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

Abstract

Acute kidney injury complicates the clinical course of nearly half of all critically ill patients admitted to intensive care, conferring a three- to five-fold elevation in mortality risk. The management of these patients has evolved considerably beyond standardized protocols toward individualized therapeutic strategies. Within this paradigm shift, two modalities warrant particular attention: Slow continuous ultrafiltration (SCUF) and prolonged intermittent renal replacement therapy (PIRRT). SCUF operates through isolated fluid extraction at rates between 100 mL and 500 mL per hour, targeting patients whose preserved kidney function nonetheless fails to manage severe volume overload. The clinical experience with SCUF reveals a complex picture, while certain patient populations, particularly those receiving extracorporeal membrane oxygenation or battling refractory cardiac failure, have shown encouraging results with shortened intensive care stays, equally robust cohorts have experienced concerning progression rates to complete renal replacement therapy and mortality approaching or exceeding 50%. The distinction appears to hinge on meticulous patient selection, with systolic perfusion pressure emerging as a pivotal hemodynamic threshold. PIRRT extends conventional intermittent therapy from the traditional 3-4 hours window to sessions lasting 6-12 hours. Multiple investigations support that this approach achieves comparable mortality and renal recovery outcomes to continuous modalities while reducing costs, facilitating patient mobilization, and decreasing nursing requirements. Current guideline recommendations increasingly favor restrictive, patient-centered approaches over rigid algorithmic initiation. Accumulating evidence supports ultrafiltration rates of 1-1.5 mL/kg/hour, adjusted dynamically according to hemodynamic tolerance and disease trajectory. Yet despite these refinements in our understanding of optimal therapy delivery, fundamental questions persist: Which patients derive maximal benefit from alternative modalities? When should these therapies be initiated or withdrawn, and how can we predict individual treatment response? This review synthesizes current evidence to establish practical decision frameworks for implementing SCUF and PIRRT in critically ill populations, examining clinical indications, safety parameters, fluid removal strategies, and outcome determinants. Our objective is to advance renal replacement therapy from a standardized intervention toward precision nephrology for high-acuity patients.

Key Words: Heart failure; Chronic kidney disease; Acute kidney injury; Diuretic resistance; Renal failure; Intensive care unit; Slow continuous ultrafiltration; Prolonged intermittent renal replacement therapy

Core Tip: Acute kidney injury in intensive care settings requires more than choosing a dialysis modality. An overall understanding of each patient’s fragility, priorities, and capacity for recovery is needed. Slow continuous ultrafiltration offers gentle decongestion for those burdened by volume overload, while prolonged intermittent renal replacement therapy provides steady support that preserves hemodynamic tolerance and allows meaningful time off therapy. Continuous treatments are essential when instability leaves no room for abrupt physiologic shifts. The central insight is that renal-replacement therapy succeeds when tailored to the patient’s evolving physiology, transforming a technical intervention into truly individualized organ support.

INTRODUCTION

Acute kidney injury (AKI) represents a substantial clinical burden, affecting approximately 10% to 15% of hospitalized patients and over half of those admitted to intensive care units (ICU) worldwide[1]. Population-based surveillance data indicate an annual incidence ranging from 114 to 174 cases per 10000 person-years, which translates to roughly 13.3 million cases globally in 2017[1]. The incidence is particularly elevated in low- and middle-income countries, where endemic infectious diseases, environmental hazards, and constrained healthcare infrastructure converge to amplify risk[2].

Among critically ill patients with severe AKI, 5% to 10% will require renal replacement therapy (RRT) as a life-sustaining intervention[3]. In high-income and upper-middle-income countries, continuous RRT (CRRT) is employed in approximately 30% of patients receiving RRT[4]. A multinational cross-sectional study demonstrated that 22% of AKI patients underwent dialysis, with CRRT comprising about one-third of RRT modalities in resource-rich environments[4]. Japanese ICUs data reveal that 3.9% of critically ill patients received CRRT for AKI management, though in-hospital mortality in this cohort reached 50.6%[5]. These findings are in line with broader international observations which reported that mortality rates for AKI patients requiring RRT consistently range from 50% to 60%, highlighting the severe prognosis associated with this condition[6].

CRRT comprises several modalities, each defined by its mechanism of solute and fluid removal. Continuous venovenous hemofiltration utilizes convective clearance, continuous venovenous hemodialysis relies on diffusive clearance, and continuous venovenous hemodiafiltration combines both mechanisms. The selection among these modalities is guided by the patient’s clinical context, such as the need to remove middle-sized molecules, manage fluid overload, or optimize filter lifespan and nursing workload[7]. The heterogeneity of critically ill patients call for tailored CRRT therapy in the ICU. Individualization of CRRT prescription involves dynamic adjustment of modality, dose, anticoagulation strategy, and membrane selection. These decisions are based on real-time response to clinical parameters such as hemodynamic stability, metabolic demands, and comorbidities[1,8].

Research indicates that no single treatment method stands out as the best for all patients. Instead, it’s important to customize therapy to fit the individual needs and objectives of each patient in the ICU[9]. Slow continuous ultrafiltration (SCUF) and prolonged intermittent RRT (PIRRT) deserve closer attention as practical solutions for challenging clinical scenarios. While they may not be appropriate for every patient, both modalities fill important gaps in our therapeutic options.

In patients presenting with persistent fluid overload, such as those with decompensated heart failure and refractory to maximal dose of diuretic, SCUF demonstrates particular clinical utility. Rather than subjecting these patients to the full complexity of CRRT, SCUF offers a more gentle and steady fluid removal that respects often-fragile hemodynamic status. What makes SCUF particularly attractive is its lower logistical burden, as the technique does not require dialysate or replacement fluid bags. In carefully selected patients, vascular access for this modality can even be established through existing central venous catheters rather than requiring dedicated hemodialysis catheters[10].

On the other hand, PIRRT presents a solution that bridge the gap between CRRT and intermittent hemodialysis (IHD). This modality encompasses characteristics of both. Treatment sessions typically last 6 hours to 12 hours and are scheduled 4 times to 7 times per week. It provides sufficient and gradual solute clearance while maintaining hemodynamic stability and operational ICU workflow. The equipment requirements are notably flexible, as either intermittent or continuous dialysis machines may be used, depending on institutional availability and resource allocation.

However, due to absence of standardized protocols, the practice patterns vary considerably across institutions. Furthermore, drug dosing during PIRRT remains uncertain, and delivery parameters are not yet well-defined, highlighting the need for further investigation and consensus-building[11]. This review aims to clarify the clinical role of SCUF and PIRRT in contemporary ICU practice. We examine how SCUF serves patients who primarily need fluid removal, offering a gentler alternative to full CRRT. Similarly, we explore how PIRRT’s prolonged, gradual approach may benefit hemodynamically fragile patients who struggle with conventional dialysis (Table 1).

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.

CONTINUOUS RRT: FUNDAMENTALS AND CURRENT PRACTICE

Principles and mechanisms of conventional CRRT

Conventional CRRT represents an indispensable lifeline in the ICU to critically ill patients. Understanding CRRT requires appreciating three fundamental mechanisms: Diffusion, convection, and ultrafiltration. Each plays an essential role in managing solutes and fluid. In continuous venovenous hemodialysis diffusion drives the process. The solutes, such as urea and creatinine, migrate across the membrane in response to concentration gradients between the blood and dialysate compartments. Continuous venovenous hemofiltration operates differently, relying on convection. The hydrostatic pressure forces plasma water across the membrane, carrying dissolved solutes along with it. Lastly, continuous venovenous hemodiafiltration combines both mechanisms, offering broader therapeutic coverage.

Ultrafiltration is the primary tool for managing fluid balance. The rate of fluid removal can be precisely adjusted to meet needs while minimizing hemodynamic stress, a critical advantage when treating unstable patients[12]. Replacement fluids and dialysate composition must be tailored to address each patient’s specific metabolic requirements. Anticoagulation presents another important consideration; regional citrate has emerged as the preferred approach in most centers, effectively preventing circuit clotting while minimizing systemic bleeding risk. CRRT dosing is typically prescribed as total effluent flow, commonly 20-25 mL/kg/hour for most patients, though continuous reassessment based on evolving solute control and fluid status remains necessary[3]. The defining characteristic of CRRT lies in its continuous nature. This enables gradual, consistent removal of toxins and fluid over extended periods, while avoiding the rapid shifts in blood pressure and electrolytes that can destabilize critically ill patients[13].

Indications for CRRT in critically ill patients

The indications for CRRT in critically ill patients are primarily the presence of life-threatening complications such as hyperkalemia that persists despite aggressive medical therapy, profound metabolic acidosis that refuses to correct, pulmonary edema causing significant hypoxemia despite maximal diuretic therapy, and the dreaded uremic complications, pericarditis, encephalopathy, or uremic bleeding, that signal the body’s toxic burden has become intolerable. These situations demand urgent intervention. CRRT is also essential when severe fluid overload overwhelms diuretic responsiveness and begins compromising organ function, particularly in patients whose hemodynamic fragility or acute brain injury makes them vulnerable to the rapid fluid shifts that characterize IHD[14].

Certain toxic ingestions expand the indication for CRRT beyond kidney injury alone. When patients present with life-threatening levels of lithium, ethylene glycol, methanol, salicylates, or metformin, and their hemodynamic instability precludes intermittent IHD, CRRT offers a gentler approach to extracorporeal toxin removal[1,15].

Not all indications carry the same timeline. Persistent, severe AKI with prolonged oliguria or anuria, typically lasting more than 72 hours, or markedly elevated blood urea nitrogen levels, may warrant CRRT initiation even in the absence of immediately life-threatening complications[16].

The choice of CRRT over IHD becomes particularly compelling in specific patient populations. Those in shock, suffering from acute brain injury, or facing fulminant hepatic failure benefit from CRRT’s superior hemodynamic stability and its avoidance of rapid osmotic shifts that could prove catastrophic in already vulnerable patients[13]. Ultimately, the decision to initiate CRRT should reflect careful consideration of these indications within each patient’s unique clinical context, recognizing that textbook criteria must always be tempered by bedside judgment.

Limitations and challenges of traditional CRRT approaches

Traditional CRRT methods come with a tough set of technical, clinical, and logistical hurdles that healthcare professionals must confront every day. The therapy relies heavily on continuous vascular access and anticoagulation, creating a delicate balance that can easily result in complications. Bleeding, filter clotting, and catheter-related infections represent persistent threats. The anticoagulation dilemma is particularly vexing. Heparin increases the risk of bleeding in already vulnerable patients, while citrate anticoagulation, though generally safer, introduces its own metabolic complexities. Hypocalcemia, hypophosphatemia, and magnesium depletion can develop insidiously, demanding vigilant monitoring that adds to the clinical workload[8].

Resource demands represent another substantial burden. CRRT requires intensive nursing attention and technical expertise, yet circuit interruptions due to clotting or equipment malfunctions occur with disappointing frequency. These interruptions lead to underdosing and inconsistent solute clearance, undermining the very continuity that theoretically makes CRRT superior[14].

Despite the possible physiological advantages of CRRT in maintaining hemodynamic stability, available randomized trials have not consistently shown superiority of CRRT over intermittent modalities in terms of mortality or renal recovery. Data are heterogeneous and further well-designed trials are needed to define net clinical benefits in specific patient subgroups. Moreover, more intensive dialytic dosing, once hoped to improve outcomes, has proven disappointing, offering no survival benefit while increasing the risk of electrolyte disturbances[15].

Practical considerations further complicate CRRT implementation. The therapy restricts patient mobility, limiting early mobilization efforts that have become central to modern critical care. Cost and resource utilization consistently exceed those of intermittent therapies, raising sustainability questions in resource-limited settings. These challenges make it clear that CRRT, while valuable, requires individualised application, strong multidisciplinary collaboration, and comprehensive quality assurance programmes to optimise patients’ quality of life and life expectancy and reduce adverse outcomes[17].

