Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus
Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM) and chronickidney disease (CKD). Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomer...
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Endocrinology Research Centre
2010
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diabetes mellitus diabetic nephropathy ischemic nephropathy tubulointerstitial fibrosis endothelial dysfunction mediators of inflammation and fibrosis Nutritional diseases. Deficiency diseases RC620-627 |
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diabetes mellitus diabetic nephropathy ischemic nephropathy tubulointerstitial fibrosis endothelial dysfunction mediators of inflammation and fibrosis Nutritional diseases. Deficiency diseases RC620-627 Minara Shamkhalovna Shamkhalova Kseniya Olegovna Kurumova Inna Igorevna Klefortova Ivan Ivanovich Sitkin Alexander Viktorovich Il'in Margarita Ivanovna Arbuzova Nikolay Petrovich Goncharov Gul'nara Viktorovna Katsiya Andrey Alexeevich Aleksandrov Svetlana Semenovna Kukharenko Marina Vladimirovna Shestakova Ivan Ivanovich Dedov Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus |
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Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM) and chronickidney disease (CKD). Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR) > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33), 2 - DM2 patients with diabetic nephropathy (n=24), 3 - DM2 patients with ischemic nephropathy (IN) (n=33) verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta), 4 - DM1 patients with DN (n=30). Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU) by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy). Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b), angiotensin II (AT II), monocyte chemoattractant protein (MCP-1),regulated on activation normal T cell expressed and secreted (RANTES), adhesion factors (intracellular adhesion molecule (ICAM-1), vascular celladhesion molecule (VCAM-1) vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylargnine (ADMA), homocysteine(HCYST), metalloproteinases (MMP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-I). Results. DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6) and extracellular matrix degradation factor(MMP-9) levels compared with patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF), and endothelium-affecting factors (ADMA, homocysteine). Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function. Conclusion. The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency. |
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| author |
Minara Shamkhalovna Shamkhalova Kseniya Olegovna Kurumova Inna Igorevna Klefortova Ivan Ivanovich Sitkin Alexander Viktorovich Il'in Margarita Ivanovna Arbuzova Nikolay Petrovich Goncharov Gul'nara Viktorovna Katsiya Andrey Alexeevich Aleksandrov Svetlana Semenovna Kukharenko Marina Vladimirovna Shestakova Ivan Ivanovich Dedov |
| author_facet |
Minara Shamkhalovna Shamkhalova Kseniya Olegovna Kurumova Inna Igorevna Klefortova Ivan Ivanovich Sitkin Alexander Viktorovich Il'in Margarita Ivanovna Arbuzova Nikolay Petrovich Goncharov Gul'nara Viktorovna Katsiya Andrey Alexeevich Aleksandrov Svetlana Semenovna Kukharenko Marina Vladimirovna Shestakova Ivan Ivanovich Dedov |
| author_sort |
Minara Shamkhalovna Shamkhalova |
| title |
Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus |
| title_short |
Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus |
| title_full |
Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus |
| title_fullStr |
Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus |
| title_full_unstemmed |
Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus |
| title_sort |
factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus |
| publisher |
Endocrinology Research Centre |
| publishDate |
2010 |
| url |
https://doaj.org/article/14455e0a2f3b4597856a4401c1fcf52e |
| work_keys_str_mv |
AT minarashamkhalovnashamkhalova factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT kseniyaolegovnakurumova factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT innaigorevnaklefortova factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT ivanivanovichsitkin factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT alexanderviktorovichilin factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT margaritaivanovnaarbuzova factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT nikolaypetrovichgoncharov factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT gulnaraviktorovnakatsiya factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT andreyalexeevichaleksandrov factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT svetlanasemenovnakukharenko factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT marinavladimirovnashestakova factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus AT ivanivanovichdedov factorspromotingdevelopmentofrenaltubulointerstitiallesionsinpatientswithdiabetesmellitus |
| _version_ |
1718429633519550464 |
| spelling |
oai:doaj.org-article:14455e0a2f3b4597856a4401c1fcf52e2021-11-14T09:00:15ZFactors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus2072-03512072-037810.14341/2072-0351-5502https://doaj.org/article/14455e0a2f3b4597856a4401c1fcf52e2010-09-01T00:00:00Zhttps://www.dia-endojournals.ru/jour/article/view/5502https://doaj.org/toc/2072-0351https://doaj.org/toc/2072-0378Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM) and chronickidney disease (CKD). Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR) > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33), 2 - DM2 patients with diabetic nephropathy (n=24), 3 - DM2 patients with ischemic nephropathy (IN) (n=33) verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta), 4 - DM1 patients with DN (n=30). Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU) by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy). Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b), angiotensin II (AT II), monocyte chemoattractant protein (MCP-1),regulated on activation normal T cell expressed and secreted (RANTES), adhesion factors (intracellular adhesion molecule (ICAM-1), vascular celladhesion molecule (VCAM-1) vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylargnine (ADMA), homocysteine(HCYST), metalloproteinases (MMP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-I). Results. DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6) and extracellular matrix degradation factor(MMP-9) levels compared with patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF), and endothelium-affecting factors (ADMA, homocysteine). Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function. Conclusion. The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency.Minara Shamkhalovna ShamkhalovaKseniya Olegovna KurumovaInna Igorevna KlefortovaIvan Ivanovich SitkinAlexander Viktorovich Il'inMargarita Ivanovna ArbuzovaNikolay Petrovich GoncharovGul'nara Viktorovna KatsiyaAndrey Alexeevich AleksandrovSvetlana Semenovna KukharenkoMarina Vladimirovna ShestakovaIvan Ivanovich DedovEndocrinology Research Centrearticlediabetes mellitusdiabetic nephropathyischemic nephropathytubulointerstitial fibrosisendothelial dysfunctionmediators of inflammation and fibrosisNutritional diseases. Deficiency diseasesRC620-627ENRUСахарный диабет, Vol 13, Iss 3, Pp 134-141 (2010) |