Version May 2024
INTRODUCTION — Dialysis-requiring acute kidney injury (AKI-D) affects a large percentage of hospitalized and, particularly, critically ill patients [1-6]. The incidence has increased by 10 percent per year and affects approximately 0.4 percent of hospitalized patients and between 3 to 13 percent of critically ill patients [1-6].
The reasons for this growth are not known, though an aging population, broadening array of nephrotoxins, growth in conditions associated with AKI such as sepsis, and liberalization of thresholds to initiate kidney replacement therapy (KRT) are likely contributors [7-10].
Patients who survive AKI-D are at risk for permanent loss of kidney function and poor quality of life [11-16]. Cardiovascular risks and mortality are increased when kidney function does not recover [17,18], and growing attention is being paid toward optimizing outcomes after AKI [19].
This topic reviews dialysis-related factors that may influence the recovery from AKI-D. Overall outcomes of AKI and patient-related risk factors that may affect recovery of kidney function are discussed elsewhere:
●(See "Kidney and patient outcomes after acute kidney injury in adults", section on 'Degree of recovery'.)
The indications, prescriptions, dose, and modalities of KRT in AKI are discussed separately:
DIALYSIS-RELATED FACTORS — Dialysis–related factors that may influence recovery from AKI include recurrent intradialytic hypotension, management of fluid overload, increased susceptibility to infection, and challenges associated with appropriate dosing of medication. Nutritional factors and characteristics of the dialysis membrane may also play a role in the likelihood of kidney recovery.
Repeated episodes of hypotension — Hypotension is a common complication of hemodialysis. (See "Intradialytic hypotension in an otherwise stable patient".)
Hypotension can cause kidney injury. (See "Pathogenesis and etiology of ischemic acute tubular necrosis", section on 'Etiology'.)
The effects of hypotension may be more pronounced among patients who already have acute tubular necrosis (ATN), which renders the kidney sensitive to diminished perfusion in preclinical studies. Normal kidneys vasodilate in the presence of ischemia as part of the autoregulatory response to maintain renal blood flow and glomerular filtration rate (GFR). Autoregulation is impaired in ATN, possibly because vascular endothelial injury reduces the release of vasodilating substances such as prostacyclin and nitric oxide [20-22]. As a result, recurrent ischemic tubular injury may be more likely to occur among patients treated with dialysis, thereby delaying the recovery of function [23-26].
The modality of kidney replacement therapy (KRT) may influence the likelihood of recovery because of the degree to which each modality causes hypotension. As an example, fluid and solute removal is slower and hypotension is less common with peritoneal dialysis and other continuous kidney replacement therapies (CKRTs) compared with intermittent hemodialysis. However, data do not conclusively support the superiority of any particular mode of KRT on kidney recovery in adult patients with AKI. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Optimal modality'.)
Management of fluid overload — In patients with AKI-D, the optimal strategy for managing fluid overload has not yet been defined [27]. Several observational studies in critically ill cohorts suggest that higher rates of ultrafiltration are associated with a longer time to independence from KRT and with mortality [28-31]. However, fluid overload itself at the time of KRT initiation and during the KRT course also is associated with lower rates of kidney recovery and mortality [32-36].
Recent international surveys of critical care clinicians and nephrologists have demonstrated a wide heterogeneity in the management of fluid overload in patients with AKI-D [37,38], highlighting the need for clinical trials to define the optimal rates, targets, and methods of assessment of fluid removal among patients with AKI-D and fluid overload.
Infection risk — Sepsis may further injure the kidneys and therefore delay recovery. Patients who experience AKI are at high risk for infection. In one study of 618 critically ill patients, 40 percent of patients developed sepsis after developing AKI [39]. Predictors of incident sepsis after AKI included prolonged oliguria (≥3 days), higher severity of illness, fluid accumulation (>25 percent of post-AKI days with cumulative fluid balance >10 percent of body weight), invasive nonsurgical procedures after AKI, and receiving dialysis. The reasons for increased infection risk are not known but may be related to immune dysfunction and fluid overload [40].
