Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

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 (Glycophos™ 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: Forty-seven 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 Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. 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 6 June 2019).

Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions.

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 < .05 for all). The frequency of hypophosphatemia increased after the first through the third SLED session (P = .012). Intravenous phosphate supplementation was scheduled after 12/45 (26.7%) SLED sessions complicated by hypophosphataemia. The overall ICU mortality was 23.1% (15/65). In Cox regression models, after adjusting for potential confounders and for current s-P, intravenous phosphate supplementation was associated with a decrease in ICU mortality [adjusted hazard ratio: 0.24 (95% confidence interval: 0.06 to 0.89; P = 0.033)]. 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.

Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients.

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

Prevention of hypomagnesemia in critically ill patients with acute kidney injury on continuous kidney replacement therapy: the role of early supplementation and close monitoring.

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.

Effects of intradialytic aerobic exercise on hemodialysis patients: a systematic review and meta-analysis.

OBJECTIVE: Intradialytic exercise (IDE) is not yet a routine practice for hemodialysis patients, the lack of guidelines supporting it being a major reason. This systematic review and meta-analysis of aerobic IDE interventions examined the efficacy of IDE regarding quality of life (QOL), serum phosphorus, dialysis efficiency, inflammatory status, vitamin D3, parathyroid hormone, intake of phosphate binders, mortality and hospitalization rate. METHODS: Pubmed, Medline (Ovid), Embase (Ovid), Cochrane, and Cinahl (EBSCO) databases were searched to retrieve studies up to June 12, 2018. A manual reference search was also performed. Studies were included if they evaluated (a) aerobic IDE effect on at least one of our study parameters, (b) adult hemodialysis patients, (c) patients for > 1 month. RESULTS: Twenty-two studies were retrieved (706 participants), of which 12 were eligible for meta-analysis. Aerobic IDE had a significant positive effect on the QOL physical component score (QOL-PSC) and on mental component score (QOL-MCS) of SF36, but not on serum phosphorus or Kt/V. CONCLUSIONS: IDE incorporation into clinical practice has a significant positive effect on QOL-PSC and QOL-MCS. In the reviewed studies, IDE did not result in any health hazard in hemodialysis patients. Nevertheless, future research should assess the long-term effectiveness and safety of IDE. The limitations of this review include the lack of quality analysis of the studies, the limited number of studies that could be included in the meta-analysis, the diversity in the exercise intensity, duration and modality, and the limited data for several outcomes. PROSPERO REGISTRATION ID: CRD42016052062.

[Nutritional diet therapy in the management of the patient with Chronic Kidney Disease in advanced phase to delay the beginning and reduce the frequency of dialysis. An option also in the pre-emptive transplant program].

The Italian nephrology has a long tradition and experience in the field of dietetic-nutritional therapy (DNT), which is an important component in the conservative management of the patient suffering from a chronic kidney disease, which precedes and integrates the pharmacological therapies. The objectives of DNT include the maintenance of an optimal nutritional status, the prevention and / or correction of signs, symptoms and complications of chronic renal failure and, possibly, the delay in starting of dialysis. The DNT includes modulation of protein intake, adequacy of caloric intake, control of sodium and potassium intake, and reduction of phosphorus intake. For all dietary-nutritional therapies, and in particular those aimed at the patient with chronic renal failure, the problem of patient adherence to the dietetic-nutritional scheme is a key element for the success and safety of the DNT and it can be favored by an interdisciplinary and multi-professional approach of information, education, dietary prescription and follow-up. This consensus document, which defines twenty (20) essential points of the nutritional approach to patients with advanced chronic renal failure, has been written, discussed and shared by the Italian nephrologists together with representatives of dietitians (ANDID) and patients (ANED).

Nutrients, Nutraceuticals, and Xenobiotics Affecting Renal Health.

Chronic kidney disease (CKD) affects 8⁻16% of the population worldwide. In developed countries, the most important risk factors for CKD are diabetes, hypertension, and obesity, calling into question the importance of educating and acting on lifestyles and nutrition. A balanced diet and supplementation can indeed support the maintenance of a general health status, including preservation of renal function, and can help to manage and curb the main risk factors for renal damage. While the concept of protein and salt restriction in nephrology is historically acknowledged, the role of some nutrients in renal health and the importance of nutrition as a preventative measure for renal care are less known. In this narrative review, we provide an overview of the demonstrated and potential actions of some selected nutrients, nutraceuticals, and xenobiotics on renal health and function. The direct and indirect effects of fiber, protein, fatty acids, curcumin, steviol glycosides, green tea, coffee, nitrates, nitrites, and alcohol on kidney health are reviewed here. In view of functional and personalized nutrition, understanding the renal and systemic effects of dietary components is essential since many chronic conditions, including CKD, are related to systemic dysfunctions such as chronic low-grade inflammation.

