Materiały źródłowe

• #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. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. […] In response to these developments, members of OxalEurope a network of European scientists and physicians who specialize in PH and the metabolic workgroup of the European Rare Kidney Disease Reference Network (ERKNet), formed a workgroup. Our goal was to update the 2012 guidelines and formulate new clinical practice recommendations for the diagnostic approach to patients with a suspicion of PH and the management of all types of PH with various stages of kidney dysfunction.

• #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. […] All young people with kidney stones should have a checkup. The checkup should include a test that measures oxalate in the urine. Adults who keep getting kidney stones also should be tested for oxalate in the urine. […] Without treatment, primary hyperoxaluria can damage the kidneys. Over time the kidneys may stop working. This is called kidney failure. […] 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. First it builds up in the blood, then in the eyes, bones, skin, muscles, blood vessels, heart and other organs.

• #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. […] Healthcare professionals will start with reviewing your medical history, family history and symptoms to diagnose PH1. They will likely also do a physical exam and test your blood and urine. Getting the right diagnosis is important since each PH type comes with a different level of severity and risk for complications. […] Screening for hyperoxaluria is important for the following situations: Babies and children after their first kidney stone; Adults who have calcium oxalate stones often; Before a baby is born if there is a concern for PH (also known as prenatal testing); You have a family history of stone disease at any age; Close relatives of a person who is newly diagnosed with PH.

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

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

  A single kidney stone in children or recurring kidney stones in adults should cause suspicion of primary hyperoxaluria (PH). […] Many patients are asymptomatic for years, with 18% of people with primary hyperoxaluria type 1 being diagnosed by familial screening before they show any symptoms. […] Children should not develop bladder or kidney stones, and the presence of even a single kidney stone in an infant or child should immediately raise suspicion of a genetic condition like primary hyperoxaluria. […] A single kidney stone in an adult is not uncommon, but recurring kidney stones can be indications of an underlying metabolic disorder or genetic disease. […] Suspect primary hyperoxaluria when a patient presents with reduced renal function combined with nephrocalcinosis or a high occurrence of kidney stones.

• #1 Hyperoxaluria and oxalosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hyperoxaluria/diagnosis-treatment/drc-20352258

  You’ll likely have a thorough physical exam. You might be asked questions about your health history and eating habits. […] Tests to diagnose hyperoxaluria may include: […] Urine tests, to measure oxalate and other substances in the urine. You’re given a special container to collect your urine over 24 hours. It’s then sent to a lab. […] Blood tests, to check how well your kidneys work and measure oxalate levels in the blood. […] Stone analysis, to find out what kidney stones are made of after you’ve passed them through urine or gotten them removed with surgery. […] Kidney X-ray, ultrasound or computerized tomography (CT) scan, to check for any kidney stones or calcium oxalate buildup in the body. […] You may need more tests to find out for sure if you have hyperoxaluria and see how the disease has affected other parts of your body. These tests may include:

• #1 Primary hyperoxaluria | Nefrología

  https://revistanefrologia.com/en-primary-hyperoxaluria-articulo-X2013251414054186

  A PH diagnosis algorithm was recently published by the European guidelines. […] Testing oxalate in urine is the first step in diagnosing PH. […] Oxaluria higher than 45mg/day (0.5mmol/1.73m2/day) in at least two 24-hour urine samples is typical of PH, once causes of SHO have been ruled out. […] An abundance of oxalate crystals in the renal biopsy is indicative of PH, particularly if they appear in the interstitium, surrounded by a strong inflammatory reaction in the form of foreign body granulomas. […] The diagnosis of PH must be confirmed with a DNA analysis of the AGT gene (AGXT), which furthermore provides information about the type of mutation and polymorphisms affecting patients.

• #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. The normal upper level of urinary oxalate excretion is 40 mg (440 mol) in 24 hours. Men have a slightly higher normal value (43 mg/d in men vs 32 mg/d in women), but this is primarily due to larger body habitus and larger average meal size rather than to any real intrinsic metabolic difference. Stone formation risk probably depends more on absolute total oxalate excretion and concentration than on arbitrary normal values. […] Reflecting these normal values, the usual definition of hyperoxaluria is urinary oxalate excretion that exceeds 40 mg/day. An alternative definition of hyperoxaluria that corrects for size differences is 30 mg of urinary oxalate per 24 hours per gram of excreted creatinine. Still, the relative concentration of oxalate is probably more significant than either of these definitions acknowledges.