In addition, the provision of dialysis may be associated with an increased risk for sepsis. In the study cited above, compared with patients who had AKI but did not develop sepsis, septic patients were more likely to have been dialyzed (70 versus 50 percent) [39].
The mechanism by which dialysis may increase the risk for sepsis is not known but may, in part, be related to the hemodialysis catheter and its attendant risk for bacteremia (see "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology"). In one trial comparing an early or delayed strategy of KRT initiation in critically ill patients, catheter-related bloodstream infections were increased in patients in the early initiation group (10 versus 5 percent) [41].
Other dialysis-related factors that may increase infection risk include the prolongation of hospitalization and, possibly, rare exposure to endotoxin or bacteria through the dialyzer membrane [39,42,43]. (See 'Characteristics of the dialysis membrane' below.)
There may be an increase in infection-related morbidity and mortality related to subtherapeutic antibiotic serum and tissue concentrations among patients who are on dialysis and develop infection [42-46]. Subtherapeutic antibiotic concentration is due to dialytic clearance of the antibiotic or reductions in the administered dose. Ongoing changes in kidney function or volume of distribution render the appropriate dosing of antibiotics challenging [44-46].
Exposure to nephrotoxic medications — Patients with dialysis-requiring AKI (AKI-D) may be more susceptible to nephrotoxic injury. The increased risk is related to the administration of nephrotoxins (either drugs or contrast medium) in the setting of diminished clearance, a higher likelihood of drug-drug interactions due to the increased number of concomitant medical exposures, an already injured parenchyma, and dialysis-induced volume depletion. The susceptibility to nephrotoxin injury may also be higher in older patients who are on multiple medications.
Nutritional factors — Providing adequate nutrition to patients with AKI-D therapy is challenging. (See "Overview of the management of acute kidney injury (AKI) in adults", section on 'Managing nutrition'.)
Patients with AKI, particularly those requiring dialysis, are at high risk for protein-energy wasting due to the catabolic effects of illness and as nutrients, particularly amino acids, are lost during dialysis. Observational studies have estimated that mean amino acid loss during KRT can be up to 23 grams per day, depending upon the modality [47-50].
Few studies have assessed the impact of providing nutritional support on recovery of kidney function in this population. The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial randomly assigned 4640 critically ill patients already receiving enteral nutrition to early initiation of parenteral nutrition (within 48 hours of intensive care unit [ICU] admission) or later initiation (after seven days in the ICU) [51]. Although there was no difference in the overall proportion of patients who required KRT, the duration of KRT was shorter in the late-initiation compared with the early-initiation group (7 versus 10 days, respectively). Further studies are needed to adequately address the impact of nutrition on recovery of kidney function in AKI-D. (See "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription".)
Characteristics of the dialysis membrane — Two variables of dialysis membranes have been suggested to affect kidney recovery. These include membrane biocompatibility and the degree to which membranes allow the back-transport from dialysate to blood of potentially harmful waterborne molecules (ie, high-flux versus low-flux membranes). These variables are discussed here.
●Membrane biocompatibility – There are three types of dialyzer membranes, including cellulose, substituted cellulose, and synthetic noncellulose. Cellulose membranes (cuprophan or cuprophane) are considered bioincompatible, meaning that exposure to the membrane activates complement. Substituted cellulose and noncellulose membranes are more biocompatible. (See "Clinical consequences of hemodialysis membrane biocompatibility", section on 'Types of hemodialysis membranes'.)
The use of biocompatible membranes may be associated with improved rates of recovery of kidney function [52-54], although not all studies have shown this [55-57].
This is largely of historical concern since bioincompatible membranes are rarely used today (due to a reduction in cost of biocompatible membranes and due to concerns about biocompatibility). The use of biocompatible membranes has been widely adopted into contemporary practice and is recommended in the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for AKI [58,59].
