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Background Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged Kidney Replacement Therapy (KRT). We evaluated the efficacy and safety of a simplified Regional Citrate Anticoagulation (RCA) protocol for Continuous Venovenous Hemofiltration (CVVH), Continuous Venovenous Hemodiafiltration (CVVHDF) and Sustained Low Efficiency Dialysis Filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. Methods KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/l pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42− 1.0 mmol/L, HCO3− 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (GlycophosTM 20 mmol/20 ml, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. Results 47 patients with Acute Kidney Injury (AKI) or End Stage Kidney Disease (ESKD) requiring KRT were included (11 CVVH, 11 CVVHDF, and 25 SLED-f sessions; mean APACHE II score 25 ± 7.0). Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels Conclusions Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. Trial registration: NCT03976440 registered June 6, 2019.

Background In patients admitted to the Intensive Care Unit (ICU), Kidney Replacement Therapy (KRT) is an important risk factor for hypophosphataemia. However, studies addressing the development of hypophosphatemia during prolonged intermittent KRT modalities are lacking. Thus, we evaluated the incidence of hypophosphatemia during Sustained Low-Efficiency Dialysis (SLED) in ICU patients; we also examined the determinants of post-SLED serum phosphate level (s-P) and the relation between s-P and phosphate supplementation and ICU mortality. Methods We conducted a retrospective analysis on a cohort of critically ill patients with severe renal failure and KRT need, who underwent at least three consecutive SLED sessions at 24–72 h time intervals with daily monitoring of s-P concentration. SLED with Regional Citrate Anticoagulation (RCA) was performed with either conventional dialysis machines or continuous-KRT monitors and standard dialysis solutions. When deemed necessary by the attending physician, intravenous phosphate supplementation was provided by sodium glycerophosphate pentahydrate. We used mixed-effect models to examine the determinants of s-P and Cox proportional hazards regression models with time-varying covariates to examine the adjusted relation between s-P, intravenous phosphate supplementation and ICU mortality. Results We included 65 patients [mean age 68 years (SD 10.0); mean Acute Physiology and Chronic Health Evaluation II score 25 (range 9–40)] who underwent 195 SLED sessions. The mean s-P before the start of the first SLED session (baseline s-P) was 5.6 ± 2.1 mg/dL (range 1.5–12.3). Serum phosphate levels at the end of each SLED decreased with increasing age, SLED duration and number of SLED sessions (P Conclusions Hypophosphatemia is a frequent complication in critically ill patients undergoing SLED with standard dialysis solutions, that worsens with increasing SLED treatment intensity. In patients undergoing daily SLED, phosphate supplementation is strongly associated with reduced ICU mortality.

AIM Acute kidney injury (AKI) shows an increasing incidence, accounting for a remarkable proportion of nephrology team in-hospital activity. The aim was to describe main features and outcomes of AKI observed in patients admitted to a tertiary care hospital. METHODS We conducted a retrospective analysis in all consecutive AKI patients referred for nephrology consultation (November 2018-February 2020) focusing on the factors associated with in-hospital mortality within 90 days and kidney function recovery (KFR) upon discharge. Demographic, clinical and laboratory data, as well as main features of AKI episodes, were collected from medical records of the entire hospital stay. AKI was defined according to KDIGO Clinical Practice Guideline. RESULTS Among 1145 patients referred for nephrology consultation, 559 were evaluated for AKI (598 episodes). Pre-existing CKD was present in 54.7% of patients. In 69.2% of cases AKI was evaluated within 48 h from its onset. Most of the episodes (66.6%) were classified as KDIGO Stage 3. In-hospital mortality within 90 days since admission was 43.3%. Multivariate Cox regression analysis showed a higher mortality risk for advancing age (HR 1.02/unit, 95% CI 1.01-1.03) and oliguria (HR 1.91, 95% CI 1.45-2.52), while a higher eGFR (HR 0.72/unit, 95% CI 0.54-0.95) and KFR within 7 days (HR 0.62, 95% CI 0.41-0.94) were associated to a lower mortality. KFR was observed in 96.4% of survivors. In patients with partial KFR, the loss of eGFR was -29.2 ± 17.9 ml/min. KFR incidence rate was 6.79 per 100-person days (95% CI 6.72-6.87) in survivors and 2.30 (95% CI 2.25-2.35) in non-survivors. CONCLUSION AKI-related nephrology activity accounts for most of the nephrologist workload as consultant. Referred AKI episodes are frequently severe and superimposed on CKD, carrying a relatively high mortality in a patient population developing AKI outside ICU. Early KFR appears strongly associated with a favourable impact upon in-hospital survival.

Introduction: Acute kidney injury (AKI) is a frequent complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care unit (ICU) for severe respiratory failure. The aim is to evaluate the rate of AKI, defined according to Kidney Disease: Improving Global Outcome guidelines, in a series of critical COVID-19 patients admitted to the ICU of a single tertiary teaching hospital. Methods: From April to May 2020, all consecutive critically ill COVID-19 patients admitted to the ICU who did not meet exclusion criteria (length of ICU stay Results: Sixty-one patients were included in the analysis. AKI was observed in 35/61 patients (57.4%): 25/35 episodes (71.4%) were observed within the first 7 days. AKI was classified as follows: 17.1% stage 1, 25.7% stage 2, and 57.2% stage 3. Fourteen out of 20 stage-3 patients required continuous renal replacement therapy (CRRT), mostly related to persistent oliguria. The overall ICU mortality was 68.9%, and it was higher in patients developing AKI if compared to no-AKI patients (p = 0.006). Renal function recovery of any grade was observed in 14 out of 35 AKI patients (40%). Among patients undergoing CRRT, 13 patients were still dialysis dependent at the time of death. Conclusion: In critical COVID-19 patients, ICU mortality is particularly high, especially in patients developing AKI. An accurate monitoring of renal function in early phases of respiratory failure should be ensured in order to timely apply any strategy aimed at limiting renal complications during ICU stay.

