Slow continuous ultrafiltration and prolonged intermittent renal replacement therapy: Tailoring renal replacement therapy in intensive care unit

Table 1 Comparative table of renal replacement therapy modalities

Characteristic	CRRT (CVVH/CVVHD/CVVHDF)	SCUF	PIRRT (CRRT platforms)	SLED	SLEDD-F
Full name/concept	Continuous renal replacement therapy	Slow continuous ultrafiltration	Prolonged intermittent RRT (via CRRT machines)	Sustained low-efficiency dialysis	Sustained low-efficiency daily dialysis with filtration
Typical session duration	24 hours/day	12-24 hours/day	6-12 hours/session	6-12 hours/session	6-12 hours/session
Blood flow rate	Approximately 100-200 mL/minute	Approximately 50-150 mL/minute	Approximately 150-250 mL/minute	Approximately 150-250 mL/minute	Approximately 150-250 mL/minute
Dialysate/effluent rate	Effluent 20-35 mL/kg/hour	None; ultrafiltration 100-500 mL/hour	20-25 mL/kg/hour	Dialysate approximately 100-300 mL/minute	As in SLED + convective filtration
Predominant clearance mechanism	Diffusion/convection mixed	Convection (volume removal)	Mixed diffusive/convective	Diffusion	Diffusion + Convection
Hemodynamic profile	Best tolerated in unstable patients	Very well tolerated	Intermediate tolerance	Intermediate tolerance	Similar to SLED; slightly higher impact
Primary clinical indication	AKI with hemodynamic instability	Refractory fluid overload	Hybrid/step-down therapy	AKI in ICU where extended sessions feasible	AKI requiring enhanced solute clearance
Equipment	Continuous RRT machines	Continuous RRT machines	CRRT machines	Hemodialysis machines	Hemodialysis machines with HDF capability

This table compares major renal replacement therapy modalities used in the intensive care unit, highlighting differences in treatment duration, equipment, hemodynamic tolerance, and solute/fluid clearance mechanisms. Continuous renal replacement therapy modalities provide continuous support for unstable patients, while sustained low-efficiency dialysis, sustained low-efficiency daily dialysis with filtration, and prolonged intermittent renal replacement therapy represent extended intermittent therapies with varying diffusive and convective components. Slow continuous ultrafiltration is a fluid-focused modality with minimal solute removal. CRRT: Continuous renal replacement therapy; CVVH: Continuous veno-venous hemofiltration; CVVHD: Continuous veno-venous hemodialysis; CVVHDF: Continuous veno-venous hemodiafiltration; SCUF: Slow continuous ultrafiltration; PIRRT: Prolonged intermittent renal replacement therapy; SLED: Sustained low-efficiency dialysis; SLEDD-F: Sustained low-efficiency daily dialysis with filtration; RRT: Renal replacement therapy; AKI: Acute kidney injury; ICU: Intensive care units; HDF: Hemodiafiltration.

Table 2 Standardized slow continuous ultrafiltration prescription

Standardized slow continuous ultrafiltration prescription
Modality	Slow continuous ultrafiltration
Indication	Fluid overload without need for solute clearance (preserved renal function or adequate clearance)
Duration	Continuous 24 hours or until target fluid removal achieved
Blood flow	150 mL/minute
Replacement fluid	0 mL/hour (none)
Dialysate flow	0 mL/hour (none)
Ultrafiltration rate	200 mL/hour (adjust 100-500 mL/hour based on clinical needs)
Net fluid removal target	-3 to -5 kg over 24-48 hours (or until euvolemia achieved)
Anticoagulation	Option 1: Heparin (activated partial thromboplastin time 45-60 sec or anti-Xa 025-0.35 U/mL). Option 2: None (if contraindicated - use higher blood flow rate 200 mL/minute). Option 3: Citrate regional (if available and trained staff)
Vascular access	Double-lumen dialysis catheter (11.5-13 Fr). Preferred sites: Internal jugular > femoral > subclavian
Filter	Standard hemofilter 1.0-1.5 m2 surface area
Monitoring	Blood pressure: Every 30-60 minutes. Fluid balance: Hourly. Weight: Every 12 hours. Electrolytes: Baseline, then every 12 hours. TMP (transmembrane pressure): Continuous. Clinical assessment: Volume status, lung auscultation every 4-6 hours
Adjustments	Increase UF rate if persistent overload and hemodynamically stable. Decrease UF rate if hypotension or signs of hypovolemia. Stop if hemodynamic instability despite fluid resuscitation. Monitor for hemoconcentration (hematocrit rise > 5%)
Special considerations	Cirrhosis: Use lower UF rates (50-150 mL/hour) + albumin replacement (8-10 g per 2-3 L removed). Heart failure: Monitor BNP, consider lower UF rates initially. Post-operative: Avoid anticoagulation if recent surgery

