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. 2017 Oct;225(4):488-497e2.
doi: 10.1016/j.jamcollsurg.2017.06.012. Epub 2017 Jul 6.

Hypophosphatemia after Hepatectomy or Pancreatectomy: Role of the Nicotinamide Phosphoribosyltransferase

Jian Zheng  1 , Ilya G Glezerman, Eran Sadot, Anjuli McNeil, Cristina Zarama, Mithat Gönen, John Creasy, Linda M Pak, Vinod P Balachandran, Michael I D'Angelica, Peter J Allen, Ronald P DeMatteo, Peter T Kingham, William R Jarnagin, Edgar A Jaimes
Affiliations

Hypophosphatemia after Hepatectomy or Pancreatectomy: Role of the Nicotinamide Phosphoribosyltransferase

Jian Zheng et al. J Am Coll Surg. 2017 Oct.

Abstract

Background: Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy, but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia.

Study design: We prospectively enrolled 120 patients who underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy (n = 30), and laparotomy without resection (control group, n = 30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide.

Results: We found that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD 2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to POD 1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in the control group. The fibroblast growth factor-23 levels were significantly decreased postoperatively in all 4 groups, and parathyroid hormone levels did not change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups postoperatively.

Conclusions: This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant additional investigation.

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Figures

Fig. 1
Fig. 1
(A) Study tests were obtained from serum and urine. Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme in the NAM metabolism whereas (B) 2-PY and 4-PY are urinary end products of the NAM metabolism. POD, postoperative day; eNAMPT, extracellular nicotinamide phosphoribosyltransferase; FGF-23, fibroblast growth factor-23; PTH, parathyroid hormone; 2-PY, N-methyl-2-pyridone-5-carboxamide; 4-PY, N-methyl-4-pyridone-3-carboxamide; NAM, nicotinamide; NMN, nicotinamide mononucleotide; NAD, nicotinamide adenine dinucleotide; MNA, N1- methylnicotinamide.
Fig. 1
Fig. 1
(A) Study tests were obtained from serum and urine. Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme in the NAM metabolism whereas (B) 2-PY and 4-PY are urinary end products of the NAM metabolism. POD, postoperative day; eNAMPT, extracellular nicotinamide phosphoribosyltransferase; FGF-23, fibroblast growth factor-23; PTH, parathyroid hormone; 2-PY, N-methyl-2-pyridone-5-carboxamide; 4-PY, N-methyl-4-pyridone-3-carboxamide; NAM, nicotinamide; NMN, nicotinamide mononucleotide; NAD, nicotinamide adenine dinucleotide; MNA, N1- methylnicotinamide.
Fig. 2
Fig. 2
(A) Significant hypophosphatemia on POD2 was preceded by (B) significant hyperphosphaturia on POD1 in all 4 groups. *Significant. IQR, interquartile range; Phos, phosphorus; POD, postoperative day; Preop, preoperative.
Fig. 2
Fig. 2
(A) Significant hypophosphatemia on POD2 was preceded by (B) significant hyperphosphaturia on POD1 in all 4 groups. *Significant. IQR, interquartile range; Phos, phosphorus; POD, postoperative day; Preop, preoperative.
Fig. 3
Fig. 3
(A) Significant increase in eNAMPT levels on POD2 compared to preoperative levels occurred in all 3 resected groups, whereas (B) FGF-23 levels were significantly decreased postoperatively and (C) PTH were not significantly affected by operation in all 4 groups. *Significant. eNAMPT, extracellular nicotinamide phosphoribosyltransferase; FGF-23, fibroblast growth factor-23; IQR, interquartile range; POD, postoperative day; Preop, preoperative; PTH, parathyroid hormone.
Fig. 3
Fig. 3
(A) Significant increase in eNAMPT levels on POD2 compared to preoperative levels occurred in all 3 resected groups, whereas (B) FGF-23 levels were significantly decreased postoperatively and (C) PTH were not significantly affected by operation in all 4 groups. *Significant. eNAMPT, extracellular nicotinamide phosphoribosyltransferase; FGF-23, fibroblast growth factor-23; IQR, interquartile range; POD, postoperative day; Preop, preoperative; PTH, parathyroid hormone.
Fig. 3
Fig. 3
(A) Significant increase in eNAMPT levels on POD2 compared to preoperative levels occurred in all 3 resected groups, whereas (B) FGF-23 levels were significantly decreased postoperatively and (C) PTH were not significantly affected by operation in all 4 groups. *Significant. eNAMPT, extracellular nicotinamide phosphoribosyltransferase; FGF-23, fibroblast growth factor-23; IQR, interquartile range; POD, postoperative day; Preop, preoperative; PTH, parathyroid hormone.
Fig. 4
Fig. 4
Significant decrease in (A) urinary 2-PY and (B) 4-PY excretions on POD2 compared to their preoperative levels in all 4 groups. * Significant. 2-PY, N-methyl-2-pyridone-5-carboxamide; 4-PY, N-methyl-4-pyridone-3-carboxamide; IQR, interquartile range; POD, postoperative day; Preop, preoperative.
Fig. 4
Fig. 4
Significant decrease in (A) urinary 2-PY and (B) 4-PY excretions on POD2 compared to their preoperative levels in all 4 groups. * Significant. 2-PY, N-methyl-2-pyridone-5-carboxamide; 4-PY, N-methyl-4-pyridone-3-carboxamide; IQR, interquartile range; POD, postoperative day; Preop, preoperative.
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