FC 063DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE 2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Niels Jong ◽  
Glenn Chertow ◽  
Fan Fan Hou ◽  
John McMurray ◽  
Ricardo Correa-Rotter ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Urinary Albumin ◽  
Creatinine Ratio ◽  
Once Daily ◽  
Diabetes Status ◽  
Subgroup Analyses

Abstract Background and Aims Reductions in albuminuria are consistently associated with a subsequent lower risk of kidney failure. The sodium glucose co-transporter 2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes. Whether this effect persist in patients with chronic kidney disease (CKD) with and without diabetes is unknown. We therefore assessed and compared the effects of dapagliflozin on albuminuria in patients with CKD with and without type 2 diabetes from the DAPA-CKD trial. Method We randomized 4304 patients with CKD and an eGFR of 25-75 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g to dapagliflozin (10 mg once daily) or placebo. Change in albuminuria was a pre-specified exploratory outcome. We used regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to micro- or normoalbuminuria (<300 mg/g), and progression in UACR stage, defined as a transition from non-nephrotic (<3000 mg/g) to nephrotic range albuminuria (≥3000 mg/g), as additional endpoints. Subgroup analyses were performed according to baseline type 2 diabetes status. Results Median (25th to 75th Percentile) UACR was 949 (477-1885) mg/g. In patients with and without type 2 diabetes baseline median UACR was 1017 mg/g and 861 mg/g, respectively. Dapagliflozin, compared to placebo, reduced UACR by 29.3% (95% confidence interval [CI] 25.2, 33.1; p<0.001), with a 35.1% (95%CI 30.6, 39.4) reduction in patients with type 2 diabetes and 14.8% (95%CI 5.9, 22.9) reduction in patients without type 2 diabetes (p for interaction <0.001). Among 3860 patients with UACR ≥300 mg/g at baseline, dapagliflozin significantly increased the likelihood of regression in UACR stage (hazard ratio [HR] 1.81; 95%CI 1.60, 2.05). The corresponding HRs for patients with and without type 2 diabetes were 2.06 (95%CI 1.78, 2.39) and 1.33 (95%CI 1.07, 1.66), respectively (p for interaction 0.001). Among 3820 patients with UACR <3000 mg/g at baseline, dapagliflozin significantly decreased the risk of nephrotic range albuminuria (HR 0.41; 95%CI 0.32, 0.52). The corresponding HRs for patients with and without type 2 diabetes were 0.39 (95%CI 0.29, 0.51) and 0.50 (95%CI 0.30, 0.82), respectively (p for interaction 0.401). Conclusion In patients with CKD with and without type 2 diabetes dapagliflozin significantly reduced albuminuria, with a larger reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR suggest that part of dapagliflozin’s protective effect in patients without diabetes is mediated through pathways unrelated to UACR reduction.

scholarly journals The Role of Paricalcitol In Urinary Albumin-To-Creatinine Ratio in Patients with Type 2 Diabetes and Chronic Kidney Disease

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Filipa Brito Mendes ◽  
Eduarda Carias ◽  
Ana Paula Silva ◽  
Pedro Leão Neves
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Urinary Albumin ◽  
Creatinine Ratio

Insulin degludec allows for better glycaemic control with a lower risk of hypoglycaemia in patients with chronic kidney disease and type 2 diabetes

2020 ◽  
Vol 162 ◽  
pp. 108094
Author(s):  
María Dolores García de Lucas ◽  
Beatriz Avilés Bueno ◽  
Francisco Rivas Ruiz ◽  
Julián Olalla Sierra
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glycaemic Control ◽  
Lower Risk ◽  
Insulin Degludec

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 FP152EFFECT OF BARDOXOLONE METHYL TREATMENT ON URINARY ALBUMIN IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE - POST-HOC ANALYSIS FROM BEAM AND BEACON

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i27-i27
Author(s):  
Peter Rossing ◽  
Geoffrey Block ◽  
Glenn Chertow ◽  
Melanie Chin ◽  
Angie Goldsberry ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Urinary Albumin ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses from the FIGARO-DKD Trial

Circulation ◽  
2021 ◽  
Author(s):  
Gerasimos Filippatos ◽  
Stefan D. Anker ◽  
Rajiv Agarwal ◽  
Luis M. Ruilope ◽  
Peter Rossing ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Cardiovascular Death ◽  
History Of ◽  
The Impact ◽  
New Onset

Background: Chronic kidney disease (CKD) and type 2 diabetes (T2D) are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. These prespecified analyses from FIGARO-DKD assessed the impact of finerenone on clinically important HF outcomes. Methods: Patients with T2D and albuminuric CKD (urine albumin-to-creatinine ratio [UACR] ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] ≥25 to ≤90 ml/min/1.73 m 2 , or UACR ≥300 to ≤5000 mg/g and eGFR ≥60 ml/min/1.73 m 2 ,), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first event outcomes included: new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators). Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI 0.50-0.93]; P =0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including a 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI 0.70-0.95]; P =0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI 0.56-0.90]; P =0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52- 0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups. Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with CKD and T2D, irrespective of a history of HF.

scholarly journals Cardiorenal outcomes with sodium/glucose cotransporter-2 inhibitors in patients with type 2 diabetes and low kidney risk: real world evidence

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Meir Schechter ◽  
Cheli Melzer-Cohen ◽  
Aliza Rozenberg ◽  
Ilan Yanuv ◽  
Gabriel Chodick ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Propensity Score ◽  
Lower Risk ◽  
Urinary Albumin ◽  
Sodium Glucose Cotransporter ◽  
Myocardial Infraction ◽  
Specific Outcome ◽  
End Stage

