Hepatic resection-related hypophosphatemia is of renal origin as manifested by isolated hyperphosphaturia.

OBJECTIVE: The objective of this study was to elucidate and define the pathophysiological mechanism(s) responsible for the clinically relevant phenomenon of posthepatic resection hypophosphatemia. SUMMARY BACKGROUND DATA: Although biochemically significant hypophosphatemia has been described after major hepatic resection, no mechanism or validated scientific explanation exists. The phenomenon is of considerable clinical relevance because numerous patients, after hepatic resection, develop significant hypophosphatemia requiring large doses of phosphate replacement to maintain metabolic homeostasis. This event has previously been empirically ascribed to amplified phosphate utilization of regenerating hepatocytes, although no rigorous data attest to this postulate. Recent data identifying a novel mechanism of phosphaturia in X-linked hypophosphatemic rickets, autosomal-dominant hypophosphatemic rickets, and oncogenic osteomalacia demonstrate that elevated levels of novel circulating phosphaturic factors such as fibroblast growth factor 23 (FGF-23) and PHEX are responsible for phosphate wasting. We hypothesize that posthepatectomy hypophosphatemia reflects a derangement of normal hepatorenal messaging and is the result of a disruption of renal phosphate handling consequent on aberrations in the metabolism of an as yet unrecognized chemical messenger(s) responsible for tubular phosphate homeostasis. This postulate has not previously been proposed or examined.
METHODS: Twenty patients undergoing hepatic resection were studied prospectively with respect to serum phosphate, phosphate requirements, as well as renal phosphate handling. Fractional excretion of phosphate was calculated on a daily basis. To confirm the relationship between phosphate loss and a circulating renal-targeted messenger, the plasma levels of the circulating phosphaturic factor FGF-23 were measured using a c-terminal assay both pre- and postoperatively.
RESULTS: All patients developed hypophosphatemia with a nadir on postoperative day 2 (average drop of 47% despite phosphate administration). This phenomenon was associated with hyperphosphaturia (mean +/- standard error) with high fractional excretion of phosphate. A consistent change in FGF-23 was not identified.
CONCLUSION: Hypophosphatemia after hepatic resection is a frequent occurrence. Transient isolated hyperphosphaturia and not increased phosphate utilization is the predominant cause of this phenomenon, although the identity of the agent involved remains to be identified.