Hyperoxaluria
Disease Details
Family Health Simplified
- Description
- Hyperoxaluria is a condition characterized by excessive urinary excretion of oxalate, which can lead to kidney stones and nephrocalcinosis.
- Type
-
Hyperoxaluria can be classified into two major types: primary and secondary.
Primary hyperoxaluria is a genetic disorder that is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disease. - Signs And Symptoms
-
**Signs and Symptoms of Hyperoxaluria:**
- **Kidney Stones:** Recurrent formation of kidney stones, which may cause severe pain in the side and back, below the ribs.
- **Urinary Issues:** Frequent urination, pain during urination, and blood in the urine.
- **Reduced Kidney Function:** Over time, can lead to chronic kidney disease and potentially kidney failure.
- **Urinary Tract Infections (UTIs):** Increased risk of UTIs.
- **Systemic Oxalosis:** In severe cases, oxalate crystals may deposit in other organs and tissues, causing bone pain, anemia, and skin ulcers.
Prompt diagnosis and management are essential to prevent severe complications. - Prognosis
- Prognosis for hyperoxaluria varies depending on the type (primary or secondary) and the effectiveness of the treatment. Primary hyperoxaluria can lead to kidney damage and failure if not properly managed, potentially requiring dialysis or a kidney transplant. Early diagnosis and treatment, such as hydration, dietary restrictions, and medications, can improve outcomes. Secondary hyperoxaluria, caused by dietary factors or gastrointestinal disorders, often has a better prognosis if the underlying cause is addressed.
- Onset
- The onset of hyperoxaluria can vary widely depending on whether it is primary or secondary hyperoxaluria. Primary hyperoxaluria, which is a rare genetic disorder, often presents in childhood or early adulthood. Symptoms can start as early as infancy but may not be apparent until later in life. Secondary hyperoxaluria is typically acquired due to dietary factors or other medical conditions and can occur at any age, usually manifesting after the precipitating factor is present.
- Prevalence
- The global prevalence of primary hyperoxaluria is estimated to be between 1 to 3 cases per million people.
- Epidemiology
-
Hyperoxaluria is a rare condition characterized by the excessive excretion of oxalate in the urine. Its epidemiology varies depending on the type:
1. **Primary Hyperoxaluria (PH):**
- **Prevalence:** It is estimated to affect 1-3 individuals per million.
- **Genetics:** It is a genetic disorder with autosomal recessive inheritance.
- **Onset:** Often diagnosed in childhood or early adulthood.
2. **Secondary Hyperoxaluria:**
- **Prevalence:** Exact prevalence is not well-documented but is considered more common than primary hyperoxaluria.
- **Causes:** Can result from dietary factors, gastrointestinal diseases, or increased intake of oxalate-rich foods or vitamin C.
Overall, hyperoxaluria is more common in regions where genetic predispositions or dietary habits that increase oxalate intake are prevalent. Rates can also vary based on access to healthcare and diagnostic capabilities. - Intractability
- Hyperoxaluria is often considered intractable, particularly in cases where it is of a genetic origin, such as primary hyperoxaluria. Management typically focuses on controlling symptoms and preventing complications, as there is no definitive cure. In advanced stages, kidney damage may require interventions like dialysis or a kidney transplant.
- Disease Severity
-
Hyperoxaluria can vary in severity depending on whether it is primary or secondary.
- **Primary Hyperoxaluria** is a genetic disorder that often leads to severe kidney problems, including kidney stones, nephrocalcinosis, and eventually kidney failure if untreated.
- **Secondary Hyperoxaluria** occurs due to an excess intake of oxalate from the diet or other conditions like gastrointestinal disorders. Its severity can be mild to moderate but may still result in recurrent kidney stones and potential renal damage.
Overall, prompt diagnosis and tailored treatment are crucial to managing the disease effectively and mitigating complications. - Healthcare Professionals
- Disease Ontology ID - DOID:2977
- Pathophysiology
- Hyperoxaluria is a condition characterized by an excessive excretion of oxalate in the urine. The pathophysiology involves the overproduction or inadequate elimination of oxalate, a byproduct of metabolism. This can result from genetic disorders, such as Primary Hyperoxaluria types 1, 2, and 3, where enzyme deficiencies in the liver lead to abnormal oxalate synthesis. It can also be secondary to dietary factors or gastrointestinal conditions that increase oxalate absorption. Elevated oxalate levels can bind with calcium to form calcium oxalate crystals, leading to kidney stones, nephrocalcinosis, and potentially renal failure.
