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01-07-2004 | Review

Protein reabsorption in renal proximal tubule—function and dysfunction in kidney pathophysiology

Authors: Erik I. Christensen, Jakub Gburek

Published in: Pediatric Nephrology | Issue 7/2004

Abstract

The endocytic receptors megalin and cubilin are highly expressed in the early parts of the endocytic apparatus of the renal proximal tubule. The two receptors appear to be responsible for the tubular clearance of most proteins filtered in the glomeruli. Since cubilin is a peripheral membrane protein it has no endocytosis signaling sequence. Cubilin binds to megalin and it appears that megalin is responsible for internalization of cubilin and its ligands, in addition to internalizing its own ligands. The importance of the receptors is underscored by the proteinuria observed in megalin-deficient mice, in dogs lacking functional cubilin, and in patients with distinct mutations of the cubilin gene. In this review we focus on the role of megalin- and cubilin-mediated endocytosis in renal pathophysiology. Association between disorders characterized by tubular proteinuria, such as megaloblastic anemia type-1, Dent disease, cystinosis, and Fabry disease and the dysfunction of proximal tubular endocytosis is discussed. The correlation between the high capacity of endocytosis in the proximal tubule and progressive renal disease in overload proteinuria is considered.

Rosenberg ME, Hostetter TH (2003) Proteinuria. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology, 2nd edn. Raven, New York, pp 3039–3061

Abbate M, Remuzzi G (1999) Proteinuria as a mediator of tubulointerstitial injury. Kidney Blood Press Res 22:37–46CrossRefPubMed

Zoja C, Morigi M, Remuzzi G (2003) Proteinuria and phenotypic change of proximal tubular cells. J Am Soc Nephrol 14:S36–S41PubMed

Hsu SI, Couser WG (2003) Chronic progression of tubulointerstitial damage in proteinuric renal disease is mediated by complement activation: a therapeutic role for complement inhibitors? J Am Soc Nephrol 14:S186–S191PubMed

Straus W (1964) Occurrence of phagosomes and phago-lysosomes in different segments of the nephron in relation to the reabsorption, transport, digestion and extrusion of intravenously injected horseradish peroxidase. J Cell Biol 21:295–308

Christensen EI, Carone FA, Rennke HG (1981) Effect of molecular charge on endocytic uptake of ferritin in renal proximal tubule cells. Lab Invest 44:351–358PubMed

Madsen KM, Harris RH, Tisher CC (1982) Uptake and intracellular distribution of ferritin in the rat distal convoluted tubule. Kidney Int 21:354–361PubMed

Christensen EI, Birn H (2002) Megalin and cubilin: multifunctional endocytic receptors. Nat Rev Mol Cell Biol 3:256–266PubMed

Christensen EI, Birn H (2001) Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol 280:F562–F573PubMed

10.

Verroust PJ, Birn H, Nielsen R, Kozyraki R, Christensen EI (2002) The tandem endocytic receptors megalin and cubilin are important proteins in renal pathology. Kidney Int 62:745–756CrossRefPubMed

11.

Christensen EI, Moskaug JO, Vorum H, Jacobsen C, Gundersen TE, Nykjaer A, Blomhoff R, Willnow TE, Moestrup SK (1999) Evidence for an essential role of megalin in transepithelial transport of retinol. J Am Soc Nephrol 10:685–695PubMed

12.

Moestrup SK, Birn H, Fischer PB, Petersen CM, Verroust PJ, Sim RB, Christensen EI, Nexø E (1996) Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis. Proc Natl Acad Sci USA 93:8612–8617CrossRefPubMed

13.

Birn H, Willnow TE, Nielsen R, Norden AG, Bonsch C, Moestrup SK, Nexo E, Christensen EI (2002) Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B(12). Am J Physiol Renal Physiol 282:F408–F416PubMed

14.

Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell 96:507–515PubMed

15.

Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, Chapelle A de la, Moestrup SK, Ray R, Gliemann J, Willnow TE, Christensen EI (2001) Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). Proc Natl Acad Sci USA 98:13895–13900CrossRefPubMed

16.

Kozyraki R, Fyfe J, Verroust PJ, Jacobsen C, Dautry-Varsat A, Gburek J, Willnow TE, Christensen EI, Moestrup SK (2001) Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc Natl Acad Sci USA 98:12491–12496CrossRefPubMed

17.

Gburek J, Birn H, Verroust PJ, Goj B, Jacobsen C, Moestrup SK, Willnow TE, Christensen EI (2003) Renal uptake of myoglobin is mediated by the endocytic receptors megalin and cubilin. Am J Physiol Renal Physiol 285:F451–F458PubMed

18.

Gburek J, Verroust PJ, Willnow TE, Fyfe JC, Nowacki W, Jacobsen C, Moestrup SK, Christensen EI (2002) Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin. J Am Soc Nephrol 13:423–430PubMed

19.

Raychowdhury R, Niles JL, McCluskey RT, Smith JA (1989) Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor. Science 244:1163–1165PubMed

20.

Saito A, Pietromonaco S, Loo AK, Farquhar MG (1994) Complete cloning and sequencing of rat gp330/”megalin,” a distinctive member of the low density lipoprotein receptor gene family. Proc Natl Acad Sci USA 91:9725–9729PubMed

21.

Hjälm G, Murray E, Crumley G, Harazim W, Lundgren S, Onyango I, Ek B, Larsson M, Juhlin C, Hellman P, Davis H, Åkerström G, Rask L, Morse B (1996) Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties. Eur J Biochem 239:132–137PubMed

22.

Davis CG, Goldstein JL, Sudhof TC, Anderson RG, Russell DW, Brown MS (1987) Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature 326:760–765CrossRefPubMed

23.

Takeda T, Yamazaki H, Farquhar MG (2003) Identification of an apical sorting determinant in the cytoplasmic tail of megalin. Am J Physiol Cell Physiol 284:C1105–C1113PubMed

24.

Petersen HH, Hilpert J, Militz D, Zandler V, Jacobsen C, Roebroek AJ, Willnow TE (2003) Functional interaction of megalin with the megalin binding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule. J Cell Sci 116:453–461CrossRefPubMed

25.

Oleinikov AV, Zhao J, Makker SP (2000) Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin. Biochem J 347:613–621CrossRefPubMed

26.

Nagai M, Meerloo T, Takeda T, Farquhar MG (2003) The adaptor protein ARH escorts megalin to and through endosomes. Mol Biol Cell 14: 4984–4996CrossRefPubMed

27.

Morris SM, Tallquist MD, Rock CO, Cooper JA (2002) Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport. EMBO J 21:1555–1564CrossRefPubMed

28.

Garcia CK, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M, Calandra S, Bertolini S, Cossu F, Grishin N, Barnes R, Cohen JC, Hobbs HH (2001) Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science 292:1394–1398PubMed

29.

Moestrup SK, Kozyraki R, Kristiansen M, Kaysen JH, Rasmussen HH, Brault D, Pontillon F, Goda FO, Christensen EI, Hammond TG, Verroust PJ (1998) The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins. J Biol Chem 273:5235–5242PubMed

30.

Kozyraki R, Kristiansen M, Silahtaroglu A, Hansen C, Jacobsen C, Tommerup N, Verroust PJ, Moestrup SK (1998) The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region. Blood 91:3593–3600PubMed

31.

Xu D, Kozyraki R, Newman TC, Fyfe JC (1999) Genetic evidence of an accessory activity required specifically for cubilin brush-border expression and intrinsic factor-cobalamin absorption. Blood 94:3604–3606PubMed

32.

Bork P, Beckmann G (1993) The CUB domain. A widespread module in developmentally regulated proteins. J Mol Biol 231:539–545CrossRefPubMed

33.

Kristiansen M, Kozyraki R, Jacobsen C, Nexø E, Verroust PJ, Moestrup SK (1999) Molecular dissection of the intrinsic factor-vitamin B12 receptor, cubilin, discloses regions important for membrane association and ligand binding. J Biol Chem 274:20540–20544PubMed

34.

Kozyraki R, Fyfe J, Kristiansen M, Gerdes C, Jacobsen C, Cui S, Christensen EI, Aminoff M, Chapelle A de la, Krahe R, Verroust PJ, Moestrup SK (1999) The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein. Nat Med 5:656–661CrossRefPubMed

35.

Hammad SM, Barth JL, Knaak C, Argraves WS (2000) Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. J Biol Chem 275:12003–12008CrossRefPubMed

36.

Cui S, Verroust PJ, Moestrup SK, Christensen EI (1996) Megalin/gp330 mediates uptake of albumin in renal proximal tubule. Am J Physiol 271:F900–F907PubMed

37.

Birn H, Fyfe JC, Jacobsen C, Mounier F, Verroust PJ, Orskov H, Willnow TE, Moestrup SK, Christensen EI (2000) Cubilin is an albumin binding protein important for renal tubular albumin reabsorption. J Clin Invest 105:1353–1361PubMed

38.

Zhai XY, Nielsen R, Birn H, Drumm K, Mildenberger S, Freudinger R, Moestrup SK, Verroust PJ, Christensen EI, Gekle M (2000) Cubilin- and megalin-mediated uptake of albumin in cultured proximal tubule cells of opossum kidney. Kidney Int 58:1523–1533PubMed

39.

Birn H, Leboulleux M, Moestrup SK, Ronco PM, Aucouturier P, Christensen EI (2003) Megalin, cubilin and immunoglobulin light chains: receptor-mediated uptake of light chains in kidney proximal tubule. In: Touchard G, Aucouturier P, Hermine O, Ronco PM (eds) Monoclonal gammopathies and the kidney. Kluwer, The Netherlands, pp 37–48

40.

Batuman V, Verroust PJ, Navar GL, Kaysen JH, Goda FO, Campbell WC, Simon E, Pontillon F, Lyles M, Bruno J, Hammond TG (1998) Myeloma light chains are ligands for cubilin (gp280). Am J Physiol 275:F246–F254PubMed

41.

Birn H, Verroust PJ, Nexø E, Hager H, Jacobsen C, Christensen EI, Moestrup SK (1997) Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein. J Biol Chem 272:26497–26504PubMed

42.

Seetharam B, Christensen EI, Moestrup SK, Hammond TG, Verroust PJ (1997) Identification of rat yolk sac target protein of teratogenic antibodies, gp280, as intrinsic factor-cobalamin receptor. J Clin Invest 99:2317–2322PubMed

43.

Imerslund O (1960) Idiopathic chronic megaloblastic anemia in children. Acta Paediatr Scand 49 [Suppl 119]:1–115

44.

Gräsbeck R, Gordin R, Kantero I, Kuhlbäck B (1960) Selective vitamin B12 malabsorption and proteinuria in young people. Acta Med Scand 167:289–296PubMed

45.

Rosenblatt DS, Fenton WA (1999) Inborn errors of cobalamin metabolism. In: Banerjee R (ed) Chemistry and biochemistry of vitamin B12. Wiley, New York, pp 367–384

46.

Aminoff M, Carter JE, Chadwick RB, Johnson C, Grasbeck R, Abdelaal MA, Broch H, Jenner LB, Verroust PJ, Moestrup SK, Chapelle A de la, Krahe R (1999) Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. Nat Genet 21:309–313PubMed

47.

Wahlstedt-Froberg V, Pettersson T, Aminoff M, Dugue B, Grasbeck R (2003) Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption. Pediatr Nephrol 18:417–421PubMed

48.

Fyfe JC, Ramanujam KS, Ramaswamy K, Patterson DF, Seetharam B (1991) Defective brush-border expression of intrinsic factor-cobalamin receptor in canine inherited intestinal cobalamin malabsorption. J Biol Chem 266:4489–4494PubMed

49.

Leheste JR, Rolinski B, Vorum H, Hilpert J, Nykjaer A, Jacobsen C, Aucouturier P, Moskaug J, Otto A, Christensen EI, Willnow TE (1999) Megalin knockout mice as an animal model of low molecular weight proteinuria. Am J Pathol 155:1361–1370PubMed

50.

Tanner SM, Aminoff M, Wright FA, Liyanarachchi S, Kuronen M, Saarinen A, Massika O, Mandel H, Broch H, Chapelle A de la (2003) Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Nat Genet 33:426–429CrossRefPubMed

51.

He Q, Fyfe JC, Schäffer AA, Kilkenney A, Werner P, Kirkness EF, Henthorn PS (2003) Canine Imerslund-Gräsbeck syndrome maps to a region orthologous to HSA14q. Mamm Genome 14:765–777CrossRefPubMed

52.

Kalantry S, Manning S, Haub O, Tomihara-Newberger C, Lee HG, Fangman J, Disteche CM, Manova K, Lacy E (2001) The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain. Nat Genet 27:412–416CrossRefPubMed

53.

Fyfe JC, Madsen M, Hojrup P, Christensen EI, Tanner SM, Chapelle A de la, He Q, Moestrup SK (2004) The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood 103:1573–1579CrossRefPubMed

54.

Scheinman SJ (1998) X-linked hypercalciuric nephrolithiasis: clinical syndromes and chloride channel mutations. Kidney Int 53:3–17

55.

Thakker RV (2000) Pathogenesis of Dent’s disease and related syndromes of X-linked nephrolithiasis. Kidney Int 57:787–793CrossRefPubMed

56.

Günther W, Lüchow A, Cluzeaud F, Vandewalle A, Jentsch TJ (1998) ClC-5, the chloride channel mutated in Dent’s disease, colocalizes with the proton pump in endocytotically active kidney cells. Proc Natl Acad Sci USA 95:8075–8080CrossRefPubMed

57.

Devuyst O, Christie PT, Courtoy PJ, Beauwens R, Thakker RV (1999) Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent’s disease. Hum Mol Genet 8:247–257PubMed

58.

Piwon N, Gunther W, Schwake M, Bosl MR, Jentsch TJ (2000) CIC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent’s disease. Nature 408:369–373CrossRefPubMed

59.

Wang SS, Devuyst O, Courtoy PJ, Wang XT, Wang H, Wang Y, Thakker RV, Guggino S, Guggino WB (2000) Mice lacking renal chloride channel, CLC-5, are a model for Dent’s disease, a nephrolithiasis disorder associated with defective receptor-mediated endocytosis. Hum Mol Genet 9:2937–2945CrossRefPubMed

60.

Marshansky V, Ausiello DA, Brown D (2002) Physiological importance of endosomal acidification: potential role in proximal tubulopathies. Curr Opin Nephrol Hypertens 11:527–537

61.

Christensen EI, Devuyst O, Dom G, Nielsen R, Van Der SP, Verroust P, Leruth M, Guggino WB, Courtoy PJ (2003) Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci USA 100:8472–8477CrossRefPubMed

62.

Norden AG, Lapsley M, Igarashi T, Kelleher CL, Lee PJ, Matsuyama T, Scheinman SJ, Shiraga H, Sundin DP, Thakker RV, Unwin RJ, Verroust P, Moestrup SK (2002) Urinary megalin deficiency implicates abnormal tubular endocytic function in Fanconi syndrome. J Am Soc Nephrol 13:125–133PubMed

63.

Lowe CUTM, MacLachlan EA (1952) Organic-aciduria, decreased renal amonia production, hydrophtalmos and mental retardation. Am J Dis Child 83:164–184

64.

Suchy SF, Olivos-Glander IM, Nussabaum RL (1995) Lowe syndrome, a deficiency of phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus. Hum Mol Genet 4:2245–2250PubMed

65.

Dressman MA, Olivos-Glander IM, Nussbaum RL, Suchy SF (2000) Ocrl1, a PtdIns(4,5)P(2) 5-phosphatase, is localized to the trans-Golgi network of fibroblasts and epithelial cells. J Histochem Cytochem 48:179–190PubMed

66.

Grabowski GA, Hopkin RJ (2003) Enzyme therapy for lysosomal storage disease: principles, practice, and prospects. Annu Rev Genomics Hum Genet 4:403–36:403–436

67.

Branton M, Schiffmann R, Kopp JB (2002) Natural history and treatment of renal involvement in Fabry disease. J Am Soc Nephrol 13 [Suppl 2]:S139–143

68.

Thurberg BL, Rennke H, Colvin RB, Dikman S, Gordon RE, Collins AB, Desnick RJ, O’Callaghan M (2002) Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 62:1933–1946CrossRefPubMed

69.

Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, Callen DF, Gribouval O, Broyer M, Bates GP, Hoff W van’t, Antignac C (1998) A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 18:319–324PubMed

70.

Kalatzis V, Antignac C (2003) New aspects of the pathogenesis of cystinosis. Pediatr Nephrol 18:207–215PubMed

71.

Gibson IW, More IA (1998) Glomerular pathology: recent advances. J Pathol 184:123–129CrossRefPubMed

72.

Koop K, Eikmans M, Baelde HJ, Kawachi H, De Heer E, Paul LC, Bruijn JA (2003) Expression of podocyte-associated molecules in acquired human kidney diseases. J Am Soc Nephrol 14:2063–2071PubMed

73.

David WS (2000) Myoglobinuria. Neurol Clin 18:215–243PubMed

74.

Don BR, Rodriguez RA, Humphreys MH (2003) Acute renal failure associated with pigmenturia or crystal deposits. In: Schrier RW (ed) Diseases of the kidney and urinary tract. Lippincott, Williams and Williams, Philadelphia, pp 1299–1326

75.

Goldschmidt H, Lannert H, Bommer J, Ho AD (2000) Multiple myeloma and renal failure. Nephrol Dial Transplant 15:301–304CrossRefPubMed

76.

Ying WZ, Sanders PW (2001) Mapping the binding domain of immunoglobulin light chains for Tamm-Horsfall protein. Am J Pathol 158:1859–1866PubMed

77.

Sanders PW (1993) Renal involvement in plasma cell dyscrasias. Curr Opin Nephrol Hypertens 2:246–252PubMed

78.

Olbricht CJ, Gutjahr E, Cannon JK, Irmler H, Tisher CC (1990) Effect of low molecular weight proteins and dextran on renal cathepsin B and L activity. Kidney Int 37:918–926PubMed

79.

Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J (2000) Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J Biol Chem 275:25616–25624CrossRefPubMed

80.

Rader K, Orlando RA, Lou X, Farquhar MG (2000) Characterization of ANKRA, a novel ankyrin repeat protein that interacts with the cytoplasmic domain of megalin. J Am Soc Nephrol 11:2167–2178PubMed

81.

Willnow TE, Hilpert J, Armstrong SA, Rohlmann A, Hammer RE, Burns DK, Herz J (1996) Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci USA 93:8460–8464CrossRefPubMed

82.

Dixon R, Brunskill NJ (1999) Activation of mitogenic pathways by albumin in kidney proximal tubule epithelial cells: implications for the pathophysiology of proteinuric states. J Am Soc Nephrol 10:1487–1497PubMed

83.

Deret S, Denoroy L, Lamarine M, Vidal R, Mougenot B, Frangione B, Stevens FJ, Ronco PM, Aucouturier P (1999) Kappa light chain-associated Fanconi’s syndrome: molecular analysis of monoclonal immunoglobulin light chains from patients with and without intracellular crystals. Protein Eng 12:363–369CrossRefPubMed

84.

Paul S, Li L, Kalaga R, Wilkins-Stevens P, Stevens FJ, Solomon A (1995) Natural catalytic antibodies: peptide-hydrolyzing activities of Bence Jones proteins and VL fragment. J Biol Chem 270:15257–15261CrossRefPubMed

85.

Matsuura K, Ikoma S, Watanabe M, Togawa A, Sinohara H (1999) Some Bence-Jones proteins enter cultured renal tubular cells, reach nuclei and induce cell death. Immunology 98:584–589CrossRefPubMed

86.

Pool R (1990) Slow going for blood substitutes. Science 250:1655–1656PubMed

87.

Thomas ME, Schreiner GF (1993) Contribution of proteinuria to progressive renal injury: consequences of tubular uptake of fatty acid bearing albumin. Am J Nephrol 13:385–398PubMed

88.

Goyer RA (1990) Environmentally related diseases of the urinary tract. Med Clin North Am 74:377–389PubMed

89.

Moestrup SK, Cui S, Vorum H, Bregengård C, Bjørn SE, Norris K, Gliemann J, Christensen EI (1995) Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs. J Clin Invest 96:1404–1413PubMed

90.

Sabolic I, Ljubojevic M, Herak-Kramberger CM, Brown D (2002) Cd-MT causes endocytosis of brush-border transporters in rat renal proximal tubules. Am J Physiol Renal Physiol 283:F1389–F1402PubMed

91.

Takano M, Nakanishi N, Kitahara Y, Sasaki Y, Murakami T, Nagai J (2002) Cisplatin-induced inhibition of receptor-mediated endocytosis of protein in the kidney. Kidney Int 62:1707–1717CrossRefPubMed

Title: Protein reabsorption in renal proximal tubule—function and dysfunction in kidney pathophysiology
Authors: Erik I. Christensen
Jakub Gburek
Publication date: 01-07-2004
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 7/2004
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-004-1494-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Protein reabsorption in renal proximal tubule—function and dysfunction in kidney pathophysiology

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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