End-Stage Renal Disease

What is End-Stage Renal Disease?

Over 500,000 people in the United States are currently living with end-stage renal disease (ESRD), also known as severe kidney failure. When chronic kidney disease (CKD), or long-term kidney damage, develops and worsens, it can lead to ESRD. This condition can significantly lower a person’s quality of life and can also lead to premature death. Chronic kidney disease is a serious illness, and medical care for it involves regular health check-ups to look for signs of the disease getting worse, along with early referrals for specialist treatments like dialysis or even a kidney transplant.

The Kidney Disease Improving Global Outcomes (KDIGO) foundation, an organization that works towards improving kidney health worldwide, provides guidelines to define CKD. They use markers to check for kidney damage, such as proteinuria (excess protein in the urine) and glomerular filtration rate (GFR, the rate at which your kidneys filter blood). Being diagnosed with CKD means having a GFR of less than 60 milliliters per minute and a high level of albumin (a protein that can indicate kidney damage) alongside other kidney abnormalities for more than three months. On the other hand, having a GFR of less than 15 milliliters per minute indicates ESRD or severe kidney failure.

According to guidelines from KDIGO in 2012, CKD is divided into five stages based on GFR levels:

Stage 1: Kidney damage with normal GFR (greater than 90 ml/min).
Stage 2: Mild reduction in GFR (60-89 mL/min).
Stage 3a: Moderate reduction in GFR (45 to 59 mL/min).
Stage 3b: Moderate reduction in GFR (30 to 44 mL/min).
Stage 4: Severe reduction in GFR (15 to 29 mL/min).
Stage 5: Renal failure (GFR less than 15 mL/min), or end-stage renal disease.

Thus, understanding these stages can help monitor disease progression and plan the best treatments.

What Causes End-Stage Renal Disease?

Chronic diseases, or long-term health problems, can cause end-stage renal disease, a serious condition where the kidneys stop working properly. One common cause of this issue is diabetes, especially in both developed and underdeveloped countries.

Other causes of end-stage renal disease can include having high blood pressure, problems with blood vessels, diseases that affect the kidney’s tiny filtering units, cysts in the kidney, issues with the tissue and channels in the kidneys, blockages or dysfunctions in the urinary tract, repeated instances of kidney stones, birth defects of the kidney or bladder, failing to recover from an acute kidney injury, as well as taking certain types of medication, like non-steroidal anti-inflammatory drugs (known as NSAIDs), immuno-suppressants (calcineurin inhibitors), and some antiviral drugs.

Vascular diseases related to the kidneys include renal artery stenosis (narrowing of the kidney’s main artery), certain immune system related conditions that cause inflammation in blood vessels (both C-ANCA and P-ANCA positive ones, as well as vasculitides that don’t produce ANCA), atheroemboli (likely cause by fat droplets blocking blood vessels), illness caused by high blood pressure, and kidney vein clots.

Some known primary diseases affecting the kidney’s filtering units include membranous nephropathy, Alport syndrome, IgA nephropathy, focal and segmental glomerulosclerosis (FSGS), minimal change disease, complement-related illnesses.

Secondary causes leading to issues with the kidneys’ filtering units can include diabetes, lupus, rheumatoid arthritis, skin hardening, an inflammation of the blood vessels known as vasculitis, repeated instances of blood clotting disorders, certain infectious diseases like hepatitis B, C, and HIV, parasitic infections, drug misuse and certain medication, as well as disease conditions where abnormal protein is deposited in organs & tissues like amyloidosis etc.

Causes for the tissue in the kidney and the channels carrying the urine developing issues include certain medications, infections, immune system disorders, inherited diseases, and exposure to heavy metals or radiation.

Urinary tract obstructions leading to this condition can be due to an enlarged prostate, kidney stones, narrow urethra, tumors, a neurogenic bladder (which is a bladder dysfunction due to nerve damage), birth defects of the kidney or bladder, and a condition known as retroperitoneal fibrosis, where fibrous tissue develops in the back of the abdomen.

Risk Factors and Frequency for End-Stage Renal Disease

In 2015, the United States saw a rise in kidney failure, with 124,411 new cases of End-Stage Renal Disease (ESRD). Kidney disease is increasingly common, with about 20,000 new cases every year, and it is the ninth leading cause of death in the US.

