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Objective:To investigate the expression of microRNA-155 (miR-155) in serum and kidney of C57BLKS/db (db/db) mice and its role in the pathogenesis of diabetic kidney disease (DKD).Methods:The db/db mice ( n=24) were divided into 6, 8, and 10 weeks old groups ( n=8) with age increasing according to the random number table, and C57BL/6 mice of the same age were used as control group. The expression of miR-155 in mouse serum and kidney tissue was determined using real-time quantitative PCR. The mRNA and protein expression of Ets-1, eNOS, AGTR1 in renal tissues was verified by real-time quantitative PCR, Western blotting and immunohistochemistry. Results:Compared with the control group, the expression of miR-155 in serum of db/db mice at 6, 8 and 10 weeks of age were significantly increased (all P<0.01), and the increase of miR-155 was most obvious at 10 weeks of age ( P<0.01). Meanwhile the expression of miR-155 in kidney tissues of 6, 8 and 10 weeks old db/db mice was significantly up-regulated (all P<0.01), and the highest expression of miR-155 was at 10 weeks of age ( P<0.01). Immunohistochemistry showed that Ets-1, eNOS and AGTR1 were localized in glomerular endothelial cells. The results of real-time quantitative PCR showed that the mRNA expression of Ets-1, eNOS and AGTR1 were down-regulated in the kidney tissues of db/db mice at 6, 8 and 10 weeks of age compared to the control(all P<0.05), and the level of down-regulation was the most obvious at 10 week. Western blotting results showed that there was no significant change in Ets-1, eNOS and AGTR1 in 6-week-old db/db mice compared to the control group; the eNOS protein expression was down-regulated at 8 weeks of age ( P<0.05); the expression of AGTR1 protein was down-regulated ( P<0.05), and the protein expression of Ets-1 and eNOS were significantly down-regulated at 10-week age (both P<0.01). Conclusions:The expression of miR-155 in serum and kidney tissues of db/db mice increases during the progression of DKD, while the expression of miR-155 target genes Ets-1, eNOS and AGTR1 decreases with the progression of DKD. MiR-155 may participate in the development and progression of DKD by inhibiting its target genes Ets-1, eNOS and AGTR1, affecting endothelial cell function.
ABSTRACT
Objective@#To investigate the incidence of renal insufficiency in solitary kidney patients and analyze the risk factors.@*Methods@#Patients with solitary kidney who were admitted to the Second Hospital of Lanzhou University from January 2012 to January 2019 were retrospectively selected as subjects. According to estimated glomerular filtration rate (eGFR) level, the patients were divided into two groups: eGFR<60 ml·min-1·(1.73 m2)-1 group and eGFR≥60 ml·min-1·(1.73 m2)-1 group. The data of the general information, laboratory examinations and kidney size were collected, and the differences of the above indicators between the two groups were compared. Logistic regression model was used to analyze the related factors of renal function decline.@*Results@#(1) A total of 323 solitary kidney patients with age of (53.8±15.8) years and median duration of 10.0 years were enrolled in the study, including 203 males (62.8%). There were 150 cases (46.4%) with hypertension, 136 cases(42.1%) with proteinuria, and 134 cases (41.5%) with renal insufficiency, even 29 cases(9.0%) had developed into end-stage renal disease. (2) Compared with those in eGFR≥60 ml·min-1·(1.73 m2)-1group, patients in eGFR<60 ml·min-1·(1.73 m2)-1 group had higher age, mean arterial pressure, serum creatinine, serum uric acid, fasting blood glucose, and higher proportion of hypertension and proteinuria, but had lower proportion of congenital solitary kidney, hemoglobin, plasma albumin and residual kidney diameter. The differences of above indicators were statistically significant (all P<0.05). (3) Logistic regression analysis showed that increasing age (every ten years, OR=1.752, 95% CI 1.455-2.109, P<0.001), anemia (OR=2.327, 95% CI 1.356-3.994, P=0.002), hyperuricemia (OR=5.097, 95% CI 2.873-9.042, P<0.001) and high urine protein level (every 1+, OR=1.515, 95% CI 1.197-1.919, P=0.001) were independent risk factors for renal dysfunction in solitary kidney patients.@*Conclusions@#The incidence of renal insufficiency in solitary kidney patients is 41.5%. Patients with solitary kidney may perform varying degrees of kidney damage, such as hypertension, proteinuria and eGFR decline. Increasing age, anemia, hyperuricemia and high urine protein level are independent risk factors for renal insufficiency in solitary kidney patients.
ABSTRACT
Objective To investigate the incidence of renal insufficiency in solitary kidney patients and analyze the risk factors. Methods Patients with solitary kidney who were admitted to the Second Hospital of Lanzhou University from January 2012 to January 2019 were retrospectively selected as subjects. According to estimated glomerular filtration rate (eGFR) level, the patients were divided into two groups: eGFR<60 ml·min-1·(1.73 m2)-1 group and eGFR≥60 ml·min-1·(1.73 m2)-1 group. The data of the general information, laboratory examinations and kidney size were collected, and the differences of the above indicators between the two groups were compared. Logistic regression model was used to analyze the related factors of renal function decline. Results (1) A total of 323 solitary kidney patients with age of (53.8 ± 15.8) years and median duration of 10.0 years were enrolled in the study, including 203 males (62.8％). There were 150 cases (46.4％) with hypertension, 136 cases(42.1％) with proteinuria, and 134 cases (41.5％) with renal insufficiency, even 29 cases(9.0％) had developed into end-stage renal disease. (2) Compared with those in eGFR≥60 ml·min-1·(1.73 m2)-1group, patients in eGFR<60 ml·min-1·(1.73 m2)-1 group had higher age, mean arterial pressure, serum creatinine, serum uric acid, fasting blood glucose, and higher proportion of hypertension and proteinuria, but had lower proportion of congenital solitary kidney, hemoglobin, plasma albumin and residual kidney diameter. The differences of above indicators were statistically significant ( all P<0.05). (3) Logistic regression analysis showed that increasing age (every ten years, OR=1.752, 95％CI 1.455-2.109, P<0.001), anemia (OR=2.327, 95％CI 1.356-3.994, P=0.002), hyperuricemia (OR=5.097, 95％CI 2.873-9.042, P<0.001) and high urine protein level (every 1+, OR=1.515, 95％CI 1.197-1.919, P=0.001) were independent risk factors for renal dysfunction in solitary kidney patients. Conclusions The incidence of renal insufficiency in solitary kidney patients is 41.5％. Patients with solitary kidney may perform varying degrees of kidney damage, such as hypertension, proteinuria and eGFR decline. Increasing age, anemia, hyperuricemia and high urine protein level are independent risk factors for renal insufficiency in solitary kidney patients.