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).

Quality improvement project in a neonatal intensive care unit reduced the prevalence and duration of hypophosphatemia with significant and sustainable results.

BACKGROUND: Hypophosphatemia is associated with prolonged mechanical ventilation and may affect growth, bone mineralization, nephrocalcinosis, and mortality in preterm infants. Optimal nutrition practices may decrease risk for hypophosphatemia and improve outcome. METHODS: A quality improvement project was established to improve parenteral and enteral phosphorus intake with the goal to decrease prevalence and duration of hypophosphatemia in the first 14 days in infants <32 weeks' gestation. RESULTS: Among 406 preterm infants, the prevalence of moderate hypophosphatemia decreased from 44% to 19% (P < 0.01) over 4 years. The median duration of moderate hypophosphatemia decreased from 72 h (48-128) to 24 (24-53) (P < 0.01). Daily intakes of parenteral calcium and phosphorus on the fourth day of life increased from 1.5 to 2.5 mEq/kg/day (P < 0.01) and 0.6 to 1.3 mmol/kg/day (P < 0.01), respectively. The median postnatal age of first serum phosphorus concentration assessment decreased from 53 h (41-64) to 32 (24-40) (P < 0.01). CONCLUSION: During this quality improvement project, reduced prevalence and duration of hypophosphatemia in infants <32 weeks' gestation in the first 14 days of life was achieved through the optimization of parenteral and enteral phosphorus intake and improved response to acute hypophosphatemia.

Higher Parenteral Electrolyte Intakes in Preterm Infants During First Week of Life: Effects on Electrolyte Imbalances.

OBJECTIVES: This study aimed to investigate the effects of a higher intake of electrolytes from parenteral nutrition (PN) on plasma electrolyte concentrations in very low birth weight (VLBW, <1500 g) infants. METHODS: This was a single-center cohort study including all VLBW infants born before (n = 81) and after (n = 53) the implementation of a concentrated PN regimen. Daily nutritional intakes and plasma concentrations of sodium, chloride, potassium, phosphate, and calcium were collected from clinical charts. RESULTS: During the first postnatal week, electrolyte intakes were higher in infants who received concentrated PN compared with infants who received original PN. Infants who received concentrated PN had a lower incidence of hypokalemia (<3.5 mmol/L; 30% vs 76%, P < 0.001) and severe hypophosphatemia (<1.0 mmol/L; 2.2% vs 17%, P = 0.02). While the relatively high prevalence of severe hypophosphatemia in infants who received original PN can be explained by a phosphorus intake below the recommendation, the potassium intake during the first 3 postnatal days (mean ± SD: 0.7 ± 0.2 mmol/kg/d) was within the recommendation. The prevalence of early hypernatremia was not affected by the different sodium intake in the 2 groups. CONCLUSIONS: In VLBW infants, a sodium-containing PN solution (about 2.7 mmol/100 mL) does not cause hypernatremia during the first days of life. Furthermore, providing at least 1 mmol potassium/kg/d during the first 3 postnatal days might be necessary to prevent early hypokalemia.

Early vs late initiation of sodium glycerophosphate: Impact on hypophosphatemia in preterm infants <32 weeks.

BACKGROUND & AIMS: Early electrolyte and mineral imbalances have emerged as a conspicuous problem in very preterm babies since the revision of nutrition guidelines and the eventual implementation of early aggressive parenteral nutrition (PN). We opted to carry out a study with the introduction of phosphorus as sodium glycerophosphate in PN from the first day onward to reveal the impact on serum phosphorus and calcium levels following the surge in the incidence of hypercalcemia and hypophosphatemia. METHODS: In this single-center, prospective, observational cohort study, inborn babies <32 gestational weeks and <1500 g between August 2017 and July 2018 were enrolled consecutively. Infants born in the first 6-month of this period were initiated PN (Early phosphorus group) containing phosphorus (1 mmol P as sodium glycerophosphate/100 ml PN) immediately after birth, and in the latter six-months, mineral-free standard PN (Control group) was commenced up until 48 h of life. Parenteral nutritional prescriptions of both groups were similar in terms of macro and micronutrient intakes except for early phosphorus, calcium, and sodium. Serum mineral and electrolyte levels were measured on Days 1-3-7 and compared between the groups. The primary outcome was the presence of hypophosphatemia in the first week of life. The secondary outcome was hypercalcemia, preterm morbidity, and mortality. RESULTS: A total of 261 infants were included in this study. There were 130 babies in Early phosphorus group and 131 in control group. Gestational ages (28.79 ± 2.1 vs 28.46 ± 2.2 weeks, respectively) and birth weights (1138 ± 273 vs 1090 ± 274 g, respectively) were similar in the groups. Mean serum phosphorus levels were higher on all days in Early phosphorus group (p < 0.001). Early phosphorus group had a lower incidence of hypophosphatemia on days 1-3 and 7 (p < 0.001). The percentage of hypercalcemic infants was significantly lower in Early phosphorus group on day 3 (p < 0.001). No difference was noted in terms of hypernatremia in the groups. CONCLUSIONS: Adding phosphorus to PN in the first hours of life reduced the frequency of hypophosphatemia and hypercalcemia without any surge in hypernatremia or morbidity. Nutrition guidelines need to be revised accordingly in terms of early mineral/electrolyte supplementation.

