Materiały źródłowe

• #1 Hyperoxaluria and oxalosis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hyperoxaluria/symptoms-causes/syc-20352254

  Hyperoxaluria can be caused by a change in a gene, an intestine disease or eating too many foods that are high in oxalate. […] Oxalosis happens if you have primary or enteric hyperoxaluria and your kidneys stop working well enough. The body can no longer get rid of the extra oxalate, so the oxalate starts building up. […] Primary hyperoxaluria. This type is a rare inherited disease, which means that it’s passed down in families. It’s caused by changes in a gene. […] Enteric hyperoxaluria. Some intestine problems cause the body to absorb more oxalate from foods. […] Hyperoxaluria tied to eating foods with lots of oxalate. Eating large amounts of foods high in oxalate can raise your risk of hyperoxaluria or kidney stones.

• #1 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  Hyperoxaluria is a significant contributor to nephrolithiasis, and the causes of excess urinary oxalate can be classified based on etiology into primary and secondary hyperoxaluria. […] Depending on etiology, hyperoxaluria can be broadly divided into primary (rare) and secondary (common). […] Primary Hyperoxaluria (PH) is caused by an inherent genetic defect or absence of a specific enzymatic activity, ultimately leading to significantly increased oxalate levels in the body. […] Symptoms typically appear in childhood, with a median age of presentation of only 4 to 5 years old. […] PH often leads to multiple recurrent calcium oxalate nephrolithiasis episodes, nephrocalcinosis, and progressive renal damage, which may become end-stage renal disease (ESRD). […] Secondary Hyperoxaluria mainly pertains to excess exogenous oxalate gained either through diet or due to intestinal pathologies.

• #1 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. […] Primary hyperoxaluria (PH) is a group of autosomal recessive disorders of glyoxylate metabolism that cause the overproduction of endogenous oxalate a redundant metabolic end product that is excreted primarily via the kidneys. […] In PH, the combination of intra-tubular and interstitial deposits of calcium oxalate, chronic tubulo-interstitial inflammation and kidney obstruction by stones leads to kidney failure in more than 70% of patients. […] As soon as glomerular filtration rate (GFR) falls below 30-40ml/min/1.73m², hepatic oxalate production exceeds renal removal, leading to systemic oxalate storage in various tissues, including bone, heart, vessels, nerves and eye, and causing life-threatening multi-organ disease.

• #1 Primary hyperoxaluria – UpToDate

  https://www.uptodate.com/contents/primary-hyperoxaluria

  Primary hyperoxalurias (PHs) are rare inborn errors of glyoxylate metabolism characterized by the overproduction of oxalate, which is poorly soluble and is deposited as calcium oxalate in various organs. […] Genetics — Primary hyperoxaluria (PH) is primarily caused by autosomal recessive variants in three genes that encode enzymes involved in glyoxylate metabolism. These pathologic variants result in enhanced oxalate production. […] As oxalate is typically excreted in the urine, the kidney is the prime target for excessive oxalate deposition resulting in nephrocalcinosis and kidney stones and, in some cases, end-stage kidney disease (ESKD). […] PH type 1 (MIM #259900) is due to variants of AGXT that encodes the hepatic peroxisomal enzyme alanine glyoxylate aminotransferase (AGT), a pyridoxal 5′-phosphate-dependent enzyme, which is involved in the transamination of glyoxylate to glycine.

• #1 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  PH2 results from a deficiency in the enzyme glyoxylate and hydroxypyruvate reductase (GRHPR), which is expressed in many tissues and is encoded by GRHPR. […] PH3 results from the loss of function of the mitochondrial enzyme, 4-hydroxy-2-oxoglutarate aldolase (HOGA), which is predominantly found in the liver and kidney. […] Evidence exists for associations between genotype, disease phenotype and therapeutic responsiveness in PH1. […] Biochemical assessment has an important role in the diagnostic work-up of patients with symptoms suggestive of PH and can focus genetic testing. […] Urine dilution is key to preventing the formation of calcium oxalate kidney stones in patients with PH. […] Pyridoxine (vitamin B6) is effective in lowering urinary oxalate excretion in a subgroup of patients with PH1.

• #1 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  Hyperoxaluria, that is, elevated urinary excretion of the metabolic end product oxalate, can contribute to kidney stone formation and other health problems. Etiologically, the 4 main types of hyperoxaluria are the following: primary hyperoxaluria (types I, II, and III), enteric hyperoxaluria, dietary hyperoxaluria, and idiopathic or mild hyperoxaluria. Treatment depends to some extent on the underlying etiology and severity of the hyperoxaluria. […] High levels of oxalate in the system can produce various health problems, particularly kidney stone formation. The 4 main types of hyperoxaluria—primary hyperoxaluria, enteric hyperoxaluria, dietary hyperoxaluria, and idiopathic or mild hyperoxaluria—are the results of different pathophysiologic processes. […] Primary hyperoxaluria is a group of rare disorders due exclusively to genetic defects that cause a loss of specific enzymatic activity. With the normal metabolic pathway blocked, the alternative pathway that leads to oxalate production as an end-product of glyoxylate metabolism becomes extremely active, resulting in extremely high oxalate production.

• #1 Primary and secondary hyperoxaluria: Understanding the enigma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4419133/

  Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. […] The causes of SH are increase in dietary and intestinal absorption (enteric hyperoxaluria), excessive intake of oxalate precursors and alteration in intestinal microflora. […] Increased dietary absorption may occur in juicing which is being propagated as a health fad for clearing toxins from the body and also for weight loss. […] This form of hyperoxaluria is seen in partial gastrectomy, bariatric surgery, jejunoileal bypass, and inflammatory bowel disease. […] Oxalobacter formigenes (O. formigenes) is an aerobic gram negative bacterium that uses oxalate as its energy source and decreases intestinal absorption of oxalate and thus reduces urinary oxalate excretion.

• #1 Enteric Hyperoxaluria | OHF

  https://ohf.org/enteric/

  Enteric Hyperoxaluria (EH) is caused by the increased absorption of oxalate from foods in the digestive tract (also called the gut or intestines). This leads to high levels of oxalate in the urine. EH may be acquired as a result of certain weight loss surgeries or in inflammatory bowel disease including Crohns disease, cystic fibrosis or chronic pancreatitis. […] Currently the most common cause of Enteric Hyperoxaluria in western countries is malabsorption after bariatric surgery. […] Enteric Hyperoxaluria diagnosed after bariatric surgery is a result of malabsorption caused by the surgery in order to promote weight loss, and does not have an inherited or genetic cause. […] Although a high oxalate diet alone can lead to hyperoxaluria, diet is not a cause of Enteric Hyperoxaluria. However, a higher oxalate, lower calcium, or higher fat diet can make EH worse.

