Morphometry Predicts Early GFR Change in Primary Proteinuric Glomerulopathies: A Longitudinal Cohort Study Using Generalized Estimating Equations

Kevin V. Lemley, Serena M. Bagnasco, Cynthia C. Nast, Laura Barisoni-Thomas, Catherine M. Conway, Stephen M. Hewitt, Peter X.K. Song

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

OBJECTIVE: Most predictive models of kidney disease progression have not incorporated structural data. If structural variables have been used in models, they have generally been only semi-quantitative.

METHODS: We examined the predictive utility of quantitative structural parameters measured on the digital images of baseline kidney biopsies from the NEPTUNE study of primary proteinuric glomerulopathies. These variables were included in longitudinal statistical models predicting the change in estimated glomerular filtration rate (eGFR) over up to 55 months of follow-up.

RESULTS: The participants were fifty-six pediatric and adult subjects from the NEPTUNE longitudinal cohort study who had measurements made on their digital biopsy images; 25% were African-American, 70% were male and 39% were children; 25 had focal segmental glomerular sclerosis, 19 had minimal change disease, and 12 had membranous nephropathy. We considered four different sets of candidate predictors, each including four quantitative structural variables (for example, mean glomerular tuft area, cortical density of patent glomeruli and two of the principal components from the correlation matrix of six fractional cortical areas-interstitium, atrophic tubule, intact tubule, blood vessel, sclerotic glomerulus, and patent glomerulus) along with 13 potentially confounding demographic and clinical variables (such as race, age, diagnosis, and baseline eGFR, quantitative proteinuria and BMI). We used longitudinal linear models based on these 17 variables to predict the change in eGFR over up to 55 months. All 4 models had a leave-one-out cross-validated R2 of about 62%.

CONCLUSIONS: Several combinations of quantitative structural variables were significantly and strongly associated with changes in eGFR. The structural variables were generally stronger than any of the confounding variables, other than baseline eGFR. Our findings suggest that quantitative assessment of diagnostic renal biopsies may play a role in estimating the baseline risk of succeeding loss of renal function in future clinical studies, and possibly in clinical practice.

Original languageEnglish (US)
Pages (from-to)e0157148
JournalPLoS One
Volume11
Issue number6
DOIs
StatePublished - 2016

Fingerprint

glomerulopathy
glomerular filtration rate
morphometry
cohort studies
Glomerular Filtration Rate
Longitudinal Studies
Cohort Studies
Biopsy
biopsy
patents
kidney diseases
Kidney
kidneys
Lipoid Nephrosis
Membranous Glomerulonephritis
Pediatrics
Confounding Factors (Epidemiology)
Blood vessels
Kidney Diseases
sclerosis

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Morphometry Predicts Early GFR Change in Primary Proteinuric Glomerulopathies : A Longitudinal Cohort Study Using Generalized Estimating Equations. / Lemley, Kevin V.; Bagnasco, Serena M.; Nast, Cynthia C.; Barisoni-Thomas, Laura; Conway, Catherine M.; Hewitt, Stephen M.; Song, Peter X.K.

In: PLoS One, Vol. 11, No. 6, 2016, p. e0157148.

Research output: Contribution to journalArticle

Lemley, Kevin V. ; Bagnasco, Serena M. ; Nast, Cynthia C. ; Barisoni-Thomas, Laura ; Conway, Catherine M. ; Hewitt, Stephen M. ; Song, Peter X.K. / Morphometry Predicts Early GFR Change in Primary Proteinuric Glomerulopathies : A Longitudinal Cohort Study Using Generalized Estimating Equations. In: PLoS One. 2016 ; Vol. 11, No. 6. pp. e0157148.
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AU - Conway, Catherine M.

AU - Hewitt, Stephen M.

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AB - OBJECTIVE: Most predictive models of kidney disease progression have not incorporated structural data. If structural variables have been used in models, they have generally been only semi-quantitative.METHODS: We examined the predictive utility of quantitative structural parameters measured on the digital images of baseline kidney biopsies from the NEPTUNE study of primary proteinuric glomerulopathies. These variables were included in longitudinal statistical models predicting the change in estimated glomerular filtration rate (eGFR) over up to 55 months of follow-up.RESULTS: The participants were fifty-six pediatric and adult subjects from the NEPTUNE longitudinal cohort study who had measurements made on their digital biopsy images; 25% were African-American, 70% were male and 39% were children; 25 had focal segmental glomerular sclerosis, 19 had minimal change disease, and 12 had membranous nephropathy. We considered four different sets of candidate predictors, each including four quantitative structural variables (for example, mean glomerular tuft area, cortical density of patent glomeruli and two of the principal components from the correlation matrix of six fractional cortical areas-interstitium, atrophic tubule, intact tubule, blood vessel, sclerotic glomerulus, and patent glomerulus) along with 13 potentially confounding demographic and clinical variables (such as race, age, diagnosis, and baseline eGFR, quantitative proteinuria and BMI). We used longitudinal linear models based on these 17 variables to predict the change in eGFR over up to 55 months. All 4 models had a leave-one-out cross-validated R2 of about 62%.CONCLUSIONS: Several combinations of quantitative structural variables were significantly and strongly associated with changes in eGFR. The structural variables were generally stronger than any of the confounding variables, other than baseline eGFR. Our findings suggest that quantitative assessment of diagnostic renal biopsies may play a role in estimating the baseline risk of succeeding loss of renal function in future clinical studies, and possibly in clinical practice.

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