Introduction

Sarcoidosis is a rare disease characterised by granuloma formation in different organs. But what is a granuloma? These are benign clusters of immune cells which cause inflammation.² These can be confused with cancerous tumours, however, they are benign. Clinical manifestations of this disease can look like:

• Skin lesions
• Fatigue
• Shortness of breath
• Weight loss and more, depending on which body part is affected

Most commonly, this disease affects the lungs which can be dangerous if left untreated as scarring of the tissues may make it harder to breathe.³ 

When we understand and look at the function of the kidneys we can comprehend the effects of granulomas in the kidney. The kidney is like a sieve, filtering the blood and keeping the nutrients, whilst disregarding the waste. If something is wrong with this process, it can cause an excess of urea and can cause other issues such as muscle cramps or fatigue. Renal complications can make a person’s life very uncomfortable. These types of problems may cause symptoms such as:

• Going to the toilet less often
• Itchy skin
• Muscle cramps 

The common treatment for renal complications is mainly lifestyle changes, medication to treat any associated condition (such as hypertension) or dialysis to replicate some kidney functions that may be lost. In this article, we will look at how sarcoidosis can be identified, its effect on the kidneys and how this condition can be treated and managed.

Understanding sarcoidosis

Sarcoidosis can be caused due to both genetic and environmental factors. Americans and Scandinavian populations are usually the most common groups globally to be diagnosed with sarcoidosis. A study was conducted with 610 people who were unrelated and were healthy or were affected by sarcoidosis. This study was essentially for testing the genetic cause of sarcoidosis. Different variants of a gene called HLA were found to have different effects on sarcoidosis, either causing protection, a more benign phenotype or acting as a risk factor.¹ 

Understanding the root of a disease allows more information and precision when formulating a treatment plan. Sarcoidosis is also suspected to be an autoimmune disease. This means that the immune system can not differentiate between foreign and its own tissues, causing it to attack its own tissues. The increased number of T cells and inflammatory response seen in this condition is triggered by an antigen which is not yet known. This antigen could be from the body itself, which is why it is thought that sarcoidosis could be an autoimmune disease. 

The formation of granulomas is similar to construction workers controlling a hazardous spill, in two key steps:

• A spill is detected which causes the workers (immune cells) to be called to the location
• The workers come together to form a barrier to contain and isolate the spill

This structure can remain long-term in the body, mainly in the lungs. The mortality rate of pulmonary sarcoidosis has increased in the last three decades as more patients appear asymptomatic and are only diagnosed in the later stages.¹ Renal sarcoidosis is less common and can present at any stage of the disease. The kidney can also be affected by other diseases causing granulomas, so it is important to rule these out.

Renal complications in sarcoidosis

There are four main types of abnormalities that are produced by renal sarcoidosis:^5,6

Granulomatous interstitial nephritis (GIN)

This is when granulomas form in the interstitial tissue around the nephron and the areas between the kidney tubules become inflamed. This may affect the filtering process and allow some proteins (proteinuria) and blood (haematuria) to pass into the urine.

It may also cause a reduction in kidney function, thus potentially causing some discomfort for a person. GIN can also be caused by certain medications, such as antibiotics and infections, so it is key to rule these out before associating it with sarcoidosis.⁴

Hypercalcemia and hypercalciuria

Hypercalcemia is an increased level of calcium in the blood and hypercalciuria is an increased calcium in the urine. Calcium is important for the functioning of muscles and heart health, however, too much of it in the blood can make you feel sick, thirsty and confused, and too much in your urine can cause kidney stones. This is common with renal sarcoidosis as there is reduced filtering due to the granulomas. 

Kidneys convert vitamin D in the active form of calcitriol. This causes an increased reabsorption of calcium, which explains these symptoms.¹⁰

Nephrocalcinosis

Hypercalcemia and hypercalciuria can cause nephrocalcinosis which are calcium deposits in the kidney. This can lead to kidney stones and reduced kidney function. This can be identified by CT scans which show the calcium deposits and are treated by looking at the root cause.^6,8 

Glomerular diseases (rare)

The glomerulus is a small filter in the kidney. Inflammation of the glomerulus due to the granuloma causes proteins to leak into the urine. Reduced kidney function can cause fatigue and swelling in the rest of the body (hands, feet, etc).^7,8

The main reason for this is aberrant filtration. Granulomas in the kidney can damage the filtration processes, causing calcium uptake to be greatly increased and dysregulated. 

Diagnosis

Renal sarcoidosis can be easily misdiagnosed as the symptoms could also be related to other issues. Most people consult many physicians before this disease is identified. Effective diagnostic measures help to detect this disease early to prevent fatal problems. 

The most common investigations are urine and blood samples to check for kidney functions, calcium and serum creatinine levels. 

Scans such as CT scans, MRIs and ultrasounds can confirm the presence of granulomas and any other abnormalities. Biopsies are also performed to investigate granulomas. It is important to rule out other diseases, that could be possible differential diagnoses.²

Management and treatment

Lifestyle changes can make life more comfortable with renal sarcoidosis. Regular activity can help with energy levels and muscle weakness. A healthy diet can also help regulate nutrient levels and reduce calcium/vitamin D intake. 

Regular checkups can also help manage renal sarcoidosis and monitor kidney function. Corticosteroids can reduce inflammation and granuloma formation however, as renal sarcoidosis doesn’t usually cause long-term harm, this course of treatment isn’t mandatory. This medication works as an immunosuppressant, reducing cytokine production responsible for signalling immune responses, and reducing antigen-presenting. 

The immunosuppressive effect of corticosteroids helps the autoimmune component of sarcoidosis as well. Corticosteroids can reduce the size of the existing granulomas and prevent the formation of new ones. For some people, it isn’t recommended to use this medication as it can cause side effects such as diabetes, hypertension and central obesity. If the kidney is severely damaged, dialysis may be considered.⁹

A person's lifestyle would have to be assessed by a doctor to decide the most suitable course of action. Another target for treatment with renal sarcoidosis is looking at the treatment options for hypercalcemia. Glucocorticoids are commonly used to treat hypercalcemia. These work by decreasing calcium absorption and will also alleviate some symptoms. It’s key to have treatment when it is required as renal sarcoidosis can lead to chronic kidney disease and potentially cause renal failure in severe cases. 

Summary

To conclude, renal sarcoidosis is a suspected autoimmune condition characterised by the formation of granulomas in the kidney. The cause of this disease is still unclear but is thought to be a combination of genetic and environmental factors. The kidneys are important organs, helping regulate the body and flush out toxins. The main symptoms of renal sarcoidosis are triggered by an increased level of calcium in the blood and urine, also known as hyperglycemia and hypercalciuria. This increased amount of calcium affects the muscles, heart and nervous system. The diagnosis is based on the urine and blood tests and can be confirmed by scans to rule out other conditions.

The main line of treatment is medications like corticosteroids and glucocorticoids. Lifestyle changes such as increased exercise, changes in diet, reducing calcium and vitamin D intake are also recommended. However, more research is required about the causative factors of renal sarcoidosis to enable a better understanding of treating it and developing newer, safer medications.