Hypophosphatemia During Kidney Replacement Therapy and Ventilator-Free Days: A Post Hoc Analysis of the STARRT-AKI...

Critically ill patients receiving kidney replacement therapy (KRT), especially continuous KRT (CKRT), have a high risk of hypophosphatemia due to extracorporeal losses, which may contribute to muscle weakness and prolonged respiratory failure. This study evaluated the relationship between incident hypophosphatemia and respiratory function in these patients.

Post hoc observational study of STARRT-AKI Trial participants.

Eligible trial participants (1) received CKRT >24 hours or intermittent hemodialysis (IHD) or sustained low-efficiency dialysis (SLED) for >1 session, (2) had a serum phosphate level ≥ 0.5 mmol/L on the day of KRT initiation, and (3) had ≥1 serum phosphate measurement during KRT.

Hypophosphatemia (<0.7 mmol/L) and severe hypophosphatemia (<0.5 mmol/L) during KRT.

Primary outcome was ventilator-free days (VFD) at 28 days of follow-up. Secondary outcomes included mortality and KRT dependence at 90 days.

A truncated hurdle model was fit to describe clinical characteristics associated with hypophosphatemia. Adjusted analyses of VFD used an inverse probability weighted zero-inflated negative binomial model and a win-ratio analysis. Secondary outcomes were assessed with logistic regression.

Of 1,942 trial participants, 634 patients (32.6%) developed hypophosphatemia, and 192 patients (9.9%) developed severe hypophosphatemia. Clinical factors independently associated with incident hypophosphatemia during KRT were female sex, lower body weight, lower serum phosphate levels at KRT initiation, CKRT as the initial KRT modality, and randomization to accelerated KRT initiation. Incident hypophosphatemia and severe hypophosphatemia were associated with fewer VFD at 28 days (β, 0.91 [95% CI, 0.87-0.95] and β, 0.87 [95% CI, 0.82-0.93], respectively; P < 0.001 for both). By win-ratio for any random pair of patients, those with incident hypophosphatemia and severe hypophosphatemia had a 27% and 25% lower likelihood of combined 28-day survival and fewer days on the ventilator, respectively. There was no association between hypophosphatemia and 90-day mortality or KRT dependence.

Selection bias and unmeasured confounding.

Incident hypophosphatemia during KRT was independently associated with fewer VFD at 28 days.