Target phosphate and calcium levels in patients undergoing hemodialysis: a post-hoc analysis of the LANDMARK study.

BACKGROUND: It is necessary to re-examine the optimal phosphate (P) and calcium (Ca) target values in the contemporary management of chronic kidney disease-mineral and bone disorder to reduce the risks of cardiovascular events in patients receiving hemodialysis. METHODS: We performed a post-hoc analysis of the LANDMARK study. The outcomes were defined as cardiovascular events and all-cause death. Data from 2135 patients receiving hemodialysis at risk of vascular calcification were analyzed using a time-dependent Cox proportional hazard model adjusted for background factors. RESULTS: On the hazard ratio (HR) curve, the ranges where the lower 95% confidence interval (CI) were below the minimum of HR (= 1.00) were as follows: P = 3.5-5.5 mg/dL; albumin-adjusted Ca < 9.1 mg/dL for cardiovascular events; and P = 3.6-5.3 mg/dL; albumin-adjusted Ca < 9.1 mg/dL for all-cause mortality. In stratified analysis, the HRs for cardiovascular events in P < 3.5 mg/dL and P ≥ 5.5 mg/dL were similar to that of P = 3.5-5.5 mg/dL (P ≥ 0.05), and albumin-adjusted Ca ≥ 9.1 mg/dL had higher HR than values < 9.1 mg/dL [1.30 (95% CI 1.00-1.68; P = 0.046)]. For all-cause mortality, the HR in P < 3.6 mg/dL was higher than that in P = 3.6-5.3 mg/dL [1.76 (95% CI 1.25-2.48; P = 0.001)], while the HRs between P ≥ 5.3 mg/dL and P = 3.6-5.3 mg/dL as well as those between albumin-adjusted Ca ≥ 9.1 and < 9.1 mg/dL were not significantly different (P ≥ 0.05). CONCLUSIONS: Managing albumin-adjusted Ca < 9.1 mg/dL may reduce the cardiovascular risk among patients undergoing hemodialysis. Hypophosphatemia < 3.6 mg/dL may be associated with mortality.

Electrolyte disorders during the initiation of nutrition therapy in the ICU.

PURPOSE OF REVIEW: To summarize recent evidence on prevalence, risk factors, significance, treatment, and prevention of electrolyte disorders in critically ill with a specific focus on disorders during the initiation of nutrition. RECENT FINDINGS: Electrolyte disturbances appear to occur often during critical illness, and most of them seem to be associated with impaired outcome. However, a recent systematic review indicated insufficient evidence to answer clinically relevant questions regarding hypophosphatemia. Similar questions (which thresholds of serum levels are clinically relevant; how serum levels should be corrected and how do different correction regimens/approaches influence outcome) are not clearly answered also for other electrolytes. The most crucial feature of electrolyte disturbances related to feeding is refeeding syndrome. Recent evidence supports that additionally to the correction of electrolyte levels, a temporary restriction of calories (reducing the magnitude of this metabolic feature, including electrolyte shifts) may help to improve outcome. SUMMARY: Diverse electrolyte disorders often occur in critically ill patients. Hypophosphatemia, hypokalemia, and hypomagnesemia that are encountered after initiation of feeding identify refeeding syndrome. Along with correction of electrolytes, reduction of caloric intake may improve the outcome of the refeeding syndrome.

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.

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.

[Lack of phosphorus intake and nutrition].

Since one gram of protein in food provides approximately 15 mg of phosphorus, phosphorus deficiency frequently observed in patients with protein-energy malnutrition (PEM). Chronic phosphorus deficiency in humans causes proximal myopathy. Acute hypophosphatemia may precipitate rhabdomyolysis. Plasma low phosphorus concentration suppresses erythrocyte synthesis and stores of 2,3-diphosphoglycerate (2,3-DPG) , which plays an important role in the affinity of hemoglobin for oxygen. Symptoms of nervous system dysfunction, such as weakness, apathy, a bedridden state, and intention tremors, are also observed in severe hypophosphatemia. Refeeding syndrome is caused by rapid refeeding in PEM, characterized by hypophosphatemia and has metabolic and clinical complications. This is potentially fatal, yet is preventable. Awareness and identification of at-risk patients is crucial to improving management.

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.

The refeeding syndrome and glucose load.

OBJECTIVE: A 10-year-old girl with anorexia nervosa developed the refeeding syndrome following cautious reintroduction of nutrition, emphasizing that even with cautious refeeding a shift in fluid, glucose, and electrolytes can still occur, increasing the risk of morbidity and mortality in this ever growing vulnerable group. METHOD: Biochemical, nutritional, and anthropometrical monitoring in the patient, who followed a conservative refeeding program after a prolonged period of nutritional inadequacy. RESULTS: The refeeding syndrome presented itself with hypophosphatemia, hypotension, and cardiac abnormalities whilst refeeding at 25 kcal/kg (600 kcal/day). DISCUSSION: Comprises of a literature review, highlighting this case as the youngest reported case of refeeding syndrome in anorexia nervosa. Discussion focuses on the possible deleterious affects that carbohydrates may have in exacerbating the refeeding syndrome.

