Potassium Chromate as The Primary Constituent of Renal Stones in a Child With Chronic Chromium Ingestion: The First Case Report of Chromate Urolithiasis

doi:10.21203/rs.3.rs-4478098/v1

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Case Report

Potassium Chromate as The Primary Constituent of Renal Stones in a Child With Chronic Chromium Ingestion: The First Case Report of Chromate Urolithiasis

https://doi.org/10.21203/rs.3.rs-4478098/v1

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Background

Paediatric urolithiasis is increasingly recognised and involves significant morbidity to patients. Most of the renal stones are either calcareous, consisting of oxalate, calcium phosphate or both but stones with potassium chromate as the primary constituent were never reported in literature.

Case presentation

A nine-year-old girl presented with a passing couple of stones per day in her urine for the preceding twelve days, without any other urinary symptoms. Her initial serum and urine biochemical investigations were within reference range. Abdominal imaging did not reveal any significant structural abnormalities.

A macroscopic assessment of her stones revealed a rare reddish-orange colour. Stone analysis by Fourier transform-infrared spectroscope revealed potassium chromate as the main component of her stone.

On further questioning, the patient’s mother revealed that the child was treated with an Ayurvedic medicine named ‘Thalisadhi Chooranam’ which was prescribed for bronchial asthma for six years. Analysis of the Ayurveda medicine revealed the presence of Chromium in it. She was kept under observation with sufficient hydration. Now the child is well without any complaints to date and the passage of stones has settled spontaneously.

Conclusion

This case highlights the fact that chronic oral chromium ingestion can lead to urolithiasis, in the absence of other systemic involvement of chromium toxicity. So care must be taken when prescribing the drugs that have chromium more specifically in the context of alternative medicines and prescriptions for children.

Urolithiasis

Potassium Chromate

Ayurvedic Medicine

Fourier transform-Infrared spectroscope

Case Report

Urolithiasis is increasingly recognized in children. The presentation ranges from incidental findings on imaging to urinary tract infections. Metabolic abnormalities, urinary tract infections and/or structural abnormalities are some of the risk factors for renal stones. The common compositions of renal stones are calcium oxalate, calcium phosphate, magnesium ammonium phosphate, cystine and uric acid.

Chromium is a transitional metal with different colours depending on the state of its oxidation. The recommended dietary requirement of chromium in a nine-year-old female is 21 micrograms/ day [1]. Oral chromium exposure-related respiratory, cardiac, gastrointestinal, haematological and hepatic effects were reported in the literature [2, 3]. There are human and animal study-based evidences of acute tubular necrosis and renal failure following oral ingestion of chromium [2].

However, up to now no scientific studies or reports revealed chromium-containing renal stones in the literature. Our patient presented with a history of renal stones which is mainly made up of chromium, without any other features of chromium toxicity according to her clinical and biochemical analysis and is the first case of potassium chromate urolithiasis in humans.

A nine-year-old Sri Lankan girl presented to a local (base) hospital with the complaint of passing a couple of stones per day in her urine for the preceding twelve days. She did not have abdominal or flank pain, hematuria, dysuria, urgency, nausea, vomiting or fever. Her oral fluid intake was inadequate, though clinically not dehydrated. She did not have any similar previous episodes, anatomical abnormalities in the urinary tract, metabolic disorders or recurrent urinary tract infections. She underwent appendicectomy 2 months back for acute appendicitis. She did not have a significant family history related to renal stones. On examination, she was well, with no dysmorphic features, afebrile, haemodynamically stable and with a soft abdomen. Her growth and development were age-appropriate.

Her initial blood investigations included electrolytes [sodium – 133 mmol/L, potassium − 3.8 mmol/L, chloride – 100 mmol/L), renal function test [creatinine (Cr) – 0.45 mg/dL, urea – 28.7 mg/dl], albumin corrected calcium (10.2 mg/dL) and phosphate (1.58 mmol/L) were within age and sex-related reference range of the particular assay.

