Hypophosphatemia after Hepatectomy or Pancreatectomy: Role of the Nicotinamide Phosphoribosyltransferase

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 designs 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 (FGF-23), and parathyroid hormone (PTH) were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide (2-PY) and N-methyl-4-pyridone-3-carboxamide (4-PY). Results We found that significant hypophosphatemia occurred from postoperative day (POD) to POD2 in all 4 groups were preceded by hyperphosphaturia from preoperative day to POD1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD2 in all 3 resected groups but not in the control group. FGF-23 levels were significantly decreased postoperatively in all 4 groups while PTH levels did not change in any of the 4 groups. Urine levels of 2-PY and 4-PY significantly decreased 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 further investigation.

Implications of Postpancreatectomy Hypophosphatemia

“…5 However, the condition is also observed following surgical procedures. 13,14 The observation of hypophosphatemia following pancreatectomy in this study supports prior literature citing reports of postoperative hypophosphatemia in hepatectomy, colectomy, and gastrectomy patients. 14-17 Within these patient cohorts, severe hypophosphatemia was also associated with organ-specific complication incidence following gastrointestinal operations.…”

“…13,14 The observation of hypophosphatemia following pancreatectomy in this study supports prior literature citing reports of postoperative hypophosphatemia in hepatectomy, colectomy, and gastrectomy patients. 14-17 Within these patient cohorts, severe hypophosphatemia was also associated with organ-specific complication incidence following gastrointestinal operations. 3,18 Because of the prevalence of hypophosphatemia postoperatively, it may be important to determine if complication incidence is associated with the severity of hypophosphatemia.…”

Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial

“…Elegant work has demonstrated that the nicotinamide phosphoribosyl transferase (Nampt)/ (NAD + ) intracellular pathway plays a fundamentally important role in the expression of renal and intestinal phosphate transporters (NaPi-2a, NaPi-2b, and NaPi-2c), and likely plays an additional role in the transcellular shifts from other organs that occur independent of oral phosphate ingestion, and which determine diurnal variation in serum phosphate concentration. [25][26][27] Even our understanding of what constitutes a "phosphate-restricted diet" is now known to be on the basis of basic misunderstandings about the relative contribution of animal-versus plant-versus additive-based phosphate exposure. 9,28 Our findings here indicate a clear and substantial contribution of paracellular phosphate transport to net phosphate absorption.…”

Hypophosphatemia as a Predictor of Organ‐Specific Complications Following Gastrointestinal Surgery: Analysis of 8034 Patients

“…Although dextrose may cause transcellular shift of phosphate, this shift would be transient. In a prospective cohort study, the authors found postoperative hypophosphatemia was related to hyperphosphaturia, as likely mediated by nicotinamide phosphoribosyltransferase (NAMPT), which acted as a phosphaturic factor as well as a metabolic enzyme that synthesizes nicotinamide adenine dinucleotides [34,35], The role of NAMPT on OSC was not studied and it warrants additional investigation. Furthermore, whether hypophosphatemia is the symptom or cause of complication is also unclear.…”