Table 1.

Potential RRT-related interventions to limit HIRRT

Intervention	Potential mechanism(s)	Supporting evidence	Additional comments
Limit UF rate  Reduce UF goal  Lengthen treatment time	Allows for adequate plasma refilling to replace intravascular fluid removed by UF and thereby prevents intravascular hypovolemia.	Hemodynamic benefits of CRRT/SLED vs IHD are presumed but high-level evidence from comparative trials is lacking (as they may not be feasible/safe)	Reducing fluid removal goals may result in greater fluid overload which is associated with increased mortality. More healthcare resources needed if more dialysis time is required. HIRRT is common across RRT modalities (including CRRT)
‘Slower’ RRT modality (i.e., SLED/CRRT) (lower QB, lower QD, increased treatment time)	Less osmotic shift and decreased UF rate: increased plasma refilling and less intravascular hypovolemia	As above	No clear evidence regarding benefit of ‘slower’ RRT modalities on mortality, renal recovery
Isolated UF (i.e., pure ultrafiltration with no dialysis component)	No osmotic shift, increased plasma refilling	Hemodynamic stability of UF without diffusive clearance vs HD	Isolated UF allows for fluid removal but not solute clearance. [It involves only convective clearance (through solute drag) if dilutional fluid is added. There is no diffusive clearance which is much more efficient in clearing small molecules]
Hypertonic infusions (hypertonic saline, mannitol, albumin)	Less osmotic shift, increased oncotic pressure prevents intravascular hypovolemia	Higher pre-HD plasma osmolality and hypoalbuminemia associated with increased risk of HIRRT; lack of evidence for albumin infusion	In critically ill patients, the effective crystalloid:colloid ratio is lower than expected. In septic patients with leaky capillaries, albumin (or mannitol) may be less likely to remain in the intravascular space to exert an osmotic or oncotic effect
Higher dialysate Na+ and Na+ profiling	Less osmotic shift; less intravascular hypovolemia	Hemodynamic benefit in critically ill patients has mixed results	May result in positive sodium balance which correlates with greater interdialytic weight gain in maintenance HD. Unclear if this is relevant to the AKI/critically ill patient population
Lower dialysate temperature	Promotes vasoconstriction, increases SVR, limits myocardial stunning	Hemodynamic benefit in ESKD patients on maintenance HD and cardioprotection: reduced LV mass, preserved LV function	Strong evidence that it improves hemodynamic stability in maintenance hemodialysis patients. Limits intradialytic myocardial stunning in this population. Studies show that myocardial stunning also occurs in critically ill patients on HD and CRRT
Relatively higher dialysate Ca2+ Lower serum to dialysate Ca2+ gradient	Increased myocardial contractility, decreased arrhythmia risk, increased vascular tone	Improved hemodynamic tolerance; increased risk of cardiac arrest with lower dialysate Ca2+; increased mortality with hypoCa2+ in critically ill AKI	Less intradialytic hypotension in maintenance hemodialysis patients. Potential harms related to positive calcium balance in this population. Risks/benefits unclear in critically ill patients
Bicarbonate buffer (versus lactate)	Does not cause lactic acidosis. Acidosis may lead to vasoplegia, less responsiveness to vasopressors	Less HIRRT (and acidosis) with bicarbonate buffer vs lactate buffer	Lactate accumulation occurs with lactate buffer when liver dysfunction prevents the usual rapid conversion of lactate to bicarbonate
Bio-compatible dialyzer membranes	Minimize complement activation and inflammatory response	Unmodified cellulose (cuprophane) associated with worse outcomes	Bio-compatible dialyzer membranes are standard in current practice
Inclusion of convective clearance (hemofiltration); HVHF	Improved clearance of higher molecular weight pro-inflammatory solutes may reduce inflammation and thereby reduce vasodilation, myocardial stunning	Mixed evidence for hemodynamic benefit or improved mortality; HVHF not shown to be beneficial in septic AKI	Removal of high molecular weight anti-inflammatory factors also occurs with HVHF and might negate any potential benefits in sepsis/septic AKI

AKI acute kidney injury, HIRRT hemodynamic instability related to RRT, CRRT continuous renal replacement therapy, SLED sustained low-efficiency dialysis, IHD intermittent hemodialysis, SVR systemic vascular resistance, LV left ventricular, UF ultrafiltration, RRT renal replacement therapy, Q_B blood flow rate (mL/min), ESKD end-stage kidney disease, cAMP cyclic AMP, iNOS inducible nitric oxide synthase, NO nitric oxide, HVHF high-volume hemofiltration