Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia.
OBJECTIVE
To determine precisely the role of parathyroid hormone (PTH) and of phosphatonins in the genesis of posthepatectomy hypophosphatemia.


BACKGROUND
Posthepatectomy hypophosphatemia has recently been related to increased renal fractional excretion of phosphate (FE P). To address the cause of hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins, and the number of removed hepatic segment in patients with this disorder.


METHODS
Serum phosphate (PO4), ionized calcium (Ca++), HCO3-, pH and FE P, intact PTH (I-PTH), carboxyl-terminal fibroblast growth factor 23 (C-FGF-23) and intact fibroblast growth factor 23 (I-FGF-23), FGF-7, and secreted frizzled related-protein-4 (sFRP-4) were measured before and on postoperative (po) days 1, 2, 3, 5, and 7, in 18 patients undergoing liver resection. The number of removed hepatic segments was also assessed.


RESULTS
Serum PO4 concentrations decreased within 24 hours, were lowest (0.66 +/- 0.03 mmol/L; P < 0.001) at 48 hours, and returned to normal within 5 days of the procedure. FE P peaked at 25.07% +/- 2.26% on po day 1 (P < 0.05). Decreased ionized calcium concentrations (1.10 +/- 0.01 mmol/L; P < 0.01) were observed on po day 1 and were negatively correlated with increased I-PTH concentrations (8.8 +/- 0.9 pmol/L; P < 0.01; correlation: r = -0.062, P = 0.016). FE P was positively related to I-PTH levels on po day 1 (r = 0.52, P = 0.047) and negatively related to PO4 concentrations (r = -0.56, P = 0.024). Severe hypophosphatemia and increased urinary phosphate excretion persisted for 72 hours even when I-PTH concentrations had returned to normal. I-FGF-23 decreased to its nadir of 7.8 +/- 6.9 pg/mL (P < 0.001) on po day 3 and was correlated with PO4 levels on po days 0, 3, 5, and 7 (P < 0.001). C-FGF-23, FGF-7 and sFRP-4 levels could not be related to either PO4 concentrations or FE P.


CONCLUSIONS
Posthepatectomy hypophosphatemia is associated with increased FE P unrelated to I-FGF-23 or C-FGF-23, FGF-7, or sFRP-4. I-PTH contributes to excessive FE P partially on po day 1 but not thereafter. Other yet defined factors should explain post hepatectomy hypophosphatemia.
Nafidi
Otmane
O
Department of Surgery, Centre hospitalier de l'Université de Montréal, (CHUM)-Hôpital Saint-Luc, Montréal, Québec, Canada.
Lapointe
Real W
RW
Lepage
Raymond
R
Kumar
Rajiv
R
D'Amour
Pierre
P
D000328:Adult; D000368:Aged; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000097:blood / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000502:physiology; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D017674:Hypophosphatemia / Q000209:etiology / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood / Q000502:physiology; D010710:Phosphates / Q000097:blood / Q000502:physiology / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000502:physiology; D000094742:Secreted Frizzled-Related Proteins
D051523:Fibroblast Growth Factor 7; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D010281:Parathyroid Hormone; D010710:Phosphates; D011518:Proto-Oncogene Proteins; C000717427:FGF23 protein, human; C496453:FGF7 protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins