Frequently Asked Questions
Acute Kidney Injury (AKI)
AKI is an abrupt loss of kidney function that develops rapidly over a few hours or days, defined by KDIGO as an increase in creatinine by more than 0.3 mg/dl within 48 hours or a reduction in urine volume to less than 0.5ml/kg/hour for 6 hours.i Learn more about AKI.
AKI is a silent epidemic that affects 13.3 million patients worldwide.ii It affects 10-15% of hospitalized patients, and 25-57% of those in intensive care units.iii Episodes of in-hospital AKI are steadily increasing – the U.S. saw an increase of 29% in the period from 2011-2021.iv
AKI is a diverse clinical spectrum. Patients with the highest risk of developing AKI in a hospital setting include those undergoing cardiac surgery (up to 30%)v, on mechanical ventilation for respiratory support (29%)vi and those receiving nephrotoxic medications (14-26%)vii. Other AKI risk factors include sepsis, multiple organ failure and solid organ or bone marrow transplant.viii Patients with diabetes and chronic kidney disease are also at greater risk of developing AKI.ix
AKI is associated with prolonged length of stay in the ICU and hospital, as well as poorer outcomes. Increased AKI severity and duration correlates with increased morbidity, the need for dialysis, prolonged time on mechanical ventilation and increased mortality.x Annually, AKI contributes to as many as 1.7 million deaths globally.xi
One to five years post-discharge, individuals who have had even one episode of AKI have been found to have a 30% higher rate of hospital re-admissionxii, are 38% more likely to have a major cardiac eventxiii and 25% progress to chronic kidney diseasexiv.
AKI is frequently asymptomatic and painless, and is often a complication of another illness or surgery. The standard definition of AKI is based on a change in serum creatinine (SCr) levels and urine output (UO). SCr and UO are measures of kidney function, not kidney damage. Functional changes reflective of AKI are not detectable until 48 to 72 hours after kidney damage begins.xv
AKI can be hard to predict or prevent. The earlier AKI or risk of AKI is identified, the sooner clinical action can be taken to mitigate or prevent permanent kidney damage. Understanding the risk factors for AKI is important, and the addition of damage biomarkers like NGAL provides another data point for clinicians to consider in their clinical assessment.xvi
AKI in lower-middle income countries is considered largely preventable with public health initiatives such as improved sanitation and water hygiene, education, and access to healthcare.xvii
It is estimated that acute kidney injury costs a health system an additional $7,000 per episodexviii and $5-$20 billion annually.xix AKI can impact re-hospitalization rates and long-term patient health, necessitating additional healthcare utilization.
The NGAL Biomarker
Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of renal injury that can be detected in urine and plasma as early as 2 hours after injury.xx Expressed in proximal and distal nephron tubules, it is one of the most upregulated genes and over-expressed proteins in the kidney following ischemic or nephrotoxic injury. It is not filtered by the kidney, and therefore, elevations in NGAL directly correlate with kidney damage, not functional impairment.xx Learn more about the NGAL biomarker.
In contrast, serum creatinine (SCr) is a product of muscle breakdown that can be impacted by nonrenal factors including age, nutrition and muscle mass. It is an indirect measure of kidney function and takes 48-72 hours to respond to kidney injury. It is estimated that 50% of kidney function must be lost before serum creatinine rises. Elevations in SCr may not always reflect kidney injury and subclinical AKI may occur without a rise in SCr.xv
NGAL is a rapid response biomarker that can be detected in both urine and plasma that increases as early as 2 hours after injury.xx Early identification of AKI, with an injury biomarker like NGAL, may provide more time for targeted intervention and management before permanent kidney damage occurs.xx
ProNephro AKI™ (NGAL)
ProNephro AKI™ (NGAL) is a particle-enhanced turbidimetric immunoassay for the in vitro quantitative determination of neutrophil gelatinase-associated lipocalin (NGAL) in human urine. In conjunction with a clinical assessment, it is intended to be used in the first 24 hours of ICU admission as an aid to identify patients aged 3 months to 22 years at risk of developing or having persistent moderate-to-severe AKI within 48-72 hours; for the management of cardiovascular or respiratory compromise or solid organ or bone marrow transplant. The full indication for use can be found at www.bioporto.us/pronephro-aki.
ProNephro AKI (NGAL) was clinically validated in GUIDANCE, a multicenter, prospective observational clinical trial in 660 pediatric patients.xxi In this trial, BioPorto assessed the effectiveness of a ProNephro AKI (NGAL) result in determining a pediatric patient's risk for developing or having persistent Stage 2/3 AKI within 48-72 hours post ICU admission.
Yes. ProNephro AKI (NGAL) received FDA clearance for use in the US on December 7, 2023. Learn more about ProNephro AKI.