Her urine pH and specific gravity at the time of presentation were not documented. The urine full report does not show any pus cells, red cells or crystals. There was no growth in the urine culture. She had adequate urine output (1.7 mL/kg/hr) with normal fractional excretion of electrolytes in urine [sodium/Cr – 10.2 mmol/mmol (7.5–42), potassium/Cr – 5.2 mmol/mmol (4.5–22), calcium/Cr – 0.3 (0.04–0.7 mmol/mmol), magnesium/Cr – 0.5 (0.2–0.7 mmol/mmol), and phosphate/Cr – 1.2 (0.8–3.2 mmol/mmol)]

She was discharged with Bisacodyl 10 mg noct and micro enema mane and re-evaluated with an X-ray kidney, ureter and bladder as an outpatient. Radio-opaque stones were identified in X-ray. Ultrasound scan of the abdomen did not reveal significant structural abnormalities and computerized tomography was not performed as it was not available in that base hospital.

A macroscopic assessment of her stones revealed a rare reddish-orange colour (Fig. 1) which is similar to potassium chromate compounds. Stone analysis by Fourier transform-infrared spectroscope (FTIR) using an attenuated total reflection technique revealed potassium chromate as the main component of her stone (Fig. 2) which is an uncommon finding. We could not quantify the amount of chromate in the stone using this technique.

On further questioning, the patient’s mother revealed that the child was treated with an Ayurveda medicine named ‘Thalisadhi Chooranam’ for bronchial asthma from 2015 to 2021. Analysis of the Ayurveda medicine revealed the presence of Chromium in it.

She was kept under observation with sufficient hydration. Now the child is well without any complaints to date and the passage of stones has settled spontaneously.

The incidence of renal stones in children is comparatively lower than in adults, probably due to the presence of high concentrations of stone formation inhibitors in children (calcium oxalate, magnesium) [4]. However the prevalence of stones in children has been rising over the past few decades, this could be due to improved diagnostic facilities, dietary and lifestyle changes like consumption of soft drinks and animal proteins, environmental changes, and medications [5, 6].

The pathophysiology of stone formation is supersaturation in the urine by specific components. This component is identified by analysing the calculus after passage or removal using wet chemistry, thermo-gravimetry, X-ray diffraction crystallography or infrared spectroscopy. Most of the nephroliths are calcareous, consisting of oxalate, calcium phosphate or both [4, 7]. Uric acid, struvite or magnesium ammonium phosphate, cystine and ammonium urate are also commonly identified compositions of renal stones. However, the composition varies with age and sex [8]. Xanthine, 2, 8-dihydroxyadenine, protein matrix, drugs like indinavir and atazanavir and dietary contaminants like melamine also have been documented in the literature of adult urolithiasis [7]. Up to now, no data were available on potassium chromate as a composition of renal stones.

Chromium (Cr) is a transitional metal with different oxidization forms among which Cr³⁺ and Cr⁶⁺ are commonly occurring whereas Cr²⁺ accounts for the least. Depending on the oxidization, the colour of the compound also changes [3, 9]. Of this potassium chromate (K₂CrO₄) is yellow; potassium dichromate (K₂Cr₂O₇) is orange and potassium trichromate (K₂Cr₃O₁₀) is red. With the macroscopic colour of the stone (reddish brown), it was thought to be made up of a mixture of K₂Cr₂O₇ and K₂Cr₃O₁₀. However unfortunately with our FTIR analysis, we could not differentiate the level of chromate oxidation that was present.

FIIR method is a type of infrared (IR) spectroscopy. Here IR radiation is passed through the sample and the resulting spectrum is compared with the spectrum that was already inserted in the library. The resulting spectrum represents the molecular absorption and transmission of the sample which is unique for a particular molecular structure. As the potassium chromate urolithiasis was absent in the literature, the molecular spectrum of K₂CrO₄, K₂Cr₂O₇ and K₂Cr₃O₁₀ was not well defined in the library.

