End-stage renal disease (ESRD) development of chronic kidney disease (CKD) and its progression to this terminal disease remains a significant source of reduced quality of life and significant premature mortality. Chronic kidney disease (CKD) is a debilitating disease, and standards of medical care involve aggressive monitoring for signs of disease progression and early referral to specialists for dialysis or possible renal transplant. The Kidney Disease Improving Global Outcomes (KDIGO) foundation guidelines define CKD using kidney damage markers, specifically markers that determine proteinuria and glomerular filtration rate. By definition, the presence of both of these factors (glomerular filtration rate [GFR] less than 60 mL/min and albumin greater than 30 mg per gram of creatinine) along with abnormalities of kidney structure or function for greater than three months signifies chronic kidney disease. End-stage renal disease, moreover, is defined as a GFR less than 15 mL/min.[rx][rx]
Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guidelines: CKD classification considers the GFR level and the severity of albuminuria.
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)
As a part of kidney disease staging, your doctor also may test whether protein is present in your urine.
|Kidney disease stage||GFR, mL/min||Kidney function|
|National Kidney Foundation|
|Stage 1||90 or above||Normal or near-normal kidney function|
|Stage 2||60 to 89||Mild loss of kidney function|
|Stage 3a||45 to 59||Mild to moderate loss of kidney function|
|Stage 3b||30 to 44||Moderate to severe loss of kidney function|
|Stage 4||15 to 29||Severe loss of kidney function|
|Stage 5||Less than 15||Kidney failure|
Causes of End-Stage Renal Disease
Many chronic diseases can cause end-stage renal disease. In the United States, diabetes mellitus is the leading cause. Other causes include hypertension, glomerulonephritis, polycystic kidney disease, prolonged obstruction of the urinary tract, vesicoureteral reflux, recurrent pyelonephritis, and certain medications, including non-steroidal anti-inflammatory drugs (NSAIDs), calcineurin inhibitors, and antiretrovirals.[rx][rx]
The decline of kidney function is gradual and initially may present asymptomatically. The natural history of renal failure depends on the etiology of the disease but ultimately involves early homeostatic mechanisms involving hyperfiltration of the nephrons. As nephrons become damaged, the kidney increases the rate of filtration in the residual normal ones. As a result, the patient with mild renal impairment can show normal creatinine values, and the disease can go undetected for some time.[rx] This adaptive mechanism will run its course and eventually cause damage to the glomeruli of the remaining nephrons. At this point, antihypertensives such as ACEs or ARBs may be beneficial in slowing the progress of the disease and preserving renal function.
Factors that may worsen renal injury include:
- Glomerulonephritis (gloe-mer-u-low-nuh-FRY-tis), an inflammation of the kidney’s filtering units (glomeruli)
- Interstitial nephritis (in-tur-STISH-ul nuh-FRY-tis), an inflammation of the kidney’s tubules and surrounding structures
- Polycystic kidney disease
- Prolonged obstruction of the urinary tract, from conditions such as enlarged prostate, kidney stones and some cancers
- Vesicoureteral (ves-ih-koe-yoo-REE-tur-ul) reflux, a condition that causes urine to back up into your kidneys
- Recurrent kidney infection also called pyelonephritis (pie-uh-low-nuh-FRY-tis)
Rapidly progressive glomerulonephritis
Nephropathy of pregnancy/pregnancy toxemia
Polycystic kidney disease
Systemic lupus erythematosus nephritis
Renal failure due to a congenital abnormality of metabolism
Renal/urinary tract tuberculosis
Renal/urinary tract calculus
Renal/urinary tract tumor
Obstructive urinary tract disease
Symptoms of End-Stage Renal Disease
Early in chronic kidney disease, you may have no signs or symptoms. As chronic kidney disease progresses to end-stage renal disease, signs and symptoms might include:
- Loss of appetite
- Fatigue and weakness
- Sleep problems
- Changes in how much you urinate
- Decreased mental sharpness
- Muscle twitches and cramps
- Swelling of feet and ankles
- Persistent itching
- Chest pain, if fluid builds up around the lining of the heart
- Shortness of breath, if fluid builds up in the lungs
- High blood pressure (hypertension) that’s difficult to control
Signs and symptoms of kidney disease are often nonspecific, meaning they can also be caused by other illnesses. Because your kidneys are highly adaptable and able to compensate for lost function, signs and symptoms may not appear until irreversible damage has occurred.
You may experience a wide range of symptoms, including
- a decrease in how much you urinate
- inability to urinate
- malaise, or a general ill feeling
- unexplained weight loss
- loss of appetite
- nausea and vomiting
- dry skin and itching
- changes in skin color
- bone pain
- confusion and difficulty concentrating
- bruising easily
- frequent nosebleeds
- numbness in your hands and feet
- bad breath
- excessive thirst
- frequent hiccups
- the absence of menstrual cycles
- sleeping problems, such as obstructive sleep apnea and restless leg syndrome (RLS)
- low libido or impotence
- edema, or swelling, especially in your legs and hands
See your doctor right away if any of these symptoms interfere with your life, especially if you can’t urinate or sleep, are vomiting frequently, or feel weak and unable to do daily tasks.
