Original Article Annals of Clinical Biochemistry 2015, Vol. 52(1) 82–87 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0004563214523739 acb.sagepub.com
Predicting refeeding hypophosphataemia: insulin growth factor 1 (IGF-1) as a diagnostic biochemical marker for clinical practice Atul Goyale1, Sarah L Ashley2, David R Taylor1, Manal O Elnenaei1, Jamshid Alaghband-Zadeh1, Roy A Sherwood1, Carel W le Roux1,3 and Royce P Vincent1
Abstract Background: Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH). Methods: A prospective study included 52 patients referred for parenteral nutrition (PN). The sensitivity and specificity of IGF-1 measured using a sensitive assay was compared to the RI in predicting the development of RH (a 530% drop in PO4 during the first 36-h of PN administration). Leptin and IGF-1 were analysed on baseline samples using a quantitative enzyme-linked immunoassay. Daily blood samples were collected from all patients for routine biochemistry for the full duration of PN administration. Results: High sensitivity IGF-1 measurement alone was comparable with the RI, using receiver–operating characteristic (ROC) curve analysis, with areas under the curve being 0.79 and 0.80, respectively, and superior to leptin alone (0.72) for predicting 530% drop in PO4. The cut-off value for IGF-1 that gave best sensitivity (91% [95% CI 75–98%]) and specificity (65% [95% CI 41–85%]) was 63.7 mg/L, with a likelihood ratio of 2.59. Conclusion: Baseline IGF-1 is an objective, sensitive and specific biochemical marker in identifying patients who are at high risk of developing RH prior to PN administration and therefore may have a role in clinical practice.
Keywords Refeeding syndrome, insulin-like growth factor-1, leptin, refeeding hypophosphataemia Accepted: 22nd January 2014
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Introduction Refeeding syndrome (RS) is a well described but often forgotten medical condition. RS occurs in patients following the re-introduction of nutrition after a prolonged period of relative or absolute starvation.1 Patients with low body mass index, unintentional weight loss, poor nutritional intake (five days or more) and those with low baseline phosphate (PO4),
Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK 2 Department of Nutrition and Dietetics, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK 3 Experimental Pathology, UCD Conway Institute, School of Medicine and Medical Science, University College Dublin, Ireland Corresponding author: A Goyale, Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK. Email:
[email protected]
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potassium (K) and magnesium (Mg) concentration are at greatest risk of developing RS.2 The true incidence of the RS is not known, owing to difficulties in recognition and diagnosis.3 The condition is potentially fatal and clinical features may include a wide range of neurological, cardiac, respiratory and neuromuscular symptoms.4 However, in the majority of patients clinical features are absent and the condition can be diagnosed only on the hallmark biochemical feature of hypophosphataemia or refeeding hypophosphataemia (RH).5 Other biochemical disturbances in sodium, K, Mg, glucose and fluid distribution can also occur.2 No randomised controlled trials of treatment have been published on RS, although there are guidelines that use best available evidence for managing the condition. The UK National Institute of Clinical Excellence clinical guideline 32 (NICE, 2006) aids the recognition of patients at risk of RS based on clinical history and features2 and are summarised in Table 1. However, these criteria are not always reliable in predicting and preventing RS as an accurate history regarding weight loss and recent oral intake may not be available from all patients. Also, increasingly patients are transferred both between and within hospitals, making maintaining a careful account of nutritional intake and patients’ weights more difficult. We have previously shown that using clinical criteria alone, not only underestimates the risk of RS, but also overestimates the risk, potentially leading to overtly cautious feeding.6 Hypophosphataemia following reintroduction of nutrition after a period of starvation is a key objective feature of the RS5 whereas clinical features and predictors are all subjective. At present there is no universally agreed parameter for PO4 concentration fall that defines RH. However, a previous study by Marik and Bedigian7 showed that 20–24% fall in PO4 concentration as being indicative of RS. Also Zeki et al. defined RH as a fall in serum PO4 to
