Morphometry Predicts Early GFR Change in Primary Proteinuric Glomerulopathies: A Longitudinal Cohort Study Using Generalized Estimating Equations.
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.
Department of Pediatrics, Division of Pediatric Nephrology, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
Kevin V
http://orcid.org/0000-0001-8342-5458
KV
Lemley
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
Serena M
SM
Bagnasco
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Cynthia C
CC
Nast
Department of Pathology, University of Miami, Miami, Florida, United States of America.
Laura
L
Barisoni
National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Catherine M
CM
Conway
National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Stephen M
SM
Hewitt
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
Peter X K
PX
Song
D000328:Adult; D001706:Biopsy; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D042241:Early Diagnosis; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000648:ultrastructure; D007674:Kidney Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D016014:Linear Models; D008137:Longitudinal Studies; D009929:Organ Size; D011379:Prognosis; D011507:Proteinuria / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D013223:Statistics as Topic