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The prevalence of chronic kidney disease (CKD), as defined by the NFK-KDOQI (the national kidney foundation kidney disease outcomes quality initiative) guidelines, is a glomerular filtration rate less than 60 mL/min/1.73 m(2) or the presence of microalbuminuria. CKD is increasing worldwide, leading to an increased risk of cardiovascular disease. There is general agreement on the importance of an early referral to a nephrologist and predialysis educational programs. Establishing the protocol for an early approach may assist in preventing the progression, and the most common complications of renal disease. Predialysis education helps patients in order to choose a renal replacement therapy (hemodialysis, peritoneal dialysis, transplantation) and improve their quality of life. Furthermore, adequate predialysis care allows the nephrologist to promptly prepare for vascular or peritoneal treatment. Regrettably, patients are often referred to the nephrologist when renal failure is already fall in the advanced stage. This is caused primarily by non-nephrologists failing to identify patients at risk for imminent renal failure. Furthermore, they may be defining the patient's degree of renal failure according to the KDOQI classification. To further complicate matters, the serum creatinine alone does not provide an adequate estimate of renal function; however, both the MDRD (the modification of diet in renal disease) equation and the Cockcroft-Gault formula permit the more reliable and accurate estimation of the all-important glomerular filtration rate (GFR). Using the MDRD equation, the KDOQI guidelines recommend referral when GFR is less than 30 mL/min/1.73 m(2). Late nephrology referral is an independent risk factor for early death while on dialysis; it is also associated with a more frequent use of temporary catheters, particularly in the elderly individuals. This subject underlines the importance of a multidisciplinary predialysis approach that may bring additional benefits - beyond referral to a nephrologist - including a reduced hospitalization period and a lower mortality rate. The KDOQI guidelines recommend evaluating the benefits and risks of starting renal replacement therapy when patients reach stage 5 (estimated GFR less than 15 mL/min/1.73 m(2)), although the ideal period for initiation of the replacement therapy remained a source of debate.

Background. Citrate anticoagulation is gaining popularity in renal replacement therapies (RRT) for critically ill patients. In order to study whether citrate accumulates in septic shock patients, we determined citrate in plasma and dialysate during continuous venovenous haemodiafiltration (CVVHDF). Methods. An automated routine determination of citrate was set up using a commercial kit (citrate lyase method). Twelve patients with septic shock on CVVHDF and citrate anticoagulation were studied ex vivo for citrate levels in systemic and circuit blood and in the ultrafiltrate (at 0, 0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). Results. In vitro blood studies showed a near unit correlation between the plasma measured and predicted citrate concentrations for an exclusive extracellular distribution of citrate. Median systemic arterial citratemias were 0.09 (0.06–0.12) mmol/L (Time 0) and 0.23 (0.18–0.31) mmol/ L during treatment; median sieving coefficient for citrate was 0.95 (0.88–1.02) and did not change with different volumes of CVVHDF effluent (from 1350 to 5100 mL/h). Net citrate and calcium removal by filter significantly correlated with effluent volume (r ¼ 0.85 and 0.78, respectively). Median citrate load entering in the patients’ bloodstream was 13.60 (9.1–19.6, n ¼ 68) mmol/h. Although cost analysis of the citrate test demonstrated a minimally increased daily cost (from 2.96 to 3.51V), saving costs could be potentially relevant with more extended use of citrate anticoagulation. Conclusions. In septic shock patients with liver dysfunction citratemia is useful in guiding clinical application of RRT, where the citrate losses in the ultrafiltrate can be efficiently modulated by increasing the effluent volume.

Background. Automatic systems for stabilizing blood pressure (BP) during dialysis are few and only control those variables indirectly related to BP. Due to complex BP regulation under dynamic dialysis conditions, BP itself appears to be the most consistent input parameter for a device addressed to preventing dialysis hypotension (DH). Methods. An automatic system (ABPS, automatic blood pressure stabilization) for BP control by fluid removal feedback regulation is implemented on a dialysis machine (Dialog Advanced, Braun). A fuzzy logic (FL) control runs in the system, using instantaneous BP as the input variable governing the ultrafiltration rate (UFR) according to the BP trend. The system is user-friendly and just requires the input of two data: critical BP (individually defined as the possible level of DH risk) and the highest UFR applicable (percentage of the mean UFR). We evaluated this system’s capacity to prevent DH in 55 RDT hypotension-prone patients. Sessions with (treatment A) and without (treatment B) ABPS were alternated one-by-one for 30 dialysis sessions per patient (674 with ABPS vs 698 without). Results. Despite comparable treatment times and UF volumes, severe DH appeared in 8.3% of sessions in treatment A vs 13.8% in treatment B (� 39%, P ¼ 0.01). Mild DH fell non-significantly (� 12.3%). There was a similar percentage of sessions in which the planned body weight loss was not achieved and dialysis time was prolonged. Conclusions. In conclusion, FL may be suited to interpreting and controlling the trend of a determined multi-variable parameter like BP. The medical knowledge of the patient and the consequent updating of input parameters depending on the patient’s clinical conditions seem to be the main factors for obtaining optimal results.

