Clinical Focus

Getting ahead of AKI benefits patients

and clinical teams.

AKI has many causes, affecting patients and
providers across multiple specialties.

Critical Care

Acute Kidney Injury (AKI) occurs frequently in critically ill patients and is independently associated with poor outcomes.

Risk-stratifying patients in danger of AKI gives intensivists the chance to get ahead of kidney damage and initiate measures to tailor management.


“Our data demonstrates that prediction of AKI severity on Day 3 [following PICU admission] can be made more precise via the integration of an AKI biomarker with SCr.…This is supported by existing evidence suggesting that early recognition of post-surgical patients at high risk for AKI followed by the implementation of standardized KDIGO management bundles can decrease AKI disease burden.”

   — Stanski, N. et al.Journal of Critical Care 2019
Cardiac Surgery

AKI complicates recovery from cardiac surgery in up to 30% of patients, placing them at a 5x increased risk of death during hospitalization.i

Characteristics of cardiac surgery that increase risk of kidney injury include:

  • Cardiopulmonary bypass (CPB)
  • High rates/volumes of exogenous blood product transfusion
  • High doses of exogenous vasopressors

These interventions change renal perfusion, induce cycles of ischemia and reperfusion, increase oxidative damage, and increase inflammation, which can induce the development of AKI.i



AKI affects roughly 25% of all recipients of deceased donor organs and is associated with shortened graft survival as well as with longer ICU stays, need for postoperative dialysis, infectious complications, acute rejection, and reduced patient survival.ii

Using novel biomarkers to assess AKI risk in pediatric transplant recipients can provide information beyond serum creatinine when considering management decisions about fluid balance and/or the use of nephrotoxic drugs.



AKI in neonates is “a challenging diagnosis in a challenging population.”iii

Despite being under-recognized and under-diagnosed, recent studies “suggest an incidence of 19–40% in very low birth weight infants, and 38% in term neonates with perinatal asphyxia.”iii

Diagnosis is complicated by the lack of reliable tests – neonates often have non-oliguric renal failure and creatinine measurements they take several days to equilibrate postnatally. Furthermore, they may not increase until up to half of kidney function is lost. An additional challenge is that diagnosis relies on serial measurements of creatinine, which can be a concern in preterm babies.iv


“The unique renal physiology of preterm and term infants creates challenges for the use of serum creatinine (sCr) as an AKI biomarker in these patients. Neonatal sCr initially reflects maternal values and then decreases over subsequent weeks after birth at different rates depending on gestational age. In addition, “normal” serum creatinine levels vary widely based on weight and gestational age.”

   — Jetton J.Pediatr. 2016.

Nephrotoxic medication exposure is common in hospitalized patients and represents one of the most common causes of hospital-acquired AKI.v In a study at a tertiary care children’s hospital, 16% of AKI was caused by nephrotoxic

Whether managing the complex side effects of antibiotics, chemotherapy or other medications, balancing treatment benefits with the risks of kidney damage is an ever-present concern, particularly when standard lab tests can be confounded by clinical factors such as dehydration and anemia.

Nephrotoxin-induced AKI in hospitalized children is often caused by exposure to multiple drugs, which may include:vii,viii

  • Cefotaxime
  • Ceftazidime
  • Cisplatin
  • Gentamicin
  • Ibuprofen
  • IV aminoglycoside exposure for >5 days
  • Piperacillin/piperacillin and tazobactam
  • Trimethoprim/Sulfamethoxazole
  • Vancomycin

Identifying AKI earlier in the course of kidney injury may allow clinicians to review and expeditiously adjust dosages.


“In the setting of AKI and in patients at risk for AKI, such as those with dehydration or acute infection, clinicians must balance the risk of nephrotoxicity versus the therapeutic benefit that led to their prescription in the first place.”

   — Goldstein, SLF1000Research 2017.

Laboratory medicine for critically ill patients centers around delivering timely and accurate results when they offer maximal clinical value, and ideally when they anticipate changes in a patient’s health status.

Identifying AKI faster has been shown to reduce time on ventilation and dialysis, as well as shorten length of stay (LOS).ix


“A modest literature search indicates that [with AKI] there’s a substantial increase in-hospital mortality, increased transition to chronic kidney disease is substantial, and a substantial increase in hospitalization costs. So, if you scale this up, it is on the radar screen for health care costs in the United States.”

   — James Crawford, MD, PhDSenior Vice President, Laboratory Services Northwell Health, CAP Today, July 2016
Healthcare System

The cost of hospital-acquired AKI has been conservatively estimated to be at least $10 Billion annually.x This staggering cost is in part due to the challenging reality that AKI is recognized late, when mitigating kidney damage requires more intensive, costly and challenging intervention.

Studies indicate that AKI results in higher hospital resource utilization and that the average cost of hospital stays involving AKI was nearly double the cost of stays without renal failure.xi


“Even the most conservative estimates still attribute approximately $1,700 in excess costs for each epi­sode of AKI and $11,000 in excess costs for each episode of dialysis-requiring AKI. In the United States, at least $5 billion in hospital costs are related to AKI, and the true costs are likely much, much higher.”

   — Silver, SA.Nephron 2017


i O’Neal JB, Shaw AD, Billings FT. Acute kidney injury following cardiac surgery: current understanding and future directions. Crit Care. 2016;20(1):187.

ii De Santo LS,  Romano G,  Amarelli C, Maiello C, Baldascino F,  Bancone C, Grimaldi F,  Nappi G. Implications of acute kidney injury after heart transplantation: what a surgeon should know. Eur. J. Cardio-Thoracic Surg; 2011;40(6):1355–1361.

iii Nada A, Bonachea EM, Askenazi DJ. Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med. 2017;22(2):90–97.

iv Jetton JG, Guillet R, Askenazi DJ, et al. Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a Retrospective Cohort Study. Front Pediatr. 2016;4:68.

v Goldstein SL. Nephrotoxicities [version 1; referees: 2 approved] F1000Research 2017, 6 (F1000 Faculty Rev):55.

vi Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001. Am J Kidney Dis. 2005;45(1):96–101.

vii Goldstein SL, Kirkendall E, Nguyen H et. Al. Electronic Health Record Identification of Nephrotoxin Exposure and Associated Acute Kidney Injury. Pediatrics 2013;132(3):e756.

viii Moffett BS, Goldstein SL. Acute kidney injury and increasing nephrotoxic-medication exposure in noncritically-ill children. Clin J Am Soc Nephrol. 2011;6(4):856–863.

ix Hobson C, Ozrazgat-Baslanti T, Kuxhausen A, et al. Cost and mortality associated with postoperative acute kidney injury. Ann Surg. 2014;00:1-8.

x Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized Patients. JASN. 2005;16 (11) 3365-3370.

xi Moore, B, Torio, C. Acute Renal Failure Hospitalizations, 2005–2014. Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. 2017; Statistical Brief #231.

xii Ciccia E, Devarajan P. Pediatric acute kidney injury: prevalence, impact and management challenges. Int J Nephrol Renovasc Dis. 2017;10:77–84.

xiii Silver SA, Chertow GM. Economic Consequences of Acute Kidney Injury. Nephron 2017;137:297–301.

xiv O’Reilly, KB. Laboratory 2.0: Changing the conversation. CAP Today. July 2016.