scholarly journals Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

2021 ◽  
Vol 22 (9) ◽  
pp. 4374
Author(s):  
Tomoaki Takata ◽  
Hajime Isomoto
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glycemic Control ◽  
Kidney Injury ◽  
Sglt2 Inhibitors ◽  
Pleiotropic Effects ◽  
Future Research ◽  
Diabetic Patients ◽  
Sodium Glucose Cotransporter ◽  
Stage Renal Disease

Diabetes mellitus is a major cause of chronic kidney disease and end-stage renal disease. However, the management of chronic kidney disease, particularly diabetes, requires vast improvements. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for the treatment of diabetes, have been shown to protect against kidney injury via glycemic control, as well as various other mechanisms, including blood pressure and hemodynamic regulation, protection from lipotoxicity, and uric acid control. As such, regulation of these mechanisms is recommended as an effective multidisciplinary approach for the treatment of diabetic patients with kidney disease. Thus, SGLT2 inhibitors are expected to become key drugs for treating diabetic kidney disease. This review summarizes the recent clinical evidence pertaining to SGLT2 inhibitors as well as the mechanisms underlying their renoprotective effects. Hence, the information contained herein will advance the current understanding regarding the pleiotropic effects of SGLT2 inhibitors, while promoting future research in the field.

STUDY OF OUTCOME OF CHRONIC KIDNEY DISEASE IN DIABETIC PATIENTS IN THANJAVUR MEDICAL COLLEGE HOSPITAL

2021 ◽  
pp. 17-20
Author(s):  
S.Hema Akilandeswari ◽  
K. Rajkanth ◽  
S. Janani
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glycemic Control ◽  
Medical College Hospital ◽  
Diabetic Patients ◽  
Type I ◽  
Strong Positive Correlation ◽  
College Hospital ◽  
Medical College

Background: Diabetes Mellitus is one of the common causes of Chronic Kidney Disease which usually leads to end-stage kidney disease. Thus this study was planned to nd out the outcome of CKD in DM, disease progression, appropriate management and the complications. Methods: A cross sectional study among Diabetes Mellitus patients with Chronic Kidney Disease attending the Department of Nephrology and Department of Medicine in Thanjavur Medical College Hospital during the period of July and August 2018. The duration of study period was 2 months. All patients who attended the outpatient department (OPD) and in-patients departments with Type I and Type II diabetes mellitus associated with chronic kidney disease, on any line of management were included in this study. A total of 101 patients were included. Statistical Package for Social Sciences (SPSS for Windows V20) was used for data analysis. Results: Poor glycemic control, albuminuria, hypertriglyceridemia (greater than 150), increase in LDLlevels (greater than 100), BMI (greater than or equal to 25), poor BP control and a longer duration of diabetes mellitus had a strong positive correlation with decrease in eGFR less than 60 ml/min. Glycemic control, weight reduction and adequate BPcontrol retard the progression of CKD. Conclusion: Albuminuria and decline in eGFR both are independent risk factors for diabetic CKD and are strong predictors of morbidity and mortality from a major vascular event, especially cardiovascular complications and stroke.

Management of acute kidney injury and chronic kidney disease

2017 ◽  
pp. 1087-1096
Author(s):  
Natalie Ebert ◽  
Elke Schaeffner
Keyword(s):  
Older Adults ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Staging System ◽  
Kidney Damage ◽  
The Right ◽  
Stage Renal Disease ◽  
End Stage

Both acute and chronic states of kidney disease have considerable healthcare impact as they can produce enormous disease burden and costs. To classify chronic kidney disease into the CKD staging system, glomerular filtration rate as an index of kidney function, as well as albuminuria as a marker of kidney damage have to be assessed as correctly as possible. Misclassification is a serious concern due to the difficulties in precise GFR assessment and correct interpretation of results. Differentiating between pure senescence and true disease among older adults can be a delicate issue. To find the right renal replacement option for individuals that progress to end-stage renal disease can be challenging, and some older patients may even benefit from conservative care without dialysis. To prevent acute kidney injury as a frequent and potentially life-threatening complication, clinicians need to develop an understanding of the common vulnerability to kidney damage among older adults.

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 PROTON PUMP INHIBITORS AND THE RISK OF CHRONIC KIDNEY DISEASES: A CRITICAL REVIEW

2020 ◽  
pp. 11-14
Author(s):  
SHAREEF J. ◽  
SRIDHAR S. B. ◽  
SHARIFF A.
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
End Stage Renal Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Stage Renal Disease ◽  
End Stage

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.