The prevalence of kidney failure differs widely across different racial and ethnic groups in America. For example, in 2015:

African Americans experienced ESRD three times more than Whites (393.5 vs 139.9 per million population).
American Indians or Alaska Natives, and Native Hawaiians or Pacific Islanders had about ten times the prevalence rate.
Asian Americans had 1.3 times the average rate.
Interestingly, the number of new cases among African Americans has been decreasing every year since 2006.

In terms of age, kidney disease is more common in older people, especially those over 60 years. For example, only 6.0% of those aged 18 to 44 suffer from it, but the rate shoots up to 38.1% in people over 65.

Last, but not least, kidney failure is more prevalent in males than in females.

Signs and Symptoms of End-Stage Renal Disease

End-stage kidney disease, also called end-stage renal disease (ESRD), comes with a range of symptoms that can be challenging to manage. Some people might experience fluid retention not responsive to water pills, high blood pressure not controlled by medication, anemia, bone disorders, and mineral imbalances. These could include high levels of potassium, low sodium, imbalances in calcium/phosphorus, and metabolic acidosis.

Metabolic acidosis in advanced chronic kidney disease could result in malnutrition, muscle weakness, and a loss of muscle mass. Excessive salt and water in the body can cause swelling in the legs and lungs, and high blood pressure. Anemia, from ESRD, often appears as fatigue, difficulty thinking, and a lower quality of life. It can also lead to heart failure if not treated.

Besides these, urinary toxicity or ‘uremia’ due to ESRD can also cause:

Inflammation around the heart (pericarditis)
Brain condition (encephalopathy)
Nerve damage in the hands and feet (peripheral neuropathy)
Restless leg syndrome
Loss of appetite, nausea, vomiting, diarrhea
Dry skin, itchiness, bruising (ecchymosis)
Malnutrition
Sexual dysfunction including erectile dysfunction, reduced sex drive, and missed menstrual periods in women
Problems with blood clotting due to dysfunction of platelets

When uremic toxicity becomes severe, urgent dialysis is typically necessary. In general, the symptoms of ESRD usually begin to appear in later stages when the kidney’s filtering ability, also known as glomerular filtration rate (GFR), drops below 30 ml/min. However, in some patients with certain kidney conditions like nephrotic syndrome and cystic kidney disease, symptoms may appear earlier. It’s also very common for patients with ESRD to experience depression, so it’s important to screen for this during medical evaluation.

Testing for End-Stage Renal Disease

Chronic kidney disease, or CKD, is diagnosed when there’s proof of kidney damage for at least three months or when a person has a GFR, or glomerular filtration rate, less than 60 mL/min for the same amount of time. The GFR is the rate at which blood is filtered in the kidneys, and a low GFR can suggest kidney disease. There are three formulas that doctors use to calculate GFR, but the most accurate one is the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which also takes into account a person’s age, race, and gender.

In order to understand kidney disease more accurately, doctors might use several tests. For example, a complete blood count can show if a person has anemia (a blood disorder), and a basic metabolic panel can reveal if levels of blood urea nitrogen and serum creatinine are elevated – this typically indicates that the kidneys aren’t filtering properly.

A renal ultrasound, a kind of imaging test that uses sound waves to create pictures of the kidneys, can also be useful. In people with kidney disease, the kidneys might appear small and bright on an ultrasound. Other types of imaging, such as CT scans or an MRI, can also hold helpful information about the kidneys. For example, a CT scan can provide a better view of any growths or cysts in the kidneys and is very good at spotting kidney stones.

Doctors might also order a urinalysis, which is a routine test of the urine. If this shows large amounts of protein, it might mean that the kidneys aren’t filtering waste products properly. A urine test that shows more than 30 mg of albumin (a type of protein) for each gram of creatinine (a waste product) is considered abnormal.

A kidney biopsy, where a small sample of kidney tissue is removed and examined under the microscope, can also help doctors make a diagnosis, especially if other tests aren’t clear.

As well as all of these tests, doctors might use some more specific tests to rule out other conditions. For example, they might look for certain proteins in the blood and urine to rule out a type of cancer called multiple myeloma, or they might check levels of certain antibodies to rule out conditions such as systemic lupus erythematosus, a disease where the immune system attacks the body’s own tissues and organs.

Treatment Options for End-Stage Renal Disease

Treatment for the final stage of kidney disease, also known as end-stage renal disease, involves managing symptoms and trying to slow down the progress of the disease. The focus is on making the patient feel better and avoiding further complications. Here’s a brief overview:

Firstly, doctors aim to treat the root cause of the disease as well as manage symptoms like high blood pressure and protein in urine, known as proteinuria. High blood pressure should ideally be kept below 130/80 mmHg (systolic/diastolic) regardless of whether the patient has diabetes or not, especially if there’s excessive protein in their urine. Certain drugs, like angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin 2 receptor blockers (ARB), can slow the disease progression especially when started early.

