Advertisement

Urolithiasis

pp 1–11 | Cite as

Genetics of common complex kidney stone disease: insights from genome-wide association studies

  • Runolfur Palsson
  • Olafur S. Indridason
  • Vidar O. Edvardsson
  • Asmundur Oddsson
Invited Review
  • 7 Downloads

Abstract

Kidney stone disease is a common disorder in Western countries that is associated with significant suffering, morbidity, and cost for the healthcare system. Numerous studies have demonstrated familial aggregation of nephrolithiasis and a twin study estimated the heritability to be 56%. Over the past decade, genome-wide association studies have uncovered several sequence variants that confer increased risk of common complex kidney stone disease. The first reported variants were observed at the CLDN14 locus in the Icelandic population. This finding has since been replicated in other populations. The CLDN14 gene is expressed in tight junctions of the thick ascending limb of the loop of Henle, where the protein is believed to play a role in regulation of calcium transport. More recent studies have uncovered variants at the ALPL, SLC34A1, CASR, and TRPV5 loci, the first two genes playing a role in renal handling of phosphate, while the latter two are involved in calcium homeostasis. Although genetic data have provided insights into the molecular basis of kidney stone disease, much remains to be learned about the contribution of genetic factors to stone formation. Nevertheless, the progress made in recent years indicates that exciting times lie ahead in genetic research on kidney stone disease.

Keywords

Genealogy Genomics Genotyping Whole-genome sequencing Nephrolithiasis 

Notes

Acknowledgements

Drs. Edvardsson and Palsson are members of the Rare Kidney Stone Consortium which is funded through a collaboration between the NCATS and NIDDK in the US (2U54DK083908). Drs. Edvardsson, Indridason and Palsson have received grants from Landspitali University Hospital Science Fund and the University of Iceland Science Fund.

Compliance with ethical standards

Conflict of interest

Dr. Oddsson is an employee of deCODE genetics. Drs. Edvardsson, Indridason and Palsson are research collaborators of deCODE genetics. The authors declare no other conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors. The article contains no original data. The data presented are solely drawn from previously published work.