Diagnosis of End-Stage Renal Disease
History and Physical
End-stage renal disease can present with a constellation of signs and symptoms. Some include volume overload refractory to diuretics, hypertension poorly responsive to medication, anemia, mineral and bone disorders, and metabolic derangements including hyperkalemia, hyponatremia, metabolic acidosis, hypo/hypercalcemia, and hyperphosphatemia. Uremic toxicity can present as anorexia, nausea, vomiting, bleeding diatheses, pericarditis, uremic neuropathy or encephalopathy, seizure, coma, and death. Uremic toxicity is an indication for urgent dialysis.[rx]
In general, ESRD symptoms appear in stages 4 and 5 when the GFR is less than 30 ml/min. Some patients with nephrotic syndrome and cystic renal disease may present earlier.
Depression is ubiquitous in patients with ESRD and should be screened for on presentation.[rx]
Lab Test and Imaging
ESRD changes the results of many tests. People receiving dialysis will need these and other tests done often:
- A physical exam – during which your doctor measures your height, weight, and blood pressure and also looks for signs of problems with your heart or blood vessels and conducts a neurological exam.
- Blood tests – Complete blood count (CBC) and measure the number of waste products, such as creatinine and urea, in your blood.
- Urine tests – to check the level of the protein albumin in your urine — a high albumin level may indicate kidney disease.
- Urinalysis – This test helps your doctor check for protein and blood in your urine. These substances indicate that your kidneys aren’t processing waste properly.
- Serum creatinine test – This test helps your doctor check whether creatinine is building up in your blood. Creatinine is a waste product that your kidneys should filter out of your body.
- Blood urea nitrogen test – This test helps your doctor check how much nitrogen is in your blood.
- Estimated glomerular filtration rate (GFR) – This test allows your doctor to estimate how well your kidneys filter waste.
- Imaging tests – such as ultrasound, magnetic resonance imaging or computed tomography (CT) scan, to assess your kidneys’ structure and size and look for abnormalities.
- Removing a sample of kidney tissue (biopsy) – to examine under a microscope to learn what type of kidney disease you have and how much damage there is.
To calculate GFR, three equations are commonly used (the MDRD [Modification of Diet in Renal Disease Study], CKD-EPI, and Cockcroft-Gault formula). However, the best estimate of GFR is the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, which adjusts for age, race, and gender. However, it is important to note that the formula tends to underestimate the actual GFR at a GFR greater than 60 mL/min.[rx]
To quantitate albuminuria, a spot urine protein/creatinine ratio can be done. A value higher than 30 mg of albumin per gram of creatinine is considered abnormal, while values greater than 300mg/g are considered severely impaired renal function. Additionally, a 24-hour urine protein can also be performed. A value greater than 3.5 g is concerning for nephrotic range proteinuria.
Further evaluation of kidney disease can include a renal ultrasound, complete blood count (CBC), basic metabolic panel (BMP), urinalysis, and/or kidney biopsy. An ultrasound can provide data estimating size, obstructions, stones, cystic renal disease, mass lesions, echogenicity, and cortical thinning. Blood work will determine if there is secondary anemia and will detect evidence of electrolyte derangement. In cases of severe anemia secondary to CKD, erythropoiesis-stimulating agents should be started at a hemoglobin level below 10 g/dL. Finally, a renal biopsy may be necessary if the etiology remains unclear.[rx]
Treatment of End-Stage Renal Disease
Treatment of end-stage renal disease involves correcting parameters at the level of the patient’s presentation.[rx] Interventions aimed at slowing the rate of kidney disease should be initiated and can include:
Treating the underlying cause and managing blood pressure and proteinuria. Blood pressure should be targeted to a systolic blood pressure less than 130 mmHg and diastolic blood pressure less than 80 mmHg in adults with or without diabetes mellitus whose urine albumin excretion exceeds 30 mg for 24 hours. For diabetic patients with proteinuria, an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) should be started in cases where urine albumin values range between 30 and 300 mg in 24 hours and greater than 300 mg in 24 hours. These drugs slow the disease progression, particularly when initiated before the GFR decreases to less than 60 mL/min or before plasma creatinine concentration exceeds 1.2 and 1.5 in women and men, respectively.[rx]
Other targets in preventive care and monitoring should include tight glycemic control, cardiovascular risk reduction, and general lifestyle recommendations such as smoking cessation and dietary restriction. Glycemic control is critical. A hemoglobin A1C of less than 7% is generally recommended to prevent or delay microvascular complications in this population. Management with sodium-glucose transporter 2 (SGLT-2) inhibitors may reduce the disease burden in those with type II diabetes mellitus.[rx]
Treatment of chronic metabolic acidosis with supplemental renal bicarbonate also may slow the progression of end-stage renal disease.[rx]
Patients with CKD tend to have dyslipidemia, particularly hypertriglyceridemia. Monitoring fasting lipid panels and initiation of cholesterol-lowering agents such as HMG-CoA reductase inhibitors should be done early in the course of the disease.[rx]
Lifestyle modification and dietary restrictions are routinely recommended. Adhering to a low salt diet (less than 2 g/day), a renal diet (avoiding foods that are high in phosphorus), and restricting daily protein to 0.8 g per kg body weight per day is essential to managing disease burden.
Hypocalcemia should also be monitored. A 25-OH vitamin D level less than 10 ng/mL warrants initiation of ergocalciferol 50,000 IU weekly for 6 to 8 weeks before switching to cholecalciferol 800 to 1000 IU daily.[rx]
A kidney transplant is a surgical procedure to place a healthy kidney from a live or deceased donor into a person whose kidneys no longer function properly. A kidney transplant is often the treatment of choice for end-stage renal disease, compared with a lifetime on dialysis.
The kidney transplant process takes time. It involves finding a donor, living or deceased, whose kidney best matches your own. You then undergo a surgical procedure to place the new kidney in your lower abdomen and attach the blood vessels and ureter — the tube that links the kidney to the bladder — that will allow the new kidney to function.
You’ll spend several days to a week in the hospital. After leaving the hospital, you’ll have frequent checkups as your recovery continues. You’ll take a number of medications to help keep your immune system from rejecting your new kidney and to reduce the risk of post-surgery complications, such as infection.
After a successful kidney transplant, your new kidney filters your blood, and you no longer need dialysis.
Dialysis does some of the work of your kidneys when your kidneys can’t do it themselves. This includes removing extra fluids and waste products from your blood, restoring electrolyte levels, and helping control your blood pressure.
Dialysis options include peritoneal dialysis and hemodialysis.
- Peritoneal dialysis – During peritoneal dialysis, blood vessels in your abdominal lining (peritoneum) fill in for your kidneys with the help of a fluid that washes in and out of the peritoneal space. Peritoneal dialysis is done in your home.
- Hemodialysis – During hemodialysis, a machine does some of the work of the kidneys by filtering harmful wastes, salts, and fluid from your blood. Hemodialysis may be done at a center or in your home.[rx]
For dialysis to be successful, you may need to make lifestyle changes, such as following certain dietary recommendations.
With supportive care, your symptoms are managed so that you feel better. You may choose supportive care alone or combine it with other treatment options.
Without either dialysis or a transplant, kidney failure progresses, eventually leading to death. In some people, the disease progresses slowly over months and years, while in others the disease progresses quickly.
Potential future treatments
Regenerative medicine holds the potential to fully heal damaged tissues and organs, offering solutions and hope for people who have conditions that today are beyond repair.
Regenerative medicine approaches include:
- Boosting the body’s natural ability to heal itself
- Using healthy cells, tissues, or organs from a living or deceased donor to replace damaged ones
- Delivering specific types of cells or cell products to diseased tissues or organs to restore tissue and organ function
For people with kidney disease, regenerative medicine approaches may be developed in the future to help slow the progression of the disease.
Kidney damage, once it occurs, can’t be reversed. Potential complications can affect almost any part of your body and can include:
- Fluid retention, which could lead to swelling in your arms and legs, high blood pressure, or fluid in your lungs (pulmonary edema)
- A sudden rise in potassium levels in your blood (hyperkalemia), which could impair your heart’s ability to function and may be life-threatening
- Heart and blood vessel (cardiovascular) disease
- Weak bones and an increased risk of bone fractures
- Decreased sex drive, erectile dysfunction or reduced fertility
- Damage to your central nervous system, which can cause difficulty concentrating, personality changes or seizures
- Decreased immune response, which makes you more vulnerable to infection
- Pericarditis, an inflammation of the saclike membrane that envelops your heart (pericardium)
- Pregnancy complications that carry risks for the mother and the developing fetus
- Irreversible damage to your kidneys (end-stage kidney disease), eventually requiring either dialysis or a kidney transplant for survival
Health problems that can result from ESRD include
- Bleeding from the stomach or intestines
- Bone, joint, and muscle pain
- Changes in blood sugar (glucose)
- Damage to nerves of the legs and arms
- Fluid buildup around the lungs
- High blood pressure, heart attack, and heart failure
- High potassium level
- Increased risk of infection
- Liver damage or failure
- Miscarriages or infertility
- Restless legs syndrome
- Stroke, seizures, and dementia
- Swelling and edema
- Weakening of the bones and fractures related to high phosphorous and low calcium levels
If you have kidney disease, you may be able to slow its progress by making healthy lifestyle choices:
- Lose weight if you need to
- Be active most days
- Eat a balanced diet of nutritious, low-sodium foods
- Control your blood pressure
- Take your medications as prescribed
- Have your cholesterol levels checked every year
- Control your blood sugar level
- Don’t smoke or use tobacco products
- Get regular checkups
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