Mechanisms of Renal Phosphate Loss in Liver Resection-Associated Hypophosphatemia

Abstract

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. Conclusion 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.

Phosphate homeostasis and disorders

“…108 Serum phosphate starts to decrease on the first or second post-operative day and returns to normal by the ninth day. 169 The mechanism for hypophosphataemia post-hepatic surgery is not known, but it has been suggested that uptake of phosphate by rapidly regenerating liver cells may be a possible cause. This is supported by the correlation between hypophosphataemia and liver regeneration 170 although another study suggests that the quantity of phosphate taken up by regenerating liver cannot account for the degree of hypophosphataemia.…”

Hepatectomy-Related Hypophosphatemia

“…The changes in the biochemical parameters in PH rats were similar to those in human PH patients. 14 Renal Na/Pi Transport Activity in PH Rats We then investigated renal and intestinal Na/Pi transport activities at 12 hours after PH. Renal and intestinal Na/Pi transport activities were significantly reduced in PH rats compared with sham-operated rats ( Figure 2, A and B).…”

“…The magnitude of Pi uptake by the recovering liver, however, cannot explain the severity of the resulting hypophosphatemia. 11 Hepatectomy-induced hypophosphatemia is associated with an increased renal fractional excretion index for Pi unrelated to intact FGF23, FGF7, or secreted frizzled-related protein 4 as a phosphaturic factor, 14 indicating that other factors have a role in the pathogenesis of hypophosphatemia.…”

Untitled

“…A similar finding was observed in a more recent study by Nafidi and associates. 20 Again, hypophosphatemia after liver resection was associated with hyperphosphaturia due to increased fractional excretion of phosphate. In these 2 studies, liver resection was carried out in patients with primary or metastatic liver tumors, and all patients had normal preoperative renal function.…”