scholarly journals Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone

2020 ◽  
Author(s):  
Rajiv Agarwal ◽  
Stefan D Anker ◽  
George Bakris ◽  
Gerasimos Filippatos ◽  
Bertram Pitt ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Diabetic Kidney Disease ◽  
Standard Of Care ◽  
Phase Iii ◽  
Diabetic Kidney ◽  
Mortality And Morbidity

Abstract Despite the standard of care, patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) progress to dialysis, are hospitalized for heart failure and die prematurely. Overactivation of the mineralocorticoid receptor (MR) causes inflammation and fibrosis that damages the kidney and heart. Finerenone, a nonsteroidal, selective MR antagonist, confers kidney and heart protection in both animal models and Phase II clinical studies; the effects on serum potassium and kidney function are minimal. Comprising the largest CKD outcomes program to date, FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) are Phase III trials investigating the efficacy and safety of finerenone on kidney failure and cardiovascular outcomes from early to advanced CKD in T2D. By including echocardiograms and biomarkers, they extend our understanding of pathophysiology; by including quality of life measurements, they provide patient-centered outcomes; and by including understudied yet high-risk cardiorenal subpopulations, they have the potential to widen the scope of therapy in T2D with CKD. Trial registration number: FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049)

scholarly journals Diabetic kidney disease: update on clinical management and non-glycaemic effects of newer medications for type 2 diabetes

2021 ◽  
Vol 12 ◽  
pp. 204201882110206
Author(s):  
Áine M. de Bhailís ◽  
Shazli Azmi ◽  
Philip A. Kalra
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Kidney ◽  
Renal Outcomes ◽  
First Choice ◽  
Treatment Of Diabetes

Type 2 diabetes is a leading cause of chronic kidney disease worldwide and continues to increase in prevalence. This in turn has significant implications for healthcare provision and the economy. In recent years there have been multiple advances in the glucose-lowering agents available for the treatment of diabetes, which not only modify the disease itself but also have important benefits in terms of the associated cardiovascular outcomes. The cardiovascular outcome trials of agents such as glucagon-like peptide-1 receptor agonists (GLP-RAs) and sodium glucose cotransporter 2 inhibitors (SGLT-2) have demonstrated significant benefits in reducing major adverse cardiovascular events, admissions for heart failure and in some cases mortality. Secondary analysis of these trials has also indicated significant renoprotective benefit. Canagliflozin and Renal Outcomes in Type 2 Diabetes Mellitus and Nephropathy (CREDENCE) a renal-specific trial, has shown major benefits with canagliflozin for renal outcomes in diabetic kidney disease, and similar trials with other SGLT-2 inhibitors are either underway or awaiting analysis. In this article we review current goals of treatment of diabetes and the implications of advancing renal impairment on choice of treatments. Areas discussed include the diagnosis of diabetic kidney disease and current treatment strategies for diabetic kidney disease ranging from lifestyle modifications to glycaemic control. This review focuses on the role of GLP-RAs and SGLT-2 inhibitors in treating those with diabetes and chronic kidney disease with some illustrative cases. It is clear that these agents should now be considered first choice in combination with metformin in those with diabetes and increased cardiovascular risk and/or reduced renal function, and in preference to other classes such as dipeptidyl peptidase-4 (DPP-4) inhibitors or sulphonylureas.

scholarly journals Performance of prediction models for nephropathy in people with type 2 diabetes: systematic review and external validation study

BMJ ◽  
2021 ◽  
pp. n2134
Author(s):  
Roderick C Slieker ◽  
Amber A W A van der Heijden ◽  
Moneeza K Siddiqui ◽  
Marlous Langendoen-Gort ◽  
Giel Nijpels ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
General Population ◽  
Diabetic Kidney Disease ◽  
Prediction Models ◽  
External Validation ◽  
Diabetic Kidney

Abstract Objectives To identify and assess the quality and accuracy of prognostic models for nephropathy and to validate these models in external cohorts of people with type 2 diabetes. Design Systematic review and external validation. Data sources PubMed and Embase. Eligibility criteria Studies describing the development of a model to predict the risk of nephropathy, applicable to people with type 2 diabetes. Methods Screening, data extraction, and risk of bias assessment were done in duplicate. Eligible models were externally validated in the Hoorn Diabetes Care System (DCS) cohort (n=11 450) for the same outcomes for which they were developed. Risks of nephropathy were calculated and compared with observed risk over 2, 5, and 10 years of follow-up. Model performance was assessed based on intercept adjusted calibration and discrimination (Harrell’s C statistic). Results 41 studies included in the systematic review reported 64 models, 46 of which were developed in a population with diabetes and 18 in the general population including diabetes as a predictor. The predicted outcomes included albuminuria, diabetic kidney disease, chronic kidney disease (general population), and end stage renal disease. The reported apparent discrimination of the 46 models varied considerably across the different predicted outcomes, from 0.60 (95% confidence interval 0.56 to 0.64) to 0.99 (not available) for the models developed in a diabetes population and from 0.59 (not available) to 0.96 (0.95 to 0.97) for the models developed in the general population. Calibration was reported in 31 of the 41 studies, and the models were generally well calibrated. 21 of the 64 retrieved models were externally validated in the Hoorn DCS cohort for predicting risk of albuminuria, diabetic kidney disease, and chronic kidney disease, with considerable variation in performance across prediction horizons and models. For all three outcomes, however, at least two models had C statistics >0.8, indicating excellent discrimination. In a secondary external validation in GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland), models developed for diabetic kidney disease outperformed those for chronic kidney disease. Models were generally well calibrated across all three prediction horizons. Conclusions This study identified multiple prediction models to predict albuminuria, diabetic kidney disease, chronic kidney disease, and end stage renal disease. In the external validation, discrimination and calibration for albuminuria, diabetic kidney disease, and chronic kidney disease varied considerably across prediction horizons and models. For each outcome, however, specific models showed good discrimination and calibration across the three prediction horizons, with clinically accessible predictors, making them applicable in a clinical setting. Systematic review registration PROSPERO CRD42020192831.

