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1.
J. bras. nefrol ; 43(3): 340-348, July-Sept. 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1340124

ABSTRACT

Abstract Introduction: GFR is estimated by using creatinine and cystatin C to determine renal dysfunction. Our aim was to evaluate estimated GFR (eGFR) based on cystatin C in type 2 diabetic patients with diabetic nephropathy (DN). Methods: Study group included 52 controls (46% male, age: 54.5±12.4) and 101 diabetic patients (46.5% male, age: 58.2±11). The diabetics were divided into three subgroups according to 24-hour urine albumin: normal to mildly increased (A1) (n=51), moderately increased (A2) (n=25), severely increased (A3) (n=25) albuminuria. Creatinine clearance (CrCl) was determined. Correlations between CrCl and eGFRs estimated according to the CKD-EPI, MDRD, and Cockcroft-Gault (CG) formulas, and ROC curves were evaluated. Data were analyzed using SPSS 22.0. Results: Only CKD-EPI-cys eGFR was significantly lower in the A1 group than the controls (p=0.021). All GFRs were lower in the A3 group than the control (CKD-EPI-cr, MDRD, CKD-EPI-cys, CKD-EPI-cr-cys: p=0.0001, CG and CrCl: p=0.001) and A1 (for all GFRs p=0.0001) groups. CKD-EPI-cr (p=0.004), MDRD (p=0.01), CG (p=0.037), CKD-EPI-cys (p=0.033), and CKD-EPI-cr-cys (p=0.016) eGFRs in the A2 group were significantly different from the A1 group. All eGFRs showed a moderate correlation with CrCl in the A1group (CKD-EPI-cr and CKD-EPI-cr-cys: r=0.49, p=0.0001, MDRD: r=0.44, p=0.001, CG r=0.48, p=0.0001: CKD-EPI-cys r=0.40, p=0.004). The area under the CKD-EPI-cys ROC curve was the highest and found to be 0.847 (95%CI 0.763-0.931, p=0.0001). Conclusions: Our results showed that the CKD-EPI-cys eGFR can be useful in detecting the early stage of DN and more predictive than the others for prediction of DN.


Resumo Introdução: A TFG é estimada usando creatinina e cistatina C para determinar a disfunção renal. Nosso objetivo foi avaliar a TFG estimada (TFGe) com base na cistatina C em pacientes com diabetes do tipo 2 com nefropatia diabética (ND). Métodos: O grupo de estudo incluiu 52 controles (46% homens, idade: 54,5±12,4) e 101 pacientes diabéticos (46,5% homens, idade: 58,2±11). Os diabéticos foram divididos em três subgrupos de acordo com a albumina na urina de 24 horas: albuminúria normal a levemente aumentada (A1) (n=51), moderadamente aumentada (A2) (n=25) e severamente aumentada (A3) (n=25). Foi determinado o clearance de creatinina (Clcr). As correlações entre Clcr e TFGe calculadas de acordo com as fórmulas CKD-EPI, MDRD, e Cockcroft-Gault (CG), e as curvas ROC foram avaliadas. Os dados foram analisados usando o SPSS 22.0. Resultados: Somente a TFGe CKD-EPI-cis foi significativamente menor no grupo A1 do que nos controles (p=0,021). Todas as TFGs foram mais baixas no grupo A3 do que no grupo controle (CKD-EPI-cr, MDRD, CKD-EPI-cis, CKD-EPI-cr-cis: p=0,0001, CG e Clcr: p=0,001) e no grupo A1 (para todas as TFGs p=0,0001). As TFGes CKD-EPI-cr (p=0,004), MDRD (p=0,01), CG (p=0,037), CKD-EPI-cis (p=0,033), e CKD-EPI-cr-cis (p=0,016) no grupo A2 foram significativamente diferentes do grupo A1. Todas as TFGes mostraram uma correlação moderada com Clcr no grupo A1 (CKD-EPI-cr e CKD-EPI-cr-cis: r=0,49, p=0,0001, MDRD: r=0,44, p=0,001, CG r=0,48, p=0,0001: CKD-EPI-cis r=0,40, p=0,004). A área sob a curva ROC CKD-EPI-cis foi a mais alta e foi considerada 0,847 (95%IC 0,763-0,931, p=0,0001). Conclusões: Nossos resultados mostraram que a TFGe CKD-EPI-cis pode ser útil na detecção do estágio inicial de ND e com maior valor de predição do que as outras para a predição da ND.

2.
Chinese Journal of Radiology ; (12): 1301-1307, 2021.
Article in Chinese | WPRIM | ID: wpr-910296

ABSTRACT

Objective:To explore the value of quantitative susceptibility mapping (QSM) in evaluating renal injury in patients with early diabetic nephropathy (DN).Methods:From October 2019 to December 2020, 32 patients with early DN were prospectively enrolled in the Third Affiliated Hospital of Soochow University. According to the estimated glomerular filtration rate (eGFR), they were divided into three groups: DN1 (eGFR≥90 ml·min -1·1.73 m -2, 11 cases), DN2 (60-<90 ml·min -1·1.73 m -2, 11 cases) and DN3 (30-<60 ml·min -1·1.73 m -2, 10 cases). At the same time, 32 normal volunteers were recruited as the control group. Both kidneys were scanned by QSM to measure the susceptibility of renal cortex and medulla. Paired samples t-test was used to compare the differences of the susceptibility between left and right kidneys and between cortex and medulla. One-way analysis of variance was performed to compare the differences of corresponding susceptibility values among different groups, and LSD- t was used for the pairwise comparison. Pearson correlation test was performed between the susceptibility value of the medulla and eGFR. The ROC curve was used to analyze the diagnostic efficacy of QSM parameters in the diagnosis of DN and different degrees of severity of DN. Results:The susceptibility values of bilateral renal medulla in normal volunteers and patients with DN were lower than those of renal cortex (all P<0.001). There was no significant difference in the susceptibility value between left and right renal cortex (all P>0.05). There was significant difference in the susceptibility value between left and right medulla (all P<0.05). There was no significant difference in the susceptibility value of bilateral renal cortex among the control group and the DN1-DN3 groups (both P>0.05). The susceptibility values of left renal medulla in control group, DN1, DN2 and DN3 groups were (-4.46±1.16)×10 -2, (-5.96±0.97)×10 -2, (-7.97±1.25)×10 -2, (-9.58±1.45)×10 -2 ppm, of right renal medulla were (-3.70±0.65)×10 -2, (-5.06±1.28)×10 -2, (-7.33±1.46)×10 -2, (-9.09±2.22)×10 -2 ppm, respectively. The overall difference of the susceptibility value of bilateral renal medulla was statistically significant (both P<0.05), and there were significant differences between each two groups (all P<0.05). The linear positive correlation were found between the susceptibility values of renal medulla and the corresponding eGFR (left kidney r=0.732, P<0.001; right kidney r=0.684, P<0.001). The areas under the ROC curve (AUC) of left and right renal medulla susceptibility value in diagnosis of normal and DN were 0.931 and 0.943, of DN1 and DN (2 and 3) were 0.952 and 0.883, of DN (1 and 2) and DN3 were 0.888 and 0.831, respectively. Conclusion:The susceptibility value of QSM quantitative parameter has a certain value in the staging and differential diagnosis of early DN, among which the susceptibility value of renal medulla has higher diagnostic efficiency.

3.
Article in Chinese | WPRIM | ID: wpr-909276

ABSTRACT

Objective:To correlate neutrophil/lymphocyte ratio and platelet/lymphocyte ratio with diabetic nephropathy (DN).Methods:A total of 160 patients with type 2 diabetes mellitus (T2DM) who received treatment between January 2017 and October 2020 in People's Hospital of Suzhou National New & Hi-Tech Industrial Development Zone were included in this study. These patients were randomly divided into DN [urinary albumin-to-creatinine ratio (UACR) ≥ 30 μg/mg, n = 85) and non-DN (UACR < 30 μg/mg, n = 75)] groups according to UACR values. A total of 150 healthy controls who concurrently received health examination were included in the control group. The clinical data and biochemical indicators were collected in each group and their clinical characteristics were compared. The factors that affect DN were analyzed using a logistic regression model. Results:Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with T2DM were (2.14 ± 1.12) and (175.00 ± 56.21), respectively, which were significantly higher than those in the healthy controls [(1.53 ± 0.29), (142.70 ± 37.25), t = 3.584, 5.642, both P < 0.05). NLR and PLR in the DN group were (2.64 ± 1.22) and (278.00 ± 72.23), respectively, which were significantly higher than those in the non-DN group [(1.80 ± 0.90), (193.00 ± 62.40), t = 2.738, 3.166, both P < 0.05)]. Logistic regression analysis showed that NLR and PLR are the risk factors of DN ( OR = 5.981, 1.807; 95% CI = 2.104-15.563, 1.327-2.795). Conclusion:Combined detection of NLR and PLR in the clinic may help early prediction of DN.

4.
Article in Chinese | WPRIM | ID: wpr-907644

ABSTRACT

Objective:To evaluate the clinical efficacy of Jianpi-Huazhuo Decoction in the treatment of complication patients with phlegm-dampness in type 2 diabetes mellitus (T2DM) and Diabetic nephropathies (DN). Methods:A total of 72 patients with with phlegm dampness T2DM and DN in Huaibei Traditional Chinese Medicine Hospital of Anhui Province from June 2018 to June 2020 were randomly divided into two groups with 36 in each group. The control group were treated with oral metformin sustained-release tablets on the basis of diabetes propaganda. The observation group was treated with Jianpi-Huazhuo Decoction on the basis of the control group. Both groups were treated for 4 weeks. The blood glucose (plasma, enzyme method), HbA1c (whole blood, high performance liquid chromatography) and fasting insulin (serum, chemiluminescence method) were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Plasma BUN, SCR and urinary albumin excretion rate (UAER) were measured by automatic biochemical analyzer. The plasma laminin (LN), procollagen Ⅲ (PC Ⅲ) and collagen type Ⅳ (Ⅳ-c) were detected by ELISA. The adverse events during treatment were observed and the clinical efficacy was evaluated. Results:The total effective rate was 86.1% (31/36) in the observation group and 58.3% (21/36) in the control group ( χ2 =6.923, P=0.009). After treatment, the levels of FBG, 2 hPG, HbA1c, FINS and HOMA-IR in the observation group were significanlty lower than those in the control group ( t values were 4.242, 2.751, 3.565, 3.613 and 4.512, respectively, all Ps<0.05). After treatment, the plasma levels of LN, PC Ⅲ and Ⅳ-c were significanlty lower than those in the control group ( t values were 3.612, 1.864 and 2.046, respectively, all Ps<0.05). After treatment, the levels of serum creatinine and urinary albumin excretion rate in the control group were significanlty lower than those in the control group ( t values were 5.864 and 3.286, respectively, all Ps<0.05). Conclusion:The Jianpi-Huazhuo Decoction can reduce the blood glucose level and renal fibrosis related factors in patients with phlegm dampness T2DM complicated with DN, improve the clinical symptoms and improve the clinical curative effect.