Favorable effects of burosumab on tumor-induced osteomalacia caused by an undetectable tumor: A case report.

RATIONALE: Tumor-induced osteomalacia (TIO) is curable by tumor resection, but detection of the tumor can be challenging. Overproduction of fibroblast growth factor 23 (FGF23) by the tumor causes hypophosphatemia and consequently induces inappropriate bone turnover. Conventionally oral phosphate supplementation was the only treatment for TIO, but had risks of hypercalciuria and nephrocalcinosis. Burosumab, a human monoclonal anti-FGF23 antibody, was recently post-marketed in Japan against for FGF23-related hypophosphatemia. Herein, we present a case of TIO with undetectable tumor that was successfully treated with burosumab. PATIENT CONCERNS: A 47-year-old woman was forced to use a wheelchair because of pain in both feet. DIAGNOSIS: Laboratory findings showed hypophosphatemia, elevated bone markers, and high serum FGF23 without renal tubular defects. Imaging studies revealed bone atrophy in the feet, decreased bone density, and multiple pseudofractures in the talar, sacral, and L5 vertebral regions. After excluding drug-induced and hereditary osteomalacia, we diagnosed her as TIO. INTERVENTIONS: Comprehensive imaging studies and stepwise venous sampling failed to localize the tumor, and we started to administer subcutaneous burosumab. OUTCOMES: After administration of burosumab, her serum phosphate was normalized without phosphate supplementation within 2 months. Improvement of pseudofractures, relief of pain evaluated by a visual analog scale, and normalization of bone biomarkers were observed. The patient was able to stand by herself after 6 months administration of burosumab. LESSONS: This is the first report in clinical practice to demonstrate favorable effects of burosumab, including not only normalization of serum phosphate but also improvements of pseudofractures and subjective pain, in a patient with TIO and undetectable tumor.

Hungry Bone Syndrome After Living Donor Liver Transplant for Biliary Atresia.

Hungry bone syndrome is a rare but potentially lethal complication that is characterized by rapid, severe, long-lasting hypocalcemia and hypophosphatemia secondary to increased bone metabolism. We present a case of hungry bone syndrome after living donor liver transplant for biliary atresia. Following a failed Kasai procedure for biliary atresia, a 5-month-old boy underwent living donor liver transplant with reduced left lateral lobe from his father. Despite the oral administration of alfacalcidol, the patient exhibited severe craniotabes before the surgery. He developed severe hypocalcemia and hypophosphatemia im-mediately after liver transplant and required supplementation of calcium and phosphorus for 1 month thereafter. After serum levels of calcium and phosphate had normalized, there was a rapid increase in the serum bone-type alkaline phosphatase level, and the craniotabes subsided remarkably. To our knowledge, this is the world's first reported case of hungry bone syndrome after liver transplant for cholestatic cirrhosis. It underscores the importance of strict nutritional and electrolyte management in the perioperative period. A prompt diagnosis and correction of hungry bone syndrome are imperative to prevent the associated significant morbidity and mortality.

A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial).

BACKGROUND: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group. METHOD: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified. RESULTS: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25). CONCLUSIONS: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).

Pheochromocytoma crisis in a patient with newly diagnosed neurofibromatosis type 1.

Pheochromocytoma occasionally engenders catecholamine-induced hypertension crisis. Pheochromocytoma is clinically identified in 0.1%-5.7% of patients with neurofibromatosis type 1 (NF1), which is 10 times more frequently than in healthy individuals. This report describes a case of newly diagnosed NF1 presenting with pheochromocytoma crisis, with severe electrolyte depletion and deteriorating recurrent ventricular tachycardia storm. Characteristic skin lesions such as café-au-lait macules and neurofibromas contributed to the diagnosis of NF1 and pheochromocytoma. No recurrence of electrolyte depletion was found after the adrenalectomy. Primary care physicians must distinguish the characteristic skin lesions of NF1, such as café-au-lait macules and neurofibromas and recognise the risk for pheochromocytoma.

Metastatic prostate cancer presenting as tumour-induced osteomalacia.

Tumour-induced osteomalacia (TIO), or oncogenic osteomalacia, is a paraneoplastic syndrome marked by hypophosphataemia, renal phosphate wasting, bone pain, weakness, and fractures. The syndrome has been reported with both benign and malignant tumours including parotid gland basal cell tumours, thyroid carcinomas, colon adenocarcinomas, and prostate cancer. Often, the syndrome is marked by an insidious course during which patients present with generalised bony pain and weakness, which do not resolve until the underlying tumour is identified and treated. We present a case of a patient with Parkinson's disease whose subacute weakness, lower extremity paresis, and renal phosphate wasting led to the synchronous diagnosis of metastatic prostate adenocarcinoma and TIO.

