scholarly journals The SGLT2 Inhibitor Empagliflozin Might Be a New Approach for the Prevention of Acute Kidney Injury

2019 ◽  
Vol 44 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Chang Chu ◽  
Yong-Ping Lu ◽  
Lianghong Yin ◽  
Berthold Hocher
Keyword(s):  
Acute Kidney Injury ◽  
Sglt2 Inhibitor ◽  
Safety Data ◽  
Kidney Injury ◽  
The United States ◽  
Sglt2 Inhibitors ◽  
Tubuloglomerular Feedback ◽  
Beneficial Effects ◽  
Cardiovascular Assessment ◽  
Glomerular Hemodynamics

Three randomized control trials (Canagliflozin Cardiovascular Assessment Study, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients [EMPA-REG OUTCOME], and Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 [DECLARE-TIMI 58]) showed that the sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering drugs, are associated with a lower rate of adverse renal outcomes, such as need for renal replacement therapy, doubling of serum creatinine, and loss of glomerular filtration rate (GFR) compared to those in placebo groups. Besides, canagliflozin and empagliflozin also showed a lower risk of progression to macroalbuminuria. The EMPA-REG OUTCOME trial and DECLARE-TIMI 58 trial also indicated that these SGLT2 inhibitors might have beneficial effects on the prevention of acute kidney injury. The United States Food and Drug Administration (FDA) warned of the risk of acute kidney injury for canagliflozin and dapagliflozin. We compared canagliflozin, empagliflozin, and dapagliflozin with respect to chemical structure and pharmacological properties, to explain the observed differences in preventing acute kidney injury, and put forward the hypotheses of the potential mechanisms of different effects of SGLT2 inhibitors on acute kidney injury. Given the raising clinical use of SGLT2 inhibitors, our review should stimulate further basic science and clinical studies in order to definitively understand the role of SGLT2 inhibitors in acute kidney injury. A weakness of the clinical data obtained so far is the fact that the statements concerning acute kidney injury are just based on safety data – mainly creatine measurements. However, given the mode of action of SGLT2 blockers, initiation of a therapy with a SGLT2 blocker will cause an increase of creatine because of its effects on the tubuloglomerular feedback mechanisms/glomerular hemodynamics like RAAS blocking agents do. To really understand the potential effects of SGLT2 inhibitors, we need preclinical and clinical SGLT2 inhibitor studies focusing on all aspects of acute kidney injury – not just changes in GFR biomarkers.

scholarly journals Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks

2020 ◽  
Vol 295 (42) ◽  
pp. 14379-14390
Author(s):  
Rachel J. Perry ◽  
Gerald I. Shulman
Keyword(s):  
Diabetes Management ◽  
Sglt2 Inhibitor ◽  
Healthy Person ◽  
The United States ◽  
Sglt2 Inhibitors ◽  
Beneficial Effects ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Almost All ◽  
The Impact

In a healthy person, the kidney filters nearly 200 g of glucose per day, almost all of which is reabsorbed. The primary transporter responsible for renal glucose reabsorption is sodium-glucose cotransporter-2 (SGLT2). Based on the impact of SGLT2 to prevent renal glucose wasting, SGLT2 inhibitors have been developed to treat diabetes and are the newest class of glucose-lowering agents approved in the United States. By inhibiting glucose reabsorption in the proximal tubule, these agents promote glycosuria, thereby reducing blood glucose concentrations and often resulting in modest weight loss. Recent work in humans and rodents has demonstrated that the clinical utility of these agents may not be limited to diabetes management: SGLT2 inhibitors have also shown therapeutic promise in improving outcomes in heart failure, atrial fibrillation, and, in preclinical studies, certain cancers. Unfortunately, these benefits are not without risk: SGLT2 inhibitors predispose to euglycemic ketoacidosis in those with type 2 diabetes and, largely for this reason, are not approved to treat type 1 diabetes. The mechanism for each of the beneficial and harmful effects of SGLT2 inhibitors—with the exception of their effect to lower plasma glucose concentrations—is an area of active investigation. In this review, we discuss the mechanisms by which these drugs cause euglycemic ketoacidosis and hyperglucagonemia and stimulate hepatic gluconeogenesis as well as their beneficial effects in cardiovascular disease and cancer. In so doing, we aim to highlight the crucial role for selecting patients for SGLT2 inhibitor therapy and highlight several crucial questions that remain unanswered.

