Sodium–glucose cotransporter 2 inhibitors: renal outcomes according to baseline albuminuria
TL;DR: In this article, the effect of albuminuria and renal outcomes on renal protection with SGLT2is without significant interaction (P < 0.001) and a trend in relative (P for interaction = 0.25) risk of renal events versus those with lower UACR levels.
Abstract: ABSTRACT Sodium–glucose co-transporter 2 inhibitors (SGLT2is) reduce albuminuria and hard renal outcomes (decline of renal function, renal replacement therapy and renal death) in patients with/without type 2 diabetes at high cardiovascular or renal risk. The question arises whether baseline albuminuria also influences renal outcomes with SGLT2is as reported with renin–angiotensin–aldosterone system inhibitors. Post hoc analyses focusing on albuminuria and renal outcomes of four cardiovascular outcome trials [EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), CANVAS (Canagliflozin Cardiovascular Assessment Study), DECLARE-TIMI 58 (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) and VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial)] and some renal data from two heart failure trials [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) and EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction)] showed renal protection with SGLT2is without significant interaction (P > 0.10) when comparing renal outcomes according to baseline levels (A1, A2 and A3) of urinary albumin:creatinine ratio (UACR), a finding confirmed in a dedicated meta-analysis. Two trials [CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) and DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease)] specifically recruited patients with CKD and UACRs of 200–5000 mg/g. A post hoc analysis of CREDENCE that distinguished three subgroups according to UACR (300–1000, 1000–3000 and >3000 mg/g) showed a greater relative reduction in UACR in patients with lower baseline albuminuria levels (P for interaction = 0.03). Patients with a UACR >1000 mg/g showed a significantly greater reduction in absolute (P for interaction < 0.001) and a trend in relative (P for interaction = 0.25) risk of renal events versus those with lower UACR levels. In conclusion, baseline UACR levels do not significantly influence the nephroprotection by SGLT2is, yet the greater protection in patients with very high UACRs in CREDENCE deserves confirmation. The underlying mechanisms of renal protection with SGLT2is might be different in patients with or without (high) UACR.
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TL;DR: In this paper, a comprehensive review of the results obtained with indirect methods that assess a diuretic effect of SGLT2is is presented, and the specificities of the diuretic activity of the SGL-glucose cotransporter type 2 inhibitors compared with other classical diuretics are discussed.
12 citations
TL;DR: In this paper , the authors showed that there is no evidence of an increased risk of acute kidney injury with RAAS blocker-SGLT2i combinations in absence of haemodynamic instability, despite the fact that a majority of patients received RAAS blockers at baseline.
9 citations
TL;DR: In this paper , albuminuria is used for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden.
Abstract: Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review discusses albuminuria as a marker of kidney damage and cardiorenal risk, highlights the importance of early screening and routine testing for albuminuria in people with T2D, and provides new insights on the optimum management of CKD in T2D using albuminuria as a target in a proposed algorithm. Elevated urine albumin can be used to detect CKD in people with T2D and monitor its progression; however, obstacles preventing early detection exist, including lack of awareness of CKD in the general population, poor adherence to clinical guidelines, and country-level variations in screening and treatment incentives. With albuminuria being used as an entry criterion and a surrogate endpoint for kidney failure in clinical trials, and with novel treatment interventions available to prevent CKD progression, there is an urgent need for early screening and diagnosis of kidney function decline in people with T2D or pre-diabetes.
7 citations
TL;DR: Iceland was one of six European countries with an adjusted incidence of kidney replacement therapy (KRT) in 2018 lower than 100 per million persons and represents one of the best genetically characterized populations in the world, facilitating studies on the influence of the genetic background versus environment and lifestyle on CKD.
