What is Systemic Lupus Erythematosus?

Systemic Lupus Erythematosus (SLE) is an illness where your body’s immune system attacks you by creating antibodies in the lymph nodes that can attack your body’s specific cells. These are called autoantibodies, and the act of your body attacking itself is called autoimmune disease. Ordinarily, your body will have many checkpoints to not only prevent the production of autoantibodies, but also filter out silly cells that manage to create them to keep you safe. However, a series of missteps can lead to autoimmune disease, although it is not yet entirely understood what causes this. The autoantibodies produced can attack various regions of the body, and during the course of the disease, the part of the body attacked can change as well. Typically, in SLE, a vast array of symptoms may be experienced, including:¹

• A ‘butterfly’ rash across the cheeks and bridge of the nose
• Fatigue
• Round scaly rash on the body
• Abdominal pain
• Swelling in the lower extremities or on the face
• Painless sores in the mouth
• Pain during deep inhalation from inflammation in the chest cavity
• Arthritis
• Seizures
• Dizziness
• Depression
• Kidney failure

Organs affected range from the brain, the joints, the kidneys, the visceral layers of the lungs, to the heart.¹ The inflammation can lead to scarring of whichever organ is attacked, either to part of the functional area, to the supportive tissue lining the outside of the organ or to the main flesh of the organ itself, which helps it function. For example, SLE affecting the heart may cause damage to the heart valves, may lead to scarring of the lining of the heart (pericardium) and/or inflame the heart muscle itself (myocardium), thus leading to scarring that can alter its functional efficiency.¹ In the same way, SLE can affect the kidneys.

How are the kidneys affected in SLE?

One of the many organs affected in SLE is the kidneys, with effects of the condition ranging from simple to severe. The kidneys ordinarily function to push small blood components out of a tangle of blood vessels called the glomeruli into the kidney loops, where the blood is filtered, thus allowing clean blood to be reabsorbed. The waste products filtered out are collected and emptied into the renal papillae, which feed into the renal pelvis and then the urethra, which expels the waste as urine.

When affected by SLE, a number of different parts of the kidney can be affected, with over half of SLE patients experiencing some kind of kidney effect due to their disease³. The glomeruli can be attacked by your body, causing damage and thus permitting large blood components into the filtering system, such as red blood cells and protein. Consequently, these large molecules may make it into the urine as well, showing up as either blood or protein in the urine. This damage to the kidney structure can make them less efficient at their job.

Inflammation and scarring of the scarring loops can also affect kidney function, again decreasing efficiency but perhaps also leaving toxins within the blood. Excess products may also not be removed as a result, which can lead to swelling and oedema in parts of the body from the imbalance of electrolytes and water. The kidneys also play a key role in controlling blood pressure, both through water-balance and through other systems, so kidney damage may lead to high blood pressure too.¹⁰

Figure 1: Coronal diagram of a kidney depicting gross structures.²

The renal papilla can also be affected by SLE, making it difficult for toxins and waste to be collected and emptied into the renal pelvis as urine. Their death (necrosis) can occur as a complication of SLE, causing inflammation of the kidney (lupus nephritis) and has serious consequences on kidney function.^9,10 If the glomeruli are inflamed, the rest of the blood vessels in the kidney may also sustain damage, such as those supplying the renal papillae. Because this part of the kidney already receives little blood flow, diminishing this further can cause part of the renal papillae to die from lack of oxygen and nutrients, meaning they couldn’t create enough energy to survive through respiration (necrosis).¹²

Another cause of renal papillae necrosis in SLE is via comorbidities that exist in SLE, such as antiphospholipid syndrome.¹³ This can result in an increased risk of blood clots forming within blood vessels (atheromas), and if one forms and blocks the blood flow to the renal papillae, then again blood will not reach them and they will necrose from a lack of energy and hypoxia.

Scarring of the filtering tubes can also limit the amount of urine that is filtered and prevent it from draining into the renal papillae. This pressure increase within the filtering system can, over time, affect the drainage capacity of the renal papillae, and over a long period of time this may cause renal papillary necrosis.

Frequent urinary tract infections (UTIs), which are quite common in women due to their 4x shorter urethra compared to men, may also infect the renal pelvis and papillae in very severe cases, thus causing necrosis, especially if the woman in question is diabetic.¹¹ The necrosed renal papillae in any of these cases may detach from the renal pyramids and wander, thus possibly leading to painful kidney stones forming.

Ultimately, if the inflammation continues, especially in different parts of the kidney, then eventually the kidneys will stop working (end-stage renal disease). With the body no longer able to remove water-soluble waste and toxins, this can build up in the bloodstream and be deadly. Dialysis can help resolve the situation, but it is very time-consuming and costly, thus not a perfect plan. Transplants may be an option in this case.

What causes SLE?

SLE is a complex autoimmune disorder that arises from your own body’s immune system attacking itself with autoantibodies. This may be caused by a combination of genetic predispositions, environmental factors and hormonal influences. The exact cause is not fully understood, but several key factors are known to contribute to its development.

Genetic factors

Certain genes are associated with an increased risk of developing SLE. These genes often influence the immune system, making it more likely to malfunction and attack the body's own tissues. However, having these genes alone doesn't mean a person will develop lupus; it simply increases the susceptibility.³ 

Environmental triggers

Many different environmental factors are thought to be able to trigger SLE in those with genetic susceptibility, including:

• Infections: Viral or bacterial infections can sometimes trigger lupus symptoms or cause flares. Epstein-Barr virus (EBV) is strongly associated with SLE, so it is possible that the damage the EBV does to one’s DNA may be related to this⁴
• Ultraviolet (UV) light: Exposure to sunlight can trigger skin rashes and flare-ups in SLE patients, although it is not known whether it causes SLE⁵
• Medications: Some drugs, such as certain antibiotics, anti-seizure medications, and blood pressure medications, can cause your body to exhibit SLE symptoms by causing auto-antibody production in some susceptible individuals. However, once the drug in question is stopped, typically this can be resolved and the symptoms such as rashes won’t last⁶

Hormonal influences

SLE is more common in women, particularly during their childbearing years, although kidney involvement in SLE is more likely in males.^4,7 Oestrogen has been found to directly influence the maturation, survival and antibody production of cells involved in SLE and the immune system.⁷ Hormonal fluctuations may also influence flare-ups, such as those during menstruation or pregnancy.

Stress

Physical or emotional stress can contribute to the development or exacerbation of lupus. Stress increases the levels of cortisol in the blood, continuously high levels of which in turn may weaken the immune system or inflame the blood vessels, increasing the likelihood of a lupus flare up.⁸

Gender and Age

Although lupus can affect people of all genders and ages, it is much more common in women, particularly between the ages of 15 and 45. However, of those with SLE, people of colour such as blacks, asians and Hispanics are twice as likely as white people to develop kidney issues, so it is likely that genes and gender play some role, although this isn’t yet entirely understood.³ This also reinforces the idea that hormonal factors play a significant role in its development.

Summary

In summary, SLE is caused by a combination of genetic susceptibility, environmental factors, hormonal changes, and immune system dysregulation. These factors interact in ways that can trigger the immune system to mistakenly attack the body’s own tissues, leading to the development of SLE. Males are more likely to have their kidneys affected in SLE, and a complication of the nephrotic lupus is renal papillae necrosis, which in turn can contribute to kidney failure and kidney stones, amongst other complications. Kidney transplant may be a viable option in some individuals, as dialysis treatment can be quite trying.