Special Feature: UT Southwestern Internal Medicine Conference
Acute Kidney Injury: The Beginning of the End of the Dark Ages

https://doi.org/10.1097/MAJ.0b013e318228aef8Get rights and content

Abstract

There has been enormous progress in the understanding of acute kidney injury (AKI) over the past 5 years. This article reviews some of the salient new findings, the challenges revealed by these findings and new insights into the pathogenesis of ischemic AKI. Clinical studies have demonstrated that even a small, transient rise in serum creatinine increases the risk of mortality in hospitalized patients and that a single event of AKI increases the risk for developing chronic kidney disease. Although the overall mortality rate from AKI has improved over the past 2 decades, it continues to be significant. Current treatment is focused on maintaining renal perfusion and avoiding volume overload. However, new therapeutic targets are emerging for the treatment of AKI as our understanding of the pathogenesis of ischemic injury and inflammation increases. Early diagnosis, however, continues to be challenging as the search continues for sensitive and specific biomarkers.

Section snippets

INTRODUCTION AND DEFINITIONS

Early studies of acute renal failure (ARF) were compromised by inconsistent definitions of this disease by different investigators. Although all agreed that a decrease in renal function over the course of hours to days is the hallmark of ARF, there was no agreement on what constituted renal dysfunction. A major step forward was the formation of the Acute Dialysis Quality Initiative and the Acute Kidney Injury Network.1., 2. In 2005, these consensus groups of nephrologists and intensive care

AKI IS ONE MAJOR CAUSE OF ACUTE RENAL DYSFUNCTION

One of the difficulties in treating acute renal dysfunction is making the diagnosis early enough to alter the course of the disease. The problem lies, in part, in differentiating AKI (structural injury to the kidney) from the other etiologies of acute renal dysfunction (increase in serum creatinine and/or decreased urine output). These etiologies have been divided into 3 broad categories and have been discussed in many excellent standard textbooks and review articles.4 We summarize them briefly

Patients With AKI Have a Higher Mortality Than Matched Patients Without AKI

The importance of AKI is often underappreciated. In fact, even mild AKI has profound implications for mortality and progression of chronic kidney disease.

Two multicenter clinical studies, Program to Improve Care in Acute Renal Disease (PICARD) and Beginning and Ending Therapy for the Kidney (BEST Kidney) showed that in-hospital mortality for patients with AKI in participating academic medical centers ranged from as low as 24% to as high as 75%.5

Studies of administrative databases have shown an

TREATMENT OF ISCHEMIC AKI IN 2011—BEFORE DIALYSIS IS NEEDED

The management of patients with ischemic AKI may be divided into 2 different objectives: one is the treatment of the kidney; the other is the treatment of the patient. Confusion in these 2 different objectives will result in serious errors in management and complaications.

Successful management of ischemic AKI rests on a firm understanding of the pathophysiology of renal failure. After the initial precipitous drop in GFR during hypoperfusion, secondary effects such as exposure to nephrotoxins

USE AND MISUSE OF IV FLUIDS—EARLY VERSUS LATE IN THE COURSE OF ISCHEMIC AKI

Optimization of cardiac filling pressures, and thus, improved renal perfusion is the mainstay of treating and preventing ischemic AKI in 2011. This is usually accomplished by a combination of intravenous (IV) fluids and vasopressors. It is becoming increasingly apparent that early, appropriate administration of IV crystalloid solution may prevent AKI, particularly in patients with septic shock.42., 43., 44. Early goal-directed therapy for sepsis as originally described by Rivers, has been shown

USE AND MISUSE OF DIURETICS

Recall our earlier division of the therapy of ischemic AKI into 2 different objectives: treatment of the kidney and treatment of the patient.

EFFECTS OF DIALYSIS ON RENAL RECOVERY

Conventional wisdom states that intermittent hemodialysis impairs recovery of the kidney from ischemic AKI. This is believed to occur because of hemodynamic instability during dialysis, vascular catheter-related infection and/or cytokine release after blood interacts with the dialyzer membrane. On the basis of these issues, continuous renal replacement therapy has been proposed to be a better dialysis modality for AKI. In fact, there is limited data that any of these factors have a negative

CHALLENGES IN MEASURING RENAL FUNCTION AND RENAL INJURY

Because we lack an easy, direct method of measuring renal injury, our current diagnosis of AKI relies on assaying 2 major renal functions and assuming that decreased functions are directly correlated with injury. Unfortunately, this may not be true, particularly early after injury.57., 58.

One function is the GFR. Even if we were able to easily and reliably measure the GFR, this would be a poor indicator of injury because, in many patients, the renal mass must be markedly reduced before the GFR

CONCLUSION

Clinical research during the past decade has advanced our understanding of the implications of AKI and redefined the goals of fluid management. Despite these advances, the mortality rate of patients with AKI remains high. We also appreciate that renal injury is an inflammatory condition that affects multiple organ systems. Basic research in the inflammatory response to AKI has the potential of identifying novel therapeutic targets; however, until we have accurate and sensitive tests that can

REFERENCES (66)

  • JonesA.E. et al.

    Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock

    Chest

    (2007)
  • StewartR.M. et al.

