The management of acute kidney injury

Contact: Audrey Hu audrey.hu@wecistanche.com

Abstract

In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury. The guideline was derived from the evidence available through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing acute kidney diseases. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating Acute Kidney Injury; review key relevant literature published since the 2012 KDIGO acute kidney diseases guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO acute kidney diseases guideline, and outline research needed to improve acute kidney diseases management. Here, we present the findings of this conference and describe key areas that future guidelines may address.

Keywords： acute kidney disease; acute kidney injury; fluid management; nephrotoxicity; renal replacement therapy; risk stratification

NOMENCLATURE AND DIAGNOSTIC CRITERIA

Acute Kidney Injury (acute kidney injury) -related definitions

Acute Kidney Injury and chronic kidney disease are increasingly recognized as related entities representing a continuum of disease. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) 2002 guideline and the 2012 KDIGO acute kidney diseases guideline defined chronic kidney disease as measured or estimated glomerular filtration rate (GFR) <60 ml/min per 1.73 m2, or the presence of markers of kidney damage (e.g., albuminuria) for >90 days.1 The 2012 KDIGO guideline defined Acute Kidney Injury as an abrupt decrease in kidney function occurring over 7 days or fewer (Table 1).1 To complete the continuum, the 2012 guideline proposed the term acute kidney diseases and disorders (acute kidney disease) to define conditions of impaired kidney function not meeting the criteria for either Acute Kidney Injury or chronic kidney disease but having adverse outcomes and requiring clinical care. However, consensus on the exact criteria and indicators of severity is urgently needed.

Because the diagnosis of Acute Kidney Injury should be tied to management decisions, and because changing disease definitions may have major implications for disease epidemiology, the case for revising the 2012 KDIGO definition of acute kidney injury should be strong before changes are proposed. Furthermore, in the context of an acute kidney injury guideline revision, several classification systems in addition to the stages of acute kidney diseases should be rigorously defined. These relate to the distinctions among persistent, transient, relapsing, and recovered acute kidney injury; various etiologies of acute kidney injury; and community-onset versus hospital-onset acute kidney injury. In addition, there is emerging acute kidney injury, or should be incorporated into the acute kidney injury definition. Finally, the future guideline should use nomenclature that is precise and patient-centered.

The clinical importance of acute kidney disease needs to be further assessed. Retrospective cohort data based only on changes in serum creatinine values and with limited clinical context suggest a relevance for acute kidney disease: the population of patients who meet laboratory criteria for acute kidney disease but not chronic kidney disease or acute kidney injury is relatively large, and these individuals have increased risks of the incident and progressive chronic kidney disease, kidney failure (formally referred to as “end-stage kidney disease”), and death,28 confirming the need to better define and classify chronic kidney diseases. Furthermore, a revised definition and classification of acute kidney disease could be better harmonized with both the definitions and classifications of acute kidney injury and chronic kidney disease and tie to clinical management. As in adults, the acute kidney injury/acute kidney disease/chronic kidney disease spectrum should be unified in children, and definitions should be the same for children and adults. Special consideration in children, as well as in adults with low muscle mass is a reduced serum creatinine concentration, which may impact Acute Kidney Injury diagnosis.

The assessment of renal recovery is still controversial, and its definition is essential given the implications for patients and clinicians. Issues related to assessment of recovery include changes in creatinine generation due to reduction in muscle mass, among others.

Advances in the Diagnosis of Acute Kidney Injury

Serum creatinine and urine output continue to be the foundational measures for Acute Kidney Injury diagnosis even though their limitations are well known. In the future, kidney damage biomarkers, biopsy, and imaging may be useful for staging acute kidney injury, classification of cause, prognosis, and treatment. However, currently, there is insufficient information about any of these measures to warrant addition to the acute kidney injury definition. Given that the global availability of novel biomarkers is limited, incorporating them into definitions will be challenging.