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

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

  Treatment depends to some extent on the underlying etiology and severity of the hyperoxaluria. However, many treatments (eg, dietary measures) can be used in any case of hyperoxaluria, and treatments can be combined for increased efficacy. […] Hyperoxaluria has been reported to be the most common urinary metabolic abnormality in patients with stones who have undergone bariatric surgery. […] The prognosis of patients with primary hyperoxaluria depends on early treatment and management of hyperoxaluria and associated renal deterioration. If medical treatment cannot help the patient maintain a normal oxalate level, nephrocalcinosis may develop, with subsequent renal failure. In this situation, combined liver-renal transplantation is necessary for cure. […] In primary hyperoxaluria, urinary oxalate excretion is typically more than 100 mg/d. Primary hyperoxaluria may result in kidney failure due to nephrocalcinosis. In the past, liver biopsy was typically used to identify the enzyme defect in the different types of primary hyperoxaluria; however, with the increasingly lower cost and improved sensitivity of molecular genetic testing, the need for liver biopsy has substantially decreased.

• #1 Hyperoxaluria – StatPearls – NCBI Bookshelf

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

  The American Urological Association (AUA) Guidelines recommend genetic testing for PH if urinary oxalate is 75 mg/day (or 0.85 mmol/24h/1.73 m). […] Patients with recurrent episodes and children with early-onset nephrolithiasis are examples of patient groups that would understandably require a high level of motivation to follow the recommended preventive measures.

• #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 and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Diagnosis of hyperoxaluria is established using a combination of clinical, radiological, biochemical, histopathological and genetic studies in primary hyperoxaluria. In patients with a clinical suspicion for hyperoxaluria, the diagnostic workup should begin with ultrasound or other radiological imaging of the kidneys and the rest of the urinary tract to confirm the presence of nephrocalcinosis and urolithiasis. The initial biochemical tests include urinary oxalate excretion preferably measured in 24 h urine collection and adjustment of the oxalate excretion per 1.73 m2 of the body surface area is recommended. Non-invasive, definitive diagnosis of PH is provided by testing of AGXT, GRHPR and HOGA1 genes. In SH, stones are usually mixed (whewellite and weddellite) in contrast to PH. The excretion of urinary oxalate is increased in SH and may be 0.7 mmol/1.73 m2 per 24 h but in some cases may exceed 1.0 mmol/1.73 m2 per 24 h.

• #1 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. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Diagnosis of hyperoxaluria is established using a combination of clinical, radiological, biochemical, histopathological and genetic studies in primary hyperoxaluria. Precise diagnosis is of paramount importance for prognostic and treatment implications and also for prenatal screening in appropriate cases where PH is suspected. In patients with a clinical suspicion for hyperoxaluria, the diagnostic workup should begin with ultrasound or other radiological imaging of the kidneys and the rest of the urinary tract to confirm the presence of nephrocalcinosis and urolithiasis. The initial biochemical tests include urinary oxalate excretion preferably measured in 24 h urine collection and adjustment of the oxalate excretion per 1.73 m2 of the body surface area is recommended. Non-invasive, definitive diagnosis of PH is provided by testing of AGXT, GRHPR and HOGA1 genes. When DNA screening is non diagnostic but clinical suspicion is high, liver biopsy is undertaken for establishing the diagnosis. In SH, stones are usually mixed (whewellite and weddellite) in contrast to PH. The excretion of urinary oxalate is increased in SH and may be 0.7 mmol/1.73 m2 per 24 h but in some cases may exceed 1.0 mmol/1.73 m2 per 24 h. Other available diagnostic tests include use of PCR in stool samples to identify oxalobacter formigenes. Also, Increased intestinal oxalate absorption can be assessed by an absorption test using (13C2) oxalate. This test can help identify hyperabsorbers who would benefit from dietary interventions focusing on lowering oxalate and increasing calcium in the diet.

