1 Department of Nephrology 2 Department of Clinical Chemistry, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands
Sir,
We have read with interest the paper by Jones et al. (NDT volume 14, number 4, p. 944946, 1999). The authors demonstrate that the gelatine-derived plasma expander `gelofusine'® (Braun/NPBI, Oss, the Netherlands) causes interference when measuring urinary protein with the pyrogallol-red method. Since gelofusine is a protein derivate and pyrogallol-red reacts with basic amino groups such an interference may not be unexpected. However, we recently stumbled upon the same problem and must admit that unawareness of these laboratory `artefacts' can lead to serious misinterpretations. We have done some additional experiments which we feel confirm and extend the data reported by Jones et al.
Case.
A 34-year-old male patient was admitted to the intensive care unit with an intracranial haemorrhage. After confirmation of braindeath, he received 750 ml of a modified gelatin solution (Gelofusine®) because of hypotension. The patient's relatives agreed with kidney donation. The patient's medical history revealed that he had been under investigation because of fatigue for over 3 years, no apparent cause being found. On dip-stick analysis a small amount of protein was detected. A quantitative analysis of the urine by the biuret method revealed a protein concentration of 19.6 g/l. Because of the medical history and the remarkable difference between the dip-stick test and the quantitative urinalysis the possibility of the presence of urinary paraproteins was considered and the kidneys were rejected for transplantation purpose. Histological examination of the kidneys later on did not show abnormalities on light microscopy or immunofluorescence. In search for substances that could have interfered with the urinary protein assay we questioned the role of modified gelatin solution. Further investigations indeed disclosed the gelatin as the culprit.
Experimental procedures
. We have infused 500 ml of Gelofusine® in a healthy volunteer and measured the urinary protein excretion with the biuret method and with a turbidimetric method (trichloroacetic acid, TCA). In addition we determined urinary albumin with a sensitive ELISA method. The results are depicted in Figure 1 and clearly demonstrate that the gelatin is excreted in large amounts in the urine (at a rate of 5 g/h!), as detected with the biuret method, whereas proteinuria is absent when using TCA or the albumin assay. We also have studied in more detail the performance of various protein assays (Table 1). Complete results will be published elsewhere [1]. In brief, we observed that both protein-derived plasma expanders that are regularly used in our hospital (Gelofusine® and Haemaccel®) interfered with the following dye-binding protein assays: biuret, pyrogallol-red molybdate and Lowry. No interference was seen in the dye-binding assays: Coomassie Brilliant Blue and Ponceau S nor with the turbidimetric assays using TCA or benzethonium chloride. For practical purposes it is important to note that the simple dipstick test also remained negative. A dipstick test provides an easy way to prevent the above mentioned confusion.
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