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Michael Mauer - One of the best experts on this subject based on the ideXlab platform.

  • quantitating glomerular Endothelial Fenestration an unbiased stereological approach
    American Journal of Nephrology, 2011
    Co-Authors: Behzad Najafian, Michael Mauer
    Abstract:

    Background/Aims: Glomerular Endothelial cells are fenestrated, allowing for especially high transcellular hydraulic conductivity. Current knowledge about Endothelial Fenestration structural changes in disease conditions is limited, partly due to the absence of robust methodologies to quantitate these structures. Herein, we propose a novel method for estimating the percentage of Endothelial Fenestration. Methods: An unbiased stereological method based on contiguity of two phases and surface area density estimation using isotropic uniform random line probes was developed. A line grid for intercept counting and classifying Endothelial coverage of fenestrated versus non-fenestrated areas was designed. The method was applied to renal biopsies from 15 patients with Fabry disease and 9 normal living kidney donor controls. Results: The percentage of glomerular capillary Endothelial coverage which was fenestrated was lower in Fabry patients (43 ± 12%) versus controls (53 ± 9%; p = 0.047). The fraction of Endothelial surface which was fenestrated was greater on the peripheral versus mesangial zones of the capillary walls in both Fabry patients (p = 0.00002) and controls (p = 0.0005). Conclusion: The proposed method provides an unbiased tool to quantitate Endothelial Fenestration changes in glomeruli. The practical example introduced showed reduced glomerular Endothelial Fenestration in Fabry nephropathy.

  • Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease
    Kidney international, 2010
    Co-Authors: Behzad Najafian, Einar Svarstad, Leif Bostad, Marie Claire Gubler, Camilla Tøndel, Chester B. Whitley, Michael Mauer
    Abstract:

    Progressive renal failure often complicates Fabry disease, the pathogenesis of which is not well understood. To further explore this we applied unbiased stereological quantitative methods to electron microscopic changes of Fabry nephropathy and the relationship between parameters of glomerular structure and renal function in 14 young Fabry patients (median age 12 years). Renal biopsies were obtained shortly before enzyme replacement therapy from these patients and from nine normal living kidney donors as controls. Podocyte globotriaosylceramide (GL-3) inclusion volume density increased progressively with age; however, there were no significant relationships between age and Endothelial or mesangial inclusion volume densities. Foot process width, greater in male Fabry patients, also progressively increased with age compared with the controls, and correlated directly with proteinuria. In comparison to the biopsies of the controls, Endothelial Fenestration was reduced in Fabry patients. Thus, our study found relationships between quantitative parameters of glomerular structure in Fabry nephropathy and age, as well as urinary protein excretion. Hence, podocyte injury may play a pivotal role in the development and progression of Fabry nephropathy.

  • podocyte detachment and reduced glomerular capillary Endothelial Fenestration in human type 1 diabetic nephropathy
    Diabetes, 2007
    Co-Authors: Masao Toyoda, Youngki Kim, Behzad Najafian, Luiza M Caramori, Michael Mauer
    Abstract:

    The aim of this study was to investigate the structural characteristics of podocytes and Endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [S S (Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR ( r = −0.71, P = 0.001) and directly with AER ( r = 0.66, P = 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects ( P = 0.001), normoalbuminuric patients ( P = 0.0002) and microalbuminuric patients ( P = 0.04) and correlated with renal structural and functional parameters, including AER ( r = −0.52, P = 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. S S (Fenestrated/cap) was reduced in normoalbuminuric ( P = 0.03), microalbuminuric ( P = 0.03), and proteinuric ( P = 0.002) patients versus control subjects. S S (Fenestrated/cap) correlated with mesangial fractional volume per glomerulus ( r = −0.57, P = 0.01), IFP ( r = 0.61, P = 0.007), and FPW ( r = −0.58, P = 0.01). These novel studies document that podocyte detachment and diminished Endothelial cell Fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/Endothelial cell functional interactions in diabetic nephropathy.

  • podocyte detachment and reduced glomerular capillary Endothelial Fenestration in human type 1 diabetic
    2007
    Co-Authors: Nephropathy Toyoda, Behzad Najafian, Youngki Kim, Luiza M Caramori, Michael Mauer
    Abstract:

    The aim of this study was to investigate the structural characteristics of podocytes and Endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [SS(Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR (r 0.71, P 0.001) and directly with AER (r 0.66, P 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects (P 0.001), normoalbuminuric patients (P 0.0002) and microalbuminuric patients (P 0.04) and correlated with renal structural and functional parameters, including AER (r 0.52, P 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. SS(Fenestrated/cap) was reduced in normoalbuminuric (P 0.03), microalbuminuric (P 0.03), and proteinuric (P 0.002) patients versus control subjects. SS(Fenestrated/cap) correlated with mesangial fractional volume per glomerulus (r 0.57, P 0.01), IFP (r 0.61, P 0.007), and FPW (r 0.58, P 0.01). These novel studies document that podocyte detachment and diminished Endothelial cell Fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/Endothelial cell functional interactions in diabetic nephropathy. Diabetes 56:2155‐2160, 2007

Behzad Najafian - One of the best experts on this subject based on the ideXlab platform.