Prophylactic supplementation of phosphate, magnesium, and potassium for the prevention of refeeding syndrome in hospitalized individuals with anorexia nervosa.

Medical stabilization, nutrition rehabilitation, and weight restoration, while minimizing risk for the potentially fatal complication of refeeding syndrome, are the primary goals for the treatment of hospitalized individuals with anorexia nervosa and other restrictive-type eating disorders. The purpose of this review was to examine the literature exploring the prophylactic supplementation of phosphate, magnesium, and potassium, in addition to routine thiamin and multivitamin supplementation, for the prevention of refeeding syndrome in adolescents and adults with anorexia nervosa. Through evaluation of outcomes (including serum electrolyte levels and clinical signs and symptoms such as respiratory failure, cardiac failure, peripheral edema, rhabdomyolysis, and encephalopathy), three studies found that prophylactic supplementation of potassium, magnesium, and/or phosphate were effective in preventing refeeding syndrome or refeeding hypophosphatemia (a characteristic of refeeding syndrome). Although all studies found that prophylactic supplementation was effective in preventing refeeding syndrome, refeeding approaches (including the method, amount, and duration of nutrient delivery) as well as the populations studied varied considerably, making it difficult to arrive at specific recommendations for practice. Randomized controlled trials are needed to further examine the safety and effectiveness of prophylactic supplementation of phosphate, magnesium, and potassium on the prevention of refeeding syndrome, utilizing similar feeding and supplementation protocols.

Impact of different hemodiafiltration solutions on ionemia in long-term CRRT.

Critical patients with Acute Kidney Injury (AKI) requiring renal replacement therapy are in most cases eligible only for continuous modalities where the electrolyte balance control is a critical issue. The standard solutions used for hemodiafiltration, containing potassium at 2 mmol/L and no phosphorus, determines during the extended renal replacement therapy hypokalemia and hypophosphatemia. Therefore, solutions containing potassium and phosphate in physiological concentrations were formulated to avoid electrolyte imbalances and reduce ion alterations in prolonged treatments, these solutions are not routinely used in the standard clinical practice. To avoid electrolyte imbalances, we have first introduced in our practice two different solutions and then we have retrospectively analyzed the electrolyte balance upon these two solutions in order to identity the impact of these solutions on potassium and phosphate according to our clinical practice. We retrospectively analyzed 96 patients treated with Continuous Renal Replacement Therapy (CRRT) in the intensive care units (ICU) at Padua's University Hospital to evaluate the role on electrolyte balance of Phoxilium® and Prismasol 2® that differ in their composition and the need for electrolytes infusions. In the Phoxilium group the frequency of hypokalemia, hypophosphatemia, and the need of potassium and phosphate replacement were significantly reduced resulting in a reduction in complications, workload, and clinical risk associated with infusions of electrolytes. Our data demonstrated that the use of these two different hemodiafiltration solutions can reduce the occurrence of hypokalemia and hypophosphatemia during CRRT performing personalized treatments without the use of potassium and phosphate infusions.

The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis.