Maintaining good glucose levels is also crucial. This means that people with kidney disease and diabetes should aim to achieve a hemoglobin A1C (an average blood sugar measure) of less than 7%. Certain medications, like sodium-glucose transporter 2 (SGLT-2) inhibitors may help reduce disease impact in those with type 2 diabetes. Addressing chronic metabolic acidosis, a condition marked by excessive acidic build up, with supplemental renal bicarbonate may also slow disease progression.

Doctors also focus on managing high cholesterol, especially high triglycerides, which is common in people with kidney disease. It’s generally advised to start treatment with cholesterol-lowering medications earlier in the disease course. In cases where there’s severe fluid buildup or lung congestion, loop diuretics or ultrafiltration could be used. In severe cases where kidney function is significantly impaired, long-term kidney replacement therapies (like dialysis or kidney transplant) may be needed. Other issues that may need to be addressed include anemia which can be treated with erythropoiesis-stimulating agent (ESA) such as erythropoietin, and high phosphate levels, which can be managed with phosphate binders and a low phosphate diet.

People with kidney disease are recommended lifestyle changes and dietary restrictions, which include low salt intake, avoiding foods high in phosphorus, and limiting daily protein intake. It’s also important to monitor calcium levels. If calcium levels are too low (with a 25-OH vitamin D level less than 10 ng/mL), vitamin D supplements are required. Overactive parathyroid glands, a common issue in kidney disease, can be managed with calcitriol, vitamin D analogs, or calcimimetics.

Careful preparation is also necessary when long-term kidney replacement therapies, like dialysis or kidney transplant, are anticipated. Patients should be educated about disease progression, how dialysis works, and about kidney transplantation. If a transplant isn’t immediately possible, a connection should be made in one of the blood vessels to prepare for future dialysis treatments. It’s also advised to consider kidney transplantation timely for every patient with end-stage renal disease.

Patients should be referred for renal replacement therapy or other long-term treatments when they experience severe acidic blood, high potassium levels, heart inflammation, mental confusion, uncontrollable fluid retention, poor growth and malnutrition, peripheral neuropathy, unbearable gastric symptoms, or when the kidney’s filtration rate drops to dangerously low levels regardless of other symptoms or health conditions.

End-stage kidney disease can look like many other health problems. Also, many conditions can eventually lead to end-stage kidney disease. When a doctor checks a patient with end-stage kidney disease, they should think about different conditions that might also be causing the symptoms. These include:

Chronic inflammation of the kidney’s filtering units (chronic glomerulonephritis)
Long-term kidney infection (chronic pyelonephritis)
Quickly worsening inflammation of the kidney’s filters (rapidly progressive glomerulonephritis)
Kidney disease during pregnancy (nephropathy of pregnancy/pregnancy toxemia)
Unclassifiable nephritis (a type of kidney inflammation)
Polycystic kidney disease (a condition with numerous cysts in the kidneys)
Hardening of the kidney’s blood vessels (nephrosclerosis)
Very high blood pressure (malignant hypertension)
Kidney damage from diabetes (diabetic nephropathy)
Kidney inflammation related to a disease that causes inflammation in the body (systemic lupus erythematosus nephritis)
Amyloid kidney (a condition with abnormal proteins in the kidneys)
Gouty kidney (a condition related to high levels of uric acid)
Renal failure caused by a birth defect of metabolism
Renal/urinary tract tuberculosis (a type of infection)
Kidney or urinary tract stones (calculi)
Kidney or urinary tract tumor

Other conditions might include obstructive urinary tract disease, myeloma (a type of bone marrow cancer), and renal hypoplasia (underdevelopment of the kidneys).

What to expect with End-Stage Renal Disease

End-stage kidney disease is a condition that worsens over time, with patients eventually needing replacement therapy like dialysis to avoid fatal outcomes. This condition often leads to frequent hospital stays, higher medical costs, and changes in the body’s metabolism. The death rates for individuals with end-stage kidney disease are considerably higher than those without this disease. Even with prompt dialysis, the death rate in the following two years can range from 20% to 50%.

