ABSTRACT
INTRODUCTION: Black and African American (AA) people are over-represented in the kidney failure population; therefore, the safety and efficacy of difelikefalin in Black/AA patients was evaluated. METHODS: This was a post hoc, pooled exploratory subgroup analysis of the Phase 3 KALM-1 and -2 studies. Patients undergoing hemodialysis (HD) who had moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) at enrollment were stratified into self-reported Black/AA or White subgroups. Patients were randomized (1:1) to receive intravenous (IV) difelikefalin 0.5 µg/kg or placebo for 12 weeks. Difelikefalin efficacy was assessed with validated patient-reported outcome questionnaires: 24-h Worst Itch Numerical Rating Scale (WI-NRS), 5-D itch, and Skindex10. RESULTS: There were 249 (29.3%) patients from the KALM studies that self-identified as Black/AA (n = 135 difelikefalin; n = 114 placebo). Clinically meaningful (≥3-point) reduction in WI-NRS score was achieved by 47.9% of Black/AA patients with difelikefalin versus 24.6% with placebo (p < 0.001). More Black/AA patients achieved a ≥5-point 5-D itch total improvement (54.9% vs. 35.7%; p = 0.013) and a ≥15-point Skindex-10 score improvement with difelikefalin versus placebo (49.0% vs. 28.9%; p = 0.006) compared with White patients. Incidence of treatment-emergent adverse events (TEAEs) was higher for Black/AA patients (difelikefalin: 78.5%; placebo: 70.8%) versus White patients (difelikefalin: 64.8%; placebo: 61.8%). CONCLUSION: In this post hoc analysis, difelikefalin was efficacious in the Black/AA population and had an acceptable safety profile.
Subject(s)
Black or African American , Pruritus , Renal Dialysis , Humans , Pruritus/etiology , Pruritus/drug therapy , Male , Female , Middle Aged , Black or African American/statistics & numerical data , Aged , Adult , Severity of Illness Index , Double-Blind Method , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/complications , Treatment Outcome , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/complicationsABSTRACT
BACKGROUND: Tumor Lysis syndrome (TLS) is a well-recognized medical emergency in patients with cancer diagnosis. The diagnostic criteria of TLS have been revised many times since it was recognized, but still have many drawbacks limit diagnosis accuracy. SUMMARY: Autopsy studies in patients with perimortem diagnoses of TLS have shown that they may not have actually had TLS. Therefore, many cancer patients who are at risk for TLS, clinical and laboratory criteria may be fulfilled due to other causes of acute kidney injury. In this review, we aim to cast a spotlight on the shortcomings and pitfalls of the current diagnostic criteria for TLS, and propose a roadmap for developing a more rigorous criteria that improve on the diagnostic accuracy. KEY MESSAGES: Causes of AKI in patients with cancer other than TLS should be considered. Because current diagnostic criteria may miss those differential diagnosis, specific biomarkers that can tell when TLS is the underlying process is an important need, besides appropriate criteria that can jump over the pitfalls in the current criteria and enhance the recognition of TLS among other causes.
ABSTRACT
Patients with acromegaly carry a high risk of developing cardiovascular diseases (CVD). In fact, CVD is the leading cause of mortality among this group of patients. The most frequent cardiovascular complications are heart failure (HF), valvular disease, hypertension, arrhythmias, and coronary artery disease (CAD). The pathophysiology centers on the family of growth hormone (GH). These hormones are involved in normal cardiac development and function; however, excess of insulin-like growth factor-1 (IGF-1), the principally active hormone, can also cause negative effects on the cardiovascular system. HF in acromegaly usually presents with biventricular enlargement and diastolic dysfunction and is strongly associated with the duration of GH excess rather than the degree of hormone elevation. There is a high prevalence of valvular disease affecting aortic and mitral valves among patients with longer disease duration. The development of hypertension in acromegaly may be attributed to the effects of chronic GH/IGF-1 excess on different organ systems, which act via several mechanisms. The aspect of arrhythmia and CAD complicating acromegaly are currently not fully understood.