5.
Chinese Journal of Nephrology ; (12): 817-823, 2021.
Article in Chinese | WPRIM | ID: wpr-911904

ABSTRACT

Objective:To investigate the effect of acteoside on the expressions of high mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) in the renal tissue of diabetic nephropathy mice.Methods:Among 20 healthy 8-week old C57BL/6J mice, 5 mice were randomly selected as normal control group, the rest were established as type 1 diabetes mellitus (T1DM) models by a single intraperitoneal injection of streptozocin (STZ, 150 mg/kg). T1DM mice were randomly divided into three groups: 5 mice without treatment, 5 mice treated with acteoside and 5 mice treated with irbesartan. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected for biochemical, pathological, and related mRNA and protein detection. The renal tubular epithelial cells (NRK-52E cells) were divided into control group (1 g/L glucose), high glucose group (4.5 g/L glucose) and high glucose+acteoside group (4.5 g/L glucose+32 μmol/L acteoside). Real-time PCR and Western blotting were used to assess the expressions of HMGB1 and NF-κB after 48 hours and 72 hours culturing.Results:Compared with normal control group, blood glucose, 24-hour quantitative urinary protein, blood urea nitrogen (BUN), serum creatinine (Scr) and blood and urine HMGB1 were significantly increased in model group (all P<0.05), along with interstitial inflammatory cell infiltration and messangial matrix expantion, and the expressions of HMGB1 and NF-κB were significantly enhanced (all P<0.05). Compared with model group, histopathologic changes were alleviated and the mRNA and protein expression levels of HMGB1 and NF-κB were lower in the acteoside group (all P<0.05), while the blood glucose level was maintained at high level ( P>0.05), excluding reduced quantitative 24-hour urinary protein, BUN, Scr, and serum and urine HMGB1 (all P<0.05). Compared with control group, the mRNA and protein expressions of HMGB1 and NF-κB were increased in high glucose group of NRK-52E cells (all P<0.05). Compared with high glucose group, the mRNA and protein expressions of HMGB1 and NF-κB in high glucose+acteoside group were down-regulated (all P<0.05). Conclusion:Acteoside may alleviate the nephropathy in STZ-induced diabetic nephropathy mice by down-regulating the expressions of HMGB1 and NF-κB.

6.
Chinese Journal of Nephrology ; (12): 507-515, 2021.
Article in Chinese | WPRIM | ID: wpr-911880

ABSTRACT

Objective:To investigate the role of mitofusion 2 (Mfn2) in high glucose (HG)-induced endoplasmic reticulum stress (ERS) and apoptosis of podocytes.Methods:(1) Streptozocin was used to induce a diabetes mellitus (DM) rat model. Renal histopathological changes in rats were observed by HE staining. Expression of Mfn2 and CCAAT/enhancer-binding protein homologous protein (CHOP) in glomeruli was observed by immunohistochemistry. Protein levels of Mfn2, protein kinase RNA-like ER kinase (PERK), phospho(p)-PERK, and CHOP in glomeruli were analyzed by Western blotting. (2) Conditionally immortalized human podocytes (HPC) cultured in vitro were divided into control, mannitol (MA) and HG groups. Expression of Mfn2 was observed by immunofluorescence. Protein levels of Mfn2, p-PERK, PERK and CHOP in HPC were analyzed by Western blotting. Podocyte apoptosis in each group was evaluated by flow cytometry with AnnexinⅤ-PE/7AAD double staining method. (3) HPC were divided into control, HG, HG+Mfn2-Myc plasmid-transfected and HG+control plasmid-transfected groups. Protein levels of Mfn2, p-PERK, PERK and CHOP in HPC were analyzed by Western blotting. Expression of CHOP was observed by immunofluorescence. Mitochondrial membrane potential in each group was observed by mitochondrial membrane potential assay kit with JC-1. Podocyte apoptosis in each group was evaluated by flow cytometry with AnnexinⅤ-PE/7AAD double staining method. Results:(1) Compared with the control group, the glomerular mesangial matrix of the DM group rats was significantly proliferated, and the expression of Mfn2 was down-regulated with the expression of ERS-related proteins p-PERK/PERK and CHOP up-regulated (all P<0.05). (2) Compared with the control group, Mfn2 was down-regulated and p-PERK/PERK and CHOP were up-regulated in HPC of HG group (all P<0.05). Apoptosis of HPC was also increased in HG group. There was no significant difference in the above indicators between the control group and the mannitol group (all P>0.05). (3) Compared with the HG group, mitochondrial membrane potential of HPC was alleviated and apoptosis of HPC was decreased in HG+Mfn2-Myc plasmid-transfected group ( P<0.05). P-PERK/PERK and CHOP were down-regulated in HG+Mfn2-Myc plasmid-transfected group (both P<0.05). There was no significant difference in the above indicators between the HG group and the HG+control plasmid-transfected group (all P>0.05). Conclusions:Mfn2 down-regulation in HG-stimulated podocytes may induce ERS to increase apoptosis of podocytes. Up-regulation of Mfn2 can alleviate the HG-induced ERS and apoptosis in podocytes.

7.
Chinese Journal of Geriatrics ; (12): 778-783, 2021.
Article in Chinese | WPRIM | ID: wpr-910917

ABSTRACT

Objective:To examine the effects of liraglutide on the transforming growth factor-β1(TGF-β1)/Smads signaling pathway in renal tissues of elderly rats with type 2 diabetes mellitus(T2DM)and to explore the underlying mechanisms.Methods:A total of 75 healthy elderly male Sprague-Dawley rats aged 20 months and weighing(500±100)g were divided into the normal control group(Group N, n=25)and the model group( n=50)by using a random number table.Rats in the model group were given high-glucose and high-fat diets for 8 weeks and then were injected with a single dose(30 mg/kg)of 1% streptozotocin into the abdominal cavity.Forty-eight rats in the model group were successfully molded and were divided into the T2DM group(Group D, n=24)and the intervention group(Group LD, n=24). Rats in Group LD were abdominally injected with liraglutide in a dose of 200 μg·kg -1·d -1, and the other two groups were given an equal volume of saline.At the end of 4, 8 and 12 weeks, eight rats in each group were randomly selected and 24-hour urine collections were made to measure 24-hour urinary protein.Then the rats were anesthetized, blood samples were collected for biochemical tests, and renal tissues were removed for microscopic examination of pathological changes after HE staining.The expression of type Ⅳ collagen(Col-Ⅳ)was detected by using an immunohistochemical method, and the mRNA expression of TGF-β1, Smad3 and Smad7 was detected by using real-time fluorescence quantitative polymerase chain reaction.One-way analysis of variance was used for comparisons between the groups, and the LSD-t test was used for pairwise comparisons. Results:Compared with Group N, Group D showed thickening of the glomerular basement membrane, mesangial proliferation and interstitial fibrosis at each time-point, which grew worse with time, and the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ also increased significantly(12-week: 0.69±0.01 vs.0.15±0.01, 0.51±0.02 vs.0.02±0.01, 183.33±2.08 vs.221.67±2.08, t=89.22, 60.87 and 24.52, P<0.05), while Smad7 mRNA levels decreased( t=13.42, P<0.05). Compared with Group D, the degree of renal fibrosis was reduced, and the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ at 12-week significantly decreased( t=71.703, 37.58 and 20.04, P<0.05), while Smad7 mRNA increased( t=9.96, P<0.05)in Group LD.With prolonged intervention of liraglutide, the lesions were mitigated, the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ decreased, and Smad7 mRNA increased gradually( P<0.05)in Group LD. Conclusions:Liraglutide has anti-renal fibrosis effects via inhibiting the TGF-β1/Smads pathway, thereby reducing the production of Col-Ⅳ, and can delay the progression of renal lesions in elderly T2DM rats.

8.
Einstein (Säo Paulo) ; 19: eAO6000, 2021. tab, graf
Article in English | LILACS | ID: biblio-1345968

ABSTRACT

ABSTRACT Objective To analyze whether passive inhalation of cigarette smoke causes morphological, structural, and functional changes in kidneys of rats. Methods Wistar rats, aged eight weeks, weighing on average 260g, were divided into Control Group and Smoking Group. Each group was subdivided into four groups of ten animals for morphofunctional analysis, in a period of seven and 28 days. The Smoking Group was exposed to smoke of 40 cigarettes per day, at certain times and in automated equipment for cigarette burning, called smoking machine (SM-MC-01). After the exposure period, urine and blood samples were collected for the functional analyses, and the kidneys were dissected and submitted to histological procedures for morphoquantitative analyses. Results After exposure of animals of the Smoking Group, the following were observed: lower weight gain; lower water and feed intake; decreased renal weight, diameter, and volume; reduction in cortical thickness and glomerular volume density; decrease in glomerular and capsular diameter; increase in mesangial density; decreased urine volume; increased levels of glucose, serum creatinine and microalbuminuria; decreased urinary creatinine levels and creatinine clearance rate. Conclusion Passive smoking negatively influences renal morphology and glomerular filtration rate, with effects similar to those described in the literature regarding active smoking.