• #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. Kidney stones are usually the first symptom. The goal of treatment is to lower oxalate levels in your body and prevent calcium oxalate crystals from forming. […] Hyperoxaluria occurs when you have excess oxalate in your pee. Oxalate can combine with calcium in your pee and cause kidney stones and crystals to form. […] In addition to a physical exam, medical history and diet history, typical tests used to diagnose hyperoxaluria include: Urine tests to measure levels of oxalate and enzymes in your pee. Blood test to measure kidney function and the amount of oxalate in your blood. Imaging tests (X-rays, ultrasound and/or CT scan) of your kidneys and urinary tract to check for kidney stones or calcium oxalate crystals.

• #1 Hyperoxaluria and oxalosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hyperoxaluria/diagnosis-treatment/drc-20352258

  DNA testing to look for the gene changes that cause primary hyperoxaluria. […] Kidney biopsy to check for buildup of oxalate. […] Echocardiogram, an imaging test that can check for oxalate buildup in the heart. […] Eye exam to check for oxalate deposits in the eyes. […] Bone marrow biopsy to check for buildup of oxalate in the bones. […] Liver biopsy to look for low levels of proteins, also called enzyme deficiencies. This test is needed only in rare cases when genetic testing doesn’t show the cause of hyperoxaluria. […] If you learn you have primary hyperoxaluria, your siblings also are at risk of the disease. They should have tests as well. If your child has primary hyperoxaluria, you may want to get genetic testing if you and your partner plan to have more children. Medical genetics counselors who have experience with hyperoxaluria can help guide your decisions and testing.

• #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

  The diagnostic work-up for patients with estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 and suspected primary hyperoxaluria (PH) should include at least two urine oxalate assessments (preferably from a 24h urine collection). If genetic assessment reveals a mutation consistent with vitamin B6 (VB6; also known as pyridoxine) non-responsive PH1, RNA interference (RNAi) therapy is indicated. Patients who are partially responsive to VB6 therapy may also be eligible for RNAi therapy if hyperoxaluria persists. […] An exhaustive review of the genetic basis of PH has been published elsewhere. In brief, we regard genetic testing as the gold standard for the diagnosis of all three types of PH. We therefore recommend that all patients who are suspected to have PH should undergo genetic assessment, as genetic confirmation of PH and typing are pivotal to the management of these patients, and assessment of biochemical parameters can be unreliable.

• #1 Primary Hyperoxaluria Type 1 | National Kidney Foundation

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

  Examples of the types of tests your healthcare professional may do if they suspect PH1, include: Blood or saliva (spit) test for AGXT, GRHPR, and/or HOGA1 genes; Ultrasound, CT scan, or other type of medical imaging; 24-hour urine collection; Analysis of the stones found in your urine; Estimated glomerular filtration rate (eGFR); Oxalate level in your blood; Kidney biopsy and/or liver biopsy (a small piece of your kidney and/or liver is removed and looked at with a microscope).

• #1 Invitae Primary Hyperoxaluria Panel | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-06227

  The Invitae Primary Hyperoxaluria panel analyzes 3 genes associated with primary hyperoxaluria, a disorder of glyoxylate metabolism associated with renal damage that may progress to kidney failure. […] The primary hyperoxalurias are inherited disorders of glyoxylate metabolism in which hepatic peroxisomal enzyme deficiencies result in excessive production of oxalate. The excess oxalate cannot be degraded and is excreted in large amounts by the kidneys, resulting in high urinary oxalate levels. Insoluble calcium oxalate crystals accumulate in the kidneys, leading to nephrolithiasis and nephrocalcinosis, which may progress to end-stage renal disease (ESRD) and systemic oxalosis. […] Most patients present with signs or symptoms related to kidney stones. Kidney stones are present in 65% of patients before 10 years of age and in 85% before 20 years of age. A minority of patients present with failure to thrive and ESRD due to calcification of kidney tissue without discrete kidney stones. Recurring stones throughout childhood, adolescence, and adulthood are characteristic. Over time, however, progressive renal damage leads to reduced kidney function that can be evident as early as 4 months of age. In up to 30% of cases the diagnosis was not confirmed until patients reached end-stage renal failure.

• #1 How Is Primary Hyperoxaluria Type 1 Diagnosed?

