Lungs and Kidneys in Collision: The ARDS–AKI Crossroads by Prof. Dr. Marcus J. Schultz

Lungs and Kidneys in Collision: The ARDS–AKI Crossroads

👨‍⚕️ Author of the Month

Prof. Dr. Marcus J. Schultz

Amsterdam UMC, Amsterdam the Netherlands
Medical University of Vienna, Vienna, Austria.
Mahidol-Oxford Tropical Medicine Research Unit,
Bangkok, Thailand, and Nuffield department of
Medicine, Oxford University, Oxford, UK.
Co-founder, PROVE Network

Brief Bio:

Prof. Marcus J. Schultz is an internationally acclaimed intensivist and researcher known for his pioneering work in ARDS physiology, mechanical ventilation, and multi-organ interactions. He leads collaborative research across Europe and Asia, uniting translational science with bedside precision. As Co-founder of the PROVE Network, he has redefined the approach to lung-protective ventilation and its systemic effects — bridging the gap between respiratory and renal critical care.

His academic appointments at Amsterdam UMC, Vienna Medical University, and the University of Oxford reflect his commitment to advancing evidence-based, physiology-guided care in complex ICU syndromes such as ARDS–AKI overlap.

Clinical Vignette

A 52-year-old male with severe community-acquired pneumonia develops moderate ARDS (PaO₂/FiO₂ = 140) on day 2 of invasive ventilation. Over the next 48 hours, urine output falls to <0.3 mL/kg/h, and serum creatinine doubles from baseline. He’s now on norepinephrine 0.15 µg/kg/min with cumulative positive fluid balance of +3.2 L.
Ventilator settings: PEEP 12 cmH₂O, FiO₂ 0.6, tidal volume 6 mL/kg PBW.
CVP 14 mmHg, MAP 68 mmHg. CXR shows bilateral infiltrates with worsening B-lines on POCUS.

At the bedside, the team faces a classic Nephrocritical Care puzzle:
Where does one organ’s protection become another’s burden?

Key Questions at the Bedside

(Click / Tap on Questions to Reveal Content)

Q 1. How can we distinguish when lung-protective PEEP begins to compromise renal perfusion through elevated intrathoracic pressure and venous congestion?

Achieving an open lung is not a goal in itself; nor is the lowest possible driving pressure. What matters is the delicate balance between sufficient lung recruitment and adequate renal circulation. Use physiology not dogma; match rising PEEP against falling urine output, echocardiographic signs of venous congestion, and renal Doppler. Step down PEEP or optimise intravascular volume briefly to test renal response while tracking oxygenation and perfusion.

Q 2. Does permissive hypercapnia and high transpulmonary driving pressure during mechanical ventilation directly worsen renal vasoconstriction and tubular injury?

Evidence is limited and mostly indirect; hypercapnia and increased driving pressure can raise sympathetic tone and transiently reduce renal perfusion, but clear clinical harm is unproven. Maintain acidaemia within tolerable limits, minimise unnecessary pressure swings, and monitor renal function pragmatically rather than assuming inevitable injury.

Q 3. To what extent does systemic inflammation and cytokine spillover from ARDS contribute to renal tubular dysfunction independent of hemodynamics?

Substantial evidence supports direct injury, wherein cytokine spillover from ARDS provokes endothelial dysfunction, tubular inflammation and impaired microcirculation independent of blood pressure. However, most evidence comes from animal studies, and only one clinical study showed an association between rising cytokine levels and increased non-pulmonary organ failure. Notably, that study compared lung-protective ventilation with highly conventional ventilation using excessively large tidal volumes.

Q 4. In patients with ARDS and evolving lung fibrosis on CRRT, how do we approach ventilator weaning when renal compensation for acidosis is lost?

This is a field where much evidence is needed but little is available. My approach is to coordinate CRRT and ventilator strategy; restore acid base with CRRT buffers, accept pragmatic pH targets, reduce ventilatory demand gradually, and consider extracorporeal carbon dioxide removal if available. Others may choose differently.

Q 5. How should enteral nutrition be personalised in this setting—balancing protein requirements with reduced carbohydrate load to minimise carbon dioxide generation and facilitate liberation from the ventilator?

Close to the question above, one may opt for feeding that limit carbon dioxide production while preserving lean mass. The approach in my team is to prioritise adequate protein, shift calories toward fat rather than carbohydrate, use energy dense formulas, monitor nitrogen balance and glycaemia, and adjust as respiratory workload and ventilator dependence change.

Q 6. How should we balance fluid offloading for lung protection against maintaining adequate renal perfusion once AKI develops, and can dynamic measures like VeXUS or right atrial pressure monitoring guide safe ultrafiltration targets?

I personally have little experience with VeXUS. It is a bedside ultrasound score assessing venous congestion by examining hepatic, portal, and intra-renal veins. Evidence remains limited; small studies suggest it can help guide safe fluid removal and prevent renal hypoperfusion, but large prospective trials are lacking. Currently I would advise to use it cautiously alongside clinical judgement.

Q 7. How do CRRT parameters—particularly ultrafiltration rate, buffer type, and dose—modulate lung mechanics, oxygenation, and systemic haemodynamics in severe ARDS?

CRRT settings matter to the lung; higher ultrafiltration, i.e., fluid de–resuscitation, reduces pulmonary oedema but risks hypovolaemia and worse oxygenation. One large RCT showed a restrictive fluid strategy increased ventilator-free days without raising AKI risk, but did not address AKI recovery. A current study is exploring this in critically ill patients with or without ARDS. Bicarbonate-based buffers alter carbon dioxide generation and ventilatory demand, potentially increasing ventilation intensity and affecting pulmonary outcomes. Intensity also influences haemodynamics via preload and vasomotor effects, and safe limits of permissive hypercapnia for the kidneys remain uncertain.

Q 8. When CRRT alters acid–base status and CO2 kinetics, how can we explicitly synchronise ventilator targets (PaCO2, pH, tidal volume) with the patient’s metabolic state to prevent CO2 retention, drive mismatch, and weaning failure?

Lung and kidney care are inseparable; protecting the lungs with lung-protective ventilation requires attention to the kidneys, and kidney therapy can help reduce ventilatory intensity. Thinking about interventions, we are further from home: how to protect both organs simultaneously is complex: LPV alone is already challenging (lower tidal volume versus lower respiratory rate, high PEEP versus high oxygen fraction), now add kidney targets. We urgently need multi-organ studies and may need AI in the future to guide this delicate balance.

Q9. Are poor outcomes in ARDS with AKI primarily driven by overlapping inflammatory pathways or by conflicting therapeutic goals, and could identifying specific ARDS–AKI subphenotypes allow a more precision-guided, physiology-based management strategy?

This is the number one question; both overlapping inflammation and conflicting therapies drive poor outcomes. We do not know which is more important, or whether one drives the other, though they may interact. As in my answer to the question above, we need to identify treatable traits, which can be difficult to recognise. AI may help, but expectations must remain realistic. Identifying ARDS–AKI subphenotypes by physiology and biomarkers could allow precision-guided, multi-organ strategies, protecting lungs and kidneys simultaneously rather than treating each in isolation.