scholarly journals SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, ‘diabetic nephropathy’, IgA nephropathy and podocytopathies with FSGS lesions

2020 ◽  
Author(s):  
Hans-Joachim Anders ◽  
Anna Julie Peired ◽  
Paola Romagnani
Keyword(s):  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Glucose Transporter ◽  
Immunoglobulin A ◽  
Adverse Outcomes ◽  
Glucose Transporter 2 ◽  
Research Activities ◽  
Background Therapy ◽  
Sglt2 Inhibition

Abstract In 2020, the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial first demonstrated that inhibition of the sodium–glucose transporter-2 (SGLT2) with dapagliflozin attenuates the progression of chronic kidney disease (CKD) with proteinuria in patients with or without diabetes at an unprecedented effect size. These results have far-reaching implications for a series of traditional concepts in Nephrology. It now became obvious that CKD with and without diabetes involves a predominant SGLT2-driven pathophysiology compared with the other pathogenic pathways currently under consideration. As SGLT2 inhibition is similarly efficacious in diabetic and non-diabetic CKD with proteinuria, treating CKD rather than ‘diabetic nephropathy’ becomes the central paradigm. Indeed, in older adults with type 2 diabetes, CKD is rather of multifactorial origin. As the DAPA-CKD trial included more patients with immunoglobulin A nephropathy (IgAN) than any of the previous IgAN trials, dual renin-angiotensin/SGLT2 inhibition may become the new standard. The same applies for patients with podocytopathy-related focal segmental glomerulosclerosis lesions. From now on, IgAN and podocytopathy trials without SGLT2 inhibition as background therapy and without glomerular filtration rate decline as primary outcome criterion will be of limited value. These and other potential implications will trigger broad discussions and secondary research activities with conclusions difficult to predict today. However, one is for sure: Nephrology after the DAPA-CKD trial will be not the same as it was before. Finally!

scholarly journals Clinical Effectiveness and Safety of Gliclazide MR and Linagliptin Combination in the Management of Patients With T2DM and Chronic Kidney Disease (CKD) Switched From Glimepiride - a Real-World, Retrospective, Observational Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A407-A408
Author(s):  
Supratik Bhattacharyya ◽  
Maneesha Khalse
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Clinical Effectiveness ◽  
Adverse Outcomes ◽  
Average Dose ◽  
Urine Albumin ◽  
Medical Study ◽  
Background Therapy ◽  
Stage 1

Abstract Background: Type 2 diabetes (T2DM) patients are at high risk of developing to CKD and progressing to adverse outcomes vs Nondiabetics. The aim was to evaluate the effectiveness and safety of gliclazide MR switched from glimepiride in combination with linagliptin considering their associated potential benefits in albuminuria reduction and delaying progression of adverse renal outcomes in T2DM patients with kidney disease as shown in previous data. Methodology: The medical study database of the author’s hospital identified T2DM patients with stage 1–3 CKD with mean eGFR of 50.4 ± 8.56 ml/min/1.73 m2 and were inadequately controlled with glimepiride (mean dose 3.24mg) for the last 3 months. These patients were switched to gliclazide MR with appropriate equivalent dose while DPP-4 inhibitors like linagliptin (5 mg OD) (79%), sitagliptin (14%), vildagliptin (7%), were continued as background therapy. About 59.35% of subjects were on glimepiride 2 mg, 21.93% subjects on glimepiride 3 mg and 18.7% on glimepiride 4 mg. The gliclazide dose was up titrated by 30 mg every 15 days to achieve a target post-prandial glucose (PPG) ≤180 mg/dL. The average dose of gliclazide MR during the study was 44 mg; approximately two-thirds of patients 61% were on 60 mg, 22% on 90mg, and 7% on 30 mg. Patients were counselled to recognize the symptoms and record the hypoglycemic episodes. The statistical analysis included the analysis of changes in glycemic control, risk of hypoglycemia & renal function parameters. The patients were followed up for 24 weeks duration. Results: A total 218 eligible patients (110 female & 108 male) with CKD (stages 1–3) were included. The mean age, body weight, baseline HbA1c, FPG, PPG levels, mean eGFR, and UACR (urine albumin creatinine ratio) were 62.94 ± 8.72 years, 67.9 ± 9.33 kg, 8.51 ±0.81%, 148.53 ± 16.72, 202 ± 18.45 mg/dL, 50.49 ± 8.56 ml/min/1.73 m2 and 154.34 mg/g respectively. Gliclazide MR was initiated substituting glimepiride with appropriate dosing determined by the physician. Two subjects discontinued the therapy due to intolerability. At 24 weeks follow up, HbA1c, FPG, PPG level was reduced by -0.63, -10.33, -30.04%, respectively (p< 0.001). There was a significant reduction in events of overall hypoglycemia (22.25%). Improvement in renal function with respect to eGFR level (+1.77 ml/min/1.73 m2) and albuminuria reduction (-45.56 mg/g) were also observed in patients. Conclusion: This study demonstrates the clinical effectiveness and safety of gliclazide MR with the combination of DPP-4is like linagliptin as an alternate option to glimepiride in diabetes patients with chronic kidney disease.