RESUMO Objetivo Analisar se a inalação passiva da fumaça do cigarro proporciona alterações morfológicas, estruturais e funcionais nos rins de ratos. Métodos Ratos Wistar, com oito semanas de idade, pesando, em média, 260g, foram divididos em Grupo Controle e Grupo Tabagista. Cada grupo foi subdividido em quatro grupos de dez animais para análise morfofuncional, em um período de sete e 28 dias. O Grupo Tabagista foi exposto à fumaça de 40 cigarros por dia, em horários determinados e equipamento automatizado de queima de cigarros, denominado smoking machine (SM-MC-01). Após o período de exposição, foram coletadas amostras de urina e sangue para as análises funcionais, e os rins foram dissecados e submetidos a procedimentos histológicos para análises morfoquantitativas. Resultados Após a exposição dos animais do Grupo Tabagista, observou-se menor ganho de peso; menor consumo de água e ração; menor peso, diâmetro e volume renal; redução em espessura cortical e densidade de volume glomerular; diminuição no diâmetro glomerular e capsular; aumento na densidade mesangial; volume urinário diminuído; níveis aumentados de glicose, creatinina sérica e microalbuminúria; níveis reduzidos de creatinina urinária e redução da taxa de depuração da creatinina. Conclusão O tabagismo passivo influencia negativamente na morfologia renal e na taxa de filtração glomerular, com efeitos semelhantes aos descritos na literatura em relação ao tabagismo ativo.


Subject(s)
Animals , Rats , Tobacco Smoke Pollution/adverse effects , Smoking/adverse effects , Rats, Wistar , Glomerular Filtration Rate , Kidney
9.
J. bras. nefrol ; 42(4): 484-488, Oct.-Dec. 2020. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1154625

ABSTRACT

ABSTRACT Introduction: Idiopathic nodular glomerulosclerosis (ING) is a condition that has a vasculopathic glomerular histological pattern. Case presentation: The authors present the case of a 44-year-old Hispanic smoker female with hypertension and peripheral arterial disease who presented nephrotic syndrome for 2 weeks. The patient was diagnosed with ING by percutaneous renal biopsy results, which showed global nodular mesangial matrix expansion, with linear staining accentuation of glomerular and tubular basement membrane for Immunoglobulin G (IgG) and albumin on immunofluorescence. Conclusions: ING is a rare disease with a poor renal prognosis and wide diagnostic approach; we highlight the importance of analyzing every piece of detail together to reach a definitive diagnosis.


RESUMO Introdução: A glomerulosclerose nodular idiopática (GNI) tem um padrão histológico glomerular vasculopático. Apresentação do caso: Os autores apresentam o caso de uma mulher latino-americana, de 44 anos, fumante, com hipertensão e doença arterial periférica; com síndrome nefrótica por 2 semanas. Ela foi diagnosticada com GNI por biópsia renal percutânea, que mostrou expansão generalizada da matriz mesangial nodular, com acentuação de coloração linear na membrana basal glomerular e tubular para imunoglobulina G (IgG) e albumina à imunofluorescência. Conclusões: A GNI é uma doença rara, com mau prognóstico renal, e com necessidade de uma ampla abordagem diagnóstica. Demonstramos aqui a importância de se analisar todos os detalhes em conjunto para realizar um diagnóstico definitivo.

10.
J. bras. nefrol ; 42(4): 393-399, Oct.-Dec. 2020. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1154630

ABSTRACT

ABSTRACT Objective: To investigate the efficacy and safety of febuxostat on renal function in CKD stage 3 diabetic nephropathy patients. Methods: Patients in our hospital with chronic kidney disease (CKD) stage 3 diabetic nephropathy (DN) complicated by high serum uric acid (360 µmol/L) were recruited. Patients were then divided into treatment group and control group according to the random number table method. All the patients received low purine diet, renin-angiotensin-aldosterone system (RAAS) inhibitors, and adequate routine hypoglycemic treatment. Febuxostat was employed only in the treatment group. The levels of blood uric acid (sUA), serum creatinine (Scr), cystatin C (cys-c), eGFR, 24-hour urine protein quantification, albuminuria, and creatinine ratio (ACR) were evaluated in all patients before and after treatment at 4, 8, 12, and 24 week. Results: No difference was found before treatment between the two groups. After treatment at 4, 8, 12, and 24 week, the levels of sUA, SCr, cys-c, and eGFR between the two groups were significant different (P<0.05). There was no difference in 24-hour urine protein quantification, albuminuria, and creatinine ratio between two groups before treatment, and significant differences were observed after treatment. Fifty percent of patients from the treatment group achieved the treatment goal with 20 mg febuxostat at 4 weeks. Tubular markers were also decreased with the treatment. Conclusions: Febuxostat can reduce uric acid and improve renal function effectively in patients with CKD stage 3 diabetic nephropathy, while being well tolerated. However, the conclusion is still uncertain due to the short term of the study.