ABSTRACT
Gender inequities negatively impact productivity and career advancement for women. Social media platforms like Twitter can be used to achieve greater parity and address underrepresentation by providing a medium for education, research and mentorship, however, it is unknown how it may contribute to gender inequity. Our aim was to examine gender interactions during a nephrology medical conference.
Subject(s)
Education, Medical , Nephrology , Social Media , Female , HumansABSTRACT
Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.
Subject(s)
Acute Kidney Injury , COVID-19 , Apolipoprotein L1/genetics , Humans , Kidney , Retrospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1-3 CKD. METHODS: Adults with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24-72 h until normokalaemia (i-STAT K+ 3.5-5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for ≤12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or ≥30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). RESULTS: Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, ≥30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and ≥30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 ≥30 mL/min/1.73 m2 subgroup. CONCLUSIONS: SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.
Subject(s)
Biomarkers/blood , Hyperkalemia/drug therapy , Kidney Failure, Chronic/complications , Potassium/blood , Renal Insufficiency, Chronic/complications , Severity of Illness Index , Silicates/therapeutic use , Aged , Female , Humans , Hyperkalemia/blood , Hyperkalemia/etiology , Hyperkalemia/pathology , Male , Middle Aged , Prognosis , Prospective StudiesABSTRACT
BACKGROUND: Sodium zirconium cyclosilicate (SZC) binds potassium and ammonium in the gastrointestinal tract. In addition to serum potassium reduction, Phase 2 trial data have shown increased serum bicarbonate with SZC, which may be clinically beneficial because maintaining serum bicarbonate ≥22 mmol/L preserves kidney function. This exploratory analysis examined serum bicarbonate and urea, and urine pH data from three SZC randomized, placebo-controlled Phase 3 studies among patients with hyperkalaemia [ZS-003 (n = 753), HARMONIZE (n = 258) and HARMONIZE-Global (n = 267)]. METHODS: In all studies, patients received ≤10 g SZC 3 times daily (TID) for 48 h to correct hyperkalaemia, followed by randomization to maintenance therapy with SZC once daily (QD) versus placebo for ≤29 days among those achieving normokalaemia. RESULTS: Significant dose-dependent mean serum bicarbonate increases from baseline of 0.3 to 1.5 mmol/L occurred within 48 h of SZC TID in ZS-003 (all P < 0.05), which occurred regardless of chronic kidney disease (CKD) stage. Similar acute increases in HARMONIZE and HARMONIZE-Global were maintained over 29 days. With highest SZC maintenance doses, patient proportions with serum bicarbonate <22 mmol/L fell from 39.4% at baseline to 4.9% at 29 days (P = 0.005) in HARMONIZE and from 87.9% to 70.1%, (P = 0.006) in HARMONIZE-Global. Path analyses demonstrated that serum urea decreases (but not serum potassium or urine pH changes) were associated with SZC effects on serum bicarbonate. CONCLUSIONS: SZC increased serum bicarbonate concentrations and reduced patient proportions with serum bicarbonate <22 mmol/L, likely due to SZC-binding of gastrointestinal ammonium. These SZC-induced serum bicarbonate increases occurred regardless of CKD stage and were sustained during ongoing maintenance therapy.
Subject(s)
Silicates , Bicarbonates/therapeutic use , Blood Urea Nitrogen , Gastrointestinal Tract , Humans , Hyperkalemia/blood , Male , Middle Aged , Potassium/blood , Renal Insufficiency, Chronic/complications , Sodium Bicarbonate , UreaABSTRACT
Cardiorenal syndrome encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in 1 organ may induce acute or chronic dysfunction in the other organ. It represents the confluence of heart-kidney interactions across several interfaces. These include the hemodynamic cross-talk between the failing heart and the response of the kidneys and vice versa, as well as alterations in neurohormonal markers and inflammatory molecular signatures characteristic of its clinical phenotypes. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Finally, it outlines the need for a cardiorenal education track that will guide future cardiorenal trials and integrate the clinical and research needs of this important field in the future.