Measurements of real-time or kinetic GFR are research tools at present, and more evidence is needed regarding their clinical applicability. Both urine output and serum creatinine level should continue to be used29; ideally, the new Acute Kidney Injury guideline would provide further clarification as to the role of these measurements. If possible, both should be ascertained. However, if serum creatinine measurements are not immediately available, urine output criteria should be used. It remains unclear how to best determine baseline kidney function. What constitutes a baseline serum creatinine level is controversial and inconsistently defined. It would be ideal to have prior serum creatinine or GFR measurements widely available through electronic medical records, but this is not current practice in many parts of the world. Prior serum creatinine or GFR measures may also further elucidate the risk of acute kidney injury in patients considered at high risk on the basis of either comorbidity or an intervention. There is controversy about whether an acute decrease in serum creatinine level indicates Acute Kidney Injury that has already occurred, and more research is needed in this area. For example, small declines in serum creatinine levels need to be interpreted with caution because they may be the result of acute changes creatinine levels should be measured during follow-up as necessary for clinical management and care transitions (e.g., transfer to and from intensive care) and for determining changes in acute kidney injury staging and classification (acute kidney injury vs. acute kidney disease), including the onset of chronic kidney disease (chronic kidney disease) at 90 days.

How urine output should be evaluated is also an area that needs further investigation to avoid variability in reporting of acute kidney injury incidence (i.e., use of actual or ideal body weight, strict time period vs. time-averaged values).30 Future guidelines should address how differences in body composition (overweight, fluid overload) affect the interpretation of urine output, and whether these differences need to be considered in regard to the thresholds for acute kidney injury. Similarly, fluid status should be considered when evaluating acute kidney injury. Fluid overload is associated with increased mortality and acute kidney injury, and it may impact the diagnosis of acute kidney injury through its impact on the volume of distribution of serum creatinine. Although there are research methods to define fluid overload, these are not routinely used in clinical practice, and it is unclear whether there is sufficient evidence to define a clinical threshold for fluid overload. In the next acute kidney injury guideline, fluid overload should be defined operationally through a rigorous literature review.

ACUTE KIDNEY INJURY RISK STRATIFICATION AND ASSESSMENT

Risk stratification

In community and hospital settings, risk stratification of patients using a combination of baseline risks and acute exposures is important.31 In the future, risk stratification could incorporate various clinical contexts: geographic region, onset in the community or hospital settings, and location within hospitals. Although the 2012 guideline discussed risk models and clinical scores, these were limited to models for cardiothoracic surgery, contrast exposure, and aminoglycoside administration. Many other clinical scenarios and contexts, such as sepsis and cardiac failure, require guidance for risk assessment. In clinical practice, risk models may be tailored for location and context. Multicenter studies are needed for externally validating models as well as standardization and correlation with outcomes.

Furthermore, since 2012, biomarkers for Acute Kidney Injury risk stratification have been approved by the US Food and Drug Administration (https://www.accessdata.fda.gov/cdrh_docs/reviews/ DEN130031.pdf) and integrated into recent guideline recommendations for cardiac surgery.32

Determining cause and prognosis

Determining the etiology of Acute Kidney Injury is essential for management; however, this can be difficult, especially in the presence of multifactorial mechanisms. Newer developments related to monitoring and evaluating risk progression include e-alert systems, machine-learning algorithms, and artificial intelligence for Acute Kidney Injury recognition and monitoring,20,33–36 as well as models based upon the renal angina index,37,38 furosemide stress test (FST),39 or biomarkers.40–43 In revisiting the guideline for acute kidney injury, the severity of acute kidney injury should be based not only upon serum creatinine elevation and urine output but also upon duration, possibly with the inclusion of biomarkers. The need to increase attention for persistent (>48 hours) acute kidney injury should also be considered.44

The 2012 KDIGO guideline suggests performing a kidney biopsy when the cause of acute kidney injury is unclear. Potential benefits for biopsy in acute kidney injury are controversial and further research is needed.45 Since the 2012 guideline, which recommended ultrasound for assessing kidney size and the presence of an obstruction, new imaging techniques have become available, such as contrast-enhanced ultrasound, doppler ultrasound, and blood oxygenation level-dependent functional magnetic resonance imaging.46–48 The role of these techniques in changing outcomes of Acute Kidney Injury is yet to be determined.

