Gearoid did a nice job reviewing the recent exciting findings surrounding primary Focal Segment Glomerulosclerosis (FSGS) and I thought it would be a good opportunity to review some of the sometimes confusing terminology and clinical basics.
To start, it's helpful to realize that the term "FSGS" is used both by pathologists and clinicians to describe related but different things.
In the pathology world FSGS is a nonspecific renal biopsy finding (there are multiple pathophysiologies that can lead to it).
A useful way to understand the key light microscopy findings is to break the name down stepwise. Glomerulosclerosis refers to an increased glomerular extracellular matrix with obliteration of the glomerular capillary lumen. You can see this in the image at the top where on the right side of the glomerulus the capillary loops are open and over on the left they're mostly filled in with pink extracellular material.
The pattern of glomerulosclerotic distribution in FSGS is focal and segmental. The term focal (as opposed to diffuse) refers to only some glomeruli displaying changes while the term segmental (as opposed to global) refers to portions of an individual glomeruli being involved rather than the entire glomerulus which again, you can see nicely in the top image.
To make matters more complex there are five recognized FSGS histologic subtypes:
1. Not Otherwise Specified (NOS) variant
2. Collapsing variant
3. Tip variant
4. Cellular variant
5. Perihilar variant
Each of these has pathogenic and prognostic implications which we'll leave for another post.
In the clinician's world the FSGS histologic pattern is seen in the disease states of primary (or idiopathic) FSGS and secondary FSGS which has multiple associated etiologies (genetic, infectious, drug induced, nephron loss from a variety of other renal diseases and so on). Distinguishing between primary and secondary forms is important because while primary disease is treated with immunnosuppressives, secondary disease treatment involves general CKD management and addressing the associated illness.
Clinically primary FSGS often presents with the insidious onset nephrotic syndrome. Microscopic dysmorphic hematuria is found in roughly half of cases. At presentation, around a third have hypertension and a quarter have impaired renal function. Individuals with continued nephrotic syndrome despite therapy often progress to the need for renal replacement therapy. Secondary forms of FSGS are less likely to present with nephrotic syndrome though exceptions do exist (eg HIV associated secondary FSGS with collapsing variant histology).
The image at the top is taken from the July NephSap which, if you haven't seen it yet, is a fantastic must read. For ASN members it's available online here.