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Hyperoxaluria

MedGen UID:
43782
Concept ID:
C0020500
Disease or Syndrome
Synonym: Oxaluria
SNOMED CT: Hyperoxaluria (367621000119107)
 
HPO: HP:0003159

Definition

Primary hyperoxaluria results from the overproduction of a substance called oxalate. Oxalate is filtered through the kidneys and excreted as a waste product in urine, leading to abnormally high levels of this substance in urine (hyperoxaluria). During its excretion, oxalate can combine with calcium to form calcium oxalate, a hard compound that is the main component of kidney and bladder stones. Deposits of calcium oxalate can damage the kidneys and other organs and lead to blood in the urine (hematuria), urinary tract infections, kidney damage, ESRD, and injury to other organs. Over time, kidney function decreases such that the kidneys can no longer excrete as much oxalate as they receive. As a result oxalate levels in the blood rise, and the substance gets deposited in tissues throughout the body (systemic oxalosis), particularly in bones and the walls of blood vessels. Oxalosis in bones can cause fractures.

There are three types of primary hyperoxaluria that differ in their severity and genetic cause. In primary hyperoxaluria type 1, kidney stones typically begin to appear anytime from childhood to early adulthood, and ESRD can develop at any age. Primary hyperoxaluria type 2 is similar to type 1, but ESRD develops later in life. In primary hyperoxaluria type 3, affected individuals often develop kidney stones in early childhood, but few cases of this type have been described so additional signs and symptoms of this type are unclear.

Primary hyperoxaluria is a rare condition characterized by recurrent kidney and bladder stones. The condition often results in end stage renal disease (ESRD), which is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively. [from MedlinePlus Genetics]

Conditions with this feature

Primary hyperoxaluria, type I
MedGen UID:
75658
Concept ID:
C0268164
Disease or Syndrome
Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver peroxisomal enzyme alanine:glyoxylate-aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is absent, glyoxylate is converted to oxalate, which forms insoluble calcium oxalate crystals that accumulate in the kidney and other organs. Individuals with PH1 are at risk for recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis / urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), or end-stage renal disease (ESRD). Age at onset of symptoms ranges from infancy to the sixth decade. Approximately 10% of affected individuals present in infancy or early childhood with nephrocalcinosis, with or without nephrolithiasis, and failure to thrive related to renal failure. The majority of individuals with PH1 present in childhood or early adolescence, usually with symptomatic nephrolithiasis and normal or reduced kidney function. The remainder of affected individuals present in adulthood with recurrent renal stones and a mild-to-moderate reduction in kidney function. The natural history of untreated PH1 is one of progressive decline in renal function as a result of calcium oxalate deposits in kidney tissue and complications of nephrolithiasis (e.g., obstruction and infection) with eventual progression to oxalosis (widespread tissue deposition of calcium oxalate) and death from ESRD and/or complications of oxalosis.
Primary hyperoxaluria, type II
MedGen UID:
120616
Concept ID:
C0268165
Disease or Syndrome
Primary hyperoxaluria type 2 (PH2), caused by deficiency of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GR/HPR), is characterized by recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis/urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), and end-stage renal disease (ESRD). After ESRD, oxalosis (widespread tissue deposition of calcium oxalate) usually develops. Symptom onset is typically in childhood.
Peroxisome biogenesis disorder 1B
MedGen UID:
79470
Concept ID:
C0282527
Disease or Syndrome
Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term "ZSD" is now used to refer to all individuals with a defect in one of the ZSD-PEX genes regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and the long bones), and liver disease that can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss), neurologic involvement (ataxia, polyneuropathy, and leukodystrophy), liver dysfunction, adrenal insufficiency, and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.
Primary hyperoxaluria type 3
MedGen UID:
462228
Concept ID:
C3150878
Disease or Syndrome
Primary hyperoxaluria is an autosomal recessive disorder of glyoxylate metabolism that results in excessive endogenous oxalate synthesis and the formation of calcium oxalate kidney stones. Progressive renal inflammation and interstitial fibrosis from advanced nephrocalcinosis, recurrent urolithiasis, and urinary tract infections can cause reduced renal function, systemic oxalate deposition, and end-stage renal failure. Compared to hyperoxaluria type I (HP1; 259900) and type II (HP2; 260000), HP3 appears to be the least severe, with good preservation of kidney function in most patients. The typical clinical characteristic is early onset of recurrent urolithiasis, but less active stone formation later (summary by Wang et al., 2015). For a discussion of genetic heterogeneity of primary hyperoxaluria, see 259900.
Nephrolithiasis susceptibility caused by SLC26A1
MedGen UID:
1830325
Concept ID:
C5779632
Disease or Syndrome
Nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis
MedGen UID:
1841152
Concept ID:
C5830516
Disease or Syndrome
Calcium oxalate nephrolithiasis-2 with or without nephrocalcinosis (CAON2) is an autosomal dominant disorder of renal function characterized by the recurrent formation of CaOx kidney stones. The age at onset is highly variable, ranging from childhood to adult. Most affected individuals have concurrent nephrocalcinosis. Renal function is generally preserved (Majmundar et al., 2023). See also CAON1 (167030).

Professional guidelines

PubMed

Kachkoul R, Touimi GB, El Mouhri G, El Habbani R, Mohim M, Lahrichi A
Malays J Pathol 2023 Dec;45(3):333-352. PMID: 38155376
Groothoff JW, Metry E, Deesker L, Garrelfs S, Acquaviva C, Almardini R, Beck BB, Boyer O, Cerkauskiene R, Ferraro PM, Groen LA, Gupta A, Knebelmann B, Mandrile G, Moochhala SS, Prytula A, Putnik J, Rumsby G, Soliman NA, Somani B, Bacchetta J
Nat Rev Nephrol 2023 Mar;19(3):194-211. Epub 2023 Jan 5 doi: 10.1038/s41581-022-00661-1. PMID: 36604599
Demoulin N, Aydin S, Gillion V, Morelle J, Jadoul M
Am J Kidney Dis 2022 May;79(5):717-727. Epub 2021 Sep 9 doi: 10.1053/j.ajkd.2021.07.018. PMID: 34508834

Recent clinical studies

Etiology

Groothoff JW, Metry E, Deesker L, Garrelfs S, Acquaviva C, Almardini R, Beck BB, Boyer O, Cerkauskiene R, Ferraro PM, Groen LA, Gupta A, Knebelmann B, Mandrile G, Moochhala SS, Prytula A, Putnik J, Rumsby G, Soliman NA, Somani B, Bacchetta J
Nat Rev Nephrol 2023 Mar;19(3):194-211. Epub 2023 Jan 5 doi: 10.1038/s41581-022-00661-1. PMID: 36604599
Kovacevic L
Pediatr Clin North Am 2022 Dec;69(6):1149-1164. Epub 2022 Oct 29 doi: 10.1016/j.pcl.2022.07.008. PMID: 36880927
Garrelfs SF, Frishberg Y, Hulton SA, Koren MJ, O'Riordan WD, Cochat P, Deschênes G, Shasha-Lavsky H, Saland JM, Van't Hoff WG, Fuster DG, Magen D, Moochhala SH, Schalk G, Simkova E, Groothoff JW, Sas DJ, Meliambro KA, Lu J, Sweetser MT, Garg PP, Vaishnaw AK, Gansner JM, McGregor TL, Lieske JC; ILLUMINATE-A Collaborators
N Engl J Med 2021 Apr 1;384(13):1216-1226. doi: 10.1056/NEJMoa2021712. PMID: 33789010
Hopp K, Cogal AG, Bergstralh EJ, Seide BM, Olson JB, Meek AM, Lieske JC, Milliner DS, Harris PC; Rare Kidney Stone Consortium
J Am Soc Nephrol 2015 Oct;26(10):2559-70. Epub 2015 Feb 2 doi: 10.1681/ASN.2014070698. PMID: 25644115Free PMC Article
Lorenzo V, Torres A, Salido E
Nefrologia 2014 May 21;34(3):398-412. Epub 2014 Apr 30 doi: 10.3265/Nefrologia.pre2014.Jan.12335. PMID: 24798559

Diagnosis

Groothoff JW, Metry E, Deesker L, Garrelfs S, Acquaviva C, Almardini R, Beck BB, Boyer O, Cerkauskiene R, Ferraro PM, Groen LA, Gupta A, Knebelmann B, Mandrile G, Moochhala SS, Prytula A, Putnik J, Rumsby G, Soliman NA, Somani B, Bacchetta J
Nat Rev Nephrol 2023 Mar;19(3):194-211. Epub 2023 Jan 5 doi: 10.1038/s41581-022-00661-1. PMID: 36604599
Demoulin N, Aydin S, Gillion V, Morelle J, Jadoul M
Am J Kidney Dis 2022 May;79(5):717-727. Epub 2021 Sep 9 doi: 10.1053/j.ajkd.2021.07.018. PMID: 34508834
Dimer NW, Schuck PF, Streck EL, Ferreira GC
An Acad Bras Cienc 2015 Aug;87(2 Suppl):1409-14. Epub 2015 Aug 4 doi: 10.1590/0001-3765201520150021. PMID: 26247153
Lorenzo V, Torres A, Salido E
Nefrologia 2014 May 21;34(3):398-412. Epub 2014 Apr 30 doi: 10.3265/Nefrologia.pre2014.Jan.12335. PMID: 24798559
Cochat P, Rumsby G
N Engl J Med 2013 Aug 15;369(7):649-58. doi: 10.1056/NEJMra1301564. PMID: 23944302

Therapy

Egli M, Manoharan M
Nucleic Acids Res 2023 Apr 11;51(6):2529-2573. doi: 10.1093/nar/gkad067. PMID: 36881759Free PMC Article
Ermer T, Nazzal L, Tio MC, Waikar S, Aronson PS, Knauf F
Nat Rev Nephrol 2023 Feb;19(2):123-138. Epub 2022 Nov 3 doi: 10.1038/s41581-022-00643-3. PMID: 36329260Free PMC Article
Friedrich M, Aigner A
BioDrugs 2022 Sep;36(5):549-571. Epub 2022 Aug 23 doi: 10.1007/s40259-022-00549-3. PMID: 35997897Free PMC Article
Garrelfs SF, Frishberg Y, Hulton SA, Koren MJ, O'Riordan WD, Cochat P, Deschênes G, Shasha-Lavsky H, Saland JM, Van't Hoff WG, Fuster DG, Magen D, Moochhala SH, Schalk G, Simkova E, Groothoff JW, Sas DJ, Meliambro KA, Lu J, Sweetser MT, Garg PP, Vaishnaw AK, Gansner JM, McGregor TL, Lieske JC; ILLUMINATE-A Collaborators
N Engl J Med 2021 Apr 1;384(13):1216-1226. doi: 10.1056/NEJMoa2021712. PMID: 33789010
Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS
Drug Saf 2008;31(1):53-65. doi: 10.2165/00002018-200831010-00005. PMID: 18095746

Prognosis

Demoulin N, Aydin S, Gillion V, Morelle J, Jadoul M
Am J Kidney Dis 2022 May;79(5):717-727. Epub 2021 Sep 9 doi: 10.1053/j.ajkd.2021.07.018. PMID: 34508834
McDougall R, Ramsden D, Agarwal S, Agarwal S, Aluri K, Arciprete M, Brown C, Castellanos-Rizaldos E, Charisse K, Chong S, Cichocki J, Fitzgerald K, Goel V, Gu Y, Guenther D, Habtemariam B, Jadhav V, Janas M, Jayaraman M, Kurz J, Li J, Liu J, Liu X, Liou S, Maclauchlin C, Maier M, Manoharan M, Nair JK, Robbie G, Schmidt K, Smith P, Theile C, Vaishnaw A, Waldron S, Xu Y, Zhang X, Zlatev I, Wu JT
Drug Metab Dispos 2022 Jun;50(6):781-797. Epub 2021 Jun 21 doi: 10.1124/dmd.121.000428. PMID: 34154993
Capolongo G, Zacchia M, Perna A, Viggiano D, Capasso G
Urolithiasis 2019 Feb;47(1):91-98. Epub 2018 Dec 18 doi: 10.1007/s00240-018-01104-y. PMID: 30564846
Hopp K, Cogal AG, Bergstralh EJ, Seide BM, Olson JB, Meek AM, Lieske JC, Milliner DS, Harris PC; Rare Kidney Stone Consortium
J Am Soc Nephrol 2015 Oct;26(10):2559-70. Epub 2015 Feb 2 doi: 10.1681/ASN.2014070698. PMID: 25644115Free PMC Article
Scheinman SJ
Semin Nephrol 1999 Jul;19(4):381-8. PMID: 10435676

