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Calcium oxalate nephrolithiasis

MedGen UID:
318935
Concept ID:
C1833683
Disease or Syndrome
Synonyms: Calcium oxalate urolithiasis; Nephrolithiasis susceptibility caused by SLC26A1
SNOMED CT: Calcium oxalate urolithiasis (444717006)
 
Gene (location): SLC26A1 (4p16.3)
 
HPO: HP:0008672
Monarch Initiative: MONDO:0020722
OMIM®: 167030

Definition

Kleta (2006) reviewed aspects of renal stone disease. Nephrolithiasis and urolithiasis remain major public health problems of largely unknown cause. While disorders such as cystinuria (220100) and primary hyperoxaluria (see 259900) that have nephrolithiasis as a major feature have advanced understanding of the metabolic and physiologic processes of stone formation in general, they have not addressed the etiology of calcium oxalate stone formation, responsible for approximately 75% of urolithiasis cases in humans. Men are affected twice as often as women, but children show no such gender bias. The recurrence rate is also high. In populations of European ancestry, 5 to 10% of adults experience the painful precipitation of calcium oxalate in their urinary tracts. Thorleifsson et al. (2009) noted that between 35 and 65% of hypercalciuric stone formers and up to 70% of subjects with hypercalciuria have relatives with nephrolithiasis, and twin studies have estimated the heritability of kidney stones to be 56%. Genetic Heterogeneity of Calcium Oxalate Nephrolithiasis See also CAON2 (620374), caused by mutation in the OXGR1 gene (606922) on chromosome 13q32. [from OMIM]

Clinical features

From HPO
Hyperoxaluria
MedGen UID:
43782
Concept ID:
C0020500
Disease or Syndrome
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.\n\nPrimary 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.\n\nThere 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.
Ureteropelvic junction obstruction
MedGen UID:
105482
Concept ID:
C0521619
Anatomical Abnormality
Blockage of urine flow from the renal pelvis to the proximal ureter.
Calcium oxalate nephrolithiasis
MedGen UID:
318935
Concept ID:
C1833683
Disease or Syndrome
Kleta (2006) reviewed aspects of renal stone disease. Nephrolithiasis and urolithiasis remain major public health problems of largely unknown cause. While disorders such as cystinuria (220100) and primary hyperoxaluria (see 259900) that have nephrolithiasis as a major feature have advanced understanding of the metabolic and physiologic processes of stone formation in general, they have not addressed the etiology of calcium oxalate stone formation, responsible for approximately 75% of urolithiasis cases in humans. Men are affected twice as often as women, but children show no such gender bias. The recurrence rate is also high. In populations of European ancestry, 5 to 10% of adults experience the painful precipitation of calcium oxalate in their urinary tracts. Thorleifsson et al. (2009) noted that between 35 and 65% of hypercalciuric stone formers and up to 70% of subjects with hypercalciuria have relatives with nephrolithiasis, and twin studies have estimated the heritability of kidney stones to be 56%. Genetic Heterogeneity of Calcium Oxalate Nephrolithiasis See also CAON2 (620374), caused by mutation in the OXGR1 gene (606922) on chromosome 13q32.
Acute kidney injury
MedGen UID:
388570
Concept ID:
C2609414
Injury or Poisoning
Sudden loss of renal function, as manifested by decreased urine production, and a rise in serum creatinine or blood urea nitrogen concentration (azotemia).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCalcium oxalate nephrolithiasis