SCUF

Technical aspects and mechanisms

SCUF is a form of CRRT specifically designed to remove excess fluid in patients with diuretic-resistant fluid overload who do not require significant solute clearance. The typical SCUF candidate presents with acute or chronic heart failure complicated by severe systemic fluid overload. In these situations, aggressive diuresis has failed or proven too risky. The therapy demands attentive titration based on ongoing assessment of volume status, hemodynamic response, and fluid balance trends. Vigilant monitoring helps avoid the twin perils of hypotension and organ hypoperfusion that can emerge with overzealous fluid removal[18].

The technical approach is elegantly simple. The blood circulates extracorporeally through a hemofilter where a transmembrane pressure gradient gently pulls plasma water across a semipermeable membrane, generating ultrafiltrate. What distinguishes SCUF from its CRRT cousins is what it does not use, there’s no dialysate, no replacement fluids. The sole objective is controlled fluid removal, not metabolic correction[19].

The therapy’s conservative parameters reflect its philosophy of gentleness. Blood flow rates remain deliberately low, typically 50-200 mL/minute[20]. In contrast, the ultrafiltration rate must further be individualized based on multiple clinical and circuit-related factors, including the target volume removal, hemodynamic stability, vascular refill capacity from the interstitial compartment, and circuit pressure limitations. In clinical practice, a commonly adopted starting rate is approximately 100-200 mL/hour[21], with subsequent adjustments guided by the patient’s tolerance and clinical goals.

This cautious approach minimizes hemodynamic perturbations and avoids the intravascular volume shifts that could destabilize fragile patients[10]. From a practical standpoint, SCUF offers an appealing simplicity. it can be performed using standard central venous catheters already in place, eliminating the need for additional procedures and reducing associated risks[22].

Anticoagulation warrants careful consideration in SCUF. Although regional citrate is commonly used to prevent circuit clotting in CRRT, clinicians must exercise particular caution with this approach. The combination of SCUF’s very low blood flow rates and the absence of dialysate or replacement fluids create conditions in which citrate clearance can be problematic. Unlike conventional CRRT modalities that actively clear citrate via dialysis or convection, SCUF provides minimal solute removal, allowing citrate to accumulate, particularly in patients with impaired hepatic metabolism. This risk becomes especially concerning in those with liver dysfunction, shock, or hypothermia, where hepatic citrate metabolism is already compromised. Close monitoring of ionized calcium levels and acid-base status is of pivotal importance when using citrate anticoagulation with SCUF.

Clinicians should recognize SCUF’s fundamental limitation, it addresses volume, not chemistry, and this distinction should guide patient selection. It does not provide meaningful solute clearance. Patients with severe metabolic derangements such as profound acidosis, dangerous hyperkalemia, or uremic complications require more comprehensive renal replacement strategies[15].

Clinical indications and patient selection

Knowing when to initiate SCUF requires recognizing a specific clinical scenario. The classic candidate presents with diuretic-resistant congestion in the context of acute or chronic heart failure. These patients remain stubbornly volume overloaded despite aggressive pharmacologic combinations[23]. SCUF also finds its role in patients with oliguria or anuria, provided they have not developed severe metabolic derangements such as profound uremia, dangerous acidosis, or life-threatening electrolyte abnormalities that would demand more comprehensive solute clearance[24]. The decision in favor of SCUF becomes particularly compelling when hemodynamic fragility raises concerns about intermittent ultrafiltration. Patients prone to hypotension or those with marginal blood pressure tolerance benefit from SCUF’s slow, continuous approach, which produces less dramatic blood pressure variability and better hemodynamic tolerance[25].

One of SCUF’s most valuable attributes lies in its protective potential for kidney function. When aggressive or rapid fluid removal threatens to worsen renal function, a legitimate concern with more intensive approaches, SCUF’s moderate ultrafiltration rates offer a slow, controlled therapeutic path. This measured approach correlates with improved hemodynamic stability and reduced risk of organ injury, making it particularly attractive for patients whose renal function remains precariously balanced[18].

Patient selection demands careful attention to specific criteria. The selection begins with clinical examination revealing peripheral edema and pulmonary congestion, objective measurements demonstrating elevated central venous or pulmonary pressures, and progressive weight gain that defies medical management[26]. SCUF should not be considered a first-line intervention but rather represents an appropriate choice when conventional approaches have demonstrably failed[27]. Documentation of failed maximal diuretic therapy and exhaustion of reasonable pharmacologic options is essential. The metabolic profile carries substantial importance in patient selection. SCUF remains appropriate only in the absence of severe metabolic derangements. Patients presenting with marked uremia, profound acidosis, or dangerous electrolyte disturbances require modalities capable of significant solute clearance, as SCUF cannot adequately address these metabolic needs[24].

Practical considerations include guaranteeing adequate vascular access, ideally utilizing existing central venous catheters to minimize additional procedural risk and complications[28]. Hemodynamic stability, or at a minimum the capacity to tolerate slow, controlled fluid removal, is an essential prerequisite. Target ultrafiltration rates typically range from 50 mL/hour to 200 mL/hour, with the understanding that these parameters should be dynamically adjusted based on patient response rather than rigidly adhered to predetermined numbers[18]. Continuous assessment of intravascular volume status becomes paramount. Tools such as inferior vena cava ultrasound or blood volume monitoring provide objective data to guide therapeutic adjustments and help prevent hypotension that signals overly aggressive fluid removal[29]. SCUF requires ongoing clinical attention to evolving patient conditions rather than passive observation following initiation (Table 2).

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.

Clinical evidence for SCUF in fluid overload and diuretic resistance

SCUF emerged in 1980 as an innovative solution for patients with oliguric acute renal failure, introduced by Paganini and Nakamoto[30] as an extension of the CRRT techniques first described by Kramer et al[31] in 1977. What distinguished SCUF was its approach in removing fluid slowly and continuously rather than in large boluses. This technique circumvented the hemodynamic compromise that often complicated aggressive intermittent decongestive strategies. Unlike its predecessor, continuous arteriovenous hemofiltration, which relied on arterial blood flow, SCUF evolved in the early 1980s to utilize venovenous access with pump-driven blood flow, dramatically expanding its practical applicability[32].

