Renal tubular dysfunction is observed in all patients and it is usually Fanconi type RTA associated with glucosuria, phosphaturia
and proteinuria and less frequently as renal diabetes insipidus.
Fanconi syndrome caused by TDF is characterized by generalized proximal tubular dysfunction resulting in one or more of the following: bicarbonaturia, glucosuria, phosphaturia
, uricosuria, aminoaciduria, and tubular proteinuria.
The differentiation of PHP-I from PHP-II is made by comparing the in vivo response to exogenous PTH in terms of nephrogenic cAMP synthesis and phosphaturia
. The presence of cAMP elevation without phosphaturia
marks PHP-II (24,25).
In the biochemical analyses done at the hospital, urinalysis revealed hemoglobin 1+ and protein 2 + ; 24-hr urine analysis results were phosphorus: 14.4 mg/dL (phosphaturia
), creatinine: 16.6 mg/dL (reduced clearance), phosphorus: 3.73 mg/dL (hypophosphatemia); and blood biochemistry test showed normal albumin, calcium, and sodium levels.
There he had normal serum calcium (S-Ca 2.36 mmol/L), serum phosphate (S-P 1.51 mmol/L), alkaline phosphatase (S-ALP 3.99 [micro]at/L), parathyroid hormone (S-PTH 1.42 pmol/L) levels, together with normal calciuria and phosphaturia
. The wrist X-ray was normal.
FGF-23 is stimulated by high serum phosphate levels and promotes phosphaturia
to maintain serum phosphate levels within the normal range .
Fibroblast growth factor 23 (FGF-23), a circulating peptid secreted by bone cells, known for inducing phosphaturia
, lowering 1,25 dihydroxy-vitamin D, and suppressing PTH secretion, a new marker of inflammation, insulin resistance, and visceral fat accumulation, has been also associated with cardiovascular events and arterial stiffness [50,69].
The 24 h urine analysis showed a tubular phosphorus reabsorption rate of 88%, with phosphaturia
of 16.9 mmol/24 h.
Nevertheless, after 5 months of TDF-treatment, normoglycemic glycosuria (glycemia 88 mg/dl, glycosuria 70 mg/dl), phosphaturia
with hypophosphatemia (reduced tubular absorption of phosphorus (56%), phosphatemia 1.9 mg/dl, proteinuria (albuminuria 100 mg/dl at dipstick, proteinuria: 0.2 g/24 h), glomerular filtration rate (GFR) 70 ml/min/1.73 [m.sup.2], and urine creatinine 0.47 g/day were detected, leading to diagnosis of Fanconi Syndrome associated with TDF-therapy.
Recently, prolonged intravenous SFO induced hypophosphatemic osteomalacia has been reported to be associated with fibroblast growth factor 23 (FGF-23), which has the critical factor of maintaining serum phosphate homeostasis via suppression of 25-hydroxyvitamin D activation and promotion of phosphaturia
, and the patient exhibited high serum FGF 23 levels .
Diagnosis of TIO should always be suspected in case of hypophosphatemia and excessive phosphaturia
. Some of the notable causes of hypophosphatemia are listed in Table 1.
In early CKD, compensatory mechanisms mediated by FGF23 maintain phosphaturia
at a sufficient level.