TMP: Transmembrane pressure; UF: Ultrafiltration; BNP: B-type natriuretic peptide.

Table 3 Standardized prolonged intermittent renal replacement therapy prescription

Standardized PIRRT prescription
Modality	PIRRT mode: Continuous venovenous hemodiafiltration
Indication	Acute kidney injury kidney disease: Improving Global Outcomes stage 3 with hemodynamic instability or inability to tolerate standard intermittent hemodialysis
Duration/frequency	10-12 hours per session, daily (adjust based on clinical needs: 8-16 hours possible)
Blood flow	200 mL/minute (range: 150-250 mL/minute)
Dialysate flow	1500 mL/hour (25 mL/kg/hour for 60 kg patient), adjust based on weight: 20-30 mL/kg/hour target
Pre-dilution replacement	1200 mL/hour (20 mL/kg/hour for 60 kg patient), ratio: 80% of dialysate flow
Post-dilution replacement	0-300 mL/hour (optional, use if need higher efficiency), typically 0 mL/hour for standard PIRRT
Total effluent	2700 mL/hour (dialysate 1500 + pre-dilution 1200), effective dose: Approximately 22-24 mL/kg/hour
Net ultrafiltration	According to fluid balance goals (typical 100-300 mL/hour), for 12 hours session: 1.2-3.6 L net removal
Filtration fraction	Target: < 20% formula: Filtration fraction = ultrafiltration flow rate/[blood flow × (1 - hematocrit/100)] × 100 example (blood flow = 200, hematocrit = 30%): Filtration fraction = 1200/60/(200 × 0.7) = 14%
Anticoagulation	Option 1 (preferred): Regional citrate anticoagulation per protocol. Option 2: Heparin - activated partial thromboplastin 45-60 sec or anti-Xa 025-0.35 U/mL. Option 3: None - if contraindicated (increase blood flow to 250 mL/minute, use PBP 40% + pre 60%)
Vascular access	Double-lumen dialysis catheter (11.5-13 Fr) preferred sites: Internal jugular > femoral > subclavian
Filter	High-flux hemofilter, 1.5-2.0 m2 surface area biocompatible membrane (polysulfone, polyethersulfone)
Dialysate/replacement composition	Standard composition: Na+ 140 mEq/L; K+ 2-3 mEq/L (adjust based on serum K+: 0 mEq/L if K+ > 6.0); Ca2+ 3.0-3.5 mEq/L (if not using citrate); Mg2+ 1.0 mEq/L; bicarbonate 32-35 mEq/L
Monitoring	Blood pressure: Every 30 minutes. Fluid balance: Hourly. Electrolytes: Pre-treatment, mid-treatment (6 hours), post-treatment. Blood gas/pH: Pre and post-treatment. TMP, pressures: Continuous. BUN, Creatinine: Daily. Filter inspection: Visual check every 2-4 hours for clotting
Dose calculation	Target: 20-25 mL/kg/hour effective dose. Example for 70 kg patient: Target total dose: 70 kg × 22 mL/kg/hour = 1540 mL/hour. With pre-dilution: Need approximately 1800-1900 mL/hour prescribed. Prescription: Dialysate flow 1500 + pre 1200 = 2700 mL/hour. Effective dose: 2700/1.17 approximately 2300 mL/hour or approximately 23 mL/kg/hour
Adjustments	Increase dose (to 25-35 mL/kg/hour) if: Sepsis, hypercatabolic state, persistent azotemia (BUN >100 mg/dL), hyperkalemia (K+ > 5.5 mEq/L). Decrease duration/dose if: Hemodynamic instability, improving renal function, transitioning to IHD
Transition strategy	From CRRT to PIRRT: Start with 12 hours sessions, assess tolerance from PIRRT to IHD: Gradually reduce session length (12 hours to 8 hours to 6 hours), then transition to 4 hours IHD alternate days criteria for transition: Hemodynamic stability for 24 hours, improving urine output, stable electrolytes

