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Art of Medicine: Minimal Change Disease

minimal change disease
The above painting shows podocytes with foot processes extending along the glomerular basement membrane of neighboring capillary loops.  Effacement of podocyte foot processes occurs in primary podocytopathies, including minimal change disease (see electron photomicrograph below). Minimal change disease is the most common etiology of idiopathic nephrotic syndrome in children and is the third most common cause in adults, after focal segmental glomerulosclerosis and membranous glomerulopathy.  A majority of cases are “primary”, require no additional workup, and are due to a circulating permeability factor.   Several possible secondary causes have also been identified.  Although these are rare, these should be considered in...

Twitter Poll (January 23, 2019)

CLL/SLL Patients, arkana laboratories,
ANSWER: A Although glomerular disease in patients with CLL/SLL is less common, the most frequent patterns of glomerular injury seen include MPGN (immune complex mediated), MCD, membranous GN, and monoclonal immunoglobulin deposition disease. The most common form of kidney involvement in patients with CLL/SLL is the presence of direct infiltration of the kidney parenchyma by leukemic cells. Although glomerular disease in patients with CLL/SLL is less common, they can be present.  The glomerular pattern of injury frequently seen in these group of patients include membranoproliferative glomerulonephritis (immune complex mediated), minimal change disease, membranous nephropathy, and monoclonal immunoglobulin deposition disease (nonamyloid...

Art of Medicine: Membranous Glomerulopathy

Membranous Glomerulopathy, Art of Medicine
The painting above depicts membranous glomerulopathy.   A single glomerular capillary loop with confluent subepithelial and intramembranous electron dense deposits along the glomerular basement membrane is shown.  Podocytes are showing foot process effacement and microvillous transformation, which results in loss of the filtration barrier leading to nephrotic syndrome.  An electron micrograph from a patient with membranous glomerulopathy is shown below. Membranous glomerulopathy is the second most common cause of nephrotic syndrome in adults.  A majority of cases are considered primary with autoantibodies directed against the podocyte antigens phospholipase A2 receptor (PLA2R, ~70% of cases) or thrombospondin type 1 domain containing 7A...

FSGS Types

Focal segmental glomerulosclerosis (FSGS)
Are there clues to help distinguish among primary, genetic, and secondary focal segmental glomerulosclerosis (FSGS) lesions?  Focal segmental glomerulosclerosis (FSGS) (Fig. 1) represents a morphologic pattern of injury rather than a specific disease.  Current thinking on this important subject is thoroughly presented in a recent review by De Vriese AS, Sethi S, et al (J Am Soc Nephrol 29: 759–774, 2018).   The authors discuss the three main etiologic categories of disease associated with FSGS lesions:  primary FSGS, genetic FSGS, and secondary (“maladaptive”) type FSGS.  The authors also emphasize the importance of determining whether the patient has nephrotic syndrome (defined by...

Foot Process Effacement and Focal Segmental Glomerulosclerosis

Focal Segmental Glomerulosclerosis
Knowing whether a patient has clinical nephrotic syndrome and knowing the degree of podocyte foot process effacement can be helpful diagnostic clues in separating “primary” from “secondary” forms of focal segmental glomerulosclerosis (FSGS). For example, in a patient with the nephrotic syndrome whose biopsy shows FSGS lesions and no significant immune deposits by immunofluorescence, the presence of global effacement of podocyte foot processes by electron microscopy (as seen in Fig 1) provides support for a “primary” FSGS (see reference). Sethi S et al. Focal and segmental glomerulosclerosis: clinical and kidney biopsy correlations. Clin Kidney J. 2014 Dec;7(6):531-7.PMID: 25503953.

Minimal Change Disease and New Onset DM type I

AN ODD COINCIDENCE? OR ARE THEY RELATED? This biopsy is from a teenager who had a viral illness 6 weeks ago. Five weeks ago, he developed polyphagia and polydipsia and was found to have new onset Type I Diabetes Mellitus. One week prior to renal biopsy, he had the sudden onset of facial edema and a urine protein/creatinine ratio of 7.8. Image 1. No change by light microscopy. Image 2. Diffuse and complete foot process effacement. Diagnosis: Minimal Change Disease Simultaneous occurrence of Type 1 Diabetes and Minimal Change Disease has been reported. Here is a link to a case...

Diffuse Mesangial Hypercellularity

This biopsy is from a previously healthy 3 year old female, who presented with sudden onset nephrotic syndrome, hypertension and microscopic hematuria. Light microscopy shows greater than 4 cells per mesangial region in most glomeruli (Fig 1), with absence of segmental glomerulosclerosis. Immunofluorescence is completely negative and electron microscopy shows diffuse epithelial foot process effacement (Fig 2). The findings are consistent with minimal change disease with diffuse mesangial hypercellularity. This pattern of injury is considered a variant of minimal change disease. Patients with diffuse mesangial hypercellularity have a higher risk of initial resistance to steroid therapy; however, it is not...