Hypomagnesemia is a common electrolyte disorder in critically ill patients and is associated with increased morbidity and mortality risk. Many clinical conditions may contribute to hypomagnesemia through different pathogenetic mechanisms. In patients with acute kidney injury (AKI) the need for continuous or prolonged intermittent kidney replacement therapy (CKRT and PIKRT, respectively) may further add to other causes of hypomagnesemia, especially when regional citrate anticoagulation (RCA) is used. The basic principle of RCA is chelation of ionized calcium by citrate within the extracorporeal circuit, thus blocking the coagulation cascade. Magnesium, a divalent cation, follows the same fate as calcium; the amount lost in the effluent includes both magnesium-citrate complexes and the free fraction directly diffusing through the hemofilter. While increasing the magnesium content of dialysis/replacement solutions may decrease the risk of hypomagnesemia, the optimal concentration for the variable combination of solutions adopted in different KRT protocols has not yet been identified. An alternative and effective approach is based on including early intravenous magnesium supplementation in the KRT protocol, and close monitoring of serum magnesium levels, especially in the setting of RCA. Thus, strategies aimed at precisely tailoring both dialysis prescriptions and the composition of KRT fluids, as well as early magnesium supplementation and close monitoring, could represent a cornerstone in reducing KRT-related hypomagnesemia.

Background and Aims Patients with chronic kidney disease (CKD) represent a frail population with severe co-morbidities and different degrees of immune dysfunction. These patients might be at higher risk of SARS-CoV-2 infection and might experience severe consequences of COVID-19. In March 2020, the Lazio Regional Dialysis and Transplantation Registry (LRDTR) implemented a questionnaire to obtain information on dialysis patients who have developed SARS-CoV-2 infection. The aims of this study is to evaluate the incidence and the short-term lethality of SARS-CoV-2 infection in the population undergoing dialysis treatment in Lazio Region. Method A cohort of patients treated in the dialysis units of Lazio Region was enrolled. Prevalent dialysis patients at 1/1/2020 and incident patients during the period 01/01/2020-08/01/2020 were included. The LRDTR collects information on dialysis patients from the start of chronic dialysis treatments with biannual update and immediately informing about the end of dialytic treatment (death, renal transplant, etc). Infection was traced in the LRDTR from March 2020 to 08/13/2020. The information on vital status was obtained from LRDTR and the mortality Lazio registry up to 10/30/2020. Poisson models, crude and adjusted for sex and age, were used to estimate incident rate of infection and mortality rate on dialysis patients and on dialysis patients who have developed SARS-CoV-2 infection, and respective confidence intervals of 95% (CI95%). Results During the study period, the estimate of the number of patients undergoing dialysis treatment was 5196 in Lazio Region, 65% were males with mean age of 70 years. Thirty-seven patients were infected with SARS-CoV-2: 70% males, mean age 73 years. These patients were treated in 24 different dialysis units. The cumulative incidence rate of SARS-CoV-2 infection was 0.71% (95% CI 0.52-0.98) and the adjusted incidence rate was 3.3 *100,000 Person Days (PD) (95% CI 2.4-4.7). The distribution of positive swabs by month was: 21 in March 7 in April, 6 in May, 1 in June, 2 in July. Twenty-seven patients had symptoms while 10 patients, who have had contact with infected individuals, had positive swabs in absence of symptoms. Infected and hospitalised dialysis patients were 78%. Of the 29 hospitalized patients: 6 were in sub-intensive care, 16 in intensive care, of these 7 needed intubations, 9 underwent non-invasive ventilation. The adjusted cumulative mortality rate in dialysis patients was 6.8% (95% CI 6.0-7.6), the same measure for SARS-CoV-2 infected patients was 37.4% (95% CI 19.8-70.4) with an average follow-up of 205 PD. The adjusted mortality rate was 3.3 * 10,000PD (95% CI: 2.9-3.7) among dialysis patients and 21.2*10,000PD (95% CI: 11.1-40.7) among infected dialysis patients. Conclusion This study highlights a greater susceptibility of dialysis patients to SARS-CoV-2 infection, with a rate three times higher than that observed in the general population (source: Civil Protection Department). Mortality risk for dialysis patients with SARS-CoV-2 infection is about 6 times higher than in the dialysis patients it suggesting a major impact of infection on this fragile population.

Drug poisoning is a significant source of morbidity, mortality and health care expenditure worldwide. Lithium, methanol, ethylene glycol and salicylates are the most important ones, included in the list of poisons, that may require extracorporeal depuration. Lithium is the cornerstone of treatment for bipolar disorders, but it has a narrow therapeutic window. The therapeutic range is 0.6-1.2 mEq/L and toxicity manifestations begin to appear as soon as serum levels exceed 1.5 mEq/L. Severe toxicity can be observed when plasma levels are more than 3.5 mEq/L. Lithium poisoning can be life threatening and extracorporeal renal replacement therapies can reverse toxic symptoms. Currently, conventional intermittent hemodialysis (IHD) is the preferred extracorporeal treatment modality. Preliminary data with prolonged intermittent renal replacement (PIRRT) therapies - hybrid forms of renal replacement therapy (RRT) such as sustained low efficiency dialysis (SLED) - seem to justify their role as potential alternative to conventional IHD. Indeed, SLED allows rapid and effective lithium removal with resolution of symptoms, also minimizing rebound phenomenon.

Neurological, psychological, and cognitive disorders in chronic kidney disease may contribute to poor quality of life in these patients. The aim of this study was to assess the electroencephalographic, psychological, and cognitive changes before and after hemodialysis (HD) compared with healthy controls (HC). Sixteen HD patients and 15 HC were enrolled. Electroencephalogram (EEG), Minnesota multiphasic personality inventory (MMPI-2) Satisfaction profile (SAT-P), and Neuropsychological test Global z-scores (NPZ5) were performed before (T0) and after (T1) HD treatment and in HC. Renal function, inflammatory markers and mineral metabolism indexes were also evaluated. Patients did not show significant differences before and after HD in the absolute and relative power of band of EEG, except in Theta/Alpha index (P < 0.001). At T1, HD patients showed significant differences in Beta, Delta and Theta band, in addition to Theta/alpha index, with respect to HC. Moreover, HD patients showed significant differences in specific MMPI-2 clinical and content scales, SAT-P domains and NPZ5 tests of memory and concentration with respect to HC. We also observed significant correlations between renal function, mineral metabolism, inflammatory markers and psychocognitive alterations. In our sample EEG abnormalities tend to reduce, but not significantly, after HD treatment and differences remain present with respect to HC. In HD patients cognitive and psychological alterations were associated with reduced quality of life and correlated with mineral metabolism and inflammation. Modification in EEG and in psychological and cognitive parameters should be assessed in a larger HD population to confirm our observation.

