Uremia

Uremia is caused by the accumulation of uremic toxins, which are waste products from protein and cellular metabolism that are normally filtered by the kidneys and excreted through the urine. When kidney function declines significantly, especially when the glomerular filtration rate (GFR) falls below 10-15 mL/min, the kidneys lose their ability to remove these toxins leading to their accumulation in the blood.  

Most commonly, this happens in individuals with advanced chronic kidney disease (CKD). CKD is often caused by damage to the kidneys by other comorbid conditions, such as hypertension and diabetes mellitus. However, it can also be caused by renal disorders, like polycystic kidney disease or glomerulonephritis, among others. More rarely, a sudden severe loss of kidney function, such as due to dehydration, shock, or nephrotoxic medications, can also cause uremia.  

Finally, uremia can also develop in individuals with known end-stage renal disease (ESRD) who are already on long-term dialysis, most often due to underdialysis from missed dialysis sessions or a change in the individual’s metabolic requirements. This can happen with severe infections (e.g., sepsis) or in individuals who have undergone recent surgery or trauma.  

Initially, signs and symptoms of uremia are non-specific, and may include fatigue, weakness, loss of appetite, nausea and vomiting, and a metallic taste in the mouth. As kidney function worsens, more specific manifestations may develop. For example, uremic encephalopathy occurs when uremic toxins accumulate in the central nervous system, leading to a wide range of symptoms, ranging from confusion, difficulty concentrating, seizures, and altered mental status to even coma. 

Due to its vascularization, uremic toxins can also accumulate in the pericardium, the double-walled membrane surrounding the heart, resulting in uremic pericarditis. Pericarditis, or inflammation of the pericardium, can result in sharp chest pain that worsens with deep breaths and with certain positions, such as lying flat on the back. Pain is usually accompanied by a friction rub, which is a squeaky sound produced by the rubbing of the inflamed pericardial layers that can be heard with a stethoscope over the heart.  

Similarly, there may be inflammation of the lining of the lungs called pleuritis, which may lead to a pleural effusion, which is when fluid collects in the pleural space. Signs and symptoms of a pleural effusion vary depending on its size. A small effusion might go unnoticed, whereas a large one may cause pain while inhaling and shortness of breath due to restricted lung expansion.  

Due to widespread inflammation, individuals with uremia may also have a weakened immune system predisposing them to infections, as well as platelet dysfunction resulting in an increased risk of bleeding and easy bruising. Finally, a rare but characteristic manifestation of uremia is uremic frost, which occurs when levels of urea in the blood are so elevated that urea seeps through the sweat and crystallizes in the skin, giving it a frosty appearance.   

Diagnosis of uremia is based on a combination of clinical symptoms and laboratory findings. Typically, blood tests such as a basic metabolic panel will show signs of renal failure, including elevated creatinine, a decrease in glomerular filtration rate (GFR), and high blood urea nitrogen (BUN) levels. Additionally, there may be electrolyte imbalances, such as high levels of potassium and phosphate and low levels of calcium in the blood.  

Since uremia is linked to renal function, a urine analysis may reveal proteins or blood in the urine, both of which may indicate damage to the kidney’s filtration system. Imaging tests, like a kidney ultrasound, may be performed to determine the size of the kidneys and identify structural abnormalities such as the presence of cysts or kidney stones. In some cases, a kidney biopsy may be required to determine the cause of kidney damage, especially if an underlying condition such as glomerulonephritis is suspected. 

Treatment of uremia requires some form of renal replacement therapy, which may involve dialysis or a kidney transplant. There are two main types of dialysis: hemodialysis and peritoneal dialysis. With hemodialysis, blood is drawn from the body through a vascular access (e.g., an arteriovenous fistula, graft, or catheter) and pumped into a machine that acts as an artificial kidney, removing waste and extra fluid from the blood.   

Hemodialysis is very effective at removing small water-soluble uremic toxins, like urea and creatinine in a short amount of time; however, it's not as effective at clearing protein-bound toxins and larger molecules like β2-microglobulin which also contribute to uremic syndrome. 

On the other hand, in peritoneal dialysis, the lining of the abdomen, (i.e., peritoneum) acts as a natural filter due to its selective permeability. A dialysis solution is introduced into the abdominal cavity via a catheter, and waste products and extra fluid are absorbed from the peritoneal blood vessels into the solution, which is then drained out. Peritoneal dialysis allows more flexibility and can be done at home but is less efficient than hemodialysis at clearing toxins rapidly from the body. 

Some individuals with ESRD may be eligible for a kidney transplant, which is the best long-term solution for treating uremic syndrome, as it replaces the damaged kidneys with a functioning one from a living or deceased donor. 

In addition to renal replacement therapy, the treatment plan may include addressing the underlying cause of kidney failure, as well as dietary restrictions and medications to prevent a further decline in kidney function. Lifestyle modifications include a low-protein diet to reduce uremic toxin production and fluid and salt restriction to prevent fluid build-up. Diuretics like furosemide may be used to promote the excretion of extra fluid, and other medications like sodium bicarbonate and potassium binders may be needed to manage certain metabolic abnormalities.