Chronic Kidney Disease
Disease Details
Family Health Simplified
- Description
- Chronic kidney disease (CKD) is a long-term condition characterized by a gradual loss of kidney function over time, potentially leading to kidney failure.
- Type
- Chronic kidney disease (CKD) is generally not considered a genetic disorder. It is primarily caused by other conditions such as diabetes, hypertension, and glomerulonephritis. However, certain hereditary forms of kidney disease, like polycystic kidney disease (PKD), do exist and can lead to CKD. The genetic transmission of PKD is typically autosomal dominant, but less commonly, it can be autosomal recessive.
- Signs And Symptoms
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CKD is initially without symptoms, and is usually detected on routine screening blood work by either an increase in serum creatinine, or protein in the urine. As the kidney function decreases, more unpleasant symptoms may emerge:
Blood pressure is increased due to fluid overload and production of vasoactive hormones created by the kidney via the renin–angiotensin system, increasing the risk of developing hypertension and heart failure. People with CKD are more likely than the general population to develop atherosclerosis with consequent cardiovascular disease, an effect that may be at least partly mediated by uremic toxins. People with both CKD and cardiovascular disease have significantly worse prognoses than those with only cardiovascular disease.
Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Due to its high systemic concentration, urea is excreted in eccrine sweat at high concentrations and crystallizes on skin as the sweat evaporates ("uremic frost").
Potassium accumulates in the blood (hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias). Hyperkalemia usually does not develop until the glomerular filtration rate falls to less than 20–25 mL/min/1.73 m2, when the kidneys have decreased ability to excrete potassium. Hyperkalemia in CKD can be exacerbated by acidemia (which leads to extracellular shift of potassium) and from lack of insulin.
Fluid overload symptoms may range from mild edema to life-threatening pulmonary edema.
Hyperphosphatemia results from poor phosphate elimination in the kidney, and contributes to increased cardiovascular risk by causing vascular calcification. Circulating concentrations of fibroblast growth factor-23 (FGF-23) increase progressively as the kidney capacity for phosphate excretion declines, which may contribute to left ventricular hypertrophy and increased mortality in people with CKD .
Hypocalcemia results from 1,25 dihydroxyvitamin D3 deficiency (caused by high FGF-23 and reduced kidney mass) and resistance to the action of parathyroid hormone. Osteocytes are responsible for the increased production of FGF-23, which is a potent inhibitor of the enzyme 1-alpha-hydroxylase (responsible for the conversion of 25-hydroxycholecalciferol into 1,25 dihydroxyvitamin D3). Later, this progresses to secondary hyperparathyroidism, kidney osteodystrophy, and vascular calcification that further impairs cardiac function. An extreme consequence is the occurrence of the rare condition named calciphylaxis.
Changes in mineral and bone metabolism that may cause 1) abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism; 2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength (kidney osteodystrophy); and 3) vascular or other soft-tissue calcification. CKD-mineral and bone disorders have been associated with poor outcomes.
Metabolic acidosis may result from decreased capacity to generate enough ammonia from the cells of the proximal tubule. Acidemia affects the function of enzymes and increases excitability of cardiac and neuronal membranes by the promotion of hyperkalemia.
Anemia is common and is especially prevalent in those requiring haemodialysis. It is multifactorial in cause, but includes increased inflammation, reduction in erythropoietin, and hyperuricemia leading to bone-marrow suppression. Hypoproliferative anemia occurs due to inadequate production of erythropoietin by the kidneys.
In later stages, cachexia may develop, leading to unintentional weight loss, muscle wasting, weakness, and anorexia.
Cognitive decline in patients experiencing CKD is an emerging symptom revealed in research literature. Current research suggests that patients with CKD face a 35-40% higher likelihood of cognitive decline and or dementia. This relation is dependent on the severity of CKD in each patient; although emerging literature indicates that patients at all stages of CKD will have a higher risk of developing these cognitive issues.
Sexual dysfunction is very common in both men and women with CKD. A majority of men have a reduced sex drive, difficulty obtaining an erection, and reaching orgasm, and the problems get worse with age. Most women have trouble with sexual arousal, and painful menstruation and problems with performing and enjoying sex are common. - Prognosis
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CKD increases the risk of cardiovascular disease, and people with CKD often have other risk factors for heart disease, such as high blood lipids. The most common cause of death in people with CKD is cardiovascular disease rather than kidney failure.