Dietary protein and nutritional supplements in conventional hemodialysis.

Protein energy wasting (PEW) is a condition commonly occurring among patients with ESRD on hemodialysis. PEW is characterized by depletion of protein and energy stores and is caused by multiple factors related to chronic kidney disease, acute and chronic comorbidities and by renal replacement therapy itself. Anorexia is central in the pathogenesis of PEW; it is frequently observed in these patients whose protein and energy intakes are typically lower than guidelines recommendations. If untreated, PEW invariably leads to major complications, and may activate a vicious circle with further worsening of nutritional status. Dietary counseling and nutritional status monitoring play a key role in the prevention and treatment of PEW, since they allow an early identification of high risk patients, as well as the assessment of the response to nutritional intervention. Different nutritional approaches can be implemented following thorough nutritional counseling. These are chosen on the basis of patients' spontaneous dietary intake, severity of PEW and acute comorbidities. Initially, regular encounters with the dietitian allow patients to clarify doubts and strengthen basic concepts on nutrition to improve dietary intake and prevent PEW. When PEW is present or the patient is at high risk, the clinician may opt for the administration of oral intradialytic or daily supplements, aiming at increasing energy and protein intake, while in selected cases intradialytic parenteral nutrition may be used. This review addresses the main issues of nutritional status in ESRD patients on hemodialysis-its evaluation and monitoring, as well as at describing the available nutritional interventions.

Nutritional treatment of advanced CKD: twenty consensus statements.

The Italian nephrology has a long tradition and experience in the field of dietetic-nutritional therapy (DNT), which is an important component in the conservative management of the patient suffering from a chronic kidney disease, which precedes and integrates the pharmacological therapies. The objectives of DNT include the maintenance of an optimal nutritional status, the prevention and/or correction of signs, symptoms and complications of chronic renal failure and, possibly, the delay in starting of dialysis. The DNT includes modulation of protein intake, adequacy of caloric intake, control of sodium and potassium intake, and reduction of phosphorus intake. For all dietary-nutritional therapies, and in particular those aimed at the patient with chronic renal failure, the problem of patient adherence to the dietetic-nutritional scheme is a key element for the success and safety of the DNT and it can be favored by an interdisciplinary and multi-professional approach of information, education, dietary prescription and follow-up. This consensus document, which defines twenty essential points of the nutritional approach to patients with advanced chronic renal failure, has been written, discussed and shared by the Italian nephrologists together with representatives of dietitians (ANDID) and patients (ANED).

Efficacy of Nutritional Interventions on Inflammatory Markers in Haemodialysis Patients: A Systematic Review and Limited Meta-Analysis.

Low-grade chronic inflammation is prevalent in patients undergoing haemodialysis (HD) treatment and is linked to the development of premature atherosclerosis and mortality. The non-pharmacological approach to treat inflammation in HD patients through nutritional intervention is well cited. We aimed to assess the efficacy of different nutritional interventions at improving inflammatory outcomes in HD patients, based on markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). We searched PubMed, Cochrane Library, and Embase for randomized controlled trials (RCT) published before June 2017. Inclusion criteria included RCTs on adult patients on maintenance HD treatment with duration of nutritional interventions for a minimum 4 weeks. Risk of bias was assessed using the Jadad score. In total, 46 RCTs experimenting different nutritional interventions were included in the review and categorized into polyphenols rich foods, omega-3 fatty acids, antioxidants, vitamin D, fibres, and probiotics. Meta-analyses indicated significant reduction in CRP levels by omega-3 fatty acids (Random model effect: -0.667 mg/L, p < 0.001) and vitamin E (fixed model effect: -0.257 mg/L, p = 0.005). Evidence for other groups of nutritional interventions was inconclusive. In conclusion, our meta-analysis provided evidence that omega-3 fatty acids and vitamin E could improve inflammatory outcomes in HD patients.

Preventing Continuous Renal Replacement Therapy-Induced Hypophosphatemia: An Extended Clinical Experience with a Phosphate-Containing Solution in the Setting of Regional Citrate Anticoagulation.

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 (<0.81 mmol/l) or moderate (<0.61 mmol/l) hypophosphatemia; severe hypophosphatemia (<0.32 mmol/l) never occurred. After 72 h 88% of the patients were normophosphatemic, 9% hyperphosphatemic and 3% hypophosphatemic. 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.

Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review.

BACKGROUND: Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. METHOD: Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported. RESULTS: Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2-2.3 L/h for CVVH, 0.9-2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only. CONCLUSIONS: Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug monitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research settings.

[Protein-energy wasting and nutritional supplementation in chronic hemodialysis]. / Deplezione proteico-energetica e supplementazione nutrizionale nei pazienti in emodialisi cronica.

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.

Severe hypokalemia and hypophosphatemia presenting with carpopedal spasm associated with rhabdomyolysis.