Doppler ultrasoundgraphy capability in the evaluation of renal circulation in patients with type 2 diabetes mellitus and chronic kidney disease

2020 ◽  
Vol 22 (3) ◽  
pp. 99-102
Author(s):  
D. A. Shipilova ◽  
O. A. Nagibovich ◽  
N. A. Shchukina
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Blood Flow ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renal Circulation ◽  
Diabetic Kidney

Abstract. The 72 patients with type 2 diabetes mellitus and chronic kidney were examined to clarify Doppler ultrasound capability in assessing the renal circulation. Hemodynamics changes in kidney tissue appeared on early stage of diabetic kidney disease. Intrarenal hemodynamics disturbances in patients with type 2 diabetes mellitus is revealed through a decrease in the minimum blood flow velocity and an increase in the intrarenal vascular resistance parameters. We found the correlation between dopplerographic indicators, kidney functions and other parameters (age, disease duration, glycated hemoglobin level), which play a pathogenetic role in diabetic kidney disease. Serum creatinine level and glomerular filtration rate were indicators of renal hemodynamic changes. Resistant index above 0,7 conventional units, pulsatility index above 1,54 conventional units, systolic diastolic ratio above 3,8 conventional units were ultrasound signs of kidney damage. Patients without standard signs of chronic kidney disease have diagnostically significant index of resistance in 72% of cases, a pulsation index in 50%, a systolic-diastolic ratio in 28%. Renal blood flow examination in right segmental artery area will be use for non-invasive diagnosis and estimation of kidney dysfunction in patients with type 2 diabetes mellitus.

Albuminuria Is More Closely Associated with Vascular Endothelial Function than eGFR in Type 2 Diabetes with Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 443-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
YUKO YAMAZAKI ◽  
KOKA MOTOYAMA ◽  
TOMOAKI MORIOKA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Diabetic Kidney Disease ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Diabetic Kidney

scholarly journals Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease

2021 ◽  
Author(s):  
Alberto Ortiz ◽  
Charles J Ferro ◽  
Olga Balafa ◽  
Michel Burnier ◽  
Robert Ekart ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Mineralocorticoid Receptor ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Cardiovascular Death ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Diabetic Kidney

Abstract Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease.

Progression of diabetic kidney disease and trajectory of kidney function decline in Chinese patients with Type 2 diabetes

2019 ◽  
Vol 95 (1) ◽  
pp. 178-187 ◽  
Author(s):  
Guozhi Jiang ◽  
Andrea On Yan Luk ◽  
Claudia Ha Ting Tam ◽  
Fangying Xie ◽  
Bendix Carstensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Kidney Function ◽  
Diabetic Kidney Disease ◽  
Chinese Patients ◽  
Diabetic Kidney ◽  
Kidney Function Decline

scholarly journals Association Between Classical and Emerging Risk Factors for Diabetic Kidney Disease and Albuminuria in a Cohort of Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 18 (3) ◽  
pp. 17-25
Author(s):  
Stoiţă Marcel ◽  
Popa Amorin Remus
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Significant Positive Association ◽  
Diabetic Kidney

Abstract The presence of albuminuria in patients with type 2 diabetes mellitus is a marker of endothelial dysfunction and also one of the criteria for diagnosing diabetic kidney disease. The present study aimed to identify associations between cardiovascular risk factors and renal albumin excretion in a group of 218 patients with type 2 diabetes mellitus. HbA1c values, systolic blood pressure, diastolic blood pressure were statistically significantly higher in patients with microalbuinuria or macroalbuminuria compared to patients with normoalbuminuria (p <0.01). We identified a statistically significant positive association between uric acid values and albuminuria, respectively 25- (OH)2 vitamin D3 deficiency and microalbuminuria (p <0.01).

scholarly journals Diabetic kidney disease: Act now or pay later

2008 ◽  
Vol 11 (4) ◽  
pp. 988-991
Author(s):  
Robert C Atkins ◽  
Paul Zimmet
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
International Society ◽  
Diabetic Kidney Disease ◽  
International Diabetes Federation ◽  
Diabetic Kidney ◽  
Global Pandemic

In 2003, the International Society of Nephrology and the International Diabetes Federation launched a booklet called “Diabetes in the Kidney: Time to act” [1] to highlight the global pandemic of type 2 diabetes and diabetic kidney disease. ration (PZ)

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