The 2012 KDIGO guideline-recommended urine sediment analysis for differential diagnosis in patients with acute kidney injury, especially when the glomerular disease is expected. Meeting participants noted that urine sediment analysis is not routinely performed in many centers despite its potential role in the workup of acute kidney injury.49,50 Additionally, the value of urine biochemistry analysis has been challenged, especially in sepsis.51 The FST may be useful for identifying patients with acute kidney injury who are likely to have progressive disease and need dialysis.52 There is also evidence that the FST is useful in predicting delayed graft function following deceased donor kidney transplantation.53 This test was not included in the 2012 guideline but should now be considered. Importantly, unregulated diagnostics tests such as FST or urine sediment analysis require careful standardization and quality control. Their introduction into clinical practice should include local evaluation for correct performance and interpretation.

The traditional approach to classifying acute kidney injury as pre-renal, renal, and post-renal is still found in many medical textbooks. A different framework is needed because these terms are considered unhelpful, especially the term pre-renal, which is often misinterpreted as “hypovolemic” and may encourage indiscriminate fluid administration. For classifying acute kidney injury, it may be more beneficial to distinguish between conditions that reduce glomerular function, conditions that result in injury of tubules and/or glomeruli, and conditions that do both. Endpoints for clinical trials and quality improvement initiatives for Acute Kidney Injury include mortality, new-onset or progression of chronic kidney disease, and dialysis dependency. Additional endpoints are needed for both clinical management and research, and these might include recovery of function, maximum changes in creatinine concentration, stage of acute kidney injury / acute kidney disease, impact on renal reserve, and patient experience. Additionally, there is a need to better define renal recovery and its functional (filtration, tubular, endocrine) and anatomic/structural dimensions.

Follow-up

Increased risks for mortality, cardiovascular events, and progression of kidney disease are well-documented outcomes of acute kidney injury.28,54–56 However, not everyone with acute kidney injury has a poor outcome, and predictors of poor outcomes have been identified.57 Follow-up recommendations (Figure 1)31 have been proposed that could be integrated into a KDIGO guideline revision. Although it has been suggested that patients be screened at hospital discharge or seen within 1 month of acute kidney injury diagnosis,58 there is no consensus on the optimal strategy and duration of follow-up to improve short- and long-term outcomes.

FLUID MANAGEMENT AND HEMODYNAMIC SUPPORT

Timing of fluid administration

Ensuring adequate hydration and volume status is essential in preventing and treating acute kidney injury. Oral or i.v. fluid may be administered depending on the local environment and clinical context. The administration of i.v. fluids should be guided by hemodynamic assessment for specific indications and contraindications. When deciding on fluid therapy, consideration for the clinical context and history, including the timing of the insult, is critical. Table 3 lists clinical contexts in which indications for fluid administration should be balanced against potential coexisting conditions that require a more cautious approach. Because both the physiological response to fluids and the underlying condition related to acute kidney injury are dynamic over time, fluid administration should be based on the repeated assessment of overall fluid and hemodynamic status and dynamic tests of fluid responsiveness.59,60. There continues to be concern about excessive fluid administration for hypotension, and earlier use of vasoactive medications may be appropriate for some patients.61,62 The effect of these strategies on kidney function is not clearly defined and is likely to be context-specific.63 Ongoing major multicenter RCTs examining kidney endpoints are evaluating fluid administration and vasoactive medications, and their results are likely to impact Acute Kidney Injury treatment recommendations.

Methods of fluid administration

Significant new evidence from several large multicenter RCTs regarding the use of protocolized goal-directed fluid therapy in early septic shock has suggested a lack of benefits for survival and kidney outcome.64–66 However, there is some evidence to suggest that goal-directed protocols have benefits in perioperative patients.67,68 Therefore, recommendations regarding goal-directed fluid therapy for preventing or treating acute kidney injury may emerge to become more context-specific. Additionally, clinical fluid therapy targets have evolved to include more dynamic indices, including the passive leg-raising test, pulse/stroke volume variation, and parameters derived from ultrasound. However, there is limited evidence that specific physiological targets for fluid therapy improve kidney outcomes.