- Carrier Status
- Carrier status in hyperoxaluria refers to individuals who possess one copy of a mutated gene associated with the condition but do not exhibit symptoms themselves. This is typically observed in autosomal recessive forms of hyperoxaluria, where two copies of the mutated gene (one from each parent) are necessary to manifest the disease. Carriers can pass the gene mutation to their offspring, and if both parents are carriers, there is a 25% chance with each pregnancy that the child will have hyperoxaluria.
- Mechanism
-
Hyperoxaluria is a condition characterized by excessive urinary excretion of oxalate. The mechanisms and molecular mechanisms underlying hyperoxaluria can be summarized as follows:
### Mechanism
1. **Overproduction of Oxalate:** The liver produces excess oxalate due to enzymatic defects.
2. **Reduced Kidney Function:** The kidneys are less able to excrete oxalate, leading to accumulation.
3. **Dietary Intake:** High intake of oxalate-rich foods or vitamin C, which is metabolized to oxalate, can contribute.
4. **Intestinal Absorption:** Increased absorption of oxalate from the gut.
### Molecular Mechanisms
1. **Primary Hyperoxaluria Type 1 (PH1):**
- Caused by mutations in the *AGXT* gene encoding alanine-glyoxylate aminotransferase (AGT).
- AGT deficiency leads to accumulation of glyoxylate, which is converted to oxalate.
2. **Primary Hyperoxaluria Type 2 (PH2):**
- Caused by mutations in the *GRHPR* gene encoding glyoxylate reductase/hydroxypyruvate reductase (GRHPR).
- GRHPR deficiency results in excessive glyoxylate, converted to oxalate.
3. **Primary Hyperoxaluria Type 3 (PH3):**
- Caused by mutations in the *HOGA1* gene encoding 4-hydroxy-2-oxoglutarate aldolase (HOGA).
- Disruption in this enzyme increases production of oxalate precursors.
4. **Enteric Hyperoxaluria:**
- Associated with conditions like inflammatory bowel disease or gastric bypass surgery.
- Altered gut microbiota or reduced calcium binding leads to higher oxalate absorption.
Understanding these mechanisms helps in diagnosing and developing targeted therapeutic strategies for hyperoxaluria. - Treatment
-
The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e. kidney transplantation once the disease has already reached mature or terminal stages. However, through genomics and proteomics approaches, efforts are currently being made to elucidate the kinetics of AGXT folding which has a direct bearing on its targeting to appropriate subcellular localization. A child with primary hyperoxaluria was treated with a liver and kidney transplant. A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver.
Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation. - Compassionate Use Treatment
-
Hyperoxaluria is characterized by an excessive urinary excretion of oxalate, which can lead to kidney stones and renal damage. For compassionate use, off-label, or experimental treatments, the following approaches may be considered:
1. **Lumasiran (OXLUMO)**: An RNA interference (RNAi) therapeutic specifically designed to reduce oxalate production, approved for both primary and severe secondary hyperoxaluria in some jurisdictions.
2. **Pyridoxine (Vitamin B6)**: Used off-label, particularly effective in certain types of primary hyperoxaluria (PH1) as it can decrease oxalate production in patients with specific genetic mutations.
3. **Aldurazyme (recombinant human anaplerotic enzyme treatment)**: Although still experimental, it aims to enzymatically degrade oxalate or its precursors in the body.
4. **CRISPR/Cas9 and Gene Therapy**: Experimental approaches focusing on correcting the underlying genetic mutations responsible for primary hyperoxaluria.
5. **Oxalobacter formigenes Probiotics**: Currently under investigation, these probiotics are thought to degrade oxalate in the gut, potentially reducing systemic oxalate levels.
6. **Stool Transplantation**: A very experimental and investigational approach aimed at modifying gut microbiota to include bacteria that degrade oxalate.