BACKGROUND & AIMS: Heavy alcohol consumption is a common cause of acute pancreatitis; however, alcohol abuse does not always result in clinical pancreatitis. As a consequence, the factors responsible for alcohol-induced pancreatitis are not well understood. In experimental animals, it has been difficult to produce pancreatitis with alcohol. Clinically, alcohol use predisposes to hypophosphatemia, and hypophosphatemia has been observed in some patients with acute pancreatitis. Because of abundant protein synthesis, the pancreas has high metabolic demands, and reduced mitochondrial function leads to organelle dysfunction and pancreatitis. We proposed, therefore, that phosphate deficiency might limit adenosine triphosphate synthesis and thereby contribute to alcohol-induced pancreatitis. METHODS: Mice were fed a low-phosphate diet (LPD) before orogastric administration of ethanol. Direct effects of phosphate and ethanol were evaluated in vitro in isolated mouse pancreatic acini. RESULTS: LPD reduced serum phosphate levels. Intragastric administration of ethanol to animals maintained on an LPD caused severe pancreatitis that was ameliorated by phosphate repletion. In pancreatic acinar cells, low-phosphate conditions increased susceptibility to ethanol-induced cellular dysfunction through decreased bioenergetic stores, specifically affecting total cellular adenosine triphosphate and mitochondrial function. Phosphate supplementation prevented ethanol-associated cellular injury. CONCLUSIONS: Phosphate status plays a critical role in predisposition to and protection from alcohol-induced acinar cell dysfunction and the development of acute alcohol-induced pancreatitis. This finding may explain why pancreatitis develops in only some individuals with heavy alcohol use and suggests a potential novel therapeutic approach to pancreatitis. Finally, an LPD plus ethanol provides a new model for studying alcohol-associated pancreatic injury.

Impact of electrolyte-rich dialysate during continuous renal replacement therapy on serum phosphate and potassium in ICU patients.

BACKGROUND: Hypophosphatemia and hypokalemia occur frequently during continuous renal replacement therapy (CRRT). We evaluated serum phosphate and potassium levels in patients administered three different types of dialysis solution. METHODS: The study population consisted of 324 intensive care unit patients who underwent CRRT between January 2015 and December 2018. Patients were divided into three groups: group 1 (n = 105) received Hemosol B0 (no potassium or phosphate); group 2 (n = 78) received Hemosol B0 and potassium-containing solution (MultiBic); and group 3 (n = 141) received phosphate- and potassium-containing solution (Phoxilium), Hemosol B2, Prismasol 2, and Prismasol 4. A different protocol was followed in each group. RESULTS: The incidence rate of hypophosphatemia was 55% lower in group 3 compared to group 1 (incidence rate ratio (IRR) 0.45, 95% confidence interval (CI): 0.33 to 0.61) and 61% lower compared to group 2 (IRR 0.39, 95% CI: 0.29 to 0.53). Group 3 also had a 50% lower incidence rate of hypokalemia compared to group 1 (IRR 0.50, 95% CI: 0.29 to 0.88). The negative slope in phosphate level in group 3 was greater than that in group 1 (ß = 0.19, 95% CI: 0.02 to 0.37, p = 0.032), while the negative slope in the potassium level was greater in group 2 than in group 1(ß = 0.10, 95% CI: 0.03 to 0.17, p = 0.008). Additional intravenous calcium was not used in any case, and most cases of acid-base disturbances were well controlled. CONCLUSIONS: The use of phosphate- and potassium-containing with a proper CRRT protocol prevented decreases in serum phosphate and potassium levels, thus also preventing hypophosphatemia and hypokalemia, and additional replacement during CRRT.

Long-Term Follow-up of Hypophosphatemic Bone Disease Associated With Elemental Formula Use: Sustained Correction of Bone Disease After Formula Change or Phosphate Supplementation.

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus (R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution (R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

[Hypophosphatemia after iron infusion†: can we still ignore it†?] / Hypophosphatémie après perfusion de fer†: pouvons-nous encore l'ignorer†?

The occurrence of hypophosphatemia after iron infusion has been known for a long time but has only recently led to clinical concerns. It was considered to be of low clinical importance. The elucidation of the physiological mechanisms responsible for this effect, involving FGF23 and the ever-increasing number of cases with regard to the potentially very serious consequences on bone metabolism have recently raised probably justified concerns. In this article, we summarize the mechanisms of phosphate homeostasis, how intravenous iron can induce a phosphate deficiency and what precautions and treatments needs to be undertaken to prevent it.

La survenue d'une hypophosphatémie après une perfusion de fer est connue de longue date mais n'a que depuis peu suscité des inquiétudes cliniques. L'élucidation des mécanismes physiologiques à l'origine de cet effet indésirable, impliquant le facteur de croissance des fibroblastes 23 (FGF23), et les rapports de cas toujours plus nombreux quant aux conséquences potentiellement graves sur le métabolisme osseux ont récemment soulevé des préoccupations probablement justifiées. Dans cet article, nous résumons les mécanismes de régulation du phosphate et la manière dont le fer par voie intraveineuse peut induire un déficit en phosphate, ainsi que les précautions et traitements à mettre en œuvre pour le prévenir.

