BACKGROUND: Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates. METHODS: We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin's concordance coefficient (R(C)), coefficient of variation (CV) and coefficient of error (CE) measured reliability. RESULTS: IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P < 0.01), by race (P < 0.05) and in obese individuals (P < 0.01). Subjects with multiple chronic kidney disease (CKD) comorbidities showed significant increases in IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (R(C) > 0.95, <5% difference in CV and CE). These observations were not affected by a reduced sample size and did not disrupt the inverse linear correlation between mean IGV and estimated total glomerular number. CONCLUSIONS: Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.
BACKGROUND: Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates. METHODS: We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin's concordance coefficient (R(C)), coefficient of variation (CV) and coefficient of error (CE) measured reliability. RESULTS: IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P < 0.01), by race (P < 0.05) and in obese individuals (P < 0.01). Subjects with multiple chronic kidney disease (CKD) comorbidities showed significant increases in IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (R(C) > 0.95, <5% difference in CV and CE). These observations were not affected by a reduced sample size and did not disrupt the inverse linear correlation between mean IGV and estimated total glomerular number. CONCLUSIONS: Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.
Authors: Victor G Puelles; Rebecca N Douglas-Denton; Luise A Cullen-McEwen; Jinhua Li; Michael D Hughson; Wendy E Hoy; Peter G Kerr; John F Bertram Journal: J Am Soc Nephrol Date: 2015-01-07 Impact factor: 10.121
Authors: Victor G Puelles; Rebecca N Douglas-Denton; Monika A Zimanyi; James A Armitage; Michael D Hughson; Peter G Kerr; John F Bertram Journal: Nephrol Dial Transplant Date: 2014-05-02 Impact factor: 5.992
Authors: Aleksandar Denic; Mariam P Alexander; Vidhu Kaushik; Lilach O Lerman; John C Lieske; Mark D Stegall; Joseph J Larson; Walter K Kremers; Terri J Vrtiska; Harini A Chakkera; Emilio D Poggio; Andrew D Rule Journal: Am J Kidney Dis Date: 2016-02-06 Impact factor: 8.860
Authors: Aleksandar Denic; Jerry Mathew; Venkata V Nagineni; R Houston Thompson; Bradley C Leibovich; Lilach O Lerman; John C Lieske; Mariam P Alexander; Joshua J Augustine; Walter K Kremers; Andrew D Rule Journal: J Am Soc Nephrol Date: 2018-05-22 Impact factor: 10.121
Authors: Scott C Beeman; Luise A Cullen-McEwen; Victor G Puelles; Min Zhang; Teresa Wu; Edwin J Baldelomar; John Dowling; Jennifer R Charlton; Michael S Forbes; Amanda Ng; Qi-zhu Wu; James A Armitage; Gary F Egan; John F Bertram; Kevin M Bennett Journal: Am J Physiol Renal Physiol Date: 2014-03-19
Authors: Jennifer A Schaub; Christopher L O'Connor; Jian Shi; Roger C Wiggins; Kerby Shedden; Jeffrey B Hodgin; Markus Bitzer Journal: J Clin Pathol Date: 2021-01-11 Impact factor: 4.463
Authors: Michael D Hughson; Victor G Puelles; Wendy E Hoy; Rebecca N Douglas-Denton; Susan A Mott; John F Bertram Journal: Nephrol Dial Transplant Date: 2013-12-09 Impact factor: 5.992