• #1 Hyperoxaluria and oxalosis – Augusta HealthSearchClose SearchSearch IconSearch IconClose Search IconMobile Menu IconMobile Menu Close IconInstagramFacebookTwitterYoutube

  https://www.augustahealth.com/disease/hyperoxaluria-and-oxalosis/

  Hyperoxaluria can be caused by inherited (genetic) disorders, an intestinal disease or eating too many oxalate-rich foods. […] Oxalosis happens after the kidneys fail in people who have primary and intestinal causes of hyperoxaluria, and excess oxalate builds up in the blood. […] Primary hyperoxaluria is a rare inherited (genetic) condition present at birth. […] Oxalosis occurs if you have primary hyperoxaluria and your kidneys fail. […] Several intestinal diseases, including Crohn’s disease and short bowel syndrome as a result of surgical procedures, increase the absorption of oxalate from foods, which can then increase the amount of oxalate excreted in the urine. […] Eating large amounts of foods high in oxalate can increase your risk of hyperoxaluria or kidney stones.

• #1 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  Enteric hyperoxaluria accounts for approximately 5% of all cases of hyperoxaluria. It is due to a gastrointestinal problem usually associated with chronic diarrhea. Malabsorption from any cause can result in enteric hyperoxaluria. Such causes include intestinal bacterial overgrowth syndromes, fat malabsorption, chronic biliary or pancreatic disease, various intestinal bypass surgical procedures, inflammatory bowel disease, and any medical condition that causes chronic diarrhea. […] Previously, dietary oxalate was thought to play a relatively minor role in hyperoxaluria and to account for only 10-20% of the total urinary oxalate produced. More recent evidence suggests that dietary oxalate plays a much more important role and may be responsible for 50% of the total urinary oxalate. […] This is by far the most common variety of hyperoxaluria observed in patients with calcium oxalate stones. It may be due to a simple dietary excess of high-oxalate food sources or to increased endogenous oxalate production.

• #1 Hyperoxaluria and oxalosis

  https://www.mymlc.com/health-information/diseases-and-conditions/h/hyperoxaluria-and-oxalosis/?section=Symptoms

  Hyperoxaluria can be caused by inherited (genetic) disorders, an intestinal disease or eating too many oxalate-rich foods. […] Oxalosis occurs if you have primary hyperoxaluria and your kidneys fail. […] Several intestinal diseases, including Crohn’s disease and short bowel syndrome as a result of surgical procedures, increase the absorption of oxalate from foods, which can then increase the amount of oxalate excreted in the urine. […] Eating large amounts of foods high in oxalate can increase your risk of hyperoxaluria or kidney stones. […] Primary hyperoxaluria is a rare inherited (genetic) condition present at birth. […] To date, experts have identified three different genetic causes of primary hyperoxaluria.

• #1 Secondary hyperoxaluria: Cause and consequence of chronic kidney disease | Nefrología

  https://revistanefrologia.com/en-secondary-hyperoxaluria-cause-consequence-chronic-articulo-S2013251424002359

  Regarding its pathophysiology, hyperoxaluria is due to three predominant etiologies. Firstly, increased intake of foods rich in oxalate (spinach, cabbage, beets, nuts, or tea), vitamin C (1000 mg/day) or diets low in calcium. Secondly, alterations in elimination at the GI level (pancreatic insufficiency or chronic pancreatitis, celiac disease, inflammatory bowel disease or bariatric surgery). […] The rising number of cases occurs alongside the group of entities encompassed by metabolic syndrome. The chronic inflammation produces an alteration in the SLC26A6 transporter which is present both at the intestinal and renal level, and this is key in the etiopathogenesis of this disease. […] The main organ affected in secondary hyperoxaluria is the kidney, which may suffer damage from nephrocalcinosis or renal lithiasis, potentially progressing to end-stage renal failure. However, calcium oxalate deposits can manifest in other organs, such as the retina, heart and peripheral nervous system, with a notable absence of deposits in the liver. […] Treatment and prevention focus on reducing the intake of oxalate and its precursors, promoting renal elimination by avoiding the precipitation of oxalate crystals at the tubular level, and establishing targeted measures to reduce oxalate absorption and increase its intestinal elimination.

• #1 Oxalosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/oxalosis?lang=us

  Oxalosis is supersaturation of calcium oxalate in the urine (hyperoxaluria), which in turn results in nephrolithiasis and cortical nephrocalcinosis. […] Secondary: usually related to an over-ingestion of oxalic acids or its precursors (e.g. vitamin C) in patients with kidney or hepatic chronic diseases, especially during long-term dialysis. […] A few causes of secondary hyperoxaluria include Crohn disease, cystic fibrosis, chronic biliary disease, pancreatic pathologies, and short bowel syndrome. […] When left untreated, hyperoxaluria will ultimately lead to renal failure, which in turn results in oxalosis: a condition in which calcium oxalate crystals are deposited in extrarenal organs.

• #1 Enteric Hyperoxaluria | OHF

  https://ohf.org/enteric/

  In the absence of malabsorption, oxalate binds to calcium in the gastrointestinal (GI) tract and is then eliminated through solid waste. However, in the case of Enteric Hyperoxaluria, fat malabsorption causes fat to remain in the GI tract instead of being absorbed by the body. The fat is therefore capable of binding to calcium within the gut. As a result, oxalate in the gut is unable to bind to calcium. Instead, it is absorbed by the body, enters the bloodstream, and raises oxalate levels. This elevation in oxalate levels leads to symptoms associated with Enteric Hyperoxaluria.

• #1 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  The problem with oxalate is its strong chemical affinity for calcium and the relatively low solubility of the resulting salt. Most people have a relative supersaturation of calcium oxalate in their urine, which is kept from precipitating by various factors, including dilutional volume and specific inhibitors such as citrate. […] Increased intestinal membrane oxalate transport and absorption may also occur through direct exposure of the intestinal lining to excess bile salts and fatty acids, which increases the oxalate permeability of the colonic mucosa. […] Oxalate absorption by the colon has been shown to increase up to 300-fold following small-bowel bypass surgery; therefore, these individuals must be screened for enteric hyperoxaluria. […] Many patients, perhaps as many as 80%, have an abnormal or altered cellular membrane oxalate transport mechanism, which causes abnormally high absorption of dietary oxalate. Others may have a deficiency of Oxalobacter formigenes, an intestinal facultative anaerobic bacterium that naturally digests oxalate.

