Fanconi Fun

 Reuben yesterday with my birthday "cupcake on ice cream!"

I wrote this rather slapdash report last week for my Coursera Chemistry mini research paper. If you've been interested in Reuben's kidney disease, well, THIS TREAT IS FOR YOU.

My five year old son Reuben has Fanconi syndrome, diagnosed during a period of poor growth after chemotherapy treatment for a synovial sarcoma in his right shoulder. Fanconi syndrome is a kidney disorder caused by damage to the proximal tubules in the kidney, in his case from therapeutic use of the drug ifosfamide [2,3]. The result is a diminished reabsorption of solutes by the proximal tubule. Clinical manifestations of this disorder can be more complex, depending on the biological cause of the tubule damage, but in Reuben's case his symptoms and management are limited to nutritional electrolyte levels and prevention of acidosis. [1,2]

Reuben was promptly treated with heavy supplementation of electrolytes and bicarbonate, and avoided the side effects (rickets from phosphorus and vitamin D deficiency is one concern) that could be caused by nutritional deficiency of essential electrolytes [3]. This treatment has continued for four years. More advanced biochemistry can be applied to the mechanisms of his renal tubules and the biological effects of these electrolytes, but I will limit this brief discussion to inorganic chemistry. As we learned about electrolytic reactions and precipitates in Week 4, I immediately thought of the precipitates I have observed in Reuben's urine. "Tell your doctor about cloudy urine" urge parenting articles, so I asked his nephrologist, who has assured me (from theoretical knowledge and the urinalysis done regularly) that the cloudiness in the toilet bowl, what I saw crystalized at the bottom of his wee toilet during potty training, and the residue I sometimes observe in his underwear is expected. I'm seeing a solid result of most of  the electrolyte solution I deliver three times daily orally, processed inefficiently by his damaged kidneys ("It's chemistry in action!" I told my physician and biologist siblings. Our inner chemistry geeks were very excited). This paper--and the refreshing of my 20-year-dormant inorganic chemistry skills with this class--gives me the opportunity to make a prediction exactly what the precipitates are.

I theoretically know that Reuben likely has excessive urination of many solutes, including glucose, amino acids, calcium, phosphate, uric acid, bicarbonate and many organic compounds [3]. I can reasonably conclude, however, that he is excreting most what he receives most of. His daily oral supplementation regimen gives him the following, which represents a massive excess of what his little 43 pound body uses: 

*30 mL of CYTRA-2, a formulation that includes sodium citrate and citric acid in a neutralizing buffer. For the purposes of this paper, I'm going to ignore the inactive ingredients, and just consider the stated concentrations in 5 mL aqueous solution: 500 mg Sodium Citrate Dihydrate and 334 mg Citric Acid Monohydrate. The label states that each mL contains 1 mEq Sodium Ion and is equivalent to 1 mEq Bicarbonate (HCO3) [4].

*1 1/2 packets of PHOS-NaK, a powdered concentrate. Each packet contains (again, just the active ingredients) 160 mg sodium, 280 mg potassium, and 250 mg phosphorus in the form of potassium phosphate and sodium phosphate.

Calculations:

part 1: the ions

From CYTRA-2: Na+, HCO3 -2  (the sodium citrate and citric acid in the CYTRA-2 are converted to bicarbonate by the liver [7]).

From Phos-NaK: K+, Na+, PO4 -3 (phosphorus is transported and processed in the intestine, kidneys, and urine in phosphate form [8]).

Resultant cations: Na+,  K+

Resultant anions: HCO3 -2, PO4 -3

part 2: the precipitates 

I expected to discover in this step that one of the resultant ionic compounds was insoluble, and that would be the precipitate that I observe, but according to solubility rule #1, "Most compounds of Group 1 metal cations are soluble." Because both of the supplemental cations are Group 1 metals, I can expect that the possible compounds of the ions listed above would be primarily in solution. The precipitate I observe must therefore be the result of an already fully saturated aqueous solution in Reuben's urine. I predict the following possible electrolyte salts in excess: Na2HCO3, K2HCO3, Na3PO4, K3PO4 (sodium bicarbonate, potassium bicarbonate, sodium phosphate, and potassium phosphate).

If this chapter of my education extends to a laboratory portion of my chemistry review, I may, in the future, be able to test the accuracy of the predictions made by my chemical figuring above. I could do further research on the way the digestive system uses and transforms elements and their ions to be more accurate in my chemical predictions, but the above exercise was interesting, and appropriate at my current chemistry knowledge level. "Fanconi syndrome" describes a class of disorders whose variable symptoms depend on the cause and extent of the proximal tubule damage [2]. I would like to know exactly what Reuben's body disposes of, and how this changes as his body and metabolic needs grow. More specific research could still be done on the chemistry of affected patients' urine and blood to see exactly the sort of damage done to a 6 month old child with high doses of ifosfamide (it was reported as early as 1974 [3,6]), but I hope that the incidence of cases remain low enough that such studies cannot be categorically conclusive, particularly at stages of early development, such as my 6-month old baby. 

Sources cited:

1. "Fanconi Syndrome." Author: Sahar Fathallah-Shaykh, MD; Chief Editor: Craig B Langman, MD. Accessed on web at http://emedicine.medscape.com/article/981774-overview.

2. Discussions with the subject's mother and nephrologists.

3. " Ifosfamide induced Fanconi syndrome." Samantha Buttemer, Mohan Pai2 and Keith K Lau. BMJ Case Rep. 2011; 2011.  Accessed on web at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246161/

4. Label for Cypress Pharmaceutical, Inc.'s CYTRA-2 oral solution.

5. Label for Cypress Pharmaceutical, Inc.'s PHOS-NaK powder concentrate supplements.

6. "Renal dysfunction after treatment with isophosphamide." DeFronzo RA, Abeloff M, Braine H, Humphrey RL, Davis PJ. Cancer Chemother Rep. 1974 May-Jun;58(3):375-82. Accessed on web at http://www.ncbi.nlm.nih.gov/pubmed/4842666.
7. "Urinary Alkalization" by David S Goldfarb, M.D.(Director, Kidney Stone Prevention Program, St. Vincents Hospital & Professor of Medicine and Physiology, NYU School of Medicine). Accessed on web at http://www.cystinuria.com/articles/urinary-alkalization/.

8. "Potassium Phosphate/Pharmacology." Accessed on the web at http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=516951#x94