The first systematic investigation of SCUF in cardiac failure was conducted by Wei et al[33], who demonstrated hemodynamic safety in 7 patients with cardiac failure and diuretic resistance, achieving a mean fluid removal of 2189 ± 699 mL per session with stable blood pressure. The RAPID-CHF trial expanded the therapeutic landscape by randomizing 40 patients to single 8-hour ultrafiltration vs usual care, demonstrating significantly greater fluid removal (4650 mL vs 2838 mL, P = 0.001) with simplified devices requiring neither central venous access nor intensive monitoring[34]. The landmark UNLOAD trial strengthened the case for early ultrafiltration in 200 acute decompensated heart failure (ADHF) patients, achieving superior weight loss (5.0 kg vs 3.1 kg, P = 0.001) and fluid removal (4.6 L vs 3.3 L, P = 0.001) at 48 hours compared to intravenous diuretics, with similar dyspnea relief and renal function but remarkably demonstrating 44% reduction in 90-day heart failure rehospitalizations (18% vs 32%, P = 0.037)[35]. Paladino et al[36] contributed preliminary evidence that SCUF may reduce not only cardiac preload but also respiratory workload in ADHF, showing improvements in both hemodynamic parameters and correction of carbon dioxide retention in hypercapnic patients, likely attributable to both lung water reduction and decreased work of breathing, thereby suggesting potential benefits extending to pulmonary mechanics.

Technical refinements followed with Guiotto et al[26] using ultrasound-guided inferior vena cava collapsibility monitoring to achieve 5.8 L removal per session while minimizing hemodynamic instability, while the ULTRADISCO study revealed that ultrafiltration produced not only greater symptom reduction but also significantly decreased aldosterone (0.24 ± 0.25 nmol/L vs 0.86 ± 1.04 nmol/L, P < 0.001) and N-terminal pro-B-type natriuretic peptide alongside substantial improvements in stroke volume index (+14%), cardiac index (+23%), and cardiac power output (+14%), all P < 0.001, suggesting benefits extending beyond volume removal to favorable neurohormonal modulation and enhanced cardiac performance[37]. Giglioli et al[38] corroborated these findings in 15 NYHA III-IV patients, demonstrating 7.4% weight reduction, improved NYHA class (3.5 to 2.4, P < 0.01), dramatic pro-BNP reductions, and enhanced contractile cardiac efficiency.

The field’s trajectory changed dramatically with CARRESS-HF[39], which enrolled 188 patients with ADHF and worsening renal function (creatinine increase ≥ 0.3 mg/dL) and persistent congestion, randomizing them to fixed-rate ultrafiltration (200 mL/hour) vs stepped pharmacologic therapy. Ultrafiltration caused significant renal function worsening at 96 hours (creatinine increase 0.23 ± 0.70 mg/dL vs decrease 0.04 ± 0.53 mg/dL, P = 0.003) without superior weight loss (5.7 ± 3.9 kg vs 5.5 ± 5.1 kg, P = 0.58) and with higher serious adverse events (72% vs 57%, P = 0.03), including bleeding and catheter complications, fundamentally challenging ultrafiltration’s role in established cardiorenal syndrome. Patarroyo et al[21] reinforced these concerns in 63 consecutive patients with advanced ADHF refractory to intensive medical therapy, observing that despite hemodynamic improvements and substantial weight loss, 59% progressed to dialysis and 30% died during hospitalization. Wehbe et al[40] identified that higher baseline creatinine and lower systolic perfusion pressure predicted dialysis-requiring renal failure, which carried 95% 12-month mortality, emphasizing the critical importance of patient selection. Grodin et al[41] performed per-protocol analysis of CARRESS-HF accounting for substantial crossover (39% ultrafiltration arm, 6% pharmacologic arm), revealing that ultrafiltration achieved greater cumulative fluid loss (P = 0.003), net fluid loss (P = 0.001), and relative weight reduction (P = 0.02), corroborating UNLOAD’s decongestion findings but without reduced rehospitalizations, likely because 90% of patients remained inadequately decongested at primary endpoint evaluation[41].

Attempts to reconcile the conflicting results between UNLOAD and CARRESS-HF led to the CUORE trial[42], which randomized 56 severe heart failure patients with overt overload to ultrafiltration plus continued diuretics vs standard therapy, employing continuous hematocrit monitoring to prevent intravascular depletion and demonstrating significantly fewer heart failure rehospitalizations at one-year follow-up despite similar discharge weight loss, with preserved renal function at 6 months (creatinine 1.8 ± 0.6 mg/dL vs 2.3 ± 1.1 mg/dL, P = 0.69), suggesting that appropriately monitored ultrafiltration initiated before severe renal dysfunction may confer sustained clinical stability. The AVOID-HF trial implemented adjustable ultrafiltration rates tailored to individual hemodynamics. Still, it was prematurely terminated due to enrolment difficulties. The study comprised only 224 of 810 planned patients, revealing trends toward longer time to first event (62 days vs 34 days, P = 0.106), significantly greater net fluid removal (12.9 L vs 8.9 L, P = 0.006), and fewer 30-day rehospitalizations, though with increased therapy-related adverse events (14.6% vs 5.4%, P = 0.03)[43]. In their study Hu et al[44] randomized 100 ADHF patients within 24 hours of admission to early ultrafiltration for 3 days vs torasemide plus tolvaptan, demonstrating markedly superior weight loss (2.94 ± 3.76 kg vs 0.64 ± 0.91 kg, P < 0.001) and urine output increase (198.00 ± 170.70 mL vs 61.77 ± 4.67 mL, P < 0.001) by day 4, supporting the hypothesis that early mechanical fluid removal may restore diuretic responsiveness. Technical innovations by Nalesso et al[10] demonstrated the feasibility of SCUF with regional citrate anticoagulation (RCA) via a standard central venous catheter rather than specialized dialysis catheters, achieving 1 kg weight loss over 10 hours without complications. Collectively, these studies indicate that the efficacy of ultrafiltration is critically contingent upon timing (early vs delayed intervention), baseline renal function, protocol design (fixed vs individualized fluid-removal rates), monitoring intensity, and the severity of congestion. In this context, early implementation in appropriately selected patients appears beneficial, whereas fixed-rate protocols applied in established cardiorenal syndrome have been associated with adverse outcomes.