A careful management of antimicrobials is essential in the critically ill with acute kidney injury, especially if renal replacement therapy is required. Acute kidney injury may lead per se to clinically significant modifications of drugs' pharmacokinetic parameters, and the need for renal replacement therapy represents a further variable that should be considered to avoid inappropriate antimicrobial therapy. The most important pharmacokinetic parameters, useful to determine the significance of extracorporeal removal of a given drug, are molecular weight, protein binding, and distribution volume. In many cases, the extracorporeal removal of antimicrobials can be relevant, with a consistent risk of underdosing-related treatment failure and/or potential onset of bacterial resistance. It should also be taken into account that renal replacement therapies are often not standardized in critically ill patients, and their impact on plasma drug concentrations may substantially vary in relation to membrane characteristics, treatment modality, and delivered dialysis dose. Thus, in this clinical scenario, the knowledge of the pharmacokinetic and pharmacodynamic properties of different antimicrobial classes is crucial to tailor maintenance dose and/or time interval according to clinical needs. Finally, especially for antimicrobials known for a tight therapeutic range, therapeutic drug monitoring is strongly suggested to guide dosing adjustment in complex clinical settings, such as septic patients with acute kidney injury undergoing renal replacement therapy.

Hypophosphatemia is a common but often underestimated electrolyte derangement among intensive care unit (ICU) patients. Low phosphate levels can lead to cellular dysfunction with potentially relevant clinical manifestations (e.g., muscle weakness, respiratory failure, lethargy, confusion, arrhythmias). In critically ill patients with severe acute kidney injury (AKI) renal replacement therapies (RRTs) represent a well-known risk factor for hypophosphatemia, especially if the most intensive and prolonged modalities of RRT, such as continuous RRT or prolonged intermittent RRT, are used. Currently, no evidence-based specific guidelines are available for the treatment of hypophosphatemia in the critically ill; however, considering the potentially negative impact of hypophosphatemia on morbidity and mortality, strategies aimed at reducing its incidence and severity should be timely implemented in the ICUs. In the clinical setting of critically ill patients on RRT, the most appropriate strategy could be to anticipate the onset of RRT-related hypophosphatemia by implementing the use of phosphate-containing solutions for RRT through specifically designed protocols. The present review is aimed at summarizing the most relevant evidence concerning epidemiology, prognostic impact, prevention and treatment of hypophosphatemia in critically ill patients with AKI on RRT, with a specific focus on RRT-induced hypophosphatemia.

Acute Kidney Injury (AKI) is an important issue for the healthcare system, as it is associated with high mortality and increased risk of readmission, with consequent elevated healthcare resource utilization. We investigated the incidence of AKI based on the examination of the discharge cards of all patients admitted between January 1 2011 and December 31 2015 at the Parma University Hospital, as well as the frequency and type of 30-day hospital readmission in the patients discharged with a first AKI diagnosis (index admission). The mean pooled 5-year incidence of AKI was 2.4%. The mean frequency of 30-day readmission for any disease in patients discharged with a first AKI diagnosis in the selected time interval was 23.1%/year. The main four disease categories, as assessed by the Diagnosis Related Group (DRG) classification, responsible for patient 30-day readmission were a new AKI episode, heart failure, respiratory failure requiring or not requiring mechanical ventilation, and sepsis. The mean lenght of hospital stay of patients discharged with AKI as a principal or secondary diagnosis was 14.4 and 21.8 days, respectively. Based on the evaluation of administrative data from all hospital admissions at the Parma University Hospital in the 2011-2015 5-year period, we conclude that AKI represents a serious challenge for the healthcare system, with high short-term morbidity and increased resource utilization due to frequent hospital readmissions.

Abnormalities of blood glucose (BG) concentration (hyper- and hypoglycemia), now referred to with the cumulative term of dysglycemia, are frequently observed in critically ill patients, and significantly affect their clinical outcome. Acute kidney injury (AKI) may further complicate glycemic control in the same clinical setting. This narrative review was aimed at describing the pathogenesis of hyper- and hypoglycemia in the intensive care unit (ICU), with special regard to patients with AKI. Moreover, the complex relationship between AKI, glycemic control, hypoglycemic risk, and outcomes was analyzed.An extensive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, treatment and outcome of hypo- and hyperglycemia in critically ill patients with AKI.Patients with AKI are at increased risk of both hyper-and hypoglycemia. The available evidence does not support a protective effect on the kidney by glycemic control protocols employing Intensive Insulin Treatment (IIT), i.e. those aimed at maintaining normal BG concentrations (80-110 mg/dl). Recent guidelines taking into account the high risk for hypoglycemia associated with IIT protocols in critically ill patients, now suggest higher BG concentration targets (180 mg/dl or 140-180 mg/dl) than those previously recommended (80-110 mg/dl). Notwithstanding the limited evidence available, it seems reasonable to extend these indications also to ICU patients with AKI.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease. The prognosis is usually unfavorable with nearly half of patients progressing to end-stage renal disease within 4 years. We report a case of biopsy-proven FGN characterized by an unusual benign clinical course in which a kidney biopsy, repeated after an extended follow-up of 26 years, confirmed the presence of fibrils deposition. In 1993, a 32-year-old Caucasian man was admitted to our nephrology ward because of macroscopic hematuria. Renal function was normal. Kidney biopsy displayed an FGN with mesangial pattern. The patient was treated with lisinopril, titrated for blood pressure; the therapy was maintained during 26 years of follow-up. The yearly slope of estimated glomerular filtration rate was -3.17 mL/ min). Starting from March 2018, a rapid worsening of renal function was observed and proteinuria increased up to a nephrotic range. We planned a second renal biopsy to assess the cause of the rapid change of clinical course. The diagnosis of FGN on advanced sclerosis was made, and the severity of glomerular sclerosis. We report a case of FGN with an unusually benign clinical course, characterized by a slow progression to end-stage renal disease over a very extended follow-up time; thus, to better clarify the reason for renal function worsening, a second renal biopsy was performed. The persistence of fibrils deposition confirmed the initial diagnosis of FGN, and a histological pattern characterized by global glomerular sclerosis and interstitial fibrosis has been observed.

Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of hospital-acquired acute kidney injury. It is more commonly observed following intra-arterial administration of iodinated contrast media (CM) for cardiac procedures in patients with pre-existing chronic kidney disease (CKD), and is associated with increased short- and long-term morbidity and mortality. This review investigates the key current evidence on CI-AKI definition, epidemiology and pathogenesis, as a basis for recommending preventive measures that can be implemented in clinical practice. An extensive literature search was performed to identify the relevant studies describing the epidemiology, pathogenesis, outcome and prevention of CI-AKI. Pre-existing CKD, intra-arterial administration and CM volume are the most important risk factors for CI-AKI. Since risk factors for CI-AKI are well defined, and the timing of renal insult is known, patients should be carefully stratified before the administration of CM, in order to reduce the negative impact of modifiable risk factors on renal function. The intravenous administration of moderate amounts of isotonic saline solution or bicarbonate solution still represents the principal intervention with documented and acceptable effectiveness for CI-AKI prevention. More data are needed on aggressive volume expansion strategies along with diuretics, targeting forced diuresis with high urinary output. The role of antioxidant agents remains controversial, and only moderate evidence exists in favour of N-acetylcysteine. Statins could contribute to reducing the incidence of CI-AKI, although their mechanism of action is not fully ascertained. No robust data demonstrate a reduction of CI-AKI incidence by peri-procedural hemodialysis/hemofiltration; renal replacement therapies may carry instead unnecessary risks. Remote ischemic preconditioning might represent a simple, non-invasive and cost effective preventive measure for CI-AKI prevention, but few data are currently available about its clinical application in patients at high risk of CI-AKI.

Acute kidney injury (AKI) represents a major complication of cardiac surgery. Our aim was to evaluate, in patients undergoing continuous renal replacement therapy (CRRT) for cardiac surgery-associated AKI (CS-AKI), prognostic factors related to in-hospital survival and renal function recovery to independence from RRT. We conducted a retrospective analysis in patients with severe CS-AKI who underwent CRRT for at least 48 h. The sequential organ failure assessment (SOFA) score was calculated on a daily basis to evaluate illness severity throughout the intensive care unit (ICU) stay. In 264 patients (age 66.4 ± 11.7 years, 192 males), 30-day survival was 57.6 % while survival to discharge from the hospital was 40.5 %. Renal function recovery occurred in 96.3 % of survivors and in 13.4 % of non-survivors (p

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

Aims: To evaluate the efficacy and safety of a commercially available phosphate-containing solution for continuous renal replacement therapy (CRRT) in preventing CRRT-related hypophosphatemia. Methods: In heart surgery patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), we combined an 18 mmol/l citrate solution with a phosphate-containing (1.2 mmol/l) dialysate/replacement fluid evaluating the incidence of hypophosphatemia and the need for parenteral phosphorus supplementation. Results: In 75 patients on RCA-CVVHDF, the mean filter life was 53.9 ± 33.6 h. Regardless of baseline levels, phosphoremia was progressively corrected and maintained in a narrow normality range throughout RCA-CRRT days (after 72 h: 1.14 ± 0.25 mmol/l). Considering the whole CRRT period, 45 out of 975 (4.6%) serum phosphorus determinations met the criteria for mild (Conclusions: RCA-CVVHDF with a phosphate-containing solution enabled the maintenance of phosphorus levels within normophosphatemic range in most of the patients, minimizing the occurrence of CRRT-related hypophosphatemia.

BACKGROUND: Cerebral blood flow (CBF) decreases during intermittent hemodialysis (HD) in patients with acute kidney injury (AKI). Since cerebral hemodynamics may be impaired in liver cirrhosis (LC), this condition could aggravate cerebral hypoperfusion during HD in patients with AKI. We examined CBF during the first HD session in patients admitted for AKI, with or without LC. METHODS: CBF was examined by measuring middle cerebral artery mean flow velocity (MCAmfv) with transcranial Doppler at baseline and at the end of the first 4-hour HD session in 11 patients with both AKI and LC (median age 69 years, range 40-87, 7 men). Eleven patients with AKI without LC (median age 77 years, range 69-92, 6 men) served as controls. RESULTS: Median net ultrafiltration volume at the end of the HD session was slightly, albeit not significantly, smaller in the patients with LC than in those without (-0.25 kg [range 0.00 to -1.50] vs. -1.00 kg [range 0.00 to -2.00], p = 0.18). At end of HD session, median MCAmfv had decreased by -5.5 cm/s (range -41.3 to 9.9) in the patients with LC, and by -4.5 cm/s (range -11.0 to -2.5) in those without LC (p = 0.79). At end of HD session, the mean MCAmfv of the 2 groups, adjusted for baseline MCAmfv and net ultrafiltration volume, was 25.7 and 21.1 cm/s in AKI patients with and without LC, respectively (difference between groups: 4.6 cm/sec; 95% confidence interval, -3.8 to +13.0). CONCLUSION: In patients with AKI, concomitant LC does not confer greater vulnerability to cerebral hypoperfusion during intermittent HD.

Regional citrate anticoagulation (RCA) is a valid anticoagulation method in continuous renal replacement therapies (CRRT) and different combination of citrate and CRRT solutions can affect acid-base balance. Regardless of the anticoagulation protocol, hypophosphatemia occurs frequently in CRRT. In this case report, we evaluated safety and effects on acid-base balance of a new RCA- continuous veno-venous hemofiltration (CVVH) protocol using an 18 mmol/L citrate solution combined with a phosphate-containing replacement fluid. In our center, RCA-CVVH is routinely performed with a 12 mmol/L citrate solution and a postdilution replacement fluid with bicarbonate (protocol A). In case of persistent acidosis, not related to citrate accumulation, bicarbonate infusion is scheduled. In order to optimize buffers balance, a new protocol has been designed using recently introduced solutions: 18 mmol/L citrate solution, phosphate-containing postdilution replacement fluid with bicarbonate (protocol B). In a cardiac surgery patient with acute kidney injury, acid-base status and electrolytes have been evaluated comparing protocol A (five circuits, 301 hours) vs. protocol B (two circuits, 97 hours): pH 7.39 ± 0.03 vs. 7.44 ± 0.03 (P < 0.0001), bicarbonate 22.3 ± 1.8 vs. 22.6 ± 1.4 mmol/L (NS), Base excess −2.8 ± 2.1 vs. −1.6 ± 1.2 (P = 0.007), phosphate 0.85 ± 0.2 vs. 1.3 ± 0.5 mmol/L (P = 0.027). Protocol A required bicarbonate and sodium phosphate infusion (8.9 ± 2.8 mmol/h and 5 g/day, respectively) while protocol B allowed to stop both supplementations. In comparison to protocol A, protocol B allowed to adequately control acid-base status without additional bicarbonate infusion and in absence of alkalosis, despite the use of a standard bicarbonate concentration replacement solution. Furthermore, the combination of a phosphate-containing replacement fluid appeared effective to prevent hypophosphatemia.