A case of entecavir-induced Fanconi syndrome.

Acquired Fanconi syndrome has been associated with the long-term ingestion of several nucleoside analogs used to treat chronic hepatitis B virus infection. However, the nucleoside analog entecavir has not been found to cause nephrotoxicity. We report a case of entecavir-induced Fanconi syndrome. Our patient was a 73-year-old man admitted to our hospital because of renal dysfunction. He also presented with hyperaminoaciduria, renal diabetes, phosphaturia, hypophosphatemia, hypokalemia, hypouricemia, and hyperchloremic metabolic acidosis, supporting a diagnosis of Fanconi syndrome. In this case, the cause of Fanconi syndrome was most likely entecavir, which had been administered as needed depending on his renal function for 5 years. After drug discontinuation and replacement with tenofovir alafenamide fumarate therapy once a week, the patient's kidney function recovered and electrolyte anomalies partially improved. We highlight the fact that entecavir may induce severe renal dysfunction, which can cause the development of Fanconi syndrome; therefore, close monitoring of proximal tubular function is recommended during entecavir therapy.

A case of osteomalacia due to deranged mineral balance caused by saccharated ferric oxide and short-bowel syndrome: A case report.

RATIONALE: Saccharated ferric oxide has been shown to lead to elevation of fibroblast growth factor 23, hypophosphatemia, and, consequently, osteomalacia. Moreover, mineral imbalance is often observed in patients with short-bowel syndrome to some degree. PATIENT CONCERNS: A 62-year-old woman with short-bowel syndrome related with multiple resections of small intestines due to Crohn disease received regular intravenous administration of saccharated ferric oxide. Over the course of treatment, she was diagnosed with tetany, which was attributed to hypocalcemia. Additional assessments of the patient revealed not only hypocalcemia, but also hypophosphatemia, hypomagnesemia, osteomalacia, and a high concentration of fibroblast growth factor 23 (314 pg/mL). DIAGNOSES: We diagnosed her with mineral imbalance-induced osteomalacia due to saccharated ferric oxide and short-bowel syndrome. INTERVENTIONS: Magnesium replacement therapy and discontinuation of saccharated ferric oxide alone. OUTCOMES: These treatments were able to normalize her serum mineral levels and increase her bone mineral density. LESSONS: This case suggests that adequate evaluation of serum minerals, including phosphate and magnesium, during saccharated ferric oxide administration may be necessary, especially in patients with short-bowel syndrome.

Tumor-induced hypophosphatemic osteomalacia associated with tertiary hyperparathyroidism: a case report.

BACKGROUND: Tumor-induced hypophosphatemic osteomalacia is a syndrome characterized by urinary phosphate wasting related to the presence of a slowly-growing tumor of mesenchymal origin. The characteristic laboratory findings are normal serum calcium, marked hypophosphatemia, increased serum alkaline phosphatase, markedly reduced renal tubular reabsorption of phosphorus and inappropriately low levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D]. CASE PRESENTATION: A 65-year-old woman presented with a 17-year clinical history of musculoskeletal pain, muscular weakness in the pelvic girdle, spontaneous fractures and difficulty in walking. Over the ensuing years the patient suffered other multiple spontaneous fractures, surgically treated, and the muscular pains worsened until she became bedridden. During the years before hospital admission the patient received treatment with clodronate, oral calcium salts and vitamin D therapy. Standard laboratory, ultrasonography and scintigraphic findings provided a "convenient" diagnosis of primary hyperparathyroidism, but the low plasma level of phosphorus induced to perform an Indium111-octreotide scintigraphy. Scintigraphy visualized an area of pathologic increased signal uptake in the left groin, consistent with a mass containing a high density of somatostatin receptors. After surgery, histologic examination and immunostaining of the resected specimen indicated an hemangiopericytoma. Nevertheless, the persistently low blood phosphorus level, in association with the increased serum calcium and PTH levels, were attributed to the prolonged phosphate therapy the patient underwent over the years, and the persisting abnormal laboratory indexes indicated the development of a tertiary hyperparathyroidism. We performed a subtotal parathyroidectomy and intraoperative assay of serum PTH showed that levels had diminished by more than 80% from preoperative values. Over the ensuing months Ca+2, PTH and serum phosphorus values returned to normal, and the pain symptoms disappeared. CONCLUSIONS: Tumour-induced osteomalacia is a very rare syndrome associated in 5% of cases with tertiary hyperparathyroidism due to long-term therapy with phosphorus and vitamin D. The initial diagnosis of primary hyperparathyroidism, confirmed by the parathyroid MIBI-scintigraphy, would lead us to an inappropriate surgical treatment. Therefore we want to stress the importance of In111-octreotide scintigraphy in detecting tumours, rich in somatostatin receptors, in presence of an hypophosphatemic syndrome.

