Pseudohypocalcaemia in an elderly patient with advanced renal failure and renovascular disease
Patrick B. Mark1,
Emmanouil Mazonakis1,
David Shapiro2,
Richard J. Spooner2 and
R. Stuart C. Rodger1
1 Renal Unit, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, UK and 2 Department of Biochemistry, Gartnavel General Hospital, Great Western Road, Glasgow G12 0YN, UK
Correspondence and offprint requests to: Patrick B. Mark, Renal Unit, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, UK. Email: pm124p{at}clinmed.gla.ac.uk
Keywords: atherosclerotic renovascular disease; calcium; chronic renal failure; gadolinium; magnetic resonance angiography
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Introduction
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Hypocalcaemia is a common clinical problem in patients with advanced renal failure, frequently related to abnormal vitamin D metabolism. However, not all causes are due to 1,25-dihydroxycholecalciferol deficiency and in this case we would like to demonstrate the confusion which may be caused by iatrogenic pseudohypocalcaemia.
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Case report
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An 84-year-old man with advanced chronic renal failure (glomerular filtration rate
15 ml/min) was admitted due to rapid deterioration of his kidney function and was established on haemodialysis. There were no obvious precipitating factors for this deterioration. He had known renovascular disease (5070% ostial stenosis of his right renal artery and irregular left renal artery). On admission his adjusted serum calcium level was 1.99 mmol/l (normal range 2.12.6 mmol/l; uncorrected calcium 1.92 mmol/l, serum albumin 39 g/l; correction formula used: [adjusted calcium] = [measured calcium] + 0.0171 (43 albumin), with 43 g/l being the mean normal albumin) and phosphate level was 1.84 mmol/l. His parathyroid hormone level, measured 2 months earlier, was 10 pmol/l. Although he had not been prescribed oral supplementation with a vitamin D analogue, he was already on calcium carbonate 1.25 g three times daily, which had been doubled the day of admission. One week later, after his second dialysis session (at which point his adjusted calcium level had decreased to 1.91 mmol/l), a magnetic resonance angiogram (Figure 1) of his renal arteries showed no difference in the degree of the stenoses. The morning following the magnetic resonance angiogram, his adjusted calcium level was 1.12 mmol/l and his phosphate level was 2.44 mmol/l. He had no alarming symptoms, both Chostvek's and Trousseau's signs were negative and there was no clinical evidence of tetany. An electrocardiogram was essentially normal, with no prolongation of the QT or QTc interval. In light of the severe hypocalcaemia he was initially treated with i.v. 30 ml 10% calcium gluconate, was dialysed against a high calcium dialysate (calcium concentration 1.75 mmol/l), and 4 h later his repeated adjusted serum calcium level was 2.57 mmol/l.

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Fig. 1. Gadolinium-enhanced magnetic resonance angiogram demonstrating right renal artery stenosis (arrowed).
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The next morning, his adjusted calcium was 2.11 mmol/l, phosphate was 1.92 mmol/l and serum parathyroid hormone was 20 pmol/l.
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Discussion
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Although the patient on admission had not been treated with vitamin D analogues, the decrease in his adjusted calcium level (0.79 mmol/l) was so dramatic that it could not be attributed to solely 1,25-dihydroxycholecalciferol deficiency. The patient had initially been dialysed with a dialysate ionised calcium concentration of 1.25 mmol/l, which would have maintained his adjusted serum calcium in the normal range. The striking feature was that the patient had no symptoms of severe hypocalcaemia or evidence of tetany.
The intravenous administration of gadolinium (as gadodiamide) can cause pseudohypocalcaemia (spurious hypocalcaemia). Two of the four commercially available (gadodiamide, Omniscan® and gadoversetamide, OptiMARK®) intravenously administered gadolinium-based contrast agents used in magnetic resonance imaging (MRI) may undergo dechelation (both in vivo and in vitro) and interfere with o-cresolphthalein based colorimetric methods of measuring total serum calcium [14]. These compounds have been hypothesized to dechelate in the presence of o-cresolphthalein, releasing Gd3+ ions, which subsequently form a dimeric gadoliniumo-cresolphthalein complex (2Gd2OCP). The formation of the 2Gd2OCP complex reduces the ultra violet absorbance of o-cresolphthalein, hence altering the results for serum calcium if tested by this method [3]. A decrease in serum calcium has only been demonstrated with o-cresolphthalein-based colorimetric methods. This effect on colorimetric analysis is not seen with dimeglumine gadopentetate (Magnevist®) or gadoteridol (ProHance®). Alteration is not seen in the serum calcium level as measured by atomic emission spectroscopy with the addition of gadodiamide. However, this method is more expensive and less convenient in daily practice. This recently described cause of pseudohypocalcaemia is enhanced in both duration and severity in patients with renal insufficiency [2,4] because of delayed excretion of the gadolinium chelate and may be seen more often with the increased use of MRI to investigate such patients. Fortunately there were no adverse effects from supplemental calcium administration in our patient, who remains well on an outpatient haemodialysis program.
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Teaching point
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Gadolinium-based contrast agents used in MRI may cause pseudohypocalcaemia. With increasing use of contrast-enhanced MR angiography it is likely that this effect will be seen with increasing frequency. Moreover a clinically significant high calcium level may be incorrectly overlooked due the falsely lowered value. Awareness of this effect is important to avoid inappropriate and potentially harmful treatment as occurred in our case.
Conflict of interest statement. None declared.
[see related Letter by Decupere et al. (doi:10.1093/ndt/gfh902)]
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References
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- Doorenbos CJ, Ozyilmaz A, van Wijnen M. Severe pseudohypocalcemia after gadolinium-enhanced magnetic resonance angiography. N Engl J Med 2003; 349: 817818[Free Full Text]
- Emerson J, Kost G. Spurious hypocalcemia after Omniscan- or OptiMARK-enhanced magnetic resonance imaging: an algorithm for minimizing a false-positive laboratory value. Arch Pathol Lab Med 2004; 128: 11511156[ISI][Medline]
- Lin J, Idee JM, Port M et al. Interference of magnetic resonance imaging contrast agents with the serum calcium measurement technique using colorimetric reagents. J Pharm Biomed Anal 1999; 21: 931943[CrossRef][ISI][Medline]
- Prince MR, Erel HE, Lent RW et al. Gadodiamide administration causes spurious hypocalcemia. Radiology 2003; 227: 639646[Abstract/Free Full Text]
Received for publication: 21.12.04
Accepted in revised form: 22. 3.05