Background: Contrast-induced acute kidney injury (CI-AKI) represents an important cause of hospital-ac- quired AKI. The aim of this study was to evaluate the incidence of CI-AKI after coronary angiography (CA) or percutaneous coronary intervention (PCI) and the role of patient-/procedure-related risk factors. Methods: For 11 months, patients undergoing CA or PCI were prospectively evaluated for CI-AKI, and factors possibly affecting CI-AKI were analyzed. Statistical anal- ysis was completed using Student's t-test, chi-square or Fisher exact test, and multivariate logistic regression. Results: Among 585 consecutive patients, incidence of CI-AKI was 5.1% (n=30) and renal replacement therapy was required in 10% of those (n=3). Incidence of CI-AKI was higher in patients with anemia or chronic kidney disease (CKD) associated with diabetes. Basal hemo- globin was significantly lower in CI-AKI patients while Mehran score, contrast medium (CM) volume, contrast ratio (CM volume / maximum contrast dose) and ratio glomerular filtration rate (CM volume / GFR) were sig- nificantly higher. Multivariate analysis selected a higher contrast ratio as a factor independently associated with a higher risk of CI-AKI which otherwise appeared to be lower with increasing basal hemoglobin. Conclusions: The incidence of CI-AKI after CA or PCI was higher in patients with CKD associated with diabe- tes. Lower levels of basal hemoglobin appeared to be re- lated to a higher risk of CI-AKI, and contrast media vol- ume, especially if exceeding the dose adjusted for renal function, was a strong modifiable risk factor for CI-AKI.

Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed.

Background The aim of this study was to evaluate indocyanine green angiographic findings in patients with systemic lupus erythematosus (SLE) with or without lupus nephritis. In particular, the presence of choroidal abnormalities at indocyanine green angiography (ICG-A) that could not be detected by fluorescein angiography (FAG) was investigated. Methods Sixteen patients with SLE underwent simultaneous ICG-A and FAG. Patients were divided into 2 groups based on whether renal disease was present (group A, n=9) or not (group B, n=7). Results Drusen-like deposits were ophthalmoscopically evident in only 1 out of 9 group A patients (11.1%). While FAG disclosed the deposits in 4 out of 9 group A patients (44.4%), drusen-like deposits were otherwise found in all group A patients (100%) by ICG-A. FAG and ICG-A did not show choroidal alterations in group B patients. Conclusions ICG-A can provide information that is not detectable by clinical or FAG examination in patients with lupus nephritis (group A). The findings of choroidopathy by ICG-A represent an indicator of ocular involvement and could be an indirect sign of renal involvement. Given that histological lesions may be present where there are no anomalies in urinary sediment and/or proteinuria, the positivity of ICG-A could help in deciding whether or not to carry out a renal biopsy. Therefore, ICG-A could be useful in the screening of patients with SLE, especially where there are no evident signs of renal involvement.

Acute kidney injury (AKI) following major heart surgery (MHS) is associated with early decrease in renal blood flow and worsened prognosis. Doppler-derived renal resistive index (RRI), which reflects renal vascular resistance, may predict the development of AKI in patients undergoing MHS. We studied 60 consecutive patients (mean age 69.5 years, range 30–88, 41 males) undergoing MHS. We measured RRI, both at the renal sinus and intraparenchymally, by transesophageal echo-Doppler ultrasound (TE-EDus) at anesthesia induction and at the end of surgery in all patients. Additionally, we measured RRI by external transparietal echo-Doppler ultrasound (TP-EDus) at the following time points: anesthesia induction, end of surgery, 4 and 24 h from cardiopulmonary bypass (CPB) start. We also measured serum neutrophil gelatinase associated lipocalin (NGAL) at the same time points. AKI [serum creatinine (sCr) increase ≥0.3 mg/dl vs. baseline within 72 h] developed in 23/60 (38.3 %) patients, with two requiring dialysis. Systemic hemodynamic parameters were similar in the patients who developed AKI (AKI+) and in those who did not (AKI−). Intraparenchymal RRI at end-surgery was significantly higher in AKI+ compared to AKI− patients, both at TE-EDus and TP-EDus (TE-EDus mean difference, p = 0.004; TP-EDus mean difference, p = 0.013; difference between TE-EDus and TP-EDus results, p = 0.066), although the predictive performance was limited with both methods (area under the curve [AUC] of the receiver-operator characteristics: 0.71 and 0.70 for TE-EDus and TP-EDus, respectively). Serum NGAL values were higher in AKI + than in AKI− patients (anesthesia induction, p = 0.037; end-surgery, p = 0.007; 4 h from CPB start, p = 0.093; 24 h from CPB start, p = 0.024. However, combining RRI with serum NGAL at end-surgery did not provide a clear-cut advantage in predicting AKI. In patients undergoing MHS, increased echo-Doppler ultrasound-derived RRI at end-surgery is significantly associated with the risk of AKI, but has limited practical utility for identifying the patients who will develop AKI.

Protein Energy Wasting (PEW) is a pathological condition characterized by a progressive reduction of protein and energy stores. PEW has a high prevalence among patients with CKD/ESRD (Chronic Kidney Disease/End Stage Renal Disease) and is closely associated with adverse clinical outcomes and increased rate of hospitalization, complications and mortality. The multifactorial pathogenesis of PEW is complex. A key role is played both by the reduced intake of nutrients and the condition of hypercatabolism/reduced anabolism typical of renal patients. The approach to prevent or treat PEW has several milestones such as reduction of potential risk factors, improvement in lifestyle and correction of any factor related to dialysis. It also needs a periodic assessment of nutritional status by using biochemical markers, body and muscle mass variables, nutritional scores and instrumental methods, aiming for an early diagnosis. In case of reduced protein and energy intake, the administration of nutrients during dialysis, or the use of oral supplements specific for renal patients are the first nutritional interventions recommended. In fact, oral nutritional supplementation represents the most effective nutritional approach to PEW prevention and treatment. It is simple and safe and it has a positive impact on quality of life and survival of haemodialysis patients. In the case of failure of oral supplementation, nutritional support should be enhanced by using intradialytic parenteral nutrition (IDPN). If the patient has difficulty in swallowing or IDPN is insufficient, total enteral nutrition should be considered.