PIRRT

PIRRT, which includes methods such as sustained low efficiency dialysis (SLED) and sustained low-efficiency daily diafiltration (SLEDD-f), derives much of its value from recalibrating standard dialysis platforms to emphasise stability, precision, and operational coherence both inside and outside the ICU. By operating at reduced blood and dialysate flow rates, these treatments lessen shear forces within extracorporeal circuits and decrease the frequency of pressure alarms, often improving session continuity. Longer treatment durations enhance solute-membrane interaction, supporting more effective middle-molecule clearance without relying on the high effluent volumes required by continuous therapies. Volumetric ultrafiltration, controlled over several hours, promotes steadier intravascular refill and minimises the abrupt osmotic and volume shifts that can destabilise patients during conventional IHD. In SLEDD-f, the availability of online haemodiafiltration provides an additional convective dimension, allowing substitution flows to be adjusted to evolving metabolic and inflammatory demands. Just as importantly, these modalities can be integrated into ICU routines, run overnight, paused briefly for procedures, or aligned with staffing patterns, transforming engineering refinements into meaningful bedside advantages[45,46].

Technical aspects and mechanisms in the use of PIRRT and SLED

PIRRT, SLED, and SLEDD-f offer a novel approach by adapting standard haemodialysis and CRRT equipment to provide gentler, slower exchanges that better suit the needs of critically ill, unstable patients, rather than simply following a conventional dialysis schedule. These methods utilize familiar machines, water systems, and catheters, repurposed to deliver personalized therapy over extended periods. These modalities are commonly delivered either with CRRT platforms using commercial premixed solutions, with prescriptions adjusted to lower blood and dialysate or effluent flows, or standard IHD consoles connected to central ultrapure water or portable reverse-osmosis systems. Regional citrate or low-dose heparin anticoagulation is used when bleeding risk permits, although many SLED/SLEDD-f programs report successful delivery with minimal anticoagulation[47].

The core processes behind PIRRT and SLED primarily involve diffusive clearance of smaller solutes, such as urea and potassium, and ultrafiltration to remove excess fluid. By extending the treatment duration and using lower flow rates, these methods promote more gradual removal of solutes and fluids[48]. This approach helps to avoid sudden osmotic changes, which can lower the risk of issues like intradialytic hypotension and dialysis disequilibrium syndrome. SLED can be carried out with standard hemodialysis machines or batch dialysis systems, and it can even be scheduled at night to make daytime care for patients easier[49].

For SLED, the required equipment rarely exceeds what is already present in a modern chronic dialysis unit. This is reflected in the results of observational cohorts and meta-analyses (1160 patients in 11 studies) showing SLED to be non-inferior to CRRT for mortality [rate ratio: 0.67; 95% confidence interval (CI): 0.44-1.00], renal recovery, and dialysis dependence in hemodynamically unstable adults[50]. SLEDD-f adds one further layer of technology: Machines with on-line hemodiafiltration capability, separate pumps for dialysate and substitution fluid, and high-flux membranes that can safely support combined dialysate flows around 200 mL per minute and convective replacement of about 100 mL per minute for 8-hour sessions, yielding single-session urea Kt/V values around 1.4 and equivalent renal clearance near 36 mL per minute in the original ICU series[51].

Currently, PIRRT sessions typically last between 6 hours and 12 hours and are performed 4 days to 7 days per week. Blood flow rates are generally between 150 mL/minute and 250 mL/minute, while dialysate (or replacement fluid) flow rates range from 60 mL/minute to 150 mL/minute with CRRT platforms and from 200 mL/minute to 300 mL/minute with IHD machines with modified prescription[45,46]. This intermediate “dose” achieves small-solute clearances and per-treatment Kt/V values comparable to both adequately dosed CRRT and traditional IHD. For example, in SLEDD-f, an 8-hour session with a blood flow of 200 mL/minute and a dialysate flow of 200 mL/minute, plus an additional 100 mL/minute of convective flow, achieved a mean Kt/V of 1.43 ± 0.28 and a renal urea clearance of 35.7 ± 6.4 mL/minute, values that fall within the effective solute control range observed in large CRRT dose-response studies[51,52]. Mechanistically, the slower dialysate and ultrafiltration rates help minimise shifts in osmolarity, temperature, and volume. Drug clearance is more complex. Although SLED generally clears small molecules more efficiently per hour than CRRT, the non-continuous nature of the treatment alters the daily exposure profile, requiring specific dosing strategies that are now available for many antimicrobials[52].

From a technical perspective, the appeal of these modalities extends beyond simply fitting into existing dialysis systems. Their true value emerges when considering the potential operational benefits gained by deliberately slowing time, flow, and membrane physics. By reducing blood flow rates, shear stress on fragile central venous catheters is minimised, often resulting in fewer pressure alarms within the circuits. Additionally, volumetric ultrafiltration control during extended sessions is useful for maintaining steady intravascular refill and reducing the cyclic hypotension frequently seen with conventional IHD. Longer treatment durations also improve solute-membrane contact, enhancing the clearance of middle molecules without requiring the high effluent volumes typical of CRRT. In SLEDD-f, the capacity for online hemodiafiltration provides further flexibility: Convective dosing can be adjusted in real time to match a patient’s inflammatory or catabolic needs, achieving better clearance without increasing osmotic or thermal stress. Importantly, all three methods can be integrated into ICU workflows, operating overnight to free daytime imaging slots, pausing briefly for procedures without compromising effectiveness, or being tailored for patients whose conditions fluctuate hourly.