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

  A molecular genetic test can show whether you have the AGXT gene mutation and confirm the diagnosis. […] If you’re planning to have children and someone in your family (or your partner’s) has been diagnosed with PH1, genetic screening is important. […] If you’re pregnant and have family members with the AGXT gene mutation, you may want prenatal testing for PH1. […] People with a family history of PH1 who conceive through in vitro fertilization may be able to have a test called pre-implantation genetic diagnosis (PGD).

• #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

  Biochemical assessment has an important role in the diagnostic work-up of patients with symptoms suggestive of PH and can focus genetic testing. It can also be used as an indication of therapeutic response. However, measurement of oxalate and relevant metabolites is not without difficulty and one must interpret the results carefully, taking all potential flaws into account. […] Urine oxalate above 1mmol/1.73m2 per day is strongly suggestive of PH. Exclusion of enteric causes of hyperoxaluria (for example, chronic pancreatitis, cystic fibrosis, inflammatory bowel syndrome or bariatric surgery) in which the degree of hyperoxaluria may overlap with PH is required before further metabolic or genetic investigations. […] The finding of 200 pure whewellite crystals per cubic millimetre in the urinary sediment is highly suggestive of PH1, especially in young children. The specificity of this finding is lower in the adult population. Nonetheless, this rapid, non-invasive and inexpensive test enables the rapid exclusion of other crystal species not normally found in the urine, such as cystine.

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

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

  Enteric hyperoxaluria is characterized by very high urinary oxalate levels (usually 80 mg/d or more) and hypocalciuria, with urinary calcium excretion usually less than 100 mg/d. Generally, a chronic diarrheal state is present, leading to hypocitraturia and relative dehydration in addition to the hyperoxaluria. It should be considered in any patient with calcium oxalate stone disease and any type of chronic diarrhea. […] Urinary oxalate excretion in idiopathic or mild hyperoxaluria is usually 40-60 mg/d. Most patients with relatively mild hyperoxaluria (approximately 40-60 mg/d) have dietary hyperoxaluria. […] The mean urinary glycosaminoglycans concentration is lower in men with stones than in women with stones; this may play a role in the difference in the stone formation rate between the sexes.

• #1 About Primary Hyperoxaluria (PH) | Uncovering PH

  https://www.uncoveringph.com/about-ph.html

  Hyperoxaluria is a condition defined by increased urinary excretion of oxalate. Oxalate is a metabolic end product that is not naturally broken down. It can also be ingested through food and has no known function in the body.2,3 […] Systemic oxalosis occurs when glomerular filtration rate (GFR) drops below 30 to 45 mL/min and oxalate is no longer adequately filtered by the kidneys. At this point, CaOx crystals begin to deposit in tissues of other organs such as the heart, bone, eyes, and skin.1,10-13 […] All subtypes of primary hyperoxaluria can have a significant impact on kidney function.14-18 […] Primary hyperoxaluria is more common than previously thought and significantly underdiagnosed. […] Approximately 11% of patients with signs and symptoms consistent with a diagnosis of PH do not have 1 of the 3 known PH mutations. These patients likely have a PH mutation that has not been discovered yet.14 […] Patients are often diagnosed years after symptoms begin33.

• #1

  https://link.springer.com/article/10.1007/s00467-003-1234-x

  Primary hyperoxaluria (PH) is a heterogeneous disease with a variable age of onset and a variable progression into kidney failure. Early diagnosis is mandatory to avoid the damaging effects of systemic calcium oxalate deposition. […] A significant delay of diagnosis was seen in 42% of patients and 30% of patients were diagnosed only at end-stage renal disease (ESRD). Diagnosis was usually based on history and urinary oxalate excretion. […] In conclusion, the time between first symptom and diagnosis of PH must be minimized, and the diagnostic procedures have to be improved.

• #1 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. […] 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. 59% to 70% of people diagnosed with PH1 as adults are in ESRD at the time of diagnosis.

• #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. […] If they think PH may be causing your symptoms, they can do these tests to see if you have PH: urine tests to measure the levels of oxalate or look for crystals, blood tests to see oxalate levels in your blood and check how well your kidneys are working, genetic (DNA) tests to see if you have the gene that causes PH this can help you understand the chance of passing PH to your children, kidney x-ray or ultrasound. […] Some people may not find out they have PH until their kidneys fail and they need dialysis.

