Browsing by Author "Nicol, Simone"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    The aetiology of hypophosphatemia in children recovering from Kwashiorkor
    (Stellenbosch : Stellenbosch University, 2015-12) Nicol, Simone; Nel, Etienne De la Rey; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health
    ENGLISH ABSTRACT : Abstract Background The aetiology of hypophosphatemia in children recovering from kwashiorkor is poorly understood. Current theory of the pathophysiology of hypophosphatemia due to refeeding syndrome in adults describes intracellular phosphate trapping, mediated by a metabolic shift from lipid-based catabolism to carbohydrate metabolism. Treatment of hypophosphatemia associated with severe acute malnutrition (SAM) presents a challenge to the control of serum phosphate levels. Hypothesis This study explores the hypothesis that hypophosphatemia is caused by impaired renal tubular phosphate reabsorption in children recovering from oedematous malnutrition. Study Design A prospective pilot study was based at the Tygerberg Children’s Hospital Gastroenterology Unit, a tertiary referral unit in Cape Town, South Africa. Written informed consent was obtained from the legal guardian and ethical approval was obtained from Stellenbosch University’s Human Research Ethics Committee. Ten children between the ages 6-59 months admitted to the Gastroenterology Unit and classified as having kwashiorkor or marasmic kwashiorkor were included. Children were excluded if they were known with pre-existing renal or endocrine disease involving phosphate, magnesium or calcium metabolism. Additionally patients transferred from referring hospitals who had already initiated a refeeding and treatment regimen, any patient with a haemoglobin of ≤6g/dl on admission or any child known to be HIV positive were also excluded from the study. Methods Biochemical and anthropometric variables were monitored during the course of treatment and refeeding. Management of the patients was standardised as per the Tygerberg Children’s Hospitals protocol for refeeding in severe acute malnutrition, which is in accordance with the WHO 10 step protocol. Treatment of hypophosphatemia included oral administration of 75-100 mg/kg/day of 0.8g Na2HPO4 + 0.2g KH2PO4 + 10 ml H2O providing a solution of 100 mg PO4/ml (7.8 mmol of phosphate per 10 mls solution). If patients were unable to tolerate oral feeds intravenous KPO4 was administered at 1 mmol/kg/day of phosphate. Results On admission 70% of children were assessed as severely underweight for age (median WAZ: -2.77, IQR: -5.07; -1.10) and 60% as stunted (median HAZ: -2.52, IQR: -5.23; -1.14) based on the WHO Z-score classification. All children were oedematous. Serum phosphate levels fell within the reference range for age (median: 1.3 mmol/l, IQR: 0.9; 1.4) and decreased to a nadir on day 7 (median: 1.15 mmol/l, IQR: 0.82; 1.5) despite routine phosphate supplementation. Low serum ionised calcium concentration at baseline (median: 1.8, IQR: 1.6; 1.88) reached a nadir at day 3 of treatment (median: 1.71, IQR: 1.53; 1.98), associated with a peak in PTH secretion on day 7 (median: 11.35, IQR: 9.1; 13.6), and an increased urinary phosphate (median: 3.85 IQR: 0.9; 37.85) on day 14. Renal threshold for phosphate reabsorption remained low throughout the course of refeeding and none of the patients developed biochemical evidence of refeeding syndrome. A significant positive correlation between ionised calcium and phosphate (p=0.004) was determined when calculating the Spearman Rank co-efficient; indicating that low serum ionised calcium concentration contributed to hypophosphatemia. This finding was confirmed by appropriate physiologic response to ionised serum hypocalcaemia by the parathyroid hormone axis. Although a positive correlation between urinary and serum phosphate; and a negative correlation between urinary phosphate and serum calcium were observed as expected; these were not found to be statistically significant, possibly due to the limited sample size and missing variables. However, a significant negative correlation (p=0.0012) was demonstrated between ionised calcium levels and PCT; this finding is previously undescribed in the setting of SAM. Conclusion This study demonstrated that in children recovering from SAM, low serum ionised calcium levels are a potential driver for phosphaturia in the face of hypophosphatemia. This is mediated via an appropriate PTH response. Further investigation of calcium supplementation and the contribution of vitamin D to phosphate homeostasis in SAM should be undertaken.