PIRRT: Prolonged intermittent renal replacement therapy; PBP: Pre blood pump; TMP: Transmembrane pressure; BUN: Blood urea nitrogen; CRRT: Continuous renal replacement therapy; IHD: Intermittent hemodialysis.

Table 4 Standardized sustained low-efficiency dialysis prescription

Standardized SLED prescription
Modality	SLED also known as: Extended daily dialysis, slow extended daily dialysis
Indication	Acute kidney injury kidney disease: Improving Global Outcomes stage 3 with hemodynamic instability or inability to tolerate standard intermittent hemodialysis. Alternative to CRRT when continuous therapy not required
Duration/frequency	8-12 hours per session, daily or 6 times per week (adjust based on clinical needs: 6-16 hours possible) typical: 10 hours nocturnal (allows daytime mobilization)
Machine	Standard hemodialysis machine (conventional dialysis equipment) advantage: No need for dedicated CRRT machines
Blood flow	250 mL/minute (range: 200-300 mL/minute) lower than conventional HD (350-450 mL/minute), higher than CRRT (150-200 mL/minute)
Dialysate flow	200 mL/minute (range: 100-300 mL/minute) much lower than conventional HD (500-800 mL/minute). This is the key parameter that defines ‘low-efficiency’
Dialysate temperature	35.5-36.5 °C (cooler than standard 37 °C) improves hemodynamic tolerance and reduces hypotension
Ultrafiltration rate	According to fluid balance goals (typical 100-400 mL/hour) for 10 hours session: 1-4 L net removal maximum recommended: 500 mL/hour if tolerated
Sodium profile	Optional: Start 145 mEq/L, taper to 140 mEq/L improves hemodynamic stability standard: Fixed 140 mEq/L acceptable
Ultrafiltration profile	Optional: Higher rate in first half, lower in second half example: 300 mL/hour × 5 hours to 200 mL/hour × 5 hours reduces hypotension risk
Anticoagulation	Option 1: Heparin - activated partial thromboplastin 45-60 sec or anti-Xa 025-0.35 U/mL. Bolus: 1000-2000 units. Maintenance: 500-1000 units/hour. Option 2: Regional citrate anticoagulation (if available). Option 3: None - if contraindicated (frequent saline flushes every 30 minutes)
Vascular access	Double-lumen dialysis catheter (11.5-14 Fr) preferred sites: Internal jugular > femoral > subclavian can use existing chronic HD access (fistula/graft) if available
Dialyzer	High-flux dialyzer, surface area 18-2.1 m2 biocompatible membrane (polysulfone, polyethersulfone, polyamix) standard dialysis filters (not hemofilters)
Dialysate composition	Standard composition: Na+ 140 mEq/L (or profiled 145 to 140); K+ 2-3 mEq/L (adjust based on serum K+: 0-1 mEq/L if K+ > 6.0). Ca2+ 2.5-3.0 mEq/L, Mg2+ 1.0 mEq/L, bicarbonate 32-35 mEq/L, glucose 100-200 mg/dL
Treatment time calculation	Target weekly Kt/V: ≥ 3.0-3.6 for daily SLED standard urea kinetic modeling: For daily 10 hours SLED at blood flow 250, dialysate flow 200: Single session Kt/V approximately 1.0-1.2 weekly Kt/V (6 sessions) approximately 6.0-7.2 (adequate), alternate day SLED: May need longer sessions (12 hours)