Report of Dialysis-Induced Hypophosphatemia Leading to Reversible Encephalopathy Prevented by Adding Phosphorus to the Dialysate.

Patients with advanced chronic kidney disease have an inability to excrete phosphorus normally leading to high serum concentrations of phosphorus. The hyperphosphatemia is even more pronounced in dialysis patients who often require large doses of phosphorus binders to combat the problem. Hemodialysis is able to remove fair amount of the extra phosphorus; however, the removal is often hampered by the fact that the phosphorus is removed only from the extracellular compartment and phosphorus is mainly intracellular. The end result being a high serum phosphorus concentration at the beginning of dialysis, a sharp decline in the value by the end of dialysis and significant rebound of serum phosphorus concentration a few hours after stopping dialysis as phosphorus moves out of the cells. Here, we describe 2 hemodialysis patients with normal predialysis serum phosphorus concentration and preexisting conditions that made them at risk for developing encephalopathy who developed recurrent obtundation toward the end of the dialysis treatments. After confirming critical postdialysis hypophosphatemia, phosphorus was added to the dialysate baths and the episodes of encephalopathy associated with dialysis ceased.

Iron Infusion and Induced Hypophosphatemia: The Role of Fibroblast Growth Factor-23.

The mechanism of action of fibroblast growth factor-23 (FGF23) is becoming increasingly clearer as a result of studies that have defined its structure and pleiotropic effects. Furthermore, data are emerging on the effects exerted on this hormone by iron administration. Ten main iron formulations are recognized (with clear differences in composition and possible reactions of intolerance and anaphylaxis), which are indicated for iron deficiency anemia, including nephropathic subjects, as suggested by medical guidelines. With some types of iron formulation (especially iron carboxymaltose) a particular side effect has been observed: hypophosphatemia, mediated by FGF23. This review aims to draw attention to this correlation and the contradiction represented by the presence of both positive and negative modulation by FGF23, with the effects induced by its increase even after long-term treatment with iron formulation. However, more evidence is needed to understand the reasons for this differential stimulation.

Changing paradigms in metabolic support and nutrition therapy during critical illness.

PURPOSE OF REVIEW: To summarize the most recent advances in acute metabolic care and critical care nutrition. RECENT FINDINGS: Recent research has demonstrated unknown consequences of high protein and amino acid administration in the early phase of ICU stay associated with dysregulated glucagon release leading to hepatic amino acid breakdown and suggested adverse effects on autophagy and long-term outcome. Progress has been made to measure body composition in the ICU. Refeeding hypophosphatemia and refeeding syndrome are common during critical illness, phosphate monitoring is essential after the start of nutrition therapy, and caloric restriction is recommendable in these patients.In recent studies, enteral nutrition is no longer superior to parenteral nutrition and signals of harm using the enteral route in shock have been suggested. However, during extracorporeal life support, enteral nutrition seems well tolerated. Intermittent or bolus enteral feeding seems an exciting concept concerning its potential anabolic effects. Studies on vitamin C, thiamine, and corticosteroid combinations suggest potential to improve outcome. SUMMARY: These new findings will probably change the practice of metabolic and nutrition therapy in critical illness and challenge paradigms advocated for long.

Prevention of hypophosphatemia during continuous renal replacement therapy-An overlooked problem.

Hypophosphatemia is a common and potentially serious complication occurring during continuous renal replacement therapy (CRRT). Phosphate supplementation is required in the vast majority of patients undergoing CRRT, particularly beyond the first 48 hours. Supplementation can be provided either as a standalone oral or parenteral treatment or as an additive to CRRT solutions. Each approach has advantages and disadvantages, and clinicians must weigh the individual factors most relevant in their practice setting. Currently there are no consensus protocols for phosphate replacement in CRRT, and many centers replete phosphate in response to hypophosphatemia as opposed to pre-emptively. Repletion protocols have also been challenged in recent years by shortages in injectable phosphate solutions. More recently a commercially available phosphate-containing CRRT solution was approved in the United States, but there has been limited clinical experience with this product. In this review, we present recommendations for phosphate repletion in CRRT to prevent hypophosphatemia, and describe our experience using phosphate-containing CRRT solutions.

