Leukemia (Blood Cancer)

 The term ‘lupus’ refers to systemic lupus erythematosus, ‘nephritis’ refers to the ‘nephron,’ the Greek word for kidney, and ‘itis’ means inflammation, so lupus nephritis refers to inflammation of the kidney that results from having systemic lupus erythematosus. Lupus is an autoimmune disease in which the immune system attacks various parts of the body, including the skin, joints, lungs, heart, central nervous system, and, of course, kidneys.

In fact, about half of all individuals with lupus develop some form of lupus nephritis. In lupus, what happens is that some cells have their DNA so badly damaged, that the cell undergoes programmed cell death, or apoptosis, and it dies. This produces all these little apoptotic bodies, and exposes the insides of the cell, including parts of the nucleus, like DNA, histones, and other proteins, to the rest of the body. Now in lupus, the immune system is more likely to think that cellular parts are foreign, or antigens, and since they’re from the nucleus, they're referred to as nuclear antigens, and immune cells try to attack them. Not only that though, but individuals with lupus also have less effective clearance, essentially they aren’t as good at getting rid of the apoptotic bodies and so they end up having more nuclear antigens floating around.

So as a result of all of this, B cells start producing antibodies against these pieces of the nucleus, which are called antinuclear antibodies. These antinuclear antibodies bind to nuclear antigens, forming antigen-antibody complexes, which drift away in the blood and deposit in various places including the kidneys. These immune complexes can then initiate an inflammatory reaction, which is known as a type III hypersensitivity reaction. Lupus nephritis is classified into various types depending on the exact site of these immune complexes and subsequent inflammatory reactions. The most common site of deposition is just underneath the capillary wall, also known as the endothelium, but deposits can also be within the Bowman’s space of the nephron, the basement membrane, or near the mesangial cells.

The extent of inflammation within the kidney can be focal, involving nephrons in just one area, or diffuse, involving almost all of the nephrons in both kidneys. In the majority of cases, lupus nephritis presents as a nephrotic syndrome, which means that the damage to the nephron allows plasma proteins to get into the urine, which causes proteinuria—typically greater than 3.5gms/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. However, in some cases, lupus nephritis can present as a nephritic syndrome, which means that the damage to the nephron ends up allowing red blood cells to filter into the urine, which causes hematuria or blood in the urine. The location of the lesions and the extent of kidney injury often predict whether the general presentation will be nephrotic versus nephritic, but it’s far from exact.

This brings us to the diagnosis of lupus nephritis. Which typically requires a kidney biopsy? Deposition of immune complexes in the Bowman’s space results in a characteristic crescent-shaped swelling of the area and deposition in the basement membrane can cause thickening of the structure, giving rise to a ‘wire-loop’ pattern. It’s also possible to look for the presence of immune markers like complement proteins and immunoglobulins in the glomerulus by staining them with fluorescent markers. Lupus nephritis is treated the same way that lupus is treated, by suppressing the immune system. This is often done with corticosteroids as well as specific medications like mycophenolate and cyclophosphamide.

Alright, as a quick recap. Lupus nephritis is inflammation of the kidneys caused by lupus and it can present as a nephrotic or nephritic syndrome. It occurs due to the deposition of the immune complexes in the nephron, type III hypersensitivity reaction, and the resulting inflammation causes damage that can be detected on a kidney biopsy.