Chronic kidney disease results in worse all-cause mortality (the overall death rate) which increases as kidney function decreases. The leading cause of death in chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.While kidney replacement therapies can maintain people indefinitely and prolong life, the quality of life is negatively affected. Kidney transplantation increases the survival of people with stage 5 CKD when compared to other options; however, it is associated with an increased short-term mortality due to complications of the surgery. Transplantation aside, high-intensity home hemodialysis appears to be associated with improved survival and a greater quality of life, when compared to the conventional three-times-a-week hemodialysis and peritoneal dialysis.People with ESKD are at increased overall risk for cancer. This risk is particularly high in younger people and gradually diminishes with age. Medical specialty professional organizations recommend that physicians do not perform routine cancer screening in people with limited life expectancies due to ESKD because evidence does not show that such tests lead to improved outcomes.In children, growth failure is a common complication from CKD. Children with CKD will be shorter than 97% of children the same age and sex. This can be treated with additional nutritional support, or medication such as Growth hormone - Onset
- Chronic kidney disease (CKD) often has a gradual onset, developing over months or years. It is typically asymptomatic in the early stages, and symptoms may not appear until the disease is advanced.
- Prevalence
- The prevalence of chronic kidney disease (CKD) varies globally, but it is estimated to affect approximately 10% to 15% of the adult population worldwide.
- Epidemiology
- About one in ten people have chronic kidney disease. In Canada 1.9 to 2.3 million people were estimated to have CKD in 2008. CKD affected an estimated 16.8% of U.S. adults aged 20 years and older in the period from 1999 to 2004. In 2007 8.8% of the population of Great Britain and Northern Ireland had symptomatic CKD.Chronic kidney disease was the cause of 956,000 deaths globally in 2013, up from 409,000 deaths in 1990.
- Intractability
- Chronic kidney disease (CKD) is generally considered intractable, meaning it cannot be cured. Management focuses on slowing the progression of the disease, treating underlying conditions, and addressing complications to improve quality of life. Advanced stages may require dialysis or kidney transplantation.
- Disease Severity
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Chronic kidney disease (CKD) severity is classified into five stages based on the glomerular filtration rate (GFR):
- **Stage 1**: GFR ≥ 90 mL/min with evidence of kidney damage (e.g., proteinuria).
- **Stage 2**: GFR 60-89 mL/min with evidence of kidney damage.
- **Stage 3**: GFR 30-59 mL/min, subdivided into:
- **Stage 3a**: GFR 45-59 mL/min.
- **Stage 3b**: GFR 30-44 mL/min.
- **Stage 4**: GFR 15-29 mL/min.
- **Stage 5**: GFR < 15 mL/min, indicating kidney failure that typically requires dialysis or transplantation.
The severity increases as the stage advances, with Stage 5 being the most severe, often referred to as end-stage renal disease (ESRD). - Healthcare Professionals
- Disease Ontology ID - DOID:784
- Pathophysiology
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Chronic kidney disease (CKD) is characterized by a gradual loss of kidney function over time. The pathophysiology involves complex interactions between various factors:
1. **Initiating Factors**: Often starts with primary conditions like diabetes mellitus, hypertension, or glomerulonephritis, which cause initial kidney damage.
2. **Nephron Loss**: As the kidney sustains damage, there is a reduction in the number of functioning nephrons (the filtering units of the kidney).
3. **Compensatory Hyperfiltration**: The remaining nephrons undergo hyperfiltration to compensate for the loss, leading to increased glomerular pressure and further kidney damage.
4. **Inflammation and Fibrosis**: Persistent injury and repair processes result in inflammation and fibrosis (scarring) of kidney tissue, progressively worsening kidney function.
5. **Altered Biochemistry**: Disruption in normal balance of electrolytes, acid-base, and fluid regulation. Typically, there’s an accumulation of waste products like urea and creatinine in the blood.
6. **Hormonal Dysregulation**: Reduced kidney function impairs the production of erythropoietin (leading to anemia) and affects the activation of Vitamin D (leading to bone disease).
As CKD progresses through its stages (1 to 5), kidney function becomes increasingly impaired, eventually requiring renal replacement therapies such as dialysis or kidney transplantation in end-stage kidney disease (ESKD). - Carrier Status
- Chronic kidney disease (CKD) is not typically caused by a single genetic mutation that would result in a "carrier status." CKD is usually the result of a complex interplay of genetic factors, underlying health conditions, and lifestyle factors such as hypertension, diabetes, and long-term exposure to certain medications or toxins. Therefore, the concept of "carrier status" does not apply to chronic kidney disease.
- Mechanism
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Chronic kidney disease (CKD) is characterized by the gradual loss of kidney function over time. The mechanisms and molecular mechanisms involved in CKD encompass a range of complex processes:
### Mechanism:
1. **Glomerular Damage**: Initial kidney injury often affects the glomeruli, the filtering units of the kidneys. This can be due to conditions like hypertension (high blood pressure) and diabetes.