Renal Failure

2012 ◽  
Author(s):  
Kianoush B. Kashani ◽  
Amy W. Williams
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Renal Failure ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
Clinical Approach ◽  
Mortality And Morbidity ◽  
Electrolyte Disturbances ◽  
Metabolic Bone

Renal failure is caused by acute kidney injury or chronic kidney disease. Acute kidney injury (AKI) is a common, devastating complication that increases mortality and morbidity among patients with various medical and surgical illnesses. Also known as acute renal failure, AKI is a rapid deterioration of kidney function that results in the accumulation of nitrogenous metabolites and medications and in electrolyte and acid-base imbalances. This chapter discusses the definition, epidemiology, pathophysiology, and etiology of AKI; the clinical approach to patients with AKI; and the management of AKI. Chronic kidney disease (CKD) has been categorized into 5 stages. When renal function decreases to stage 3, the complications of CKD become evident. These complications include hypertension, cardiovascular disease, lipid abnormalities, anemia, metabolic bone disease, and electrolyte disturbances. To prevent the progression of CKD, therapy must be directed toward preventing these complications and achieving adequate glucose control in diabetic patients with CKD.

scholarly journals Association of HbA1C Variability and Renal Progression in Patients with Type 2 Diabetes with Chronic Kidney Disease Stages 3–4

2018 ◽  
Vol 19 (12) ◽  
pp. 4116 ◽  
Author(s):  
Mei-Yueh Lee ◽  
Jiun-Chi Huang ◽  
Szu-Chia Chen ◽  
Hsin-Ying Chiou ◽  
Pei-Yu Wu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Glycosylated Hemoglobin ◽  
Diabetic Patients ◽  
Patients With Diabetes ◽  
Cox Analysis ◽  
Stage Renal Disease ◽  
End Stage ◽  
Hba1c Variability

Little is known about the predictive value of glycosylated hemoglobin (HbA1C) variability in patients with advanced chronic kidney disease (CKD). The aim of this study was to investigate whether HbA1C variability is associated with progression to end-stage renal disease in diabetic patients with stages 3–5 CKD, and whether different stages of CKD affect these associations. Three hundred and eighty-eight patients with diabetes and stages 3–5 CKD were enrolled in this longitudinal study. Intra-individual HbA1C variability was defined as the standard deviation (SD) of HbA1C, and the renal endpoint was defined as commencing dialysis. The results indicated that, during a median follow-up period of 3.5 years, 108 patients started dialysis. Adjusted Cox analysis showed an association between the highest tertile of HbA1C SD (tertile 3 vs. tertile 1) and a lower risk of the renal endpoint (hazard ratio = 0.175; 95% confidence interval = 0.059–0.518; p = 0.002) in the patients with an HbA1C level ≥ 7% and stages 3–4 CKD, but not in stage 5 CKD. Further subgroup analysis showed that the highest two tertiles of HbA1C SD were associated with a lower risk of the renal endpoint in the group with a decreasing trend of HbA1C. Our results demonstrated that greater HbA1C variability and a decreasing trend of HbA1C, which may be related to intensive diabetes control, was associated with a lower risk of progression to dialysis in the patients with stages 3–4 CKD and poor glycemic control (HbA1c ≥ 7%).

scholarly journals Found in Translation: Reasons for Optimism in the Pursuit to Prevent Chronic Kidney Disease After Acute Kidney Injury

2019 ◽  
Vol 6 ◽  
pp. 205435811986874
Author(s):  
Samuel A. Silver ◽  
Casimiro Gerarduzzi
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Animal Models ◽  
Kidney Injury ◽  
Narrative Review ◽  
Sources Of Information ◽  
Stage Renal Disease ◽  
End Stage ◽  
Injury Progression

Purpose of review: The current review will discuss on the progress of studying the transition phase between acute kidney injury (AKI) and chronic kidney disease (CKD) through improved animal models, common AKI and CKD pathways, and how human studies may inform different translational approaches. Sources of information: PubMed and Google Scholar. Methods: A narrative review was performed using the main terms “acute kidney injury,” “chronic kidney disease,” “end-stage renal disease,” “animal models,” “review,” “decision-making,” and “translational research.” Key findings: The last decade has shown much progress in the study of AKI, including evidence of a pathophysiological link between AKI and CKD. We are now in a phase of redesigning animal models and discovering mechanisms that can replicate the pathological conditions of the AKI-to-CKD continuum. Translating these findings into the clinic is a barrier that must be overcome. To this end, current efforts include prediction of AKI onset and maladaptive repair, detecting patients susceptible to the progression of chronic maladaptive repair, and understanding shared signaling mechanisms between AKI and CKD. Limitations: This is a narrative review of the literature that is partially influenced by the knowledge, perspectives, and experiences of the authors and their research background. Implications: Overall, this new knowledge from the AKI-to-CKD continuum will help bridge the discontinuity that exists between animal models and patients, resulting in more effective translational biomarkers and therapeutics to test in known AKI pathologies thereby preventing the chronicity of kidney injury progression.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors Improve Cardiovascular Dysfunction in Type 2 Diabetic East Asians

Metabolites ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 794
Author(s):  
Muhammad Afzal ◽  
Fahad A. Al-Abbasi ◽  
Muhammad Shahid Nadeem ◽  
Sultan Alshehri ◽  
Mohammed M. Ghoneim ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Diabetes Management ◽  
Cardiovascular Effects ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
East Asians ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