●Membrane flux – Membranes can be low or high flux. High-flux membranes contain large pores that allow for enhanced permeability of larger molecules [60]. Although large pores can enhance removal of putative toxins, they can also allow the back-transport (from dialysate to blood) of potentially harmful waterborne substances (such as bacteria or endotoxin) or increased loss of potentially beneficial ones. The risk of contamination from water with bacteria or endotoxin is minimized, but may not be eradicated, by the use of highly purified dialysate water. (See "Assuring water quality for hemodialysis".)
Only a few studies have compared low- and high-flux membranes among patients with AKI-D, and most found no difference in terms of survival or recovery of kidney function [56,57,61]. Definitive studies of high-flux dialysis are available from the chronic hemodialysis population and suggest no difference in outcomes [62,63]. (See "Dialysis modality and patient outcome".)
Timing of initiation and dose of dialysis — The optimal timing of dialysis initiation for patients who experience severe AKI in the absence of immediate, life-threatening complications is not known [64,65]. Some early observational studies suggested improved kidney recovery with early versus delayed initiation of KRT [66-74]. However, results have not been consistent, and subsequent trials have not demonstrated a benefit of earlier initiation on dialysis dependence [41,75-78]. This issue is discussed elsewhere. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Timing of elective initiation'.)
High-quality evidence also suggests that a delivered dose of dialysis beyond a minimum acceptable threshold does not increase the likelihood of recovery [79,80]. These studies are discussed elsewhere. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Optimal dosing'.)
FALL IN URINE OUTPUT — A reduction in urine output is sometimes observed following initiation of hemodialysis in AKI. In a multicenter, randomized trial that compared high-intensity versus low-intensity kidney replacement therapy (KRT) among critically ill patients, higher-intensity KRT was associated with higher risk of a decline in urine output (relative risk [RR] 1.29, 95% CI 1.10-1.51) [81]. However, these differences did not associate with differences in dialysis dependence at day 28 or 60.
Both removal of excess volume and solutes retained in uremia may contribute to this response [82]. Urea may also be a surrogate marker of other substances that are removed by dialysis that stimulate urine output. (See "Residual kidney function in kidney failure".)
The clinical significance of this is unclear. A patient with dialysis-requiring AKI (AKI-D) typically has few remaining functioning nephrons [83]. The decline in urine output following dialysis may reflect an increase in tubular reabsorption in these few nephrons. Even if the function of these nephrons became impaired (perhaps because slow flow promotes obstruction by tubular debris), an adverse impact of the fall in urine output on repair of other tubules and restoration of function in nonfunctioning nephrons has not been demonstrated.
PROTECTING THE KIDNEY FROM FURTHER INJURY — It is important to prevent further injury to the kidney.
General measures to prevent ongoing kidney injury among dialysis-requiring AKI (AKI-D) patients are the same as for critically ill patients who have nondialysis-requiring AKI. (See "Possible prevention and therapy of ischemic acute tubular necrosis", section on 'Our approach'.)
Preventive measures that are specifically related to dialysis include minimizing hypotension during dialysis, avoiding aggressive ultrafiltration rates when feasible, monitoring hemodynamics closely during ultrafiltration, preventing catheter-related infection by minimizing duration of use for nontunneled catheters and optimizing infection control measures, and limiting exposure to nephrotoxins as much as possible. (See "Intradialytic hypotension in an otherwise stable patient" and "Central venous catheters for acute and chronic hemodialysis access and their management" and "Routine care and maintenance of intravenous devices".)
We also advise frequent evaluation of kidney function by assessing urine output and obtaining interdialytic measurements of serum creatinine. In some patients with prolonged acute illness, loss of muscle mass and reduced creatinine generation may lead to an overestimate of kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFR) equations. Using measurements of creatinine clearance or serum cystatin C in such patients may provide more accurate assessments of kidney function. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Discontinuation of therapy' and "Assessment of kidney function", section on 'Assessment of GFR'.)
Although indwelling urinary catheters help quantify urine output and can guide decision-making regarding dialysis, their continued use must be weighed against the risk of catheter-associated urinary tract infection. Thus, when these are used, there should be frequent ongoing assessment of their need. Other methods to assess urine output, such as bedside bladder ultrasound with or without intermittent catheterization, are preferred instead.
