What is the Effect of Acute Kidney Injury on Weaning From Mechanical Ventilation in Critically Ill Adult Patients?

Acute kidney injury (AKI) is a frequent and serious complication in critically ill patients receiving invasive mechanical ventilation, affecting up to onethird of ICU admissions and contributing substantially to morbidity and mortality(1,2). AKI is associated with prolonged organ dysfunction, increased length of ICU stay, higher healthcare costs, and poorer overall outcomes, particularly in patients who require respiratory support.

Mechanical ventilation itself can influence renal perfusion and function through hemodynamic alterations, intrathoracic pressure changes, and activation of neurohormonal and inflammatory pathways. Positive endexpiratory pressure (PEEP) and large tidal volumes may reduce renal blood flow and glomerular filtration rate, thereby increasing the risk of AKI in ventilated patients. Conversely, AKI can aggravate pulmonary dysfunction by promoting fluid overload, interstitial edema, and systemic inflammation, which may impair gas exchange and respiratory muscle performance.

Several clinical studies have demonstrated that AKI is associated with prolonged duration of mechanical ventilation and higher rates of difficult or prolonged weaning. One observational cohort of mechanically ventilated ICU patients showed that AKI was an independent predictor of prolonged mechanical ventilation exceeding 21 days, even after adjusting for disease severity. In another study focusing on cancer patients, AKI was linked to significantly longer weaning duration, higher weaningfailure rates, and increased ICU mortality.

In patients with chronic obstructive pulmonary disease (COPD) and respiratory failure, AKI occurring within the first 48 hours of ICU admission has been shown to reduce glomerular filtration rate, increase the use of PEEP and ventilatory support, prolong mechanical ventilation, and decrease weaning success. These patients with AKI also had higher APACHE II scores, more days in the ICU, and greater likelihood of difficult weaning or death compared with nonAKI counterparts. Fluid overload and oliguria related to AKI likely contribute to positive net fluid balance, which in turn worsens pulmonary congestion and respiratory mechanics and may delay successful liberation from the ventilator.

The bidirectional "kidney-lung" interaction means that pulmonary injury can precipitate AKI and vice versa, creating a vicious cycle that complicates criticalcare management. Mechanical ventilationinduced AKI has been associated with worse respiratory system mechanics and higher levels of inflammatory biomarkers, further impairing cardiorespiratory reserve and weaning potential. Despite these associations, the exact mechanisms by which AKI affects weaning outcomes, such as diaphragmatic dysfunction, systemic inflammation, or drug accumulation, remain incompletely elucidated.

Given the high prevalence of AKI among mechanically ventilated patients and its potential to prolong ICU stay, increase mortality, and hinder successful weaning, a focused investigation is needed to clarify the independent contribution of AKI to weaning failure and prolonged ventilation. Understanding this relationship may help refine risk stratification, optimize renal protective ventilation strategies, guide fluid management, and ultimately improve weaning protocols and patient outcomes.

The rationale for this study is to determine whether AKI is an independent factor influencing weaning success and duration from mechanical ventilation in critically ill adults, and to provide evidence based data that can inform early identification of highrisk patients and guide tailored interventions to facilitate earlier and safer liberation from the ventilator.

Inclusion criteria

• • Age ≥ 18 years of either sex.

• Admission to the ICU and receiving invasive mechanical ventilation via endotracheal tube.
• Expected duration of mechanical ventilation ≥ 24 hours.
• Hemodynamically stable or stabilized at the time of first spontaneous breathing trial (SBT) according to unit protocol (e.g., mean arterial pressure ≥ 65 mmHg with or without low dose vasopressors).
• Availability of baseline and daily serum creatinine, urine output, and relevant clinical data to diagnose and stage acute kidney injury according to KDIGO criteria.

Exclusion criteria

• Pre existing end stage renal disease on chronic dialysis (hemodialysis or peritoneal dialysis).

• Known advanced chronic kidney disease (e.g., baseline estimated GFR < 30 mL/min/1.73 m²) if baseline creatinine is available.
• Previous tracheostomy before current ICU admission.
• Neuromuscular diseases or spinal cord injury causing chronic ventilatory dependence.
• Severe pre existing cognitive impairment or brain death at ICU admission.
• Do not intubate or comfort care only orders at time of eligibility assessment.
• Re intubation after ICU discharge (only the first ICU admission episode will be considered).
• Patients or legal representatives refusing or withdrawing consent