2. **Tubulointerstitial Fibrosis**: As kidney disease progresses, damage spreads to the tubules and interstitial tissue, leading to scarring (fibrosis) and loss of functional kidney tissue.
3. **Vascular Changes**: Blood vessels within the kidney may become narrowed or blocked, reducing blood flow and oxygen delivery to kidney tissues.
### Molecular Mechanisms:
1. **Inflammation**: Inflammatory cytokines such as TNF-alpha, IL-6, and IL-1 contribute to kidney damage by promoting inflammation and further injury.
2. **Fibrosis**: Transforming growth factor-beta (TGF-β) plays a crucial role in fibrosis by stimulating the production of extracellular matrix components, leading to scarring.
3. **Oxidative Stress**: Increased production of reactive oxygen species (ROS) contributes to cellular damage and inflammation.
4. **Renin-Angiotensin-Aldosterone System (RAAS)**: Overactivation of RAAS leads to increased blood pressure and promotes fibrosis and inflammation.
5. **Podocyte Injury**: Damage to podocytes, specialized cells in the glomeruli, disrupts the filtration barrier, leading to proteinuria (protein in the urine) which further damages the kidney.
6. **Epithelial-to-Mesenchymal Transition (EMT)**: Tubular epithelial cells can transform into myofibroblasts, contributing to fibrosis.
7. **Autophagy and Apoptosis**: Dysregulation of autophagy (cellular cleaning process) and increased apoptosis (programmed cell death) contribute to the loss of functional kidney cells.
These mechanisms and molecular pathways interplay to progressively impair kidney function, ultimately leading to end-stage renal disease if left unchecked. - Treatment
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Treatment for chronic kidney disease (CKD) focuses on managing symptoms, slowing progression, and addressing underlying causes. Key approaches include:
1. **Lifestyle Changes**: Eating a balanced diet low in sodium, potassium, and phosphorus, maintaining a healthy weight, quitting smoking, and exercising regularly.
2. **Medications**: Controlling blood pressure and blood sugar levels with medications such as ACE inhibitors, ARBs, and diabetes medications. Use of phosphate binders, vitamin D supplements, and erythropoiesis-stimulating agents (ESAs) to manage complications.
3. **Dialysis**: In advanced stages (end-stage renal disease), dialysis may be necessary to filter waste from the blood.
4. **Kidney Transplant**: For suitable candidates, a kidney transplant may be an option.
5. **Monitoring and Specialist Care**: Regular check-ups with a nephrologist, monitoring kidney function, and managing associated health issues like cardiovascular disease.
Early detection and intervention can significantly improve outcomes. - Compassionate Use Treatment
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For chronic kidney disease (CKD), compassionate use treatments and off-label or experimental treatments may include:
1. **Sodium Bicarbonate**: Used off-label to manage metabolic acidosis in CKD patients. It helps to neutralize excess acid in the blood and slow the progression of kidney disease.
2. **Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors**: Though primarily approved for diabetes, these drugs have shown promise in CKD for improving kidney outcomes and are sometimes used off-label.
3. **Bardoxolone Methyl**: An investigational drug aimed at reducing inflammation and oxidative stress, potentially slowing CKD progression. It's currently under study in clinical trials.
4. **Finerenone**: A non-steroidal mineralocorticoid receptor antagonist being investigated for its effects on kidney and cardiovascular outcomes in CKD.
5. **Stem Cell Therapy**: An experimental approach that aims to repair and regenerate damaged kidney tissues. This is still largely in the research phase and not widely available.
These treatments should ideally be considered under the guidance of a healthcare provider, often within the context of clinical trials or specialized care settings. - Lifestyle Recommendations
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For chronic kidney disease (CKD), the following lifestyle recommendations are typically suggested:
1. **Dietary Changes**:
- **Limit Protein Intake**: Reducing protein can decrease the kidneys' workload.
- **Control Sodium**: Lower sodium intake to manage blood pressure and reduce fluid retention.
- **Reduce Potassium and Phosphorus**: Monitor and limit these minerals if levels become too high.
2. **Fluid Management**:
- **Stay Hydrated**: Maintain adequate fluid intake but avoid excessive consumption, as advised by your healthcare provider.
3. **Blood Pressure and Diabetes Control**:
- **Monitor Blood Pressure**: Keep it within recommended levels to prevent further kidney damage.
- **Manage Blood Sugar**: Control diabetes through diet, medications, and lifestyle adjustments.
4. **Exercise Regularly**:
- **Stay Active**: Regular physical activity can help control blood pressure, maintain a healthy weight, and improve overall health.
5. **Avoid Smoking and Limit Alcohol**:
- **Quit Smoking**: Smoking can worsen CKD and lead to cardiovascular problems.
