MO654REAL LIFE EXPERIENCE AFTER 20 MONTHS USING SGLT2 INHIBITORS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Renata Carvalho ◽  
Bárbara Ribeiro ◽  
Joana Medeiros ◽  
José Mário Bastos ◽  
Raquel Vaz ◽  
...  

Abstract Background and Aims Diabetic kidney disease (DKD) develops in almost half of diabetic patients and is the leading cause of chronic kidney disease (CKD). SGLT2 inhibitors (SGLT2i) have consistently shown to confer kidney protection in patients with type 2 diabetes (T2D). The recent KDIGO guidelines suggest their use as a first line medication along with metformin. After the study CREDENCE was published, in mid-2019, DKD patients at the Nephrology outpatient department of the Hospital of Braga were started on SGLT2i. We aimed at assessing these patients’ clinical and laboratory data after the introduction of the new drug. Method We collected data on age, gender, weight, blood pressure (BP) values, the use of renin-angiotension-aldosterone system inhibitors (RAASi), kidney function, glycated hemoglobin (HbA1c), glycosuria, proteinuria and albuminuria at baseline and during the two next patient assessments. Data was analyzed using SPSS®. Results Twenty-nine DKD patients who started SGLT2i between May 2019 and August 2020 were followed. Mean age was 71.2±13.5 years, 22 patients were male and their mean weight was 86.9±13.9 kg. They had had T2D for a mean of 15.9±10.3 years and a significant percent had end organ damage: 34% had diabetic retinopathy, 24% complaints suggestive of neuropathy, 51% had documented heart failure and 27% had cerebral vascular disease. Most were hypertensive with a mean BP of 156±19/83±11mmHg and 72.4% were taking RAASi. One third were treated with insulin. Most patients were started on canagliflozin (n=28) and one patient started empagliflozin. After starting the drug, patients were evaluated at a mean time of 141±55 days and had a second reevaluation at a mean time of 254±72 days. On the first evaluation they showed a significant reduction in the mean systolic BP to 140±15.1mmHg (p=0.001). Glycated hemoglobin decreased from a mean of 7.4±1.3% to 7.1±1.1% although this difference was not significant (p=0.4). Protein-creatinine urinary ratio was significantly reduced from a median value of 1.48 (IQR 0.24-1.85) to 0.93 (IQR 0.40-1.56). Mean serum creatinine increased significantly from baseline until the first evaluation at 1.96±0.49 to 2.27±0.66mg/dL (p=0.00) but remained stable on the second evaluation (2.29±0.79mg/dL). Seventy percent of the patients developed significant glycosuria (urinary concentration >500mg/dL) after starting SGLT2i. When asked about adherence, most non-glycosuric patients admitted not having started the drug. Conclusion Despite having a weak effect in the reduction of HbA1c, SGLT2i are an exciting drug for kidney protection in DKD. Patient adherence is easy to assess based on glycosuria. In our experience and based on this criterion drug compliance was acceptable (at least 70%) and we were able to reinforce instructions among non-compliant patients. Some of the benefits of SGLT2i were evident soon after they were started such as the improvement in BP and proteinuria. The initial increase in plasma creatinine was expected due to reduction in intraglomerular pressure and hyperfiltration and was noticeable only on the first assessment. We expect to continue SGLT2i use DKD patients.

2021 ◽  
Vol 22 (9) ◽  
pp. 4374
Author(s):  
Tomoaki Takata ◽  
Hajime Isomoto

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.


2018 ◽  
Vol 40 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Rodrigo Reis Abrita ◽  
Beatriz dos Santos Pereira ◽  
Neimar da Silva Fernandes ◽  
Renata Abrita ◽  
Rosalia Maria Nunes Henriques Huaira ◽  
...  