Composition of i.v. fluid preparations

Crystalloids.—Evidence of biochemical abnormalities and adverse clinical outcomes associated with 0.9% saline compared with more physiological crystalloids (e.g., lactated Ringer’s) has continued to accumulate since 2012.11,12 Results from two large ongoing multicenter RCTs (NCT02875873, NCT02721654) are awaited. This evidence will require careful evaluation to provide the community with a new consensus regarding the magnitude of risks associated with 0.9% saline in acute illness and surgery, including considerations for resource-limited settings in which alternatives may be limited. perioperative patients remain controversial, and this question is being examined in ongoing trials.Albumin.—In RCTs, the use of albumin (including hyper-oncotic solutions) has not been shown to be harmful to kidneys or other outcomes.71,72 However, clear evidence of benefit is also lacking, and any benefits may be limited to specific patient populations.73–75.

Fluid removal

Physiological and epidemiologic evidence indicates that volume overload and venous congestion have adverse effects on kidney function and outcomes in both acute and chronic illnesses.76–78 In children, there is evidence that >10%–15% fluid overload by body weight is associated with adverse outcomes.79,80 However, the method for determining fluid overload and the threshold for clinically significant fluid overload in adults are not well defined, nor is the precise role of timing of fluid removal on kidney function and other outcomes. Therefore, there is a need to develop a consensus around methods and thresholds for fluid overload evaluation in adults and to establish recommendations for its management (Table 2).

NEPHROTOXIC AGENTS AND DRUGS THAT AFFECT KIDNEY FUNCTION

The use of drugs associated with kidney injury or dysfunction is common both in the hospital setting and in the community for patients with chronic illnesses such as hypertension, congestive heart failure, diabetes mellitus, cancer, and chronic kidney disease. These drugs are often referred to as “nephrotoxic,” although many of them lead to kidney dysfunction without direct glomerular or tubular cell damage. Furthermore, some drugs that may cause a rise in serum creatinine are actually reno-protective and associated with improved outcomes (i.e., angiotensin-converting enzyme inhibitors or sodium-glucose co-transporter-2 inhibitors81 in diabetic nephropathy). Although it would be ideal to propose a simple yet inclusive term to encompass the various mechanisms by which drugs interface with the kidney, meeting participants were unable to identify one. Thus, here the term “nephrotoxic drugs” is retained for consistency with the literature. A new classification should also encompass drugs that are not directly harmful to kidney function but are eliminated by the renal route, and where there is concern about harm from the accumulation of parent drug or metabolites in the setting of acute kidney injury and chronic kidney disease. Similarly, failure to increase drug doses and intervals in renal recovery or with enhanced elimination via extracorporeal clearance may lead to therapeutic failure.82

In the past 10 years, significant progress has been made regarding susceptibility, management, and preventive strategies to avoid or ameliorate drug- and drug combination– associated kidney injury and dysfunction more broadly. Overarching nephrotoxic medication management considerations are as follows:

• Patients should receive potentially nephrotoxic medications only if needed and only for as long as needed.

• Potentially nephrotoxic agents should not be withheld in life-threatening conditions, owing to concern for chronic kidney disease, including i.v. contrast.

• Kidney function must be monitored in patients who are exposed to agents that are associated with kidney injury or dysfunction, to limit the risk and progression of chronic kidney disease.

• Patients and clinicians need appropriate and effective education as to the potential for kidney injury and dysfunction from nephrotoxic agents.

Classifying drugs that affect kidney function and/or are nephrotoxic

There are multiple mechanisms by which drugs affect the kidney. They are summarized in 2 major categories: systemic or renal/glomerular hemodynamic effects (i.e., kidney dysfunction); and tubular or structural damage (i.e., kidney injury). Kidney dysfunction can result from drugs that lead to systemic hypotension (e.g., systemic arterial vasodilation) and/or altered intraglomerular hemodynamics (e.g., afferent arteriole constriction, efferent arteriole dilation). As a result, renal perfusion pressure is decreased, and if the decrease is sustained or severe, it can lead to ischemic injury. In comparison, drug-associated kidney injury is characterized by glomerular or tubular cell injury triggered by filtered toxins, tubular obstruction, endothelial dysfunction, or an allergic reaction.83–85 Important to note is that a given drug may lead to both dysfunction and injury.