• #1 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  The causes of secondary hyperoxaluria include dietary sources, enteric hyperoxaluria, and other causes such as pancreatic insufficiency and ethylene glycol ingestion. […] Increased vitamin C is a risk factor for hyperoxaluria, as vitamin C is a potential precursor to oxalate. […] Enteric hyperoxaluria: Free intestinal calcium will tightly bind to free oxalate, creating an insoluble molecule of calcium oxalate. […] While usually associated with gastrointestinal bypass surgery, enteric hyperoxaluria can be found in any condition that results in chronic diarrhea. […] Oxalobacter formigenes are gram-negative, facultative anaerobic, oxalate-degrading bacteria normally colonizing the colon by age 3. […] The estimated overall incidence of secondary hyperoxaluria appears to be increasing over time. […] The prognosis of hyperoxaluria depends on the type of hyperoxaluria, time of diagnosis, and early initiation of treatment.

• #1 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  In humans, however, oxalate seems to have no substantially beneficial role and acts as a metabolic end-product, much like uric acid. If not for oxalate’s high affinity for calcium and the low solubility of calcium oxalate, oxalate and oxalate metabolism would be of little interest. […] Urinary oxalate is the single strongest chemical promoter of kidney stone formation. Ounce for ounce, it is roughly 15-20 times more potent than excess urinary calcium. […] Daily oxalate intake in humans is usually 80-120 mg/d; it can range from 44-350 mg/d in individuals who eat a typical Western diet. […] The solubility of oxalate at body temperature is only approximately 5 mg/L at a pH of 7.0.

• #1 Secondary hyperoxaluria: Cause and consequence of chronic kidney disease | Nefrología

  https://revistanefrologia.com/en-secondary-hyperoxaluria-cause-consequence-chronic-articulo-S2013251424002359

  Secondary hyperoxaluria is a metabolic disorder characterized by an increase in urinary oxalate excretion. The etiology may arise from an increase in the intake of oxalate or its precursors, decreased elimination at the digestive level, or heightened renal excretion. […] Recently, the role of the SLC26A6 transporter in the etiopathogenesis of this disease has been identified. This transporter is active at both the intestinal and renal levels, and its mechanism of action is disrupted during systemic inflammation and metabolic syndrome, which could explain the rising incidence of secondary hyperoxaluria in recent decades. […] Secondary hyperoxaluria is a much more frequent cause of increased oxalate than primary hyperoxaluria, and it is produced by an increased exogenous supply of oxalate or by a deficit in its metabolism or elimination.

• #1 Primary hyperoxaluria and oxalate: Symptoms, causes and treatment | American Kidney Fund

  https://www.kidneyfund.org/all-about-kidneys/other-kidney-diseases/primary-hyperoxaluria-and-oxalate-symptoms-causes-and-treatment

  Primary hyperoxaluria (PH) is a rare liver disease that causes oxalate to build up in your body and damage your kidneys. […] What causes it? A mutation (change) in the gene called AGXT. This prevents your liver from making enough of the protein called alanine-glyoxylate aminotransferase (AGT). […] PH is a genetic disease. This means that it is caused by a mutation (change) in a gene. People who have PH were born with it. […] To have PH, you must have 2 copies of a mutated gene that causes PH: one from each of your parents. […] When oxalate levels are high, the extra oxalate combines with calcium in your kidneys to form kidney stones and calcium oxalate crystals in your urine. […] This is called oxalosis and can cause more serious health problems, such as: Bone disease, Blood problems, Heart problems, Skin problems, such as skin ulcers (open sores), Nerve problems, such as pain.

• #1

  https://homeopathyaajtak.in/diseases/h/hyperoxaluria-and-oxalosis-469

  Hyperoxaluria can be caused by inherited (genetic) disorders, an intestinal disease or eating too many oxalate-rich foods. […] Oxalosis happens after the kidneys fail in people who have primary and intestinal causes of hyperoxaluria, and excess oxalate builds up in the blood. […] Primary hyperoxaluria is a rare inherited (genetic) condition present at birth. […] Oxalosis occurs if you have primary hyperoxaluria and your kidneys fail. […] Several intestinal diseases, including Crohn’s disease and short bowel syndrome as a result of surgical procedures, increase the absorption of oxalate from foods, which can then increase the amount of oxalate excreted in the urine. […] Eating large amounts of foods high in oxalate can increase your risk of hyperoxaluria or kidney stones. […] Untreated primary hyperoxaluria can eventually damage your kidneys. […] Oxalosis in its late stages can cause a variety of complications outside the kidney, including bone disease, anemia, skin ulcers, heart and eye problems, and in children, a failure to develop and grow normally.

• #1 Primary Hyperoxaluria Type 1 | National Kidney Foundation

  https://www.kidney.org/kidney-topics/primary-hyperoxaluria-type-1

  Primary hyperoxaluria type 1 (PH1) is a rare genetic condition causing high oxalate levels in urine, leading to kidney stones and potential kidney failure. […] PH1 is a genetic condition. So, it is passed from parent to child. […] In PH1, there is a variant (change) in your AGXT (alanine-glyoxylate aminotransferase) gene. This gene provides instructions for making a substance that helps break down waste products like oxalate in your liver. People living with PH1 either make less of this important substance or don’t make it at all. This causes high levels of oxalate in the blood and urine, leading to kidney stones, kidney failure, and other complications. […] More specifically, PH1 is considered an autosomal recessive condition. This means both parents must either have the condition or have one AGXT gene variant and pass it on to the child to cause PH1. So, PH1 is not very common.

• #1 Primary hyperoxaluria | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/primary-hyperoxaluria?lang=us

  Primary hyperoxaluria, also referred to as primary oxalosis, is a congenital autosomal recessive disease related to a liver enzyme deficiency leading to massive cortical nephrocalcinosis and renal failure. […] Hyperoxaluria is an autosomal recessive disorder and is more common in Mediterranean countries. The most common subtype is primary hyperoxaluria type 1, which is responsible for approximately 80% of cases. […] It has three types due to the defects in the gene that encodes the following enzymes: glyoxylate aminotransferase, glyoxylate reductase/hydroxypyruvate reductase, liver-specific mitochondrial 4-hydroxy-2-oxoglutarate aldolase enzyme. […] As in primary hyperoxaluria type 1, enzyme deficiency leads to high oxalate levels.