ABSTRACT Introduction: The diagnosis and treatment of mineral and bone disorder of chronic kidney disease (CKD-MBD) is a challenge for nephrologists and health managers. The aim of this study was to evaluate the prevalence, biochemical profile, and drugs associated with CKD-MBD. Methods: Cross-sectional study between July and November 2013, with 1134 patients on dialysis. Sociodemographic, clinical, and laboratory data were compared between groups based on levels of intact parathyroid hormone (iPTH) (< 150, 150-300, 301-600, 601-1000, and > 1001 pg/mL). Results: The mean age was 57.3 ± 14.4 years. The prevalence of iPTH < 150 pg/mL was 23.4% and iPTH > 601 pg/mL was 27.1%. The comparison between the groups showed that the level of iPTH decreased with increasing age. Diabetic patients had a higher prevalence of iPTH < 150 pg/mL (27.6%). Hyperphosphatemia (> 5.5 mg/dL) was observed in 35.8%. Calcium carbonate was used by 50.5%, sevelamer by 14.7%, 40% of patients had used some form of vitamin D and 3.5% used cinacalcet. Linear regression analysis showed a significant negative association between iPTH, age, and diabetes mellitus and a significant positive association between iPTH and dialysis time. Conclusion: The prevalence of patients outside the target for iPTH was 50.5%. There was a high prevalence of hyperphosphatemia (35.8%), and the minority of patients were using active vitamin D, vitamin D analogs, selective vitamin D receptor activators, and cinacalcet. These data indicate the need for better compliance with clinical guidelines and public policies on the supply of drugs associated with CKD-MBD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Philipp Tauber ◽  
Frederick Sinha ◽  
Raffaela S. Berger ◽  
Wolfram Gronwald ◽  
Katja Dettmer ◽  
...  

Large-scale clinical outcome studies demonstrated the efficacy of SGLT2 inhibitors in patients with type II diabetes. Besides their therapeutic efficacy in diabetes, significant renoprotection was observed in non-diabetic patients with chronic kidney disease (CKD), suggesting the existence of glucose-independent beneficial effects of SGLT2 inhibitors. However, the relevant mechanisms by which SGLT2 inhibition delays the progression of renal injury are still largely unknown and speculative. Previous studies showed that SGLT2 inhibitors reduce diabetic hyperfiltration, which is likely a key element in renoprotection. In line with this hypothesis, this study aimed to investigate the nephroprotective effects of the SGLT2 inhibitor empagliflozin (EMPA) in different mouse models with non-diabetic hyperfiltration and progressing CKD to identify the underlying diabetes-independent cellular mechanisms. Non-diabetic hyperfiltration was induced by unilateral nephrectomy (UNx). Since UNx alone does not result in renal damage, renal disease models with varying degrees of glomerular damage and albuminuria were generated by combining UNx with high NaCl diets ± deoxycorticosterone acetate (DOCA) in different mouse strains with and without genetic predisposition for glomerular injury. Renal parameters (GFR, albuminuria, urine volume) were monitored for 4–6 weeks. Application of EMPA via the drinking water resulted in sufficient EMPA plasma concentration and caused glucosuria, diuresis and in some models renal hypertrophy. EMPA had no effect on GFR in untreated wildtype animals, but significantly reduced hyperfiltration after UNx by 36%. In contrast, EMPA did not reduce UNx induced hyperfiltration in any of our kidney disease models, regardless of their degree of glomerular damage caused by DOCA/salt treatment. Consistent with the lack of reduction in glomerular hyperfiltration, EMPA-treated animals developed albuminuria and renal fibrosis to a similar extent as H2O control animals. Taken together, the data clearly indicate that blockade of SGLT2 has the potential to reduce non-diabetic hyperfiltration in otherwise untreated mice. However, no effects on hyperfiltration or progression of renal injury were observed in hypervolemic kidney disease models, suggesting that high salt intake and extracellular volume might attenuate the protective effects of SGLT2 blockers.


2021 ◽  
Vol 22 (9) ◽  
pp. 4441
Author(s):  
Giovanna Leoncini ◽  
Elisa Russo ◽  
Elisabetta Bussalino ◽  
Cecilia Barnini ◽  
Francesca Viazzi ◽  
...  

In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs.


2011 ◽  
Vol 15 (2) ◽  
pp. 316-317 ◽  
Author(s):  
Tomonari Okada ◽  
Toshiyuki Nakao ◽  
Hiroshi Matsumoto ◽  
Yume Nagaoka ◽  
Toshikazu Wada

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Masajtis-Zagajewska ◽  
Katarzyna Pä™czek ◽  
Tomasz Holub ◽  
Michal Nowicki