A useful framework for classifying the mechanisms of drug-induced kidney injury or dysfunction is depicted in a 2x2 table to classify functional, structural, and combined functional/structural chronic kidney disease 86 (Figure 2). Drugs can affect the kidney by each of these mechanisms, and the figure depicts susceptibilities for chronic kidney disease, as well as accelerants to develop dysfunction or injury and transition to dysfunction and injury. An important aspect of the framework is the consideration of risk-mitigation strategies. Currently, there is sufficient evidence to classify drugs that affect kidney function or are nephrotoxic, in a clinically useful way.87,88

Preventing and mitigating drug-associated chronic kidney disease

A number of strategies have emerged for preventing or mitigating drug-associated kidney injury or dysfunction. The most important of these are drug stewardship,21,89,90 with a primary goal of balancing the changing risks and benefits of drug utilization and dosing in chronic kidney disease /acute kidney disease (Table 4).82 Specifically, it is critical to balance the risk of toxicity caused by excessive doses or drug/metabolite accumulation in acute kidney injury/acute kidney disease versus the risk of therapeutic failure caused by either overly conservative drug avoidance or under-dosing, or the risk of failing to adapt to renal recovery or use of renal replacement therapy (RRT).

Recent literature has demonstrated that certain drug combinations and overall drug burden are associated with chronic kidney disease 91. These include the “triple whammy” of renin-angiotensin system inhibitors, diuretics, and nonsteroidal anti-inflammatory drugs, and an increased acute kidney injury risk when patients receive 3 or more nephrotoxic drugs daily.92 A single-center has utilized electronic health records to identify children exposed to 3 or more nephrotoxic drugs, and the approach has led to a sustained decrease in the incidence of acute kidney injury.

Preventing and managing contrast-associated chronic kidney disease

The only nephrotoxic agent addressed in any detail by the 2012 KDIGO chronic kidney disease guideline was iodinated radiocontrast media.1 The 2012 guideline included several recommendations to prevent contrast-induced chronic kidney disease, including the use of volume expansion with sodium bicarbonate solutions and oral N-acetylcysteine. Results of the Prevention of Serious Adverse Events Following Angiography (PRESERVE) and POSEIDON trials demonstrated the lack of efficacy of these interventions (and instead found improvement using a personalized approach targeting cardiac filling pressures in POSEIDON).93,94 Furthermore, recent evidence suggests that the risks associated with i.v. contrast is far less with modern agents and practice patterns, and significant kidney injury is unusual in patients with normal or mildly reduced baseline kidney function.95 I.v. contrast should not be withheld owing to concern for acute kidney injury in life-threatening conditions in which the information gained from the contrast study could have important therapeutic implications.

RENAL REPLACEMENT THERAPY

RRT terminology and initiation

In recent years, the suggestion has been made that the English term “renal” should be replaced by “kidney,” because the latter is more familiar to most English speakers. Additionally, the term “replacement” may not be sufficient, and terms such as “support” or “partial replacement” may be more accurate. The implications of changes in nomenclature are not insignificant. Additionally, the distinction between kidney versus renal does not apply in all languages. Accordingly, KDIGO has convened a separate Nomenclature Consensus Conference for the purpose of recommending nomenclature consistent with guidelines for acute and chronic kidney disease.96 Above all, patients should be the focus of all communication and care. Whenever possible, all decisions about treatment should be shared with patients, their families, and/or next of kin, and if required, all members of the end-of-life care multidisciplinary team. All communication with patients and their supporting families/friends should be provided in simple lay language at regular intervals, with the awareness that patients may be traumatized. “Life support,” “kidney machine,” or similar words are preferred to the term RRT. If RRT becomes permanent, and the patient enters the chronic dialysis pathway, all relevant medical or nursing personnel should change their language to specify the type of RRT (transplant, hemodialysis, or peritoneal dialysis). planning for and deciding to initiate RRT.39,52,109,110 In determining whether or not to start RRT, risk of complications, global prognosis, the potential for recovery, and patient preferences should be considered (Figure 3). Although some regions of the globe have challenges and constraints in providing universal access to RRT,111 we recommend a similar approach be undertaken for considering for whom and when to start RRT in all regions112–114. Additionally, a similar approach should be undertaken in both intensive care unit and non–intensive care unit settings.