7. **Hydroxyproline restriction**: Experimental dietary intervention reducing intake of hydroxyproline, a precursor to oxalate, to reduce oxalate production.
These treatments are considered based on individual patient circumstances and their specific type of hyperoxaluria. Consultation with healthcare professionals specializing in metabolic disorders is crucial for appropriate management. - Lifestyle Recommendations
-
For hyperoxaluria, lifestyle recommendations generally include:
1. **Hydration:** Drink plenty of fluids to help dilute the oxalate in urine and reduce the risk of kidney stone formation.
2. **Dietary Modifications:**
- **Limit Oxalate-Rich Foods:** Avoid or reduce intake of foods high in oxalates, such as spinach, rhubarb, beets, nuts, and chocolate.
- **Increase Calcium Intake:** Consume adequate calcium through diet (e.g., dairy products) or supplements, as calcium can bind with oxalate in the gut and reduce absorption.
- **Moderate Sodium Intake:** High sodium levels can increase calcium excretion in urine, potentially contributing to stone formation.
- **Limit Vitamin C:** Excessive vitamin C can convert to oxalate in the body, so it's important to avoid high doses.
3. **Medication Compliance:** Follow any prescribed medication regimens to manage hyperoxaluria, such as pyridoxine (vitamin B6), which may help reduce oxalate production in some cases.
4. **Regular Monitoring:** Keep regular appointments with healthcare providers to monitor kidney function and oxalate levels.
These recommendations are general, and it's important to work with healthcare providers for personalized guidance. - Medication
-
For hyperoxaluria, specific medications may be prescribed depending on the type and cause of the condition:
- **Primary Hyperoxaluria:** Commonly treated with pyridoxine (vitamin B6), which may reduce oxalate production in some patients.
- **Secondary Hyperoxaluria:** Might involve the use of calcium supplements to bind oxalate in the intestine, reducing its absorption.
Other treatments can include high fluid intake, dietary modifications, and, in severe cases, dialysis or liver and kidney transplants. - Repurposable Drugs
-
Hyperoxaluria is a condition characterized by excessive urinary excretion of oxalate, which can lead to kidney stones and renal damage. Regarding repurposable drugs:
1. **Pyridoxine (Vitamin B6)**: It can reduce the oxalate production in some patients, particularly those with primary hyperoxaluria type 1.
2. **Potassium Citrate**: Often used to alkalinize the urine and inhibit crystal formation.
3. **Thiazide diuretics**: These may help in reducing calcium excretion, which can mitigate calcium oxalate stone formation.
These medications are used based on the type and severity of hyperoxaluria and the patient's overall health profile. - Metabolites
-
Hyperoxaluria is characterized by the excessive excretion of oxalate in the urine. Elevated oxalate levels lead to the formation of calcium oxalate crystals, which can contribute to kidney stone formation and potentially lead to kidney damage.
Primary metabolite: Oxalate (oxalic acid).
Secondary effects: Increased calcium oxalate crystal formation.
Further metabolic considerations: Glycolate (in primary hyperoxaluria type 1 due to glyoxylate metabolism abnormalities).
Risk of secondary metabolites: Accumulation of glyoxylate and its conversion to oxalate. - Nutraceuticals
- Nutraceuticals that may be considered for managing hyperoxaluria include probiotics like Lactobacillus and Bifidobacterium species, which can help degrade oxalate in the gut. Additionally, calcium and magnesium supplements can bind to oxalate in the intestines, reducing its absorption. Vitamin B6 (pyridoxine) may also be helpful, as it can decrease oxalate production in the body. However, it's important for individuals to consult a healthcare provider before starting any nutraceutical regimen.
- Peptides
- Hyperoxaluria refers to a condition where there is an excessive amount of oxalate in the urine. This can lead to the formation of kidney stones and other kidney-related issues. Currently, peptides and nanotechnology are being explored as potential treatment or management strategies. Peptides could potentially act as inhibitors of oxalate production or promote its breakdown. Nanotechnology might provide targeted drug delivery systems to improve the efficacy and reduce side effects of treatments. However, these approaches are largely investigational and not yet standard treatments.