Clinical indications and patient selection in the use of PIRRT and SLED

Clinical indications for PIRRT, including SLED, emerge at the bedside when the nephrologist and intensivist aim to provide appropriate kidney support for a hemodynamically fragile patient while avoiding additional strain. Although current Kidney Disease: Improving Global Outcomes guidelines and expert consensus still recommend CRRT as the preferred option for patients in shock, they acknowledge that hybrid modalities can be viable alternatives if administered with appropriate dosing and monitoring[53]. Importantly, no single method has demonstrated a clear survival advantage over the others[50]. In practice, PIRRT is typically considered for adults with Kidney Disease: Improving Global Outcomes stage 2-3 AKI or acute-on-chronic kidney failure, especially when they have standard emergency indications for RRT, such as refractory hyperkalaemia, severe metabolic acidosis, uremic complications, or significant fluid overload, but are too unstable for traditional IHD, or have already experienced haemodynamic instability due to IHD[54,55]. SLED is particularly suitable for these “in-between” patients. It uses lower blood and dialysate flow rates and more prolonged treatment durations than IHD, which help minimise osmotic and volume shifts, thereby improving haemodynamic tolerance. Moreover, the intermittent aspect of SLED allows valuable time off the machine for activities such as mobilisation, imaging, family visits, and procedures. Observational studies and small trials suggest that, for carefully selected ICU patients, often intubated and frequently on vasopressors, PIRRT and SLED can effectively manage solute levels and fluid removal while maintaining acceptable rates of intradialytic hypotension[56]. Mortality and renal recovery outcomes appear broadly comparable to continuous techniques, although confounding factors and selection bias remain significant concerns[57].

Selecting appropriate patients for treatment is not solely based on strict creatinine or urea thresholds. It depends on relevant factors such as haemodynamic reserve, vasopressor dose, intracranial pressure status, urgency of solute and volume management, and the expertise of local nursing and technical staff. Throughout this process, a more person-centred approach involves open discussions with the care team and family about how PIRRT or SLED can balance organ support with comfort, allow for treatment-free daylight hours, and align with the patient’s care goals. It is important to remember that the “best” treatment option is not determined solely by medical details; it is also about what is manageable and meaningful for the person receiving care (Tables 3 and 4).

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.

Clinical evidence and outcomes in the use of PIRRT and SLED

PIRRT, including SLED, has emerged as a pragmatic “hybrid” strategy for critically ill patients with AKI. These methods aim to strike a balance between hemodynamic stability, effective solute clearance, and the real-world challenges faced in crowded ICUs[11,45].

In a large multicenter time-series cohort of 1347 ICU patients, a unit-wide switch from CRRT to PIRRT was not associated with excess mortality (adjusted incidence rate ratio for death: 1.02; 95%CI: 0.61-1.71), supporting clinical equipoise between these modalities[58]. This foundational observation has been reinforced by subsequent comparative investigations. A prospective observational study of 67 ICU patients (35 CRRT, 32 SLED) analyzed 58 CRRT sessions and 87 SLED sessions, revealing comparable 28-day mortality rates (77.14% CRRT vs 78.12% SLED) while suggesting potential logistical advantages for SLED, particularly regarding reduced filter clotting incidents, a consideration of genuine importance in resource-limited settings where every hour of circuit patency translates into nursing time, material costs, and uninterrupted therapy delivery[59].

Focusing specifically on SLED, a cohort of 232 patients (158 treated with CRRT, 74 with SLED) reported 30-day mortality of 54% vs 61%, respectively, with no significant difference after multivariable adjustment (adjusted odds ratio: 1.07; 95%CI: 0.56-2.03) and similar rates of RRT dependence and early clinical deterioration[60]. Subsequent work in 284 patients found that, despite greater initial illness severity among CRRT recipients, 90-day and 1-year mortality and dialysis dependence did not differ between SLED and CRRT[61]. A retrospective cohort from a quaternary care center treating 58 hemodynamically unstable patients with SLED [mean Acute Physiology and Chronic Health Evaluation (APACHE) II score 17, overall mortality 56.9%] identified higher APACHE II scores, elevated international normalized ratio, thrombocytopenia, and septic shock as poor prognostic markers, reminding clinicians that severity of underlying illness, rather than dialysis modality per se, remains the dominant determinant of outcome[62]. The therapeutic scope of SLED has broadened considerably beyond classical AKI management. The ELDICS trial, a randomized controlled study of 50 critically ill cirrhotic patients (90% male, 87% alcohol-related, 72% with pneumonia) presenting with septic shock, compared early SLED initiation (within 6-12 hours) against late initiation (when absolute criteria were met). Though 28-day mortality did not differ significantly between groups (56% early vs 76% late; P = 0.14), early SLED was associated with clinically meaningful benefits: A 75% reduction in intradialytic hypotension (12% vs 48%; P = 0.005), superior urea reduction (75% vs 41%; P = 0.019), greater reversal of shock (60% vs 16%; P = 0.001), enhanced recovery of renal function (68% vs 12%; P < 0.001), and notably lower early mortality at day 7 (20% vs 52%; P = 0.038). These data suggest that, in the precarious hemodynamic landscape of decompensated cirrhosis with sepsis, timely initiation of SLED may avert metabolic catastrophe and buy precious time for hepatic and immunologic recovery[63]. Perhaps even more striking is the emerging role of SLED in cardiorenal medicine. A single-center retrospective cohort compared 107 patients with advanced heart failure and persistent congestion treated with SLED against 32 patients who declined SLED and continued standard medical therapy alone. During the first year following SLED initiation, heart failure hospitalization occurred in only 13% of SLED patients compared to 78% of controls; annual heart failure hospitalization rates in the SLED group plummeted from 1.5 events to 0.3 events (P < 0.001), and hospital days diminished from 21.4 days to 2.5 days (P < 0.001). In contrast, no significant change occurred in the standard therapy group. Moreover, SLED facilitated meaningful optimization of guideline-directed medical therapy, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists, and β-blockers, which remained largely static in the control arm. Most compellingly, median survival extended to 23 months (95%CI: 17-29) in the SLED group vs only 3 months (95%CI: 1-7; P < 0.001) in those receiving standard therapy. These findings invite us to reconsider SLED not merely as a temporizing measure in acute decompensation, but as a bridge to medical optimization and, for some, a dignified extension of functional life when mechanical support or transplantation is not an option[64].

