#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Serum uromodulin is associated with the severity of clinicopathological findings in ANCA-associated glomerulonephritis


Autoři: Shohei Tachibana aff001;  Masayuki Iyoda aff001;  Taihei Suzuki aff001;  Nobuhiro Kanazawa aff001;  Ken Iseri aff001;  Yukihiro Wada aff001;  Kei Matsumoto aff001;  Takanori Shibata aff001
Působiště autorů: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224690

Souhrn

Background

Uromodulin (UMOD), also known as Tamm-Horsfall protein, is a kidney-specific protein expressed by epithelial cells lining the thick ascending limb of the loop of Henle. In the current study, we aimed to clarify the clinical significance of UMOD in ANCA-associated glomerulonephritis (AAG).

Materials and methods

Sixty-one biopsy-proven AAG patients were included in this study. UMOD was measured using ELISA. The relationships between serum UMOD (sUMOD) levels and various clinicopathological findings were evaluated.

Results

AAG was classified into four categories (focal, crescentic, mixed, and sclerotic). In addition, tubulointerstitial lesions were classified as mild, moderate, and severe. The levels of sUMOD and urinary UMOD (uUMOD) were correlated with each other. A negative correlation between sUMOD levels and serum Cr levels, and positive correlation between sUMOD levels and eGFR were found. Patients in the high sUMOD group were associated with low serum Cr levels, focal classification, and mild tubulointerstitial injury compared to the low sUMOD group. Comparing the characteristics among histopathological classes, patients in the focal class had the best renal function and the highest levels of uUMOD/Cr and sUMOD. The focal class had significantly better renal survival compared with the severe histopathological classes (crescentic, mixed, and sclerotic). In univariate logistic regression analyses, prognostic factors for severe histopathological classes were low uUMOD/Cr, high serum Cr, and low sUMOD. Multivariate analyses revealed that low sUMOD predicted severe histopathological classes independent of serum Cr. The mean levels of sUMOD were significantly different between the focal class and severe histopathological classes, with a sensitivity of 70.6% and specificity of 90.0% (cut-off 143 ng/ml, AUC 0.80) by ROC curves.

Conclusion

Low sUMOD levels were associated with severe clinicopathological findings and might be considered as a risk factor for end stage renal disease in AAG.

Klíčová slova:

Biopsy – Glomerulonephritis – Chronic kidney disease – Kidneys – Lesions – Proteinuria – Renal analysis – Renal system


Zdroje

1. Tamm I, Horsfall FL Jr. Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proceedings of the Society for Experimental Biology and Medicine Society for Experimental Biology and Medicine. 1950;74(1):106–8. 15430405.

2. Tamm I, Horsfall FL Jr. A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses. The Journal of experimental medicine. 1952;95(1):71–97. doi: 10.1084/jem.95.1.71 14907962; PubMed Central PMCID: PMC2212053.

3. Muchmore AV, Decker JM. Uromodulin: a unique 85-kilodalton immunosuppressive glycoprotein isolated from urine of pregnant women. Science. 1985;229(4712):479–81. doi: 10.1126/science.2409603 2409603.

4. Pennica D, Kohr WJ, Kuang WJ, Glaister D, Aggarwal BB, Chen EY, et al. Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. Science. 1987;236(4797):83–8. doi: 10.1126/science.3453112 3453112.

5. Duncan JL. Differential effect of Tamm-Horsfall protein on adherence of Escherichia coli to transitional epithelial cells. The Journal of infectious diseases. 1988;158(6):1379–82. doi: 10.1093/infdis/158.6.1379 3058823.

6. Serafini-Cessi F, Malagolini N, Cavallone D. Tamm-Horsfall glycoprotein: biology and clinical relevance. American journal of kidney diseases: the official journal of the National Kidney Foundation. 2003;42(4):658–76. doi: 10.1016/s0272-6386(03)00829-1 14520616.

7. Wangsiripaisan A, Gengaro PE, Edelstein CL, Schrier RW. Role of polymeric Tamm-Horsfall protein in cast formation: oligosaccharide and tubular fluid ions. Kidney international. 2001;59(3):932–40. doi: 10.1046/j.1523-1755.2001.059003932.x 11231348.

8. Renigunta A, Renigunta V, Saritas T, Decher N, Mutig K, Waldegger S. Tamm-Horsfall glycoprotein interacts with renal outer medullary potassium channel ROMK2 and regulates its function. The Journal of biological chemistry. 2011;286(3):2224–35. doi: 10.1074/jbc.M110.149880 21081491; PubMed Central PMCID: PMC3023518.

9. Mutig K, Kahl T, Saritas T, Godes M, Persson P, Bates J, et al. Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner. The Journal of biological chemistry. 2011;286(34):30200–10. doi: 10.1074/jbc.M111.222968 21737451; PubMed Central PMCID: PMC3191059.

10. Kottgen A, Glazer NL, Dehghan A, Hwang SJ, Katz R, Li M, et al. Multiple loci associated with indices of renal function and chronic kidney disease. Nature genetics. 2009;41(6):712–7. doi: 10.1038/ng.377 19430482; PubMed Central PMCID: PMC3039280.

11. Devuyst O, Bochud M. Uromodulin, kidney function, cardiovascular disease, and mortality. Kidney international. 2015;88(5):944–6. Epub 2015/11/19. doi: 10.1038/ki.2015.267 26579681.

12. Garimella PS, Jaber BL, Tighiouart H, Liangos O, Bennett MR, Devarajan P, et al. Association of Preoperative Urinary Uromodulin with AKI after Cardiac Surgery. Clinical journal of the American Society of Nephrology: CJASN. 2017;12(1):10–8. Epub 2016/11/01. doi: 10.2215/CJN.02520316 27797887; PubMed Central PMCID: PMC5220649.

13. Zhou J, Chen Y, Liu Y, Shi S, Wang S, Li X, et al. Urinary uromodulin excretion predicts progression of chronic kidney disease resulting from IgA nephropathy. PloS one. 2013;8(8):e71023. Epub 2013/08/31. doi: 10.1371/journal.pone.0071023 23990922; PubMed Central PMCID: PMC3750049.

14. Steubl D, Block M, Herbst V, Nockher WA, Schlumberger W, Satanovskij R, et al. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients. Medicine. 2016;95(10):e3011. doi: 10.1097/MD.0000000000003011 26962815; PubMed Central PMCID: PMC4998896.

15. Scherberich JE, Gruber R, Nockher WA, Christensen EI, Schmitt H, Herbst V, et al. Serum uromodulin-a marker of kidney function and renal parenchymal integrity. Nephrol Dial Transplant. 2018;33(2):284–95. Epub 2017/02/17. doi: 10.1093/ndt/gfw422 28206617.

16. Risch L, Lhotta K, Meier D, Medina-Escobar P, Nydegger UE, Risch M. The serum uromodulin level is associated with kidney function. Clinical chemistry and laboratory medicine. 2014;52(12):1755–61. Epub 2014/06/17. doi: 10.1515/cclm-2014-0505 24933630.

17. Kusnierz-Cabala B, Gala-Bladzinska A, Mazur-Laskowska M, Dumnicka P, Sporek M, Matuszyk A, et al. Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis. Molecules (Basel, Switzerland). 2017;22(6). Epub 2017/06/15. doi: 10.3390/molecules22060988 28613246.

18. Berden AE, Ferrario F, Hagen EC, Jayne DR, Jennette JC, Joh K, et al. Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol. 2010;21(10):1628–36. Epub 2010/07/10. doi: 10.1681/ASN.2010050477 20616173.

19. Marco H, Draibe J, Villacorta J, Quintana LF, Martin N, Garcia-Osuna R, et al. Determinants of renal and patient outcomes in a Spanish cohort of patients with ANCA-associated vasculitis and renal involvement. Clinical rheumatology. 2018;37(4):1065–74. doi: 10.1007/s10067-017-3973-2 29520673.

20. Chang DY, Wu LH, Liu G, Chen M, Kallenberg CG, Zhao MH. Re-evaluation of the histopathologic classification of ANCA-associated glomerulonephritis: a study of 121 patients in a single center. Nephrol Dial Transplant. 2012;27(6):2343–9. Epub 2011/11/29. doi: 10.1093/ndt/gfr643 22121235.

21. Muso E, Endo T, Itabashi M, Kakita H, Iwasaki Y, Tateishi Y, et al. Evaluation of the newly proposed simplified histological classification in Japanese cohorts of myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in comparison with other Asian and European cohorts. Clinical and experimental nephrology. 2013;17(5):659–62. Epub 2012/12/25. doi: 10.1007/s10157-012-0755-7 23263238; PubMed Central PMCID: PMC3824231.

22. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis and rheumatism. 1994;37(2):187–92. Epub 1994/02/01. doi: 10.1002/art.1780370206 8129773.

23. Bjornstad P, Wiromrat P, Johnson RJ, Sippl R, Cherney DZI, Wong R, et al. Serum Uromodulin Predicts Less Coronary Artery Calcification and Diabetic Kidney Disease Over 12 Years in Adults With Type 1 Diabetes: The CACTI Study. Diabetes care. 2019;42(2):297–302. doi: 10.2337/dc18-1527 30482755; PubMed Central PMCID: PMC6341281.

24. Lieberthal JG, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, et al. urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. J Rheumatol. 2013;40(5):674–83. Epub 2013/04/03. doi: 10.3899/jrheum.120879 23547217; PubMed Central PMCID: PMC4505819.

25. Saemann MD, Weichhart T, Horl WH, Zlabinger GJ. Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infection. Eur J Clin Invest. 2005;35(4):227–35. Epub 2005/04/09. doi: 10.1111/j.1365-2362.2005.01483.x 15816991.

26. Weichhart T, Zlabinger GJ, Saemann MD. The multiple functions of Tamm-Horsfall protein in human health and disease: a mystery clears up. Wien Klin Wochenschr. 2005;117(9–10):316–22. Epub 2005/07/02. 15989109.

27. Wu TH, Hsieh SC, Li KJ, Wu CH, Yu CL, Yang AH, et al. Altered glycosylation of Tamm-Horsfall glycoprotein derived from renal allograft recipients leads to changes in its biological function. Transpl Immunol. 2008;18(3):237–45. Epub 2007/12/01. doi: 10.1016/j.trim.2007.07.001 18047931.

28. Rhodes DC, Hinsman EJ, Rhodes JA. Tamm-Horsfall glycoprotein binds IgG with high affinity. Kidney international. 1993;44(5):1014–21. Epub 1993/11/01. doi: 10.1038/ki.1993.343 8264130.

29. Rhodes DC. Binding of Tamm-Horsfall protein to complement 1q and complement 1, including influence of hydrogen-ion concentration. Immunol Cell Biol. 2002;80(6):558–66. Epub 2002/10/31. doi: 10.1046/j.1440-1711.2002.01125.x 12406390.

30. Su SJ, Chang KL, Lin TM, Huang YH, Yeh TM. Uromodulin and Tamm-Horsfall protein induce human monocytes to secrete TNF and express tissue factor. J Immunol. 1997;158(7):3449–56. Epub 1997/04/01. 9120306.

31. Schmid M, Prajczer S, Gruber LN, Bertocchi C, Gandini R, Pfaller W, et al. Uromodulin facilitates neutrophil migration across renal epithelial monolayers. Cell Physiol Biochem. 2010;26(3):311–8. Epub 2010/08/28. doi: 10.1159/000320554 20798515.

32. Hession C, Decker JM, Sherblom AP, Kumar S, Yue CC, Mattaliano RJ, et al. Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines. Science. 1987;237(4821):1479–84. Epub 1987/09/18. doi: 10.1126/science.3498215 3498215.

33. Steubl D, Block M, Herbst V, Schlumberger W, Nockher A, Angermann S, et al. Serum uromodulin predicts graft failure in renal transplant recipients. Biomarkers. 2017;22(2):171–7. Epub 2016/10/30. doi: 10.1080/1354750X.2016.1252957 27790922.

34. Bostom A, Steubl D, Garimella PS, Franceschini N, Roberts MB, Pasch A, et al. Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure. Am J Nephrol. 2018;47(4):275–82. Epub 2018/04/27. doi: 10.1159/000489095 29698955.


Článek vyšel v časopise

PLOS One


2019 Číslo 11
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#