Chronic Kidney Disease: Overview and Emerging Therapies

Chronic kidney disease is a condition marked by the progressive loss of kidney function and life-threatening complications such as high blood pressure and heart disease. It is estimated that chronic kidney disease affects more than 1 in 7 Americans. Although kidney diseases rank as a leading cause of death in the United States, 40% of people with severely reduced kidney function remain unaware of their condition.

What is chronic kidney disease?

Chronic kidney disease is a progressive condition in which the kidneys struggle to filter blood properly. As a result, your body may accumulate dangerous levels of fluid, electrolytes, and waste products.

Based on the level of kidney function impairment, chronic kidney disease is divided into 5 stages, with the last stage labeled as “end-stage renal disease.” The condition is not reversible and progresses slowly over time.

Whether you will need dialysis and transplantation in a few years depends on the underlying cause of your chronic kidney disease and how well you manage it. It will also depend on your diet and lifestyle, use of medications, and genetic composition.

Who is at risk for chronic kidney disease?

Some people have a greater risk of developing chronic kidney disease. Here are the most common risk factors:

• Diabetes
• High blood pressure
• Heart disease
• Family history of chronic kidney disease
• Smoking
• Obesity
• Older age
• Being Black, Native American, or of Asian descent
• Frequent use of drugs or medications that can damage the kidneys 

How is chronic kidney disease diagnosed?

To assess how well your kidneys work, your healthcare provider will perform specific tests measuring your kidney function. Blood tests are done to evaluate creatinine and urea levels, and to calculate the glomerular filtration rate. A series of urine tests are used to determine the presence of proteins. Your doctor may also conduct imaging tests such as ultrasounds and CT scans.

What are the symptoms of chronic kidney disease?

You might have very few signs or symptoms in the early stages of chronic kidney disease. These symptoms are non-specific and may include:

• Nausea
• Vomiting
• Reduced appetite
• Fatigue and weakness
• Sleep problems
• Urinating more or less
• Decreased mental sharpness
• Muscle cramps
• Swelling
• Dry, itchy skin
• High blood pressure
• Shortness of breath and chest pain

What are the complications of chronic kidney disease?

Chronic kidney disease affects every part of your body. Potential complications of kidney function loss include fluid retention, swelling, high blood pressure, increased blood potassium levels, heart disease and inflammation, anemia, fragile bones and fractures, nervous system damage and difficulty concentrating, decreased immune response and frequent infections, decreased sex drive, erectile dysfunction or reduced fertility, pregnancy risks, and irreversible damage to your kidneys, also known as end-stage kidney disease.

How is chronic kidney disease treated?

The most common treatment of chronic kidney disease is based on measures to help control signs and symptoms, reduce complications, and slow the progression of the disease.

• Lifestyle modifications.  A healthy lifestyle is the basis for slowing down the progression of the disease. Maintaining a healthy weight, exercising regularly, and quitting smoking are important.
• Dietary changes.  People with impaired kidney function need to limit their protein, sodium (salt), potassium, and phosphorus intake.
• Medications.  Your healthcare provider may prescribe some of the following medications:
  • An angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) to lower your blood pressure.
  • Phosphate binder if your kidneys can’t eliminate phosphate.
  • A diuretic to help your body eliminate extra fluid.
  • Medications to lower cholesterol levels.
  • Erythropoietin to build red blood cells if you’re anemic.
  • Vitamin D and calcitriol to prevent bone loss.
• Dialysis.  If your kidneys get severely damaged, the excessive waste products must be artificially removed from your body through dialysis. Hemodialysis uses a machine to filter your blood, while peritoneal dialysis involves the placement of a dialysis solution into your stomach through a catheter.
• Kidney transplantation. Getting a kidney transplant is the preferred option when feasible, as it provides a better life quality and long-term outcomes.

The decision between dialysis and transplantation depends on several factors. These include but are not limited to your overall health condition, whether your kidneys are so severely damaged that you need transplantation, and whether you have other medical conditions that make transplantation less or not feasible.

Available and emerging therapies

Two recently approved therapies are currently available for some patients with chronic kidney disease, and several promising therapies are under development for chronic kidney disease:

• Sodium-Glucose-Cotransporter 2 (SGLT2) Inhibitors. These medications may slow and limit the progression of the disease. The FDA approved dapagliflozin, for patients with chronic kidney disease and no other chronic disorder, in 2021. The agency has also recently approved empagliflozin for the same indication, although evidence shows it may be equally effective in patients with and without diabetes.
• Non-Steroidal Mineralocorticoid Receptor Antagonists. These medications may reduce the levels of potassium and limit the progression of the disease. Researchers are planning to investigate finerenone for patients with type 1 diabetes and chronic kidney disease.
• Targeted Gene Therapy. Researchers have identified a protein-coding gene, transmembrane and immunoglobulin domain containing 1 (TMIGD1) that is inactivated in chronic kidney disease. This gene may become a new therapeutic target for future medications.