Monitoring	During treatment: Blood pressure: Every 15-30 minutes, intradialytic hypotension protocol ready, fluid balance: Hourly, access pressures: Continuous, clinical assessment: Every 2 hours, laboratory: Electrolytes: Pre-treatment, post-treatment, blood gas/pH: Pre and post-treatment, BUN, creatinine: Daily, CBC: Every 2-3 days
Advantages vs conventional IHD	Better hemodynamic tolerance (50%-70% less hypotensive episodes). More gradual solute and fluid removal. Less osmotic shifts (reduced dialysis disequilibrium). Reduced risk of arrhythmias. Better preservation of residual renal function. Allows higher total UF without hemodynamic compromise
Advantages vs CRRT	50%-60% cost reduction (less fluid consumption, standard machines). Nurse not dedicated 24 hours (typically nocturnal treatment). Allows daytime mobilization and rehabilitation. Easier nursing care (familiar equipment). No need for specialized CRRT equipment. Adequate clearance for most acute kidney injury cases
Adjustments	Increase efficiency if: Persistent azotemia (BUN > 80-100 mg/dL), hyperkalemia (K+ > 5.5 mEq/L), severe metabolic acidosis → increase dialysate flow to 250-300 mL/minute or increase session length to 12 hours. Decrease intensity if: Hemodynamic instability, intradialytic hypotension (> 2 episodes/session) → decrease dialysate flow to 100-150 mL/minute or decrease UF rate or use profiling
Hypotension management	Prevention: Cool dialysate (35.5-36 °C), sodium profiling (145 mEq/L to 140 mEq/L), UF profiling (higher first, lower later), avoid excessive UF rates (keep < 500 mL/hours). Treatment: Trendelenburg position, reduce or stop UF temporarily 100-250 mL saline bolus, consider midodrine or vasopressor support if recurrent
Transition strategy	From CRRT to SLED: Start with 10-12 hours daily sessions, assess tolerance for 2-3 sessions, if stable, continue until recovery or transition to conventional HD from SLED to conventional IHD: Gradually reduce session length: 10 hours → 8 hours → 6 hours → 4 hours. Gradually increase dialysate flow: 200 mL/minute → 300 mL/minute → 400 mL/minute → 500 mL/minute. Transition when hemodynamically stable for 48 hours. Consider alternate day schedule (Monday-Wednesday-Friday). Criteria for transition: Hemodynamic stability (no vasopressors), improving urine output, stable electrolytes and acid-base
Relative contraindications	Severe hemodynamic instability requiring continuous vasopressor titration (consider CRRT). Intracranial hypertension with cerebral edema (prefer CRRT for slower changes). Multiple organ failure requiring multiple continuous therapies. Massive fluid overload requiring urgent removal > 8 L in 24 hours (consider CRRT or IHD)
Special populations	Elderly patients: Start conservatively: Dialysate flow 150 mL/minute, UF 200 mL/hour, monitor closely for hypotension. Post-cardiac surgery: Prefer nocturnal schedule, consider minimal/no anticoagulation, watch for bleeding. Septic shock: May need daily treatment even if marginally stable, higher clearance beneficial for cytokine removal, monitor lactate trends

SLED: Sustained low-efficiency dialysis; CRRT: Continuous renal replacement therapy; HD: Hemodialysis; BUN: Blood urea nitrogen; CBC: Complete blood count; UF: Ultrafiltration; IHD: Intermittent hemodialysis.