Providing RRT

Although the timing of RRT initiation is controversial, the provision of RRT itself has become fairly well established. Patients with chronic kidney disease requiring RRT have an evolving clinical status and should be supported by the appropriate and available modality. Modality choice should also be tailored to patient clinical status. As suggested in the 2012 KDIGO guideline, in hemodynamically unstable patients, continuous RRT, rather than intermittent hemodialysis, is more physiologically appropriate, but RCTs have not demonstrated better outcomes with continuous RRT.1 Both continuous and intermittent RRT can lead to changes in intracranial pressure, but the risk is higher with intermittent RRT. The selection of modalities should be considered in the context of available resources and the expertise of personnel.

An uncuffed non-tunneled dialysis catheter of appropriate length and gauge should be used to initiate RRT in chronic kidney disease patients. In patients with expected prolonged indications for RRT, a cuffed catheter can be considered.115 The first choice for the site is the right jugular vein or femoral vein, although the femoral site is inferior in patients with increased body mass. The next choice would be the left jugular vein followed by the subclavian vein. Anticoagulation type should be selected based on local resources and expertise of personnel. The recommendation from 2012 to use regional citrate anticoagulation for continuous RRT in patients who do not have a contraindication remains supported by existing data.116–118 Delivery of RRT must reach the goals of electrolyte, acid-base, solute, and fluid balance for each specific patient.119 When using intermittent or extended RRT, a Kt/V of at least 1.2 per treatment 3 times a week should be delivered.120 For peritoneal dialysis, future studies should focus on dosing in chronic kidney disease, although currently, we suggest a dose of 0.3 Kt/V per session. An effluent volume of 20–25 ml/kg per h should be delivered when continuous RRT is used. This will sometimes require a higher prescription of effluent volume.121,122 The rate of fluid removal for a given patient with fluid overload is controversial,123,124, and more research is needed. Methods to better assess fluid management goals during RRT would also be valuable. Finally, RRT should be discontinued when kidney function has recovered or when RRT becomes inconsistent with shared care goals. Modality transition from continuous RRT to intermittent hemodialysis in intensive care unit patients should be considered when vasopressor support has been stopped, intracranial hypertension has resolved, and positive fluid balance can be controlled by intermittent hemodialysis.

RRT in the context of multi-organ support

unresolved: the optimal approach to patient selection, techniques, and timing/indications; circuit integration; and monitoring for ECLS and concomitant blood-purification techniques. Several observational studies on this theme warrant analysis and interpretation.125–131. Decisions regarding how to combine RRT with ECLS devices will depend on local expertise, technology, and human resources. Such combined treatment should be based on a multidisciplinary approach to patient care and shared decision of acute kidney injury. More studies are needed to define the best strategy for training and practice.

Although different RRT modalities can be used to support patients during ECLS, and comparative studies are not available, because of hemodynamic status, continuous RRT is more appropriate in this setting. It would be useful to develop a registry focused on

patients receiving ECLS-RRT, to understand the epidemiology, technology, indications, and complications associated with current practice. There is no clear evidence that usual RRT indications should vary according to the presence or absence of an ECMO/ECCO2R circuit. Nonetheless, patients for whom ECMO or ECCO2R is required are very sensitive to fluid overload. Therefore, in patients with versus without ECMO/ECCO2R, earlier RRT may be required for preventing and managing fluid overload. A registry of patients combining ECMO/ECCO2R and RRT could improve understanding of current practice for initiating RRT in patients (adults and children) with ECMO/ECCO2R and fluid management. Respiratory dialysis (ECCO2R and ECMO) with modified dialysis solutions are currently limited to in vitro and experimental studies,132–134 and research focused on this technical aspect is needed.