• #1 Hyperoxaluria | UK Kidney Association

  https://www.ukkidney.org/rare-renal/clinician-information/hyperoxaluria

  Primary hyperoxaluriatype 2 (PH2) arises from mutations in GRHPR with subsequent dysfunction of the enzyme glyoxylate/hydroxypyruvate reductase (GRHPR) (Cregeen et al, 2003) […] Primary hyperoxaluriatype 3 (PH3) arises from mutations in HOGA1 which is encodes the mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase (Belostotsky et al, 2010). […] The prevalence of PH is unclear. PH1, the most common of the disorders, has been estimated to have a prevalence of 1-3 per million but it is highly likely that this is an underestimate of the disease. […] The overall long-term prognosis for patients with PH2 is unclear. It was originally considered to have a more benign course than PH1 with the majority of patients presenting with urolithiasis, but decline in renal function is probably more common than initially considered. […] The principles of management are the same, but in addition a role of a vegetarian diet to reduce dietary hydroxyproline is being considered. At the present time, no PH3 patient has been found in renal failure (Belostotsky et al, 2010).

• #1 Understanding Hyperoxaluria | OHF

  https://ohf.org/understanding-hyperoxaluria/

  The prevalence of Enteric Hyperoxaluria (EH) has been estimated at 5-24% of all patients with gastrointestinal diseases associated with malabsorption. […] EH is a frequent complication of inflammatory bowel diseases (IBD), ileal resection and Roux-en-Y gastric bypass (RYGB) and is well-known to cause kidney stones, and nephrocalcinosis. […] Patients with all types of hyperoxaluria are managed by very large volumes of daily fluid intake and surgery to remove recurrent kidney stones. […] Untreated forms of the disease lead to progressive kidney damage and other systemic complications.

• #1 Hyperoxaluria: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/21117-hyperoxaluria

  Hyperoxaluria is a condition that occurs when theres too much oxalate in your pee. […] Genetics, gastrointestinal (GI) conditions and eating foods high in oxalate can cause hyperoxaluria. […] The three causes of hyperoxaluria are: A genetic mutation (primary hyperoxaluria). This means you get the condition from your biological parents. […] Intestinal disorders. Certain health conditions that affect your GI tract can cause you to have too much oxalate in your pee. […] Diet. People who eat large quantities of foods that are high in oxalate can have too much oxalate in their pee. […] Kidney damage, which can lead to kidney failure, is the main complication of hyperoxaluria. […] When kidney damage sets in, your kidneys cant eliminate excess oxalate. This causes oxalate crystals to build up in other areas of your body like your blood, bones, muscles and heart. […] If hyperoxaluria becomes severe, your kidneys may not work as well. If this happens, kidney dialysis can help. If you have primary hyperoxaluria, organ transplantation (kidney, liver or both) may be necessary.

• #1 Primary hyperoxaluria – UpToDate

  https://www.uptodate.com/contents/primary-hyperoxaluria

  This inborn error of metabolism leads to an increase in the glyoxylate pool, which is converted by lactate dehydrogenase to oxalate. […] It is the most common PH type and accounts for approximately 70 to 80 percent of PH cases. […] It is the most severe form of PH, with more rapid progression to kidney dysfunction and the development of ESKD in one-half of patients by young adulthood.

• #1 Primary hyperoxaluria – Wikipedia

  https://en.wikipedia.org/wiki/Primary_hyperoxaluria

  However, recent evidence has suggested that PH2 and PH3 are not as benign as previously thought, with up to 50% of patients with PH2 developing kidney failure (chronic kidney disease [CKD] stage 5). […] Kidney failure is a serious complication requiring treatment in its own right. Dialysis can control kidney failure but tends to be inadequate to dispose of excess oxalate. Renal transplant is more effective and is the primary treatment of severe hyperoxaluria. Ultimately though, liver transplantation (often in addition to renal transplant) is required to correct the underlying metabolic defect.

• #1 Primary hyperoxaluria type 3 | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/primary-hyperoxaluria-type-3/

  Primary hyperoxaluria (PH) is an inherited disease in which a lack of a particular liver enzyme causes the body to accumulate a substance called oxalate. Excess oxalate leads to a buildup of insoluble calcium salts in the kidneys, which may cause kidney stones and progressive kidney damage. PH type 3 (PH3) is caused by harmful genetic changes (mutations) in the HOGA1 gene. Approximately 10% of PH cases are of the PH3 subtype. […] Individuals with PH3 are at increased risk of developing kidney stones. […] Treatments for PH3 mainly aim to prevent the formation and deposition of calcium oxalate. […] Individuals with PH3 often have formation of multiple kidney stones. In many individuals with PH3, kidney stone formation decreases as they reach adulthood. Transplants are not necessary in most individuals with PH3, and there are few reports of progression to kidney failure.

• #1 Large Joint Destructive Arthropathy and Tumoral Calcinosis Associated to Primary Oxalosis: Case Report and Literature Review | Reumatología Clínica

  https://www.reumatologiaclinica.org/es-large-joint-destructive-arthropathy-tumoral-articulo-S217357431300049X

  In autopsy studies, calcium oxalate deposits in joint tissue and bone oxalosis occur in approximately 90% of patients with renal insufficiency undergoing chronic hemodialysis. […] Kidney damage is usually the result of a combination of nephrolithiasis, secondary nephrocalcinosis and interstitial fibrosis. Renal failure is associated with the rapid deposit of the crystals in the kidney, myocardium, skin, blood vessels and bones; when the glomerular filtration rate decreases below 30-40ml/min/1.73m2, oxalate cannot be efficiently excreted by the kidneys and reaches saturation levels. […] Typical locations of crystal deposits in the skeleton are the segments of the metaphysis of tubular bones. […] Bone oxalosis may be due to the combination of hyperparathyroidism, renal osteodystrophy and the inflammatory response induced by calcium oxalate crystals.

• #1

  https://journals.lww.com/cjasn/fulltext/2020/07000/primary_hyperoxaluria__the_patient_and_caregiver.2.aspx

  Living with primary hyperoxaluria, a rare genetic disease with excess oxalate production leading to frequent kidney stones, kidney impairment, and oxalosis, presents many challenges to patients, caregivers, and their families. […] The consequences of kidney failure can be particularly grave in primary hyperoxaluria because plasma oxalate levels rise rapidly, leading to oxalosis. […] Patients fear progression to oxalosis and worry about the associated bone fractures, anemia, heart failure, joint damage, skin ulceration, severe weakness, vision impairment, and neuropathy. […] Because a transplanted kidney is at risk of oxalate injury, kidney transplantation alone is not satisfactory for most patients with primary hyperoxaluria. […] The survey demonstrated that 94% of patients desired new therapies that would prevent dialysis, kidney or liver transplant, avoid oxalosis, and/or improve chances of a normal life span. […] Families desperately seek new treatment options to reduce the frequency of kidney stones, the need for organ transplantation, kidney failure, and oxalosis.

