Hypophosphatemia with anti-cancer agents

 

Here is a schematic of what we know for now in 2021 in relation to anti cancer agents leading to low phosphorus. This was made using biorender.com and inspired by the article Adhikari et al. 

Concept Map: Hypomagnesemia and it's effect on other electrolytes

Topic Discussion: Phosphorus content of prescription Medications

There is a source of dietary phosphorus that has been noted but is largely unrecognized and unquantified—the phosphorus content of prescription medications. That drugs may contain phosphorus is clear, as it is indicated on the list of inert ingredients reported on their package label. Sherman et al few years back did an amazing study that showcased that medication preservatives might have phosphorus content that we don’t recognize. This might be also causing some phosphorus rises in our patients and need for increased binders.

Medication and dose	Manufacturer	Phosphorus content	Amt of Phos binders required additional
Lisinopril 10mg	Qualitest	40.1mg	2
Lisinopril 10mg	Blue Point labs	32.6mg	1.5
Amlodipine 10mg	Greenstone	27.8mg	1
Amlodipine 10mg	Lupin	8.6mg	-
Paroxetine	Glaxosmith Kline	111.5mg	5
Paroxetine	Cadila	22.7mg	1
Renavite	Cypress	37.7mg	1
Renocaps	Nnodum	1.7mg	-

How do we help our patients with this information? Better would be some way of making prescribers aware that their prescribed medications may be high in phosphorus—they are not ‘dialysis safe’. 

Perhaps creating a database of all drugs and their phosphorus content might be useful.  Or is this not consequential to our patients as diet is the biggest factors… the above is just the sample of drugs the author had inquired.. imagine the rest of the medications and other chemotherapy and other anitbiotics we give our patients.

Clinical Case 86: Answers and Summary

Which one of the following chemotherapy agents cause solitary hypophosphatemia?(select more than 1)

cisplatin	7 (38%)
sorafenib	2 (11%)
imatinib	7 (38%)
lenalidomide	4 (22%)

While many chemotherapy agents cause electrolyte disorders, hypophosphatemia is a rare occurrence.

Let’s take each chemotherapy agent at a time that is listed above.

Cisplatin classically is known to cause AKI and proximal tubular damage and hypomagnesemia but sole hypophosphatemia is rarely reported. Usually, a classic Fanconi syndrome has been described. 
So, choice A is less likely to cause solitary hypophosphatemia.

Sorafenib, a multikinase inhibitor targeting the c-Kit, RAF, VEGF and PDGF pathways, is approved for the treatment of patients with hepatocellular carcinoma and renal cell carcinoma, with a broad spectrum of activity also including selected sarcoma subtypes, thyroid cancers and melanoma. Sorafenib induces pancreatic exocrine dysfunction, leading to vitamin D malabsorption and secondary hyperparathyroidism. Patients receiving sorafenib can develop hypophosphatemia and vitamin D deficiency.

Of the 4 listed above, imatinib has been most well described with this electrolyte disorder. In NEJM, Berman and colleagues reported their findings regarding the development of hypophosphatemia and associated changes in bone and mineral metabolism in patients with either chronic myelogenous leukemia or gastrointestinal stromal tumors who are taking imatinib. A nice review article discusses the effect of all tyrosine kinase inhibitors such as imatinib and sorafenib and their effects on bone health. By inhibiting platelet-derived growth factor receptors expressed on osteoclasts, these agents cause a subsequent decrease in bone resorption and decreased calcium and phosphate egress from the bone. As a result, PTH levels increase and phosphaturia follows.

Lenalidomide and hypophosphatemia has been described in conjunction with other therapies and sole effect. It appears to be a potential renal loss mechanism. It is hard in this drug as myeloma is the primary cancer and the cancer itself can cause this electrolyte disorder. A Fanconi syndrome has also been described. 

Concept Map: Hypophosphatemia

Here is a concept map of hypophosphatemia based on two great articles. Click on it to get a larger view.

Two great references are:
http://www.ncbi.nlm.nih.gov/pubmed/17568018
http://www.ncbi.nlm.nih.gov/pubmed/16932412

Concept Map: Hypophosphatemia

A recent article in Am J of Kidney Diseases goes through a pathophysiology of diagnosis of hypophosphatemia. A concept map summarizes that article. Please review and comment to add more causes if you can.

Detective Nephron strikes again

IN THE NEWS--> Detective Nephron's next venture

Check out the March issue of ASN Kidney News 2012 for the next venture of the detective

http://onlinedigeditions.com/publication/?m=15191&l=1

Take a look at the entire series so far at

http://www.nephronpower.com/p/detective-nephron-seriesasn-kidney-news.html

Consult Rounds: Hyperphosphatemia

In the steady state, the serum phosphate concentration is primarily determined by the ability of the kidneys to excrete dietary phosphate.  When you give an acute phosphate load  over several hours, transient hyperphosphatemia can ensue.

There are three general circumstances in which this occurs: massive acute phosphate load; chronic renal failure; and a primary increase in proximal phosphate reabsorption. The fourth is pseudohyperphosphatemia.




1. CAUSES OF Phosphate Load to consider:
Tumor lysis syndrome
Rhabdomyolysis
Lactic acidosis
Ketoacidosis
Phosphate Enemas or laxatives
Vitamin D Toxicity

2. RENAL FAILURE is self explanatory

3. Increased Tubular Reabsorption of Phosphate:
    Hypoparathyroidism
    FGF-23 Deficiency
    Acromegaly
    Bisphosphanates
    Tumoral Calcinosis

4. Pseudohyperphosphatemia from elevated bilirubin, paraproteins, lipids and hemolysis

Hope this simplifies the differential of hyperphosphatemia