References

  1. 1.
    Scales CD Jr, Smith AC, Hanley JM, Saigal CS, Urologic Diseases in America Project (2012) Prevalence of kidney stones in the United States. Eur Urol 62(1):160–165.  https://doi.org/10.1016/j.eururo.2012.03.052 CrossRefGoogle Scholar
  2. 2.
    Hesse A, Brandle E, Wilbert D, Kohrmann KU, Alken P (2003) Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000. Eur Urol 44(6):709–713CrossRefGoogle Scholar
  3. 3.
    Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63(5):1817–1823CrossRefGoogle Scholar
  4. 4.
    Dwyer ME, Krambeck AE, Bergstralh EJ, Milliner DS, Lieske JC, Rule AD (2012) Temporal trends in incidence of kidney stones among children: a 25-year population based study. J Urol 188(1):247–252CrossRefGoogle Scholar
  5. 5.
    Edvardsson VO, Indridason OS, Haraldsson G, Kjartansson O, Palsson R (2013) Temporal trends in the incidence of kidney stone disease. Kidney Int 83(1):146–152.  https://doi.org/10.1038/ki.2012.320 CrossRefGoogle Scholar
  6. 6.
    Johnson CM, Wilson DM, O’Fallon WM, Malek RS, Kurland LT (1979) Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney Int 16(5):624–631CrossRefGoogle Scholar
  7. 7.
    Uribarri J, Oh MS, Carroll HJ (1989) The first kidney stone. Ann Intern Med 111(12):1006–1009CrossRefGoogle Scholar
  8. 8.
    Saigal CS, Joyce G, Timilsina AR, Urologic Diseases in America Project (2005) Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int 68(4):1808–1814.  https://doi.org/10.1111/j.1523-1755.2005.00599.x CrossRefGoogle Scholar
  9. 9.
    Lieske JC, Rule AD, Krambeck AE, Williams JC, Bergstralh EJ, Mehta RA, Moyer TP (2014) Stone composition as a function of age and sex. Clin J Am Soc Nephrol 9(12):2141–2146.  https://doi.org/10.2215/CJN.05660614 CrossRefGoogle Scholar
  10. 10.
    Coe FL, Worcester EM, Evan AP (2016) Idiopathic hypercalciuria and formation of calcium renal stones. Nat Rev Nephrol 12(9):519–533.  https://doi.org/10.1038/nrneph.2016.101 CrossRefGoogle Scholar
  11. 11.
    Coe FL, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115(10):2598–2608.  https://doi.org/10.1172/JCI26662 CrossRefGoogle Scholar
  12. 12.
    Coe FL (1977) Treated and untreated recurrent calcium nephrolithiasis in patients with idiopathic hypercalciuria, hyperuricosuria, or no metabolic disorder. Ann Intern Med 87(4):404–410CrossRefGoogle Scholar
  13. 13.
    Curhan GC (2007) Epidemiology of stone disease. Urol Clin North Am 34(3):287–293.  https://doi.org/10.1016/j.ucl.2007.04.003 CrossRefGoogle Scholar
  14. 14.
    Vezzoli G, Terranegra A, Arcidiacono T, Soldati L (2011) Genetics and calcium nephrolithiasis. Kidney Int 80(6):587–593.  https://doi.org/10.1038/ki.2010.430 CrossRefGoogle Scholar
  15. 15.
    Resnick M, Pridgen DB, Goodman HO (1968) Genetic predisposition to formation of calcium oxalate renal calculi. N Engl J Med 278(24):1313–1318CrossRefGoogle Scholar
  16. 16.
    Trinchieri A, Mandressi A, Luongo P, Coppi F, Pisani E (1988) Familial aggregation of renal calcium stone disease. J Urol 139(3):478–481CrossRefGoogle Scholar
  17. 17.
    Curhan GC, Willett WC, Rimm EB, Stampfer MJ (1997) Family history and risk of kidney stones. J Am Soc Nephrol 8(10):1568–1573Google Scholar
  18. 18.
    Goldfarb DS, Fischer ME, Keich Y, Goldberg J (2005) A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int 67(3):1053–1061CrossRefGoogle Scholar
  19. 19.
    Edvardsson VO, Palsson R, Indridason OS, Thorvaldsson S, Stefansson K (2009) Familiality of kidney stone disease in Iceland. Scand J Urol Nephrol 43(5):420–424.  https://doi.org/10.3109/00365590903151479 CrossRefGoogle Scholar
  20. 20.
    Hunter DJ, Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD (2002) Genetic contribution to renal function and electrolyte balance: a twin study. Clin Sci (Lond) 103(3):259–265CrossRefGoogle Scholar
  21. 21.
    Halbritter J, Baum M, Hynes AM, Rice SJ, Thwaites DT, Gucev ZS, Fisher B, Spaneas L, Porath JD, Braun DA, Wassner AJ, Nelson CP, Tasic V, Sayer JA, Hildebrandt F (2015) Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol 26(3):543–551.  https://doi.org/10.1681/ASN.2014040388 CrossRefGoogle Scholar
  22. 22.
    Monico CG, Milliner DS (2011) Genetic determinants of urolithiasis. Nat Rev Nephrol 8(3):151–162.  https://doi.org/10.1038/nrneph.2011.211 CrossRefGoogle Scholar
  23. 23.
    Braun DA, Lawson JA, Gee HY, Halbritter J, Shril S, Tan W, Stein D, Wassner AJ, Ferguson MA, Gucev Z, Fisher B, Spaneas L, Varner J, Sayer JA, Milosevic D, Baum M, Tasic V, Hildebrandt F (2016) Prevalence of monogenic causes in pediatric patients with nephrolithiasis or nephrocalcinosis. Clin J Am Soc Nephrol 11(4):664–672.  https://doi.org/10.2215/CJN.07540715 CrossRefGoogle Scholar
  24. 24.
    Arcidiacono T, Mingione A, Macrina L, Pivari F, Soldati L, Vezzoli G (2014) Idiopathic calcium nephrolithiasis: a review of pathogenic mechanisms in the light of genetic studies. Am J Nephrol 40(6):499–506.  https://doi.org/10.1159/000369833 CrossRefGoogle Scholar
  25. 25.
    Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273(5281):1516–1517CrossRefGoogle Scholar
  26. 26.
    International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437(7063):1299–1320.  https://doi.org/10.1038/nature04226 CrossRefGoogle Scholar
  27. 27.
    MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, Junkins H, McMahon A, Milano A, Morales J, Pendlington ZM, Welter D, Burdett T, Hindorff L, Flicek P, Cunningham F, Parkinson H (2017) The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res 45(D1):D896–D901.  https://doi.org/10.1093/nar/gkw1133 CrossRefGoogle Scholar
  28. 28.
    McCarthy S, Das S, Kretzschmar W, Haplotype Reference Consortium et al (2016) A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet 48(10):1279–1283.  https://doi.org/10.1038/ng.3643 CrossRefGoogle Scholar
  29. 29.
    1000 Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA (2012) An integrated map of genetic variation from 1092 human genomes. Nature 491(7422):56–65.  https://doi.org/10.1038/nature11632 CrossRefGoogle Scholar
  30. 30.
    Genome of the Netherlands Consortium (2014) Whole-genome sequence variation, population structure and demographic history of the Dutch population. Nat Genet 46(8):818–825.  https://doi.org/10.1038/ng.3021 CrossRefGoogle Scholar
  31. 31.
    Bomba L, Walter K, Soranzo N (2017) The impact of rare and low-frequency genetic variants in common disease. Genome Biol 18(1):77.  https://doi.org/10.1186/s13059-017-1212-4 CrossRefGoogle Scholar
  32. 32.
    NCI-NHGRI Working Group on Replication in Association Studies, Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF Jr, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL, Hoh J, Hoover R, Kong CA, Merikangas KR, Morton CC, Palmer LJ, Phimister EG, Rice JP, Roberts J, Rotimi C, Tucker MA, Vogan KJ, Wacholder S, Wijsman EM, Winn DM, Collins FS (2007) Replicating genotype-phenotype associations. Nature 447(7145):655–660.  https://doi.org/10.1038/447655a CrossRefGoogle Scholar
  33. 33.
    Pe’er I, Yelensky R, Altshuler D, Daly MJ (2008) Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 32(4):381–385.  https://doi.org/10.1002/gepi.20303 CrossRefGoogle Scholar
  34. 34.
    Sebastiani P, Solovieff N, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Perls TT (2010) Genetic signatures of exceptional longevity in humans. Science.  https://doi.org/10.1126/science.1190532 CrossRefGoogle Scholar
  35. 35.
    Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder A, Alam DS, Di Angelantonio E, Abecasis G, Chowdhury R, Erdmann J, Nordestgaard BG, Nielsen SF, Tybjaerg-Hansen A, Schmidt RF, Kuulasmaa K, Liu DJ, Perola M, Blankenberg S, Salomaa V, Mannisto S, Amouyel P, Arveiler D, Ferrieres J, Muller-Nurasyid M, Ferrario M, Kee F, Willer CJ, Samani N, Schunkert H, Butterworth AS, Howson JM, Peloso GM, Stitziel NO, Danesh J, Kathiresan S, Rader DJ, CHD Exome+ Consortium, CARDIoGRAM Exome Consortium, Global Lipids Genetics Consortium (2016) Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science 351(6278):1166–1171.  https://doi.org/10.1126/science.aad3517 CrossRefGoogle Scholar
  36. 36.
    1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA (2010) A map of human genome variation from population-scale sequencing. Nature 467(7319):1061–1073.  https://doi.org/10.1038/nature09534 CrossRefGoogle Scholar
  37. 37.
    Zhang J, Chiodini R, Badr A, Zhang G (2011) The impact of next-generation sequencing on genomics. J Genet Genomics 38(3):95–109.  https://doi.org/10.1016/j.jgg.2011.02.003 CrossRefGoogle Scholar
  38. 38.
    Sveinbjornsson G, Albrechtsen A, Zink F, Gudjonsson SA, Oddson A, Masson G, Holm H, Kong A, Thorsteinsdottir U, Sulem P, Gudbjartsson DF, Stefansson K (2016) Weighting sequence variants based on their annotation increases power of whole-genome association studies. Nat Genet 48(3):314–317.  https://doi.org/10.1038/ng.3507 CrossRefGoogle Scholar
  39. 39.
    Schork AJ, Thompson WK, Pham P, Torkamani A, Roddey JC, Sullivan PF, Kelsoe JR, O’Donovan MC, Furberg H, Tobacco and Genetics Consortium, Bipolar Disorder Psychiatric Genomics Consortium, Schizophrenia Psychiatric Genomics Consortium, Schork NJ, Andreassen OA, Dale AM (2013) All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs. PLoS Genet 9(4):e1003449.  https://doi.org/10.1371/journal.pgen.1003449 CrossRefGoogle Scholar
  40. 40.
    Thorleifsson G, Holm H, Edvardsson V, Walters GB, Styrkarsdottir U, Gudbjartsson DF, Sulem P, Halldorsson BV, de Vegt F, d’Ancona FC, den Heijer M, Franzson L, Christiansen C, Alexandersen P, Rafnar T, Kristjansson K, Sigurdsson G, Kiemeney LA, Bodvarsson M, Indridason OS, Palsson R, Kong A, Thorsteinsdottir U, Stefansson K (2009) Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density. Nat Genet 41(8):926–930.  https://doi.org/10.1038/ng.404 CrossRefGoogle Scholar
  41. 41.
    Gudbjartsson DF, Holm H, Indridason OS, Thorleifsson G, Edvardsson V, Sulem P, de Vegt F, d’Ancona FC, den Heijer M, Wetzels JF, Franzson L, Rafnar T, Kristjansson K, Bjornsdottir US, Eyjolfsson GI, Kiemeney LA, Kong A, Palsson R, Thorsteinsdottir U, Stefansson K (2010) Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases. PLoS Genet 6(7):e1001039.  https://doi.org/10.1371/journal.pgen.1001039 CrossRefGoogle Scholar
  42. 42.
    Hess B, Nakagawa Y, Coe FL (1989) Inhibition of calcium oxalate monohydrate crystal aggregation by urine proteins. Am J Physiol 257(1 Pt 2):F99–F106.  https://doi.org/10.1152/ajprenal.1989.257.1.F99 CrossRefGoogle Scholar
  43. 43.
    Urabe Y, Tanikawa C, Takahashi A, Okada Y, Morizono T, Tsunoda T, Kamatani N, Kohri K, Chayama K, Kubo M, Nakamura Y, Matsuda K (2012) A genome-wide association study of nephrolithiasis in the Japanese population identifies novel susceptible loci at 5q35.3, 7p14.3, and 13q14.1. PLoS Genet 8(3):e1002541.  https://doi.org/10.1371/journal.pgen.1002541 CrossRefGoogle Scholar
  44. 44.
    Prie D, Huart V, Bakouh N, Planelles G, Dellis O, Gerard B, Hulin P, Benque-Blanchet F, Silve C, Grandchamp B, Friedlander G (2002) Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 347(13):983–991.  https://doi.org/10.1056/NEJMoa020028 CrossRefGoogle Scholar
  45. 45.
    Oddsson A, Sulem P, Helgason H, Edvardsson VO, Thorleifsson G, Sveinbjornsson G, Haraldsdottir E, Eyjolfsson GI, Sigurdardottir O, Olafsson I, Masson G, Holm H, Gudbjartsson DF, Thorsteinsdottir U, Indridason OS, Palsson R, Stefansson K (2015) Common and rare variants associated with kidney stones and biochemical traits. Nat Commun 6:7975.  https://doi.org/10.1038/ncomms8975 CrossRefGoogle Scholar
  46. 46.
    Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjöstedt E, Lundberg E, Szigyarto CA, Skogs M, Takanen JO, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson A, von Feilitzen K, Forsberg M, Zwahlen M, Olsson I, Navani S, Huss M, Nielsen J, Ponten F, Uhlén M (2014) Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics 13(2):397–406.  https://doi.org/10.1074/mcp.M113.035600 CrossRefGoogle Scholar
  47. 47.
    Cooper GM, Stone EA, Asimenos G, Green ED, Batzoglou S, Sidow A. (2005) Distribution and intensity of constraint in mammalian genomic sequence. Genome Res 15(7):901–913CrossRefGoogle Scholar
  48. 48.
    Wang L, Holmes RP, Peng JB (2017) The L530R variation associated with recurrent kidney stones impairs the structure and function of TRPV5. Biochem Biophys Res Commun 492(3):362–367.  https://doi.org/10.1016/j.bbrc.2017.08.102 CrossRefGoogle Scholar
  49. 49.
    Li X, Dang X, Cheng Y, Zhang D, Zhang X, Zou T, Xing J (2018) Common variants in ALPL gene contribute to the risk of kidney stones in the Han Chinese population. Genet Test Mol Biomarkers 22(3):187–192.  https://doi.org/10.1089/gtmb.2017.0208 CrossRefGoogle Scholar
  50. 50.
    Tiselius HG (2011) A hypothesis of calcium stone formation: an interpretation of stone research during the past decades. Urol Res 39(4):231–243.  https://doi.org/10.1007/s00240-010-0349-3 CrossRefGoogle Scholar
  51. 51.
    Evan A, Lingeman J, Coe FL, Worcester E (2006) Randall’s plaque: pathogenesis and role in calcium oxalate nephrolithiasis. Kidney Int 69(8):1313–1318.  https://doi.org/10.1038/sj.ki.5000238 CrossRefGoogle Scholar
  52. 52.
    Jia Z, Wang S, Tang J, He D, Cui L, Liu Z, Guo B, Huang L, Lu Y, Hu H (2014) Does crystal deposition in genetic hypercalciuric rat kidney tissue share similarities with bone formation? Urology 83(2):509 e507–e514.  https://doi.org/10.1016/j.urology.2013.11.004 CrossRefGoogle Scholar
  53. 53.
    Tiselius HG (2013) The role of calcium phosphate in the development of Randall’s plaques. Urolithiasis 41(5):369–377.  https://doi.org/10.1007/s00240-013-0602-7 CrossRefGoogle Scholar
  54. 54.
    Stoller ML, Meng MV, Abrahams HM, Kane JP (2004) The primary stone event: a new hypothesis involving a vascular etiology. J Urol 171(5):1920–1924.  https://doi.org/10.1097/01.ju.0000120291.90839.49 CrossRefGoogle Scholar
  55. 55.
    Koleganova N, Piecha G, Ritz E, Schmitt CP, Gross ML (2009) A calcimimetic (R-568), but not calcitriol, prevents vascular remodeling in uremia. Kidney Int 75(1):60–71.  https://doi.org/10.1038/ki.2008.490 CrossRefGoogle Scholar
  56. 56.
    Tsukita S, Furuse M (2000) Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol 149(1):13–16CrossRefGoogle Scholar
  57. 57.
    Olinger E, Houillier P, Devuyst O (2018) Claudins: a tale of interactions in the thick ascending limb. Kidney Int 93(3):535–537.  https://doi.org/10.1016/j.kint.2017.09.032 CrossRefGoogle Scholar
  58. 58.
    Vezzoli G, Terranegra A, Soldati L (2012) Calcium-sensing receptor gene polymorphisms in patients with calcium nephrolithiasis. Curr Opin Nephrol Hypertens 21(4):355–361.  https://doi.org/10.1097/MNH.0b013e3283542290 CrossRefGoogle Scholar
  59. 59.
    Toka HR, Al-Romaih K, Koshy JM, DiBartolo S III, Kos CH, Quinn SJ, Curhan GC, Mount DB, Brown EM, Pollak MR (2012) Deficiency of the calcium-sensing receptor in the kidney causes parathyroid hormone-independent hypocalciuria. J Am Soc Nephrol 23(11):1879–1890.  https://doi.org/10.1681/ASN.2012030323 CrossRefGoogle Scholar
  60. 60.
    Gong Y, Renigunta V, Himmerkus N, Zhang J, Renigunta A, Bleich M, Hou J (2012) Claudin-14 regulates renal Ca++ transport in response to CaSR signalling via a novel microRNA pathway. EMBO J 31(8):1999–2012.  https://doi.org/10.1038/emboj.2012.49 CrossRefGoogle Scholar
  61. 61.
    Gong Y, Himmerkus N, Plain A, Bleich M, Hou J (2015) Epigenetic regulation of microRNAs controlling CLDN14 expression as a mechanism for renal calcium handling. J Am Soc Nephrol 26(3):663–676.  https://doi.org/10.1681/ASN.2014020129 CrossRefGoogle Scholar
  62. 62.
    Sato T, Courbebaisse M, Ide N, Fan Y, Hanai JI, Kaludjerovic J, Densmore MJ, Yuan Q, Toka HR, Pollak MR, Hou J, Lanske B (2017) Parathyroid hormone controls paracellular Ca2+ transport in the thick ascending limb by regulating the tight-junction protein Claudin14. Proc Natl Acad Sci USA 114(16):E3344–E3353.  https://doi.org/10.1073/pnas.1616733114 CrossRefGoogle Scholar
  63. 63.
    Arcidiacono T, Simonini M, Lanzani C, Citterio L, Salvi E, Barlassina C, Spotti D, Cusi D, Manunta P, Vezzoli G (2018) Claudin-14 gene polymorphisms and urine calcium excretion. Clin J Am Soc Nephrol 13(10):1542–1549.  https://doi.org/10.2215/CJN.01770218 CrossRefGoogle Scholar
  64. 64.
    Brown EM, MacLeod RJ (2001) Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81(1):239–297.  https://doi.org/10.1152/physrev.2001.81.1.239 CrossRefGoogle Scholar
  65. 65.
    Dimke H, Desai P, Borovac J, Lau A, Pan W, Alexander RT (2013) Activation of the Ca(2+)-sensing receptor increases renal claudin-14 expression and urinary Ca(2+) excretion. Am J Physiol Renal Physiol 304(6):F761–F769.  https://doi.org/10.1152/ajprenal.00263.2012 CrossRefGoogle Scholar
  66. 66.
    Blankenship KA, Williams JJ, Lawrence MS, McLeish KR, Dean WL, Arthur JM (2001) The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA. Am J Physiol Renal Physiol 280(5):F815–F822.  https://doi.org/10.1152/ajprenal.2001.280.5.F815 CrossRefGoogle Scholar
  67. 67.
    Sands JM, Naruse M, Baum M, Jo I, Hebert SC, Brown EM, Harris HW (1997) Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J Clin Invest 99(6):1399–1405.  https://doi.org/10.1172/JCI119299 CrossRefGoogle Scholar
  68. 68.
    Casare F, Milan D, Fernandez R (2014) Stimulation of calcium-sensing receptor increases biochemical H+-ATPase activity in mouse cortex and outer medullary regions. Can J Physiol Pharmacol 92(3):181–188.  https://doi.org/10.1139/cjpp-2013-0256 CrossRefGoogle Scholar
  69. 69.
    Capasso G, Geibel PJ, Damiano S, Jaeger P, Richards WG, Geibel JP (2013) The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule. Kidney Int 84(2):277–284.  https://doi.org/10.1038/ki.2013.137 CrossRefGoogle Scholar
  70. 70.
    Hoenderop JG, van Leeuwen JP, van der Eerden BC, Kersten FF, van der Kemp AW, Merillat AM, Waarsing JH, Rossier BC, Vallon V, Hummler E, Bindels RJ (2003) Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest 112(12):1906–1914.  https://doi.org/10.1172/JCI19826 CrossRefGoogle Scholar
  71. 71.
    Loh NY, Bentley L, Dimke H, Verkaart S, Tammaro P, Gorvin CM, Stechman MJ, Ahmad BN, Hannan FM, Piret SE, Evans H, Bellantuono I, Hough TA, Fraser WD, Hoenderop JG, Ashcroft FM, Brown SD, Bindels RJ, Cox RD, Thakker RV (2013) Autosomal dominant hypercalciuria in a mouse model due to a mutation of the epithelial calcium channel, TRPV5. PLoS One 8(1):e55412.  https://doi.org/10.1371/journal.pone.0055412 CrossRefGoogle Scholar
  72. 72.
    Wolf MT, Wu XR, Huang CL (2013) Uromodulin upregulates TRPV5 by impairing caveolin-mediated endocytosis. Kidney Int 84(1):130–137.  https://doi.org/10.1038/ki.2013.63 CrossRefGoogle Scholar
  73. 73.
    Santambrogio S, Cattaneo A, Bernascone I, Schwend T, Jovine L, Bachi A, Rampoldi L (2008) Urinary uromodulin carries an intact ZP domain generated by a conserved C-terminal proteolytic cleavage. Biochem Biophys Res Commun 370(3):410–413.  https://doi.org/10.1016/j.bbrc.2008.03.099 CrossRefGoogle Scholar
  74. 74.
    Nie M, Bal MS, Yang Z, Liu J, Rivera C, Wenzel A, Beck BB, Sakhaee K, Marciano DK, Wolf MT (2016) Mucin-1 increases renal TRPV5 activity in vitro, and urinary level associates with calcium nephrolithiasis in patients. J Am Soc Nephrol 27(11):3447–3458.  https://doi.org/10.1681/ASN.2015101100 CrossRefGoogle Scholar
  75. 75.
    Whyte MP (2010) Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci 1192:190–200.  https://doi.org/10.1111/j.1749-6632.2010.05387.x CrossRefGoogle Scholar
  76. 76.
    Moochhala SH, Sayer JA, Carr G, Simmons NL (2008) Renal calcium stones: insights from the control of bone mineralization. Exp Physiol 93(1):43–49.  https://doi.org/10.1113/expphysiol.2007.040790 CrossRefGoogle Scholar
  77. 77.
    Wagner CA, Hernando N, Forster IC, Biber J (2014) The SLC34 family of sodium-dependent phosphate transporters. Pflugers Arch 466(1):139–153.  https://doi.org/10.1007/s00424-013-1418-6 CrossRefGoogle Scholar
  78. 78.
    Escaramis G, Docampo E, Rabionet R (2015) A decade of structural variants: description, history and methods to detect structural variation. Brief Funct Genomics 14(5):305–314.  https://doi.org/10.1093/bfgp/elv014 CrossRefGoogle Scholar
  79. 79.
    Shendure J, Balasubramanian S, Church GM, Gilbert W, Rogers J, Schloss JA, Waterston RH (2017) DNA sequencing at 40: past, present and future. Nature 550(7676):345–353.  https://doi.org/10.1038/nature24286 CrossRefGoogle Scholar
  80. 80.
    Zaidi SK, Young DW, Montecino MA, Lian JB, van Wijnen AJ, Stein JL, Stein GS (2010) Mitotic bookmarking of genes: a novel dimension to epigenetic control. Nat Rev Genet 11(8):583–589.  https://doi.org/10.1038/nrg2827 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Faculty of Medicine, School of Health SciencesUniversity of IcelandReykjavikIceland
  2. 2.Division of Nephrology, Internal Medicine ServicesLandspitali–The National University Hospital of IcelandReykjavikIceland
  3. 3.Children’s Medical CenterLandspitali–The National University Hospital of IcelandReykjavikIceland
  4. 4.Department of StatisticsdeCODE geneticsReykjavikIceland

Personalised recommendations