Clinical prediction guides

Michael M, Groothoff JW, Shasha-Lavsky H, Lieske JC, Frishberg Y, Simkova E, Sellier-Leclerc AL, Devresse A, Guebre-Egziabher F, Bakkaloglu SA, Mourani C, Saqan R, Singer R, Willey R, Habtemariam B, Gansner JM, Bhan I, McGregor T, Magen D
Am J Kidney Dis 2023 Feb;81(2):145-155.e1. Epub 2022 Jul 14 doi: 10.1053/j.ajkd.2022.05.012. PMID: 35843439
McDougall R, Ramsden D, Agarwal S, Agarwal S, Aluri K, Arciprete M, Brown C, Castellanos-Rizaldos E, Charisse K, Chong S, Cichocki J, Fitzgerald K, Goel V, Gu Y, Guenther D, Habtemariam B, Jadhav V, Janas M, Jayaraman M, Kurz J, Li J, Liu J, Liu X, Liou S, Maclauchlin C, Maier M, Manoharan M, Nair JK, Robbie G, Schmidt K, Smith P, Theile C, Vaishnaw A, Waldron S, Xu Y, Zhang X, Zlatev I, Wu JT
Drug Metab Dispos 2022 Jun;50(6):781-797. Epub 2021 Jun 21 doi: 10.1124/dmd.121.000428. PMID: 34154993
Carbone A, Al Salhi Y, Tasca A, Palleschi G, Fuschi A, De Nunzio C, Bozzini G, Mazzaferro S, Pastore AL
Minerva Urol Nefrol 2018 Aug;70(4):393-400. Epub 2018 May 31 doi: 10.23736/S0393-2249.18.03113-2. PMID: 29856171
Moe OW, Xu LHR
J Nephrol 2018 Apr;31(2):189-196. Epub 2018 Jan 24 doi: 10.1007/s40620-018-0469-3. PMID: 29368300
Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS
Drug Saf 2008;31(1):53-65. doi: 10.2165/00002018-200831010-00005. PMID: 18095746

Recent systematic reviews

Metry EL, van Dijk LMM, Peters-Sengers H, Oosterveld MJS, Groothoff JW, Ploeg RJ, Stel VS, Garrelfs SF
Pediatr Nephrol 2021 Aug;36(8):2217-2226. Epub 2021 Apr 8 doi: 10.1007/s00467-021-05043-6. PMID: 33830344Free PMC Article
Witting C, Langman CB, Assimos D, Baum MA, Kausz A, Milliner D, Tasian G, Worcester E, Allain M, West M, Knauf F, Lieske JC
Clin J Am Soc Nephrol 2021 Mar 8;16(3):487-495. Epub 2020 Sep 8 doi: 10.2215/CJN.08000520. PMID: 32900691Free PMC Article
Huynh LM, Dianatnejad S, Tofani S, Carrillo Ceja R, Liang K, Tapiero S, Jiang P, Youssef RF
Scand J Urol 2020 Dec;54(6):456-462. Epub 2020 Nov 13 doi: 10.1080/21681805.2020.1840430. PMID: 33185135
Carbone A, Al Salhi Y, Tasca A, Palleschi G, Fuschi A, De Nunzio C, Bozzini G, Mazzaferro S, Pastore AL
Minerva Urol Nefrol 2018 Aug;70(4):393-400. Epub 2018 May 31 doi: 10.23736/S0393-2249.18.03113-2. PMID: 29856171
Upala S, Jaruvongvanich V, Sanguankeo A
Surg Obes Relat Dis 2016 Sep-Oct;12(8):1513-1521. Epub 2016 Apr 6 doi: 10.1016/j.soard.2016.04.004. PMID: 27396545

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