Continuous renal replacement therapies (CRRTs) have become increasingly popular in the past 10 years. The reasons for their wide acceptance in critical care nephrology are numerous, and all trace b...

Background. As removal of pro-inflammatory cytokines is limited in conventional diffusive or convective extracorporeal therapies, we studied in two polysulphone membranes with an industrial albumin sieving coefficient of 0.05 (Type A) and 0.13 (Type B) cytokine (IL-6, IL-8, IL-1b, IL-1ra, TNF-a) and plasma protein (albumin, cystatin C, total proteins) permeability profiles. Based on the convective membrane permeability, we evaluated in vitro the dialytic modality that could provide an acceptable balance between high cytokine and low albumin clearances. Methods. Cytokine and plasma protein sieving coefficient (SC) and clearance were studied in (i) postdilutional haemofiltration mode at 20% fixed ultrafiltration rate; (ii) haemodialysis mode (dialysate flow rate of 3 and 5 l/h); and (iii) haemodiafiltration mode (dialysate flow rate of 3 or 5 l/h with 0.5 l/h of ultrafiltrate). Results. In haemofiltration mode both Type A and Type B haemodialysers at QB 150 ml/min exhibited similar median SC nearly up to 1 for IL-1b and IL-1ra, at about 0.6 for IL-6, 0.4 for IL-8 and 0.7 for TNF-a, with clearance values ranging from 15 to 30 ml/min. SC were independent of blood flow and were stable throughout the whole experiment. Albumin SC was higher in Type B than in Type A and rapidly decreased from 0.2 to 0.02 and from 0.5 to 0.04 within 3 h for haemodialyser Types A and B, respectively. Cytokine SC was lower in haemodialysis than in haemodiafiltration and haemofiltration mode, and by increasing dialysate flow from 3 up to 5 l/h in both haemodialysis and haemodiafiltration mode, SC for all tested cytokines decreased. However, at 5 l/h clearances were not different or were higher, since increased amounts of dialysate outlet compensated for the decreased SC. Albumin clearances in haemodialysis and haemodiafiltration mode after 360 min at 5 l/h were 0.81 and 0.91 ml/min, respectively. Conclusions. Our studies show that a mixed convective and diffusive technique ensures high cytokine clearances with an acceptable loss of albumin.

Haemodialysis (HD) is a life-saving treatment for patients with chronic kidney disease (CKD) stage 5. CKD persists as a chronic worldwide epidemic and HD is the more frequently (70%) adopted treatment modality. Exponential growth trend continues on a global scale. The HD population becomes every year increasingly older (average age: 75 yrs) and sicker due to the associated co-morbidities such as cardiovascular disease (heart failure, coronary heart disease, and peripheral vascular disease), diabetes, hypertension, and peripheral vascular disease. Most of the complications associated with HD involve the cardiovascular system (Go et al., 2004; Culleton et al., 1999, Goodkin et al., 2003, Foley 2004; Barret, 2002). The evolution in the history of HD technology has greatly helped to make the HD procedure a safe and more biocompatible extracorporeal therapy. However, it must be admitted that despite significant improvements in HD technology and in the management of patients due to a better understanding of uremia toxicity, improvements in dialysis technology, better correction of anaemia and metabolic abnormalities, implementation of best practice guidelines, no significant improvement has been achieved in patient survival over the last decade (Rayner et al., 2004). The extracorporeal circuit offers a large surface of contact of the blood with foreign materials, namely the dialysis membrane, the tubings and the large volumes of the dialysate. The concept of biocompatibility has greatly evolved in the last two decades. Initially, numerous studies focused on the blood-dialyzer membrane interaction, leading to the activation of plasma systems (complement, coagulation, fibrinolysis). These studies helped in the understanding of some unknown effects occurring in the early stages of the HD session leading to pulmonary sequestration of leukocytes (mainly neutrophils) that explained the profound neutropenia associated with the cuproammonium membranes. The availability of reliable testing of complement-activated

Citrate anticoagulation has risen in interest so it is now a real alternative to heparin in the ICUs practice. Citrate provides a regional anticoagulation virtually restricted to extracorporeal circuit, where it acts by chelating ionized calcium. This issue is particularly true in patients ongoing CRRT, when the “continuous” systemic anticoagulation treatment is per se a relevant risk of bleeding. When compared with heparin most of studies with citrate reported a longer circuit survival, a lower rate of bleeding complications, and transfused packed red cell requirements. As anticoagulant for CRRT, the infusion of citrate is prolonged and it could potentially have some adverse effects. When citrate is metabolized to bicarbonate, metabolic alkalosis may occur, or for impaired metabolism citrate accumulation leads to acidosis. However, large studies with dedicated machines have indeed demonstrated that citrate anticoagulation is well tolerated, safe, and an easy to handle even in septic shock critically ill patients.