Table 5 Principal clinical studies of slow continuous ultrafiltration, prolonged intermittent renal replacement therapy, and sustained low-efficiency dialysis

Ref.	Population/setting	Modality and comparator	Design (n)	Principal outcomes	Key findings
Wei et al[33], 1995	Severe cardiac failure with diuretic resistance	SCUF	Prospective (n = 7)	Hemodynamic tolerance	UF approximately 2.2 L/session; stable BP
Bart et al[34], 2005 (RAPID-CHF)	ADHF with congestion	UF vs diuretics	RCT (n = 40)	Fluid removal	UF > diuretics (4650 vs 2838 mL)
Costanzo et al[35], 2007 (UNLOAD)	ADHF with overload	UF vs diuretics	RCT (n = 200)	Weight; rehospitalization	Improved decongestion; HF readmissions decrease
Paladino et al[36], 2008	ADHF + hypercapnia	SCUF	Prospective (n = 10)	Hemodynamics; gas exchange	Improved CO2 clearance
Giglioli et al[38], 2010	NYHA III-IV HF	UF	Prospective (n = 15)	New York Heart Association; BNP	Weight decreasing 7.4%; BNP improved
Guiotto et al[26], 2010	Severe ADHF	Ultrasound-guided SCUF	Prospective (n = 24)	Volume removal	Approximately 5.8 L/session; stable BP
Giglioli et al[37], 2011 (ULTRADISCO)	Severe ADHF	Hemodynamic-guided UF	Prospective (n = 30)	Neurohormonal markers	Aldosterone decreas, NT-proBNP, CO increase
Bart et al[39], 2012 (CARRESS-HF)	ADHF + renal dysfunction	UF vs stepped therapy	RCT (n = 188)	Renal function; safety	UF worsened Cr; increase adverse events
Patarroyo et al[21], 2012	Refractory ADHF	UF	Retrospective (n = 63)	Mortality	High mortality; dialysis predicted poor outcome
Marenzi et al[42], 2014 (CUORE)	Severe HF	UF + diuretics vs diuretics	RCT (n = 56)	Rehospitalization	HF readmissions decrease; stable renal function
Costanzo et al[43], 2016 (AVOID-HF)	ADHF	Adjustable UF vs diuretics	RCT (n = 224)	HF events	Trend to benefit; adverse events increase
Marshall et al[58], 2011	ICU AKI	PIRRT vs CRRT	Time-series (n = 1347)	Hospital mortality	No mortality increasing with PIRRT
Dash et al[59], 2025	ICU AKI	SLED vs CRRT	Prospective (n = 67)	28-day mortality	Similar mortality; fewer clots in SLED
Kitchluet al[60], 2015	ICU AKI	SLED vs CRRT	Retrospective (n = 232)	30-day mortality	Adjusted outcomes similar
Harveyet al[61], 2021	Critical illness AKI	SLED vs CRRT	Retrospective (n = 284)	1-year mortality	Mortality equivalent across groups
Sharieff et al[62], 2024	ICU AKI + instability	SLED	Retrospective (n = 58)	Mortality	Severity, not modality, drove outcomes
Maiwallet al[63], 2025 (ELDICS)	Cirrhosis + septic shock + AKI	Early vs late SLED	RCT (n = 50)	Mortality; hypotension	Early SLED decrease hypotension, renal recovery increase
Hu et al[44], 2020	Early ADHF	UF vs diuretics + tolvaptan	RCT (n = 100)	Weight; diuresis	Greater decongestion with UF
Di Marioet al[65], 2025	ICU AKI	SLED + RCA	Prospective (n = 27)	Safety; feasibility	88% session completion; no citrate toxicity

This table summarizes key clinical investigations of slow continuous ultrafiltration, prolonged intermittent renal replacement therapy, and sustained low-efficiency dialysis in acute heart failure and acute kidney injury. SCUF: Slow continuous ultrafiltration; ADHF: Acute decompensated heart failure; UF: Ultrafiltration; RCT: Randomized controlled trial; HF: Heart failure; BNP: B-type natriuretic peptide; BP: Blood pressure; CO: Cardiac output; ICU: Intensive care units; AKI: Acute kidney injury; PIRRT: Prolonged intermittent renal replacement therapy; SLED: Sustained low-efficiency dialysis; CRRT: Continuous renal replacement therapy; NT-proBNP: N-terminal pro-B-type natriuretic peptide; RCA: Regional citrate anticoagulation.