scholarly journals The beneficial effects of plasma exchange for treatment of acute kidney injury in minimal change nephrotic syndrome

2011 ◽  
Vol 45 (2) ◽  
pp. 179-185
Author(s):  
Hideyo Oguchi ◽  
Marohito Murakami ◽  
Takashi Araki ◽  
Mariko Meguro ◽  
Akinori Hashiguchi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Nephrotic Syndrome ◽  
Plasma Exchange ◽  
Kidney Injury ◽  
Minimal Change Nephrotic Syndrome ◽  
Minimal Change ◽  
Beneficial Effects

scholarly journals Current Concepts of Pediatric Acute Kidney Injury—Are We Ready to Translate Them into Everyday Practice?

2021 ◽  
Vol 10 (14) ◽  
pp. 3113
Author(s):  
Kinga Musiał
Keyword(s):  
Acute Kidney Injury ◽  
Surrogate Marker ◽  
Kidney Injury ◽  
Tubuloglomerular Feedback ◽  
Everyday Practice ◽  
Special Focus ◽  
Functional Reserve ◽  
Renal Functional Reserve ◽  
Acute Kidney Disease ◽  
Pediatric Acute Kidney Injury

Pediatric acute kidney injury (AKI) is a major cause of morbidity and mortality in children undergoing interventional procedures. The review summarizes current classifications of AKI and acute kidney disease (AKD), as well as systematizes the knowledge on pathophysiology of kidney injury, with a special focus on renal functional reserve and tubuloglomerular feedback. The aim of this review is also to show the state-of-the-art in methods assessing risk and prognosis by discussing the potential role of risk stratification strategies, taking into account both glomerular function and clinical settings conditioned by fluid overload, urine output, or drug nephrotoxicity. The last task is to suggest careful assessment of eGFR as a surrogate marker of renal functional reserve and implementation of point-of-care testing, available in the case of biomarkers like NGAL and [IGFBP-7] × [TIMP-2] product, into everyday practice in patients at risk of AKI due to planned invasive procedures or treatment.

scholarly journals The Current Management of Hepatorenal Syndrome‐Acute Kidney Injury in the United States and the Potential of Terlipressin

2021 ◽  
Author(s):  
Steven L. Flamm ◽  
Kimberly Brown ◽  
Hani M. Wadei ◽  
Robert S. Brown ◽  
Marcelo Kugelmas ◽  
...  
Keyword(s):  
United States ◽  
Acute Kidney Injury ◽  
Hepatorenal Syndrome ◽  
Kidney Injury ◽  
The United States ◽  
Current Management

scholarly journals Harnessing basic and clinic tools to evaluate SGLT2 inhibitor nephrotoxicity

2017 ◽  
Vol 313 (4) ◽  
pp. F951-F954 ◽  
Author(s):  
Danielle L. Saly ◽  
Mark A. Perazella
Keyword(s):  
Early Stage ◽  
Functional Decline ◽  
Healthcare Providers ◽  
Sglt2 Inhibitor ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Chip Technology ◽  
Urinary Glucose

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of medications that target the transporter that reabsorbs ~90% of glucose in the S1 segment of the proximal convoluted tubule. As a result, SGLT2 inhibition increases urinary glucose excretion, effectively lowering plasma glucose levels. In addition to reducing hemoglobin A1c levels, these drugs also lower body weight, blood pressure, and uric acid levels in Type 2 diabetes mellitus (T2DM) patients. Importantly, empagliflozin has been observed to slow progression of kidney disease and reduce dialysis requirements in T2DM patients. However, the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) has collected over 100 cases of acute kidney injury (AKI) for canagloflozin and dapagliflozin since their approval. Of the 101 patients, 96 required hospitalization, 22 required intensive care unit admission, and 15 underwent hemodialysis. The FDA now requires that AKI be listed as a potential side effect of the SGLT2 inhibitors along with cautious prescription of these drugs with other medications, such as renin-angiotensin-system antagonists, diuretics, and NSAIDs. It is unclear, however, whether this FAERS reported “AKI” actually represents structural kidney injury, as randomized, controlled trials of these drugs do not describe AKI as an adverse event despite coprescription with RAS blockers and diuretics. As a result of this FDA warning, diabetic patients with early-stage CKD may not be prescribed an SGLT2 inhibitor for fear of AKI. Thus, it is imperative to ascertain whether the reported AKI represents true structural kidney injury or a functional decline in glomerular filtration rate. We propose using readily available clinical tools with experimental biomarkers of kidney injury and kidney-on-a-chip technology to resolve this question and provide solid evidence about the AKI risk of these drugs for healthcare providers.