Abstract Background Randomized controlled trials showed that sodium/glucose cotransporter-2 inhibitors (SGLT2i) protect the heart and kidney in an array of populations with type 2 diabetes (T2D) and increased cardiorenal risk. However, the extent of these benefits also in lower kidney-risk T2D populations needs further investigation. Methods Members of Maccabi Healthcare Systems listed in their T2D registry who initiated new glucose lowering agents (GLA), were divided into SGLT2i initiators and other GLAs (oGLAs). Groups were propensity score-matched by baseline demographic and medical characteristics. Two composite cardiovascular outcomes were defined: all-cause mortality (ACM) or hospitalization for heart failure (hHF); and ACM, myocardial infraction (MI) or stroke. The cardiorenal outcome was: ACM, new end-stage kidney disease (ESKD) or  ≥  40% reduction from baseline estimated glomerular filtration rate (eGFR). Renal-specific outcome was new ESKD or  ≥  40% eGFR reduction. Single components of cardiovascular and kidney outcomes were also assessed. Three subgroup definitions of low baseline kidney-risk were used: eGFR  >  90 ml/min/1.73 m2; urinary albumin below detectable levels; and low risk according to Kidney Disease: Improving Global Outcomes (KDIGO) classification. Analyses were performed utilizing an unadjusted model, and a model adjusted to baseline eGFR and urinary albumin-to-creatinine ratio. Results Between April 1, 2015 and June 30, 2018; 68,187 patients initiated new GLAs — 11,321 SGLT2i initiators and 42,077 oGLAs initiators were eligible. Propensity score-matching yielded two comparable cohorts; each included 9219 participants. Median follow-up was 1.7 years. Compared to oGLAs, SGLT2i initiators had lower incidence of ACM or hHF [HR95%CI  =  0.62(0.51–0.75)]; ACM, MI or stroke [0.67(0.57–0.80)]; the cardiorenal outcome [0.65(0.56–0.76)]; and the renal-specific outcome [0.70(0.57–0.85)]. SGLT2i initiators also had lower risk for ACM, hHF and  ≥  30%,  ≥  40%,  ≥  50%,  ≥  57% eGFR reduction. No difference between groups was observed for MI or stroke. In the low baseline kidney-risk subgroups, SGLT2i initiation was generally associated with lower risk of the cardiovascular and cardiorenal outcomes, driven mainly by lower ACM incidence. Conclusions Our findings in the general population of patients with T2D demonstrates lower risk of cardiorenal outcomes associated with initiation of SGLT2i compared with oGLAs, including specifically in patients with low baseline kidney-risk.

scholarly journals Serum and urinary SOD3 in patients with type 2 diabetes: comparison with early chronic kidney disease patients and association with development of diabetic nephropathy

2019 ◽  
Vol 316 (1) ◽  
pp. F32-F41 ◽  
Author(s):  
Chia-Wen Kuo ◽  
Hsiao-Ling Chen ◽  
Min-Yu Tu ◽  
Chuan-Mu Chen
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Urinary Albumin ◽  
Renal Diseases ◽  
Heparin Binding ◽  
Patients With Diabetes

Extracellular superoxide dismutase 3 (SOD3), one member of the antioxidant defense system and a superoxide scavenger, has been noted to be downregulated in the kidneys of diabetic mice and is characterized by a heparin-binding domain that can anchor the protein to the endothelium and extracellular matrix. The association of the serum and urinary SOD3 levels with diabetic nephropathy in different stages has never been evaluated. It remains unclear how urinary SOD3 changes in different renal diseases. We recruited 98 Taiwanese patients with type 2 diabetes and 10 patients with early chronic kidney disease (CKD) into this study. Biochemical analyses were performed, including evaluation of the serum SOD3, urinary SOD3, urinary albumin, urinary vascular endothelial growth factor (VEGF), and urinary angiotensinogen (ANG). The Kruskal-Wallis rank sum test was used to compare various parameters among the three groups of patients: early CKD, diabetes alone, and diabetes with CKD. Results showed that lower serum and urinary SOD3 levels were observed in the group of patients with diabetes alone. Higher serum and urinary SOD3 levels were observed in the group of patients with diabetes and CKD, which had higher albuminuria and serum creatinine levels. The serum SOD3 levels were significantly positively correlated with renal function, according to the serum creatinine level. The urinary levels of SOD3 were significantly correlated with other urinary biomarkers such as urinary ANG and VEGF. Furthermore, albuminuria can positively predict the serum SOD3 level for the ratio of urinary albumin to urinary creatinine (ACR) >1,190.769 mg/g and the urinary SOD3 level for ACR ≥300 mg/g.

scholarly journals Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and stage 4 chronic kidney disease

2019 ◽  
Vol 96 (4) ◽  
pp. 1030-1036 ◽  
Author(s):  
Peter Rossing ◽  
Geoffrey A. Block ◽  
Melanie P. Chin ◽  
Angie Goldsberry ◽  
Hiddo J.L. Heerspink ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Creatinine Ratio ◽  
Urine Albumin ◽  
Stage 4

scholarly journals Cardiovascular and mortality benefits of sodium–glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jordi Real ◽  
Bogdan Vlacho ◽  
Emilio Ortega ◽  
Joan Antoni Vallés ◽  
Manel Mata-Cases ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Propensity Score ◽  
Lower Risk ◽  
Previous History ◽  
Incidence Rates ◽  
Real World Data

Abstract Background Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium–glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. Methods CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). Results After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47–0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31–0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47–0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52–0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54–0.80; p < 0.001). Conclusions In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

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