• #1 Signs & Symptoms of Primary Hyperoxaluria Type 1 (PH1) | Behind the Stone®

  https://www.aboutph1.com/ph1-clinical-features

  PH1 is a heterogeneous disease.1,4 PH1 patients with identical genotypes, and even members of the same family, can have variable disease symptoms.4 At any age, patients may present with one or more of the clinical manifestations below1,5: […] Kidney stones are the most common clinical manifestation and the one that most often leads to a diagnosis of PH1, though not all patients with PH1 may be stone formers.5,8,9 Metabolic testing through 24-hour urine collection analysis is recommended by the American Urological Association (AUA) in high-risk and recurrent stone formers.10 […] In a study, children with PH1 were characterized by presentation before adolescence, normal mobility, nephrocalcinosis, decreased eGFR, and calcium oxalate monohydrate stone composition awareness of these characteristics could help with earlier diagnosis, which is crucial given the progressive nature of the disease.11

• #1 Missed diagnosis of oxalosis with disastrous consequences. Case reports of a father and daughter – ScienceOpen

  https://www.scienceopen.com/hosted-document?doi=10.24911/ejmcr/173-1647277526

  Missed diagnosis of oxalosis with disastrous consequences. Case reports of a father and daughter […] Hyperoxalosis is a rare disease that originates from a defect in a liver enzyme and results in renal failure, if not diagnosed in time. Once end-stage renal disease is established, a transplant is the treatment of choice. But a kidney-only transplant can fail due to the mobilization of the excess oxalates in the tissue, and many authorities recommend a combined kidney-liver transplant. […] We describe a case where the diagnosis of oxalosis was missed, resulting in renal transplant failure and excision of the graft. The diagnosis was made only on noting florid heterotopic calcification. A renal transplant was performed due to end-stage renal disease, but graft failure occurred and had to be excised due to recurrent oxalosis, again without diagnosis, despite imaging and graft biopsy. It was only when muscle calcification was noted for an unrelated indication that a diagnosis was made. The case highlights the importance of excluding all causes of nephrocalcinosis, including rare ones like oxalosis, in the management of chronic renal disease. […] We hope to alert the physician to consider primary hyperoxalosis as a differential diagnosis in renal failure patients with recurrent calcium oxalate renal stones and/or nephrocalcinosis. […] The treatment of choice is a combined liver-kidney transplant for type 1 hyperoxalosis that makes up for most cases. This is associated with a 5-year survival of 80%. A kidney-only transplant is recommended for those with pyridoxine-responsive type I disease, as well as for cases of type II disease. In this case, with a kidney-only transplant, the recurrence of renal oxalosis is probable due to mobilization of oxalates in tissues. This led to graft failure in our patient. […] Our case is unusual in that repeated imaging with ultrasound and CT and biopsies of the native kidneys and the excised failed transplant did not diagnose hyperoxalosis. Oxalate crystals were seen in the failed and excised graft, but given that oxalate crystals can be seen in graft failure without hyperoxalosis, the diagnosis was not made. […] Nephrocalcinosis is a relatively easy diagnosis to make on ultrasound and CT, but most cases are of the medullary type, and cortical nephrocalcinosis is relatively rare. Oxalosis is differential in both medullary and cortical types of nephrocalcinosis. In this case, the father’s disease progressed to complete calcification of the kidneys, while the daughter’s kidneys showed medullary nephrocalcinosis.

• #1 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. […] How is primary hyperoxaluria type 1 (PH1) diagnosed? […] If PH1 is suspected, there are a few ways that might aid in the diagnosis, which include: […] A genetic test is performed to find mutations to validate a PH1 diagnosis. […] The first step to diagnosing primary hyperoxaluria type 1 (PH1) is to be aware of the signs and symptoms. […] Finding a diagnosis for a hereditary or rare disease is challenging. […] An early and accurate diagnosis, followed by aggressive supportive treatment, plays a significant role in both short- and long-term outcomes.