scholarly journals Rhabdomyolysis in a Hospitalized 16-Year-Old Boy: A Rarely Reported Underlying Cause

2016 ◽  
Vol 2016 ◽  
pp. 1-2 ◽  
Author(s):  
Rishika Singh ◽  
Dilip R. Patel ◽  
Sherry Pejka
Keyword(s):  
United States ◽  
Acute Kidney Injury ◽  
Side Effect ◽  
Kidney Injury ◽  
The United States ◽  
Multiple Factors ◽  
Case Diagnosis ◽  
Multiple Causes

Rhabdomyolysis can occur because of multiple causes and account for 7% of all cases of acute kidney injury annually in the United States. Identification of specific cause can be difficult in many cases where multiple factors could potentially cause rhabdomyolysis. We present a case of 16-year-old male who had seizures and was given levetiracetam that resulted in rhabdomyolysis. This side effect has been rarely reported previously and like in our case diagnosis may be delayed.

scholarly journals Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis

PLoS Medicine ◽  
2019 ◽  
Vol 16 (12) ◽  
pp. e1002983 ◽  
Author(s):  
Jan Menne ◽  
Eva Dumann ◽  
Hermann Haller ◽  
Bernhard M. W. Schmidt
Keyword(s):  
Systematic Review ◽  
Acute Kidney Injury ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Sglt2 Inhibitors

scholarly journals Acute Kidney Injury in Children Hospitalized With Diarrheal Illness in the United States

2019 ◽  
Vol 9 (12) ◽  
pp. 933-941 ◽  
Author(s):  
Christina Bradshaw ◽  
Jialin Han ◽  
Glenn M. Chertow ◽  
Jin Long ◽  
Scott M. Sutherland ◽  
...  
Keyword(s):  
United States ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
The United States ◽  
Diarrheal Illness

Multimodal Analgesia and Decreased Opioid Use in Adult Trauma Patients

2020 ◽  
Vol 86 (8) ◽  
pp. 950-954
Author(s):  
Andrew L. Drahos ◽  
Anthony M. Scott ◽  
Tracy J. Johns ◽  
Dennis W. Ashley
Keyword(s):  
Acute Kidney Injury ◽  
Management Strategies ◽  
Kidney Injury ◽  
Multimodal Analgesia ◽  
The United States ◽  
Control Group ◽  
Trauma Patients ◽  
Opioid Use ◽  
Trauma Service ◽  
The Impact

Background There is an opioid epidemic in the United States. With the increased concern of over-prescribing opioids, physicians are seeking alternative pain management strategies. The purpose of this study is to review the impact of instituting a multimodal analgesia (MMA) guideline on decreasing opioid use in trauma patients at a Level 1 trauma center. Methods In 2017, an MMA guideline was developed and included anti-inflammatories, muscle relaxants, neuropathic agents, and local analgesics in addition to opioids. Staff were educated and the guideline was implemented. A retrospective review of medications prescribed to patients admitted from 2016 through 2018 was performed. Patients admitted in 2016 served as the control group (before MMA). In 2018, all patients received multimodal pain therapy as standard practice, and served as the comparison group. Results A total of 10 340 patients were admitted to the trauma service from 2016 through 2018. There were 3013 and 3249 patients for review in 2016 and 2018, respectively. Total morphine milligram equivalents were 2 402 329 and 1 975 935 in 2016 and 2018, respectively, a 17.7% decrease ( P < .001). Concurrently, there was a statistically significant increase in the use of multimodal pain medications. A secondary endpoint was studied to evaluate for changes in acute kidney injury; there was not a statistically significant increase (0.56% versus 0.68%, P = .55). Discussion Implementation of an MMA guideline significantly reduced opioid use in trauma patients. The use of nonopioid MMA medications increased without an increased incidence of acute kidney injury.

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