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-Marchal; Marie 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

doi:10.1046/j.1523-1755.2001.0590062104.x

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 journal › Article › peer-review

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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 (N_v) 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. N_v 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 language	English (US)
Pages (from-to)	2104-2113
Number of pages	10
Journal	Kidney international
Volume	59
Issue number	6
DOIs	https://doi.org/10.1046/j.1523-1755.2001.0590062104.x
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Steffes, M. W., Schmidt, D., McCrery, R., Basgen, J. M., Drummond, K., Aebi, C., Belmonte, M., Gardiner, R., Goodyear, P., Kramer, M., Polychronakos, C., Suissz, S., Laforte, D., Braaten, J., Fautht, K., Khoury, K., Czernichow, P., Beaudoin, V., Beaufils, H., ... Rich, S. (2001). Glomerular cell number in normal subjects and in type 1 diabetic patients. Kidney international, 59(6), 2104-2113. https://doi.org/10.1046/j.1523-1755.2001.0590062104.x

Steffes, MW, Schmidt, D, McCrery, R, Basgen, JM, Drummond, K, Aebi, C, Belmonte, M, Gardiner, R, Goodyear, P, Kramer, M, Polychronakos, C, Suissz, S, Laforte, D, Braaten, J, Fautht, K, Khoury, K, Czernichow, P, Beaudoin, V, Beaufils, H, Levy-Marchal, C, Gubler, MC, Passa, P, Simon, D, Mauer, M, Chavers, B, Hostetter, T, Kim, Y, Manske, C, Michael, A, Saxena, K, Sinaiko, A, Vernier, R, Strand, T, Bergenstal, R, Sockalosky, J & Rich, S 2001, 'Glomerular cell number in normal subjects and in type 1 diabetic patients', Kidney international, vol. 59, no. 6, pp. 2104-2113. https://doi.org/10.1046/j.1523-1755.2001.0590062104.x

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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.",

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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.",

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doi = "10.1046/j.1523-1755.2001.0590062104.x",

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T1 - Glomerular cell number in normal subjects and in type 1 diabetic patients

AU - Steffes, Michael W.

AU - Schmidt, Derek

AU - McCrery, Rebecca

AU - Basgen, John M.

AU - Drummond, Keith

AU - Aebi, Christine

AU - Belmonte, Mimi

AU - Gardiner, Robert

AU - Goodyear, Paul

AU - Kramer, Michael

AU - Polychronakos, Constantin

AU - Suissz, Samy

AU - Laforte, Diane

AU - Braaten, Jan

AU - Fautht, Kenneth

AU - Khoury, Khalil

AU - Czernichow, Paul

AU - Beaudoin, Veronique

AU - Beaufils, Helen

AU - Levy-Marchal, Claire

AU - Gubler, Marie Claire

AU - Passa, Phillippe

AU - Simon, Dominique

AU - Mauer, Michael

AU - Chavers, Blanche

AU - Hostetter, Thomas

AU - Kim, Youngki

AU - Manske, Connie

AU - Michael, Alfred

AU - Saxena, Krisha

AU - Sinaiko, Alan

AU - Vernier, Robert

AU - Strand, Trudy

AU - Bergenstal, Richard

AU - Sockalosky, Joseph

AU - Rich, Stephen

N1 - 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.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Cell density

KW - Diabetic nephropathy

KW - Morphometry

KW - Podocytes

KW - Progressive renal disease

KW - Renal function

KW - Urine volume

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JO - Kidney international

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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