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.
5-Oxoprolinase deficiency
MedGen UID:
82814
Concept ID:
C0268525
Disease or Syndrome
5-Oxoprolinuria can be caused by genetic defects in either of 2 enzymes involved in the gamma-glutamyl cycle of glutathione metabolism: glutathione synthetase (GSS; 601002) or 5-oxoprolinase (OPLAH; 614243). GSS deficiency (266130) is best characterized as an inborn error of glutathione metabolism, but there is debate as to whether OPLAH deficiency represents a disorder or simply a biochemical condition with no adverse clinical effects because patients lack a consistent clinical picture apart from 5-oxoprolinuria (summary by Calpena et al., 2013).
Familial idiopathic hypercalciuria
MedGen UID:
137974
Concept ID:
C0342639
Congenital Abnormality
Hyperglycinuria
MedGen UID:
107456
Concept ID:
C0543541
Disease or Syndrome
The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG; 242600), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG) (summary by Broer et al., 2008). A phenotype of combined glucosuria and glycinuria has been described (see 138070).
Calcium oxalate nephrolithiasis
MedGen UID:
318935
Concept ID:
C1833683
Disease or Syndrome
Kleta (2006) reviewed aspects of renal stone disease. Nephrolithiasis and urolithiasis remain major public health problems of largely unknown cause. While disorders such as cystinuria (220100) and primary hyperoxaluria (see 259900) that have nephrolithiasis as a major feature have advanced understanding of the metabolic and physiologic processes of stone formation in general, they have not addressed the etiology of calcium oxalate stone formation, responsible for approximately 75% of urolithiasis cases in humans. Men are affected twice as often as women, but children show no such gender bias. The recurrence rate is also high. In populations of European ancestry, 5 to 10% of adults experience the painful precipitation of calcium oxalate in their urinary tracts. Thorleifsson et al. (2009) noted that between 35 and 65% of hypercalciuric stone formers and up to 70% of subjects with hypercalciuria have relatives with nephrolithiasis, and twin studies have estimated the heritability of kidney stones to be 56%. Genetic Heterogeneity of Calcium Oxalate Nephrolithiasis See also CAON2 (620374), caused by mutation in the OXGR1 gene (606922) on chromosome 13q32.
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.
Macrocephaly/megalencephaly syndrome, autosomal recessive
MedGen UID:
812742
Concept ID:
C3806412
Disease or Syndrome
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).

Professional guidelines

PubMed

Tracy CR, Pearle MS
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Pak CY, Peterson R
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Recent clinical studies

Etiology

Halbritter J
Nephrol Ther 2021 Apr;17S:S88-S94. doi: 10.1016/j.nephro.2020.02.003. PMID: 33910705
Ticinesi A, Nouvenne A, Chiussi G, Castaldo G, Guerra A, Meschi T
Nutrients 2020 Feb 20;12(2) doi: 10.3390/nu12020548. PMID: 32093202Free PMC Article
O'Kell AL, Grant DC, Khan SR
Urolithiasis 2017 Aug;45(4):329-336. Epub 2017 Mar 30 doi: 10.1007/s00240-017-0978-x. PMID: 28361470Free PMC Article
Rendina D, De Filippo G, Zampa G, Muscariello R, Mossetti G, Strazzullo P
Nephrol Dial Transplant 2011 Jul;26(7):2256-63. Epub 2010 Nov 4 doi: 10.1093/ndt/gfq664. PMID: 21051502
Evan A, Lingeman J, Coe FL, Worcester E
Kidney Int 2006 Apr;69(8):1313-8. doi: 10.1038/sj.ki.5000238. PMID: 16614720

Diagnosis

Bargagli M, Tio MC, Waikar SS, Ferraro PM
Nutrients 2020 Sep 2;12(9) doi: 10.3390/nu12092673. PMID: 32887293Free PMC Article
Nelson WK, Houghton SG, Milliner DS, Lieske JC, Sarr MG
Surg Obes Relat Dis 2005 Sep-Oct;1(5):481-5. Epub 2005 Aug 26 doi: 10.1016/j.soard.2005.07.002. PMID: 16925274
Selvam R, Kalaiselvi P
Urol Res 2003 Aug;31(4):242-56. Epub 2003 Jul 11 doi: 10.1007/s00240-003-0316-3. PMID: 12856168
Ruml LA, Pearle MS, Pak CY
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Gambaro G, Baggio B
Scanning Microsc 1992 Mar;6(1):247-54. PMID: 1626244

Therapy

Bargagli M, Tio MC, Waikar SS, Ferraro PM
Nutrients 2020 Sep 2;12(9) doi: 10.3390/nu12092673. PMID: 32887293Free PMC Article
Ticinesi A, Nouvenne A, Chiussi G, Castaldo G, Guerra A, Meschi T
Nutrients 2020 Feb 20;12(2) doi: 10.3390/nu12020548. PMID: 32093202Free PMC Article
Le Dudal M, Huguet L, Perez J, Vandermeersch S, Bouderlique E, Tang E, Martori C, Chemaly N, Nabbout R, Haymann JP, Frochot V, Baud L, Deschênes G, Daudon M, Letavernier E
J Clin Invest 2019 Apr 4;129(6):2571-2577. doi: 10.1172/JCI99822. PMID: 30946030Free PMC Article
Holmes RP, Knight J, Assimos DG
Urolithiasis 2016 Feb;44(1):27-32. Epub 2015 Nov 27 doi: 10.1007/s00240-015-0839-4. PMID: 26614109Free PMC Article
Massey L
Magnes Res 2005 Jun;18(2):123-6. PMID: 16100850

Prognosis

Liu M, Devlin JC, Hu J, Volkova A, Battaglia TW, Ho M, Asplin JR, Byrd A, Loke P, Li H, Ruggles KV, Tsirigos A, Blaser MJ, Nazzal L
Elife 2021 Mar 26;10 doi: 10.7554/eLife.63642. PMID: 33769280Free PMC Article
Tran TVM, Li X, Adams-Huet B, Maalouf NM
Urolithiasis 2021 Dec;49(6):495-504. Epub 2021 Feb 13 doi: 10.1007/s00240-021-01254-6. PMID: 33582830Free PMC Article
Rendina D, De Filippo G, Zampa G, Muscariello R, Mossetti G, Strazzullo P
Nephrol Dial Transplant 2011 Jul;26(7):2256-63. Epub 2010 Nov 4 doi: 10.1093/ndt/gfq664. PMID: 21051502
Taylor EN, Curhan GC
J Am Soc Nephrol 2007 Jul;18(7):2198-204. Epub 2007 May 30 doi: 10.1681/ASN.2007020219. PMID: 17538185
Nelson WK, Houghton SG, Milliner DS, Lieske JC, Sarr MG
Surg Obes Relat Dis 2005 Sep-Oct;1(5):481-5. Epub 2005 Aug 26 doi: 10.1016/j.soard.2005.07.002. PMID: 16925274

Clinical prediction guides

Halbritter J
Nephrol Ther 2021 Apr;17S:S88-S94. doi: 10.1016/j.nephro.2020.02.003. PMID: 33910705
Liu M, Devlin JC, Hu J, Volkova A, Battaglia TW, Ho M, Asplin JR, Byrd A, Loke P, Li H, Ruggles KV, Tsirigos A, Blaser MJ, Nazzal L
Elife 2021 Mar 26;10 doi: 10.7554/eLife.63642. PMID: 33769280Free PMC Article
Hatch M, Freel RW
Semin Nephrol 2008 Mar;28(2):143-51. doi: 10.1016/j.semnephrol.2008.01.007. PMID: 18359395Free PMC Article
Selvam R, Kalaiselvi P
Urol Res 2003 Aug;31(4):242-56. Epub 2003 Jul 11 doi: 10.1007/s00240-003-0316-3. PMID: 12856168
Gambaro G, Baggio B
Scanning Microsc 1992 Mar;6(1):247-54. PMID: 1626244

Recent systematic reviews

Liu Y, Sun Y, Kang J, He Z, Liu Q, Wu J, Li D, Wang X, Tao Z, Guan X, She W, Xu H, Deng Y
Front Immunol 2022;13:818625. Epub 2022 Jan 27 doi: 10.3389/fimmu.2022.818625. PMID: 35154136Free PMC Article
Khan A, Bashir S, Khan SR
Urolithiasis 2021 Apr;49(2):95-122. Epub 2021 Jan 23 doi: 10.1007/s00240-020-01236-0. PMID: 33484322

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