Hyponatremia is the most frequent electrolyte disorder in hospitalized patients and it is associated with unfavorable clinical outcomes as well as increased hospital costs. Its clinical presentation may be highly variable, ranging from asymptomaticity to neurologic emergencies with seizures or coma as signs of rapidly worsening cerebral edema. In these cases, prompt treatment is mandatory to avoid the patients death. On the other hand, in the case of gradual development of hyponatremia, it is imperative that its correction be also appropriately slow in order to avoid another neurological catastrophe, namely the osmotic demyelination syndrome. Whilst recent international guidelines and expert consensus agree on the approach to the treatment of acute severe and symptomatic hyponatremia, the recommendations on pharmacological therapy in chronic hyponatremia diverge, particularly as to the potential use of vasopressin antagonists. This review is aimed at summarizing essential aspects of epidemiology, pathophysiology and the diagnostic process of hyponatremia, to set the ground for a practical as well as evidence-based approach to treatment. As a guide through the discussion of the available evidence, a clinical case is presented in which the patients history and laboratory data are crucial for identifying the etiology of hyponatremia. The severe neurological signs at presentation justify an emergency treatment with hypertonic saline, as indicated. Subsequently, as the neurological emergency subsides, we discuss the need to revert the trend towards hypercorrection by an apparently counterintuitive approach, based in fact on sound pathophysiological grounds, with continuous infusion of hypotonic solutions and administration of desmopressin.

Derangements of glucose metabolism are common among critically ill patients. Critical illness- associated hyperglycemia (CIAH) is characterized by raised blood glucose levels in association with an acute event that is reversible after resolution of the underlying disease. CIAH has many causes, such as changes in counter-regulatory hormone status, release of sepsis mediators, insulin resistance, drugs and nutritional factors. It is associated with increased mortality risk. This association appears to be strongly influenced by diabetes mellitus as a comorbidity, suggesting the need for an accurate individualization of glycemic targets according to baseline glycemic status. Hypoglycemia is also very common in this clinical context and it has a negative prognostic impact. Many studies based on intensive insulin treatment protocols targeting normal blood glucose values have in fact documented both an increased incidence of hypoglycemia and an increased mortality risk. Finally, glycemic control in the ICU is made even more complex in the presence of acute kidney injury. On one hand, there is in fact a reduction of both the renal clearance of insulin and of gluconeogenesis by the kidney. On the other hand, the frequent need for renal replacement therapy (dialysis / hemofiltration) may result in an energy intake excess, under the form of citrate, lactate and glucose in the dialysate/reinfusion fluids. With regard to the possible renal protective effects afforded by intensive glycemic control protocols, the presently available evidence does not support a reduction in the incidence of AKI and/or the need for RRT with this approach, when compared with standard glucose control. Thus, the most recent guidelines now suggest higher blood glucose targets (180 mg/dl or 140-180 mg/dl) than in the past (80-110 mg/dl). Albeit with limited evidence, it seems reasonable to extend these indications also to patients with AKI in the intensive care unit. Further studies are needed in order to better ascertain the effects of dysglycemia on the outcome of patients with AKI.

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.

Colistin (CS) is a polymyxin with bactericidal activity, which is increasingly used in nosocomial infections associated with multidrug-resistant Gram-negative bacteria (MDR-GNB). Intravenous CS is usually administered as a less toxic pro-drug, i.e. colistin sodium methanesulfonate (CMS). In water-containing solutions, CMS undergoes a spontaneous hydrolysis to form a complex mixture of partially sulfomethylated derivatives and CS. Pharmacokinetic of CS is dependent on the route of administration, i.e. parenteral, intramuscular, nebulized, intrathecal/intraventricular. Renal toxicity is the most common adverse effect of CS treatment, as the drug is excreted primarily by the kidney and elevated levels of CS may further impair renal function, with a dose-dependent effect. Clinical manifestations of CS associated nephrotoxicity include acute kidney injury, proteinuria and tubular damage. Only few data are currently available on the effects of different renal replacement therapy modalities on CS pharmacokinetics. In patients undergoing the most efficient forms of renal replacement therapies, the extracorporeal clearance of CMS may result in a substantial removal of the antibiotic. Thus, in this setting, the recommended daily doses should be increased. Future studies should better explore CS pharmacokinetics in patients undergoing different modalities of renal replacement therapy.

Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years.

Introduction: Mortality in dialysis patients is higher than in the general population, and cardiovascular disease represents the leading cause of death. Hypertension and volume overload are important risk factors for the development of left ventricular hypertrophy (LVH) in hemodialysis (HD) and peritoneal dialysis (PD) patients. Other factors are mainly represented by hyperparathyroidism, vascular calcification, arterial stiffness and inflammation. The aim of this study was to compare blood pressure (BP) and metabolic parameters with cardiovascular changes [cardiothoracic ratio (CTR), aortic arch calcification (AAC) and LV mass index (LVMI)] between PD and HD patients. Materials and Methods: 45 patients (23 HD and 22 PD patients) were enrolled. BP measurements, echocardiography and chest X-ray were performed in each patient to determine the LVMI and to evaluate the CTR and AAC. Inflammatory indexes, intact parathyroid hormone (iPTH) and arterial blood gas analysis were also evaluated. Results: LVMI was higher in PD than HD patients (139 ± 19 vs. 104 ± 22; p = 0.04). In PD patients, a significant correlation between iPTH, C-reactive protein and the presence of LVH was observed (r = 0.70, p = 0.04; r = 0.70, p = 0.03, respectively). The CTR was increased in PD patients as compared to HD patients, while no significant differences in cardiac calcifications were determined. Conclusions: Our data indicate that HD patients present more effective BP control than PD patients. Adequate fluid and metabolic control are necessary to assess the adequacy of BP, which is strongly correlated with the increase in LVMI and with the increased CTR in dialysis patients. PD is a home therapy and allows a better quality of life, but PD patients may present a further increased cardiovascular risk if not adequately monitored. © 2014 S. Karger AG, Basel

Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.

