The cornerstone of successful acute kidney injury management is early detection
Acute kidney injury (AKI) is a form of kidney insufficiency characterized by a sudden drop in kidney function (1). AKI affects 13.3 million people per year and accounts for 2 million deaths around the world although it’s mostly preventable with timely detection and intervention (2). Recognition of AKI is often delayed in hospitalized patients (3) and the outcome of patients with dialysis-requiring AKI has not changed in the past decades (4), showing the great need for innovative diagnostic tools. The biomarker Proenkephalin A 119-159 (penKid*) offers a solution for overcoming the current limitation of standard diagnostics.
Hospitalization causes increased susceptibility for AKI (8)
| Conditions causing AKI |
|---|
| Sepsis |
| Critical illness |
| Circulatory shock |
| Burns |
| Trauma |
| Cardiac surgery |
| Major noncardiac surgery |
| Nephrotoxic drugs |
| Radiocontrast agents |
| Poisonous plants and animals |
| Factors for high susceptibilities |
|---|
| Dehydration or volume depletion |
| Advanced age |
| Female gender |
| Ethnicity |
| Chronic kidney disease |
| Chronic diseases (heart, lung, liver) |
| Diabetes mellitus |
| Cancer |
| Anemia |
Potential pitfalls in AKI diagnostics
Criteria for the diagnosis of AKI rely on the change of serum creatinine (SCr) (1), a common practice for estimating kidney function for decades that remains unchanged. Despite its widespread use, it has significant limitations as a tool for assessing the estimated glomerular filtration rate (eGFR) (9), which is the amount of volume filtered by the glomeruli per minute.
Delay:
The inability of SCr to detect mild kidney insufficiency is due to the delayed elevation of SCr levels when approximately 50% of kidney function is already lost (10); this is known as the creatinine-blind area. Moreover, SCr usually requires at least two measurements (10).
Variability:
A variety of nonrenal factors influence SCr production rate. Most notably, age, gender, muscle mass, diet (particularly protein intake), ethnicity, and nutritional status are major determinants of SCr production (12).
Drug interference:
Under normal conditions, tubular secretion of SCr accounts for roughly 10% of SCr clearance, but this secretion is inhibited by certain medications such as trimethoprim and cimetidine, leading to elevations in SCr independently of any change in GFR (11).
Overestimation:
Significant impairment of kidney tubules increases the proportion of SCr clearance that can be attributed to tubular secretion, resulting in a substantial overestimation of GFR once the true GFR falls below 55 mL/min/1.73 m2 (10).
Overcoming the pitfalls of standard diagnostics
Proenkephalin A 119-159 (penKid*) is a functional biomarker for an early and reliable assessment of kidney function in AKI. An emerging body of scientific evidence demonstrates that monitoring penKid overcomes the pitfalls of traditional AKI diagnosis by mirroring the true GFR (13,14).
The assessment of penKid identifies adult patients at high risk of AKI in emergency departments (EDs) and ICUs (15, 16) in real-time. This innovative biomarker has the potential to guide physicians from early detection until patient recovery (17).
- Real-time: penKid levels are reported to rise up to 48 hours earlier than serum creatinine, allowing a more rapid identification of AKI (16, 19, 20).
- Independence: penKid is not influenced by inflammation (15, 16, 17, 18) and common comorbidities (e.g. hypertension, diabetes mellitus) (16).
- Superior estimation: studies have shown that penKid strongly correlates with the in vivo measurement of true GFR, and delivers information on the GFR in healthy and hospitalized patients (13, 14, 16).
*Disclaimer
Sphingotest® penKid®, sphingotest® bio-ADM®, sphingotest® DPP3 are offered for in vitro diagnostics. “penKid”, “bio-ADM” and “DPP3” represent the analytes Proenkephalin A 119-159, bioactive Adrenomedullin 1-52, and Dipeptidyl Peptidase 3, respectively.
Reference Literature
(1) Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. (2012). Kidney Inter. Supplements.
View the paper
(2) Metha et al. (2015). International Society of Nephrology’s 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet.
View the paper
(3) Stewart et al. (2009). Adding Insult to Injury: A review of the care of patients who died in hospital with a primary diagnosis of acute kidney injury (acute renal failure). London, UK: National Confidential Enquiry into Patient Outcome and Death.
View the report
(4) Lee et al. (2019). Predicting renal recovery after dialysis-requiring acute kidney injury. Kidney International Reports.
View the paper
(5) Edelstein C. Biomarkers of kidney disease. Boston (MA): Elsevier; 2016.
Look at the book
(6) Bedford et al. (2014). What is the real impact of acute kidney injury? BMC Nephrol.
View the paper
(7) Coca et al. (2009). Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis.
View the paper
(8) Ding et al. (2016). Acute Kidney Injury – From Diagnosis to Care. Krager.
Look at the book
(9) Delanaye P et al. (2017). Serum Creatinine: Not So Simple! Nephron.
View the paper
(10) Shemesh et a. (1985). Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int.
View the paper
(11) Delanaye et al. (2011). Trimethoprim, Creatinine and Creatinine-Based Equations. Nephron Clin Pract.
View the paper
(12) Bagshaw et al. (2008). Conventional markers of kidney function. Critical Care Medicine.
View the paper
(13) Beunders et al. (2020). Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients. Shock.
View the paper
(14) Donato et al. (2018). Analytical performance of an immunoassay to measure proenkephalin. Clin Biochem.
View the paper
(15) Marino et al. (2015). Diagnostic and short-term prognostic utility of plasma pro-enkephalin (pro-ENK) for acute kidney injury in patients admitted with sepsis in the emergency department. J Nephrol.
View the paper
(16) Hollinger et al. (2018). Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study, Kidney International Reports.
View the paper
(17) Caironi et al.; ALBIOS Study Investigators (2018). Circulating Proenkephalin, Acute Kidney Injury, and Its Improvement in Patients with Severe Sepsis or Shock. Clin Chem.
View the paper
(18) Kim et al. (2017), Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis. Ann Lab Med.
View the paper
(19) Beunders et al. (2017). Proenkephalin (PENK) as a Novel Biomarker for Kidney Function, The Journal of Applied Laboratory Medicine.
View the paper
(20) Lima et al. (2022), Role of proenkephalin in the diagnosis of severe and subclinical acute kidney injury during the perioperative period of liver transplantation. Pract Lab Med.
View the paper