Astute Medical Inc, San Diego, recently shared results from a trial of the company’s NephroCheck test for early assessment of patient risk for acute kidney injury (AKI). The study resulted in improved patient outcomes, shorter hospital stays, and cost savings associated with a 66% reduction in moderate and severe acute kidney injury (AKI) following noncardiac surgery, further validating the case for early assessment of AKI risk in combination with guided therapy.

The randomized trial used Astute’s NephroCheck test to identify patients at high risk of developing AKI, triggering preventive intervention.1 Patients in the intervention group spent fewer days in the intensive care unit (ICU; approximately 1 day) and hospital (approximately 5 days), yielding net savings of more than $2,000 per patient.

The NephroCheck test system is intended for use in conjunction with clinical evaluation of ICU patients who currently have or have had acute cardiovascular or respiratory compromise within the past 24 hours, as an aid in assessing the patient’s risk for moderate or severe AKI within the following 12 hours. The NephroCheck test system is intended to be used in patients 21 years of age or older.

Ivan Göcze, MD.

Ivan Göcze, MD.

“It appears the prediction of imminent AKI at the very early stage, followed by optimal fluid resuscitation with less positive fluid balance and kidney protection, led to the improved outcomes—meaning the reduced incidence and severity of AKI, as well as a decrease in postoperative creatinine levels and length of hospital stay,” says Ivan Göcze, MD, the trial’s lead author. “In fact, these benefits were present soon after intervention.”

The findings add to evidence gathered in a trial published earlier this year, in which the NephroCheck test was used to evaluate patients after cardiac surgery, resulting in a 33.9% reduction in moderate to severe AKI.2

John Kellum, MD.

John Kellum, MD.

“Again, we are seeing that a biomarker-guided protocol can reduce AKI, providing medical and economic benefit,” says John Kellum, MD, a critical care physician and past president of the Acute Dialysis Quality Initiative. “Cell-cycle arrest biomarkers are ushering in a new era in which AKI can be reduced by identifying patients destined to develop it. More protocols are needed, especially for the most vulnerable patients.”

AKI is a frequent complication among patients undergoing major surgery, and is known to increase morbidity, mortality risk, and costs.3 A recent estimate of AKI-associated increases in US hospitalization costs ranged from $5.4 billion to $24.0 billion.4 Although the complication can be managed, today’s standard indicators of AKI, such as elevated levels of serum creatinine, may not be present until kidney damage has already occurred.5

Paul McPherson, PhD, Astute Medical.

Paul McPherson, PhD, Astute Medical.

“Today’s healthcare environment not only emphasizes outcomes, but also value and cost,” says Paul McPherson, PhD, Astute’s cofounder and chief scientific officer. “We believe the $2,000 per-patient savings from shorter hospital stays demonstrated in this trial could represent as much as a 10-to-1 return on investment in the NephroCheck test system.”

The NephroCheck test detects two biomarkers: urinary tissue inhibitor of metalloproteinases-2 (TIMP-2), and insulin-like growth factor binding protein 7 (IGFBP7). The levels of these markers increase in a patient’s urine in response to the earliest kidney cell stress, which can lead to AKI if left unmitigated. The two markers, usually elevated before serum creatinine, are involved in G1 cell-cycle arrest, a protective mechanism that prevents stressed cells from dividing in case of DNA damage. This allows the biomarkers to function as an early alarm of kidney cell stress before major damage and progression to AKI.6

In the prospective randomized and controlled trial, conducted at the University Hospital in Regensburg, Germany, patients who had undergone major noncardiac surgery were screened with the NephroCheck test immediately after admission to the ICU. Patients found to be NephroCheck test positive for the risk of AKI (AKI risk score > 0.3) were then randomized to standard care (61 patients) or intervention (60 patients). The intervention group received treatment with a kidney-sparing care bundle based on Kidney Disease: Improving Global Outcomes clinical practice guidelines, which can be provided in any ICU.

The study’s primary endpoint was the incidence of AKI during the first 7 days after surgery. In the intervention group, 19 patients (31.7%) developed some level of AKI; in the control group, 29 patients (47.5%) developed some level of AKI.

Biomarker-guided therapy significantly reduced the incidence of moderate and severe AKI in the intervention group to 6.7% compared to 19.7% in the standard care group, a 66% reduction.

For more information, visit Astute Medical.

REFERENCES

  1. Göcze I, Jauch D, Götz M, et al. Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BigpAK study. Ann Surg. Published online in advance, August 29, 2017; doi: 10.1097/sla.0000000000002485.
  1. Meersch M, Schmidt C, Hoffmeier A, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high-risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. Epub ahead of print, January 21, 2017; doi: 10.1007/s00134-016-4670-3.
  1. Hobson C, Ozrazgat-Baslanti T, Kuxhausen A, et al. Cost and mortality associated with postoperative acute kidney injury. Ann Surg. 2015;261(6):1207–1214; doi: 10.1097/SLA.0000000000000732.
  1. Silver SA, Chertow GM. The economic consequences of acute kidney injury. Nephron. Epub ahead of print, June 9, 2017; doi: 10.1159/000475607.
  1. McCullough PA, Shaw AD, Haase M, et al. Diagnosis of acute kidney injury using functional and injury biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative consensus conference. In ADQI Consensus on AKI Biomarkers and Cardiorenal Syndromes, ed. McCullough PA, et al. Contrib Nephrol, vol 182. (Basel, Switzerland: Karger, 2013):13–29; doi: 10.1159/000349963.
  1. Kellum JA, Chawla LS. Cell-cycle arrest and acute kidney injury: the light and dark sides. Nephrol Dial Transplant. 2016;31(1):16–22; doi: 10.1093/ndt/gfv130.