Background Severe hypokalemia, defined as serum potassium < 2.5 mEq/L, may lead to neuromuscular, gastrointestinal, and ECG abnormalities. Neuromuscular consequences of hypokalemia include weakness, cramps, rarely paralysis, eventually progressing to rhabdomyolysis. Case presentation We report a case of a 4-year-old girl presenting carpopedal spasm and rhabdomyolysis due to severe hypokalemia associated to hypophosphatemia and hypovolemia. At one month of age she underwent an ileal resection because of a neonatal necrotizing enterocolitis, and a bowel resection at two years of age, because of sub-occlusive episodes. The child had frequent episodes of diarrhoea and was treated with oral white clay (kaolin) and a restrictive diet. Three days prior the admission to the hospital she had numerous episodes of watery diarrhoea. Laboratory tests revealed severe hypokalemia, hypophosphatemia, normal calcium levels associated with marked dehydration. An ECG demonstrated sinus bradycardia, ST-segment depression, T-wave flattening, U-wave, and long-QTc. Symmetric carpal and pedal spasms were observed. A marked rise of creatinine phosphokinase and myoglobin associated to cola colored urine was observed. Intravenous supplementation of potassium phosphate as well as adequate volume repletion led to an improvement of the clinical condition, to the disappearance of carpal and pedal spasms, to normalisation of ECG.  Conclusions Careful electrolytes and volume supplementation led to the correction of potential life-threatening arrhythmias and obtained a complete recovery from carpopedal spasm and rhabdomyolysis. Dietary restriction and pharmacological preparations as kaolin have to be administered with caution to treat diarrhea in children and particularly in those who may present other pre-existing risk factors.

Continuous veno-venous hemofiltration using a phosphate-containing replacement fluid in the setting of regional citrate anticoagulation.

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.

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid-base status and phosphate supplementation needs.

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-Ca(2+) (≤ 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-Ca(2+) in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 ± 36.5 vs 53 ± 32.6 hours). Protocol A required additional bicarbonate supplementation (6 ± 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid-base balance without additional interventions: pH 7.43 (7.40-7.46), Bicarbonate 25.3 (23.8-26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 ± 2.4 g/day) and in only 30% of group B patients (0.5 ± 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97-1.45 mmol/l, IQR). CONCLUSIONS: The proposed RCA-CVVHDF protocol ensured appropriate acid-base balance without additional interventions, providing prolonged filter life despite adoption of a higher target circuit-Ca(2+). The introduction of a phosphate-containing solution, in the setting of RCA, significantly reduced CRRT-related phosphate depletion.

Efficacy and safety of a citrate-based protocol for sustained low-efficiency dialysis in AKI using standard dialysis equipment.

BACKGROUND AND OBJECTIVES: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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. RESULTS: 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 or < 0.9 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%). CONCLUSIONS: 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.

Regional citrate anticoagulation in CVVH: a new protocol combining citrate solution with a phosphate-containing replacement fluid.

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.

Specialized nutritional support interventions in critically ill patients on renal replacement therapy.

PURPOSE OF REVIEW: Optimal nutritional requirements and nutrient intake composition for patients with acute kidney injury remain a partially unresolved issue. Targeting nutritional support to the actual protein and energy needs improves the clinical outcome of critically ill patients, yet very few data are currently available on this topic in acute kidney injury. In this specific clinical condition the risk for underfeeding and overfeeding may be increased by factors interfering on nutrient need estimation, such as rapidly changing body weight due to fluid balance variations, nutrient losses and hidden calorie sources from renal replacement therapy. Moreover, as acute kidney injury is now considered a kidney-centered inflammatory syndrome, the renoprotective role of specific pharmaconutrients with anti-inflammatory properties remains to be fully defined. This review is aimed at discussing recently published results concerning quantitative and qualitative aspects of the nutritional approach to acute kidney injury in critically ill patients. RECENT FINDINGS: Nutrient needs in patients with acute kidney injury can be difficult to estimate, and should be directly measured, especially in the ICU setting. In fact, recent findings suggest that hidden calorie sources not routinely taken into account - for example, calories from anticoagulants and replacement solutions for renal replacement therapy - could be quantitatively relevant in these patients. Moreover, recent experimental data indicate a possible role for some pharmaconutrients with anti-inflammatory effects (glutamine, and omega-3 fatty acids), in both the prevention of renal function worsening, and in the fostering of renal function recovery after an episode of acute kidney injury. SUMMARY: Acute kidney injury includes a highly heterogeneous group of patients with widely varying nutrient needs and intakes. Nutritional requirements, in their quantitative and qualitative aspects, should be frequently assessed, individualized, and carefully integrated with renal replacement therapy, in order to avoid both underfeeding and overfeeding, as well as to exploit possible positive pharmacologic effects of specific nutrients.