• #1 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  Dialysis treatment may be indicated in patients with PH who have progressed to stage 4-5 CKD before the development of uraemia, depending on the potential risk of systemic oxalosis. […] Liver transplantation remains the only cure for PH1. […] A substantial body of evidence demonstrates that liver transplantation can reverse hyperoxaluria and prevent the further development of oxalate-related disease in patients with PH1. […] For patients with PH and kidney failure who undergo kidney transplantation, combined liver and kidney transplantation (CLKT) results in better kidney graft survival than isolated kidney transplantation. […] The burden of PH varies between regions and is dependent on several factors, including its prevalence, its rate of early detection which is determined by its recognition by health-care professionals and the availability of affordable diagnostic tools and on access to therapeutic resources.

• #1

  https://journals.lww.com/cjasn/fulltext/2020/07000/end_points_for_clinical_trials_in_primary.26.aspx

  Patients with primary hyperoxaluria experience kidney stones from a young age and can develop progressive oxalate nephropathy. […] Primary hyperoxaluria is caused by deficiencies in enzymes involved in the metabolism of glycolate, glycine, and hydroxyproline within the liver. The resulting excess of glyoxylate leads to the synthesis and release of oxalate into the bloodstream. […] Hyperoxaluria results in calcium oxalate kidney stones, progressive oxalate nephropathy, and kidney failure. […] Persistently elevated urine oxalate levels cause kidney stone formation and also contribute to progressive kidney damage and loss of kidney function. […] Epidemiologic data show a strong relationship between urine oxalate and long-term kidney function loss. […] In patients with primary hyperoxaluria who have kidney failure, dialysis cannot remove enough oxalate to prevent progressive systemic oxalosis, and kidney transplantation alone often fails due to recurrent oxalate injury in the allograft.

• #1 About Primary Hyperoxaluria Type 1 (PH1) | Behind the Stone®

  https://www.aboutph1.com/about-ph1-primary-hyperoxaluria-type-1

  PH1 is a genetic disease caused by mutations in the AGXT gene that renders the liver enzyme AGT dysfunctional.3 […] In PH1, a defect in AGT means glyoxylate is instead converted to oxalate.2 Oxalate cannot be metabolized and is typically excreted by the kidneys at normal levels.3 When overproduced as it is in PH1, oxalate can wreak progressive, irreversible damage.2 […] Oxalate combines with calcium, creating calcium oxalate crystals.2 These crystals attach to kidney tissues, where they can aggregate to form kidney stones or lead to nephrocalcinosis.2,9 As calcium oxalate accumulates, kidney excretion is impaired, and crystals deposit throughout the body.9

• #1 Primary hyperoxaluria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/primary-hyperoxaluria/

  Primary hyperoxaluria results from the overproduction of a substance called oxalate. […] Mutations in the AGXT, GRHPR, and HOGA1 genes cause primary hyperoxaluria types 1, 2, and 3, respectively. […] Mutations in the AGXT, GRHPR, or HOGA1 gene lead to a decrease in production or activity of the respective proteins, which prevents the normal breakdown of glyoxylate. […] AGXT and GRHPR gene mutations result in an accumulation of glyoxylate, which is then converted to oxalate for removal from the body as a waste product. […] HOGA1 gene mutations also result in excess oxalate, although researchers are unsure as to how this occurs. […] Oxalate that is not excreted from the body combines with calcium to form calcium oxalate deposits, which can damage the kidneys and other organs.

• #1 Subungual Oxalate Deposits in a Patient with Secondary Hyperoxaluria | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-0996

  The pathogenesis of oxalate deposition in the kidneys has been studied. It has been shown that renal epithelial cell membrane injury is essential for the deposition of calcium oxalate crystals, and that exposure to oxalate causes membrane damage. Damaged renal epithelial cells can bind oxalate crystals through crystal-binding proteins expressed on their surfaces, while intact ones cannot. Moreover, exposure to oxalate has been shown to cause toxic reactions in renal epithelial and liver portal connective tissue cells, including modification of cellular lipids and the expression of genes encoding membrane surface crystal-binding proteins such as osteopontin and hyaluronan, as well as their cell surface receptor, CD44. In addition, oxalate exposure can alter mitochondrial enzymatic activity, resulting in the formation of reactive oxygen species and, consequently, cellular oxidative damage. Further data from renal cell culture studies suggest that oxalate-induced oxidative stress leads to the production of chemokines such as monocyte chemoattractant protein-1, which is known to recruit a range of immune cells, including macrophages and monocytes, to injury sites, thereby increasing local inflammation. We can assume that similar oxalate-induced oxidative or non-oxidative injury in the endothelial cells of the dermal vasculature may lead to vascular inflammation, a subsequent increase in vascular permeability, and, finally, the release of oxalate crystals into the dermis. Alternatively, in accordance with the process by which oxalate crystals appear in the renal interstitium, it could be hypothesised that oxalate crystals may translocate to the dermis through transcytosis across vascular endothelial cells, or are formed de novo in the dermis. Which of these proposed mechanisms for initiating cutaneous oxalate deposition is correct is a matter that requires further investigation in in vitro and in vivo studies.

• #1

  https://journals.lww.com/cjasn/fulltext/2020/07000/end_points_for_clinical_trials_in_primary.26.aspx

  Plasma oxalate directly reflects hepatic synthesis of oxalate. […] When plasma oxalate exceeds 35-50 μmol/L, physicochemical properties favor crystallization, leading to systemic calcium oxalate crystal deposition. […] In CKD stages 3b-5 (GFR <45 ml/min per 1.73 m²), elevated plasma oxalate is directly related to the pathophysiology of oxalosis.

• #2 Hyperoxaluria and oxalosis // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/hyperoxaluria-and-oxalosis

  Hyperoxaluria can be caused by a change in a gene, an intestine disease or eating too many foods that are high in oxalate. […] Hyperoxaluria happens when too much of a chemical called oxalate builds up in the urine. […] Primary hyperoxaluria. This type is a rare inherited disease, which means that it’s passed down in families. It’s caused by changes in a gene. […] Enteric hyperoxaluria. Some intestine problems cause the body to absorb more oxalate from foods. […] Hyperoxaluria tied to eating foods with lots of oxalate. Eating large amounts of foods high in oxalate can raise your risk of hyperoxaluria or kidney stones.

• #2 Primary hyperoxaluria and oxalate: Symptoms, causes and treatment | American Kidney Fund

  https://www.kidneyfund.org/all-about-kidneys/other-kidney-diseases/primary-hyperoxaluria-and-oxalate-symptoms-causes-and-treatment

  Primary hyperoxaluria (PH) is a rare liver disease that causes oxalate to build up in your body and damage your kidneys. […] What causes it? A mutation (change) in the gene called AGXT. This prevents your liver from making enough of the protein called alanine-glyoxylate aminotransferase (AGT). […] PH is a genetic disease. This means that it is caused by a mutation (change) in a gene. People who have PH were born with it. […] To have PH, you must have 2 copies of a mutated gene that causes PH: one from each of your parents. […] When oxalate levels are high, the extra oxalate combines with calcium in your kidneys to form kidney stones and calcium oxalate crystals in your urine. […] This is called oxalosis and can cause more serious health problems, such as: Bone disease, Blood problems, Heart problems, Skin problems, such as skin ulcers (open sores), Nerve problems, such as pain.

