Tubular damage important, but not predictive in diabetic nephropathy
MedWire News: Increased levels of tubular damage markers are associated with a faster decline in estimated glomerular filtration rate (eGFR) in patients with diabetic nephropathy, report researchers.
However, measurement of these markers does not give additional information on renal prognosis in such patients, they say.
"Studies have previously shown that in the pathophysiology and progression of diabetic nephropathy not only glomerular but also tubulointerstitial damage are important factors," write Stine Nielsen (Steno Diabetes Center, Gentofte, Denmark) and colleagues.
The researchers determined the role of tubular markers urinary neutrophil gelatinase-associated lipocalin (u-NGAL) and urinary kidney injury molecule 1 (u-KIM1) in predicting eGFR decline in 177 diabetes patients with elevated urinary albumin (u-albumin) excretion (>30 mg/24 hr). They also investigated a potential predictive role of plasma-fibroblast growth factor 23 (p-FGF23), an inhibitor of renal phosphate absorption.
After measuring the presence of these biomarkers at baseline in 2006, the team performed yearly follow-up assessments of the patients' eGFR and u-albumin levels over a median of 3.5 years. Patients were divided into four quartiles based on their measures of each tubular marker and p-FGF23, and decline in eGFR was compared between the groups.
As reported in Diabetes Research and Clinical Practice, patients in the highest quartile for u-KIM1 had a significantly greater decline in mean eGFR by the end of follow-up than those in the lowest quartile, at 6.0 versus 3.2 mL/min per 1.73 m2 per year. The decline in mean eGFR was also significantly greater for patients in the highest versus lowest quartile for u-NGAL, at 5.1 versus 2.8 mL/min per 1.73 m2 per year.
However, linear regression analysis revealed that, although levels of u-NGAL and u-KIM1 were positively associated with decline in eGFR, the association was relatively weak. Furthermore, it was no longer statistically significant after adjustment for other known progression promoters, namely glycated hemoglobin, systolic blood pressure, and u-albumin.
The researchers found no predictive value for p-FGF23 as a marker for decline in eGFR.
"Even if this result indicates that the role of tubular markers as predictors of renal prognosis are limited in Type 2 diabetes, it still shows that tubular damage plays a role in the progression of diabetic nephropathy," say Nielsen et al.
"However, our results indicate that there is no additional information on prognosis obtained by measuring them in this situation," they conclude.
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By Sally Robertson