In East Asians, the incidence of type 2 DM (T2DM) has increased as a result of major alterations in life. Cardiovascular problems are more likely in those with T2DM. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are novel insulin-independent antihyperglycemic drugs that limit renal glucose reabsorption and thereby improve glycemic control. They are used alone or in combination with insulin and other antihyperglycemic medications to treat diabetes, and they are also helpful in protecting against the progression of complications. This review has evaluated the available evidence not only on the efficacy of SGLT2 inhibitors in T2DM, but also on their favourable cardiovascular events in East Asians. DM is an independent risk factor for cardiovascular diseases. As a result, in addition to glycemic control in diabetes management, the therapeutic goal in East Asian diabetic patients should be to improve adverse cardiovascular outcomes. Besides establishing antidiabetic effects, several studies have reported cardioprotective benefits of SGLT2 inhibitors via numerous pathways. SGLT2 inhibitors show promising antidiabetic drugs with potential cardiovascular advantages, given that a high number of diabetic patients in East Asia have co-existing cardiovascular disorders. Despite significant positive results in favour of SGLT2, more research is needed to determine how SGLT2 inhibitors exert these impressive cardiovascular effects.

scholarly journals The role of sodium-glucose cotransporter 2 inhibitors in the treatment of type 2 diabetes: from clinical research to real practice

2020 ◽  
Vol 48 ◽  
Author(s):  
I. V. Misnikova ◽  
Yu. A. Kovaleva ◽  
V. A. Gubkina
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Cardiovascular Diseases ◽  
Kidney Disease ◽  
Glycemic Control ◽  
Insulin Therapy ◽  
Insulin Dose ◽  
Therapy Regimen ◽  
Sodium Glucose Cotransporter

In type 2 diabetes mellitus (T2DM), the development and progression of cardiovascular diseases occurs, which allows it to be considered as a cardiorenal metabolic syndrome. This should be taken into account when choosing hypoglycemic drugs. Patients with T2DM receiving insulin therapy often have a long history of diabetes, cardiovascular disease, chronic kidney disease, obesity, and need to be prescribed high doses of insulin and/or complex insulin therapy regimens to maintain glycemic control, which does not always lead to the achievement of target levels of glycemia and glycated hemoglobin (HbA1c). Adding to any insulin therapy regimen drugs from the class of sodium-glucose cotransporter type 2 inhibitors (SGLT-2), which have proven their cardio- and renoprotective properties, seems to be a rational combination in patients with T2DM and may have a number of advantages. The article presents 4 clinical examples of dapagliflozin administration, a drug from the SGLT2 class, to patients who are on insulin therapy, having T2DM with a  long history (10–26 years), as well as cardiovascular diseases, chronic kidney disease, and obesity. Dapagliflozin administration allowed to improve glycemic control, to stabilize the insulin dose, as well as reduce body weight without increasing the frequency of serious episodes of hypoglycemia in patients who initially received large doses of insulin. In the long term, we can expect reduction of the progression of cardiovascular risks and the risks of hospitalization due to existing complications of the disease.

Abstract 134: Temporal Characterization of the Development Diabetic Induced Renal Disease in Strains of Goto-kakizaki Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Tiffani Slaughter ◽  
Adrienne Paige ◽  
Carlos Rucker ◽  
Patrick Kyle ◽  
Naoki Kojima ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Signaling Pathways ◽  
Molecular Transport ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Patients With Diabetes ◽  
Stage Renal Disease

End stage renal disease is a major problem of patients suffering from diabetes and the development of novel therapeutic drugs are needed to help prevent the progression of diabetic nephropathy (DN). However, little is known about the pathogenesis of DN because the lack of an appropriate rodent model that develops progressive chronic kidney disease and renal histopathology seen in diabetic patients. The current study characterized the temporal changes in renal hemodynamics during the development of renal disease in Goto-Kakizaki (GK Control ) diabetic rats that are resistant to the development of renal disease and a genetically modified GK substrain (GK T2DN ) that is far more susceptible to the development of DN. Both strains have similar elevations in plasma glucose levels by 3 months of age. The GK T2DN strain exhibited hyperfiltration reflected by an increase in GFR (measured by the clearance of FITC-inulin) at 6 months of age compared to GK Control rats. GK T2DN rats develop progressive proteinuria that increases from 39±4 to 524±64 mg/day and a decline in GFR (from 934±68 to 370±50 μL/min/gkw) (n=21) as the rats age from 3 to 18 months of age. In contrast, proteinuria only increased to 194±33 mg/day in GK Control rats and GFR remained relatively unaltered over the same time period (n=19). The kidneys of GK T2DN rats exhibited mesangial expansion, glomerulosclerosis, and interstitial and renal fibrosis characteristic of patients with diabetes while the GK Control strain did not. We next utilized microarray analysis to identify differences in gene signaling pathways in the renal cortex between the two strains at the early onset of renal disease (6 months of age). We found 1266 genes that were differential expressed in signaling pathways associated with inflammation, cell proliferation, molecular transport and apoptosis between the susceptible strain (GK T2DN ) versus the resistant strain (GK Control ). In summary, these data indicate that the GK T2DN rat exhibits hyperfiltration and progressive proteinuria and chronic kidney disease and is a useful model to explore new therapies and genetic factors in the pathogenesis of DN.

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