, Volume 47, Issue 1, pp 35–42 | Cite as

Inherited proximal tubular disorders and nephrolithiasis

  • Ben Oliveira
  • Robert Unwin
  • Stephen B. WalshEmail author
Invited Review


The proximal tubule is responsible for reclaiming water, phosphates and amino acids from the tubular filtrate. There are genetic defects in both phosphate and amino acid transporters leading to nephrolithiasis. This review also explores genetic defects in regulators of phosphate and calcium transport in this nephron segment that lead to stone formation.


Nephrolithiasis Physiology Tubular 


Compliance with ethical standards

Conflict of interest

None of the authors have any conflicts of interest to declare.


  1. 1.
    Curthoys NP, Moe OW (2014) Proximal tubule function and response to acidosis. Clin J Am Soc Nephrol 9:1627–1638. CrossRefGoogle Scholar
  2. 2.
    Jones G, Prosser DE, Kaufmann M (2012) 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. Arch Biochem Biophys 523:9–18. CrossRefGoogle Scholar
  3. 3.
    Wagner CA, Hernando N, Forster IC, Biber J (2014) The SLC34 family of sodium-dependent phosphate transporters. Pflug Arch 466:139–153. CrossRefGoogle Scholar
  4. 4.
    Villa-Bellosta R, Ravera S, Sorribas V, Stange G, Levi M, Murer H, Biber J, Forster IC (2009) The Na+-Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi. Am J Physiol Ren Physiol 296:F691–F699. CrossRefGoogle Scholar
  5. 5.
    Ullrich KJ, Murer H (1982) Sulphate and phosphate transport in the renal proximal tubule. Philos Trans R Soc Lond B Biol Sci 299:549–558CrossRefGoogle Scholar
  6. 6.
    Offermanns S, Iida-Klein A, Segre GV, Simon MI (2009) G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells. Mol Endocrinol. Google Scholar
  7. 7.
    Abou-Samra AB, Jüppner H, Force T, Freeman MW, Kong XF, Schipani E, Urena P, Richards J, Bonventre JV, Potts JT (1992) Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium. Proc Natl Acad Sci 89:2732–2736. CrossRefGoogle Scholar
  8. 8.
    Mahon MJ, Donowitz M, Yun CC, Segre GV (2002) Na(+)/H(+) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Nature 417:858–861. CrossRefGoogle Scholar
  9. 9.
    Gisler SM, Stagljar I, Traebert M, Bacic D, Biber J, Murer H (2001) Interaction of the type IIa Na/Pi cotransporter with PDZ proteins. J Biol Chem 276:9206–9213. CrossRefGoogle Scholar
  10. 10.
    Murer H, Hernando N, Forster I, Biber J (2000) Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev 80:1373–1409CrossRefGoogle Scholar
  11. 11.
    Bacic D, Schulz N, Biber J, Kaissling B, Murer H, Wagner CA (2003) Involvement of the MAPK-kinase pathway in the PTH-mediated regulation of the proximal tubule type IIa Na+/Pi cotransporter in mouse kidney. Pflug Arch 446:52–60. CrossRefGoogle Scholar
  12. 12.
    Collazo R, Fan L, Hu MC, Zhao H, Wiederkehr MR, Moe OW (2000) Acute regulation of Na+/H+ exchanger NHE3 by parathyroid hormone via NHE3 phosphorylation and dynamin-dependent endocytosis. J Biol Chem 275:31601–31608. CrossRefGoogle Scholar
  13. 13.
    Schnermann J, Huang Y, Mizel D (2013) Fluid reabsorption in proximal convoluted tubules of mice with gene deletions of claudin-2 and/or aquaporin1. Am J Physiol Ren Physiol 305:F1352–F1364. CrossRefGoogle Scholar
  14. 14.
    Agus ZS, Gardner LB, Beck LH, Goldberg M (1973) Effects of parathyroid hormone on renal tubular reabsorption of calcium, sodium, and phosphate. Am J Physiol 224:1143–1148. CrossRefGoogle Scholar
  15. 15.
    Edwards BR, Baer PG, Sutton RAL, Dirks JH (1973) Micropuncture study of diuretic effects on sodium and calcium reabsorption in the dog nephron. J Clin Investig 52:2418–2427CrossRefGoogle Scholar
  16. 16.
    Pan W, Borovac J, Spicer Z, Hoenderop JG, Bindels RJ, Shull GE, Doschak MR, Cordat E, Alexander RT (2011) The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption. Am J Physiol Ren Physiol 302:F943–F956. CrossRefGoogle Scholar
  17. 17.
    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 84:277–284. CrossRefGoogle Scholar
  18. 18.
    Ba J, Brown D, Friedman PA (2003) Calcium-sensing receptor regulation of PTH-inhibitable proximal tubule phosphate transport. Am J Physiol Ren Physiol 285:F1233–F1243. CrossRefGoogle Scholar
  19. 19.
    Riccardi D, Lee WS, Lee K, Segre GV, Brown EM, Hebert SC (1996) Localization of the extracellular Ca(2+)-sensing receptor and PTH/PTHrP receptor in rat kidney. Am J Physiol 271:F951–F956. Google Scholar
  20. 20.
    Riccardi D, Hall AE, Chattopadhyay N, Xu JZ, Brown EM, Hebert SC (1998) Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat kidney. Am J Physiol 274:F611–F622Google Scholar
  21. 21.
    Loupy A, Ramakrishnan SK, Wootla B, Chambrey R, de la Faille R, Bourgeois S, Bruneval P, Mandet C, Christensen EI, Faure H, Cheval L, Laghmani K, Collet C, Eladari D, Dodd RH, Ruat M, Houillier P (2012) PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor. J Clin Investig 122:3355–3367. CrossRefGoogle Scholar
  22. 22.
    Graca J. Schepelmann Z, Brennan M, Reens SC, Chang J, Yan W, Toka P, Riccardi H, Price D SA (2016) Comparative expression of the extracellular calcium-sensing receptor in the mouse, rat, and human kidney. Am J Physiol Ren Physiol 310:F518–F533. CrossRefGoogle Scholar
  23. 23.
    Farrow EG, Davis SI, Summers LJ, White KE (2009) Initial FGF23-mediated signaling occurs in the distal convoluted tubule. J Am Soc Nephrol 20:955–960. CrossRefGoogle Scholar
  24. 24.
    Shimada T, Yamazaki Y, Takahashi M, Hasegawa H, Urakawa I, Oshima T, Ono K, Kakitani M, Tomizuka K, Fujita T, Fukumoto S, Yamashita T (2005) Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. Am J Physiol Ren Physiol 289:F1088–F1095. CrossRefGoogle Scholar
  25. 25.
    Hartmann CM, Hewson AS, Kos CH, Hilfiker H, Soumounou Y, Murer H, Tenenhouse HS (1996) Structure of murine and human renal type II Na+-phosphate cotransporter genes (Npt2 and NPT2). Proc Natl Acad Sci USA 93:7409–7414CrossRefGoogle Scholar
  26. 26.
    Kos CH, Tihy F, Econs MJ, Murer H, Lemieux N, Tenenhouse HS (1994) Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35. Genomics 19:176–177. CrossRefGoogle Scholar
  27. 27.
    Magen D, Berger L, Coady MJ, Ilivitzki A, Militianu D, Tieder M, Selig S, Lapointe JY, Zelikovic I, Skorecki K (2010) A loss-of-function mutation in NaPi-IIa and renal Fanconi’s syndrome. N Engl J Med 362:1102–1109. CrossRefGoogle Scholar
  28. 28.
    Schlingmann KP, Ruminska J, Kaufmann M, Dursun I, Patti M, Kranz B, Pronicka E, Ciara E, Akcay T, Bulus D, Cornelissen EAM, Gawlik A, Sikora P, Patzer L, Galiano M, Boyadzhiev V, Dumic M, Vivante A, Kleta R, Dekel B, Levtchenko E, Bindels RJ, Rust S, Forster IC, Hernando N, Jones G, Wagner CA, Konrad M (2016) Autosomal-recessive mutations in SLC34A1 encoding sodium-phosphate cotransporter 2A cause idiopathic infantile hypercalcemia. J Am Soc Nephrol 27:604–614. CrossRefGoogle Scholar
  29. 29.
    Demir K, Yıldız M, Bahat H, Goldman M, Hassan N, Tzur S, Ofir A, Magen D (2017) Clinical heterogeneity and phenotypic expansion of NaPi-IIa-associated disease. J Clin Endocrinol Metab 102:4604–4614. CrossRefGoogle Scholar
  30. 30.
    Prié D, Huart V, Bakouh N, Planelles G, Dellis O, Gérard B, Hulin P, Benqué-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 347:983–991. CrossRefGoogle Scholar
  31. 31.
    Virkki LV, Forster IC, Hernando N, Biber J, Murer H (2009) Functional characterization of two naturally occurring mutations in the human sodium–phosphate cotransporter type IIa. J Bone Miner Res 18:2135–2141. CrossRefGoogle Scholar
  32. 32.
    Capuano P, Bacic D, Roos M, Gisler SM, Stange G, Biber J, Kaissling B, Weinman EJ, Shenolikar S, Wagner CA, Murer H (2007) Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. Am J Physiol Cell Physiol 292:C927–C934. CrossRefGoogle Scholar
  33. 33.
    Karim Z, Gérard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prié D (2008) NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med 359:1128–1135. CrossRefGoogle Scholar
  34. 34.
    Courbebaisse M, Leroy C, Bakouh N, Salaün C, Beck L, Grandchamp B, Planelles G, Hall RA, Friedlander G, Prié D (2012) A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism. PLoS ONE. Google Scholar
  35. 35.
    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. Google Scholar
  36. 36.
    Kestenbaum B, Glazer NL, Köttgen A, Felix JF, Hwang S-J, Liu Y, Lohman K, Kritchevsky SB, Hausman DB, Petersen A-K, Gieger C, Ried JS, Meitinger T, Strom TM, Wichmann HE, Campbell H, Hayward C, Rudan I, de Boer IH, Psaty BM, Rice KM, Chen Y-DI, Li M, Arking DE, Boerwinkle E, Coresh J, Yang Q, Levy D, van Rooij FJA, Dehghan A, Rivadeneira F, Uitterlinden AG, Hofman A, van Duijn CM, Shlipak MG, Kao WHL, Witteman JCM, Siscovick DS, Fox CS (2010) Common genetic variants associate with serum phosphorus concentration. J Am Soc Nephrol 21:1223–1232. CrossRefGoogle Scholar
  37. 37.
    Beck L, Karaplis AC, Amizuka N, Hewson AS, Ozawa H, Tenenhouse HS (1998) Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci USA 95:5372–5377CrossRefGoogle Scholar
  38. 38.
    Lorenz-Depiereux B, Benet-Pages A, Eckstein G, Tenenbaum-Rakover Y, Wagenstaller J, Tiosano D, Gershoni-Baruch R, Albers N, Lichtner P, Schnabel D, Hochberg Z, Strom TM (2006) Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet 78:193–201. CrossRefGoogle Scholar
  39. 39.
    Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabédian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Jüppner H (2006) SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 78:179–192. CrossRefGoogle Scholar
  40. 40.
    Tieder M, Modai D, Samuel R, Arie R, Halabe A, Bab I, Gabizon D, Liberman UA (1985) Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med 312:611–617. CrossRefGoogle Scholar
  41. 41.
    Phulwani P, Bergwitz C, Jaureguiberry G, Rasoulpour M, Estrada E (2011) Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis—identification of a novel SLC34A3/NaPi-IIc mutation. Am J Med Genet A 155A(3):626–633. CrossRefGoogle Scholar
  42. 42.
    Wolf MTF, Zalewski I, Martin FC, Ruf R, Müller D, Hennies HC, Schwarz S, Panther F, Attanasio M, Acosta HG, Imm A, Lucke B, Utsch B, Otto E, Nurnberg P, Nieto VG, Hildebrandt F (2005) Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2–q34.2 by total genome search for linkage. Nephrol Dial Transplant 20:909–914. CrossRefGoogle Scholar
  43. 43.
    Dasgupta D, Wee MJ, Reyes M, Li Y, Simm PJ, Sharma A, Schlingmann K-P, Janner M, Biggin A, Lazier J, Gessner M, Chrysis D, Tuchman S, Baluarte HJ, Levine MA, Tiosano D, Insogna K, Hanley DA, Carpenter TO, Ichikawa S, Hoppe B, Konrad M, Sävendahl L, Munns CF, Lee H, Jüppner H, Bergwitz C (2014) Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol 25:2366–2375. CrossRefGoogle Scholar
  44. 44.
    Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Bröking E, Fehrenbach H, Wingen AM, Güran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365:410–421. CrossRefGoogle Scholar
  45. 45.
    Nesterova G, Malicdan MC, Yasuda K, Sakaki T, Vilboux T, Ciccone C, Horst R, Huang Y, Golas G, Introne W, Huizing M, Adams D, Boerkoel CF, Collins MT, Gahl WA (2013) 1,25-(OH)2D-24 hydroxylase (CYP24A1) deficiency as a cause of nephrolithiasis. Clin J Am Soc Nephrol 8:649–657. CrossRefGoogle Scholar
  46. 46.
    Vezzoli G, Terranegra A, Soldati L (2012) Calcium-sensing receptor gene polymorphisms in patients with calcium nephrolithiasis. Curr Opin Nephrol Hypertens 21:355–361. CrossRefGoogle Scholar
  47. 47.
    Vezzoli G, Terranegra A, Arcidiacono T, Biasion R, Coviello D, Syren ML, Paloschi V, Giannini S, Mignogna G, Rubinacci A, Ferraretto A, Cusi D, Bianchi G, Soldati L (2007) R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hypercalciuria. Kidney Int 71:1155–1162. CrossRefGoogle Scholar
  48. 48.
    Harding B, Curley AJ, Hannan FM, Christie PT, Bowl MR, Turner JJO, Barber M, Gillham-Nasenya I, Hampson G, Spector TD, Thakker RV (2006) Functional characterization of calcium sensing receptor polymorphisms and absence of association with indices of calcium homeostasis and bone mineral density. Clin Endocrinol (Oxf) 65:598–605. CrossRefGoogle Scholar
  49. 49.
    Vezzoli G, Scillitani A, Corbetta S, Terranegra A, Dogliotti E, Guarnieri V, Arcidiacono T, Macrina L, Mingione A, Brasacchio C, Eller-Vainicher C, Cusi D, Spada A, Cole DEC, Hendy GN, Spotti D, Soldati L (2015) Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene. J Nephrol 28:67–72. CrossRefGoogle Scholar
  50. 50.
    Dent CE, Friedman M (1964) Hypercalcuric rickets associated with renal tubular damage. Arch Dis Child 39:240–249CrossRefGoogle Scholar
  51. 51.
    Wrong OM, Norden AGW, Feest TG (1994) Dent’s disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. QJM 87:473–493Google Scholar
  52. 52.
    Scheinman SJ, Pook MA, Wooding C, Pang JT, Frymoyer PA, Thakker RV (1993) Mapping the gene causing X-linked recessive nephrolithiasis to Xp11.22 by linkage studies. J Clin Investig 91:2351–2357CrossRefGoogle Scholar
  53. 53.
    Lloyd SE, Pearce SH, Fisher SE, Steinmeyer K, Schwappach B, Scheinman SJ, Harding B, Bolino A, Devoto M, Goodyer P, Rigden SP, Wrong O, Jentsch TJ, Craig IW, Thakker RV (1996) A common molecular basis for three inherited kidney stone diseases. Nature 379:445–449. CrossRefGoogle Scholar
  54. 54.
    Devuyst O, Thakker RV (2010) Dent’s disease. Orphanet J Rare Dis 5:28. CrossRefGoogle Scholar
  55. 55.
    Unwin R, Fine L, Cohen E, Thakker R, Tanner M (1996) Unravelling of the molecular mechanisms of kidney stones. Lancet 348:1561–1565. CrossRefGoogle Scholar
  56. 56.
    Ludwig M, Utsch B, Balluch B, Fründ S, Kuwertz-Bröking E, Bökenkamp A (2006) Hypercalciuria in patients with CLCN5 mutations. Pediatr Nephrol 21:1241–1250. CrossRefGoogle Scholar
  57. 57.
    Sayer JA, Carr G, Simmons NL (2004) Calcium phosphate and calcium oxalate crystal handling is dependent upon CLC-5 expression in mouse collecting duct cells. Biochim Biophys Acta Mol Basis Dis 1689:83–90. CrossRefGoogle Scholar
  58. 58.
    Piwon N, Günther W, Schwake M, Bösl MR, Jentsch TJ (2000) ClC-5 Cl channel disruption impairs endocytosis in a mouse model for Dent’s disease. Nature 408:369–373. CrossRefGoogle Scholar
  59. 59.
    Hoopes RR Jr, Shrimpton AE, Knohl SJ, Hueber P, Hoppe B, Matyus J, Simckes A, Tasic V, Toenshoff B, Suchy SF, Nussbaum RL, Scheinman SJ (2005) Dent disease with mutations in OCRL1. Am J Hum Genet 76:260–267. CrossRefGoogle Scholar
  60. 60.
    Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N’Guyen HV, Noël C, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M, French Cystinuria Group (2015) CKD and its risk factors among patients with cystinuria. Clin J Am Soc Nephrol 10:842–851. CrossRefGoogle Scholar
  61. 61.
    Calonge MJ, Gasparini P, Chillarón J, Chillón M, Gallucci M, Rousaud F, Zelante L, Testar X, Dallapiccola B, Di Silverio F (1994) Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine. Nat Genet 6:420–425. CrossRefGoogle Scholar
  62. 62.
    Feliubadaló L, Font M, Purroy J, Rousaud F, Estivill X, Nunes V, Golomb E, Centola M, Aksentijevich I, Kreiss Y, Goldman B, Pras M, Kastner DL, Pras E, Gasparini P, Bisceglia L, Beccia E, Gallucci M, de Sanctis L, Ponzone A, Rizzoni GF, Zelante L, Bassi MT, George AL, Manzoni M, De Grandi A, Riboni M, Endsley JK, Ballabio A, Borsani G, Reig N, Fernández E, Estévez R, Pineda M, Torrents D, Camps M, Lloberas J, Zorzano A, Palacín M, International Cystinuria Consortium (1999) Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT. Nat Genet 23:52–57. CrossRefGoogle Scholar
  63. 63.
    Chillarón J, Font-Llitjós M, Fort J, Zorzano A, Goldfarb DS, Nunes V, Palacín M (2010) Pathophysiology and treatment of cystinuria. Nat Rev Nephrol 6:424–434. CrossRefGoogle Scholar
  64. 64.
    Bowden NA, Sanders JPM, Bruins ME (2018) Solubility of the proteinogenic α-amino acids in water, ethanol, and ethanol–water mixtures. J Chem Eng Data. Google Scholar
  65. 65.
    Matsuo H, Chiba T, Nagamori S, Nakayama A, Domoto H, Phetdee K, Wiriyasermkul P, Kikuchi Y, Oda T, Nishiyama J, Nakamura T, Morimoto Y, Kamakura K, Sakurai Y, Nonoyama S, Kanai Y, Shinomiya N (2008) Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia. Am J Hum Genet 83:744–751. CrossRefGoogle Scholar
  66. 66.
    Kikuchi Y, Koga H, Yasutomo Y, Kawabata Y, Shimizu E, Naruse M, Kiyama S, Nonoguchi H, Tomita K, Sasatomi Y, Takebayashi S (2000) Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction. Clin Nephrol 53:467–472Google Scholar
  67. 67.
    Shiramoto M, Liu S, Shen Z, Yan X, Yamamoto A, Gillen M, Ito Y, Hall J (2018) Verinurad combined with febuxostat in Japanese adults with gout or asymptomatic hyperuricaemia: a phase 2a, open-label study. Rheumatol Oxf Engl 57:1602–1610. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ben Oliveira
    • 1
  • Robert Unwin
    • 1
    • 2
  • Stephen B. Walsh
    • 1
    Email author
  1. 1.Royal Free Hospital/Medical SchoolCentre for Nephrology, University College LondonLondonUK
  2. 2.AstraZeneca IMED ECD CVRM R&DGothenburgSweden

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