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Quantitative morphometrics reveals glomerular changes in patients with infrequent segmentally sclerosed glomeruli
  1. Jennifer A Schaub1,
  2. Christopher L O'Connor1,
  3. Jian Shi1,
  4. Roger C Wiggins1,
  5. Kerby Shedden2,
  6. Jeffrey B Hodgin3,
  7. Markus Bitzer1
  1. 1Internal Medicine, University of Michigan Michigan Medicine, Ann Arbor, Michigan, USA
  2. 2Department of Statistics, University of Michigan, Ann Arbor, Michigan, USA
  3. 3Pathology, University of Michigan Michigan Medicine, Ann Arbor, Michigan, USA
  1. Correspondence to Dr Markus Bitzer, University of Michigan Michigan Medicine, Ann Arbor, MI 48109, USA; markusbi{at}med.umich.edu

Abstract

Aims Detection of one segmentally sclerosed glomerulus (SSG) identifies patients with focal segmental glomerulosclerosis (FSGS) but rare SSGs may be missed in kidney biopsies. It is unknown whether alterations of unaffected glomeruli in patients with infrequent SSG can be detected by quantitative morphometrics.

Methods We determined SSG frequency and obtained quantitative morphometrics in glomeruli without a pathologic phenotype in large kidney sections of non-involved kidney tissue from 137 patients undergoing total nephrectomy. We used multivariate modelling to identify morphometrics independently associated with increasing frequency of SSG and Receiver Operator Curve (ROC) analysis to determine the ability of quantitative morphometrics to identify patients with FSGS. We used the geometric distribution to estimate the sensitivity and specificity of a needle biopsy to identify patients with FSGS.

Results In seventy-one patients (51.8%), at least one SSG was observed, and of those, 39 (54.9%) had an SSG lesion in less than 2% of all glomeruli (mean of 249 glomeruli per specimen). Increasing percent of SSG was independently associated with decreasing podocyte density and increasing mesangial index in multivariate modelling. For infrequent SSG lesions (<1% of glomeruli), kidney biopsy could miss FSGS diagnosis more than 74% of the time, and podocyte density had an area under the curve (AUC) of 0.77, and mesangial index, an AUC of 0.79 to identify patients with FSGS.

Conclusions More than half of patients had FSGS, although 30% had infrequent SSG. Quantitative morphometrics in glomeruli without pathology, such as podocyte density and mesangial index, identified patients with infrequent SSG and may serve as clinical markers to identify patients with FSGS.

  • kidney
  • morphological and microscopic findings
  • nephrology
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Footnotes

  • Handling editor Runjan Chetty.

  • JAS and CLO contributed equally.

  • Contributors Research idea and study design: MB, JBH, RCW; data acquisition: CLO; data analysis/interpretation: JAS, CLO, MB; statistical analysis: JAS, KS, JS; supervision or mentorship: MB. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author’s own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

  • Funding MB received funding from R01 DK100449. MB received funding from the Michigan Institute for Clinical & Health Research (MICHR) of the University of Michigan (grant UL1TR002240). RCW was supported by the National Institutes of Health (grants R01 DK46073 and R01 DK102643). JBH is supported by National Institutes of Health (grants UG3 DK114907 and R01 DK118431). This work was additionally supported by P30 DK081943 (University of Michigan George M. O'Brien Kidney Center). The funders and institution did not have any role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the institutional review board of the University of Michigan (HUM00052918), and the requirement for consent was waived.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request from the corresponding author.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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