O.A. SEDASHKINA¹, G.A. MAKOVETSKAYA², D.V. PECHKUROV² 

¹Samara Regional Clinical Hospital named after V.D. Seredavin, 159 Tashkentskaya St., Samara, Russian Federation, 443095

²Samara State Medical University, 10 Chapayevskaya St., Samara, Russian Federation, 443099 

Sedashkina O.A. — Cand. Med. Sc., doctor-nephrologist, tel. +7-937-060-09-96, e-mail: sedashkina@inbox.ru

Makovetskaya G.A. — D. Med. Sc., Professor of the Department of Hospital Pediatrics, tel. +7-927-261-25-32, e-mail: gmakovetskaya@yandex.ru

Pechkurov D.V. — D. Med. Sc., Professor, Head of the Department of Children’s Diseases, tel. +7-927-204-65-20, e-mail: dmpechkurov@yandex.ru

The article reveals the genetic risk factors of forming and progressing the chronic kidney disease in children. Alongside with the etiological and pathogenetic mechanisms of inflammatory process, the polymorphism of rennin-angiotensin-aldosterone system genes, iterleykine-4 genes and factor of a-tumor necrosis determine the features of clinical course of the disease and development of nephrosclerosis. The article presents a review of Russian and foreign research and authors’ own observations from the daily practice. The polymorphic markers АСЕ (D), AGT (174Met) и (235Thr), R1AGT (1166C), NOS3 (786T), END (Lys198Asn) are associated with arterial hypertension, proteinuria, reduction of the speed of glomerular filtration, distortion of the kidney structure and vascular regulation with microcirculation, progressing course of kidney lesions of various genesis and function reduction. The most unfavorable is the polymorphism of gene АСЕ and its allele D. The polymorphism of genes IL4 (C-589T), TNF (G308A) plays an important role in the regulation of inflammation, immune response, apoptosis and fibrosis formation, and is associated with the progressing course of disease. Determining the polymorphic markers of the above genes allows to reveal the groups of patients with increased risk of progressing pathological process, to provide preventive measures and lay the foundations of the personified therapy of urinary system diseases.

Key words: chronic kidney disease, children, progressing, genetic factors.

 

 

REFERENCES

1. Brenner B.M. Haemodynamically mediated glomerular injuri and the progressive nature of kidney disease. Kidney Int, 1983, 23, pp. 647-655.

2. Brenner B.M., Meyer T.W., Hostetter T.H. Dietary protein intakte and the progressive nature of kidney disease: the role of haemodynamically mediated glomerular injuri in the pathogenesis of progressive glomerular sclerosis. N. Engl. J. Med, 1982, 30, pp. 652-659.

3. Baldwin D.S. Chronic glomerulonephritis. Nonimmunological mechanism of progressive glomerular damage. Ibid, 1982, 21, pp. 109-120.

4. Barley J., Blackwood A., Miller M. et al. Angiotensin converting enzime gene I/D-polymorphism, blood pressure and the renin-angiotensin system in Caucasian and Afro-Caribbean peoples. J. Hum. Hypertens, 1996, 10 (1), pp. 31-35.

5. Mustafina O.E., Tkharkakhova Z.N., Bikmeeva A.M. et al. Gene polymorphism of angiotensin-converting enzyme inhibitors and the risk of multifactorial diseases. Med. genetika, 2002, 1 (5), pp. 212-220 (in Russ.).

6. Sivous G.K., Gorashko N.M., Nosikov V.V., Kasatkina E.P. Effect of gene polymorphism of angiotensin-converting enzyme inhibitors on antiproteinuric effect of ACE inhibitors and angiotensin II receptor type 1 in young patients with diabetic nephropathy. Molekulyarnaya meditsina, 2004, 1, pp. 42-47 (in Russ.).

7. Shulutko B.I. Arterial’naya gipertenziya [Arterial hypertension]. Saint Petersburg: RENKOR, 2001. 382 p.
8. Paunova S.S. Pathogenetic bases nephrosclerosis. Literature review. Nefrologiya i dializ, 2005, vol. 7, no. 2, 11 p (in Russ.).

9. Tomilina N.A., Bikbov B.T. Risk factors for death of patients starting treatment for the first time hemodialysis (according to the Register of the Russian Dialysis Society). Nefrologiya i dializ, 2008, no. 10, pp. 35-43 (in Russ.).

10. Jacobsen P., Tarnow L., Carstensen B., Hovind P., Poirier O., Parving H. Genetic Variation in the Renin-Angiotensis System and Progression of Diabetic Nephropathy. J. Am. Soc. Nephrol, 2005, 14, pp. 2843-2850.

11. Ignatova M.S., Dlin V.V., P.V. Novikov. Nasledstvennye bolezni organov mochevoy sistemy u detey: Rukovodstvo dlya vrachey [Hereditary diseases of the urinary system in children: a guide for physicians]. Moscow: Overley, 2014. 348 p.

