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Kidney Function Could Impact Dx Biomarker Readings, Researchers Find

NEW YORK (360Dx) – A team led by scientists at Oslo University Hospital has found that impaired renal function may impact levels of diagnostic biomarkers.

In a study published this month in the Journal of Applied Laboratory Medicine, the researchers determined that glomerular filtration rates significantly impacted plasma and urine levels of the biomarkers guanidinoacetate (GAA), creatine (CRE), human epididymis protein 4 (HE4), and neutrophil gelatinase–associated lipocalin (NGAL).

These findings, the authors wrote, indicate that patient renal function should be considered when interpreting test results as decreased function could shift marker levels above or below relevant cutoffs and cause an incorrect diagnosis.

As the researchers noted, the kidneys are key to filtering molecules in plasma, so it follows that decreased kidney function could alter the concentrations of diagnostic biomarkers in plasma and urine.

To address whether this was, in fact, the case, the team looked at GAA, CRE, HE4, and NGAL in plasma and urine in a cohort of 96 children suffering from different stages of chronic kidney disease.

GAA and creatine are biomarkers for creatine deficiency syndrome, which can lead to developmental delays and intellectual disabilities. Ratios of urinary GAA to creatinine (crn), and CRE to crn are commonly measured test for the condition. They are also used to diagnose conditions including guanidinoacetate methyltransferase (GAMT) deficiency, arginine:glycine amidinotransferase (AGAT) deficiency, and X-linked creatine transporter (CRT) defect.

HE4 is a tumor marker, and, the JALM authors noted, while it is not commonly measured in children, previous studies have found that patients with decreased kidney function present with higher HE4 levels in plasma.

NGAL is a protein biomarker often used for early detection of acute kidney injury.

The researchers measured these markers in the 96-patient cohort, which consisted of 28 patients with stage 1 chronic kidney disease; 27 with stage 2 CKD; 23 with stage 3 CKD; and 18 with stage 4 or 5 CKD. They used glomerular filtration rates [GFR] as measured by iohexol clearance to assess kidney function in these patients and used multiple linear regression analysis to determine how age, sex, and GFR influenced the marker measurements.

Their findings indicate that renal function does affect the values of some, but not all, of the markers. For instance, serum and urine GAA were significantly decreased by impaired kidney function, which also impacted measurements of urine GGA to crn ratios.

Serum HE4 was substantially increased by a decline in kidney function, which led to a decrease in urine HE4 to serum HE4 ratio.

Serum NGAL also increased as kidney function declined, while CRE remained largely unchanged by changes in kidney function, and urine CRE to crn ratios were impacted only slightly.

In several cases, the observed changes could be significant enough to change a patient's diagnosis, the authors noted. For instance, in the case of urine GAA to crn ratio, changes due to kidney function could push patient scores below the diagnostic cutoff for GAMT deficiency. Likewise, changes in kidney function could push serum HE4 above the reference limit.

"Our results indicate that several diagnostic disease markers are influenced by renal function and that this must be taken into account when interpreting test results," the authors wrote.