scholarly journals Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease

Stroke ◽  
2021 ◽  
Author(s):  
Zien Zhou ◽  
Meg J. Jardine ◽  
Qiang Li ◽  
Brendon L. Neuen ◽  
Christopher P. Cannon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Hemorrhagic Stroke ◽  
Estimated Glomerular Filtration Rate ◽  
Meta Analysis

Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR pooled , 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HR pooled , 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HR pooled , 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HR pooled , 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HR pooled , 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate ( P =0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m 2 ]) subgroup (HR pooled , 0.50 [95% CI, 0.31–0.79]). Conclusions: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02065791.

MO640LASER DOPPLER FLOWMETRY IN STUDYING OF MICROVASCULAR DISORDERS IN PATIENTS WITH DIABETIC NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Petr Vasilev ◽  
Alexander Shishkin ◽  
Nikolai Erofeev ◽  
Mikhail Erman ◽  
Ivan Pchelin
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Doppler Flowmetry

Abstract Background and Aims According to various research, vascular complications of type 2 diabetes mellitus are the main reason for patients' mortality. The most specific one, observed in patients with diabetes only, is diabetic microangiopathy, especially diabetic nephropathy. This complication accounts for more than 20% of cases of chronic kidney disease. So, the development of non-invasive methods for the diagnosis of vascular complications of type 2 diabetes mellitus is critically important. There is a perspective method for this problem - Laser Doppler flowmetry (LDF). It is currently used in the diagnosis of diabetic microangiopathy, but the limiting factor is the lack of a unified algorithmic approach to the data interpretation. This work aimed to analyze changes in the amplitude indicators of the low-frequency part of the LDF signal spectrum in patients with chronic kidney disease and type 2 diabetes and to identify their correlations with the glomerular filtration rate. Method The study included 42 patients (20 men and 22 women) with type 2 diabetes mellitus chronic kidney disease (stage C3-C4). The age of patients was 58-77 years (66 years on average). The duration of diabetes was more than 5 years (on average 7 years). All patients had diabetic nephropathy with a decrease in glomerular filtration rate, chronic kidney disease stage C3-C4. Laser Doppler flowmetry was done using the "LAZMA MC-1" system ("Lazma", Russia). Each patient had a 10-minute LDF registration. The sensor was placed on the skin of the rear of the foot. After recording the LDF curve, the special software has calculated amplitudes of endothelial, myogenic, neurogenic, respiratory, and pulse flux motions. Then we assessed the amplitude contribution of every frequency range to the total power of the local flux motion region. The next step was a correlation analysis with the estimated glomerular filtration rate. For statistical analysis, we used the GraphPad Prism 8 (GraphPad Software, USA). Results All examined patients had amplitude peaks in the neurogenic, myogenic, respiratory, and pulse ranges. There were no significant correlations between the glomerular filtration rate and the amplitudes of myogenic and neurogenic flux motions (p&gt;0.05) (Fig. 1). However, there was a significant positive correlation between the contribution of myogenic flux motions to the low-frequency range and glomerular filtration rate (p&lt;0.01), and a negative one – for the contribution of neurogenic flux motions (p&lt;0.01) (Fig. 2). In six observations there was a tendency to a decrease in the contribution of endothelial flux motions as the glomerular filtration rate decreased. Conclusion The results of this study showed that laser Doppler flowmetry has the potential to diagnosis the nature of the dysfunction of individual microcirculation modulation mechanisms. In patients with chronic kidney disease of the C3-C4 stage decreasing the glomerular filtration rate correlated with decreasing the contribution of myogenic flux motions and increasing the contribution of neurogenic flux motions to the total power of the low-frequency part of the LDF signal amplitude-frequency spectrum. These changes can be explained within the framework of the existing understanding of the pathogenesis of diabetic microangiopathy, namely, damage to the smooth muscle layer of the wall of arterioles and venules with damage to myocyte pacemakers and changes of basal vascular tone pattern. It causes an increase in the role of neurogenic modulation of the micro-vascular bloodstream. These data can be an additional argument in favor of the further development of improving laser Doppler flowmetry using for the tasks of early (preclinical) non-invasive diagnosis of microvascular disorders in patients with type 2 diabetes mellitus, as well as for monitoring the effectiveness of the therapy. The reported study was funded by RFBR, project number 19-315-90080.