• #1 Primary hyperoxaluria diagnosed after kidney transplantation: a case report and literature review | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02546-0

  This study aims to summarize the manifestations, complications, treatment, and prognosis of these cases and emphasize the need for careful pre-transplant PH screening of patients with bilateral nephrocalcinosis and nephrolithiasis. […] In summary, our case reports and literature reviews show that the proportion of kidney transplant failure caused by a missed diagnosis of PH before kidney transplantation is extremely high. Preoperative PH screening, including urine oxalate analysis, molecular genetic testing and renal biopsy, should be performed in all patients with bilateral nephrocalcinosis or nephrolithiasis.

• #1 (PDF) Primary Hyperoxaluria- Imaging of Renal Oxalosis

  https://www.academia.edu/87028553/Primary_Hyperoxaluria_Imaging_of_Renal_Oxalosis

  Primary hyperoxaluria Type 1 is a rare autosomal recessive inborn error of glyoxylate metabolism, caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase. […] The diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. […] Primary hyperoxaluria should be considered in patients of any age presenting with unexplained renal failure, and appropriate systemic pathology of oxalosis. […] The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. […] It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease.

• #2

  https://link.springer.com/article/10.1007/s00467-003-1234-x

  Primary hyperoxaluria (PH) is a heterogeneous disease with a variable age of onset and a variable progression into kidney failure. Early diagnosis is mandatory to avoid the damaging effects of systemic calcium oxalate deposition. […] A significant delay of diagnosis was seen in 42% of patients and 30% of patients were diagnosed only at end-stage renal disease (ESRD). Diagnosis was usually based on history and urinary oxalate excretion. […] In conclusion, the time between first symptom and diagnosis of PH must be minimized, and the diagnostic procedures have to be improved.

• #2 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. […] Healthcare professionals will start with reviewing your medical history, family history and symptoms to diagnose PH1. They will likely also do a physical exam and test your blood and urine. Getting the right diagnosis is important since each PH type comes with a different level of severity and risk for complications. […] Screening for hyperoxaluria is important for the following situations: Babies and children after their first kidney stone; Adults who have calcium oxalate stones often; Before a baby is born if there is a concern for PH (also known as prenatal testing); You have a family history of stone disease at any age; Close relatives of a person who is newly diagnosed with PH.

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

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

  A single kidney stone in children or recurring kidney stones in adults should cause suspicion of primary hyperoxaluria (PH). […] Many patients are asymptomatic for years, with 18% of people with primary hyperoxaluria type 1 being diagnosed by familial screening before they show any symptoms. […] Children should not develop bladder or kidney stones, and the presence of even a single kidney stone in an infant or child should immediately raise suspicion of a genetic condition like primary hyperoxaluria. […] A single kidney stone in an adult is not uncommon, but recurring kidney stones can be indications of an underlying metabolic disorder or genetic disease. […] Suspect primary hyperoxaluria when a patient presents with reduced renal function combined with nephrocalcinosis or a high occurrence of kidney stones.

• #2 Signs & Symptoms of Primary Hyperoxaluria Type 1 (PH1) | Behind the Stone®

  https://www.aboutph1.com/ph1-clinical-features

  The AUA recommends genetic testing to help confirm a PH1 diagnosis in any patient with urinary oxalate (UOx) excretion exceeding 75 mg/day (0.83 mmol/1.73 m2/day).10 Genetic testing can identify AGXT gene mutations to help confirm a PH1 diagnosis, regardless of kidney function.3,22 […] Recurrent and/or unusual kidney stones in an adult or any kidney stone in a child or adolescent could be a sign of a metabolic stone disease like PH1.6,23 Consider these patients for a full work-up and genetic testing to help confirm PH1.6

• #2 Primary hyperoxaluria: MedlinePlus GeneticsLock

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

  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. […] Oxalate that is not excreted from the body combines with calcium to form calcium oxalate deposits, which can damage the kidneys and other organs. […] This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.

• #2 Invitae Primary Hyperoxaluria Panel | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-06227

  Patients with PH1 showed a median age at progression to kidney failure of 33 years. Patients with PH2 and PH3 appear to have better outcomes, with a preservation of renal function in most of the cases. […] This panel is estimated to identify pathogenic variants in at least 90% of patients with primary hyperoxaluria.