RESUMO Objetivo: Investigar a eficácia e segurança do febuxostat na função renal em pacientes com DRC estágio 3, com nefropatia diabética. Métodos: Foram recrutados pacientes em nosso hospital com nefropatia diabética (DN) estágio 3 de doença renal crônica (DRC) complicada por ácido úrico sérico alto (360 µmol/L). Os pacientes foram então divididos em grupo de tratamento e grupo controle, de acordo com o método da tabela de números aleatórios. Todos os pacientes receberam dieta pobre em purinas, inibidores do sistema renina-angiotensina-aldosterona (RAAS) e tratamento hipoglicêmico de rotina. O Febuxostat foi empregado apenas no grupo de tratamento. Os níveis de ácido úrico no sangue (AIU), creatinina sérica (Scr), cistatina C (cys-c), TFGe, quantificação de proteínas na urina em 24 horas, razão albumina e creatinina (ACR) foram avaliados em todos os pacientes antes e após o tratamento às 4, 8, 12 e 24 semanas. Resultados: Nenhuma diferença foi encontrada antes do tratamento entre os dois grupos. Após o tratamento nas 4, 8, 12 e 24 semanas, os níveis de sUA, SCr, cys-c e TFGe entre os dois grupos foram significativamente diferentes (P <0,05). Não houve diferença na quantificação de proteínas na urina em 24 horas, albuminúria e razão de creatinina entre dois grupos antes do tratamento, e diferenças significativas foram observadas após o tratamento. Cinquenta por cento dos pacientes do grupo de tratamento atingiram a meta de tratamento com 20 mg de febuxostat em 4 semanas. Marcadores tubulares também foram reduzidos com o tratamento. Conclusões: O Febuxostat pode reduzir o ácido úrico e melhorar a função renal efetivamente em pacientes com nefropatia diabética estágio com DRC no estágio 3, sendo bem tolerado. No entanto, a conclusão ainda é incerta devido ao curto prazo do estudo.

11.
J. bras. nefrol ; 42(4): 467-477, Oct.-Dec. 2020. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1154642

ABSTRACT

ABSTRACT Sodium glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) were initially approved to improve glycemic control in the treatment of type 2 diabetes. Clinical trials have also demonstrated beneficial effects with regards to cardiovascular and renal parameters. Beyond improving glycemic control, these therapies promote weight loss and lower blood pressure when used individually, and in an additive manner when used together. Accordingly, taking advantage of complementary mechanisms of action with the combined use of these two classes of agents to further improve cardiorenal outcomes is conceptually appealing, but has yet to be explored in detail in clinical trials. In this review, we discuss proposed mechanisms for renal protection, clinical benefits, and adverse events associated with the individual and combined use of SGLT2 inhibitors and GLP-1RA. The management of type 2 diabetes has significantly changed over the last few years, moving away from solely glycemic control towards the concurrent management of associated comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors and GLP-1RA in patients with type 2 diabetes.


RESUMO Inibidores do cotransporter-2 de glicose sódica (SGLT2) e agonistas do receptor peptídeo-1 do tipo glucagon (GLP-1RA) foram inicialmente aprovados para melhorar o controle glicêmico no tratamento da diabetes tipo 2. Os ensaios clínicos também demonstraram efeitos benéficos em relação aos parâmetros cardiovasculares e renais. Além de melhorar o controle glicêmico, essas terapias promovem perda de peso e redução da pressão arterial quando usadas individualmente, e de forma aditiva quando usadas em conjunto. Consequentemente, tirar proveito de mecanismos de ação complementares com o uso combinado dessas duas classes de agentes para melhorar ainda mais os resultados cardiorrenais é conceitualmente atraente, mas ainda precisa ser explorado em detalhes em ensaios clínicos. Nesta revisão, discutimos os mecanismos propostos para proteção renal, benefícios clínicos e eventos adversos associados ao uso individual e combinado de inibidores de SGLT2 e GLP-1RA. O tratamento do diabetes tipo 2 mudou significativamente nos últimos anos, passando do controle exclusivamente glicêmico para o tratamento simultâneo de comorbidades associadas em uma população de pacientes com risco significativo de doença cardiovascular e progressão da doença renal crônica. É nessa perspectiva que procuramos delinear a justificativa para o uso sequencial e/ou combinado de inibidores de SGLT2 e GLP-1RA em pacientes com diabetes tipo 2.

