Protein predicts chronic kidney disease progression

In patients with chronic kidney disease that has not yet advanced, elevated levels of a protein called neutrophil gelatinase-associated lipocalin (NGAL) in the urine and blood is a strong and independent predictor of disease progression, researchers from Italy report.

Massive amounts of NGAL are released from kidney tubular cells after various injuries to the kidney, Dr. Michele Buemi and colleagues from University of Messina explain in their report published online ahead of print in the Clinical Journal of the American Society of Nephrology.

In a previous study, the researchers found abnormally high levels of this protein in patients who developed kidney disease and impaired kidney function. In addition, patients with higher NGAL levels had a considerably increased risk of worsening kidney function within 1 year compared with those with lower NGAL levels.

To investigate further, Buemi and colleagues examined how well blood and urine levels of NGAL predicted the progression of chronic kidney disease in a group of 96 patients (average age, 57 years) with kidney disease from a variety of sources. The subjects’ average estimated glomerular filtration rate, another kidney disease predictor, was 15 mL/min per 1.73 m² or greater.

NGAL in the blood and urine “were inversely, independently, and closely related to eGFR,” the investigators report.

Blood concentrations of NGAL were 515.4 ng/mL in kidney disease patients compared with 35.4 ng/mL in a group of 14 healthy control subjects matched for age, gender and blood pressure. The average urine levels of NGAL were 195.6 and 6.6 ng/mL, respectively.

During a follow-up of 18.5 months, 31 patients (32 percent) experienced significant kidney disease progression, in some cases developing end-stage kidney disease. The patients with significantly increased blood and urinary NGAL levels at the start of the study were compared with non-progressors.

According to Buemi and colleagues, the evolution of kidney disease was significantly faster in patients with blood NGAL values above 435 ng/mL; the average follow-up time to progression was 14.9 months in these patients compared with 18.9 months in patients with blood NGAL values below this cut-off.

Similarly, patients with urinary NGAL values above 231 ng/mL had a significantly faster progression, with an average time to progression of 13.2 months compared with 19.2 months for patients with urinary NGAL levels below this cut-off.

Blood and urine levels of NGAL predicted a higher risk of chronic kidney disease progression regardless of eGFR levels or patient age. Every increase of 10 ng/mL of urinary NGAL was associated with a 3 percent increased risk of progression, whereas an increase of 10 ng/mL of blood levels of NGAL increased this risk by 2 percent.

These findings offer a “great new tool” for preventing the progression of kidney disease, Buemi said in a statement. NGAL measurement in the blood and urine among chronic kidney disease patients could help identify those most likely to develop worsening disease who should receive aggressive treatments.

SOURCE: Clinical Journal of the American Society of Nephrology, 2009.

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