Tenofovir Associated Hypophosphatemia with Elevated Fibroblast Growth Factor 23

Presentation Number: SAT 309
Date of Presentation: April 1st, 2017

Ayesha Farooq Malik* and Robert C. Smallridge
Mayo Clinic, Jacksonville, FL


Introduction:There is evidence that tenofovir can cause hypophosphatemia and Fanconi syndrome. Tenofovir induced hypophosphatemia has been reported with a normal fibroblast growth factor 23 (FGF-23) in a few case reports and elevated in one case. We present a patient with tenofovir induced hypophosphatemia and proteinuria with an elevated FGF-23 level.

Case:A 69-year-old male with HIV for 13 years was seen for weight loss (not suspected to be from HIV) and thyroid nodules. At our facility calcium = 8.9 mg/dL (8.9 -10.1 mg/dL), phosphorus = 2.1 mg/dL (2.5-4.5mg/dL) and alkaline phosphatase (ALP) = 315 U/L (45-115 U/L). 10 days later, calcium = 8.3 mg/dL (8.6 -10.3 mg/dL), 25-hydroxyvitamin D = 32 (30-100ng/mL), parathyroid hormone = 105 (10-65 pg/mL) and alkaline phosphatase = 293 U/L. He was started on ibandronate for a T score of -5.2 (distal forearm) and -2.8 (lumbar spine).

At his local lab, a parathyroid hormone = 29, calcium =9.1mg/dL, phosphorus = 1.6mg/dL (2.1-4.3mg/dL), and alkaline phosphatase = 282 with 75% bone iso-enzyme (28-66%). He had been taking tenofovir for 3 years but this was recently changed to Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate).

A 24-hour urine phosphorus was 711mg (0-1099mg), urine protein = 1.1gm and percent tubular reabsorption of phosphorus = 45.5%. An FGF-23 was elevated at 1740 (<=180 RU/mL), with serum calcium = 8.7mg/dL, phosphorus = 1.3mg/dL, and 1,25 hydroxyvitamin D= 44 (18- 64pg/mL). He was advised to stop Atripla and two weeks later his phosphorus level normalized to 2.7mg/dL. Two months later the phosphorus was 2.3mg/dL and ALP remained elevated at 328.

Four months after stopping Atripla, a calcium was 8.6mg/dL, phosphorus was at 2.1mg/dL, and ALP= 275. FGF-23 remained elevated at 1740 RU/mL. Two months later, phosphorus was 2.3mg/dL with an improved ALP of 141 U/L. The patient also had resolution of muscle weakness and 20 pound weight gain.

Nine months after stopping tenofovir, phosphorus=2.7mg/dL and at one year a repeat 24 hour urine phosphorus = 284 mg and urine protein =207mg. Attempts to repeat an FGF 23 level were unsuccessful.

Discussion:A case series found that those on tenofovir who had hypophosphatemia had normal FGF 23 levels. Suggested mechanism of hypophosphatemia was possibly due to a parathyroid hormone-like factor. One patient had an elevated FGF-23 level that returned to normal six months after discontinuing tenofovir. This case is the second described in which FGF-23 may be implicated as a cause for hypophosphatemia in an HIV patient on tenofovir. Fibroblast Growth Factor 23 (FGF-23) is involved in regulation of calcium and phosphorus homeostasis. When elevated, it inhibits 1,25 hydroxyvitamin D thus decreasing phosphorus absorption. It also decreases expression of 1 alpha hydroxylase, decreasing renal absorption of phosphorus. It also may decrease parathyroid hormone.


Nothing to Disclose: AFM, RCS