The most common cause of death is excessively high potassium levels in the blood, known as hyperkalemia, followed by serious heart issues. Death rates are higher in men than in women, and black individuals show higher death rates due to end-stage kidney disease than white individuals. The highest death rate usually occurs within the first six months of starting dialysis. The 5-year survival rate for someone on long-term dialysis in the US is roughly 35%, and it’s around 25% for patients who also have diabetes.

In children, this condition often delays puberty in both boys and girls. It is common for these children to have low levels of vitamin D, which is considered a separate risk factor for death.

Possible Complications When Diagnosed with End-Stage Renal Disease

There are two main types of complications related to end-stage kidney disease: those caused by the disease itself, and those caused by the methods used to treat it such as dialysis or vascular access procedures.

Here are the complications due to the disease itself:

Coronary heart disease, which is a complication of chronic kidney disease and is the main reason for death among these patients. Dialysis patients have a risk of dying from heart disease that is 10 to 30 times higher than the normal population.
Peripheral vascular disease
High blood pressure
Bone and mineral disorders caused by overactive parathyroid glands and vitamin D deficiency
Hyperuricemia, or high levels of uric acid in the blood
Metabolic acidosis, a condition where there is too much acid in the body fluids
Hyperphosphatemia, or high levels of phosphate in the blood
Hypoalbuminemia, or low levels of a protein called albumin in the blood
Anemia
Decreased sexual desire and erectile problems in men

On the other hand, complications arising from dialysis or vascular access procedures include:

Bleeding
Local infections or infections that spread through the bloodstream
Blockage of the graft
Abnormal electrolyte levels after dialysis
Dialysis-related dementia
A condition called dialysis disequilibrium syndrome, which can occur when hemodialysis is started

Preventing End-Stage Renal Disease

The U.S. Preventive Services Task Force (USPSTF), an organization that provides preventive health recommendations, advises against regularly checking people who show no symptoms for Chronic Kidney Disease (CKD). However, for those at a higher risk for the disease, like people with diabetes or high blood pressure, the USPSTF recommends ongoing checks for CKD with a test that measures protein in the urine (proteinuria testing). It’s important to note, though, that if a patient is already taking ACE inhibitors or Angiotensin Receptor Blockers (drugs typically used for heart conditions and high blood pressure treatment), this test is not necessary.

Patients with advanced kidney disease, also known as end-stage renal disease, should be aware of several important pointers:

Avoid drugs that can harm the kidneys, such as non-steroidal anti-inflammatory drugs.
Seek detailed counseling for different types of kidney replacement options, including peritoneal dialysis (a treatment that uses the lining of your abdomen to filter your blood), hemodialysis (a treatment that filters your blood using a machine), and transplantation (a surgery to replace the failed kidney with a healthy one).
Ensure timely preparation for hemodialysis, including setting up the required blood vessel access.
A pregnancy could be life-threatening in their condition.
Limit foods rich in phosphate.
Lessen the amount of potassium, sodium, and water in the diet to maintain a healthy balance and prevent overloading the body with fluids.
Restrict the intake of protein, which may delay the onset of certain symptoms related to the build-up of waste products in the blood (uremic symptoms).
Reducing salt intake may slow down the progression of diabetic kidney disease.

Frequently asked questions

End-Stage Renal Disease (ESRD) is severe kidney failure, which occurs when chronic kidney disease (CKD) worsens and leads to significantly lower quality of life and potential premature death.

End-Stage Renal Disease is increasingly common, with about 20,000 new cases every year, and it is the ninth leading cause of death in the US.

Signs and symptoms of End-Stage Renal Disease (ESRD) include: - Fluid retention not responsive to water pills - High blood pressure not controlled by medication - Anemia, which can manifest as fatigue, difficulty thinking, and a lower quality of life - Bone disorders and mineral imbalances, such as high levels of potassium, low sodium, and imbalances in calcium/phosphorus - Metabolic acidosis, which can result in malnutrition, muscle weakness, and a loss of muscle mass - Swelling in the legs and lungs, and high blood pressure due to excessive salt and water in the body - Urinary toxicity or 'uremia' causing various symptoms like inflammation around the heart (pericarditis), brain condition (encephalopathy), nerve damage in the hands and feet (peripheral neuropathy), restless leg syndrome, loss of appetite, nausea, vomiting, diarrhea, dry skin, itchiness, and bruising (ecchymosis) - Sexual dysfunction including erectile dysfunction, reduced sex drive, and missed menstrual periods in women - Problems with blood clotting due to dysfunction of platelets - In some cases, patients with certain kidney conditions like nephrotic syndrome and cystic kidney disease may experience symptoms earlier - It is also common for patients with ESRD to experience depression, so screening for this during medical evaluation is important.