Targeted inhibition of Klotho binding to fibroblast growth factor 23 prevents hypophosphetemia.

Klotho is a transmembrane protein which plays significant role in the pathogenesis of phosphate ion (Pi)-related disorders. Pi accumulation in human kidney tissues results in the major metabolic disorders due to malfunctioning of Klotho-FGFR1-FGF23 trimeric complex. The potential role of Klotho in Pi metabolism was elaborated through modeling and interaction analysis of glycosyl hydrolase (GS1 and GS2) domains with Fibroblast growth factor 23 (FGF23). In order to inhibit the association of Klotho and FGF23, binding patterns of three reported hits (N-(2-chlorophenyl)-1H-indole-3-carboxamide, N-[2-(1-cyclohexen-1-yl)ethyl]-6,7,8,9-tetrahydropyrido[1,2-e]purin-4-amine and 2-(1-propyl)amino-11-chlorothiazolo[5,4-a]acridine) were evaluated through molecular docking analysis. These inhibitors effectively targeted both GS1 and GS2 domains of Klotho at the similar sites required for FGF23 binding. To further characterize the comparative binding profile of these compounds, molecular dynamics simulation assays were performed. Taken together, current study emphasizes that Klotho may be anticipated as a target molecule in familial hypophosphatemic rickets and mentioned compounds may prove to be effective therapeutic targets against hypophosphetemia induced disorders.

Severe hypercalcaemia and hypophosphataemia with an optimised preterm parenteral nutrition formulation in two epochs of differing phosphate supplementation.

OBJECTIVE: To compare in two epochs of differing phosphate provision serum calcium, phosphate, potassium, and sodium concentrations and the frequency of abnormality of these electrolytes and of sepsis in preterm infants who received an optimised higher amino acid-content formulation. DESIGN AND SETTING: Retrospective cohort study at a single tertiary-level neonatal unit. PATIENTS: Preterm infants given parenteral nutrition (PN) in the first postnatal week during two discrete 6-month epochs in 2013-2014. INTERVENTIONS: In epoch 1 the Ca2+:PO4 molar ratio of the PN formulation was ~1.3-1.5:1 (1.7 mmol Ca2+ and 1.1 mmol PO4 per 100 mL aqueous phase) and in epoch 2 was 1.0:1 via extra phosphate supplementation (1.7 mmol Ca2+ and 1.7 mmol PO4 per 100 mL). MAIN OUTCOME MEASURES: Peak calcium and nadir phosphate and potassium concentrations, and proportions with severe hypercalcaemia (Ca2+ >3.0 mmol/L), hypophosphataemia (PO4<1.5 mmol/L), and hypokalaemia (K+ <3.5 mmol/L) within the first postnatal week. RESULTS: In epoch 2, peak calcium concentrations were lower than in epoch 1 (geometric means: 2.83 mmol/L vs 3.09 mmol/L, p value<0.0001), fewer babies were severely hypercalcaemic (10/49, 20%, vs 31/51, 61%, p value<0.0001); nadir plasma phosphate concentrations were higher (means: 1.54 mmol/L vs 1.32 mmol/L, p value=0.006), and there were fewer cases of hypophosphataemia (17/49, 35% vs 31/51, 61%, p value=0.009) and hypokalaemia (12/49, 25% vs 23/51, 45%, p value=0.03). CONCLUSIONS: Reverting from a PN Ca2+:PO4 molar ratio of 1.3-1.5:1 to a ratio of 1.0:1 was associated with a lower incidence and severity of hypophosphataemia and hypercalcaemia. For preterm infants given higher concentrations of amino acids (≥2.5 g/kg/day) from postnatal day 1, an equimolar Ca2+:PO4 ratio may be preferable during the first postnatal week.

Management of mineral and bone disorders in renal transplant recipients.