The practical feasibility of SLED has been further enhanced by the refinement of RCA protocols adapted to standard hemodialysis equipment. A prospective study of 27 critically ill patients (APACHE II score 21 ± 6) undergoing 81 SLED sessions with a simplified RCA protocol using concentrated citrate solution (acid-citrate-dextrose solution A) and cellulose triacetate filters achieved the prescribed 8-hour duration in 88% of treatments. Direct enzymatic measurement of serum citrate levels throughout therapy confirmed safety; no major bleeding or citrate accumulation complications occurred, though calcium supplementation was required in 23% of sessions and phosphate or magnesium supplementation in approximately 25%. This experience demonstrates that SLED with RCA can be delivered safely using “conventional” dialysis machines when coupled with meticulous electrolyte monitoring and individualized supplementation, an approach accessible to many centers without dedicated CRRT infrastructure[65].

Multiple meta-analyses synthesize these evidences: A systematic review of SLED vs CRRT (18 studies, 1564 patients) suggested a modest mortality signal favoring SLED when the rate ratio was expressed as CRRT vs SLED [relative risk (RR): 1.21; 95%CI: 1.02-1.43], an effect that attenuated to the margins of significance in randomized trials alone (RR: 1.25; 95%CI: 1.00-1.57)[66].

A more recent comparative meta-analysis of 11 studies (1160 patients) reported no statistically significant difference in mortality between SLED and CRRT (RR: 0.67; 95%CI: 0.44-1.00; P = 0.05), and no difference in renal recovery (RR: 1.08; 95%CI: 0.83-1.42), dialysis dependence (RR: 1.03; 95%CI: 0.69-1.53), ICU length of stay, or fluid removal, confirming clinical non-inferiority of SLED in hemodynamically unstable patients[50].

Network meta-analysis across RRT modalities in AKI has similarly found no meaningful mortality difference between CRRT and IHD (RR: 1.04; 95%CI: 0.93-1.18), while hinting that slow-efficiency extended dialysis, with or without hemofiltration, may be associated with the lowest mortality and shorter hospital stay, though based on low-certainty data[67].

Contemporary systematic reviews and expert guidelines conclude that, despite overall mortality remaining distressingly high (approximately 40%-60%) in ICU patients requiring RRT, no modality, including PIRRT/SLED, has demonstrated a consistent survival or renal-recovery advantage; instead, modality choice should be individualized according to hemodynamic profile, neurological status, staffing, and local expertise, within a patient-centered framework that integrates prognosis and patient values[68,69].

These data confirm that PIRRT and SLED are not inferior alternatives; rather, they are mature and reliable options that can be as safe and effective as traditional CRRT, particularly when carefully prescribed, monitored, and tailored to the patient’s overall care goals and clinical trajectory (Table 5).

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.

DISCUSSION

The evidence supporting the use of extracorporeal fluid- and solute-management strategies ranging from SCUF to PIRRT remains heterogeneous, with critical methodological limitations but also notable physiologic and operational advantages in selected populations.

Early work in heart-failure populations suggested that isolated ultrafiltration could provide effective decongestion when diuretic resistance limits pharmacologic options. The UNLOAD trial, for example, reported greater fluid and weight loss at 48 hours and fewer heart-failure rehospitalizations at 90 days among patients randomized to early ultrafiltration compared with intravenous diuretics[35]. These findings suggest that extracorporeal, isotonic sodium-rich fluid removal may achieve greater decongestion than high-dose loop diuretics in some patients with refractory congestion. However, the trial was unblinded, the sample size was modest, and diuretic therapy was not strictly protocolized, limiting the generalizability of its positive results. Conversely, in patients with established cardiorenal syndrome and worsening renal function, the CARRESS-HF trial demonstrated the hazards of non-individualized ultrafiltration; fixed-rate ultrafiltration resulted in worsening renal function, no additional decongestion, and more adverse events than a structured pharmacologic strategy[39]. A subsequent per-protocol analysis reinforced the finding that while ultrafiltration can achieve greater net fluid removal, it may simultaneously elicit biochemical evidence of impaired renal perfusion when vascular refill is inadequate[41]. Collectively, these studies underscore that patient selection, timing, and individualized ultrafiltration rates are central determinants of safety and efficacy. Although observational series describe hemodynamic stability and meaningful decongestion during SCUF in carefully chosen patients, these studies are small, often uncontrolled, and at high risk for confounding by clinical severity[39,70,71].

Parallel development of PIRRT modalities, including SLED and SLED-f, has been driven by the need for hemodynamically tolerable solute control in critically ill patients who do not require the full burden or resource intensity of CRRT. In early prospective evaluations, SLED delivered equivalent small-solute clearance to CRRT while preserving hemodynamic stability and reducing nursing workload and circuit downtime[72,73]. Subsequent observational comparisons have consistently reported similar mortality, renal recovery, and dialysis dependence between SLED and CRRT despite SLED often being used in patients with greater initial hemodynamic fragility[74]. A large multicenter study of unit-wide transition from CRRT to PIRRT further suggested that replacing continuous therapy with extended-duration intermittent modalities does not worsen outcomes at the population level[75]. Though limited by a non-randomized design, these data support the operational feasibility of PIRRT and reinforce clinical equipoise between modalities.

In certain subgroups, PIRRT may offer potential benefits. In a randomized trial of patients with cirrhosis and septic shock, early SLED initiation was associated with fewer intradialytic hypotensive episodes, greater urea reduction, improved shock reversal, and higher rates of renal recovery at day 7 compared with delayed initiation. However, 28-day mortality did not differ significantly[63]. These findings, while promising, arise from a small, highly selected cohort and require cautious interpretation. In advanced heart failure, retrospective cohorts have reported substantial reductions in rehospitalization and improved clinical stability among patients treated with SLED. Still, these data are vulnerable to selection bias and should not be interpreted as evidence of prognostic superiority.

Several key themes emerge from the available evidence. First, no extracorporeal modality, ultrafiltration, SCUF, PIRRT, or CRRT, has demonstrated a consistent mortality or renal-recovery advantage in randomized trials, with outcomes determined mainly by the underlying severity of illness rather than the treatment modality itself. Second, SCUF may be especially suitable for patients with isolated volume overload and preserved metabolic/uremic control, provided ultrafiltration rates are titrated to vascular refilling capacity. Third, PIRRT represents a pragmatic intermediate option, offering greater hemodynamic stability than conventional IHD, along with increased scheduling flexibility, lower cost, and improved patient mobility compared to CRRT. Finally, the quality of evidence across all modalities is limited by small sample sizes, protocol heterogeneity, and reliance on observational studies.