There are several ways to get End-Stage Renal Disease, including chronic diseases like diabetes and high blood pressure, problems with blood vessels, diseases affecting the kidney's filtering units, urinary tract obstructions, repeated instances of kidney stones, birth defects of the kidney or bladder, failing to recover from an acute kidney injury, certain medications, and other factors such as infections, immune system disorders, inherited diseases, and exposure to heavy metals or radiation.

The other conditions that a doctor needs to rule out when diagnosing End-Stage Renal Disease include: - Chronic inflammation of the kidney's filtering units (chronic glomerulonephritis) - Long-term kidney infection (chronic pyelonephritis) - Quickly worsening inflammation of the kidney's filters (rapidly progressive glomerulonephritis) - Kidney disease during pregnancy (nephropathy of pregnancy/pregnancy toxemia) - Unclassifiable nephritis (a type of kidney inflammation) - Polycystic kidney disease (a condition with numerous cysts in the kidneys) - Hardening of the kidney's blood vessels (nephrosclerosis) - Very high blood pressure (malignant hypertension) - Kidney damage from diabetes (diabetic nephropathy) - Kidney inflammation related to a disease that causes inflammation in the body (systemic lupus erythematosus nephritis) - Amyloid kidney (a condition with abnormal proteins in the kidneys) - Gouty kidney (a condition related to high levels of uric acid) - Renal failure caused by a birth defect of metabolism - Renal/urinary tract tuberculosis (a type of infection) - Kidney or urinary tract stones (calculi) - Kidney or urinary tract tumor - Other conditions might include obstructive urinary tract disease, myeloma (a type of bone marrow cancer), and renal hypoplasia (underdevelopment of the kidneys).

For End-Stage Renal Disease, the following tests may be needed: - Complete blood count to check for anemia - Basic metabolic panel to measure blood urea nitrogen and serum creatinine levels - Renal ultrasound to visualize the kidneys - CT scan or MRI to provide detailed images of the kidneys - Urinalysis to check for protein levels - Kidney biopsy to examine kidney tissue - Additional tests may be ordered to rule out other conditions, such as checking for certain proteins in the blood and urine to rule out multiple myeloma or testing for certain antibodies to rule out systemic lupus erythematosus.

Treatment for end-stage renal disease (ESRD), also known as the final stage of kidney disease, involves managing symptoms and trying to slow down the progress of the disease. The focus is on making the patient feel better and avoiding further complications. Treatment includes addressing the root cause of the disease, managing symptoms like high blood pressure and protein in urine, maintaining good glucose levels, managing high cholesterol, addressing fluid buildup or lung congestion, and addressing other issues such as anemia and high phosphate levels. Lifestyle changes and dietary restrictions are also recommended. In severe cases where kidney function is significantly impaired, long-term kidney replacement therapies like dialysis or kidney transplant may be needed. Patients should be referred for renal replacement therapy or other long-term treatments when they experience certain severe symptoms or health conditions.

When treating End-Stage Renal Disease, there can be side effects related to the disease itself as well as complications arising from the treatment methods. The side effects include: - Coronary heart disease, which is the main cause of death among patients with chronic kidney disease. - Peripheral vascular disease. - High blood pressure. - Bone and mineral disorders caused by overactive parathyroid glands and vitamin D deficiency. - Hyperuricemia, or high levels of uric acid in the blood. - Metabolic acidosis, a condition where there is too much acid in the body fluids. - Hyperphosphatemia, or high levels of phosphate in the blood. - Hypoalbuminemia, or low levels of a protein called albumin in the blood. - Anemia. - Decreased sexual desire and erectile problems in men. Complications arising from dialysis or vascular access procedures include: - Bleeding. - Local infections or infections that spread through the bloodstream. - Blockage of the graft. - Abnormal electrolyte levels after dialysis. - Dialysis-related dementia. - Dialysis disequilibrium syndrome, which can occur when hemodialysis is started.

The prognosis for End-Stage Renal Disease (ESRD) is poor, with high death rates and a significant impact on quality of life. Even with prompt dialysis, the death rate in the following two years can range from 20% to 50%. The most common cause of death is excessively high potassium levels in the blood, known as hyperkalemia, followed by serious heart issues. The 5-year survival rate for someone on long-term dialysis in the US is roughly 35%, and it's around 25% for patients who also have diabetes.

Nephrologist.