The anticoagulation of RRT circuits when ECMO/ECCO2R is already running is not standardized. The administration of heparin may depend on patient factors (e.g., risk of bleeding), circuit set-up (e.g., connection to the patient or to ECMO), and institutional protocols.128,130,135–141 It is possible to have RRT circuits without dedicated heparin in this setting unless excessively frequent clotting is observed. Studies are needed to compare different anticoagulation strategies in this setting. Citrate anticoagulation during RRT added to ECMO/ECCO2R is possible.139,140 Its feasibility and performance compared with other forms of anticoagulation remain untested, and thus comparative studies of citrate anticoagulation are recommended.

RRT long-term outcomes and follow-up

Choice of RRT modality and impact on recovery.—The selection of the RRT modality does not appear to have a major impact on the recovery of kidney function.141–143 Selection of modality of RRT should therefore be based on shared decision acute kidney injury, local expertise, logistic factors, and patient characteristics. Estimated GFR in conjunction with major adverse kidney events has been used for medium- and long-term assessment but has several limitations. There is uncertainty about the best way to measure renal recovery after RRT in both the short- and medium-term. However, proteinuria is associated with worse long-term outcomes and is easy to measure.

Assessment of kidney function for renal recovery

Assessment of kidney function for renal recovery.—In addition to the development of chronic kidney disease, patient-centered outcomes (quality of life, functional recovery), along with patient experience after chronic kidney disease, should be a priority and need to be assessed. Post-chronic kidney disease proteinuria is associated with future loss of kidney function and is regarded as a valuable risk-stratification tool in the post-acute kidney injury period.144–14

Optimal follow-up for chronic kidney disease patients following RRT

The shared decision of acute kidney injury and communication among caregivers, the patient, and family members are crucial to patient recovery. Patients recovering from critical illness and chronic kidney disease are often discharged to rehabilitation/skilled nursing facilities and need close monitoring to ensure adequate overall recovery to a baseline state of health and well-being. Such patients should receive multidisciplinary, recovery-focused care. Patients with acute kidney injury who continue to require RRT at hospital discharge often receive hemodialysis in outpatient dialysis facilities. Patients with congestive heart failure are less likely to recover kidney function.147 Higher ultrafiltration rates and more intradialytic hypotensive episodes are associated with a higher risk of non-recovery of kidney function.148,149 To assess for renal recovery, hemodynamic status, intravascular volume, and urine output during dialysis should be carefully monitored.

Quality indicators for acute RRT

The importance of measuring and monitoring the quality of acute RRT provided to critically ill patients with chronic kidney disease, including the optimal “benchmarking” for acute RRT programs, is receiving great attention.119,150 Quality of acute RRT should be monitored to ensure the effective and safe delivery of care.151 At a minimum, institutions, and programs providing RRT should integrate, monitor, and report quality and outcome indicators across all forms of acute RRT therapies.31 These outcome measures should comprise a variety of metrics that incorporate patient survival, patient-centered acute RRT outcomes, safety, chronic kidney disease survivor–related outcomes, and patient experience. Quality indicators should include shared goals that are patient- and clinically centered.

CONCLUSIONS

Although much of the 2012 KDIGO chronic kidney disease guideline remains state of the art, advances over the past decade have improved our understanding of best practices. Many of these advances are widely accepted (e.g., nephrotoxic medication stewardship, shared decision acute kidney injury for RRT, but others are more controversial (Table 5). Although some centers and specific programs have embraced new technologies and ways of thinking, others have taken a more conservative, or “wait-and-see” approach. Even among conference participants, there was a lack of unanimity for various perspectives, and obvious practice variation continues to exist, even among experts. Perhaps more than any new trial or discovery, this fact provides ample rationale for revisiting the acute kidney injury guideline in the near future.

ACKNOWLEDGMENTS

This conference was sponsored by KDIGO and was in part supported by unrestricted educational grants from Akebia Therapeutics, AM-Pharma, Angion, AstraZeneca, Astute Medical, Atox Bio, Baxter, bioMérieux, BioPorto, Boehringer Ingelheim, CytoSorbents, Edwards, Fresenius Medical Care, GE Healthcare, Grifols, Kyowa Kirin, Novartis, NxStage, Outset, and Potrero.

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