Elsevier

Seminars in Nephrology

Volume 39, Issue 5, September 2019, Pages 431-441
Seminars in Nephrology

Early Recognition of Persistent Acute Kidney Injury

https://doi.org/10.1016/j.semnephrol.2019.06.003Get rights and content

Summary: Despite the vast amount of literature dedicated to acute kidney injury (AKI) and its clinical consequences, short-term renal recovery has been relatively neglected. Recent studies have suggested that timing of renal recovery is associated with longer-term risk of death, residual renal function, and end-stage renal failure risk. In addition, longer AKI duration is associated with an increased requirement for renal replacement therapy. Comorbidities, especially renal and cardiovascular, severity of AKI, criteria to reach AKI diagnosis, as well as severity of critical illness have been associated with longer AKI duration, and, more specifically, risk of persistent renal dysfunction. Because predicting short-term renal recovery is clinically relevant, several tests, imaging, and biomarkers have been tested in a way to predict the course of AKI and chances for early renal recovery. In this review, the definition of recovery, consequences of persistent AKI, and tools proposed to predict recovery are described. The performance of these tools and their limits are discussed.

Section snippets

RENAL RECOVERY AND TIME TO RECOVERY: DEFINITIONS AND PROGNOSTIC IMPACT

The renal recovery epidemiology description is limited by significant heterogeneity in the available literature regarding the population studied, the definition used (RRT independency, decrease in one AKI severity stage, complete disappearance of AKI criteria, or return to baseline creatinine concentration) or the timing of its assessment (in the intensive care unit [ICU] or at hospital discharge, or at the 3-month time point required to diagnose chronic kidney disease [CKD]). In a recent large

URINARY INDICES

Historically, nonobstructive AKI related to mere hypoperfusion (prerenal AKI) and organic renal injury (intrinsic AKI) were differentiated and the ability of the tubule to concentrate urine was assessed.24, 25 This assessment was performed using urinary indices showing the ability of the tubule to reabsorb sodium and water (fractional excretion of sodium, natriuresis, fractional excretion of urea, urinary urea/creatinine ratio).24, 25 Most of these indices were validated in studies in which the

RENAL DOPPLER

Ultrasonography (US) is performed routinely to assess the morphology of kidneys, the collecting system, and the renal arteries and veins.37 Doppler-based renal resistive index (RI), the so-called Pourcelot index, and contrast-enhanced US (CEUS) are tools derived from Doppler to assess renal perfusion and predict AKI in ICU patients.38, 39

Renal RI measurement is rapid, easy to perform, and easy to learn. A half-day course on renal Doppler allowed inexperienced junior physicians to assess renal

PREDICTIVE MODELS

Only few predictive clinical models have been developed and tested specifically to assess the probability of renal recovery. None of them has been assessed and validated adequately.

The “renal angina index” was developed and validated to assess AKI risk at day 3, mainly in pediatric settings, and is the most studied model.65, 66 This score is the result of serum creatinine or fluid overload increase multiplied by contextual variables (organ or stem cell transplantation) or organ support.65, 66

BIOMARKERS

A biomarker is an indicator than can be quantified or evaluated objectively to indicate the status of a biological process or condition. Most AKI biomarkers are biochemical parameters that have been developed to detect early onset of AKI. However, their use has ranged from early AKI detection to assessment of chances of early renal recovery. Ideally, AKI biomarkers should have high sensitivity and specificity for kidney injury in the presence of concomitant injury involving other organs and

LIMITS OF CURRENT KNOWLEDGE

Most of the studies performed to date have been limited by imperfect definitions of renal recovery, various influences of the time chosen to define transient/persistent AKI, and gold standard. The threshold of the serum creatinine level to define recovery is likely to influence the rate of recovery, as is rate of approximate renal dysfunction or of unknown pre-existing renal dysfunction.20 Moreover, patients without available baseline serum creatinine concentrations differ significantly from

CONCLUSIONS

Although the definition of renal recovery has been standardized and its clinical relevancy has been shown, several uncertainties remain. First, the exact rate of recovery, accounting for competing risk, is unknown, as well as the optimal definition to conclude renal recovery. Moreover, although predicting short-term recovery might help in optimizing patient management and anticipate outcome, available imaging tests, biomarkers, and scores have not yet been validated and, at best, were found to

REFERENCES (90)

  • K Fischer et al.

    High-resolution renal perfusion mapping using contrast-enhanced ultrasonography in ischemia-reperfusion injury monitors changes in renal microperfusion

    Kidney Int

    (2016)
  • RK Basu et al.

    Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children

    Kidney Int

    (2014)
  • RK Basu et al.

    Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study

    Lancet Child Adolesc Health

    (2018)
  • K Doi et al.

    Mild elevation of urinary biomarkers in prerenal acute kidney injury

    Kidney Int

    (2012)
  • KA Gharaibeh et al.

    Cystatin C predicts renal recovery earlier than creatinine among patients with acute kidney injury

    Kidney Int Rep

    (2018)
  • C Ronco et al.

