Author: Tanner Marshall, MS
Editor: Rishi Desai, MD, MPH
Focal segmental glomerulosclerosis, or sometimes focal glomerular sclerosis, or just sometimes FSGS, is a type of kidney disease that affects the kidney’s glomeruli, which is where small molecules are first filtered out of blood and into the urine.
From the name, you have glomerulosclerosis, which indicates sclerosis, or scar tissue, forming in the glomeruli.
Segmental means that only a segment, or part of the glomeruli is affected, and focal means that among all those glomeruli in the kidney, only some are affected.
Those glomeruli that are affected, though, allow proteins to filter through into the urine, and ultimately people with FSGS develop nephrotic syndrome.
But what exactly is nephrotic syndrome? Well usually the glomerulus only lets small molecules, like sodium and water, move from the blood into the kidney nephron, where it eventually makes its way into the urine. But with nephrotic syndromes, the glomeruli are damaged and they become more permeable, so they start letting plasma proteins come across from the blood to the nephron and then into the urine, which causes proteinuria, typically greater than 3.5 grams per day.
An important protein in the blood is albumin, and so when it starts leaving the blood, people get hypoalbuminemia—low albumin in the blood. With less protein in the blood the oncotic pressure falls, which lowers the overall osmotic pressure, which drives water out of the blood vessels and into the tissues, called edema.
Finally, it’s thought that as a result of either losing albumin or losing some protein or proteins that inhibit the synthesis of lipids, or fat, you get increased levels of lipids in the blood, called hyperlipidemia.
Just like the proteins, these lipids can also get into the urine, causing lipiduria. And those are the hallmarks of nephrotic syndrome—proteinuria, hypoalbuminemia, edema, hyperlipidemia, and lipiduria.
So focal segmental glomerulosclerosis is a type of nephrotic syndrome, that’s helpful, but why does the glomerulus develop segmental sclerosis in the first place? Well, primary FSGS is when it’s idiopathic, or there’s no clear underlying cause. What is known, though, is that the podocytes, which are the cells that have these long tentacle-like projections, called foot processes, that wrap around the capillaries in the glomeruli, are damaged. These damaged podocytes allow some plasma proteins and lipids to sneak by, which then go on to get into the urine.
Not only that though, over time, some of these proteins and lipids to get trapped and build up in the glomerulus, resulting in hyalinosis, where the tissue has a hyaline or glassy appearance on histology, and it’s thought that over time these areas move on to develop sclerosis, or scar tissue.
Some research suggests that these changes in FSGS are a continuation from another nephrotic syndrome called minimal change disease which is also characterized by podocyte injury, Other research suggests that minimal change disease and FSGS have different mechanisms of podocyte injury.
Fundamentally, FSGS is a histopathologic description, basically what it looks like under a microscope, which could be the end result of a number of different pathophysiologic mechanisms.
As opposed to primary FSGS, Secondary FSGS is when there’s a clear underlying cause, and there are several important conditions that can be associated. Sickle cell disease, where blood cells are sickle-shaped due to a structurally abnormal hemoglobin protein that can cause tissue ischemia, has been linked to FSGS. HIV, a retrovirus that infects various human cell types, can lead to FSGS and is called HIV-associated nephropathy. Heroin abuse has also been linked to FSGS, which is called heroin nephropathy. Also, other conditions like kidney hyperperfusion or increased perfusion of blood, as well as increased pressure in the glomerular capillaries have been linked to FSGS as well.
Alright so on histology, there’ll be segmental sclerosis and hyalinosis of the glomeruli, and under electron microscope, there’s effacement of the foot processes of the podocytes. And on immunofluorescence, there might be nonspecific focal deposits of IgM and complement proteins, and these get trapped in the areas of hyalinosis, but these isn’t always seen. FSGS is the most common cause of nephrotic syndrome in African-Americans and Hispanics, and can affect both children and adults. FSGS is usually treated with steroids, although it has an inconsistent response, and for that reason, especially in adults—FSGS can involve more and more segments of the kidney’s glomeruli to the point where it causes chronic renal failure.
Alright, so as a quick recap, focal segmental glomerulosclerosis is a nephrotic syndrome characterized by sclerosis and hyalinosis in some, but not all, glomeruli, and usually only affects part of the glomeruli that it affects.
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Sources edit
Pathoma (text)
Robbins Basic Pathology (text)
First Aid USMLE Step 1 (text)
Pathophysiology, the biological basis for disease in adults and children (text)
https://en.wikipedia.org/wiki/Focal_segmental_glomerulosclerosis