• #2 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  Three biochemically defined types of PH exist, of which type 1 (PH1) is by far the most prevalent and has the worst prognosis. […] Importantly, the introduction of two new therapies based on RNA interference (RNAi) both of which substantially lower endogenous oxalate production in patients with PH1 have influenced the management of this disease. […] Genetic testing for PH should be performed as early as possible, but within 30 days of a patient presenting with suspected PH and severe kidney failure (eGFR 30ml/min/1.73m²). […] Genetic confirmation of suspected PH with eGFR 30ml/min/1.73m² should be carried out promptly, but note that turnaround times for such tests can vary between countries. […] PH1 results from a deficiency in the liver-specific, peroxisomal, pyridoxal phosphate-dependent enzyme, alanine-glyoxylate aminotransferase (AGT), which is encoded by AGXT.

• #2 Primary hyperoxaluria – UpToDate

  https://www.uptodate.com/contents/primary-hyperoxaluria

  This inborn error of metabolism leads to an increase in the glyoxylate pool, which is converted by lactate dehydrogenase to oxalate. […] It is the most common PH type and accounts for approximately 70 to 80 percent of PH cases. […] It is the most severe form of PH, with more rapid progression to kidney dysfunction and the development of ESKD in one-half of patients by young adulthood.

• #2 Primary hyperoxaluria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/primary-hyperoxaluria/

  Primary hyperoxaluria results from the overproduction of a substance called oxalate. […] Mutations in the AGXT, GRHPR, and HOGA1 genes cause primary hyperoxaluria types 1, 2, and 3, respectively. […] Mutations in the AGXT, GRHPR, or HOGA1 gene lead to a decrease in production or activity of the respective proteins, which prevents the normal breakdown of glyoxylate. […] AGXT and GRHPR gene mutations result in an accumulation of glyoxylate, which is then converted to oxalate for removal from the body as a waste product. […] HOGA1 gene mutations also result in excess oxalate, although researchers are unsure as to how this occurs. […] Oxalate that is not excreted from the body combines with calcium to form calcium oxalate deposits, which can damage the kidneys and other organs.

• #2 Warning Signs of Primary Hyperoxaluria (PH) | Uncovering PH

  https://www.uncoveringph.com/warning-signs.html

  Both pediatric and adult patients with early signs of nephrocalcinosis should be screened for primary hyperoxaluria. […] Kidney failure can be the first clinical indication of primary hyperoxaluria in some patients, even in infancy. […] Systemic oxalosis can also impact bone, skin, heart, and eye health. […] In a study, infantile onset was shown to occur in 18% of patients with PH1. […] Studies have shown that many people are not diagnosed with PH until they are in ESRD (35% of all patients with PH1 and 11% of patients with PH2), although these patients often had earlier symptoms that went unrecognized, such as recurring kidney stones.

• #2 Secondary hyperoxaluria: Cause and consequence of chronic kidney disease | Nefrología

  https://revistanefrologia.com/en-secondary-hyperoxaluria-cause-consequence-chronic-articulo-S2013251424002359

  Secondary hyperoxaluria is a metabolic disorder characterized by an increase in urinary oxalate excretion. The etiology may arise from an increase in the intake of oxalate or its precursors, decreased elimination at the digestive level, or heightened renal excretion. […] Recently, the role of the SLC26A6 transporter in the etiopathogenesis of this disease has been identified. This transporter is active at both the intestinal and renal levels, and its mechanism of action is disrupted during systemic inflammation and metabolic syndrome, which could explain the rising incidence of secondary hyperoxaluria in recent decades. […] Secondary hyperoxaluria is a much more frequent cause of increased oxalate than primary hyperoxaluria, and it is produced by an increased exogenous supply of oxalate or by a deficit in its metabolism or elimination.

• #2 Understanding Hyperoxaluria | OHF

  https://ohf.org/understanding-hyperoxaluria/

  The prevalence of Enteric Hyperoxaluria (EH) has been estimated at 5-24% of all patients with gastrointestinal diseases associated with malabsorption. […] EH is a frequent complication of inflammatory bowel diseases (IBD), ileal resection and Roux-en-Y gastric bypass (RYGB) and is well-known to cause kidney stones, and nephrocalcinosis. […] Patients with all types of hyperoxaluria are managed by very large volumes of daily fluid intake and surgery to remove recurrent kidney stones. […] Untreated forms of the disease lead to progressive kidney damage and other systemic complications.

• #2 Primary and secondary hyperoxaluria: Understanding the enigma

  https://www.wjgnet.com/2220-6124/full/v4/i2/235.htm

  Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. […] The causes of SH are increase in dietary and intestinal absorption (enteric hyperoxaluria), excessive intake of oxalate precursors and alteration in intestinal microflora. […] Increased dietary intake of oxalate includes rhubarb and spinach and daily intake may be in excess of 1000 mg/d. Increased dietary absorption may occur in juicing which is being propagated as a health fad for clearing toxins from the body and also for weight loss. […] Hyperoxaluria has also been reported following renal transplantation due to mobilization of oxalate and deposition within the renal allograft. […] The differences between primary and secondary hyperoxaluria are depicted in Table 1.

• #2 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  Oxalate-rich foods can cause hyperoxaluria. Dietary excess of vitamin C can also increase oxalate absorption and excretion, although the degree and importance of vitamin C in the development of calcium oxalate stone disease is somewhat controversial. […] Oxalate is involved in various metabolic and homeostatic mechanisms in fungi and bacteria and may play an important role in various aspects of animal metabolism, including mitochondrial activity regulation, thyroid function, gluconeogenesis, and glycolysis. […] Oxalate is normally produced in plants, primarily in their leaves, nuts, fruit, and bark. The amount of oxalate manufactured depends not only on the particular variety of plant but also on the soil and water conditions in which it grows. […] Oxalate content within the same plant species can vary widely. For example, potatoes contain oxalate levels of 5.5-30 mg per 100 g, broccoli has levels of 0.3-13 mg per 100 g, and wheat bran has levels of 58-524 mg per 100 g.

