Clinical and laboratory characteristics of the patterns of chronic kidney disease in patients with type 2 diabetes
https://doi.org/10.14341/DM10277
Abstract
BACKGROUND: A growing body of evidence demonstrates increasing prevalence of normoalbuminuric chronic kidney disease (NA-CKD) in subjects with type 2 diabetes (T2D), while proportion of albuminuric pattern is decreasing.
AIMS: To determine the clinical and laboratory parameters associated with different patterns of CKD in patients with T2D.
METHODS: This observational, single-center, cross-sectional study included 360 patients with T2D duration ≥10 years. Patients with urinary albumin/creatinine ratio (UACR) <3 mg/mmol and estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 were classified as no-CKD group (n=89). Patients with UACR <3 mg/mmol and eGFR <60 ml/min/1.73 m2 formed NA-CKD group (n=111). Individuals with eGFR ≥60 ml/min/1.73 m2 and UACR mg/mmol ≥3 were recorded as albuminuric with preserved renal function (A-CKD–, n=87). Patients with eGFR <60 ml/min/1.73 m2 and UACR mg/mmol ≥3 mg/mmol were considered as albuminuric CKD group (A-CKD+, n=73). Urinary nephrin and podocin, the podocyte injury markers, and whey acidic protein four-disulfide core domain protein 2 (WFDC-2), a marker of tubulointerstitial involvement, was assessed by ELISA and compared to control (20 non-diabetic subjects).
RESULTS: Age ≥65 years (p=0.0001), duration of T2D ≥15 years (p=0.0009), female sex (p=0.04), and therapy with diuretics (p=0.0005) were found as risk factors for NA-CKD. The risk factors for A-CKD were male sex (p=0.01), smoking (p=0.01), waist-to-hip ratio >1 (p=0.01) and HbA1c levels >8% (p=0.005). The duration of T2D ≥15 years (p=0.01) and the use of dihydropyridine calcium channel blockers (p=0.01) were associated with A-CKD+. In T2D groups, the urinary excretion of nephrin and podocin was increased (all p<0.001), more markedly in albuminuric individuals (p<0.01 vs. NA-CKD). WFDC-2 excretion was increased in men from all diabetic groups (p<0.05) and in women with decreased eGFR only (p<0.05 vs. the control and NA-CKD).
CONCLUSIONS: The CKD patterns in T2D are heterogeneous according to their clinical and laboratory characteristics. The changes in the excretion of nephrin and podocin indicate the association of albuminuric patterns with podocyte injury. A decrease in eGFR in women with T2D is associated with an increase in urinary excretion of WFDC-2, tubulointerstitial fibrosis marker.
Supporting agencies: This work was carried out as part of the state assignment of the Research Institute of Clinical and Experimental Lymphology - a branch of the Federal State Budget Scientific Institution “Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences”.
About the Authors
Vadim V. Klimontov
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
MD, PhD, Professor
Anton I. Korbut
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
MD, junior research associate laboratory of Endocrinology
Olga N. Fazullina
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
MD, Junior research associate
Ilya V. Vinogradov
MBU Technology Ltd.
Russian Federation
Russian Federation
Senior Researching Developer
Vyacheslav V. Romanov
MBU Technology Ltd.
Russian Federation
Russian Federation
MD, PhD, Head of Сlinical Laboratory
References
1. Afkarian M, Zelnick LR, Hall YN, et al. Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988-2014. JAMA. 2016;316(6):602–610. doi: https://doi.org/10.1001/jama.2016.10924
2. Klimontov VV, Korbut AI. Albuminuric and non-albuminuric patterns of chronic kidney disease in type 2 diabetes. Diabetes Metab Syndr. 2019;13(1):474–479. doi: https://doi.org/10.1016/j.dsx.2018.11.014
3. Marshall SM. Natural history and clinical characteristics of CKD in type 1 and type 2 diabetes mellitus. Adv Chronic Kidney Dis. 2014;21(3):267–272. doi: https://doi.org/10.1053/j.ackd.2014.03.007
4. Ekinci EI, Jerums G, Skene A, et al. Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function. Diabetes Care. 2013;36(11):3620–3626. doi: https://doi.org/10.2337/dc12-2572
5. Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 8-й вып. // Сахарный диабет. — 2017. — Т. 20. — №1S. — C. 1–121. [Dedov II, Shestakova MV, Mayorov AY, et al. Standards of specialized diabetes care. Ed. by Dedov II, Shestakova MV, Mayorov AY. 8th ed. Diabetes Milletus. 2017;20(1S):1–121. (In Russ).] doi: https://doi.org/10.14341/DM20171S8
6. Щукина А.А., Бобкова И.Н., Шестакова М.В., и др. Экскреция с мочой маркеров повреждения подоцитов у больных сахарным диабетом // Терапевтический архив (архив до 2018 г.). — 2015. — Т. 87. — №10. — С. 62–66. [Shchukina AA, Bobkova IN, Shestakova MV, et al. Urinary excretion of markers for podocyte injury in patients with diabetes mellitus. Ter Arkh. 2015;87(10):62–66. (In Russ).] doi: https://doi.org/10.17116/terarkh2015871062-66
7. Hintsa S, Dube L, Abay M, et al. Determinants of diabetic nephropathy in Ayder Referral Hospital, Northern Ethiopia: a case-control study. PLoS One. 2017;12(4):e0173566. doi: https://doi.org/10.1371/journal.pone.0173566
8. Wang L, Sun Y, Cai X, Fu G. The diagnostic value of human epididymis protein 4 as a novel biomarker in patients with renal dysfunction. Int Urol Nephrol. 2018;50(11):2043–2048. doi: https://doi.org/10.1007/s11255-018-1930-x
9. Karlsen NS, Karlsen MA, Høgdall CK, Høgdall EV. HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors: a systematic review. Cancer Epidemiol Biomarkers Prev. 2014;23(11):2285–2295. doi: https://doi.org/10.1158/1055-9965.EPI-14-0447
10. Койчубеков Б.К., Сорокина М.А., Мхитарян К.Э. Определение размера выборки при планировании научного исследования // Международный журнал прикладных и фундаментальных исследований. — 2014. — №4. — С. 71–74. [Koichubekov BK, Sorokina MA, Mkhitaryan XE. Sample size determination in planning of scientific research. International Journal of Applied and Fundamental Research. 2014;(4):71–74. (In Russ).]
11. Hommos MS, Glassock RJ, Rule AD. Structural and functional changes in human kidneys with healthy aging. J Am Soc Nephrol. 2017;28(10):2838–2844. doi: https://doi.org/10.1681/ASN.2017040421
12. Boronat M, García-Cantón C, Quevedo V, et al. Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus. Ren Fail. 2014;36(2):166–170. doi: https://doi.org/10.3109/0886022X.2013.835266
13. Denic A, Mathew J, Lerman LO, et al. Single-Nephron glomerular filtration rate in healthy adults. N Engl J Med. 2017;376(24):2349–2357. doi: https://doi.org/10.1056/NEJMoa1614329
14. Maruta Y, Hasegawa T, Yamakoshi E, et al. Association between serum Na-Cl level and renal function decline in chronic kidney disease: results from the chronic kidney disease Japan cohort (CKD-JAC) study. Clin Exp Nephrol. 2019;23(2):215–222. doi: https://doi.org/10.1007/s10157-018-1631-x
15. Oppermann M, Hansen PB, Castrop H, Schnermann J. Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice. Am J Physiol Renal Physiol. 2007;293(1):F279–287. doi: https://doi.org/10.1152/ajprenal.00073.2007
16. Kieneker LM, Eisenga MF, Joosten MM, et al. Plasma potassium, diuretic use and risk of developing chronic kidney disease in a predominantly white population. PLoS One. 2017;12(3):e0174686. doi: https://doi.org/10.1371/journal.pone.0174686
17. Khan YH, Sarriff A, Adnan AS, et al. Chronic kidney disease, fluid overload and diuretics: a complicated triangle. PLoS One. 2016;11(7):e0159335. doi: https://doi.org/10.1371/journal.pone.0159335
18. Rezonzew G, Chumley P, Feng W, et al. Nicotine exposure and the progression of chronic kidney disease: role of the α7-nicotinic acetylcholine receptor. Am J Physiol Renal Physiol. 2012;303(2):F304–312. doi: https://doi.org/10.1152/ajprenal.00661.2011
19. Orth SR, Viedt C, Ritz E. Adverse effects of smoking in the renal patient. Tohoku J Exp Med. 2001;194(1):1–15. doi: https://doi.org/10.1620/tjem.194.1
20. MacIsaac RJ, Jerums G, Ekinci EI. Effects of glycaemic management on diabetic kidney disease. World J Diabetes. 2017;8(5):172–186. doi: https://doi.org/10.4239/wjd.v8.i5.172
21. Xin W, Li Z, Xu Y, et al. Autophagy protects human podocytes from high glucose-induced injury by preventing insulin resistance. Metabolism. 2016;65(9):1307–1315. doi: https://doi.org/10.1016/j.metabol.2016.05.015