Medications should be frequently reviewed throughout the course of AKI. For potentially nephrotoxic drugs that are deemed necessary, frequent therapeutic drug monitoring (eg, vancomycin, aminoglycosides) should be performed and the lowest effective dose utilized [84]. Medication reviews should also include doses of new and preexisting oral medications (including potential over-the-counter nephrotoxins such as nonsteroidal anti-inflammatory drugs [NSAIDs] and herbal medications) as many of these patients will continue to be treated as outpatients while awaiting recovery.
There is little evidence to guide the appropriate use of blood pressure medications during recovery from AKI-D. The benefits of aggressive blood pressure control, most of which are long term, should be weighed against the individual risk for hypotension and its potential adverse impact on kidney recovery. In general, we apply a cautious approach to blood pressure control with the goal of minimizing the risk for hypotension. The decision to continue or discontinue angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) during recovery from AKI-D has not been directly addressed in existing clinical trials. However, concerns about worsening hypotension, hyperkalemia, blunting of renal autoregulation, and masking of potential recovery generally favor discontinuation of these agents while recovery is still being considered. Although one observational study reported that continued use of ACE inhibitors or ARBs following AKI was associated with increases in hospitalizations for kidney-related complications including AKI and hyperkalemia [85], subsequent studies did not observe this association [86,87]. Notably, these studies primarily included patients with nondialysis-requiring AKI, in whom such complications would generally occur less frequently than in patients with more severe AKI. Further studies in this area are needed. (See "Perioperative medication management", section on 'ACE inhibitors and angiotensin II receptor blockers'.)
The necessity of nephrotoxic procedures (eg, iodinated contrast exposure) should also be carefully weighed against the potential risk for further injury. The timing of procedures should also be considered, if possible; delaying the exposure to contrast for nonurgent indications or procedures until recovery of kidney function may be of benefit among patients who are considered likely to recover. (See "Prevention of contrast-associated acute kidney injury related to angiography".)
As noted above, biocompatible dialysis membranes should be used, if available. We generally use high-flux membranes, although low-flux membranes should be used if high-quality water is not available. (See 'Characteristics of the dialysis membrane' above.)
It is important to monitor closely for kidney recovery so that kidney replacement therapy (KRT) may be discontinued. This is discussed elsewhere:
●(See "Acute hemodialysis prescription", section on 'Management during recovery of kidney function'.)
Recommendations regarding dialysis modality, timing and dose of dialysis, anticoagulation, and optimal nutrition are all discussed elsewhere:
●(See "Anticoagulation for continuous kidney replacement therapy".)
●(See "Overview of the management of acute kidney injury (AKI) in adults".)
●(See "Anticoagulation for the hemodialysis procedure".)
SUMMARY AND RECOMMENDATIONS
●Dialysis-related factors – Dialysis–related factors that may impair recovery from acute kidney injury (AKI) include intradialytic hypotension; increased risk of sepsis, particularly related to vascular access; and challenges associated with appropriate dosing of medication. Issues related to nutritional factors and characteristics of the dialysis membrane may also play a role. (See 'Dialysis-related factors' above.)
●Nondialysis factors – Nondialysis-related measures to prevent ongoing kidney injury among dialysis-requiring AKI (AKI-D) patients are generally the same as for critically ill patients who have nondialysis-requiring AKI. (See 'Protecting the kidney from further injury' above and "Possible prevention and therapy of ischemic acute tubular necrosis", section on 'Our approach'.)
●Preventive measures – Preventive measures that are specifically related to dialysis include minimizing hypotension during dialysis, preventing catheter-related infection, limiting exposure to nephrotoxins, and using biocompatible high-flux membranes. (See 'Protecting the kidney from further injury' above and 'Characteristics of the dialysis membrane' above and "Intradialytic hypotension in an otherwise stable patient" and "Routine care and maintenance of intravenous devices".)
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