Abstract: Abstract Iceland was one of six European countries with an adjusted incidence of kidney replacement therapy (KRT) in 2018 lower than 100 per million persons (pmp), along with Estonia, Montenegro, Russia, Serbia and Finland. It was also one of 10 countries with an adjusted KRT prevalence <900 pmp. Furthermore, the prevalence of chronic kidney disease (CKD) in Iceland is up to 2.44-fold lower and the death rate from CKD up to 3.44-fold lower than in other countries with a low incidence of KRT, suggesting that the low KRT incidence actually reflects a low need for KRT rather than low uptake or availability of KRT. This identifies Iceland as a benchmark for countries trying to reduce KRT incidence. Iceland also represents one of the best genetically characterized populations in the world, facilitating studies on the influence of the genetic background versus environment and lifestyle on CKD. This issue of CKJ reports the incidence and risk factors for CKD in Icelandic adults. Diabetes, acute kidney injury, hypertension, cardiovascular disease, chronic lung disease, malignancy and major psychiatric illness were associated with an increased risk of incident CKD, as were obesity and sleep apnea in women. However, in 75% of incident CKD cases, CKD was first detected in category G3 or higher, emphasizing the need for new tools that allow an earlier diagnosis of CKD that precedes the loss of >50% of the functioning kidney mass and/or wider use of albuminuria as a screening tool. The European Society of Cardiology just recommended assessing albuminuria for routine cardiovascular risk workups for all.
1 citations
TL;DR: The combination of L-carnitine and hemodialysis in the treatment of uremia patients improves the clinical management of the patients, enhances their quality of life, and shows good safety profile.
Abstract: Purpose: To investigate the clinical efficacy of combined use of L-carnitine and hemodialysis in the treatment of uremic patients, and its effect on their quality of life.
Methods: A total of 160 uremic patients who were admitted to Lujiang County People's Hospital from November 2018 to August 2020 were selected and divided equally into dialysis group (hemodialysis), and combined group (L-carnitine + hemodialysis). Some clinical indices and parameters, including safety profile, National Institutes of Health Stroke Scale (NIHSS) score, CD4+ and CD4+/CD8+, and plasma protein levels were evaluated for both study groups.
Results: Patients treated with L-carnitine + hemodialysis in the combined group resulted in significantly higher clinical treatment effectiveness than those in the dialysis group (p < 0.05). However, safety profiles were comparable in the two groups (p > 0.05). No significant difference in NIHSS score between the two groups before treatment, but L-carnitine + hemodialysis led to a better NIHSS score than in the dialysis group after treatment (p < 0.05). However, there were better levels of CD4+ and CD4+/CD8+ in the combined group than in the dialysis group (p < 0.05). Similarly, although pre-treatment plasma protein levels in the two groups were comparable, there were significantly lower plasma protein levels in the combined group than in the dialysis group post-treatment (p < 0.05).
Conclusion: The combination of L-carnitine and hemodialysis in the treatment of uremia patients improves the clinical management of the patients, enhances their quality of life, and shows good safety profile. However, further clinical trials should be carried out prior to the application of the combined treatment in clinical practice.
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TL;DR: Patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal.
Abstract: BackgroundCanagliflozin is a sodium–glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. MethodsThe CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. ResultsThe mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% c...
4,842 citations
TL;DR: Patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes mellitus as well as the availability of outcome data for myocardial infarction and death from cardiovascular causes.
Abstract: �Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance. Our study was limited by a lack of access to original source data, which would have enabled time-to-event analysis. Despite these limitations, patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes.
4,570 citations
University of British Columbia1, East Kent Hospitals University Nhs Foundation Trust2, Newcastle University3, Johns Hopkins University4, University of Groningen5, University of York6, University of Calgary7, University of the Ryukyus8, Tufts University9, University of California, San Francisco10, Peking University11, University of Oxford12
3,645 citations
University of Glasgow1, Brigham and Women's Hospital2, Yale University3, University of Copenhagen4, University of Missouri–Kansas City5, National University of Cordoba6, Wrocław Medical University7, Harvard University8, University of Minnesota9, Charles University in Prague10, Saarland University11, National Yang-Ming University12, Taipei Veterans General Hospital13, Slovak Medical University14, Fudan University15, University of Calgary16, Libin Cardiovascular Institute of Alberta17, Sofia Medical University18, University of Gothenburg19, Semmelweis University20, University of São Paulo21, Montreal Heart Institute22, University of Toronto23, Uppsala University24, University of Wisconsin-Madison25, AstraZeneca26
TL;DR: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than amongThose who received placebo, regardless of the presence or absence of diabetes.
Abstract: Background In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-ind...
3,541 citations
TL;DR: The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined.
Abstract: Background The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. Methods We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. Results We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, ...
3,430 citations