Antonio Santoro

Online haemodiafiltration: definition, dose quantification and safety revisited

The general objective assigned to the EUropean DIALlysis (EUDIAL) Working Group by the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) was to enhance the quality of dialysis therapies in Europe in the broadest possible sense. Given the increasing interest in convective therapies, the Working Group has started by focusing on haemodiafiltration (HDF) therapies. Several reports suggest that those therapies potentially improve the outcomes for end-stage renal disease patients. Europe is the leader in the field, having introduced the concept of ultra-purity for water and dialysis fluids and with notified bodies of the European Community having certified water treatment systems and online HDF machines. The prevalence of online HDF-treated patients is steadily increasing in Europe, averaging 15%. A EUDIAL consensus conference was held in Paris on 13 October 2011 to revisit terminology, safety and efficacy of online HDF. This is the first report of the expert group arising from that conference.

The effect of on-line high-flux hemofiltration versus low-flux hemodialysis on mortality in chronic kidney failure: a small randomized controlled trial.

BACKGROUNDnGiven the paucity of prospective randomized controlled trials assessing comparative performances of different dialysis techniques, we compared on-line high-flux hemofiltration (HF) with ultrapure low-flux hemodialysis (HD), assessing survival and morbidity in patients with end-stage renal disease (ESRD).nnnSTUDY DESIGNnAn investigator-driven, prospective, multicenter, 3-year-follow-up, centrally randomized study with no blinding and based on the intention-to-treat principle.nnnSETTING & PARTICIPANTSnPrevalent patients with ESRD (age, 16 to 80 years; vintage > 6 months) receiving renal replacement therapy at 20 Italian dialysis centers.nnnINTERVENTIONSnPatients were centrally randomly assigned to HD (n = 32) or HF (n = 32).nnnOUTCOMES & MEASUREMENTSnAll-cause mortality, hospitalization rate for any cause, prevalence of dialysis hypotension, standard biochemical indexes, and nutritional status. Analyses were performed using the multivariate analysis of variance and Cox proportional hazard method.nnnRESULTSnThere was significant improvement in survival with HF compared with HD (78%, HF versus 57%, HD) at 3 years of follow-up after allowing for the effects of age (P = 0.05). End-of-treatment Kt/V was significantly higher with HD (1.42 +/- 0.06 versus 1.07 +/- 0.06 with HF), whereas beta(2)-microglobulin levels remained constant in HD patients (33.90 +/- 2.94 mg/dL at baseline and 36.90 +/- 5.06 mg/dL at 3 years), but decreased significantly in HF patients (30.02 +/- 3.54 mg/dL at baseline versus 23.9 +/- 1.77 mg/dL; P < 0.05). The number of hospitalization events for each patient was not significantly different (2.36 +/- 0.41 versus 1.94 +/- 0.33 events), whereas length of stay proved to be significantly shorter in HF patients compared with HD patients (P < 0.001). End-of-treatment body mass index decreased in HD patients, but increased in HF patients. Throughout the study period, the difference in trends of intradialytic acute hypotension was statistically significant, with a clear decrease in HF (P = 0.03).nnnLIMITATIONSnThis is a small preliminary intervention study with a high dropout rate and problematic generalizability.nnnCONCLUSIONnOn-line HF may improve survival independent of Kt/V in patients with ESRD, with a significant decrease in plasma beta(2)-microglobulin levels and increased body mass index. A larger study is required to confirm these results.

Hemoscan: a dialysis machine-integrated blood volume monitor.

We describe an opto-electronic device capable of measuring the hemoglobin concentration (Hgb) non-invasively and continuously, hence the percentage changes in blood volume (BV) during dialysis treatment by means of the optical absorption of monochromatic light by the blood in the arterial line. This method has been validated during several in vitro and in vivo tests, during which the system has shown a low sensitivity to all the common intra-dialytic interference factors, such as oxygen saturation (max. err.=1.6%), blood flow (max. err. =1.8%), osmotic pressure (max. err.=0.7°) and hydraulic pressure (max. err.=0.6°), a high precision (std. err.≤0.1 g/dl) and a good accordance (Hgb mean err.=0.1 g/dl; std. err.=0.38 g/dl; BV mean err.=0.1%; std. err.=1.6%) with the corresponding values derived from standard laboratory tests.

Continuous Ultrafiltration for Congestive Heart Failure: The CUORE Trial

BACKGROUNDnThere are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload.nnnMETHODS AND RESULTSnFifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; n = 27). The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 5.5 and 7.9 ± 9.0 kg, respectively; P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P = .002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33).nnnCONCLUSIONSnIn HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in pathophysiology

Abstract Arginine vasopressin (AVP) plays a key role in many physiologic and pathologic processes. The most important stimulus for AVP release is a change in plasma osmolality. AVP is also involved in the response and adaptation to stress. Reliable measurement of AVP is hindered by several factors. Over 90% of AVP is tightly bound to platelets, and its estimation is influenced by the number of platelets, incomplete removal of platelets or pre-analytical processing steps. Copeptin (CTproAVP), a 39-aminoacid glycopeptide, is a C-terminal part of the precursor pre-provasopressin (pre-proAVP). Activation of the AVP system stimulates CTproAVP secretion into the circulation from the posterior pituitary gland in equimolar amounts with AVP. Therefore CTproAVP directly reflects AVP concentration and can be used as a surrogate biomarker of AVP secretion. In many studies CTproAVP represents AVP levels and its behavior represents changes in plasma osmolality, stress and various disease states, and shows some of the various physiologic and pathophysiologic conditions associated with increased or decreased AVP. Increased CTproAVP concentration is described in several studies as a strong predictor of mortality in patients with chronic heart failure and acute heart failure. Autosomal polycystic kidney disease (ADPKD) patients have both central and nephrogenic defects in osmoregulation and CTproAVP balance. A possibility raised by these clinical observations is that CTproAVP may serve to identify patients who could benefit from an intervention aimed at countering AVP.