Hemofiltration reduces the serum priming activity on neutrophil chemiluminescence in septic patients. Background Priming of the polymorphonuclear neutrophil (PMN) response has been implicated in the activation of oxidative burst and tissue injury in patients with septic shock and acute renal failure (ARF). This study evaluated whether hemofiltration (HF) removes substances able to enhance the oxidative burst of PMNs. Methods Chemiluminescence (CL) priming activity induced by sera and ultrafiltrates of seven patients with septic shock, multiorgan dysfunction syndrome, and ARF (ARF/HF group) and of 10 uremic stable patients (Control/HF group) was evaluated on normal human PMNs stimulated with bacterial formyl-methionyl-leucyl-phenylalanine (FMLP). Patients submitted to HF were studied by determining blood and ultrafiltrate interleukin-8 (IL-8), platelet-activating factor (PAF), and CL priming activity at the beginning (T 0 ), and after four hours (T 4 ) of treatment. Results Preincubation of normal human PMNs with sera and ultrafiltrates from septic patients induced a potent priming of CL activity in subsequent FMLP stimulation. In the ARF/HF group, the prefilter blood concentrations of IL-8 and CL PMN-priming activity significantly decreased during the four hours of HF treatment, with a loss of IL-8 in the ultrafiltrate of 6930 (median, range 4292 to 9282) ng per four hours. PAF detected in the ultrafiltrate and associated with the membrane (7.3 ng, range 1.45 to 9.89) was minimal. In the ARF/HF group, a significantly positive correlation between CL PMN-priming activity and IL-8 concentrations was observed. The CL priming activity in blood and ultrafiltrates was reduced to 55 and 46% by preabsorption with monoclonal antibody (mAb) anti-IL-8. In contrast, the PAF receptor antagonist WEB 2170 did not affect CL priming activity. In the control/HF group, the CL PMN-priming activity was significantly lower than in the ARF/HF group and was independent of IL-8. Conclusions Sera from septic patients demonstrate an enhanced CL priming activity on PMNs. This activity is reduced by ultrafiltration and is due, at least in part, to ultrafiltered IL-8.

Background Severe burn is a systemic illness often complicated by sepsis. Kidney is one of the organs invariably affected, and proteinuria is a constant clinical finding. We studied the relationships between proteinuria and patient outcome, severity of renal dysfunction and systemic inflammatory state in burns patients who developed sepsis-associated acute renal failure (ARF). We then tested the hypothesis that plasma in these patients induces apoptosis and functional alterations that could account for proteinuria and severity of renal dysfunction in tubular cells and podocytes. Methods We studied the correlation between proteinuria and indexes of systemic inflammation or renal function prospectively in 19 severe burns patients with septic shock and ARF, and we evaluated the effect of plasma on apoptosis, polarity and functional alterations in cultured human tubular cells and podocytes. As controls, we collected plasma from 10 burns patients with septic shock but without ARF, 10 burns patients with septic shock and ARF, 10 non-burns patients with septic shock without ARF, 10 chronic uremic patients and 10 healthy volunteers. Results Septic burns patients with ARF presented a severe proteinuria that correlated to outcome, glomerular (creatinine/urea clearance) and tubular (fractional excretion of sodium and potassium) functional impairment and systemic inflammation (white blood cell (WBC) and platelet counts). Plasma from these patients induced a pro-apoptotic effect in tubular cells and podocytes that correlated with the extent of proteinuria. Plasma-induced apoptosis was significantly higher in septic severe burns patients with ARF with respect to those without ARF or with septic shock without burns. Moreover, plasma from septic burns patients induced an alteration of polarity in tubular cells, as well as reduced expression of the tight junction protein ZO-1 and of the endocytic receptor megalin. In podocytes, plasma from septic burns patients increased permeability to albumin and decreased the expression of the slit diaphragm protein nephrin. Conclusion Plasma from burns patients with sepsis-associated ARF contains factors that affect the function and survival of tubular cells and podocytes. These factors are likely to be involved in the pathogenesis of acute tubular injury and proteinuria, which is a negative prognostic factor and an index of renal involvement in the systemic inflammatory reaction.