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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR  
Year : 2013  |  Volume : 24  |  Issue : 5  |  Page : 1019-1021
Solubility of melamine crystal in different pH conditions: Clinical implication for management of melamine intoxication


Wiwanitkit House, Bangkhae, Bangkok 10160, Thailand

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Date of Web Publication12-Sep-2013
 

How to cite this article:
Wiwanitkit S, Wiwanitkit V. Solubility of melamine crystal in different pH conditions: Clinical implication for management of melamine intoxication. Saudi J Kidney Dis Transpl 2013;24:1019-21

How to cite this URL:
Wiwanitkit S, Wiwanitkit V. Solubility of melamine crystal in different pH conditions: Clinical implication for management of melamine intoxication. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Nov 22];24:1019-21. Available from: http://www.sjkdt.org/text.asp?2013/24/5/1019/118081
To the Editor,

Melamine is a chemical substance with a high nitrogen content. It is an organic trimer of cyanamide, with a 1, 3, 5-triazine skeleton. [1],[2] Melamine intoxication is an important concern in pediatric nephrology. In the past few years, outbreaks of melamine-induced renal disorder in the pediatric population due to tainted milk led to increased concern on melamine intoxication. [1],[2] As noted earlier, melamine is added illegally into the milk in order to increase the nitrogen content. This might disguise the simple technique for indirect measurement of protein content in milk. Although melamine has a high nitrogen content, it is not useful but, on the contrary, is toxic to the human body. [3] Basically, the problem of melamine intoxication is due to melamine crystal formation. [4],[5],[6] In the human body, melamine cannot be metabolized and is rapidly eliminated via the kidney. The half-life of melamine in plasma before excretion into urine is about 3 h. [1],[2] The main toxicity of melamine in humans is renal toxicity, predominantly affecting the tubules. [4],[5],[6] The crystals that are formed can induce obstruction of the pediatric renal tubular system and lead to the clinical problems including renal failure. [7],[8]

For management of the intoxicated cases, there is still no standard specific treatment. Dialysis in cases with renal failure and removal of the obstructing particles are generally practiced. [8] Additionally, supportive care is usually given to the cases. Herein, the authors describe the solubility process of melamine crystals in different pH conditions and discuss its implication on the treatment of melamine intoxication.

In this descriptive study, a chemo-informatics approach was used to assess the solubility property of melamine crystal. Firstly, a computational tool (PROTEIN SOLUBILITY; Oklahoma, USA), developed based on previous referencing papers, [9],[10] was used for the prediction of the solubility of melamine crystal in normal physiological conditions. The structural sequence from the previous geometrical analysis study [5] was used as input for solubility prediction. Based on the computational tool, the conclusive solubility was determined based on the canonical value (CV-CV'). The CV-CV' is the specific variable to determine whether a formed molecule will be soluble or will form a solid inclusion. For interpretation of the result, "CV-CV' > 0" means soluble while "CV-CV' <0 means insoluble." [11] Following this, the change of solubility at different pH levels was assessed. Another computational tool, ACD/ Solubility DB (Toronto, Canada), was used for this assessment. This software is in good agreement to the standard experimental solubility study. [12] The simulation for pH change was done at a pH between 6.4 and 8.4, which is the detectable urine pH value.

According to the first prediction on the possible solubility of the melamine crystal in normal physiological conditions, the melamine crystal has an 18.5% chance of solubility. The CV-CV' value is equal to -0.24. On further assessment of solubility at different pH levels, the melamine crystal remains insoluble at the physiological pH range (7.35-7.45) [13] [Table 1].
Table 1: Predicted solubility of melamine crystal at different urinary pH levels.

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The treatment of the pediatric cases intoxicated with melamine is still not conclusive. Based on the pathogenesis of melamine nephropathy, melamine intoxication can be classified into the group of obstructive nephropathy. [4],[5],[6],[7],[8] An important concept in the treatment of this disease is adjustment of urine pH expecting to dissolve the obstructive stone or crystal. [14] Whether this concept can be adapted to the scenario of melamine nephropathy is an interesting research question.