Diagnostic utility of magnetic resonance imaging skeletal survey in a patient with oncogenic osteomalacia.

Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemic osteomalacia due to renal phosphate wasting. The same biochemical features are found in patients with X-linked hypophosphatemic rickets/osteomalacia and sporadic hypophosphatemic osteomalacia with unknown etiology. Oncogenic osteomalacia is cured by resection of the responsible tumor. In contrast, patients with other types of hypophosphatemic rickets/osteomalacia need long-term treatment with large doses of active vitamin D3. Therefore, detection of the responsible tumor for oncogenic osteomalacia has great clinical importance. However, there is no standard method for detecting the tumor for oncogenic osteomalacia, and the responsible tumor is often very difficult to be found. We describe a patient with adult-onset osteomalacia due to renal phosphate wasting. Although oncogenic osteomalacia was suspected, cranial, chest, and abdominal computed tomography scanning, urological and otolaryngological examinations, and detailed palpation for soft tissue mass failed to detect the responsible tumor. However, magnetic resonance imaging skeletal survey revealed a tumor in the right femoral bone. Resection of the tumor resulted in normalization of serum phosphate and renal phosphate handling. Because the most frequent causes for oncogenic osteomalacia are tumors in bone or soft tissue, magnetic resonance imaging skeletal survey is a very powerful method for detecting the responsible tumor. Vigorous search for tumors with this method in patients with hypophosphatemic osteomalacia would be helpful not only for proper management of patients, but also for clarifying the identity of sporadic hypophosphatemic osteomalacia.

The refeeding syndrome and hypophosphatemia.

The refeeding syndrome is an underappreciated entity characterized by acute electrolyte derangements--notably hypophosphatemia--that occur during nutritional repletion of patients with significant suboptimal caloric intake. Adverse effects of hypophosphatemia include cardiac failure, muscle weakness, immune dysfunction, and death. Hypokalemia and hypomagnesemia commonly complicate refeeding syndrome as well; however, this report briefly reviews the clinical manifestations of refeeding-induced hypophosphatemia.

A comparison of clinically useful phosphorus binders for patients with chronic kidney failure.

A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Over the past 30 years it has become apparent that hyperphosphatemia plays a major causative role across the entire spectrum of morbidity associated with advancing kidney dysfunction and failure. A large fraction (60% to 70%) of dietary phosphorus is absorbed and normally excreted by the kidneys. Ideally, as kidney function deteriorates, the net quantity of phosphorus absorbed from the GI tract should be proportionally reduced to match the decrease in kidney function. After initiation of chronic dialysis therapy, the absorbed phosphorus load should match the amount of phosphorus removed via dialysis plus any excreted by residual kidney function. Because it is very difficult to reduce dietary phosphorus to these levels, a variety of oral phosphorus binders have been employed. Currently available binders include alkaline aluminum, magnesium, and calcium salts (primarily calcium carbonate and calcium acetate), various iron salts, and the binding resin sevelamer hydrochloride. Lanthanum carbonate is the newest agent and will probably be released shortly. This review compares the theoretic and in vitro chemistry of these drugs with in vivo data obtained in both normal patients, and in patients with kidney failure. The clinical potency and potential toxicity of the binding agents are compared, and optimal drug administration strategies are also reviewed.

Severe hypophosphatemia in a patient with diabetic ketoacidosis and acute respiratory failure.

Although hypophosphatemia is a common complication during therapy of diabetic ketoacidosis, it is seldom severe and rarely causes clinical manifestations. We report a 39-year-old woman with diabetic ketoacidosis who developed acute respiratory failure after therapy. Although hyperglycemia and acidosis were corrected after treatment, respiratory distress and weakness still persisted. The chest radiograph showed no active lung lesion. Brain CT revealed no significant abnormality. Echocardiographic study revealed normal LV systolic wall motion. Blood biochemistry demonstrated severe hypophosphatemia of 0.3 mg/dL (normal value: 2.5 to 4.5 mg/dL). Phosphate replacement therapy with potassium phosphate was given. The patient's clinical condition improved steadily over the next few days, and after 4 weeks of hospitalization, she was discharged home without obvious long-term sequelae. In a critically ill patient, the symptoms of hypophosphatemia are not apparent and may mimic the symptoms of other underlying disease. Although phosphate replacement is not recommended routinely in diabetic ketoacidosis, if the patient develops cardiopulmonary distress, anemia or severe hypophosphatemia, phosphate therapy under close surveillance is indicated.