scholarly journals Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiaomei Yang ◽  
Xuke Han ◽  
Qing Wen ◽  
Xianliang Qiu ◽  
Huan Deng ◽  
...  
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Protective Effect ◽  
Blood Stasis ◽  
Histopathological Changes ◽  
Podocyte Injury ◽  
Persistent Proteinuria ◽  
Chinese Patent

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

scholarly journals MO638ANEMIA IN DIABETIC PATIENTS REFLECTS SEVERE TUBULOINTERSTITIAL INJURY AND ASSISTS CLINICALLY IN PREDICTING DIAGNOSIS OF DIABETIC NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Soichiro Yokota ◽  
Kenji Ito ◽  
Maho Watanabe ◽  
Koji Takahashi ◽  
Naoko Himuro ◽  
...  
Keyword(s):  
Renal Function ◽  
Regression Analysis ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Kidney Biopsy ◽  
Renal Pathology ◽  
Diabetic Patients ◽  
Pathological Findings

Abstract Background and Aims Diabetic nephropathy (DN) is currently a leading cause of end-stage kidney disease worldwide. Kidney biopsy is generally performed in diabetic patients to discriminate between DN and non-diabetic kidney disease (NDKD), and to provide more specific treatments. In addition to conventional predicting factors of DN, recent studies suggested the predictive value of anemia in the diagnosis of DN, however detailed pathophysiology and the significance of anemia in renal pathology are not fully understood. This study aimed to investigate the impact of anemia on renal pathology and clinical course in patients who underwent kidney biopsy. Method We reviewed 81 patients (60.4 ± 13.7 years, 54 men and 27 women) with type 2 diabetes who underwent percutaneous kidney biopsy in Fukuoka University Hospital from January 2001 through March 2020. DN was diagnosed by mesangial expansion or nodular glomerulosclerosis observed under a light microscope, and immunofluorescence assisted in differentiating NDKD from DN. Anemia was defined as hemoglobin level <13 g/dL in males and <12 g/dL in females in accordance with the World Health Organization standards. Laboratory and pathological findings, and clinical courses were investigated. Results According to their pathological findings, patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51). There were 11 types of NDKD. Of these, membranous nephropathy was the most common (23.5%), followed by IgA nephropathy (17.6%), and crescentic glomerulonephritis (13.7%). In multiple logistic regression analysis, absence of severe hematuria (odds ratio (OR) 11.66, 95% confidence interval (CI) 1.68 - 89.9) and presence of anemia (OR 11.38, 95% CI 2.51 - 51.52) were significantly related with the diagnosis of DN. Akaike’s information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than the NDKD group (p<0.05) regardless of the rate of global glomerulosclerosis (figure), and IF/TA was related to the prevalence of anemia (odds ratio: 7.31, 95% confidence interval: 2.33 - 23.00) in multivariate regression analysis. These results suggest DM-associated severe IF/TA (compared with NDKD) impaired erythropoietin production, resulting in earlier anemia, independent of glomerular injuries and renal function. Furthermore, the renal prognosis was significantly better in the NDKD group than in the DN group using Log-rank test (p<0.05). Conclusion DN is associated with anemia because of severe IF/TA regardless of renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.

scholarly journals The role of renal dipeptidyl peptidase-4 in kidney disease: renal effects of dipeptidyl peptidase-4 inhibitors with a focus on linagliptin

2018 ◽  
Vol 132 (4) ◽  
pp. 489-507 ◽  
Author(s):  
Keizo Kanasaki
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Kidney Disease ◽  
Dipeptidyl Peptidase ◽  
Renal Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Membrane Bound

Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin β1 that enhances signaling by transforming growth factor-β1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.

Spironolactone in type 2 diabetic nephropathy: effects on proteinuria, blood pressure and renal function

2006 ◽  
Vol 24 (11) ◽  
pp. 2285-2292 ◽  
Author(s):  
Anton H van den Meiracker ◽  
Rini GA Baggen ◽  
Sacha Pauli ◽  
Anouk Lindemans ◽  
Arnold G Vulto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
Type 2 Diabetic

scholarly journals Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

scholarly journals Administration of RAS Inhibitor before the Onset of Diabetic Nephropathy Counteracts the Adverse Effect of Chronic Hyperglycemia and Reduces the Augmentation of Urinary Albumin Excretion: A Retrospective Clinical Study

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Hidenori Hirukawa ◽  
Shinji Kamei ◽  
Tomohiko Kimura ◽  
Atsushi Obata ◽  
Kenji Kohara ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Albumin Excretion ◽  
Chronic Hyperglycemia ◽  
Retrospective Clinical Study ◽  
Japanese Subjects

It is very important to explore how we can reduce urinary albumin excretion which is an independent risk factor for ischemic heart disease. In this study, we retrospectively evaluated the effects of RAS inhibitor therapy on diabetic nephropathy in Japanese subjects whose urinary albumin levels were within normal range. We enrolled 100 subjects with type 2 diabetes who did not take any renin-angiotensin system (RAS) inhibitor. We defined the subjects taking RAS inhibitor for more than 3 years as RAS inhibitor group. RAS inhibitor exerted protective effect on the progression of urinary albumin excretion in subjects with type 2 diabetes without diabetic nephropathy. In addition, RAS inhibitor exerted more protective effects on renal function especially in subjects with poor glycemic control. In conclusion, RAS inhibitor could protect renal function against the deleterious effect of chronic hyperglycemia in Japanese subjects with type 2 diabetes even before the onset of diabetic nephropathy.

Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats

2020 ◽  
Vol 11 (4) ◽  
pp. 3706-3718 ◽  
Author(s):  
Min-you Qi ◽  
Xu-tao Wang ◽  
Hui-lin Xu ◽  
Zhang-liang Yang ◽  
Yin Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Protective Effect ◽  
Ferulic Acid ◽  
Podocyte Injury

Ferulic acid protects against diabetic nephropathy in STZ-induced rats by attenuating oxidative stress, inflammation, fibrosis and podocyte injury.

Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy

2015 ◽  
Vol 761 ◽  
pp. 116-124 ◽  
Author(s):  
Eunsoo Jung ◽  
Junghyun Kim ◽  
Sung Ho Kim ◽  
Sanghwa Kim ◽  
Myung-Haing Cho
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Podocyte Injury
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