12.
Chinese Journal of Nephrology ; (12): 131-138, 2020.
Article in Chinese | WPRIM | ID: wpr-799545

ABSTRACT

Objective@#To investigate whether Bruton's tyrosine kinase knockout (Btk-/-) in macrophages attenuates diabetic kidney disease in the streptozotocin (STZ)-induced mice.@*Methods@#Macrophages-specific Btk-/- mice and control mice (C57BL/6N) were randomly divided into WT group, diabetic group, Btk-/- group and Btk-/- diabetic group. The diabetic models were induced by STZ (50 mg/kg). After 12 weeks, relevant biochemical parameters and the histological changes of kidneys were detected. The expression of macrophages marker CD68 were detected by immunofluorescence, and the immunohistochemistry was employed to detect the expression of WT1 and Nephrin on renal podocytes. In addition, the expression of fibronectin (FN), collagen type IV (IV-Col), transforming growth factor-β1 (TGF-β1), iNOS, phospho (p)-Btk, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), MAPK and NF-κB signaling pathway were detected by Western blotting. RT-PCR was used to detect the mRNA of IL-1β, TNF-α and monocyte chemotactic protein-1 (MCP-1).@*Results@#Compared with diabetic group, the mice in Btk-/- diabetic group had reduced albuminuria and attenuated kidney histopathology significantly, significantly increased WT1 and Nephrin, significantly decreased expression of CD68, FN, IV-Col and TGF-β1, and these changes were correlated with decreased of renal inflammatory cytokines such as IL-1β, TNF-α, MCP-1 and down-regulating MAPK and NF-κB signaling pathway (all P<0.05).@*Conclusion@#Macrophages-specific Btk-/- may protect the kidney of diabetic mice by reducing the expression of renal inflammatory cytokines in MAPK and NF-κB signaling pathway.

13.
Chinese Journal of Nephrology ; (12): 34-40, 2020.
Article in Chinese | WPRIM | ID: wpr-799027

ABSTRACT

Objective@#To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice.@*Methods@#C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30), by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model. After established successfully, the mice in DKD model group were randomly divided into DKD group (n=10), benazepril group (n=10) and IGF-1R inhibitor group (n=10). IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg·kg-1·d-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg·kg-1·d-1). Normal control group and DKD group were given an equal amount of normal saline. After 8 weeks of feeding, mice were euthanatized. Body weight and kidney weight were recorded. Blood, urine and kidney samples were collected. Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated. Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting.@*Results@#Compared with the normal control group, blood glucose, kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P<0.01). In DKD mice, glomerular expansion, tubular stenosis, tubular swelling and tubular atrophy were significantly detected. Meanwhile, the number of proximal tubular epithelial (PTE) cells was decreased, and the renal tubular injury scores, the average glomerular volume, and pIGF-1R protein expression were increased (all P<0.05). Compared with the DKD group, albumin excretion rate was significantly reduced (P<0.01), the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant. Compared with the DKD group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05). Compared with the benazepril group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05).@*Conclusion@#IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.

14.
Article in Chinese | WPRIM | ID: wpr-862037

ABSTRACT

With the development of radiology, the application of contrast agent is more frequent, and the incidence of contrast-induced acute kidney injury (CI-AKI) is increasing. At present, the pathogenesis of CI-AKI is not completely clear, especially of CI-AKI in the context of diabetes mellitus (DM). The high glucose state in DM may promote CI-AKI. The research advances of the mechanism of CI-AKI in the context of DM were reviewed in this article.

15.
Article in Chinese | WPRIM | ID: wpr-861031

ABSTRACT

Objective: To observe the correlation of intra-renal arterial resistance index (RI) and abdominal aortic intima-media thickness (AA-IMT) in type 2 diabetic nephropathy (DN) patients with color Doppler ultrasonography. Methods: Ninety-three patients with type 2 DN were enrolled, and 35 healthy volunteers were enrolled as control group (group A). DN patients were divided into 3 groups according to the level of glomerular filtration rate (GFR), i.e. group B (n=33)with GFR≥90 ml/(min•1.73 m2), group C (n=31) with 60 ml/(min•1.73 m2)≤GFR<90 ml/(min•1.73 m2) and group D (n=29) with GFR<60 ml/(min•1.73 m2). The intra-renal arterial RI and AA-IMT were obtained with color Doppler ultrasonography. Results: The values of RI and AA-IMT of group B, C, D were higher than those of group A (all P<0.05), while those of group C, D were higher than group B (all P<0.05), and RI and AA-IMT of group D were higher than those of group C (both P<0.05). RI was positively correlated with AA-IMT (r=0.90, P<0.01), glycosylated hemoglobin (r=0.58, P<0.01), glucose (r=0.66, P<0.01), total cholesterol (r=0.42, P<0.01), low density lipoprotein (r=0.03, P<0.01), creatinine (r=0.64, P<0.01), uric acid (r=0.54, P<0.01) and negatively correlative with estimated GFR (eGFR) (r=-0.84, P<0.01), respectively. Taken RI=0.70 as the cut-off point as an indicator of mild renal damage (GFR<90 ml/ [min•1.73 m2] )of DN patients, patients with RI above 0.70 had higher AA-IMT than those with RI lower values (P<0.05), and the sensibility was 84.1%, specificity was 92.9%. AA-IMT and eGFR were independent predictors of RI. Conclusion: The intra-renal arterial RI and AA-IMT in the patients of type 2 DN can be noninvasively obtained with color Doppler ultrasonography for evaluation on microvascular and macrovascular injuries of type 2 DN patients.

