Glomerular cell number in normal subjects and in type 1 diabetic patients

Michael W. Steffes, Derek Schmidt, Rebecca McCrery, John M. Basgen, Keith Drummond, Christine Aebi, Mimi Belmonte, Robert Gardiner, Paul Goodyear, Michael Kramer, Constantin Polychronakos, Samy Suissz, Diane Laforte, Jan Braaten, Kenneth Fautht, Khalil Khoury, Paul Czernichow, Veronique Beaudoin, Helen Beaufils, Claire Levy-MarchalMarie Claire Gubler, Phillippe Passa, Dominique Simon, Michael Mauer, Blanche Chavers, Thomas Hostetter, Youngki Kim, Connie Manske, Alfred Michael, Krisha Saxena, Alan Sinaiko, Robert Vernier, Trudy Strand, Richard Bergenstal, Joseph Sockalosky, Stephen Rich

Research output: Contribution to journalArticlepeer-review

313 Scopus citations

Abstract

Background. The number of cells in glomeruli has been a challenging measure, especially in human kidneys, with only a small amount of tissue obtained by biopsy. However, the number of cells and their function are important determinants of renal function in health and disease. Methods. Modern morphometric techniques have now provided the means to determine the numerical density (Nv) and number (with a measure of glomerular volume) of endothelial cells, mesangial cells, and podocytes in plastic-embedded renal tissue biopsied from nondiabetic subjects (N = 36) and type 1 diabetic patients (N = 46) over an extended age range from childhood through late adult. Results. Nv values for all glomerular cells varied only slightly with age and did not change within the range of glomerular lesions of diabetes studied. Thus, the increase in glomerular volume during childhood to a steady level thereafter was the primary determinant of total glomerular cell number. The number of mesangial cells and endothelial cells increased with age, reflecting the increase in all cells, while the podocytes remained unchanged in number over all ages studied (10 to 69 years). Numbers of total glomerular cells, mesangial cells, and endothelial cells were not changed with diabetes, while podocytes were fewer in number in diabetic patients of all ages, with reduced podocyte numbers even in diabetes of short duration. Conclusions. The essentially constant glomerular cell density in nondiabetic and diabetic subjects under different circumstances possibly indicates an underlying propensity for the glomerulus to regulate its architecture to maintain a constant number of cells per volume, no matter the size of the glomerulus or the severity of diabetic nephropathy studied in this set of patients. The reductions in podocyte numbers in both younger and older diabetic patients indicate a significant risk for functional abnormalities as diabetic nephropathy progresses. Moreover, these observations do not support the suggestion of marked increases in glomerular cell number (and especially mesangial cells) with the development and progression of diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)2104-2113
Number of pages10
JournalKidney international
Volume59
Issue number6
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (RO1-43605) and the American Diabetes Association. Preliminary data were presented at the meeting of the European Diabetic Nephropathy Study Group (EDNSG) on May 12, 2000, Lund, Sweden. Discussions and insights from Timothy Meyer greatly improved the manuscript. We thank Ms. Carol El-Ghandour and Ms. Lola Blackledge for preparation of the manuscript, and we greatly appreciate the staff of Bio-medical Image Processing Laboratory who were always helpful in the use of their facilities.

Keywords

  • Cell density
  • Diabetic nephropathy
  • Morphometry
  • Podocytes
  • Progressive renal disease
  • Renal function
  • Urine volume

Fingerprint Dive into the research topics of 'Glomerular cell number in normal subjects and in type 1 diabetic patients'. Together they form a unique fingerprint.

Cite this