  • quantitating glomerular Endothelial Fenestration an unbiased stereological approach
    American Journal of Nephrology, 2011
    Co-Authors: Behzad Najafian, Michael Mauer
    Abstract:

    Background/Aims: Glomerular Endothelial cells are fenestrated, allowing for especially high transcellular hydraulic conductivity. Current knowledge about Endothelial Fenestration structural changes in disease conditions is limited, partly due to the absence of robust methodologies to quantitate these structures. Herein, we propose a novel method for estimating the percentage of Endothelial Fenestration. Methods: An unbiased stereological method based on contiguity of two phases and surface area density estimation using isotropic uniform random line probes was developed. A line grid for intercept counting and classifying Endothelial coverage of fenestrated versus non-fenestrated areas was designed. The method was applied to renal biopsies from 15 patients with Fabry disease and 9 normal living kidney donor controls. Results: The percentage of glomerular capillary Endothelial coverage which was fenestrated was lower in Fabry patients (43 ± 12%) versus controls (53 ± 9%; p = 0.047). The fraction of Endothelial surface which was fenestrated was greater on the peripheral versus mesangial zones of the capillary walls in both Fabry patients (p = 0.00002) and controls (p = 0.0005). Conclusion: The proposed method provides an unbiased tool to quantitate Endothelial Fenestration changes in glomeruli. The practical example introduced showed reduced glomerular Endothelial Fenestration in Fabry nephropathy.

  • Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease
    Kidney international, 2010
    Co-Authors: Behzad Najafian, Einar Svarstad, Leif Bostad, Marie Claire Gubler, Camilla Tøndel, Chester B. Whitley, Michael Mauer
    Abstract:

    Progressive renal failure often complicates Fabry disease, the pathogenesis of which is not well understood. To further explore this we applied unbiased stereological quantitative methods to electron microscopic changes of Fabry nephropathy and the relationship between parameters of glomerular structure and renal function in 14 young Fabry patients (median age 12 years). Renal biopsies were obtained shortly before enzyme replacement therapy from these patients and from nine normal living kidney donors as controls. Podocyte globotriaosylceramide (GL-3) inclusion volume density increased progressively with age; however, there were no significant relationships between age and Endothelial or mesangial inclusion volume densities. Foot process width, greater in male Fabry patients, also progressively increased with age compared with the controls, and correlated directly with proteinuria. In comparison to the biopsies of the controls, Endothelial Fenestration was reduced in Fabry patients. Thus, our study found relationships between quantitative parameters of glomerular structure in Fabry nephropathy and age, as well as urinary protein excretion. Hence, podocyte injury may play a pivotal role in the development and progression of Fabry nephropathy.

  • podocyte detachment and reduced glomerular capillary Endothelial Fenestration in human type 1 diabetic nephropathy
    Diabetes, 2007
    Co-Authors: Masao Toyoda, Youngki Kim, Behzad Najafian, Luiza M Caramori, Michael Mauer
    Abstract:

    The aim of this study was to investigate the structural characteristics of podocytes and Endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [S S (Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR ( r = −0.71, P = 0.001) and directly with AER ( r = 0.66, P = 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects ( P = 0.001), normoalbuminuric patients ( P = 0.0002) and microalbuminuric patients ( P = 0.04) and correlated with renal structural and functional parameters, including AER ( r = −0.52, P = 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. S S (Fenestrated/cap) was reduced in normoalbuminuric ( P = 0.03), microalbuminuric ( P = 0.03), and proteinuric ( P = 0.002) patients versus control subjects. S S (Fenestrated/cap) correlated with mesangial fractional volume per glomerulus ( r = −0.57, P = 0.01), IFP ( r = 0.61, P = 0.007), and FPW ( r = −0.58, P = 0.01). These novel studies document that podocyte detachment and diminished Endothelial cell Fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/Endothelial cell functional interactions in diabetic nephropathy.