• #2 A hidden cause of oxalate nephropathy: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-021-02732-6

  The causes of hyperoxaluria can be primary or secondary. Primary hyperoxalurias are a group of rare autosomal recessive (AR) disorders of glyoxylate metabolism, resulting in overproduction of oxalate. […] In contrast, secondary hyperoxaluria may occur due to increased absorption of oxalate, nutritional deficiencies, decreased oxalate excretion, or increased dietary oxalate consumption. […] The first mechanism leading to secondary hyperoxaluria is enteric hyperoxaluria. […] The second mechanism leading to secondary hyperoxaluria is nutritional deficiencies. […] The third mechanism occurs in the setting of significantly decreased fluid intake. […] The fourth mechanism is decreased oxalate excretion. […] Finally, increased dietary oxalate may lead to secondary hyperoxaluria, particularly in patients with underlying CKD.

• #2 Primary and secondary hyperoxaluria: Understanding the enigma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4419133/

  Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. […] The causes of SH are increase in dietary and intestinal absorption (enteric hyperoxaluria), excessive intake of oxalate precursors and alteration in intestinal microflora. […] Increased dietary absorption may occur in juicing which is being propagated as a health fad for clearing toxins from the body and also for weight loss. […] This form of hyperoxaluria is seen in partial gastrectomy, bariatric surgery, jejunoileal bypass, and inflammatory bowel disease. […] Oxalobacter formigenes (O. formigenes) is an aerobic gram negative bacterium that uses oxalate as its energy source and decreases intestinal absorption of oxalate and thus reduces urinary oxalate excretion.

• #2 Understanding Hyperoxaluria | OHF

  https://ohf.org/understanding-hyperoxaluria/

  Hyperoxaluria is a condition in which you have too much oxalate in your urine. […] High levels of oxalate are toxic because oxalate cannot be broken down by the body and accumulates in the kidneys that may cause kidney stones. […] Primary Hyperoxaluria (PH) is a genetic disease you are born with it. […] Enteric Hyperoxaluria (EH) is a medical condition caused by increased absorption of oxalate from foods in the digestive tract (also called the gut or intestines). […] Dietary Hyperoxaluria is a result of eating large quantities of foods high in oxalate. […] Idiopathic hyperoxaluria is a type of hyperoxaluria where the cause is unknown. […] PH is a family of rare, genetic liver disorders that can damage the kidneys. […] In PH, the liver doesn’t create enough of this enzyme, or the enzyme doesn’t work properly.

• #2 Hyperoxaluria: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/21117-hyperoxaluria

  Hyperoxaluria is a condition that occurs when theres too much oxalate in your pee. […] Genetics, gastrointestinal (GI) conditions and eating foods high in oxalate can cause hyperoxaluria. […] The three causes of hyperoxaluria are: A genetic mutation (primary hyperoxaluria). This means you get the condition from your biological parents. […] Intestinal disorders. Certain health conditions that affect your GI tract can cause you to have too much oxalate in your pee. […] Diet. People who eat large quantities of foods that are high in oxalate can have too much oxalate in their pee. […] Kidney damage, which can lead to kidney failure, is the main complication of hyperoxaluria. […] When kidney damage sets in, your kidneys cant eliminate excess oxalate. This causes oxalate crystals to build up in other areas of your body like your blood, bones, muscles and heart. […] If hyperoxaluria becomes severe, your kidneys may not work as well. If this happens, kidney dialysis can help. If you have primary hyperoxaluria, organ transplantation (kidney, liver or both) may be necessary.

• #2 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. […] Primary hyperoxaluria (PH) is a group of autosomal recessive disorders of glyoxylate metabolism that cause the overproduction of endogenous oxalate a redundant metabolic end product that is excreted primarily via the kidneys. […] In PH, the combination of intra-tubular and interstitial deposits of calcium oxalate, chronic tubulo-interstitial inflammation and kidney obstruction by stones leads to kidney failure in more than 70% of patients. […] As soon as glomerular filtration rate (GFR) falls below 30-40ml/min/1.73m², hepatic oxalate production exceeds renal removal, leading to systemic oxalate storage in various tissues, including bone, heart, vessels, nerves and eye, and causing life-threatening multi-organ disease.

• #2

  https://homeopathyaajtak.in/diseases/h/hyperoxaluria-and-oxalosis-469

  Hyperoxaluria can be caused by inherited (genetic) disorders, an intestinal disease or eating too many oxalate-rich foods. […] Oxalosis happens after the kidneys fail in people who have primary and intestinal causes of hyperoxaluria, and excess oxalate builds up in the blood. […] Primary hyperoxaluria is a rare inherited (genetic) condition present at birth. […] Oxalosis occurs if you have primary hyperoxaluria and your kidneys fail. […] Several intestinal diseases, including Crohn’s disease and short bowel syndrome as a result of surgical procedures, increase the absorption of oxalate from foods, which can then increase the amount of oxalate excreted in the urine. […] Eating large amounts of foods high in oxalate can increase your risk of hyperoxaluria or kidney stones. […] Untreated primary hyperoxaluria can eventually damage your kidneys. […] Oxalosis in its late stages can cause a variety of complications outside the kidney, including bone disease, anemia, skin ulcers, heart and eye problems, and in children, a failure to develop and grow normally.

• #2 What Is Primary Hyperoxaluria Type 1 (PH1)? Life Expectancy

  https://www.medicinenet.com/what_is_primary_hyperoxaluria_type_1_ph1/article.htm

  Primary hyperoxaluria type 1 (PH1) is an extremely rare hereditary condition that is characterized by excessive oxalate formation, a waste product usually removed by the kidneys and discharged in the urine. […] A genetic mutation in PH1 causes the liver to produce excess oxalate that accumulates in the kidneys and urinary system. […] Mutations in the AGXT gene lead to primary hyperoxaluria type 1 (PH1). This gene instructs the body to produce an enzyme known as alanine-glyoxylate aminotransferase, which is present in liver cells (peroxisomes). It converts a compound known as glyoxylate into the amino acid glycine. […] Mutations in the AGXT gene result in a reduction in the amount or activity of the enzyme, which prevents the breakdown of glyoxylate. Because of this, glyoxylate builds up and becomes oxalate rather than glycine. […] PH1 is an inherited condition, which means it is passed down through families. PH1 can affect members of the same family in various ways, including how the disease manifests and/or progresses.

• #2 How Is Primary Hyperoxaluria Type 1 Diagnosed?

  https://www.webmd.com/kidney-stones/primary-hyperoxaluria-type-1-diagnosis

  PH1 is caused by a mutation, or change, in the AGXT gene. This is a recessive gene. So to have the disease, you must inherit two copies of the mutation, one from each parent. […] PH1 is more likely in people whose parents are relatives and in cultures where marriages between relatives are common. […] Higher levels can lead to kidney stones, as the chemical binds to calcium. […] Calcium oxalate, formed when oxalate combines with calcium, is what most kidney stones are made of. […] You might have PH1 if the stones: Are almost entirely made of calcium oxalate monohydrate. […] A molecular genetic test can show whether you have the AGXT gene mutation and confirm the diagnosis.