Ultimately, the choice among CRRT, PIRRT, and SCUF should not be viewed as a simple technological preference but as a response to the dynamic imbalance between the patient’s metabolic and fluid demands and residual renal capacity. In critically ill patients, this balance is continually influenced by disease severity, solute burden, and volume status, and may fluctuate over time, requiring ongoing reassessment[76,77]. Within this framework, SCUF is a rational option when volume overload predominates in the absence of major metabolic derangements. At the same time, PIRRT is a practical intermediate strategy when hemodynamic tolerance, rehabilitation needs, or logistical considerations make fully continuous therapy unnecessary. Tailoring renal support to this evolving demand-capacity relationship may help optimize clinical stability while limiting overtreatment and resource burden.

Future priorities include multicenter randomized trials comparing individualized ultrafiltration or SCUF strategies vs optimized pharmacologic therapy in specific heart-failure and cardiorenal phenotypes; standardized PIRRT prescriptions with validated hemodynamic and metabolic targets; and objective tools to guide ultrafiltration tolerance, such as dynamic assessments of intravascular refill, biomarkers of tubular stress, or noninvasive hemodynamic monitoring. Until such data are available, the choice among SCUF, PIRRT, and CRRT should remain highly individualized, guided by patient phenotype, hemodynamic stability, metabolic burden, and resource availability rather than assumptions of inherent modality superiority.

LIMITATIONS OF THE CURRENT EVIDENCE

This review presents several important limitations that warrant acknowledgment. The majority of available evidence supporting SCUF, PIRRT, and SLED derives from observational studies, small randomized trials, and retrospective cohorts characterized by substantial heterogeneity in patient populations, clinical indications, and treatment protocols, which compromises the external validity and generalizability of reported outcomes.

Significant selection bias pervades most comparative studies, as treatment modality is typically determined by clinician preference, institutional resources, and perceived illness severity rather than random allocation. Patients receiving CRRT generally present with more severe illness, rendering direct comparisons vulnerable to confounding by indication.

Considerable variability in technical prescriptions, including ultrafiltration rates, session duration, anticoagulation strategies, and delivered dose, precludes meaningful synthesis and limits our ability to define optimal standardized protocols. Most studies focus on short-term outcomes such as ICU mortality or renal recovery at discharge, while long-term endpoints including chronic kidney disease progression, quality of life, and healthcare utilization remain largely unexplored.

Favorable outcomes attributed to SCUF or SLED may reflect earlier intervention and less advanced disease rather than true modality-specific effects. Current evidence therefore supports clinical equipoise among RRT modalities, and conclusions regarding superiority must be interpreted with methodological caution.

OPPORTUNITIES FOR IMPROVEMENT AND REAL-TIME IMPLEMENTATION

Advances in extracorporeal renal support will come less from technological innovation than from improved patient selection and treatment personalization. Many changes can be adopted immediately. Ultrafiltration rates should respond to real-time assessment of volume status and hemodynamic stability. Bedside ultrasound, venous congestion scoring, bioimpedance analysis, and hematocrit monitoring offer practical ways to avoid intravascular depletion during SCUF and PIRRT. It is important to move away from rigid dosing schedules toward prescriptions that adapt to physiological signals, blood pressure trends, lactate clearance, peripheral perfusion, urine output, tubular injury markers.

PIRRT protocols must balance consistency with flexibility: Session length, dialysis dose, and drug dosing need adjustment for these hybrid techniques. Future trials should use pragmatic designs across multiple centers, comparing tailored ultrafiltration against enhanced medical management and standardized intermittent approaches.

GLOBAL IMPACT, MORTALITY TRENDS, AND PREVENTION STRATEGIES

AKI remains a major global health challenge: Mortality among critically ill patients requiring RRT has remained unacceptably high despite considerable progress in intensive care medicine, not only in low- and middle-income countries but also in high-income settings[1,6]. This persistence suggests that technological advances alone cannot address the complex pathophysiology and heterogeneous clinical contexts underlying AKI. Many cases of AKI are potentially avoidable: Identifying patients at elevated risk before injury occurs, minimizing exposure to nephrotoxic agents, ensuring adequate hydration, and treating infections early constitute practical primary prevention measures[1,2]. Once injury has begun, structured surveillance programs using clinical criteria and emerging biomarkers can detect AKI earlier, allowing for prompt nephrology involvement and targeted interventions[1]. Global initiatives addressing preventable AKI deaths have emphasized critical gaps at the health systems level, particularly the need for affordable diagnostics, enhanced training of non-specialist providers, and streamlined care protocols in resource-limited settings[4]. Reducing global AKI mortality will require moving beyond reactive dialysis provision toward upstream prevention, better risk prediction, and care models designed to preserve renal function before injury becomes irreversible[1,78].

CONCLUSION

RRT in the ICU includes a variety of modalities that differ not only in solute-clearance characteristics and operational demands but also in their physiologic impact on vulnerable patients. The available evidence does not show any clear advantage in mortality or kidney recovery when comparing CRRT, SCUF, or PIRRT. Instead, the differences in outcomes largely reflect underlying illness severity rather than intrinsic modality performance. SCUF offers a targeted strategy for patients with isolated, diuretic-refractory congestion, provided ultrafiltration rates are individualized to intravascular refilling capacity. PIRRT provides an intermediate option that can achieve solute and fluid control similar to CRRT while facilitating mobilization, reducing cost, and aligning treatment with ICU workflow. Across all modalities, success hinges on the alignment of therapy with the patient’s hemodynamic profile, metabolic needs, and likelihood of renal recovery. Future progress will depend on rigorous, adequately powered trials evaluating individualized ultrafiltration strategies, standardized PIRRT prescriptions, and objective tools to assess treatment tolerance. Until such data emerge, the optimal approach is to personalize renal support by selecting the modality that best matches the patient’s physiologic reserve, clinical trajectory, and overall care objectives, while prioritizing prevention, early detection, and kidney-protective strategies to reduce the global burden of AKI[79].