In this study, using the standard chemo-informatics approach to predict the pattern of solubility of melamine crystal, it was found that the formed melamine crystal is insoluble at physiological conditions. This confirms the nature of obstructive disease. [4],[5],[6],[7],[8] Also, this result is in agreement with a recent report on the possibility of insolubility of the formed crystal in normal urine. [15]

Nevertheless, we further assessed the change of solubility of melamine crystal at different pH levels. It was found that acidification or alkalinization of urine, which can be done in the physiological range, cannot be a useful method for dissolution of the formed melamine crystals in the affected pediatric population. The other new proposed therapeutic method, the blood purification therapy, might be more appropriate. [16]

We conclude that melamine crystal is not soluble at physiological pH in the human body; hence, treatment by blood purification therapy might be more appropriate than manipulation of urine pH.

 
   References Top

1.Hau AK, Kwan TH, Li PK. Melamine toxicity and the kidney. J Am Soc Nephrol 2009;20:245-50.  Back to cited text no. 1
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2.Kuehn BM. Melamine scandals highlight hazards of increasingly globalized food chain. JAMA 2009;301:473-5.  Back to cited text no. 2
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3.Tyan YC, Yang MH, Jong SB, Wang CK, Shiea J. Melamine contamination. Anal Bioanal Chem 2009;395:729-35.  Back to cited text no. 3
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4.Wiwanitkit V. Melamine nephropathy. Urol Res 2010;38:411.  Back to cited text no. 4
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5.Wiwanitkit V. Geometric analysis of melamine crystal: A problematic molecule inducing renal failure in melamine intoxication. Ren Fail 2009;31:421-2.  Back to cited text no. 5
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6.Wiwanitkit V. Melamine induced renal disorder in pediatric patients. CMAJ, 3 Mar 2010.  Back to cited text no. 6
    
7.Zhang L, Wu LL, Wang YP, Liu AM, Zou CC, Zhao ZY. Melamine-contaminated milk products induced urinary tract calculi in children. World J Pediatr 2009;5:31-5.  Back to cited text no. 7
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8.Sun Q, Shen Y, Sun N, et al. Diagnosis, treatment and follow-up of 25 patients with melamine-induced kidney stones complicated by acute obstructive renal failure in Beijing Children's Hospital. Eur J Pediatr 2010;169: 483-9.  Back to cited text no. 8
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9.Davis GD, Elisee C, Newham DM, Harrison RG. New fusion protein systems designed to give soluble expression in Escherichia coli. Biotechnol Bioeng 1999;65:382-8.  Back to cited text no. 9
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10.Wilkinson DL, Harrison RG. Predicting the solubility of recombinant proteins in Escherichia coli. Biotechnology (N Y). 1991;9: 443-8.  Back to cited text no. 10
    
11.Koschorreck M, Fischer M, Barth S, Pleiss J. How to find soluble proteins: A comprehendsive analysis of alpha/beta hydrolases for recombinant expression in E. coli. BMC Genomics 2005;6:49.  Back to cited text no. 11
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12.Roda G, Dallanoce C, Grazioso G, Liberti V, De Amici M. Determination of acid dissociation constants of compounds active at neuronal nicotinic acetylcholine receptors by means of electrophoretic and potentiometric techniques. Anal Sci 2010;26:51-4.  Back to cited text no. 12
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13.Kellum JA. Determinants of blood pH in health and disease. Crit Care 2000;4:6-14.  Back to cited text no. 13
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14.Kobayashi T, Okada A, Fujii Y, et al. The mechanism of renal stone formation and renal failure induced by administration of melamine and cyanuric acid. Urol Res 2010;38:117-25.  Back to cited text no. 14
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15.Dominguez-Estevez M, Constable A, Mazzatorta P, Renwick AG, Schilter B. Using urinary solubility data to estimate the level of safety concern of low levels of melamine (MEL) and cyanuric acid (CYA) present simultaneously in infant formulas. Regul Toxicol Pharmacol 2010;57:247-55.  Back to cited text no. 15
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16.Shen Y, Liu XR, Zhang GJ, Zhou N. Blood purification therapy in treatment of acute renal failure in infants with melamine-induced stones. Chin Med J (Engl) 2009;122:257-61.  Back to cited text no. 16
[PUBMED]    

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Correspondence Address:
Somsri Wiwanitkit
Wiwanitkit House, Bangkhae, Bangkok 10160
Thailand
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DOI: 10.4103/1319-2442.118081

PMID: 24029276

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