scholarly journals Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

2021 ◽  
Author(s):  
John R. Prowle ◽  
Lui G. Forni ◽  
Max Bell ◽  
Michelle S. Chew ◽  
Mark Edwards ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Adverse Outcomes ◽  
Baseline Risk ◽  
Major Surgery ◽  
Increased Risk

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

scholarly journals MicroRNA-451 as an Early Predictor of Chronic Kidney Disease in Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Mostafa Abdelsalam ◽  
A. M. Wahab ◽  
Maysaa El Sayed Zaki ◽  
Mohamad Motawea
Keyword(s):  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Early Diagnosis ◽  
Serum Creatinine ◽  
High Sensitivity ◽  
Urinary Albumin ◽  
Significant Difference ◽  
Plasma Microrna ◽  
Stage Renal Disease

Background. Diabetes mellitus is the leading cause of end-stage renal disease worldwide. Microalbuminuria is the cornerstone for the diagnosis of diabetic nephropathy. However, it is an inadequate marker for early diagnosis. MicroRNAs are not only new and promising markers for early diagnosis but also, but they may also play a role in the prevention of disease progression. Methods. This study included ninety patients with type 2 DM in addition to 30 control subjects. MicroRNA-451 expression in blood and plasma using real-time PCR was evaluated in addition to the classic diabetic nephropathy markers (serum creatinine, urinary albumin, and eGFR). Results. There was a significant difference between the studied groups versus control regarding serum creatinine, eGFR, urinary, and plasma microRNA-451 with p=0.0001. Patients with eGFR 60 ml/min/1.73 m2 showed a significantly higher plasma microRNA-451 (29.6 ± 1.6) and significantly lower urinary microRNA-451 (21 ± 0.9) in comparison to patients with eGFR >60 ml/min/1.73 m2 and p=0.0001. eGFR showed a positive correlation with urinary microRNA-451 and negative correlation with both plasma microRNA-451 and urinary albumin. Both plasma and urinary microRNA-451 are highly sensitive and specific markers for chronicity in diabetic nephropathy patients with sensitivity of 90.9% and 95.5% and specificity of 67.6% and 95.6%, respectively. Conclusion. MicroRNA-451 is a promising early biomarker for chronic kidney disease in diabetic nephropathy with high sensitivity and specificity.

scholarly journals Pharmacodynamic Model of Sodium–Glucose Transporter 2 (SGLT2) Inhibition: Implications for Quantitative Translational Pharmacology

2011 ◽  
Vol 13 (4) ◽  
pp. 576-584 ◽  
Author(s):  
Tristan S. Maurer ◽  
Avijit Ghosh ◽  
Nahor Haddish-Berhane ◽  
Aarti Sawant-Basak ◽  
Carine M. Boustany-Kari ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Pharmacodynamic Model ◽  
Glucose Transporter 2 ◽  
Translational Pharmacology ◽  
Sglt2 Inhibition

scholarly journals Optimal blood pressure for patients with chronic kidney disease: a nationwide population-based cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
You-Bin Lee ◽  
Ji Sung Lee ◽  
So-hyeon Hong ◽  
Jung A. Kim ◽  
Eun Roh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Antihypertensive Treatment ◽  
Antihypertensive Agents ◽  
Population Based ◽  
Adverse Outcomes ◽  
Optimal Blood Pressure ◽  
Stage Renal Disease

AbstractThe effect of blood pressure (BP) on the incident cardiovascular events, progression to end-stage renal disease (ESRD) and mortality were evaluated among chronic kidney disease (CKD) patients with and without antihypertensive treatment. This nationwide study used the Korean National Health Insurance Service-Health Screening Cohort data. The hazards of outcomes were analysed according to the systolic BP (SBP) or diastolic BP (DBP) among adults (aged ≥ 40 years) with CKD and without previous cardiovascular disease or ESRD (n = 22,278). The SBP and DBP were ≥ 130 mmHg and ≥ 80 mmHg in 10,809 (48.52%) and 11,583 (51.99%) participants, respectively. During a median 6.2 years, 1271 cardiovascular events, 201 ESRD incidents, and 1061 deaths were noted. Individuals with SBP ≥ 130 mmHg and DBP ≥ 80 mmHg had higher hazards of hypertension-related adverse outcomes compared to the references (SBP 120–129 mmHg and DBP 70–79 mmHg). SBP < 100 mmHg was associated with hazards of all-cause death, and composite of ESRD and all-cause death during follow-up only among the antihypertensive medication users suggesting that the BP should be < 130/80 mmHg and the SBP should not be < 100 mmHg with antihypertensive agents to prevent the adverse outcome risk of insufficient and excessive antihypertensive treatment in CKD patients.

Gut microbial biomarkers for predicting adverse outcomes in people with chronic kidney disease

2022 ◽  
Vol 2022 (1) ◽  
Author(s):  
Tess E Cooper ◽  
Eric H Au ◽  
Edmund YM Chung ◽  
David J Tunnicliffe ◽  
Jonathan C Craig ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Adverse Outcomes ◽  
Microbial Biomarkers
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