The management of post-transplantation bone disease is a complex problem that remains under-appreciated in clinical practice. In these patients, pre-existing metabolic bone disorder is further impacted by the use of immunosuppressive medications (glucocorticoids and calcineurin-inhibitors), variable post-transplantation renal allograft function and post-transplantation diabetes mellitus. The treatment of post-transplantation bone loss should begin pre-transplantation. All patients active on transplant waiting lists should be screened for bone disease. Patients should also be encouraged to take preventative measures against osteoporosis such as regular weight-bearing exercise, smoking cessation and reducing alcohol consumption. Biochemical abnormalities of disordered mineral metabolism should be corrected prior to transplantation wherever possible, and because these abnormalities commonly persist, post transplant hypophosphatemia, persistent hyperparathyroidism and low vitamin D levels should be regularly monitored and treated. Bone loss is greatest in the first 6-12 months post-transplantation, during which period any intervention is likely to be of greatest benefit. There is strong evidence that bisphosphonates prevent post-transplantation bone loss; however, data are lacking that this clearly extends to a reduction in fracture incidence. Denosumab is a potential alternative to vitamin D receptor agonists and bisphosphonates in reducing post-transplantation bone loss; however, further studies are needed to demonstrate its safety in patients with a significantly reduced estimated glomerular filtration rate. Clinical judgement remains the cornerstone of this complex clinical problem, providing a strong rationale for the formation of combined endocrinology and nephrology clinics to treat patients with Chronic Kidney Disease-Mineral and Bone Disorder, before and after transplantation.

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.

Corn-Soy-Blend Fortified with Phosphorus to Prevent Refeeding Hypophosphatemia in Undernourished Piglets.

BACKGROUND: Phosphorus (P) levels in refeeding diets are very important as undernourished children are at risk of hypophosphatemia during refeeding. For this reason, conventional corn-soy-blends (CSB) have been reformulated by the World Food Programme to obtain a mono-calcium-phosphate fortified product (CSB+) and a product further fortified with skim milk powder (CBS++). METHODS: Using a piglet model of undernourished children, we hypothesized that feeding of CSB+, CSB++ or CSB+ with added whey permeate (CSB+/wp) would help to prevent refeeding hypophosphatemia. Pigs were weaned at 4 weeks of age and undernutrition was induced with a nutritionally inadequate pure maize diet for 7 weeks, after which they were refed for 3 weeks with either CSB+ (n = 10), CSB++ (n = 10) or CSB+/wp (n = 10). For reference, a fourth group continued on the maize diet (REF, n = 10). RESULTS: Following induction of undernutrition, body weight and length were 29±5% and 67±4% (means±SD) of values in age-matched pigs fed a nutritionally adequate diet, and the mean serum P level was 1.77±0.34 mmol/l. During the first week of refeeding, P levels in the CSB+ pigs decreased to 55% of values before refeeding (P < 0.05) while values in the CSB++ and CSB+/wp pigs were able to maintain their plasma phosphate at a similar level as before refeeding. CONCLUSION: We conclude that fortification of CSB with only monocalcium-phosphate does not prevent hypophosphatemia. Dairy products like skim milk powder or whey permeate may represent relevant sources of phosphorus during refeeding. The content and form of phosphorus in such diets need to be carefully evaluated, and the undernourished piglet may be used to test the efficacy of such diets.

An Institutional Change in Continuous Renal Replacement Therapy: Nutrition Support Team Resolves Resultant Severe Hypophosphatemia.

BACKGROUND: Critically ill patients with acute kidney injury may require parenteral nutrition (PN) and continuous renal replacement therapy (CRRT). Introduction of a phosphate-free premixed renal replacement fluid without system-wide education in May 2011 resulted in increased incidence of hypophosphatemia, necessitating change in practice. Changes included (1) maximizing phosphate in PN, (2) modifying the CRRT order set, and (3) developing a CRRT competency evaluation for nutrition support team members. This study evaluates the effect of these changes on the incidence of hypophosphatemia. METHODS: Phosphate levels and predicated probability of hypophosphatemia were evaluated for patients receiving PN and CRRT over 3 time periods: prior to implementing the changes (preimplementation), during change implementation (intermediate), and following implementation (postimplementation). Hypophosphatemia was defined as a serum phosphate level <2.5 mg/dL. Generalized linear mixed models were applied for statistical analysis. RESULTS: The retrospective study includes 336 measures from 49 patients. Patients in the intermediate and postimplementation periods were not significantly different from each other and had significantly higher mean phosphate levels than patients in the preimplementation period (P < .0001). They were also less likely to develop hypophosphatemia compared with preimplementation patients (intermediate: odds ratio [OR], 0.07; 95% confidence interval [CI], 0.03-0.18, P < .0001; postimplementation: OR, 0.09; 95% CI, 0.03-0.27, P < .0001). CONCLUSIONS: Modifications in phosphate dosing together with CRRT education reduced the incidence of hypophosphatemia in PN patients receiving CRRT. Communication of significant changes in clinical care should be shared with all services prior to implementation. Communication and planning between services caring for complex patients are necessary to prevent systems-based problems.