  • podocyte detachment and reduced glomerular capillary Endothelial Fenestration in human type 1 diabetic
    2007
    Co-Authors: Nephropathy Toyoda, Behzad Najafian, Youngki Kim, Luiza M Caramori, Michael Mauer
    Abstract:

    The aim of this study was to investigate the structural characteristics of podocytes and Endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [SS(Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR (r 0.71, P 0.001) and directly with AER (r 0.66, P 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects (P 0.001), normoalbuminuric patients (P 0.0002) and microalbuminuric patients (P 0.04) and correlated with renal structural and functional parameters, including AER (r 0.52, P 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. SS(Fenestrated/cap) was reduced in normoalbuminuric (P 0.03), microalbuminuric (P 0.03), and proteinuric (P 0.002) patients versus control subjects. SS(Fenestrated/cap) correlated with mesangial fractional volume per glomerulus (r 0.57, P 0.01), IFP (r 0.61, P 0.007), and FPW (r 0.58, P 0.01). These novel studies document that podocyte detachment and diminished Endothelial cell Fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/Endothelial cell functional interactions in diabetic nephropathy. Diabetes 56:2155‐2160, 2007

Hannu Jalanko - One of the best experts on this subject based on the ideXlab platform.

  • Advance Access publication xx xx xxxx Original Article Glomerular endothelium in kidneys with congenital nephrotic syndrome of the Finnish type (NPHS1)
    2016
    Co-Authors: Anne Kaukinen, Arvimatti Kuusniemi, I Lautenschlager, Hannu Jalanko
    Abstract:

    Background. The role of glomerular capillary endothe-lium in the pathophysiology of nephrotic kidney diseases is poorly known. We analysed the glomerular Endothelial lesions in kidneys from patients with congenital nephrotic syndrome of the Finnish type (NPHS1). The disorder is caused by a genetic defect in a major podocyte slit di-aphragm protein, nephrin. It manifests as nephrotic syn-drome soon after birth and leads to glomerular sclerosis in early childhood. Methods. The glomerular capillary and Endothelial cell le-sions in NPHS1 kidneys nephrectomized at infancy were studied by electron and light microscopy, immunohisto-chemistry and cytokine antibody array. Results. Mesangial expansion and capillary obliteration were evident in practically all NPHS1 glomeruli. No throm-bus formation was detected by fibrin staining. Electron microscopy revealed Endothelial blebs (endotheliosis). The Endothelial Fenestration and the attachment of Endothelial cells to the basement membrane were, however, quite nor-mal. This fits to the abundant expression of a vascular en-dothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1α (HIF-1α), in NPHS1 glomer-uli. The proliferative activity of the intracapillary cells was modest and no apoptosis was detected. The expression of an Endothelial adhesion molecule, intercellular adhesion molecule 1 (ICAM-1) and several chemokines was upreg-ulated in NPHS1 glomeruli as compared to adult control kidneys. The recruitment of leukocytes carrying ligands for the major Endothelial adhesion molecules, however, was modest in the mesangial area of NPHS1 glomeruli. Conclusions. The findings indicate that the glomerular en-dothelium is quite resistant to the nephrotic state in NPHS1 kidneys and underscores the importance of mesangial cells in the progression of glomerular sclerosis

  • glomerular endothelium in kidneys with congenital nephrotic syndrome of the finnish type nphs1
    Nephrology Dialysis Transplantation, 2007
    Co-Authors: Anne Kaukinen, Arvimatti Kuusniemi, I Lautenschlager, Hannu Jalanko
    Abstract:

    Background. The role of glomerular capillary endothelium in the pathophysiology of nephrotic kidney diseases is poorly known. We analysed the glomerular Endothelial lesions in kidneys from patients with congenital nephrotic syndrome of the Finnish type (NPHS1). The disorder is caused by a genetic defect in a major podocyte slit diaphragm protein, nephrin. It manifests as nephrotic syndrome soon after birth and leads to glomerular sclerosis in early childhood. Methods. The glomerular capillary and Endothelial cell lesions in NPHS1 kidneys nephrectomized at infancy were studied by electron and light microscopy, immunohistochemistry and cytokine antibody array. Results. Mesangial expansion and capillary obliteration wereevidentinpracticallyallNPHS1glomeruli.Nothrombus formation was detected by fibrin staining. Electron microscopy revealed Endothelial blebs (endotheliosis). The Endothelial Fenestration and the attachment of Endothelial cells to the basement membrane were, however, quite normal. This fits to the abundant expression of a vascular Endothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1α (HIF-1α), in NPHS1 glomeruli. The proliferative activity of the intracapillary cells was modest and no apoptosis was detected. The expression of an Endothelial adhesion molecule, intercellular adhesion molecule 1 (ICAM-1) and several chemokines was upregulated in NPHS1 glomeruli as compared to adult control kidneys. The recruitment of leukocytes carrying ligands forthemajorEndothelialadhesionmolecules,however,was modest in the mesangial area of NPHS1 glomeruli. Conclusions. The findings indicate that the glomerular endothelium is quite resistant to the nephrotic state in NPHS1 kidneys and underscores the importance of mesangial cells in the progression of glomerular sclerosis.

Anne Kaukinen - One of the best experts on this subject based on the ideXlab platform.

  • Advance Access publication xx xx xxxx Original Article Glomerular endothelium in kidneys with congenital nephrotic syndrome of the Finnish type (NPHS1)
    2016
    Co-Authors: Anne Kaukinen, Arvimatti Kuusniemi, I Lautenschlager, Hannu Jalanko
    Abstract:

    Background. The role of glomerular capillary endothe-lium in the pathophysiology of nephrotic kidney diseases is poorly known. We analysed the glomerular Endothelial lesions in kidneys from patients with congenital nephrotic syndrome of the Finnish type (NPHS1). The disorder is caused by a genetic defect in a major podocyte slit di-aphragm protein, nephrin. It manifests as nephrotic syn-drome soon after birth and leads to glomerular sclerosis in early childhood. Methods. The glomerular capillary and Endothelial cell le-sions in NPHS1 kidneys nephrectomized at infancy were studied by electron and light microscopy, immunohisto-chemistry and cytokine antibody array. Results. Mesangial expansion and capillary obliteration were evident in practically all NPHS1 glomeruli. No throm-bus formation was detected by fibrin staining. Electron microscopy revealed Endothelial blebs (endotheliosis). The Endothelial Fenestration and the attachment of Endothelial cells to the basement membrane were, however, quite nor-mal. This fits to the abundant expression of a vascular en-dothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1α (HIF-1α), in NPHS1 glomer-uli. The proliferative activity of the intracapillary cells was modest and no apoptosis was detected. The expression of an Endothelial adhesion molecule, intercellular adhesion molecule 1 (ICAM-1) and several chemokines was upreg-ulated in NPHS1 glomeruli as compared to adult control kidneys. The recruitment of leukocytes carrying ligands for the major Endothelial adhesion molecules, however, was modest in the mesangial area of NPHS1 glomeruli. Conclusions. The findings indicate that the glomerular en-dothelium is quite resistant to the nephrotic state in NPHS1 kidneys and underscores the importance of mesangial cells in the progression of glomerular sclerosis

  • glomerular endothelium in kidneys with congenital nephrotic syndrome of the finnish type nphs1
    Nephrology Dialysis Transplantation, 2007
    Co-Authors: Anne Kaukinen, Arvimatti Kuusniemi, I Lautenschlager, Hannu Jalanko
    Abstract:

    Background. The role of glomerular capillary endothelium in the pathophysiology of nephrotic kidney diseases is poorly known. We analysed the glomerular Endothelial lesions in kidneys from patients with congenital nephrotic syndrome of the Finnish type (NPHS1). The disorder is caused by a genetic defect in a major podocyte slit diaphragm protein, nephrin. It manifests as nephrotic syndrome soon after birth and leads to glomerular sclerosis in early childhood. Methods. The glomerular capillary and Endothelial cell lesions in NPHS1 kidneys nephrectomized at infancy were studied by electron and light microscopy, immunohistochemistry and cytokine antibody array. Results. Mesangial expansion and capillary obliteration wereevidentinpracticallyallNPHS1glomeruli.Nothrombus formation was detected by fibrin staining. Electron microscopy revealed Endothelial blebs (endotheliosis). The Endothelial Fenestration and the attachment of Endothelial cells to the basement membrane were, however, quite normal. This fits to the abundant expression of a vascular Endothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1α (HIF-1α), in NPHS1 glomeruli. The proliferative activity of the intracapillary cells was modest and no apoptosis was detected. The expression of an Endothelial adhesion molecule, intercellular adhesion molecule 1 (ICAM-1) and several chemokines was upregulated in NPHS1 glomeruli as compared to adult control kidneys. The recruitment of leukocytes carrying ligands forthemajorEndothelialadhesionmolecules,however,was modest in the mesangial area of NPHS1 glomeruli. Conclusions. The findings indicate that the glomerular endothelium is quite resistant to the nephrotic state in NPHS1 kidneys and underscores the importance of mesangial cells in the progression of glomerular sclerosis.

Robert G Nelson - One of the best experts on this subject based on the ideXlab platform.

  • podocyte detachment and reduced glomerular capillary Endothelial Fenestration promote kidney disease in type 2 diabetic nephropathy
    Kidney International, 2012
    Co-Authors: Jennifer E Weil, Kevin V Lemley, Clinton C Mason, Berne Yee, Lois I Jones, Kristina Blouch, Tracy Lovato, Meghan Richardson, Bryan D Myers, Robert G Nelson
    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.