scholarly journals Long-term prospective observation suggests that glomerular hyperfiltration is associated with rapid decline in renal filtration function: A multiethnic study

2018 ◽  
Vol 15 (5) ◽  
pp. 417-423 ◽  
Author(s):  
Serena Low ◽  
Xiao Zhang ◽  
Jiexun Wang ◽  
Lee Ying Yeoh ◽  
Yan Lun Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Odds Ratio ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Glomerular Hyperfiltration ◽  
Haemoglobin A1c ◽  
Baseline Haemoglobin

Aim: Glomerular hyperfiltration usually occurs early in development of kidney complications in diabetes. To understand hyperfiltration as a marker of renal disease progression in type 2 diabetes mellitus, we aimed to examine association between glomerular hyperfiltration (estimated glomerular filtration rate ⩾ 120 mL/min/1.73 m2) and rapid renal decline (annual estimated glomerular filtration rate loss ⩾ 3 mL/min/1.73 m2). Methods: This was a prospective cohort comprising 1014 patients with type 2 diabetes mellitus attending a Diabetes Centre of a regional hospital in 2002–2014. A separate prospective cohort, comprising 491 patients who attended Diabetes Centre or primary-care polyclinics, was used for validation. We performed binary mediation analysis to examine role of hyperfiltration on relationship between baseline haemoglobin A1c and rapid renal decline. Results: Among patients in discovery cohort, 5.2% had baseline hyperfiltration. Over mean follow-up of 6 years, 22.9% had rapid glomerular filtration rate decline. Baseline hyperfiltration was significantly associated with greater odds of rapid renal decline after adjusting for demographics, diabetes duration and clinical covariates (odds ratio: 2.57; 95% confidence interval: 1.21–5.46; p = 0.014). Similar finding was found in validation cohort (odds ratio: 2.98; 95% confidence interval: 1.06–8.42; p = 0.034). Hyperfiltration significantly accounted for 35.3% of association between increasing baseline haemoglobin A1c and rapid renal decline. Conclusion: Glomerular hyperfiltration is an independent risk factor of rapid renal decline. It mediates the association between increasing haemoglobin A1c and rapid renal decline.

scholarly journals The Error of Estimated GFR in Type 2 Diabetes Mellitus

2019 ◽  
Vol 8 (10) ◽  
pp. 1543 ◽  
Author(s):  
Sergio Luis-Lima ◽  
Tomás Higueras Linares ◽  
Laura Henríquez-Gómez ◽  
Raquel Alonso-Pescoso ◽  
Angeles Jimenez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Cystatin C ◽  
Filtration Rate

Type 2 diabetes mellitus represents 30–50% of the cases of end stage renal disease worldwide. Thus, a correct evaluation of renal function in patients with diabetes is crucial to prevent or ameliorate diabetes-associated kidney disease. The reliability of formulas to estimate renal function is still unclear, in particular, those new equations based on cystatin-C or the combination of creatinine and cystatin-C. We aimed to assess the error of the available formulas to estimate glomerular filtration rate in diabetic patients. We evaluated the error of creatinine and/or cystatin-C based formulas in reflecting real renal function over a wide range of glomerular filtration rate (from advanced chronic kidney disease to hyperfiltration). The error of estimated glomerular filtration rate by any equation was common and wide averaging 30% of real renal function, and larger in patients with measured glomerular filtration rate below 60 mL/min. This led to chronic kidney disease stages misclassification in about 30% of the individuals and failed to detect 25% of the cases with hyperfiltration. Cystatin-C based formulas did not outperform creatinine based equations, and the reliability of more modern algorithms proved to be as poor as older equations. Formulas failed in reflecting renal function in type 2 diabetes mellitus. Caution is needed with the use of these formulas in patients with diabetes, a population at high risk for kidney disease. Whenever possible, the use of a gold standard method to measure renal function is recommended.

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