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Ultrafiltration in critically ill patients treated with kidney replacement therapy

Nature Reviews Nephrology volume 17, pages 262–276 (2021)Cite this article

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Abstract

Management of fluid overload is one of the most challenging problems in the care of critically ill patients with oliguric acute kidney injury. Various clinical practice guidelines support fluid removal using ultrafiltration during kidney replacement therapy. However, ultrafiltration is associated with considerable risks. Emerging evidence from observational studies suggests that both slow and fast rates of net fluid removal (that is, net ultrafiltration (UFNET)) during continuous kidney replacement therapy are associated with increased mortality compared with moderate UFNET rates. In addition, fast UFNET rates are associated with an increased risk of cardiac arrhythmias. Experimental studies in patients with kidney failure who were treated with intermittent haemodialysis suggest that fast UFNET rates are also associated with ischaemic injury to the heart, brain, kidney and gut. The UFNET rate should be prescribed based on patient body weight in millilitres per kilogramme per hour with close monitoring of patient haemodynamics and fluid balance. Dialysate cooling and sodium modelling may prevent haemodynamic instability and facilitate large volumes of fluid removal in patients with kidney failure who are treated with intermittent haemodialysis, but the effects of this strategy on organ injury are less well studied in critically ill patients treated with continuous kidney replacement therapy. Randomized trials are required to examine whether moderate UFNET rates are associated with a reduced risk of haemodynamic instability, organ injury and improved outcomes in critically ill patients.

Key points

  • The rate of net ultrafiltration should be based on patient body weight (ml/kg/h) rather than on absolute volumes (ml/h).

  • Epidemiological studies in critically ill patients with acute kidney injury and in patients with kidney failure suggest that high and low net ultrafiltration (UFNET) rates are associated with increased mortality compared with moderate UFNET rates.

  • Intradialytic hypotension during UFNET is common with both intermittent haemodialysis and continuous kidney replacement therapy.

  • During UFNET, careful attention should be paid to patient haemodynamics, with frequent assessment of end organ perfusion and function.

  • Randomized clinical trials are required to determine whether moderate UFNET rates are associated with improved patient outcomes compared with slow or faster UFNET rates.

  • Further research is required to investigate the feasibility and efficacy of interventions such as dialysate cooling, sodium profiling, remote ischaemic preconditioning and passive intradialytic exercise for organ protection during ultrafiltration in critically ill patients.

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Fig. 1: A typical ultrafiltration circuit used in critically ill patients treated with continuous kidney replacement therapy.
Fig. 2: Schematic showing the generation of TMP across a haemofilter.
Fig. 3: UFNET rate and mortality among critically ill patients receiving continuous kidney replacement therapy.
Fig. 4: Potential links between high ultrafiltration rates and organ dysfunction in patients with kidney failure.
Fig. 5: Mechanisms of organ dysfunction associated with net ultrafiltration.

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Acknowledgements

Partial support for R.M.’s work was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK106256).

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Authors and Affiliations

  1. The Center for Critical Care Nephrology, CRISMA, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Raghavan Murugan, Paul M. Palevsky & John A. Kellum

  2. The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Raghavan Murugan & John A. Kellum

  3. Department of Intensive Care Medicine, The University of Melbourne, Austin Hospital, Melbourne, Victoria, Australia

    Rinaldo Bellomo

  4. Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Paul M. Palevsky

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  1. Raghavan Murugan
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R.M. was responsible for the concept of the review and the design and drafting of the manuscript. J.A.K., R.B. and P.M.P. contributed to critical revision of the manuscript and important intellectual content.

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Correspondence to Raghavan Murugan.

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R.M. reports receiving grants and personal fees from La Jolla Inc; grants from Bioporto, Inc, and the National Institute of Diabetes and Digestive and Kidney Diseases; and personal fees from Beckman Coulter and AM Pharma, Inc, outside the submitted work. R.B. reports receiving grants from Baxter International outside the submitted work. P.M.P. reported receiving personal fees from Novartis, GE Healthcare, HealthSpan Dx, and Baxter International and grants from Dascena outside the submitted work. J.A.K. reports receiving personal fees from NxStage and grants and personal fees from Baxter International.

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Nature Reviews Nephrology thanks Bernard Canaud, Stuart Goldstein and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Glossary

Ultrafiltration

The process of filtration of plasma water from blood using a medium such as a haemofiltration membrane that is fine enough to retain colloidal particles and large molecules.

Net ultrafiltration (UFNET) rate

The rate at which extracellular fluid volume is removed from the patient per unit of time during ultrafiltration. The UFNET rate is calculated by excluding the replacement fluid volume from the ultrafiltrate and so reflects the true volume of fluid removed from the patient during continuous kidney replacement therapy. During intermittent haemodialysis, replacement fluids are not administered, so the ultrafiltration rate is the same as the UFNET rate.

Ultrafiltration rate

The rate at which plasma water is removed from blood per unit of time. During continuous kidney replacement therapy, the ultrafiltrate typically includes the volume of replacement fluids.

Haemofiltration

The process of removing solutes from the blood using convection. Solutes are passively removed by solvent drag that occurs during ultrafiltration owing to increased transmembrane pressure. Replacement fluids are used to increase transmembrane pressure during convection. Dialysate is not used during haemofiltration.

Haemodiafiltration

The process of removing solutes from the blood using a combination of convection and diffusion. Diffusive clearance is achieved with the use of a dialysate in which solutes are transported across the haemofiltration membrane owing to the concentration gradient. Both replacement fluids and dialysate are used.

Gibbs–Donnan effect

Unequal distribution of permeant charged ions (such as chloride) on either side of a semipermeable membrane occurring because of the presence of impermeant charged ions (for example, plasma proteins). The electrochemical gradients caused by the unequal distribution of charged ions produces a transmembrane potential difference.

Starling forces

Forces governing the passive exchange of water between the capillary microcirculation and the interstitial fluid. These forces not only determine the directionality of net water movement between two different compartments but also the rate at which water exchange occurs.

Tonicity

The ability of an extracellular solution to make water move into or out of a cell by osmosis. Tonicity is a measure of the effective osmotic pressure gradient.

Osmolarity

A measure of the total concentration of all solutes present in the solution.

Stabilization

The stabilization phase reflects the point at which the patient is in a steady state without shock. In this phase, fluid therapy is used only for ongoing maintenance in the setting of normal fluid losses.

De-escalation

The de-escalation (or de-resuscitation) phase reflects the point at which the patient is in a steady state without shock or ongoing fluid losses. Fluid can be removed from patients in the de-escalation phase.

Fast Fourier transformation

A mathematical method for transforming a function of time into a function of frequency. Fast Fourier transformation is used for analysis of time-dependent phenomena.

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Murugan, R., Bellomo, R., Palevsky, P.M. et al. Ultrafiltration in critically ill patients treated with kidney replacement therapy. Nat Rev Nephrol 17, 262–276 (2021). https://doi.org/10.1038/s41581-020-00358-3

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