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Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD.

Publication ,  Journal Article
Asghar, MS; Denic, A; Mullan, AF; Moustafa, A; Barisoni, L; Alexander, MP; Stegall, MD; Augustine, J; Leibovich, BC; Thompson, RH; Rule, AD
Published in: J Am Soc Nephrol
August 1, 2023

SIGNIFICANCE STATEMENT: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) is the defining pathology of both kidney aging and CKD. Optimal thresholds for nephrosclerosis that identify persons with a progressive disease are unknown. This study determined a young-age threshold (18-29 years) and age-based 95th percentile thresholds for nephrosclerosis on the basis of morphometry of kidney biopsy sections from normotensive living kidney donors. These thresholds were 7.1-fold to 36-fold higher in older (70 years or older) versus younger (aged 18-29 years) normotensive donors. Age-based thresholds, but not young-age threshold, were prognostic for determining risk of progressive CKD among patients who underwent a radical nephrectomy or a for-cause native kidney biopsy, suggesting that age-based thresholds are more useful than a single young-age threshold for identifying CKD on biopsy. BACKGROUND: Nephrosclerosis, defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA), is a pathology of both kidney aging and CKD. A comparison of risk of progressive CKD using aged-based thresholds for nephrosclerosis versus a single young-adult threshold is needed. METHODS: We conducted morphometric analyses of kidney biopsy images for %GSG, %IFTA, and IFTA foci density among 3020 living kidney donors, 1363 patients with kidney tumor, and 314 patients with native kidney disease. Using normotensive donors, we defined young-age thresholds (18-29 years) and age-based (roughly by decade) 95th percentile thresholds. We compared age-adjusted risk of progressive CKD (kidney failure or 40% decline in eGFR) between nephrosclerosis that was "normal compared with young," "normal for age but abnormal compared with young," and "abnormal for age" in patients with tumor and patients with kidney disease. RESULTS: The 95th percentiles in the youngest group (18-29 years) to the oldest group (70 years or older) ranged from 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm 2 for IFTA foci density. Risk of progressive CKD did not differ between persons with nephrosclerosis "normal compared with young" versus "normal for age but abnormal compared with young." Risk of progressive CKD was significantly higher with %GSG, %IFTA, or IFTA foci density that was abnormal versus normal for age in both cohorts. CONCLUSIONS: Given that increased risk of progressive CKD occurs only when nephrosclerosis is abnormal for age, age-based thresholds for nephrosclerosis seem to be better than a single young-age threshold for identifying clinically relevant CKD.

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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

August 1, 2023

Volume

34

Issue

8

Start / End Page

1421 / 1432

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Renal Insufficiency, Chronic
  • Prognosis
  • Nephrosclerosis
  • Nephrectomy
  • Kidney
  • Humans
  • Fibrosis
  • Biopsy
  • Atrophy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Asghar, M. S., Denic, A., Mullan, A. F., Moustafa, A., Barisoni, L., Alexander, M. P., … Rule, A. D. (2023). Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD. J Am Soc Nephrol, 34(8), 1421–1432. https://doi.org/10.1681/ASN.0000000000000171
Asghar, Muhammad S., Aleksandar Denic, Aidan F. Mullan, Amr Moustafa, Laura Barisoni, Mariam P. Alexander, Mark D. Stegall, et al. “Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD.J Am Soc Nephrol 34, no. 8 (August 1, 2023): 1421–32. https://doi.org/10.1681/ASN.0000000000000171.
Asghar MS, Denic A, Mullan AF, Moustafa A, Barisoni L, Alexander MP, et al. Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD. J Am Soc Nephrol. 2023 Aug 1;34(8):1421–32.
Asghar, Muhammad S., et al. “Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD.J Am Soc Nephrol, vol. 34, no. 8, Aug. 2023, pp. 1421–32. Pubmed, doi:10.1681/ASN.0000000000000171.
Asghar MS, Denic A, Mullan AF, Moustafa A, Barisoni L, Alexander MP, Stegall MD, Augustine J, Leibovich BC, Thompson RH, Rule AD. Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD. J Am Soc Nephrol. 2023 Aug 1;34(8):1421–1432.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

August 1, 2023

Volume

34

Issue

8

Start / End Page

1421 / 1432

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Renal Insufficiency, Chronic
  • Prognosis
  • Nephrosclerosis
  • Nephrectomy
  • Kidney
  • Humans
  • Fibrosis
  • Biopsy
  • Atrophy