MOLECULAR NEPHROPATHOLOGY: NEW OPPORTUNITIES FOR KIDNEY DISEASES DIAGNOSTICS

In the era of modern medicine fundamental scientific installation is emerged in the diagnosis of diseases of the kidneys, which are based on traditional diagnostic tools. The presented article describes the modern view on the possibility of diagnosis of kidney diseases, based on genetic studies. The necessity of active development for molecular diagnostic methods of kidney diseases is revealed, which not only complement the traditional methods of research, but also provide insight in point of view of the molecular pathophysiology. Further study of kidney diseases from a position of molecular biology will allow us to take a modern look at the pathogenesis of many diseases and solve a number of problems from the standpoint of personalized therapy that takes into account the genetic characteristics of the patient. 

1. Benjamin A., Michael M. Molecular nephropathology: ready for prime time? Am J Physiol Renal Physiol 2015; 309: F185– F188, DOI: 10.1152/ajprenal.00153.2015.

2. Broecker V., Mengel M. The significance of histological diagnosis in renal allograft biopsies in 2014. Transpl Int 2015; 28: 136–143, DOI: 10.1111/tri.12446.

3. Mengel M., Reeve J., Bunnag S., Einecke G., Sis B., Mueller T., Kaplan B., Halloran P.F. Molecular correlates of scarring in kidney transplants: the emergence of mast cell transcripts. Am J Transplant 2009; 9: 169–178, DOI: 10.1111/j.1600- 6143.2008.02462.

4. Sethi S., Fervenza F.C. Membranoproliferative glomerulonephritis–a new look at an old entity. N Engl J Med 2012; 366: 1119–1131, DOI: 10.1056/NEJMra1108178.

5. Pickering M.C., D’Agati V.D., Nester C.M., Smith R.J., Haas M., Appel G.B. et al. HTC3 glomerulopathy: consensus report. Kidney Int 2013; 84: 1079–1089, DOI: 10.1038/ ki.2013.377.

6. Hildebrandt F. Genetic kidney diseases. Lancet 2010; 375: 1287–1295, DOI: 10.1016/S0140-6736(10)60236-X.

7. Игнатова М.С. Детская нефрология. М: OOO «МИА» 2011; 696. [Ignatova M.S. Pediatric Nephrology. Moscow: OOO «MIA» 2011; 696. (in Russ)]

8. Hinkes B.G., Mucha B., Vlangos C.N., Gbadegesin R., Liu J., Hasselbacher K. et al. Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2) Pediatrics 2007; 119(4): e907–919, DOI: 10.1542/peds.2006–2164.

9. Hinkes B., Vlangos C., Heeringa S., Mucha B., Gbadegesin R., Liu J. et al. Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2008; 19(2): 365–371, DOI: 10.1681/ ASN.2007040452.

10. Liapis H., Jain S. The interface of genetics with pathology in alport nephritis. J Am Soc Nephrol 2013; 24: 1925–1927, DOI: 10.1681/ASN.2013080913.

11. Meister G., Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature 2004; 431: 343–349, DOI: 10.1038/ nature02873.

12. Bartels C.L., Tsongalis G.J. MicroRNAs: novel biomarkers for human cancer. Clin Chem 2009; 55: 623–631, DOI: 10.1373/ clinchem.2008.112805.

13. Schena F.P., Serino G., Sallustio F. MicroRNAs in kidney diseases. New promising biomarkers for diagnosis and monitoring. Nephrol Dial Transplant 2014; 29(4): 755–763, DOI: 10.1093/ndt/gft223.

14. Szeto C.-C. Urine miRNA in nephrotic syndrome. Clin Chim Acta 2014; 436: 308–313, DOI: 10.1016/j.cca.2014.06.016.

15. Serino G., Sallustio F., Cox S.N., Pesce F., Schena F.P. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol 2012; 23: 814–824, DOI: 10.1681/ASN.2011060567.

16. Putta S., Lanting L., Sun G., Lawson G., Kato M., Natarajan R. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J Am Soc Nephrol 2012; 23: 458– 469, DOI: 10.1681/ASN.2011050485.

17. Weiland M., Gao X.H., Zhou L., Mi Q.S. Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol 2012; 9: 850–859, DOI: 10.4161/ rna.20378.

18. Zhang C., Zhang W., Chen H.M., Liu C., Wu J., Shi S., Liu Z.H. Plasma microRNA-186 and proteinuria in focal segmental glomerulosclerosis. Am J Kidney Dis 2015; 65: 223– 232; DOI: 10.1053/j.ajkd.2014.07.013

19. Doaa M.Y., Rabab M.E., Hosam S.A. Soluble Interleukine-2 Receptor and MDR1 Gene Expression Levels as Inflammatory Biomarkers for Prediction of Steroid Response in Children With Nephrotic Syndrome. IJKD 2011; 5: 154–161, DOI: 10.1053/j.ajkd.2014.07.013.

20. Julia M.B., Christine E.S., Raman V. PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet Genomics 2013; 23(10): 563–585, DOI: 10.1097/ FPC.0b013e328364db84.