    Less is more: improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring

    J Am Coll Surg

    (2009)
  • LameireN. et al.

    Acute renal failure

    Lancet

    (2005)
  • HanW.K. et al.

    Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury

    Kidney Int

    (2002)
  • MehtaR.L. et al.

    Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

    Crit Care

    (2007)
  • KellumJ.A. et al.

    Consensus development in acute renal failure: the acute dialysis quality initiative

    Curr Opin Crit Care

    (2005)
  • HosteE.A. et al.

    AKI severity class doesn’t tell all: the case for transient AKI

    Nephrol Dial Transplant

    (2010)
  • BradyH.R. et al.

    Acute renal failure

  • WalkarS.S. et al.

    Diagnosis, epidemiology and outcomes of acute kidney injury

    Clin J Am Soc Nephrol

    (2008)
  • XueJ.L. et al.

    Incidence and mortality of acute renal failure in Medicare beneficiaries. 1992 to 2001

    J Am Soc Nephrol

    (2006)
  • WalkarS.S. et al.

    Declining mortality in patients with acute renal failure, 1988 to 2002

    J Am Soc Nephrol

    (2006)
  • LameireN. et al.

    The rise of prevalence and the fall of mortality of patients with acute renal failure: what the analysis of two databases does and does not tell us

    J Am Soc Nephrol

    (2006)
  • ChertowG.M. et al.

    Acute kidney injury, mortality, length of stay, and costs in hospitalized patients

    J Am Soc Nephrol

    (2005)
  • LassniggA. et al.

    Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study

    J Am Soc Nephrol

    (2004)
  • LevyE.M. et al.

    The effect of acute renal failure on mortality. A cohort analysis

    JAMA

    (1996)
  • TsagalisG. et al.

    Long-term prognosis of acute kidney injury after first acute stroke

    Clin J Am Soc Nephrol

    (2009)
  • UchlnoS. et al.

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

    Nephrol Dial Transplant

    (2010)
  • TapiawalaS.N. et al.

    Delayed graft function and the risk for death with a functioning graft

    J Am Soc Nephrol

    (2010)
  • WaldR. et al.

    Chronic dialysis and death among survivors of acute kidney injury requiring dialysis

    JAMA

    (2009)
  • VenkatachalamM.A. et al.

    Acute kidney injury: a springboard for progression in chronic kidney disease

    Am J Physiol Renal Physiol

    (2010)
  • WalkarS.S. et al.

    Chronic on acute renal failure: long-term implications of severe acute kidney injury

    JAMA

    (2009)
  • KhoslaN. et al.

    Preexisting chronic kidney disease: a potential for improved outcomes from acute kidney injury

    Clin J Am Soc Nephrol

    (2009)
  • TokuyamaH. et al.

    Macrophage infiltration and cellular proliferation in the non-ischemic kidney and heart following prolonged unilateral renal ischemia

    Nephron Physiol

    (2007)
  • Cited by (17)

    • Could “calprotectin” and “endocan” serve as “Troponin of Nephrologists”?

      2017, Medical Hypotheses
      Citation Excerpt :

      Each of these biomarkers has its individual strengths and weaknesses and only if used together and in a panel format, these biomarkers could help the diagnosis or distinguishing the etiology of AKI. Unfortunately, none of these biomarkers have been broadly validated for clinical use and assays for these biomarkers are not widely available [11]. Even if a panel of these biomarkers would be able to detect AKI, it is still the clinician that should identify those who are at risk of AKI, and use the panel to establish or rule out the diagnosis.

    • Novel biomarkers of acute kidney injury and chronic kidney disease

      2017, Polish Annals of Medicine
      Citation Excerpt :

      Owing the limitations mentioned above and poor sensitivity and specificity at early stages of either acute or chronic kidney dysfunction,4,5 the routinely determined biochemical parameters should be mostly considered as surrogate biomarkers of renal function. In line with widely accepted criteria, acute kidney injury (AKI), also referred to as acute renal failure (ARF), is a clinical condition characterized by an abrupt and sustained deterioration of renal function, resulting in nitrogenous and non-nitrogenous waste retention, oliguria progressing to anuria, disruption of water and electrolyte balance.6–8 AKI is diagnosed in approximately 7.2% of all hospitalized patients.

    • Vascular Surgery Kidney Injury Predictive Score: A Historical Cohort Study

      2015, Journal of Cardiothoracic and Vascular Anesthesia
      Citation Excerpt :

      In addition, the authors showed the risk of AKI significantly decreased for each 10 mL/min/body surface area increase in eGFR at the baseline (odds ratio 0.8; 95% confidence interval, 0.7-0.8; p<0.001) (Table 3 and Supplementary Figure 1). Emerging data regarding the association between volume overload and poor postsurgical outcomes signify the importance of judicious use of intravenous fluids in postoperative patients.42 In a systematic analysis, early use of inotropic agents in the resuscitation phase was protective against AKI.43

    View all citing articles on Scopus

    This study was supported by NIH RO-1 DK069633 grant (to CYL), NIH T32DK07257 (to PDW), NIH DK079328 UT Southwestern O’Brien Kidney Research Core Center and a Beecherl grant (to CYL).

    View full text