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Section | Existing text | Revised text with references | Reason for suggested change |
---|---|---|---|
1. Pathophysiology | No changes to existing text | Add the following to existing text: Primary hyperoxaluria is caused by genetic defects that result in the overproduction of oxalate. This is different from secondary hyperoxaluria, which is caused by the increase in dietary and intestinal absorption of oxalate or excessive intake of oxalate precursors. [1] | To distinguish between primary hyperoxaluria and secondary hyperoxaluria (another type of hyperoxaluria). ![]() |
2. Diagnosis, Classification | There are three main types of primary hyperoxaluria, each associated with specific metabolic defects. Type 1 is the most common and rapidly progressing form, accounting for about 80% of all cases. Type 2 and 3 account for about approximately 10% each of the population. | The three main types of primary hyperoxaluria (PH1, PH2, and PH3) are each associated with mutations in specific genes involved in the metabolism of glyoxylate, the precursor of oxalate. These mutations result in decreased production or activity of the proteins that are involved in the normal breakdown of glyoxylate, which results in an overproduction of oxalate. [2] PH1 is considered to be the most common and rapidly progressing form, accounting for about 80% of all currently diagnosed cases and PH2 and PH3 accounting for approximately 10% each of the current cases. [1] [3]However, emerging evidence suggests that PH2 and PH3 are not as benign as previously thought. Up to 50% of patients with PH2 develop kidney failure ( chronic kidney disease stage 5) at some point. [4] While current estimates indicate that kidney failure is rarer in patients with PH3 compared to PH1 and PH2, chronic kidney disease has been reported in patients with PH3. Moreover, the population prevalence of PH3 variants is much higher than observed frequency of the disease, which suggests either incomplete penetrance or underdiagnosis. [5] | This adds recent literature evidence on classification, disease prevalence and severity for PH subtypes, especially the lesser understood subtypes (i.e., PH2 and PH3).
![]() ‡ Added secondary source and modified text accordingly. Please review |
2B. | The three main types of primary hyperoxaluria (PH1, PH2, and PH3) are each associated with mutations in specific genes involved in the metabolism of
glyoxylate, the precursor of oxalate. These mutations result in decreased production or activity of the proteins that are involved in the normal breakdown of glyoxylate, which results in an overproduction of oxalate.
[6] Mutations in the genes
AGXT and
GRHPR cause PH1 and PH2, respectively, through decreased production or activity of the proteins they make, which stops the normal breakdown of glyoxylate. Similarly, mutations in the gene
HOGA1 cause PH3 due to loss-of-function mutations resulting in impaired protein function.
[7]
PH1 is considered to be the most common and rapidly progressing form, accounting for about 80% of all currently diagnosed cases and PH2 and PH3 accounting for approximately 10% each of the current cases. [1] [8] 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). [9] |
(***While current estimates indicate that kidney failure is rarer in patients with PH3 compared to PH1 and PH2, chronic kidney disease has been reported in patients with PH3. Moreover, the genetic prevalence based on known PH3 variants is much higher than the diagnosed prevalence of the disease, which could mean either incomplete penetrance (i.e. variant present with no clinical symptoms) or underdiagnosis (i.e. variant present with clinical symptoms but not diagnosed). [10]***) | (This is proposed text to be added after the existing text ending in "......patients with PH2 developing kidney failure ( chronic kidney disease [CKD] stage 5). I have added the secondary source 10 to support this statement ) |
3. Diagnosis | No changes to existing text | Add the following to existing text: A diagnosis of primary hyperoxaluria is suspected based on presenting patient characteristics such as kidney stones in infants or children, recurrent kidney stones in adults, or family history of hyperoxaluria. In these patients, stone analysis and urine analysis are recommended to rule out secondary causes of hyperoxaluria. A definitive diagnosis of primary hyperoxaluria requires genetic testing. This is performed using a gene panel covering known mutations for all three types of primary hyperoxaluria. [11] [12] | Adds literature guidelines to aid in the diagnosis of this rare disorder ![]() |
4. Diagnosis | Mutations in genes causing PH1 and PH2 result in decreased production or activity of the proteins they make, which stops the normal breakdown of glyoxylate. While mutation in genes causing PH3 results in its overactivity, resulting in excess conversion of hydroxyproline to glyoxylate. | Please delete the existing sentence along with the reference (Belostotsky et al. 2010) | The genetic mutations for the basis of PH1, PH2 and PH3 and their effects on glyoxylate metabolism have already been conveyed by my suggested edits above ("the three main types of primary hyperoxaluria (PH1, PH2, and PH3) are each associated with mutations in specific genes involved in..."). The statement about PH3 mutations resulting in overactivity as stated in Belostotsky et al (2010) is outdated as this position has since then been revised to state that PH3 mutations result in a loss-of-function of the protein as opposed to gain-of-function or overactivity
[13]
[14].