22. Lin WY, Pi-Sunyer FX, Liu CS, et al. Central obesity and albuminuria: both cross-sectional and longitudinal studies in Chinese. PLoS One. 2012;7(12):e47960. doi: https://doi.org/10.1371/journal.pone.0047960
23. Nistala R, Whaley-Connell A. Resistance to insulin and kidney disease in the cardiorenal metabolic syndrome; role for angiotensin II. Mol Cell Endocrinol. 2013;378(1–2):53–58. doi: https://doi.org/10.1016/j.mce.2013.02.005
24. Hayashi K, Wakino S, Sugano N, et al. Ca2+ channel subtypes and pharmacology in the kidney. Circ Res. 2007;100(3):342–353. doi: https://doi.org/10.1161/01.RES.0000256155.31133.49
25. Ott C, Schneider MP, Raff U, et al. Effects of manidipine vs. amlodipine on intrarenal haemodynamics in patients with arterial hypertension. Br J Clin Pharmacol. 2013;75(1):129–135. doi: https://doi.org/10.1111/j.1365-2125.2012.04336.x
26. Petrica L, Vlad M, Vlad A, et al. Podocyturia parallels proximal tubule dysfunction in type 2 diabetes mellitus patients independently of albuminuria and renal function decline: A cross-sectional study. J Diabetes Complications. 2017;31(9):1444–1450. doi: https://doi.org/10.1016/j.jdiacomp.2017.01.007
27. Okada T, Nagao T, Matsumoto H, et al. Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria. Nephrology (Carlton). 2012;17(1):68–75. doi: https://doi.org/10.1111/j.1440-1797.2011.01525.x
28. Afroz T, Sagar R, Reddy S, et al. Clinical and histological correlation of diabetic nephropathy. Saudi J Kidney Dis Transpl. 2017;28(4):836–841.
Supplementary files
|
|
1. Fig. 1. Research design (scheme). Legend: CKD– - patients with type 2 diabetes without CKD; NA-CKD - normal albuminuric variant of CKD; A-CKD– - albuminuria without a decrease in GFR; A-CKD + - albuminuric variant of CKD; T2DM - type 2 diabetes mellitus; WFDC-2 - the main domain of the WAP type; stabilized with four disulfide bonds-2; rSCF - estimated glomerular filtration rate; AKM - urine albumin / creatinine ratio. | |
| Subject | ||
| Type | Other | |
View
(313KB)
|
Indexing metadata ▾ | |
|
|
2. Fig. 2. The level of urinary excretion of nephrin (A) and podocin (B) in patients with type 2 diabetes mellitus: *** - p <0.001 in comparison with the control without diabetes; ### - p <0.001 compared with the group of diabetes mellitus without chronic kidney disease; § - p <0.05; §§§ - p <0.001 in comparison with the group with normoalbuminuric variant of chronic kidney disease (nonparametric median criterion). | |
| Subject | ||
| Type | Other | |
View
(101KB)
|
Indexing metadata ▾ | |
|
|
3. Fig. 2. The level of urinary excretion of nephrin (A) and podocin (B) in patients with type 2 diabetes mellitus: *** - p <0.001 in comparison with the control without diabetes; ### - p <0.001 compared with the group of diabetes mellitus without chronic kidney disease; § - p <0.05; §§§ - p <0.001 in comparison with the group with normoalbuminuric variant of chronic kidney disease (nonparametric median criterion). | |
| Subject | ||
| Type | Other | |
View
(111KB)
|
Indexing metadata ▾ | |
|
|
4. Fig. 3. The level of urinary excretion of WFDC-2 in men (A) and women (B) with type 2 diabetes mellitus: * - p <0.05; *** - p <0.001 in comparison with the control of diabetes insipidus; # - p <0.05 compared with the group of diabetes mellitus without chronic kidney disease (nonparametric median criterion). | |
| Subject | ||
| Type | Other | |
View
(110KB)
|
Indexing metadata ▾ | |
|
|
5. Fig. 3. The level of urinary excretion of WFDC-2 in men (A) and women (B) with type 2 diabetes mellitus: * - p <0.05; *** - p <0.001 in comparison with the control of diabetes insipidus; # - p <0.05 compared with the group of diabetes mellitus without chronic kidney disease (nonparametric median criterion). | |
| Subject | ||
| Type | Other | |
View
(112KB)
|
Indexing metadata ▾ | |
Review
For citations:
Klimontov V.V., Korbut A.I., Fazullina O.N., Vinogradov I.V., Romanov V.V. Clinical and laboratory characteristics of the patterns of chronic kidney disease in patients with type 2 diabetes. Diabetes mellitus. 2019;22(6):515-525. (In Russ.) https://doi.org/10.14341/DM10277
Views:
1376
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