Diffusion tensor imaging and tractography of the kidneys: assessment of chronic parenchymal diseases

AbstractObjectiveTo assess renal dysfunction in chronic kidney diseases using diffusion tensor imaging (DTI).MethodsForty-seven patients with impaired renal function (study group) and 17 patients without renal diseases (control group) were examined using DTI sequences. Cortical and medullary regions of interest (ROIs) were located to obtain the corresponding values of the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA). The mean values of the ADC and FA, for each ROI site, were obtained in each group and were compared. Furthermore, the correlations between the diffusion parameters and the estimated glomerular filtration rate (eGFR) were determined.ResultsIn both the normal and affected kidneys, we obtained the cortico-medullary difference of the ADC and the FA values. The FA value in the medulla was significantly lower (Pu2009=u20090.0149) in patients with renal function impairment as compared to patients with normal renal function. A direct correlation between DTI parameters and the eGFR was not found. Tractography visualised disruption of the regular arrangement of the tracts in patient with renal function alteration.ConclusionDTI could be a useful tool in the evaluation of chronic kidney disease and, in particular, the medullary FA value seems to be the main parameter for assessing renal damage.Key Points• Magnetic resonance diffusion tensor imaging (MRDTI) provides new information about renal problems.n • DTI allows non-invasive repeatable evaluation of the renal parenchyma, without contrast media.n • DTI could become useful in the management of chronic parenchymal disease.n • DTI seems more appropriate for renal evaluation than diffusion-weighted imaging.

Liver support systems.

Liver insufficiency is a dramatic syndrome with multiple organ involvement. A multiplicity nof toxic substances (hydrophilic like ammonia and lipophilic like bilirubin or bile nacids or mercaptans) ar

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

Hypertension and chronic kidney disease (CKD) have a significant impact on global morbidity and mortality. The Low Birth Weight and Nephron Number Working Group has prepared a consensus document aimed to address the relatively neglected issue for the developmental programming of hypertension and CKD. It emerged from a workshop held on April 2, 2016, including eminent internationally recognized experts in the field of obstetrics, neonatology, and nephrology. Through multidisciplinary engagement, the goal of the workshop was to highlight the association between fetal and childhood development and an increased risk of adult diseases, focusing on hypertension and CKD, and to suggest possible practical solutions for the future. The recommendations for action of the consensus workshop are the results of combined clinical experience, shared research expertise, and a review of the literature. They highlight the need to act early to prevent CKD and other related noncommunicable diseases later in life by reducing low birth weight, small for gestational age, prematurity, and low nephron numbers at birth through coordinated interventions. Meeting the current unmet needs would help to define the most cost-effective strategies and to optimize interventions to limit or interrupt the developmental programming cycle of CKD later in life, especially in the poorest part of the world.

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLEDnThe task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK).nnnCONCLUSIONnIt is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group

In 2008, the World Health Assembly endorsed the Global Noncommunicable Disease (NCD) Action Plan based on the realization that NCDs caused more deaths than communicable diseases worldwide. 1 This plan strongly advocates prevention as the most effective strategy to curb NCDs. The “Life Course Approach”, also recently highlighted in the Minsk Declaration, reflects the increasing recognition that early development impacts later-life health and disease. 1,2 Optimization of early development offers the opportunity for true primary prevention of NCDs. n nDevelopmental programming in the kidney has been recognized for over 2 decades but its contribution to the global burden of kidney diseases remains underappreciated by policy makers. 3 Given the many factors known to impact fetal kidney development, including maternal health and nutrition, exposure to stress, poverty, pollutants, drugs and infections during gestation, 3 a holistic strategy to prevent such programming effects is consistent with the “Life-Course” approach and aligns with the United Nations Sustainable Development Goals (SDG) to foster health. 2,4 n nChronic kidney disease (CKD) is an important contributor to the NCD burden that has been relatively neglected in the Global NCD Action Plan, despite CKD being a major cause of hypertension, and a major risk multiplier of cardiovascular disease 1,5 While the prevalence of CKD in many lower-income countries remains unknown, CKD is more prevalent among disadvantaged populations within industrialized nations, e.g. African Americans and Aboriginal Australians. 6 People receiving dialysis or transplantation are projected to double from 2.6 million in 2010 to 5.4 million in 2030. 7 Between 2.3 and 7.1 million adult people died from lack of access to dialysis and transplantation in lower-income countries in 2010. 7 Given the clinical consequences and often prohibitively high costs of treatment, prevention and early detection are the only sustainable solutions to address this growing global burden. n nTo address the neglected issue of developmental programming of kidney disease and hypertension, a multidisciplinary workgroup, including international expert obstetricians, neonatologists and nephrologists (see Appendix), was convened. We argue that the Global NCD Action Plan does not adequately address the impact of developmental origins of NCDs which is globally but is particularly important in low- and middle-income countries (LMICs) where developmental risk is highest and the burden of NCDs is growing fastest. 8 The working group identified the need to raise awareness of the role of developmental programming in renal disease, and suggests locally adapted preventive strategies that could have long-term benefits on health and heath cost savings worldwide, integrating obstetrical, neonatal and nephrology perspectives.