To run ProNephro AKI (NGAL) in your laboratory, there are three BioPorto products required:
1. ProNephro AKI™ (NGAL) Reagent Kit, containing:
- R1: Reaction Buffer, 17.9 mL ready-to-use solution
- R2: Immunoparticle Suspension, 7.65 mL ready-to-use solution
- cobas® c pack and 2 funnels
2. ProNephro AKI™ (NGAL) Control Kit: Low Control, 3 x 1 mL; and High Control, 3 x 1 mL, ready-touse
3. ProNephro AKI™ (NGAL) Calibrator Kit: 5 vials of 1 mL: 50, 150, 600, 1500, 3000 ng/mL, ready-touse
No. ProNephro AKI (NGAL) is FDA-cleared for use in urine samples only.
It takes approximately 10 minutes for the assay to run on the Roche cobas® c 501 clinical chemistry analyzer. Reporting of results to the clinician is dependent on institutional processes and procedures; however, it is typically similar to a comprehensive metabolic panel.
ProNephro AKI (NGAL) is intended to be used in the first 24 hours of ICU admission as an aid to identify pediatric patients (≥ 3 months to < 22 years) at risk of developing or having moderate to severe AKI 48-72 hours after ICU admission; for the management of cardiovascular or respiratory compromise or solid organ or bone marrow transplant. The full Indication for Use is available at www.bioporto.us/pronephro-aki. Request the Instructions for Use from [email protected].
ProNephro AKI (NGAL) is FDA-cleared for assessing a pediatric ICU patient's risk for developing or having persistent Stage 2/3 AKI within 48-72 hours of ICU admission. Based on a high ProNephro AKI (NGAL) result and other clinical parameters, a physician should use their clinical judgment to determine the best course of action to reduce the patient’s risk of developing or having persistent Stage 2/3 AKI, This may include but is not limited to fluid and/or nephrotoxic drug management.i Please contact us at [email protected] if you'd like to connect with a peer to learn how they are using ProNephro AKI to modify clinical management in their pediatric ICU patients.
Contact us at [email protected] for ordering information.
Several educational offerings for clinicians are available through BioPorto Diagnostics. Contact us at [email protected] to describe your needs and arrange the appropriate resource.
Technical Support
For ProNephro AKI (NGAL) technical support including documentation, please contact Roche Diagnostics, or email BioPorto Diagnostics at [email protected].
iKhwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-c184.
iiMehta RL, Cerdá J, Burdmann EA, et al. International Society of Nephrology's 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet. 2015;385(9987):2616-2643.
iiiHoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-1423.
ivUnited States Renal Data System. 2023 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2023.
vO'Neal JB. Acute kidney injury following cardiac surgery: Current understanding and future directions. Crit Care. 2016;20(1).
viLombardi R. et al. An assessment of the Acute Kidney Injury Network creatinine-based criteria in patients submitted to mechanical ventilation. Clin J Am Soc Nephrol. 2011;6(7).
viiAlobaidi R. et al. Sepsis-associated acute kidney injury. Semin Nephrol. 2015;35(1).
viiiRonco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019;394(10212):1949-1964.
ixHapca S, Siddiqui MK, Kwan RSY, et al. The Relationship between AKI and CKD in Patients with Type 2 Diabetes: An Observational Cohort Study. J Am Soc Nephrol. 2021;32(1):138-150.
xHoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018;14(10):607-625.
xiLewington AJ, Cerdá J, Mehta RL. Raising awareness of acute kidney injury: a global perspective of a silent killer. Kidney Int. 2013;84(3):457-467.
xiiHessey E. et al. Healthcare Utilization after Acute Kidney Injury in the Pediatric Intensive Care Unit. Clin J Am Soc Nephrol, 2018;13(5).
xiiiOdutayo A. et al. AKI and Long-Term Risk for Cardiovascular Events and Mortality. JASN. 2017;28(1).
xivHorne KL. et al. Three-year outcomes after acute kidney injury: results of a prospective parallel group cohort study. BMJ Open. 2017;7(3).
xvMoledina DG, Parikh CR. Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine. Semin Nephrol. 2018;38(1):3-11.
xviOstermann M, Zarbock A, Goldstein S, et al. Recommendations on Acute Kidney Injury Biomarkers From the Acute Disease Quality Initiative Consensus Conference: A Consensus Statement JAMA Netw Open. 2020;3(10):e2019209.
xviiKellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers. 2021;7(1):52.
xviiiSilver SA, Chertow GM. The Economic Consequences of Acute Kidney Injury. Nephron. 2017;137(4):297-301.
xixSilver SA, Long J, Zheng Y, Chertow GM. Cost of Acute Kidney Injury in Hospitalized Patients. J Hosp Med. 2017;12(2):70-76.
xxDevarajan P. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med. 2010;4(2):265–280.
xxiGoldstein SL, Akcan-Arikan A, Afonso N, et al. Derivation and Validation of an Optimal Neutrophil Gelatinase-Associated Lipocalin Cutoff to Predict Stage 2/3 Acute Kidney Injury (AKI) in Critically Ill Children. Kidney International Reports. 2024.