scholarly journals Significance of Metformin Use in Diabetic Kidney Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4239 ◽  
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Makito Tanabe
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Glucose Lowering ◽  
Diabetic Kidney ◽  
First Line Therapy ◽  
Stage Renal Disease ◽  
End Stage ◽  
Pharmacologic Actions

Metformin is a glucose-lowering agent that is used as a first-line therapy for type 2 diabetes (T2D). Based on its various pharmacologic actions, the renoprotective effects of metformin have been extensively studied. A series of experimental studies demonstrated that metformin attenuates diabetic kidney disease (DKD) by suppressing renal inflammation, oxidative stress and fibrosis. In clinical studies, metformin use has been shown to be associated with reduced rates of mortality, cardiovascular disease and progression to end-stage renal disease (ESRD) in T2D patients with chronic kidney disease (CKD). However, metformin should be administered with caution to patients with CKD because it may increase the risk of lactic acidosis. In this review article, we summarize our current understanding of the safety and efficacy of metformin for DKD.

scholarly journals Renoprotective Effects of DPP-4 Inhibitors

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 246
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Hiroyuki Takahashi ◽  
Ryoko Motonaga ◽  
Makito Tanabe
Keyword(s):  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Review Article ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Membrane Bound ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Dipeptidyl peptidase (DPP)-4 inhibitors are widely used in the treatment of patients with type 2 diabetes (T2D). DPP-4 inhibitors reduce glucose levels by inhibiting degradation of incretins. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. It has been shown that an increased renal DPP-4 activity is associated with the development of DKD. A series of clinical and experimental studies showed that DPP-4 inhibitors have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying renoprotection by DPP-4 inhibitors under diabetic conditions.

DIPEPTIDYL-PEPTIDASE 4 INHIBITORS DID NOT IMPROVE RENAL ENDPOINTS IN ADVANCED DIABETIC KIDNEY DISEASE

2020 ◽  
Vol 26 (12) ◽  
pp. 1486-1496
Author(s):  
Edy Kornelius ◽  
Chien-Ning Huang ◽  
Shih-Chang Lo ◽  
Yu-Hsun Wang ◽  
Yi-Sun Yang
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Dipeptidyl Peptidase ◽  
Diabetic Kidney ◽  
Dipeptidyl Peptidase 4 ◽  
Urine Albumin ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Stage Renal Disease ◽  
End Stage

Objective: The efficacy of dipeptidyl-peptidase 4 inhibitors (DPP4is) in advanced diabetic kidney disease (DKD) is unknown. We investigated whether DPP4is confer renal protective benefits in DKD patients. Methods: We conducted a retrospective cohort study between 2012 and 2018 in Taiwan. We only included type 2 diabetes patients with estimated glomerular filtration rate (eGFR) between 30 and 90 mL/min/1.73 m2 and urine albumin to creatinine ratio between 300 and 5,000 mg/g. Patients with DPP4i prescriptions were selected as cases, while non-DPP4i users served as controls. We followed these patients until the presence of composite primary renal endpoints, which was defined by the earliest occur-rence of clinical renal outcomes. Results: A total of 522 patients were included in the analysis, comprising 273 patients with a DPP4i prescription who were selected as cases and 249 patients without DPP4i prescription who were assigned as controls. Median follow-up duration for DPP4i users and nonusers was 2.2 years and 3.4 years, respectively. At baseline, the mean glycated hemoglobin levels for DPP4i users and nonusers were 8.1% and 8.3%, respectively. Among patients with DPP4i prescriptions, there was no reduction in composite primary renal outcome, with a crude hazard ratio (HR) of 1.50 (95% confidence interval [CI], 0.95 to 2.36). Similar results were observed for the risk of persistent eGFR <15 mL/min/1.73 m2, with a HR of 1.68 (95% CI, 0.90 to 3.13), doubling of serum creatinine level, with a HR of 1.05 (95% CI, 0.15 to 7.45), and end-stage renal disease, with a HR of 0.87 (95% CI, 0.14 to 5.19). Conclusion: DPP4i prescription did not reduce the risk of composite renal endpoints in DKD patients. Abbreviations: BMI = body mass index; CI = confidence interval; CVOT = cardiovascular outcomes trial; DPP4i = dipeptidyl-peptidase 4 inhibitor; DKD = diabetic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = glycated hemoglobin; HR = hazard ratio; SGLT2i = sodium-glucose cotransporter 2 inhibitor; T2D = type 2 diabetes; UACR = urine albumin to creatinine ratio

scholarly journals Therapeutic Strategies for Diabetic Kidney Disease

Diabetology ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 31-35
Author(s):  
Keiichiro Matoba
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Intensive Therapy ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Hemodynamic Changes ◽  
Diabetic Kidney ◽  
Global Epidemic ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is a global epidemic leading to end-stage renal disease (ESRD) and susceptibility to cardiovascular disease, with few therapeutic interventions. A hallmark of DKD is the activation of the renin-angiotensin-aldosterone system and hemodynamic changes in glomerulus. Although intensive therapy with agents that targets those abnormalities lowers the risk of DKD progression, it does not completely abolish the risk of ESRD and cardiovascular events. Recent studies have illustrated the importance of renal inflammation, oxidative stress, and activated Rho-associated protein kinase (ROCK) signaling as essential pathogenesis for the development of DKD. In this commentary, these topics will be discussed.