![]() |
5. Treatment | Vitamin B6 (pyridoxine) is used for primary hyperoxaluria type1 as alanine glyoxylate transaminase require pyridoxine as cofactor. | Vitamin B6 (pyridoxine) is used for PH1 as alanine glyoxylate transaminase requires pyridoxine as cofactor. In a proportion of patients with PH1 (about one-third) [15], pyridoxine treatment may decrease oxalate excretion and prevent kidney stone formation. | The original statement "In a proportion of patients with primary hyperoxaluria type 1 (about 5%), pyridoxine treatment..." is outdated. Recent evidence shows different numbers. Added Wikipedia link to pyridoxine and made some grammar changes. ![]() |
6. Pathophysiology | 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 this is the primary treatment of severe hyperoxaluria. Liver transplantation (often in addition to renal transplant) may be able to control the disease by correcting the metabolic defect.[citation needed] | 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. [16] [17] | Added citations to substantiate the need for combined liver-kidney transplant. Also, this statement is better suited in the Treatment section. ![]() |
7. Treatment | Lumasiran is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages and is available under the UK Early Access to Medicines Scheme (EAMS). | Lumasiran, an RNA interference therapeutic [18] is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages and is available under the UK Early Access to Medicines Scheme (EAMS). | Added link to RNA interference Wikipedia page to explain the class of drugs Lumasiran falls under. ![]() |
8. Treatment | No changes to existing text | Add the following to existing text: In addition, there are a few agents under investigation in clinical trials for PH: Nedosiran (RNA interference therapeutic) for PH1, PH2, and PH3; Stiripentol (antiepileptic drug); Oxabact (lyophilized Oxalobacter formigenes; and Reloxaliase (oxalate-digesting enzyme) for PH [19] [20] | This lists the therapeutic agents currently being investigated in clinical trials for primary hyperoxaluria. ![]() ‡ Added secondary sources and modified text accordingly. Please review |
Iciplascarfern (
talk)
21:40, 14 April 2021 (UTC)
References
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
![]() | This article is rated Start-class on Wikipedia's
content assessment scale. It is of interest to the following WikiProjects: | ||||||||||
|
![]() | Ideal sources for Wikipedia's health content are defined in the guideline
Wikipedia:Identifying reliable sources (medicine) and are typically
review articles. Here are links to possibly useful sources of information about Primary hyperoxaluria.
|
![]() | Part of an edit requested by an editor with a conflict of interest has been implemented. See comments below. |
![]() | The
Wikimedia Foundation's
Terms of Use require that editors disclose their "employer, client, and affiliation" with respect to any paid contribution; see
WP:PAID. For advice about reviewing paid contributions, see
WP:COIRESPONSE.
|
Section | Existing text | Revised text with references | Reason for suggested change |
---|---|---|---|
1. Pathophysiology | No changes to existing text | Add the following to existing text: Primary hyperoxaluria is caused by genetic defects that result in the overproduction of oxalate. This is different from secondary hyperoxaluria, which is caused by the increase in dietary and intestinal absorption of oxalate or excessive intake of oxalate precursors. [1] | To distinguish between primary hyperoxaluria and secondary hyperoxaluria (another type of hyperoxaluria). ![]() |
2. Diagnosis, Classification | There are three main types of primary hyperoxaluria, each associated with specific metabolic defects. Type 1 is the most common and rapidly progressing form, accounting for about 80% of all cases. Type 2 and 3 account for about approximately 10% each of the population. | The three main types of primary hyperoxaluria (PH1, PH2, and PH3) are each associated with mutations in specific genes involved in the metabolism of glyoxylate, the precursor of oxalate. These mutations result in decreased production or activity of the proteins that are involved in the normal breakdown of glyoxylate, which results in an overproduction of oxalate. [2] PH1 is considered to be the most common and rapidly progressing form, accounting for about 80% of all currently diagnosed cases and PH2 and PH3 accounting for approximately 10% each of the current cases. [1] [3]However, emerging evidence suggests that PH2 and PH3 are not as benign as previously thought. Up to 50% of patients with PH2 develop kidney failure ( chronic kidney disease stage 5) at some point. [4] While current estimates indicate that kidney failure is rarer in patients with PH3 compared to PH1 and PH2, chronic kidney disease has been reported in patients with PH3. Moreover, the population prevalence of PH3 variants is much higher than observed frequency of the disease, which suggests either incomplete penetrance or underdiagnosis. [5] | This adds recent literature evidence on classification, disease prevalence and severity for PH subtypes, especially the lesser understood subtypes (i.e., PH2 and PH3).