    Recovery after acute kidney injury: a new prognostic dimension of the syndrome

    Am J Respir Crit Care Med

    (2017)
  • LS Chawla et al.

    Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

    Nat Rev Nephrol

    (2017)
  • JA Kellum et al.

    Recovery after acute kidney injury

    Am J Respir Crit Care Med

    (2017)
  • S Perinel et al.

    Transient and persistent acute kidney injury and the risk of hospital mortality in critically ill patients: results of a multicenter cohort study

    Crit Care Med

    (2015)
  • AS Truche et al.

    ICU survival and need of renal replacement therapy with respect to AKI duration in critically ill patients

    Ann Intensive Care

    (2018)
  • S Uchino et al.

    Transient azotaemia is associated with a high risk of death in hospitalized patients

    Nephrol Dial Transplant

    (2010)
  • S Gaudry et al.

    Initiation strategies for renal-replacement therapy in the intensive care unit

    N Engl J Med

    (2016)
  • SD Barbar et al.

    Timing of renal-replacement therapy in patients with acute kidney injury and sepsis

    N Engl J Med

    (2018)
  • A Zarbock et al.

    Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial

    JAMA

    (2016)
  • JA Kellum et al.

    Kidney Disease: Improving Global Outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury

    Kidney Int Suppl

    (2012)
  • J Cerdá et al.

    Promoting kidney function recovery in patients with AKI requiring RRT

    Clin J Am Soc Nephrol

    (2015)
  • C Ichai et al.

    Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies)

    Ann Intensive Care

    (2016)
  • K Doi et al.

    Reduced production of creatinine limits its use as marker of kidney injury in sepsis

    J Am Soc Nephrol

    (2009)
  • M Schetz et al.

    The impact of using estimated GFR versus creatinine clearance on the evaluation of recovery from acute kidney injury in the ICU

    Intensive Care Med

    (2014)
  • JR Prowle et al.

    Serum creatinine changes associated with critical illness and detection of persistent renal dysfunction after AKI

    Clin J Am Soc Nephrol

    (2014)
  • M Schetz et al.

    Recovery from AKI in the critically ill: potential confounders in the evaluation

    Intensive Care Med

    (2015)
  • MH Bernardi et al.

    Serum creatinine back-estimation in cardiac surgery patients: misclassification of AKI using existing formulae and a data-driven model

    Clin J Am Soc Nephrol

    (2016)
  • C Ronco et al.

    Subclinical AKI is still AKI

    Crit Care

    (2012)
  • C Ronco et al.

    Understanding renal functional reserve

    Intensive Care Med

    (2017)
  • CH Espinel

    The FENa test. Use in the differential diagnosis of acute renal failure

    JAMA

    (1976)
  • TR Miller et al.

    Urinary diagnostic indices in acute renal failure: a prospective study

    Ann Intern Med

    (1978)
  • M Darmon et al.

    Diagnostic performance of fractional excretion of urea in the evaluation of critically ill patients with acute kidney injury: a multicenter cohort study

    Crit Care

    (2011)
  • B Pons et al.

    Diagnostic accuracy of early urinary index changes in differentiating transient from persistent acute kidney injury in critically ill patients: multicenter cohort study

    Crit Care

    (2013)
  • J Vanmassenhove et al.

    Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis

    Crit Care

    (2013)
  • A Dewitte et al.

    Kinetic eGFR and novel AKI biomarkers to predict renal recovery

    Clin J Am Soc Nephrol

    (2015)
  • R Bellomo et al.

    Pre-renal azotemia: a flawed paradigm in critically ill septic patients?

    Contrib Nephrol

    (2007)
  • C Langenberg et al.

    Renal blood flow and function during recovery from experimental septic acute kidney injury

    Intensive Care Med

    (2007)
  • BA Molitoris

    Therapeutic translation in acute kidney injury: the epithelial/endothelial axis

    J Clin Invest

    (2014)
  • K Xu et al.

    Unique transcriptional programs identify subtypes of AKI

    J Am Soc Nephrol

    (2017)
  • D Schnell et al.

    Resistive Index or color-Doppler semi-quantitative evaluation of renal perfusion by inexperienced physicians: results of a pilot study

    Minerva Anestesiol

    (2014)
  • Cited by (14)

    • Acute kidney injury in hospitalized patients with COVID-19: A Portuguese cohort

      2021, Nefrologia
      Citation Excerpt :

      The impact of AKI duration on prognosis led to the development of a standardized definition of transient and persistent AKI, based on recovery of kidney function within 48 h, by the ADQI Workgroup.23 Transient AKI might reflect reversible renal impairment due to nephrotoxins or hemodynamic changes and persistent AKI is more likely a result of conditions less easily reversed and these patients may consequently require more RRT.46,47 Rubin et al. analyzed AKI in 77 critically ill patients with COVID-19 and demonstrated that persistent AKI was present in the majority of patients (93%).48

    View all citing articles on Scopus

    Financial support: none.

    Conflict of interest statement: Michaël Darmon has received consulting fees from Sanofi and Gilead-Kite, research support from Astute Medical and MSD, and speaker fees from MSD, Gilead-Kite, and Astellas.

    View full text