Diabetic kidney disease in thedb/dbmouse

2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Disease ◽  
Mouse Models ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Matrix Expansion ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.

scholarly journals Retinopathy progression and the risk of end-stage kidney disease: results from a longitudinal Japanese cohort of 232 patients with type 2 diabetes and biopsy-proven diabetic kidney disease

2019 ◽  
Vol 7 (1) ◽  
pp. e000726 ◽  
Author(s):  
Masayuki Yamanouchi ◽  
Mikiro Mori ◽  
Junichi Hoshino ◽  
Keiichi Kinowaki ◽  
Takeshi Fujii ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
End Stage Kidney Disease ◽  
Diabetic Kidney ◽  
Clinical Model ◽  
Renal Lesions ◽  
End Stage

ObjectiveThe predictive value of diabetic retinopathy on end-stage kidney disease (ESKD) has not been fully addressed in patients with type 2 diabetes and diabetic kidney disease.Research design and methodsWe studied 232 patients with type 2 diabetes and biopsy-proven diabetic kidney disease who were screened for diabetic retinopathy during the 1 month of kidney biopsy. We examined the association between retinopathy progression and renal lesions. We used Cox regression analyses to explore the risk of ESKD adjusting for known risk demographic and clinical variables. We assessed the incremental prognostic value of ESKD by adding diabetic retinopathy to the clinical variables.ResultsThe diabetic retinopathy progression positively correlated with all scores of renal lesions, especially with the glomerular-based classification (r=0.41), scores of interstitial fibrosis (r=0.41) and diffuse lesion (r=0.48). During a median follow-up of 5.7 years, 114 patients developed ESKD. Adjusting for known risk factors of ESKD, the HR for ESKD (patients with no apparent retinopathy as a reference) were 1.96 (95% CI 0.62 to 6.17) for patients with mild non-proliferative diabetic retinopathy (NPDR), 3.10 (95% CI 1.45 to 6.65) for patients with moderate NPDR, 3.03 (95% CI 1.44 to 6.37) for patients with severe NPDR, and 3.43 (95% CI 1.68 to 7.03) for patients with proliferative diabetic retinopathy, respectively. Addition of the retinopathy grading to the clinical model alone improved the prognostic value (the global χ2 statistic increased from 155.2 to 164.5; p<0.001), which is an improvement equivalent to the addition of the renal lesion grading to the clinical model.ConclusionsRetinopathy progression appeared to be associated with renal lesions and the development of ESKD. Our findings suggest that diabetic retinopathy and kidney disease share the same magnitude of disease progression, and therefore diabetic retinopathy may be useful for prognosticating the clinical course for diabetic kidney disease.

Diabetic Kidney Disease, We Need to Act Fast

JMS SKIMS ◽  
2010 ◽  
Vol 13 (1) ◽  
pp. 1-3 ◽  
Author(s):  
M Saleem Najar ◽  
Khurshid A Banday
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Chronic Glomerulonephritis ◽  
Kashmir Valley ◽  
Diabetic Kidney ◽  
Life Style Changes ◽  
Cardio Vascular ◽  
End Stage

Diabetes is the leading cause of end-stage kidney failure throughout the world in both developed and developing countries.' The same is now true of Kashmir Valley also. In a study conducted in 1999 amongst 780 patients of chronic kidney disease in the only nephrology unit of the Valley, chronic glomerulonephritis was the commonest cause of chronic kidney disease constituting 33% of the total number.2 But a decade latter in another study diabetes was the leading cause of chronic kidney disease and accounting for 33.3% of the total number.It is very important to alert doctors, patients and govern-ments to the increasing health and socioeconomic problems due to diabetic kidney disease and its sequelae (1) end stage kidney disease requiring renal replacement therapy, and (2) cardio-vascular death. There is a horrifying lack of awareness of diabetic kidney disease at all levels and we need to emphasize that its management involves prevention, recognition and treatment of its complications. Primary prevention of type 2 diabetes will require massive life-style changes. J Med Sci.2010;13(1);1-3

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