12. Baranov A.A. Klinicheskie rekomendatsii po pediatrii [Clinical guidelines in pediatrics]. Moscow, 2005. Pp. 107-112.

13. Shadrina M.M., Slominskiy P.A., Miloserdova O.V., Perova N.V., Limborskaya S.A. Analysis of gene polymorphism of angiotensin-converting enzyme inhibitors in patients with coronary heart disease in the Moscow population. Genetika, 2001, 37 (4), pp. 540-544 (in Russ.).

14. Rigat B., Hubert C., Alhenc-Gelas F., Cambien F., Corvol P., Soubrier F. An I/D-polymorphism in the ACE-gene accounting for half the variance of serum enzyme levels. J. Clin. Invest, 1990, 86, pp. 1343-1346.

15. Luther Y., Bantis C., Ivens K., Kolb-Bachhofen V., Heering P. Effects of genetic polymorphisms of the renin-angiotensin system on focal segmental glomerulosclerosis. Kidney Blood Press Res, 2003, 26 (5-6), pp. 333-337.

16. Navis G., Van Der Kleij F.G., De Zeeuw D., De Jong P.E. Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects. Circulation, 1995, 91, pp. 2933-2942.

17. Prikhodina L.S. Klinicheskie i geneticheskie zakonomernosti progressirovaniya steroid-rezistentnogo nefroticheskogo sindroma u detey i effektivnost’ immunosupressivnoy terapii: avtoref. dis. … dok. med. nauk [Clinical and genetic patterns of progression of steroid-resistant nephrotic syndrome in children and the effectiveness of immunosuppressive therapy. Synopsis of dis. Dr med. sci]. Moscow, 2012. 47 p.

18. Krege J., John S., Langenbach L. et al. Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature, 1995, 375, pp. 146-148.

19. Oktem F., Sirin A., Bilge I., Emre S., Agachan B., Turgau I. ACE I/Dgene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome. Pediatr. Nephrol, 2004, 19, pp. 384-389.

20. Sharnova Zh.P., Tikhomirov E.E., Tsygin A.N. Polymorphism of genes of the renin-angiotensin system in the nephrotic syndrome in children. Pediatricheskaya farmakologiya, 2006, vol. 3, no. 4, pp. 10-17 (in Russ.).

21. Buraczynka M., Grzebalska A.M., Spasiewicz D., Orlowska G. Ksiazek A. Genetic polymorphisms of renin-angiotensin system of interstitial nephritis. Ann Univ Mariae Curie Sclodowska (Med), 2002, 57 (2), pp. 330-336.

22. Gumprecht J., Zychma M.J., Grzeszczak W., Zukowska-Szczechowska E. and the End-Stage Renal Disease Study Group. Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T-polymorphisms: Risk of chronic renal failure. Kidney Int, 2000, 58, pp. 513-519.

23. Lee K.B., Kim U.K. Angiotensinogen and angiotensin II type 1 receptor gene polymorphism in patients with autosomal dominant polycystic kidney disease: effect on hypertension and ESRD. Yonsei Med. J, 2003, 44 (4), pp. 641-647.

24. Baranova A.V. Prognosticheskoe znachenie polimorfizma genov vazoaktivnykh sistem i kontsentratsii magniya pri tubulointerstitsial’nykh porazheniyakh pochek u detey doshkol’nogo vozrasta: avtoref. dis. … kand. med. nauk [The prognostic value of gene polymorphism of vasoactive systems and magnesium concentration with renal tubulointerstitial lesions in children of preschool age. Synopsis of dis. PhD med. sci]. Ivanovo, 2013. 18 p.

25. Minushkina L.O. Geneticheskie faktory pri gipertonicheskoy bolezni: svyaz’ s osobennostyami techeniya, razvitiem oslozhneniy, effektivnost’yu terapii: avtoref. dis. … dokt. med. nauk [Genetic factors in hypertension: the connection with the peculiarities of course, the development of complications, treatment effectiveness. Synopsis of dis. Dr med. sci]. Moscow, 2008. 42 p.

26. Litovkina O.N. Analiz assotsiatsiy polimorfizma genov vazoaktivnykh gormonov s formirovaniem khronicheskogo glomerulonefrita: avtoref. dis. … kand. biol. nauk [Analysis of gene polymorphism associations vasoactive hormones with the formation of a chronic glomerulonephritis Synopsis of dis. PhD biol. sci]. Belgorod, 2011. 21 p.

27. Belyanskaya T.V. Differentsirovannyy podkhod k vedeniyu bol’nykh khronicheskim glomerulonefritom s uchetom geneticheskoy predraspolozhennosti: avtoref. dis. … kand. med. nauk [Differentiated approach to the management of patients with chronic glomerulonephritis, taking into account the genetic predisposition. Synopsis of dis. PhD med. sci]. Moscow, 2007. 27 p.

28. Lovati E., Richard A., Frey B.M., Frey F.J., Ferrari P. Genetic polymorphisms of the renin-angiotensin-aldosterone system in endstage renal disease. Kidney Int, 2001, 60, pp. 46-54.

29. Kamysheva E.S., Kutyrina I.M., Nosikov V.V., Shvetsov M.Yu. The value of polymorphic markers of vasoactive hormones in the evaluation of the clinical features of chronic glomerulonephritis. Ter. arkhiv, 2005, 6, pp. 16-20 (in Russ.).