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Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy.

Weil EJ, Lemley KV, Mason CC, Yee B, Jones LI, Blouch K, Lovato T, Richardson M, Myers BD, Nelson RG - Kidney Int. (2012)

Bottom Line: Podocyte detachment correlated significantly with podocyte number per glomerulus and albuminuria.The mean percentage of endothelial cell fenestration was significantly lower in macroalbuminuria (19.3%) than in normal albuminuria (27.4%) or microalbuminuria (27.2%) and correlated significantly with glomerular basement membrane thickness, albuminuria, fractional mesangial area, and the glomerular filtration rate (iothalamate clearance).Whether podocyte detachment creates conduits for proteins to escape the glomerular circulation and reduced endothelial fenestration lowers glomerular hydraulic permeability requires further study.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014-4972, USA. rnelson@nih.gov

ABSTRACT
Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from 10 kidney donors (not American Indians) showed almost undetectable (0.03%) podocyte detachment and 43.5% endothelial cell fenestration. In patients with type 2 diabetes, by comparison, the mean percentage of podocyte detachment was significantly higher in macroalbuminuria (1.48%) than in normal albuminuria (0.41%) or microalbuminuria (0.37%). Podocyte detachment correlated significantly with podocyte number per glomerulus and albuminuria. The mean percentage of endothelial cell fenestration was significantly lower in macroalbuminuria (19.3%) than in normal albuminuria (27.4%) or microalbuminuria (27.2%) and correlated significantly with glomerular basement membrane thickness, albuminuria, fractional mesangial area, and the glomerular filtration rate (iothalamate clearance). Podocyte detachment and diminished endothelial cell fenestration were not correlated, but were related to classic lesions of diabetic nephropathy. Thus, our findings confirm the important role these injuries play in the development and progression of kidney disease in type 2 diabetes, just as they do in type 1 diabetes. Whether podocyte detachment creates conduits for proteins to escape the glomerular circulation and reduced endothelial fenestration lowers glomerular hydraulic permeability requires further study.

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Related in: MedlinePlus

Peripheral glomerular capillaries illustrating intact and detached podocyte foot processes from a macroalbuminuric Pima Indian with type 2 diabetes mellitus, trasnmission electron microscopy ×11,280. (a) Intact podocyte foot processes. (b) Podocyte foot process detachment. CL, capillary lumen; EC, endothelial cell; P, podocyte foot processes intact; PD, podocyte foot process detachment; RBC, red blood cell; WBC, white blood cell.
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Figure 1: Peripheral glomerular capillaries illustrating intact and detached podocyte foot processes from a macroalbuminuric Pima Indian with type 2 diabetes mellitus, trasnmission electron microscopy ×11,280. (a) Intact podocyte foot processes. (b) Podocyte foot process detachment. CL, capillary lumen; EC, endothelial cell; P, podocyte foot processes intact; PD, podocyte foot process detachment; RBC, red blood cell; WBC, white blood cell.

Mentions: Mean percentage of PD was higher in participants with macroalbuminuria (1.48%) than in those with normo- (0.41%; p=0.04) or microalbuminuria (0.37%; p=0.02). Mean percentage of normal ECF was lower in the macroalbuminuric group (19.3%) than in those with normo- (27.4%; p=0.01) or microalbuminuria (27.2; p=5.0×10−3). PD was virtually nonexistent (0.03%) and ECF was 43.5% in normal kidney donors. Figures 1 and 2 illustrate PD and abnormal ECF in T2DM. Percentage of normal ECF directly across the GBM from detached podocytes was 37.0% in the diabetic subjects, and the overall percentage of normal ECF was 27.2% in the same subjects (p=0.09).


Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy.

Weil EJ, Lemley KV, Mason CC, Yee B, Jones LI, Blouch K, Lovato T, Richardson M, Myers BD, Nelson RG - Kidney Int. (2012)

Peripheral glomerular capillaries illustrating intact and detached podocyte foot processes from a macroalbuminuric Pima Indian with type 2 diabetes mellitus, trasnmission electron microscopy ×11,280. (a) Intact podocyte foot processes. (b) Podocyte foot process detachment. CL, capillary lumen; EC, endothelial cell; P, podocyte foot processes intact; PD, podocyte foot process detachment; RBC, red blood cell; WBC, white blood cell.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472108&req=5

Figure 1: Peripheral glomerular capillaries illustrating intact and detached podocyte foot processes from a macroalbuminuric Pima Indian with type 2 diabetes mellitus, trasnmission electron microscopy ×11,280. (a) Intact podocyte foot processes. (b) Podocyte foot process detachment. CL, capillary lumen; EC, endothelial cell; P, podocyte foot processes intact; PD, podocyte foot process detachment; RBC, red blood cell; WBC, white blood cell.
Mentions: Mean percentage of PD was higher in participants with macroalbuminuria (1.48%) than in those with normo- (0.41%; p=0.04) or microalbuminuria (0.37%; p=0.02). Mean percentage of normal ECF was lower in the macroalbuminuric group (19.3%) than in those with normo- (27.4%; p=0.01) or microalbuminuria (27.2; p=5.0×10−3). PD was virtually nonexistent (0.03%) and ECF was 43.5% in normal kidney donors. Figures 1 and 2 illustrate PD and abnormal ECF in T2DM. Percentage of normal ECF directly across the GBM from detached podocytes was 37.0% in the diabetic subjects, and the overall percentage of normal ECF was 27.2% in the same subjects (p=0.09).

Bottom Line: Podocyte detachment correlated significantly with podocyte number per glomerulus and albuminuria.The mean percentage of endothelial cell fenestration was significantly lower in macroalbuminuria (19.3%) than in normal albuminuria (27.4%) or microalbuminuria (27.2%) and correlated significantly with glomerular basement membrane thickness, albuminuria, fractional mesangial area, and the glomerular filtration rate (iothalamate clearance).Whether podocyte detachment creates conduits for proteins to escape the glomerular circulation and reduced endothelial fenestration lowers glomerular hydraulic permeability requires further study.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014-4972, USA. rnelson@nih.gov

ABSTRACT
Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from 10 kidney donors (not American Indians) showed almost undetectable (0.03%) podocyte detachment and 43.5% endothelial cell fenestration. In patients with type 2 diabetes, by comparison, the mean percentage of podocyte detachment was significantly higher in macroalbuminuria (1.48%) than in normal albuminuria (0.41%) or microalbuminuria (0.37%). Podocyte detachment correlated significantly with podocyte number per glomerulus and albuminuria. The mean percentage of endothelial cell fenestration was significantly lower in macroalbuminuria (19.3%) than in normal albuminuria (27.4%) or microalbuminuria (27.2%) and correlated significantly with glomerular basement membrane thickness, albuminuria, fractional mesangial area, and the glomerular filtration rate (iothalamate clearance). Podocyte detachment and diminished endothelial cell fenestration were not correlated, but were related to classic lesions of diabetic nephropathy. Thus, our findings confirm the important role these injuries play in the development and progression of kidney disease in type 2 diabetes, just as they do in type 1 diabetes. Whether podocyte detachment creates conduits for proteins to escape the glomerular circulation and reduced endothelial fenestration lowers glomerular hydraulic permeability requires further study.

Show MeSH
Related in: MedlinePlus