• #2 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. […] Therefore, clinicians caring for these patients should become familiar with the available testing and treatments for hyperoxaluria and endpoints to measure therapy effectiveness. […] The evaluation of any underlying hyperoxaluria will be considered separately. […] Any patient suspected of hyperoxaluria should be tested for urinary oxalate excretion by collecting a 24-hour urine sample. […] The diagnosis of PH is rare and unusual. More often than not, it becomes apparent only after the development of ESRD and dialysis. […] Confirmatory tests include direct genetic testing or measuring the AGT enzyme activity following a liver biopsy.

• #2

  https://journals.lww.com/ijpm/fulltext/2018/61020/bone_marrow_oxalosis__an_unusual_cause_of.26.aspx

  Systemic oxalosis can be either primary or secondary hyperoxaluria. Oxalosis is a phenomenon in which calcium oxalate crystals deposit in various visceral organs leading to bone marrow (BM) failure and recurrent renal stones. […] Hyperoxaluria is characterized by supersaturation of calcium oxalate in the urine and is associated with nephrolithiasis and nephrocalcinosis. […] BM oxalosis should be considered as a possible diagnosis in patients in recurrent nephrolithiasis and cytopenia. […] BM oxalosis is an unusual disease presenting with renal failure and cytopenia. The development of pancytopenia is a rare and late finding. BM biopsy is necessary in most of the cases as aspirate is often hemodiluted due to crystals. […] BM oxalosis should be considered as a possible diagnosis in patients in recurrent nephrolithiasis with pancytopenia- or treatment-resistant anemia.

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

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

  Enteric hyperoxaluria is characterized by very high urinary oxalate levels (usually 80 mg/d or more) and hypocalciuria, with urinary calcium excretion usually less than 100 mg/d. Generally, a chronic diarrheal state is present, leading to hypocitraturia and relative dehydration in addition to the hyperoxaluria. It should be considered in any patient with calcium oxalate stone disease and any type of chronic diarrhea. […] Urinary oxalate excretion in idiopathic or mild hyperoxaluria is usually 40-60 mg/d. Most patients with relatively mild hyperoxaluria (approximately 40-60 mg/d) have dietary hyperoxaluria. […] The mean urinary glycosaminoglycans concentration is lower in men with stones than in women with stones; this may play a role in the difference in the stone formation rate between the sexes.

• #2 Primary hyperoxaluria | Nefrología

  http://www.revistanefrologia.com/en-relaccionados-primary-hyperoxaluria-articulo-X2013251414054186

  A PH diagnosis algorithm was recently published by the European guidelines. […] Testing oxalate in urine is the first step in diagnosing PH. Oxaluria higher than 45mg/day (0.5mmol/1.73m2/day) in at least two 24-hour urine samples is typical of PH, once causes of SHO have been ruled out. […] An abundance of oxalate crystals in the renal biopsy is indicative of PH, particularly if they appear in the interstitium, surrounded by a strong inflammatory reaction in the form of foreign body granulomas. […] The diagnosis of PH must be confirmed with a DNA analysis of the AGT gene (AGXT), which furthermore provides information about the type of mutation and polymorphisms affecting patients.

• #2 Primary hyperoxaluria diagnosed after kidney transplantation: a case report and literature review | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02546-0

  Primary hyperoxaluria (PH) is a rare inherited autosomal recessive disease caused by disturbed glyoxylate metabolism. The disease is characterized by calcium oxalate crystal deposition in various organs, especially in the kidney. Due to the lack of current understanding of PH, nearly all patients are only initially diagnosed with PH when recurrent lithiasis and progressive end-stage renal disease occur. Many cases are not diagnosed in patients until renal allograft insufficiency occurs after renal transplantation. This case report and literature review aim to emphasize the need for careful pre-transplant PH screening of patients with bilateral nephrocalcinosis or nephrolithiasis. […] By reviewing and analyzing these cases, we concluded that patients with a history of nephrocalcinosis or nephrolithiasis in both kidneys need preoperative screening for PH and appropriate treatment before kidney transplantation. Delayed graft function caused by PH is easily misdiagnosed as acute rejection, and needle biopsy should be performed at an early stage.

Zobacz więcej