![]() ‡ Added secondary source and modified text accordingly. Please review |
2B. | The three main types of primary hyperoxaluria (PH1, PH2, and PH3) are each associated with mutations in specific genes involved in the metabolism of
glyoxylate, the precursor of oxalate. These mutations result in decreased production or activity of the proteins that are involved in the normal breakdown of glyoxylate, which results in an overproduction of oxalate.
[6] Mutations in the genes
AGXT and
GRHPR cause PH1 and PH2, respectively, through decreased production or activity of the proteins they make, which stops the normal breakdown of glyoxylate. Similarly, mutations in the gene
HOGA1 cause PH3 due to loss-of-function mutations resulting in impaired protein function.
[7]
PH1 is considered to be the most common and rapidly progressing form, accounting for about 80% of all currently diagnosed cases and PH2 and PH3 accounting for approximately 10% each of the current cases. [1] [8] 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). [9] |
(***While current estimates indicate that kidney failure is rarer in patients with PH3 compared to PH1 and PH2, chronic kidney disease has been reported in patients with PH3. Moreover, the genetic prevalence based on known PH3 variants is much higher than the diagnosed prevalence of the disease, which could mean either incomplete penetrance (i.e. variant present with no clinical symptoms) or underdiagnosis (i.e. variant present with clinical symptoms but not diagnosed). [10]***) | (This is proposed text to be added after the existing text ending in "......patients with PH2 developing kidney failure ( chronic kidney disease [CKD] stage 5). I have added the secondary source 10 to support this statement ) |
3. Diagnosis | No changes to existing text | Add the following to existing text: A diagnosis of primary hyperoxaluria is suspected based on presenting patient characteristics such as kidney stones in infants or children, recurrent kidney stones in adults, or family history of hyperoxaluria. In these patients, stone analysis and urine analysis are recommended to rule out secondary causes of hyperoxaluria. A definitive diagnosis of primary hyperoxaluria requires genetic testing. This is performed using a gene panel covering known mutations for all three types of primary hyperoxaluria. [11] [12] | Adds literature guidelines to aid in the diagnosis of this rare disorder ![]() |
4. Diagnosis | Mutations in genes causing PH1 and PH2 result in decreased production or activity of the proteins they make, which stops the normal breakdown of glyoxylate. While mutation in genes causing PH3 results in its overactivity, resulting in excess conversion of hydroxyproline to glyoxylate. | Please delete the existing sentence along with the reference (Belostotsky et al. 2010) | The genetic mutations for the basis of PH1, PH2 and PH3 and their effects on glyoxylate metabolism have already been conveyed by my suggested edits above ("the three main types of primary hyperoxaluria (PH1, PH2, and PH3) are each associated with mutations in specific genes involved in..."). The statement about PH3 mutations resulting in overactivity as stated in Belostotsky et al (2010) is outdated as this position has since then been revised to state that PH3 mutations result in a loss-of-function of the protein as opposed to gain-of-function or overactivity
[13]
[14].
![]() |
5. Treatment | Vitamin B6 (pyridoxine) is used for primary hyperoxaluria type1 as alanine glyoxylate transaminase require pyridoxine as cofactor. | Vitamin B6 (pyridoxine) is used for PH1 as alanine glyoxylate transaminase requires pyridoxine as cofactor. In a proportion of patients with PH1 (about one-third) [15], pyridoxine treatment may decrease oxalate excretion and prevent kidney stone formation. | The original statement "In a proportion of patients with primary hyperoxaluria type 1 (about 5%), pyridoxine treatment..." is outdated. Recent evidence shows different numbers. Added Wikipedia link to pyridoxine and made some grammar changes. ![]() |
6. Pathophysiology | 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 this is the primary treatment of severe hyperoxaluria. Liver transplantation (often in addition to renal transplant) may be able to control the disease by correcting the metabolic defect.[citation needed] | 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. [16] [17] | Added citations to substantiate the need for combined liver-kidney transplant. Also, this statement is better suited in the Treatment section. ![]() |
7. Treatment | Lumasiran is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages and is available under the UK Early Access to Medicines Scheme (EAMS). | Lumasiran, an RNA interference therapeutic [18] is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages and is available under the UK Early Access to Medicines Scheme (EAMS). | Added link to RNA interference Wikipedia page to explain the class of drugs Lumasiran falls under. ![]() |
8. Treatment | No changes to existing text | Add the following to existing text: In addition, there are a few agents under investigation in clinical trials for PH: Nedosiran (RNA interference therapeutic) for PH1, PH2, and PH3; Stiripentol (antiepileptic drug); Oxabact (lyophilized Oxalobacter formigenes; and Reloxaliase (oxalate-digesting enzyme) for PH [19] [20] | This lists the therapeutic agents currently being investigated in clinical trials for primary hyperoxaluria. ![]() ‡ Added secondary sources and modified text accordingly. Please review |
Iciplascarfern (
talk)
21:40, 14 April 2021 (UTC)
References
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)