Subject(s)
Cardio-Renal Syndrome/epidemiology , Diabetes Mellitus/epidemiology , Graft Rejection/epidemiology , Heart/physiology , Kidney Transplantation , Kidney/physiology , Neurotransmitter Agents/metabolism , American Heart Association , Biomarkers , Cardio-Renal Syndrome/diagnosis , Cardio-Renal Syndrome/therapy , Education, Medical , Expert Testimony , Humans , Prognosis , Translational Research, Biomedical , United States/epidemiologyABSTRACT
Social Media usage has been shown to increase in situations of natural disaster and other crises. It is crucial for the scientific community to understand how social media works in order to enhance our capabilities and make a more resilient community. Through social media communication, the scientific community can collaborate around the globe in a faster way the most important findings of a disease, with a decreased knowledge transition time to other healthcare providers (HCPs). This is greatly important to coordinate research and knowledge during a time of uncertainty and protentional fake news. During the 2020 global pandemic, social media has become an ally but also a potential threat. High volumes of information compressed into a short period can result in overwhelmed HCPs trying to discern fact from noise. A major limitation of social media currently is the ability to quickly disseminate false information which can confuse and distract. Society relies on educated scientists and physicians to be leaders in delivering fact-based information to the public. For this reason, in times of crises it is important to be leaders in the conversation of social media to guide correct and helpful information and knowledge to the masses looking for answers.
Subject(s)
COVID-19/epidemiology , Pandemics , SARS-CoV-2 , Social Media/organization & administration , HumansABSTRACT
Previously it has been demonstrated that telehealth (TH) could help cover the gaps in health attention in remote locations. Today the expanded capabilities have transformed TH delivery, and from the beginning of the coronavirus pandemic, it has remained one of our biggest allies. Telehealth has become a central piece in patient healthcare delivery during COVID-19 pandemic era. Telehealth allows health care services to reach patients in their homes, keeping other patients safe through social distancing and maintaining self-quarantine. Within this administration of health, TH allows health care providers to focus more resources to pandemic usage and at the same time continue caring for the health of non COVID-19 patients. During this time, clinicians are expanding knowledge about TH capabilities, such as application of forward triage as a tool to avoid patient contact in emergency departments. While previously TH was mainly used for primary care needs, specialized and urgent care health is now being utilized more than ever before. These advantages comes with limitations, some of them include a limited physical exam, lack of access to diagnostic testing or imaging, and many other pitfalls and persistent unmet needs. The 2020 pandemic has led to significant improvements leading into the next generation of telemedicine.
Subject(s)
COVID-19/embryology , Disease Management , Pandemics , SARS-CoV-2 , Telemedicine/methods , COVID-19/therapy , HumansABSTRACT
Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.
Subject(s)
Coronavirus Infections/epidemiology , Health Resources/supply & distribution , Health Resources/statistics & numerical data , Mandatory Reporting , Mobile Applications/statistics & numerical data , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Ambulatory Care/statistics & numerical data , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/therapy , Critical Care/statistics & numerical data , Hospitalization/statistics & numerical data , Hospitals/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Residence Characteristics/statistics & numerical data , Self Report/statistics & numerical dataABSTRACT
BACKGROUND: A visual abstract is a graphic summary of a research article's question, methods, and major findings. Although they have a number of uses, visual abstracts are chiefly used to promote research articles on social media. OBJECTIVE: This study aimed to determine if the use of visual abstracts increases the visibility of nephrology research shared on Twitter. METHODS: A prospective case-control crossover study was conducted using 40 research articles published in the American Journal of Nephrology (AJN). Each article was shared by the AJN Twitter account in 3 formats: (1) the article citation, (2) the citation with a key figure from the article, and (3) the citation with a visual abstract. Tweets were spaced 2 weeks apart to allow washout of the previous tweet, and the order of the tweets was randomized. Dissemination was measured via retweets, views, number of link clicks, and Altmetric scores. RESULTS: Tweets that contained a visual abstract had more than twice as many views as citation-only tweets (1351, SD 1053 vs 639, SD 343) and nearly twice as many views as key figure tweets (1351, SD 1053 vs 732, SD 464). Visual abstract tweets had 5 times the engagements of citation-only tweets and more than 3.5 times the engagements of key figure tweets. Visual abstract tweets were also associated with greater increases in Altmetric scores as compared to citation-only tweets (2.20 vs 1.05). CONCLUSIONS: The use of visual abstracts increased visibility of research articles on Twitter, resulting in a greater number of views, engagements, and retweets. Visual abstracts were also associated with increased Altmetric scores as compared to citation-only tweets. These findings support the broader use of visual abstracts in the scientific community. Journals should consider visual abstracts as valuable tools for research dissemination.