- **Limit Alcohol**: Excessive alcohol can negatively impact kidney function.
6. **Medication Adherence**:
- **Take Prescribed Medications**: Follow your healthcare provider’s prescriptions and advice on medications.
7. **Regular Monitoring**:
- **Frequent Check-ups**: Regular kidney function monitoring and follow-up with healthcare providers.
8. **Weight Management**:
- **Maintain a Healthy Weight**: Aim for a healthy body weight through diet and exercise.
Adherence to these lifestyle recommendations can help manage symptoms and slow the progression of chronic kidney disease. Always consult with a healthcare provider for personalized advice. - Medication
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Medications commonly prescribed for managing chronic kidney disease (CKD) include:
1. **ACE Inhibitors or ARBs**: These help control blood pressure and reduce proteinuria to protect kidney function.
2. **Diuretics**: Assist in managing fluid retention and blood pressure.
3. **Phosphate Binders**: To control high phosphate levels in the blood.
4. **Erythropoiesis-Stimulating Agents (ESAs)**: To treat anemia by stimulating red blood cell production.
5. **Vitamin D Analogues**: Help address bone disease associated with CKD.
6. **Sodium Bicarbonate**: To manage metabolic acidosis by neutralizing excess acid in the blood.
It is essential for patients to follow their healthcare provider's recommendations and regularly monitor their condition. - Repurposable Drugs
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Repurposable drugs for chronic kidney disease (CKD) include:
1. **Angiotensin-Converting Enzyme (ACE) Inhibitors** - Originally used for hypertension and heart failure, these drugs help reduce proteinuria and slow CKD progression.
2. **Angiotensin II Receptor Blockers (ARBs)** - Similar to ACE inhibitors, ARBs are used to manage hypertension and protect kidney function by reducing proteinuria.
3. **Statins** - Typically used for managing lipid levels, statins are shown to reduce inflammation and may benefit CKD patients by slowing disease progression.
4. **Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors** - Initially developed for diabetes management, these drugs have been found to protect kidney function and can be beneficial for CKD patients, both diabetic and non-diabetic.
5. **Metformin** - A common diabetes medication that has shown potential kidney protective effects, although its use must be carefully managed in advanced CKD due to the risk of lactic acidosis.
These drugs are already approved for other conditions but have shown promise in managing CKD due to their additional protective effects on the kidneys. - Metabolites
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Chronic kidney disease (CKD) involves the gradual loss of kidney function over time, impacting the body's ability to filter waste from the blood. This can lead to the accumulation of various metabolites. Some key metabolites affected in CKD include:
1. **Urea**: Elevated levels in the blood due to impaired filtration.
2. **Creatinine**: Increased as kidney function declines, commonly used to estimate glomerular filtration rate (GFR).
3. **Phosphate**: Often high due to reduced excretion, leading to potential bone and cardiovascular issues.
4. **Potassium**: Can rise dangerously, causing hyperkalemia, which affects heart function.
5. **Parathyroid hormone (PTH)**: Elevated due to altered calcium and phosphate metabolism.
6. **Acid metabolites**: Accumulation can lead to metabolic acidosis, affecting overall metabolism and organ function.
Monitoring these metabolites helps manage and assess the progression of CKD. - Nutraceuticals
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For chronic kidney disease (CKD), nutraceuticals refer to food-derived compounds that may offer health benefits in managing the disease. Examples include omega-3 fatty acids, antioxidants (e.g., vitamins C and E), and certain plant-derived compounds like curcumin. These can help reduce inflammation, oxidative stress, and potentially slow disease progression.
Nanotechnology applications in CKD are still largely experimental but show promise. Nanosystems can improve drug delivery, allowing for targeted and controlled release of medications to the kidneys. They may also aid in better diagnostic techniques through enhanced imaging and biomarker detection. - Peptides
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In the context of chronic kidney disease (CKD), peptides can play significant roles in both diagnosis and treatment. Certain peptides are used as biomarkers to assess kidney function and the progression of CKD. For instance, elevated levels of serum cystatin C are considered indicative of declining renal function. Additionally, therapeutic peptides are being researched for their potential to reduce inflammation and fibrosis in kidney tissue.
Nanotechnology, including nanoparticles, offers promising advances in CKD management. Nanoparticles can improve the delivery and efficacy of drugs targeted to the kidneys, minimize side effects, and enable better imaging techniques for early detection and monitoring of the disease. For example, nanoparticle-based drug delivery systems can be designed to release therapeutic agents specifically at the site of renal injury, enhancing the treatment efficacy while reducing systemic toxicity. Additionally, nanoparticles are being explored for their potential in renal regenerative medicine and to develop novel diagnostic tools.