Age-based nephrosclerosis threshold better predicts CKD progression

Andrew D Rule

Researchers including lead Muhammad Asghar and corresponding author Andrew D Rule (both Mayo Clinic, Rochester, USA) have published the results of a study comparing the risk assessment of chronic kidney disease (CKD) progression using age-based thresholds for nephrosclerosis against a single young adult threshold. The study in the Journal of the American Society of Nephrology (JASN) aimed to determine which approach is more effective in identifying clinically relevant CKD.  

Asghar et al carried out morphometric analyses of kidney biopsy images from a total of 4,697 participants, including 3,020 living kidney donors, 1,363 patients with kidney tumours, and 314 patients with native kidney disease. The researchers measured the percentage of globally sclerotic glomeruli (GSG), percentage of interstitial fibrosis and tubular atrophy (IFTA), and IFTA foci density in the kidney biopsy samples. 

Normotensive living kidney donors were used to establish young-age thresholds for individuals aged 18–29 years. They also determined age-based 95th percentile thresholds, roughly categorised by decade, for comparison. Asghar et al then carried out a comparison of age-adjusted risk of progressive CKD, which they defined as kidney failure or a 40% decline in estimated glomerular filtration rate (eGFR), among patients with kidney tumours and patients with kidney disease in groups that they designated as “normal compared with young”, “normal for age but abnormal compared with young”, and “abnormal for age”. 

The authors found that the 95th percentiles for %GSG, %IFTA, and IFTA foci density varied across different age groups, ranging from 1.7–16%, 0.18–6.5%, and 8.2–59.3% per cm2, respectively, from the youngest group (18–29 years) to the oldest group (≥70 years).  

The risk of progressive CKD did not differ significantly between individuals with nephrosclerosis that was considered “normal compared with young” and those considered “normal for age but abnormal compared with young.” However, the risk of progressive CKD was “significantly higher” when %GSG, %IFTA, or IFTA foci density were “abnormal” compared to when normal in both patients who underwent a kidney biopsy to determine the cause of their kidney disease and patients who had a kidney removed due to a tumour. 

“Given that increased risk of progressive CKD occurs only when nephrosclerosis is abnormal for age,” Asghar et al conclude, age-based thresholds are recommended as a more accurate method for the identification of “clinically relevant CKD” compared to a single young-age threshold.


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