Sixty per cent of absorbed chromium is excreted by the kidney, mainly in the form of Cr³⁺ and the urinary excretion rate depends on the intake of chromium [3]. Measurement of chromium in the body fluid is considered the more reliable marker for chromium exposure [2]. By the time we analysed her stone, the child had become clinically asymptomatic and the patient’s residence was nearly 320 km away from our centre. So we were unable to get down her blood and urine samples for chromium analysis.

70g of brown colour ‘Thalisadhi Chooranam’ was analysed by microwave digestion followed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and found to have 0.98 mg of chromium in 1kg powder (1 microgram Cr/ 1g powder). She has been taking this medicine as two teaspoons thrice a day for almost 5 years. 1 teaspoon contains 4.2 grams of ‘Thalisadhi Chooranam’ powder which contains 4.2 micrograms of chromium. So her daily chromium intake was roughly about 25.2 microogram. Though the adequate dietary intake of chromium for a nine-year-old female is 21 micrograms/ day, a tolerable upper intake level was not established as the data were insufficient [1].

Although oral chromium exposure-related health issues were reported in the literature, none were identified in our patient [2, 3]. The data on chromium toxicity was limited due to the lack of evidence chromium chromium-containing stones in the literature. As we warrant future studies on this topic.

Urolithiasis is common among patients with metabolic abnormalities, urinary tract infections and/or structural abnormalities and is commonly composed of calcium oxalate, calcium phosphate, magnesium ammonium phosphate, cystine and uric acid. Up to now not a single case has been reported on chromium toxicity related to renal stones with potassium chromate as the primary component. This case highlights the fact that chronic oral chromium ingestion can lead to urolithiasis, in the absence of other systemic involvement of chromium toxicity. So care must be taken when prescribing the drugs that have chromium more specifically in the context of alternative medicines and prescriptions for children.

Cr Creatinine

FTIR Fourier transform-infrared spectroscopy

K₂CrO₄Potassium chromate

K₂Cr₂O₇Potassium dichromate

K₂Cr₃O₁₀Potassium trichromate

ICP-MS Inductively Coupled Plasma Mass Spectrometry

Ethics approval and consent to participate

Not applicable

Consent for publication

Written informed consent was obtained from the patient’s parents for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Availability of data and materials

The datasets used during the study are available from the corresponding author on request.

Competing interests

All authors declare no competing interests.

Funding

Authors did not receive funds of any sort from other parties for this manuscript preparation or publication and this was prepared as part of self-interest towards continued medical education

Authors contribution

SO and AO designed and drafted the manuscript; SJ collected the patient’s data; AA revised the manuscript; EJ interpreted the data and revised the manuscript.

All authors read and approved the manuscript.

Acknowledgements

The authors gratefully acknowledge Mr U.W.N.P.Silva (Medical Laboratory technologist) for helping us to analyse the renal stone using FTIR.

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DesMarias TL, Costa M. Mechanisms of chromium-induced toxicity. Curr Opin Toxicol. 2019;14:1–7.
Miyake O, Yoshimura K, Tsujihata M et al. Possible Causes for the Low Prevalence of Pediatric Urolithiasis. 1999.
Jobs K, Rakowska M, Paturej A. Urolithiasis in the pediatric population – Current opinion on epidemiology, pathophysiology, diagnostic evaluation and treatment. J Mother Child. 2018;22:201–8.
Robinson C, Shenoy M, Hennayake S. No stone unturned: The epidemiology and outcomes of paediatric urolithiasis in Manchester, United Kingdom. J Pediatr Urol. 2020;16:e3721–372. .e7.
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Lieske JC, Rule AD, Krambeck AE, et al. Stone composition as a function of age and sex. Clin J Am Soc Nephrol. 2014;9:2141–6.
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No competing interests reported.

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You are reading this latest preprint version

Potassium Chromate as The Primary Constituent of Renal Stones in a Child With Chronic Chromium Ingestion: The First Case Report of Chromate Urolithiasis

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