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors are new class of oral antidiabetic drugs that show potent cardio- and nephroprotective actions. Despite having a favorable safety profile the treatment with SGLT2 inhibitors has been associated with several side-effects including increased risk of fractures. Although the pathomechanism of this complication has not been elucidated these drugs may inhibit tubular reabsorption of phosphate which may stimulate a secretion of fibroblast growth factor 23 (FGF23). The study was designed to assess the effect of SGLT2 inhibitor on markers of calcium-phosphate metabolism, bone turnover and early glomerular injury in diabetic and non-diabetic patients with stage 3 chronic kidney disease (CKD). Method 41 patients with chronic kidney disease including 23 without diabetes (13 M, 11F, age 52.9±0.7 years, estimated glomerular filtration rate (eGFR) 38.6±10.8 ml/min/1.73 m2) and 18 with type 2 diabetes (12 M, 6F, age 58.8±1.4 years, eGFR 38.8±7.7 ml/min/1.73 m2) were recruited. Main inclusion criteria were CKD stage 3 and urine albumin secretion &gt;100 mg/g creatinine. All subjects received oral empagliflozin 10 mg once daily for 7 days. Serum calcium, phosphorus, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF23 and urine calcium, phosphate and albumin were measured at baseline and after 7 days of empagliflozin treatment. Results Plasma calcitriol, serum and urine calcium, phosphorus and BAP did not change significantly during the administration of empagliflozin. Urine phosphate/creatinine ratio was similar in both subgroups at baseline and did not change during empagliflozin administration. Plasma PTH was higher in non-diabetics than in diabetics both at baseline and after empagliflozin. The increase of PTH after empagliflozin tended to be higher in diabetic patients (p=0.07). There was only a trend towards an increase of serum FGF23 in both non-diabetic and diabetic subgroup (by 4.2±0.2 vs. 9.3±1.1 pg/mL, ns). BAP was significantly higher at baseline in diabetic patients but did not significantly change after empagliflozin in the subgroups. Albumin/creatinine ratio decrease after empagliflozin administration was significant only in non-diabetic patients (-62±17 vs. -2±8 mg/g in diabetic patients, p=0.03 for difference). Conclusion Our study showed no effect of short-time administration of empagliflozin on calcium-phosphate and bone metabolism markers in patients with both diabetic and non-diabetic CKD. Empagliflozin decreased albuminuria significantly only in non-diabetic CKD that may suggest a potentially greater nephroprotective effect of this SGLT2 inhibitor in non-diabetic than in diabetic nephropathy.


2012 ◽  
Vol 13 (2) ◽  
pp. 152-159 ◽  
Author(s):  
Nazar M Abdalla ◽  
Waleed O Haimour ◽  
Amani A Osman ◽  
Hassan Abdul Aziz

General objectives: This study aimed at assessment of factors affecting antimicrobial sensitivity in Staphylococcus aureus clinical isolates from Assir region, Saudi Arabia. Materials and Methods: In this study, eighty one patients presented with Staph. aureus infections either nosocomial or community acquired infections were involved by collecting nasal swabs from them at Aseer Central Hospital General Lab. These patients were from all age groups and from males and females during the period of Jan 2011- Jun 2011. These samples were undergone variable laboratory procedures mainly; bactech, culture media, antibiotics sensitivity test using diffusion disc test (MIC) and molecular (PCR) for detection of mec A gene. Clinical and laboratory data were recorded in special formats and analyzed by statistical computer program (SPSS). Results: Showed that; Descriptive and analytical statistical analysis were performed and final results were plotted in tables. In Staph aureus MecA gene positive cases (50) showed: Oxacillin/ Mithicillin, Ciprofloxacin and Fusidin resistant in diabetic patients were 13, 26.0%, 9, 18% and 7, 14% respectively and in non diabetic patients were 37, 74.0%, 22, 44% and 20, 40% respectively. While no sensitivity in diabetic and non diabetic patients using Oxacillin/ Mithicillin. In Staph aureus MecA gene negative cases (31) showed: Oxacillin/ Mithicillin, sensitivity in diabetic patients (5, 16.1%) and in non diabetic were (26, 83.9%). While no resistant in diabetic and non diabetic patients. In Ciprofloxacin and Fusidin resistant in diabetic patients were 1, 3.2% and 1, 3.2% respectively and in non diabetic patients were 12, 38.7% and 7, 22.6%respectively. Erythromycin in Staph aureus ( MecA gene) positive cases (50) showed: resistant in age (0-15) years were (5, 10%), (16-50) years were (16, 32%) and ( ›50 years) were (12, 24%). Erythromycin in Staph aureus (MecA gene) negative cases (31) showed: resistant in age (0-15) years were (6, 19.3%), (16-50) years were (5, 16.1%) and ( ›50 years) were (3, 9.7%). Conclusion: Drugs resistance is a major progressive multifactorial problem facing the treatment of Staph aureus infections. DOI: http://dx.doi.org/10.3329/jom.v13i2.12750 J Medicine 2012; 13 : 152-159


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  

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