16.
Chinese Journal of Nephrology ; (12): 34-40, 2020.
Article in Chinese | WPRIM | ID: wpr-870934

ABSTRACT

Objective To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice.Methods C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30),by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model.After established successfully,the mice in DKD model group were randomly divided into DKD group (n=10),benazepril group (n=10) and IGF-1R inhibitor group (n=10).IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg· kg-1· d-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg· kg-1· d-1).Normal control group and DKD group were given an equal amount of normal saline.After 8 weeks of feeding,mice were euthanatized.Body weight and kidney weight were recorded.Blood,urine and kidney samples were collected.Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated.Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS).Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting.Results Compared with the normal control group,blood glucose,kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P < 0.01).In DKD mice,glomerular expansion,tubular stenosis,tubular swelling and tubular atrophy were significantly detected.Meanwhile,the number of proximal tubular epithelial (PTE) cells was decreased,and the renal tubular injury scores,the average glomerular volume,and plGF-1R protein expression were increased (all P < 0.05).Compared with the DKD group,albumin excretion rate was significantly reduced (P < 0.01),the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant.Compared with the DKD group,the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P < 0.05).Compared with the benazepril group,the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P < 0.05).Conclusion IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.

17.
Article in Korean | WPRIM | ID: wpr-786183

ABSTRACT

Diabetic kidney disease is a microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease resulting in renal replacement therapy. Approximately 30% to 40% of diabetic patients have diabetic kidney disease, which contributes to a significant increase in morbidity and mortality. Microalbuminuria is considered the gold standard for diabetic kidney disease diagnosis; however, its predictive value is restricted. Although blood glucose control, blood pressure control, and angiotensin converting enzyme inhibitors have been the primary treatment strategies, there are no definitive treatment modalities capable of inhibiting the progression of kidney dysfunction in these patients. This study was undertaken to answer seven questions regarding the various aspects of diabetic kidney disease. Why does it develop? what kind of factors affect its development? How is it diagnosed? What are its possible biomarkers? When is a kidney biopsy necessary? What are the preventive and therapeutic options? And what are the novel treatments?


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Biomarkers , Biopsy , Blood Glucose , Blood Pressure , Diabetes Mellitus , Diabetic Nephropathies , Diagnosis , Humans , Kidney , Kidney Failure, Chronic , Mortality , Renal Replacement Therapy
18.
J. bras. nefrol ; 41(4): 509-517, Out.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1056618

ABSTRACT

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.


Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Biomarkers/analysis , Seminal Plasma Proteins/analysis , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/physiopathology , Case-Control Studies , Predictive Value of Tests , Sensitivity and Specificity , Risk Assessment , Creatinine/blood , Early Diagnosis , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/urine , Diabetic Nephropathies/blood , Albuminuria/urine , Glomerular Filtration Rate/physiology , Kidney Failure, Chronic/prevention & control
19.
J. bras. nefrol ; 41(3): 412-422, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040242

ABSTRACT

Abstract Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD. Various microRNAs are involved in the pathogenesis of DKD, while others have a role in nephroprotection and thus serve as promising therapeutic targets for DKD. Serum and urine microRNAs levels have also been considered in the early diagnosis and monitoring of individuals with DKD, since increases in albuminuria, decreases in the glomerular filtration rate, and progression of DKD have been linked to changes in the levels of some microRNAs.


Resumo A doença renal do diabetes (DRD) é uma complicação crônica do diabetes mellitus associada à elevada morbidade e mortalidade, considerada um problema de saúde mundial. Dentre os fatores associados ao desenvolvimento e à progressão da DRD, destacam-se os microRNAs, que consistem em pequenas moléculas de RNA que regulam a expressão gênica por meio da degradação pós-transcricional do RNA mensageiro ou inibição translacional da síntese proteica. Este estudo teve como objetivo realizar uma revisão narrativa buscando investigar os microRNAs como auxiliares no diagnóstico, monitoramento e tratamento da DRD. Vários microRNAs estão envolvidos na patogênese da DRD, enquanto que outros têm papel nefroprotetor, consistindo assim em alvos terapêuticos promissores para o tratamento da DRD. A dosagem laboratorial dos microRNAs no soro e na urina também é muito promissora para o diagnóstico precoce e o monitoramento da DRD, já que os níveis de alguns microRNAs se alteram antes do aumento da albuminúria e da diminuição da taxa de filtração glomerular e podem ainda se alterar com a progressão da DRD.


Subject(s)
Humans , Animals , Rats , MicroRNAs/urine , MicroRNAs/blood , Diabetic Nephropathies/drug therapy , Biomarkers/urine , Biomarkers/blood , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/genetics , Diabetic Nephropathies/pathology , Albuminuria , Molecular Targeted Therapy , Glomerular Filtration Rate
20.
J. bras. nefrol ; 41(3): 315-322, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040245

ABSTRACT

Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.


Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.


Subject(s)
Animals , Male , Rats , Macrophage Migration-Inhibitory Factors/antagonists & inhibitors , Intramolecular Oxidoreductases/antagonists & inhibitors , Protective Agents/therapeutic use , Protective Agents/pharmacology , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/therapy , Blood Glucose , Rats, Wistar , Streptozocin/pharmacology , Creatinine/urine , Creatinine/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/urine , Diabetes Mellitus, Experimental/blood , Diabetic Nephropathies/urine , Diabetic Nephropathies/pathology , Diabetic Nephropathies/blood , Albuminuria/drug therapy , Disease Models, Animal , Glycosaminoglycans/urine , Kidney/pathology , Macrophage Activation
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