• #2 Enteric Hyperoxaluria | OHF

  https://ohf.org/enteric/

  Enteric Hyperoxaluria (EH) is caused by the increased absorption of oxalate from foods in the digestive tract (also called the gut or intestines). This leads to high levels of oxalate in the urine. EH may be acquired as a result of certain weight loss surgeries or in inflammatory bowel disease including Crohns disease, cystic fibrosis or chronic pancreatitis. […] Currently the most common cause of Enteric Hyperoxaluria in western countries is malabsorption after bariatric surgery. […] Enteric Hyperoxaluria diagnosed after bariatric surgery is a result of malabsorption caused by the surgery in order to promote weight loss, and does not have an inherited or genetic cause. […] Although a high oxalate diet alone can lead to hyperoxaluria, diet is not a cause of Enteric Hyperoxaluria. However, a higher oxalate, lower calcium, or higher fat diet can make EH worse.

• #2 Primary Hyperoxaluria – Rare Kidney Stone Consortium

  https://www.rarekidneystones.org/hyperoxaluria/

  The common factor in all three types of PH is the increase in oxalate production in the liver. […] Each of the types of PH causes a decrease in activity of a specific enzyme in the liver. […] It is possible that other types of PH will be identified in the future. […] In a person with Type 1 primary hyperoxaluria, the liver creates too little of an enzyme called alanine-glyoxylate aminotransferase, or AGT. […] In Type 2, the liver is missing activity of a different enzyme, called glyoxylate reductase (GR) or hydroxypyruvate reductase. […] In Type 3 there is deficiency of hydroxy oxoglutarate aldolase. […] Very large amounts of oxalate are produced when there is not enough of these enzymes in the liver. […] Oxalosis happens after the kidneys fail and the excess oxalate builds up in the blood, and then spreads to the eyes, bones, muscles, blood vessels, heart and other major organs. […] If left untreated, PH can lead to serious illness and even death. […] Primary hyperoxaluria that goes untreated may cause the kidneys to eventually be damaged and may stop working.

• #2

  https://journals.lww.com/cjasn/fulltext/2020/07000/primary_hyperoxaluria__the_patient_and_caregiver.2.aspx

  Living with primary hyperoxaluria, a rare genetic disease with excess oxalate production leading to frequent kidney stones, kidney impairment, and oxalosis, presents many challenges to patients, caregivers, and their families. […] The consequences of kidney failure can be particularly grave in primary hyperoxaluria because plasma oxalate levels rise rapidly, leading to oxalosis. […] Patients fear progression to oxalosis and worry about the associated bone fractures, anemia, heart failure, joint damage, skin ulceration, severe weakness, vision impairment, and neuropathy. […] Because a transplanted kidney is at risk of oxalate injury, kidney transplantation alone is not satisfactory for most patients with primary hyperoxaluria. […] The survey demonstrated that 94% of patients desired new therapies that would prevent dialysis, kidney or liver transplant, avoid oxalosis, and/or improve chances of a normal life span. […] Families desperately seek new treatment options to reduce the frequency of kidney stones, the need for organ transplantation, kidney failure, and oxalosis.

• #2

  https://journals.lww.com/cjasn/fulltext/2020/07000/end_points_for_clinical_trials_in_primary.26.aspx

  Patients with primary hyperoxaluria experience kidney stones from a young age and can develop progressive oxalate nephropathy. […] Primary hyperoxaluria is caused by deficiencies in enzymes involved in the metabolism of glycolate, glycine, and hydroxyproline within the liver. The resulting excess of glyoxylate leads to the synthesis and release of oxalate into the bloodstream. […] Hyperoxaluria results in calcium oxalate kidney stones, progressive oxalate nephropathy, and kidney failure. […] Persistently elevated urine oxalate levels cause kidney stone formation and also contribute to progressive kidney damage and loss of kidney function. […] Epidemiologic data show a strong relationship between urine oxalate and long-term kidney function loss. […] In patients with primary hyperoxaluria who have kidney failure, dialysis cannot remove enough oxalate to prevent progressive systemic oxalosis, and kidney transplantation alone often fails due to recurrent oxalate injury in the allograft.

• #2 Subungual Oxalate Deposits in a Patient with Secondary Hyperoxaluria | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-0996

  The pathogenesis of oxalate deposition in the kidneys has been studied. It has been shown that renal epithelial cell membrane injury is essential for the deposition of calcium oxalate crystals, and that exposure to oxalate causes membrane damage. Damaged renal epithelial cells can bind oxalate crystals through crystal-binding proteins expressed on their surfaces, while intact ones cannot. Moreover, exposure to oxalate has been shown to cause toxic reactions in renal epithelial and liver portal connective tissue cells, including modification of cellular lipids and the expression of genes encoding membrane surface crystal-binding proteins such as osteopontin and hyaluronan, as well as their cell surface receptor, CD44. In addition, oxalate exposure can alter mitochondrial enzymatic activity, resulting in the formation of reactive oxygen species and, consequently, cellular oxidative damage. Further data from renal cell culture studies suggest that oxalate-induced oxidative stress leads to the production of chemokines such as monocyte chemoattractant protein-1, which is known to recruit a range of immune cells, including macrophages and monocytes, to injury sites, thereby increasing local inflammation. We can assume that similar oxalate-induced oxidative or non-oxidative injury in the endothelial cells of the dermal vasculature may lead to vascular inflammation, a subsequent increase in vascular permeability, and, finally, the release of oxalate crystals into the dermis. Alternatively, in accordance with the process by which oxalate crystals appear in the renal interstitium, it could be hypothesised that oxalate crystals may translocate to the dermis through transcytosis across vascular endothelial cells, or are formed de novo in the dermis. Which of these proposed mechanisms for initiating cutaneous oxalate deposition is correct is a matter that requires further investigation in in vitro and in vivo studies.

• #2

  https://journals.lww.com/cjasn/fulltext/2020/07000/end_points_for_clinical_trials_in_primary.26.aspx

  Plasma oxalate directly reflects hepatic synthesis of oxalate. […] When plasma oxalate exceeds 35-50 μmol/L, physicochemical properties favor crystallization, leading to systemic calcium oxalate crystal deposition. […] In CKD stages 3b-5 (GFR <45 ml/min per 1.73 m²), elevated plasma oxalate is directly related to the pathophysiology of oxalosis.

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