Low dialysate to blood flow rate ratios are a unique characteristic of continuous arteriovenous hemodiafiltration (CAVHDF) that should allow complete saturation of dialysis fluid with small-molecular-weight blood solutes. The aim of the investigation was to evaluate the performance of different hemofilters in CAVHDF. In 10 critically ill patients with acute renal failure, the efficiency of four hollow-fiber hemofilters, polyamide 0.6 m2, polyacrylonitrile (PAN) 0.3 and 0.6 m2, acrylonitrile sodium methallylsulfonate (AN69HF) 0.6 m2, has been evaluated. For comparison, dialysate flow rates (Qdi) were standardized to 16.6 and 25 ml/min. Samples for urea nitrogen were obtained from the arterial blood line (Cbi) and from the dialysate exit port (Cdo) within 24-hour running time. Outflowing dialysate (Qdo) was also measured at the same time. Blood flow (Qb) was calculated by the bubble transit time technique. Diffusive and total urea clearances were determined. AN69HF and PAN hemofilters provided higher clearances than the polyamide hemofilter. Despite the smaller surface area, PAN 0.3 m2 had a total urea clearance comparable to that of PAN 0.6 m2 and AN69HF at Qdi = 16.6 ml/min. While at Qdi = 16.6 ml/min equilibrium between blood and dialysate (Cdo/Cbi ≅ 1) occurred with the AN69HF and PAN hemofilters, at Qdi = 25 ml/min the equilibrium was obtained only with the AN69HF hemofilter. In conclusion, almost complete urea saturation of dialysis fluid has not been obtained with all hemofilters tested here. In our experience, membrane characteristics play an important role in determining diffusive efficiency in CAVHDF.

A simple anticoagulation protocol was developed for sustained low-efficiency dialysis (SLED) in patients with AKI, based on the use of anticoagulant citrate dextrose solution formulation A (ACD-A) and standard dialysis equipment. Patients' blood recalcification was obtained from calcium backtransport from dialysis fluid.All patients treated with SLED (8- to 12-hour sessions) for AKI in four intensive care units of a university hospital were studied over a 30-month period, from May 1, 2008 to September 30, 2010. SLED interruptions and their causes, hemorrhagic complications, as well as coagulation parameters, ionized calcium, and blood citrate levels were recorded.This study examined 807 SLED sessions in 116 patients (mean age of 69.7 years [SD 12.1]; mean Acute Physiology and Chronic Health Evaluation II score of 23.8 [4.6]). Major bleeding was observed in six patients (5.2% or 0.4 episodes/100 person-days follow-up while patients were on SLED treatment). Citrate accumulation never occurred, even in patients with liver dysfunction. Intravenous calcium for ionized hypocalcemia (3.6 mg/dl or0.9 mmol/L) was needed in 28 sessions (3.4%); in 8 of these 28 sessions (28.6%), low ionized calcium was already present before SLED start. In 92.6% of treatments, SLED was completed within the scheduled time (median 8 hours). Interruptions of SLED by impending/irreversible clotting were recorded in 19 sessions (2.4%). Blood return was complete in 98% of the cases. In-hospital mortality was 45 of 116 patients (38.8%).This study protocol affords efficacious and safe anticoagulation of the SLED circuit, avoiding citrate accumulation and, in most patients, systematic calcium supplementation; it can be implemented with commercial citrate solutions, standard dialysis equipment, on-line produced dialysis fluid, and minimal laboratory monitoring.

Protein-energy malnutrition (PEW) is highly prevalent in patients with end-stage renal disease (ESRD) and is associated with a significant increase of the already high mortality and morbidity risk typical of this clinical setting. Since a key mechanism of PEW in ESRD is inadequate nutrient intake, oral nutritional supplements are extensively employed, and have been demonstrated to be highly effective in PEW prevention and treatment. Intradialytic parenteral nutrition (IDPN), i.e. the administration of nutrients through the extracorporeal circuit during hemodialysis, has also been proposed as a modality of nutritional support for patients with ESRD. However, even though metabolic/nutritional status is improved by this nutritional approach, the evidence linking IDPN to decreased hospitalization rate and lower mortality risk is still scant. The aim of the present paper is to review the role of IDPN as a modality of nutritional supplementation for ESRD patients on hemodialysis. To this end, quantitative and qualitative aspects, practical management, the indications, and limits of IDPN are discussed. On the basis of the available evidence, it is suggested that IDPN is a safe and efficacious modality of nutritional support in ESRD, and could represent an adjunctive strategy for patients with reduced spontaneous dietary intake when intensive dietetic counseling and oral supplementation have failed.

The term 'kidney dysfunction' is increasingly used in cardiological literature to indicate different forms of impaired kidney function which can usually be grouped within the broad categories of Acute Kidney Injury (AKI) or Chronic Kidney Disease (CKD).In this review, renal function parameters commonly utilized in patients with acutely decompensated heart failure are illustrated. Some concepts of definition and classification of renal dysfunction in this clinical setting are presented, on the basis of the most recent data in the literature. Aspects of epidemiology and limits of methodologies are explored, in addition to the correct interpretation of findings, and the impact and prognostic value of renal dysfunction within the context of heart failure will be discussed.An impairment of kidney function is frequently observed in patients with heart failure, especially during the acutely decompensated phase (Acutely Decompensated Heart Failure or ADHF). Importantly, this complication may impact negatively on clinical outcomes, as well as directly affecting the choice of therapeutic approach, especially when congestive cardiac failure is present. New, recently proposed bio-markers are indicative of kidney injury and cannot be used to replace classical functional indexes.The evaluation of kidney function, together with the correct interpretation of the significance of clinical findings and the limitations of specific laboratory results, bears major methodological relevance for the care of patients with heart failure. At the present time, more extensive utilization of the new kidney injury bio-markers cannot be recommended in the care of patients with acute decompensated heart failure.

Protein-energy wasting is common in patients with acute kidney injury (AKI) and represents a major negative prognostic factor. Nutritional support as parenteral and/or enteral nutrition is frequently needed because the early phases of this are often a highly catabolic state, although the optimal nutritional requirements and nutrient intake composition remain a partially unresolved issue. Nutrient needs of patients with AKI are highly heterogeneous, depending on different pathogenetic mechanisms, catabolic rate, acute and chronic comorbidities, and renal replacement therapy (RRT) modalities. Thus, quantitative and qualitative aspects of nutrient intake should be frequently evaluated in this clinical setting to achieve better individualization of nutritional support, to integrate nutritional support with RRT, and to avoid under- and overfeeding. Moreover, AKI is now considered a kidney-centered inflammatory syndrome; indeed, recent experimental data indicate that specific nutrients with anti-inflammatory effects could play an important role in the prevention of renal function loss after an episode of AKI.

