinine between 1.4-1.5 mg/dl and glomerular filtration rate (GFR) estimated at 39-42 mL/min/1.73 m ² according to MDRD study Equation. This case shows the possibility to successfully manage a BBS-affected uremic patient, despite the complexity of the pathology and the aggravating factor of extreme rarity in diagnostic pathway.

Acute renal failure in critically ill patients: indications for and choice of extracorporeal treatment.

The prescription of extracorporeal therapy for patients with acute renal failure involves many options: dialysis sessions may be intermittent or continuous, semicontinuous or slow-extended, with controversial indications still to be defined also depending on technical and logistic issues and related to the multidisciplinary cooperation needed in the management of critically ill patients. All efforts to evaluate extracorporeal treatments in these patients must be targeted not only towards supporting renal function, but towards all functional and metabolic derangements that can result from artificial blood purification, in any way achievable.

[Clinical competence in Nephrology: proposal of an evaluation pathway and definition of professional levels]. / Le competenze in Nefrologia: proposta di un percorso di valutazione e di definizione di livelli professionali.

The need to assess clinical competencies in a medical environment is an intriguing issue due to progressive involvement of young physicians in clinical practice, as well as for connections tied to evaluation systems to define postgraduate training and career progression. To reach this goal, system must be based upon contributions that are aimed to achieve a clear and homogeneous evaluation pathway and strictly related to the continuing medical education institution (credits). All these presuppositions are instrumental for the proposal of a sheet which could allow a data retrieval useful to depict a career progression by means of: identification of reproducible parameters along with clear standards; advices for indicators; objective judgments that could drive to a score meaningful for reaching higher steps in the performance evaluation. This work had been carried out at Local Health Authority 1 of Cuneo (ASLCN1) from 2014 to 2017 in order to provide a widely usable evaluation framework for all the medical workers. Aim of this work is thus to show up an original methodology, as much as possible based upon objective items, related to the professional improvement of a nephrologist working in Hospital and following him along his clinical course.

[Hyperuricemia and gene mutations: a case report].

Hyperuricemia is frequently found in nephrology. The case presented may be useful to clarify some pathogenetic aspects. It is a patient of 18 years, hyperuricaemic. Non-consanguineous parents, hyperuricemia in the paternal line, not neuropsychiatric disorders in the family. Delay in neuromotor acquisitions, average intellectual disabilities, anxiety disorder, obsessive-compulsive personality traits. Normal renal function and renal ultrasound. Evidence of hyperuricemia in 2015. Never gouty episodes and / or lithiasis, initiated allopurinol 100 mg on alternate days, with no side effects, urea in the control range, slightly below normal uricuria. Given the complex clinical, he carried out a genetic analysis of array-CGH. He showed a deletion on the short arm of chromosome 3 (3p12.3) and a duplication of the long arm of chromosome 1 (19q13-42). The deletion 3p12.3 (paternal inheritance), involves the ROBO2 gene. Duplication 19q13.42, (maternal inheritance), includes NLRP12, DPRX, ZNF331 genes. The ROBO2 gene with its mutation, is associated with vesicoureteral reflux. The NLRP12 gene encodes proteins called "Nalps", forming a subfamily of proteins "CATERPILLAR". Many "Nalps" as well as the "Nalps 12" have an N-terminal domain (DYP) with a purin. Since uric acid is a byproduct of purine metabolism, considered the familiarity, we believe that we can hypothesize that the mutations found. In particular those concerning the NLRP-12 gene, may have a role in the presence of hyperuricemia. We believe that in patients with hyperuricemia, associated with a particular impairment of neurological picture, it is likely that there is a subtended common genetic deficiency.

Clinical effects of online dialysate and infusion fluids.

Online hemodiafiltration appears to be the most effective technique of renal replacement therapy in many respects. Removal of small and high-molecular weight substances is enhanced. Modern technology ensures a safe, online production of reinfusion fluids. Nonetheless, stringent maintenance rules are required for the production of sterile and nonpyrogenic-dialysate solutions. In this review, we will critically review the state of the art of the clinical effects derived from the use of ultrapure dialysate and the online production of dialysate fluids in high-flux hemodiafiltration.

Management of CKD-MBD in non-dialysis patients under regular nephrology care: a prospective multicenter study.

BACKGROUND: Knowledge about mineral bone disorder (MBD) management in non-dialysis chronic kidney disease (ND-CKD) patients is scarce, although essential to identifying areas for therapeutic improvement. METHODS: We prospectively evaluated current management of CKD-MBD in two visits, performed 6 months apart, in 727 prevalent ND-CKD stage 3b-5 patients from 19 nephrology clinics. Therapeutic inertia was defined as lack of treatment despite hyperphosphatemia and/or hypocalcemia, and/or hyperparathyroidism. The primary endpoint was the prevalence of achieved target for CKD-MBD parameters and related treatments (phosphate binders, vitamin D and calcium supplements). The secondary endpoint was the assessment of prevalence and clinical correlates of therapeutic inertia. RESULTS: Over 65 % of patients did not reach parathormone (PTH) targets, while 15 and 19 % did not reach phosphate and calcium targets, respectively. The proportion of untreated patients decreased from stage 3b to 5 (at baseline, from 60 to 16 %, respectively). From baseline to the 6-month visit, the achievement of targets remained stable. Low protein diet was prescribed in 26 % of patients, phosphate binders in 17.3 % (calcium-based binders 15.5 %, aluminium binders 1.8 %), and vitamin D in 50.5 %. The overall prevalence of therapeutic inertia at the 6-month visit was 34.0 % (for hyperphosphatemia, 54.3 %). Compared to CKD stage 3, the likelihood of therapeutic inertia was 40 and 68 % lower at stage 4 and 5, respectively. CONCLUSIONS: PTH, calcium and phosphate targets were not reached in a significant proportion of patients. One-third of patients with at least one MBD parameter not-at-target remained untreated. Therapeutic inertia regarding CKD-MBD treatment may be a major barrier to optimizing the prevention and cure of CKD-MBD.

Study protocol: the DOse REsponse Multicentre International collaborative initiative (DO-RE-MI).

INTRODUCTION: Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees. METHODS: DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis. CONCLUSION: The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration.