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Urine uromodulin and angiotensin converting enzyme inhibitors: is there a relationship?

https://doi.org/10.36485/1561-6274-2022-26-1-69-74

Abstract

BACKGROUND. Uromodulin (UMO) is a multifunctional glycoprotein expressed in epithelial cells of the thick ascending part of the loop of Henle. Currently, enough information has been accumulated about the participation of this glycoprotein in a number of important physiological and pathological processes. THE AIM: to evaluate the relationship between the level of urine uromodulin (Umo) and the intake of angiotensin converting enzyme (ACE) inhibitors in chronic kidney disease.
PATIENTS AND METHODS. 96 patients aged 43.6±15.4 years were examined. (M:W = 46:50). The presence of kidney disease in all cases is confirmed morphologically. The main criterion for the inclusion of patients in the study was the presence of CKD C1-C3. The exclusion criteria were age over 70 years, the presence of diabetes mellitus, immunosuppressive therapy at the time of examination, taking diuretics. Umo concentrations in blood serum (SUmo) and urine (UUmo) were measured by enzyme immunoassay. Serum and urinary concentrations of creatinine, potassium, sodium, chlorine, calcium, and inorganic phosphorus, as well as protein levels in urine, were also determined. The glomerular filtration rate (eGFR) was calculated using the formula CKD-EPI. The values of daily excretion, clearance, and fractional excretion were calculated for all ions.
RESULTS. The patients were divided into two groups: group 1 – 20 people who did not take ACE inhibitors; group 2 – 78 people who took ACE inhibitors. The content of Umo in urine correlated in the first group with the value of systolic and diastolic blood pressure and serum Umo. In the second group, associations of the concentration of Umo in urine with age, eGFR, the excreted fraction of sodium and chlorine, and serum Umo were noted.
CONCLUSION. The data obtained suggest that the nephroprotective properties of ACE inhibitors are broader than is commonly thought. Our data allow us to talk about their protective effect at the level of the tubular apparatus. The authors believe that the information currently available is quite sufficient to discuss the need to introduce the definitions of SUmo and UUmo into real clinical practice.

About the Authors

M. H. Khasun
Pavlov University
Russian Federation

Associate Prof. Khasun H. Mohamad, MD, PhD, Department of Propudeutics of Internal Diseases

197022, St-Petersburg, L. Tolstoy st., 17, build. 54

Phone (812) 346-39-26 



A. Sh. Rumyantsev
Pavlov University; St. Petersburg State University
Russian Federation

Prof. Rumyantsev Aleksandr Shalikovich, MD, PhD, DMedSci, Department of faculty therapy, Department of Propaedeutics of Internal Medicine

199106, St. Petersburg, 21st line V.O., 8a

197022, L'va Tolstogo str. 6-8, Saint Petersburg

Phone: +7 (812) 326-03-26

Phone: +7 (911) 2677413 



O. V. Galkina
Pavlov University
Russian Federation

Olga V. Galkina PhD, Institute of Nephrology Laboratory of Biochemical Homeostasis, head

197022, St-Petersburg, L. Tolstoy st., 17, build. 54

Phone (812) 3386901 



N. Yu. Korosteleva
Pavlov University
Russian Federation

Natalya Yu. Korosteleva, MD, PhD, Research Institute of Nephrology, senior researcher

197022, L'va Tolstogo str. 6-8, Saint Petersburg

Phone: +7 (911) 9184549 



References

1. Youhanna S, Weber J, Beaujean V et al. Determination of uromodulin in human urine: influence of storage and processing. Nephrol Dial Transplant 2014;29(1):136–145

2. Зверев ЯФ, Жариков АЮ, Брюханов ВМ, Лампатов ВВ. Модуляторы оксалатного нефролитиаза. Ингибиторы кристаллизации. Нефрология 2010;14(1):29–49 Zverev YaF, Zharikov AYu, Bryuhanov VM, Lampatov VV. Modulyatoryi oksalatnogo nefrolitiaza. Ingibitoryi kristallizatsii. Nefrologiya 2010;14(1):29–49

3. El-Achkar TM, Wu XR. Uromodulin in kidney injury: an instigator, bystander, or protector? Am J Kidney Dis 2012;59(3):452– 461

4. El-Achkar TM, McCracken R, Liu Y et al. Tamm-Horsfall protein translocates to the basolateral domain of thick ascending limbs, interstitium, and circulation during recovery from acute kidney injury. Am J Physiol Renal Physiol 2013; 304(8): F1066–F1075

5. Graterol F, Navarro-Muñoz M, Ibernon M et al. Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling. BMC Nephrol 2013 Apr 11;14:82. doi: 10.1186/1471-2369-14-82

6. Padmanabhan S, Melander O, Johnson T et al. Genomewide association study of blood pressure extremes identifies variant near UMOD associated with hypertension. PLoS Genet 2010; Oct 28;6(10):e1001177. doi: 10.1371/journal.pgen.1001177

7. Graham LA, Padmanabhan S, Fraser NJ et al. Validation of uromodulin as a candidate gene for human essential hypertension. Hypertension 2014;63(3):551–558

8. Han J, Chen Y, Liu Y et al. Common variants of the UMOD promoter associated with blood pressure in a community-based Chinese cohort. Hypertens Res 2012;35(7):769–774

9. Kirk R. Hypertension: Uromodulin identified as a potential therapeutic target. Nat Rev Nephrol 2014;10(1):2. doi: 10.1038/nrneph.2013.241

10. Kipp A, Olinger E. What Does Uromodulin Do? Clin J Am Soc Nephrol 2020Dec 31;16(1):150–153. doi: 10.2215/CJN.06390420

11. Kumar S, Bogle R, Banerjee D. Why do young people with chronic kidney disease die early? World J Nephrol 2014 Nov 6; 3(4):143–155. doi: 10.5527/wjn.v3.i4.143

12. Земченков АЮ, Румянцев АШ, Смирнов АВ. Оценка эффективности нефропротективной терапии (краткий обзор литературы и данные Санкт-Петербургского Регистра). Нефрология 2018;22(1):58–68. https://doi.org/10.24884/1561-6274-2018-22-1-58-68 Zemchenkov AYu, Rumyantsev AS, Smirnov AV. The efficacy evaluation of the nephroprotective therapy: Minireview and Saint Petersburg registry data. Nephrology (Saint-Petersburg) 2018;22(1):58–68 (In Russ.). https://doi.org/10.24884/1561-6274-2018-22-1-58-68

13. Хасун М, Каюков ИГ, Галкина ОВ и др. Уромодулин и экскреция ионов у пациентов с гломерулопатиями. Нефрология 2016;20(1):51–56 Khasun M, Kayukov IG, Galkina OV et al. Uromodulin and ion excretion in patients with glomerulopathy. Nephrology (SaintPetersburg) 2016;20(1):51–56 (In Russ.)

14. 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. J Biol Chem 2011 Jan 21;286(3):2224–2235. doi: 10.1074/jbc.M110.149880

15. Mutig K, Kahl T, Saritas T et al. Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner. J Biol Chem 2011;286(34):30200–30210. doi: 10.1074/jbc.M111.222968

16. Wolf MT, Wu XR, Huang CL. Uromodulin upregulates TRPV5 by impairing caveolin-mediated endocytosis. Kidney Int 2013;84(1):130–137. doi: 10.1038/ki.2013.63

17. de Baaij JH, Groot Koerkamp MJ, Lavrijsen M et al. Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg(2+) handling. Am J Physiol Renal Physiol 2013;305(11):F1563–1573. doi: 10.1152/ajprenal.00322.2013

18. Смирнов АВ, Хасун М, Каюков ИГ и др. Уромодулин сыворотки как ранний биомаркер атрофии канальцев и интерстициального фиброза у пациентов с гломерулопатиями. Терапевтический архив 2018;90(6):41–47. doi: 10.26442/terarkh201890641-47 Smirnov AV, Khasun M, Kayukov IG et al. Serum uromodulin as an early biomarker of tubular atrophy and interstitial fibrosis in patients with glomerulopathies. Terapevticheskii arkhiv 2018;90 (6):41–47. doi: 10.26442/terarkh201890641-47


Review

For citations:


Khasun M.H., Rumyantsev A.Sh., Galkina O.V., Korosteleva N.Yu. Urine uromodulin and angiotensin converting enzyme inhibitors: is there a relationship? Nephrology (Saint-Petersburg). 2022;26(1):69-74. (In Russ.) https://doi.org/10.36485/1561-6274-2022-26-1-69-74

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ISSN 1561-6274 (Print)
ISSN 2541-9439 (Online)