Background Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid–base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. Methods To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5–3 mmol/l) and a higher than usual target circuit-Ca2+ (≤0.5 mmol/l) have been adopted. Results Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca2+ in protocol B (0.37 vs 0.42 mmol/l, p

Purpose The need for prolonged anticoagulation and the occurrence of hypophosphatemia are well known drawbacks of continuous renal replacement therapies (CRRT). The aim was to evaluate the effects on acid-base status and serum phosphate of a regional citrate anticoagulation (RCA) protocol for continuous veno-venous hemofiltration (CVVH) combining the use of citrate with a phosphate-containing replacement fluid. Methods In a small cohort of heart surgery patients undergoing CRRT for acute kidney injury, we adopted an RCA-CVVH protocol based on a commercially available citrate solution (18 mmol/l) combined with a recently introduced phosphate-containing replacement fluid (HCO3− 30 mmol/l, phosphate 1.2), aimed at preventing phosphate depletion. Results In 10 high bleeding-risk patients, the RCA-CVVH protocol provided an adequate circuit lifetime (46.8 ± 30.3 h) despite the adoption of a low citrate dose and a higher than usual target circuit Ca2+ (≤0.5 mmol/l). Acid-base status was adequately maintained without the need for additional interventions on RCA-CVVH parameters and without indirect sign of citrate accumulation [(pH 7.43 (7.41-7.47), bicarbonate 24.4 mmol/l (23.2-25.6), BE 0 (-1.5 to 1.1), calcium ratio 1.97 (1.82-2.01); median (IQR)]. Serum phosphate was steadily maintained in a narrow range throughout RCA-CVVH days [1.1 mmol/l (0.9-1.4)]. A low amount of phosphorus supplementation (0.9 ± 2 g/day) was required in only 30% of patients. Conclusions Although needing further evaluation, the proposed RCA-CVVH protocol ensured a safe and effective RCA without electrolyte and/or acid-base derangements. CRRT-induced hypophosphatemia was prevented in most of the patients by the adoption of a phosphate-containing replacement solution, minimizing phosphate supplementation needs.

The aim of this study was to examine serum angiotensin converting enzyme (SACE) activity and the renin-angiotensin-aldosterone system in patients on chronic haemodialysis during one routine dialysis session. Fourteen patients (8 men and 6 women; mean age 51.9 +/- 17 years) with end stage renal disease, receiving regular haemodialysis treatment for an average of 6 months, were studied. The patients were dialysed for 4 hours three times a week using cellulose membranes (cuprophan). After an overnight fast blood samples were taken from the patients before and after the haemodialysis session. Serum and plasma were separated and stored at -20 degrees C until assayed for SACE, plasma renin activity (PRA) and plasma aldosterone (PA). For comparison, SACE, PRA and PA were also measured in 8 patients after renal allotransplantation and on treatment with cyclosporin A (5 men, 3 women; mean age 38.9 +/- 12.3 years) and in 19 healthy subjects (13 men, 6 women; mean age 38.9 +/- 12.3 years). SACE levels in patients with chronic renal failure and on haemodialysis (17.55 +/- 9.03 nmol/ml/min) and in patients with renal transplantation (18.12 +/- 3.92) were significantly higher than those of the healthy subjects (9.27 +/- 1.67) (p0.0001, respectively). At the end of the dialysis session SACE levels in patients with chronic renal failure (14.9 +/- 7.19) did not increase in respect to pre-dialysis levels (17.55 +/- 9.03; p = 0.132). PRA and PA values increased after the dialysis session (p0.026 and p0.044, respectively). Correlation of SACE with PRA and PA was not demonstrated before or after the dialysis session. In patients with chronic renal failure and on haemodialysis our findings suggest that a disarrangement exists between the circulatory components of the reninangiotensin-aldosterone system before and after the dialysis session.

In the critically ill patient, acute kidney injury (AKI) is frequently associated with infective complications requiring appropriate antimicrobial treatment. AKI and multiple organ dysfunction syndrome can affect the pharmacokinetic parameters of many drugs. Furthermore, the start of renal replacement therapy (RRT) is an additional variable to be taken into consideration to avoid inappropriate antimicrobial therapy. Continuous renal replacement therapies (CRRT) are widely adopted in the intensive care unit (ICU) and antibiotics that are significantly eliminated by the kidney are likely to be removed during RRT. Generally, drug-dosing adjustments are required if the extracorporeal clearance accounts for more than 25-30% of the total body clearance. The molecular weight cutoffs of the more widely used membranes are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the antibiotics most commonly used in ICU patients. However, CRRTs are still not standardized and the impact of RRT on plasma drug concentrations can be substantially different depending on the CRRT modality (diffusive, convective or both), membrane characteristics and delivered dialysis dose. In any case, drug-dosing adjustments should be based on the knowledge of the pharmacokinetic and pharmacodynamic properties of the different classes of antimicrobials, taking into account that high extracorporeal clearances could lead to drug underexposure in clinical conditions where appropriate antibiotic treatment is essential.

Introduction Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding who are undergoing continuous renal replacement therapy (CRRT). The aim of this study was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCA-continuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution. Methods In high bleeding-risk cardiac surgery patients, we adopted, as an alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid. Statistical analysis was performed using the Student t-test or analysis of variance (ANOVA) with post-hoc tests, Wilcoxon or Kruskal-Wallis tests for non-parametric analysis, and Kaplan-Meier survival analysis with Log Rank test. Results Thirty-three patients (age 70.8 ± 9.5, Sequential Organ Failure Assessment (SOFA) score 13.9 ± 2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8 ± 35.4 hours, median 41, 152 circuits) was significantly longer (P < 0.0001) when compared with heparin (30.6 ± 24.3 hours, median 22, 73 circuits) or no anticoagulation (25.7 ± 21.2 hours, median 20, 77 circuits). Target circuit and systemic Ca++ were easily maintained (0.37 ± 0.09 and 1.18 ± 0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8 ± 5.9 mmol/hours) in 27 patients. The probability of circuit running at 24, 48, 72 hours was higher during RCA-CVVH (P < 0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (P < 0.0001). RCA was associated with a lower transfusion rate (P < 0.02). Platelet count (P = 0.012) and antithrombin III activity (P = 0.004) increased throughout RCA-CVVH, reducing the need for supplementation. Conclusions RCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation.