Glomerular involvement in storage diseases

Rosenmann, E.; Aviram, A

doi:10.1002/path.1711110111

Cited by 21 publications

(12 citation statements)

References 6 publications

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“…Although the histological character istics and disease entities associated with these lipid storage disorders have already been described in previ ous reports [2][3][4], only one case which was similar to ours has been reported. This case was quoted recently by Faraggiana and Churg [5], Its morphological changes and the clinical course were consistent with those in our patient [pers.…”

Section: Discussionmentioning

confidence: 64%

“…Though many kinds of renal abnormalities accompan ied by lipid metabolic disorders have been reported [2][3][4], this case did not resemble any disorder reported previ ously, except for one case that was quoted by Farragiana and Churg [5]. Therefore, we report this case in a com plete form as a new type of secondary nephrotic synin the literature which could be classified as a new kind of drome related to lipoprotein metabolic alterations.…”

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confidence: 82%

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A Case of Nephrotic Syndrome with Glomerular Lipoprotein Deposition with Capillary Ballooning and Mesangiolysis

Watanabe

Ozaki

Yoshida

et al. 1989

Nephron

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A 33-year-old man with nephrotic syndrome and rapid deterioration of renal function showed curious glomerular morphological abnormalities. Ballooning of the glomerular capillaries due to a substance accumulated in the capillary lumina and mesangiolysis were prominent histological features. The deposits in the capillary lumen were positive for Sudan III staining, and also for β-lipoprotein, apoprotein B and apoprotein E by immunofluorescent technique. The staining of β-lipoprotein in a flower leaf pattern was a striking characteristic, while such staining was negative when studied in 20 patients with nephrotic syndrome who were used as controls. Based on these findings, the morphological abnormalities in this case were considered to be related to lipoprotein deposition in the glomeruli. This case is thought to be the first reported in a complete form in the literature which could be classified as a new kind of disease related to lipoprotein metabolism abnormalities.

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Section: Discussionmentioning

confidence: 64%

mentioning

confidence: 82%

A Case of Nephrotic Syndrome with Glomerular Lipoprotein Deposition with Capillary Ballooning and Mesangiolysis

Watanabe

Ozaki

Yoshida

et al. 1989

Nephron

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“…Moreover, this demonstrates a role for SMPDL-3b in the modulation of actin remodeling in podocytes. In fact, a genetic disease characterized by excessive accumulation of sphyngomyelin owing to a lack of ASMase activity (Niemann-Pick disease) causes glomerular pathology (30), which supports an important role of sphyngomyelin metabolism in the pathogenesis of glomerulopathies. The fact that the downregulation of SMPDL-3b occurs within 1 to 2 hours after transplantation (Fig.…”

Section: Discussionmentioning

confidence: 92%

Rituximab Targets Podocytes in Recurrent Focal Segmental Glomerulosclerosis

et al. 2011

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Focal segmental glomerulosclerosis (FSGS) is a prevalent glomerular disease characterized by proteinuria, progression to end stage renal disease and recurrence of proteinuria after kidney transplantation in approximately one third of patients. It has been suggested that rituximab might treat recurrent FSGS through an unknown mechanism. Rituximab recognizes CD20 on B-lymphocytes but might also bind sphingomyelin-phosphodiesterase-acid-like-3b (SMPDL-3b) and regulates acid-sphyngomyelinase (ASMase) activity. We hypothesized that rituximab prevents recurrent FSGS and preserves podocyte SMPDL-3b expression. We studied 41 patients at high risk for recurrent FSGS, 27 of whom were treated with rituximab at time of kidney transplant. Incidence of nephrotic-range proteinuria and change in estimated glomerular filtration rate (ΔeGFR) were analyzed. SMPDL-3b immunostaining was performed in post-reperfusion kidney biopsies. SMPDL-3b protein, ASMase activity, and cytoskeleton remodeling were studied in cultured normal human podocytes that had been exposed to patient sera with or without rituximab. Rituximab treatment was associated with lower incidence of post-transplant proteinuria and decreased ΔeGFR. The number of SMPDL-3b+ podocytes in post-reperfusion biopsies was reduced in patients who developed recurrent FSGS. Rituximab partially prevented SMPDL-3b and ASMase downregulation that was observed in podocytes treated with the sera of patients with recurrent FSGS. Either SMPDL-3b overexpression or treatment with rituximab prevented disruption of the actin cytoskeleton and podocyte apoptosis induced by patient sera. This effect was diminished in cultured podocytes where the gene encoding SMPDL-3b was silenced. Our study suggests that treatment of high-risk patients with rituximab at time of kidney transplant might prevent recurrent FSGS by modulating podocyte function in an SMPDL-3b–dependent manner.

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“…In their conclusion, the authors highlight that the potential role of sphingolipid metabolism in glomerular injury [69]. This is supported by observed glomerular pathology in patients afflicted by the genetic disorder Niemann-Pick disease, in which sphingomyelin accumulates due to lack to lack of ASMase activity [70]. There is therefore some evidence for targeted protective action of rituximab on the podocyte actin cytoskeleton via preservation of sphingomyelin-related enzymes which can contribute to preservation of the glomerular filtration barrier and reduction of proteinuria following podocyte injury.…”

Section: Rituximabmentioning

confidence: 75%

The Podocyte as a Therapeutic Target in Proteinuric Kidney Disease

He¹

2013

J Nephrol Ther

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Kidney podocytes are highly differentiated cells with a complex cellular morphology. They are located inside the glomerulus, a corpuscle of capillaries through which blood is filtered hydrostatically through a high-volume/highdiscrimination filter. Neighboring podocyte Foot Processes (FP) is connected by a specialized cell-cell junction, the Slit Diaphragm (SD), which represents the main size selective filtration barrier in the kidney. The podocyte is an attractive cell for drug targeting due largely to its presence on the epithelial surface of one of the best vascularized organs in the body. Podocytes are exposed to 180 liters of filtered water and solutes each day, with the glomerular basement membrane and fenestrated glomerular endothelium not likely to be obstacles to small molecule passage. Though no podocyte-specific drugs are presently available, clinical nephrology has taken advantage of the pleitropic effects of a diverse array of therapeutic agents to treat glomerular disease. Glucocorticoids, retinoic acid, cyclosporine, abatacept, ACTH, thiazolidinedione, angiotensin converting enzyme inhibitors and rituximab have been successfully repurposed from other clinical indications to treat protein uric kidney disease. By different mechanisms these agents all nonspecifically target podocytes to promote their survival under disease conditions. This review summarizes the currently understood mechanistic basis for their use.

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Glomerular involvement in storage diseases

Cited by 21 publications

References 6 publications

A Case of Nephrotic Syndrome with Glomerular Lipoprotein Deposition with Capillary Ballooning and Mesangiolysis

A Case of Nephrotic Syndrome with Glomerular Lipoprotein Deposition with Capillary Ballooning and Mesangiolysis

Rituximab Targets Podocytes in Recurrent Focal Segmental Glomerulosclerosis

The Podocyte as a Therapeutic Target in Proteinuric Kidney Disease

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