Phosphate Urine Excretion in Critically Ill Patients

Hypophosphatemia is a common disorder in critically ill patients, appearing in 15-35% of Intensive Care Unit (ICU) admissions. Its reasons are multifactorial, including sepsis, refeeding syndrome, and continuous renal replacement therapy. Hypophosphatemia is generally accepted as a predictor of poor outcomes, such as prolonged ventilation and higher mortality. However, conflicting evidence exists and several works demonstrated no effect on length of ventilation, nor mortality. We have recently demonstrated no effect of hypophosphatemia on mortality and length of ventilation. However, both parameters were affected by energy delivery to the patient, with higher energy delivery associated with lower mortality and longer length of ventilation, suggesting a complex interaction between energy delivery to the patient, hypophosphatemia appearance, and patient outcomes. This raised hypothesis that hypophosphatemia is a marker of recovery, as in fulminant hepatic failure, or recovery after hepatectomy.

Phosphate is mainly an intracellular anion, with only 1% of its total body amount is extracellular. It is absorbed from the small intestine, mainly at the jejunum, both through passive para-cellular and active trans-cellular process. Phosphate is excreted in the urine, after being filtered in the glomeruli, and reabsorbed mainly in the proximal tubule (less than 10% of the reabsorption occurs in the distal nephron), by sodium-phosphate co-transporters. Phosphate regulation in the body is complex. It is regulated by vitamin D, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23). Therefore, phosphate regulation is affected both from intestine dysfunction and kidney injury. Although hyperphosphatemia in various kidney injury is well described, the effect of kidney function regarding phosphate excretion in critically ill patients with hypophosphatemia has been scarcely described. French and Bellomo described 7 patients who had decreased phosphate kidney reabsorption during hypophosphatemia. Charrone et. al demonstrated increased phosphate excretion after IV phosphate infusion to 47 critically ill patients with hypophosphatemia. Dickerson et. al demonstrated higher rates of hypophosphatemia in 20 thermally injured patients (compared to 20 multiple trauma patients) despite greater phosphate delivery through nutrition, along with increased (although insignificant) phosphate urinary excretion in this group. This might suggest that increased renal phosphate loss has a role in hypophosphatemia development. Better understanding these processes is important, with regard to the effect of nutritional support and hypophosphatemia effects on patients' outcomes. This study aims to describe urinary phosphate excretion in critically ill patients with regard to kidney function, phosphate serum level, and phosphate intake.

Data collection

We will document the following data for each patient, for maximum of five days from admission:

* Demographic data, including age; sex, height, weight, admission reason to ICU.
* Acute Physiology And Chronic Health Evaluation II (APACHE II) Score (24 hours after ICU admission)
* Daily Sequential Organ Failure Assessment (SOFA) Score and SOFA components.
* Daily Ventilation status
* Daily vasopressor requirement
* Daily Renal replacement therapy (if any)
* Daily urine volume
* Daily fluid balance - including daily fluid input and output
* Daily 6 hours urine collection, with documentation of collection volume, urine creatinine, and urine electrolytes. Specimens from the first two days of admission will be sent to laboratory analysis only after the patient is admitted for more than 48 hours.
* Calculation of glomerular filtration rate (GFR) based on urine collection findings.
* Calculation of phosphate excretion amount based on urine collection findings - both maximal phosphate tubular reabsorption rate (TmP) and Fractional Excretion of phosphate (FePi).
* Daily serum phosphate and calcium levels
* Daily phosphate intake - from enteral nutrition, parenteral nutrition, and supplemental (enteral and parenteral).
* For the last 60 patients - a single measurement of PTH and vitamin D.
* Patient outcomes: ICU length of stay; Hospital length of stay; Length of ventilation; Ventilator free days at 28 days; Mortality - at ICU, during hospital admission, and at 28 \& 90 days.

Eligibility Criteria:
Inclusion Criteria:

Adult (\>18) Critically ill patients who are admitted for at least 48 hours in the ICU, who are being ventilated in the first time it's 00:00 during their admission, with a urinary foley catheter.

Exclusion Criteria:

* Age \< 18 years
* Pregnancy.
* Recent admission to an ICU (within 30 days)
* Chronic kidney disease treated with hemodialysis.
* Oral nutrition by the patient at admission time
* Existence of another urinary catheter (e.g nephrostomy), or ileal conduit.
* Hematuria
* RRT treatment within 48 hours of admission