Subject(s)
Audiovisual Aids/standards , Information Dissemination/methods , Social Media/standards , Cross-Over Studies , Humans , Prospective StudiesSubject(s)
Glomerulonephritis, IGA , Humans , Glomerulonephritis, IGA/genetics , Disease ProgressionABSTRACT
BACKGROUND: To summarize the four recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials: Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and explore the potential determinants for their cardiovascular, renal, and safety outcomes. RESULTS: The composite renal outcome event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 3.7, 7.0, 47%; 5.5, 9.0, 40%; 6.3, 11.5, 46%; 43.2, 61.2, 30% for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively (event definitions varied across trials). The major adverse cardiovascular (CV) event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14%; 38.7, 48.7, 20% for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively. DECLARE-TIMI 58 had the fewest cardiorenal events and CREDENCE the most. These differences were presumably due to varying inclusion criteria resulting in DECLARE-TIMI 58 having the best baseline renal filtration function and CREDENCE the worst (mean estimated glomerular filtration rate 85.2, 76.5, 74, 56.2 mL/min/1.73 m2 for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively). Additionally, CREDENCE had considerably higher rates of albuminuria (median urinary albumin-creatinine ratios (UACR) were 927, 12.3, and 13.1 mg/g for CREDENCE, CANVAS, and DECLARE-TIMI 58, respectively; EMPA-REG OUTCOME had 59.4% UACR < 30, 28.6% UACR > 30-300, 11.0% UACR > 300 mg/g). CONCLUSIONS: Dapagliflozin, empagliflozin, and canagliflozin have internally and externally consistent and biologically plausible class effects on cardiorenal outcomes. Baseline renal filtration function and degree of albuminuria are the most significant indicators of risk for both CV and renal events. Thus, these two factors also anticipate the greatest clinical benefit for SGLT2i.
Subject(s)
Benzhydryl Compounds/therapeutic use , Canagliflozin/therapeutic use , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Glucosides/therapeutic use , Renal Insufficiency, Chronic/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/adverse effects , Canagliflozin/adverse effects , Cardiovascular Diseases/mortality , Cardiovascular Diseases/physiopathology , Cardiovascular System/drug effects , Cardiovascular System/physiopathology , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/mortality , Diabetic Nephropathies/physiopathology , Disease Progression , Glucosides/adverse effects , Humans , Kidney/drug effects , Kidney/physiopathology , Protective Factors , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/physiopathology , Risk Assessment , Risk Factors , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for treatment of hyperkalemia. An open-label extension (OLE) of the -HARMONIZE study evaluated efficacy and safety of SZC for ≤11 months. METHODS: Patients from HARMONIZE with point-of-care device i-STAT K+ 3.5-6.2 mmol/L received once-daily SZC 5-10 g for ≤337 days. End points included achievement of mean serum K+ ≤5.1 mmol/L (primary) or ≤5.5 mmol/L (secondary). RESULTS: Of 123 patients who entered the extension (mean serum K+ 4.8 mmol/L), 79 (64.2%) completed the study. The median daily dose of SZC was 10 g (range 2.5-15 g). The primary end point was achieved by 88.3% of patients, and 100% achieved the secondary end point. SZC was well tolerated with no new safety concerns. CONCLUSION: In the HARMONIZE OLE, most patients maintained mean serum K+ within the normokalemic range for ≤11 months during ongoing SZC treatment.
Subject(s)
Hyperkalemia/drug therapy , Ion Exchange Resins/administration & dosage , Potassium/blood , Silicates/administration & dosage , Aged , Dose-Response Relationship, Drug , Female , Humans , Hyperkalemia/blood , Ion Exchange Resins/adverse effects , Male , Middle Aged , Potassium/metabolism , Prospective Studies , Renin-Angiotensin System , Silicates/adverse effects , Treatment OutcomeABSTRACT
Kidney transplantation (KT) is the optimal therapy for end-stage kidney disease (ESKD), resulting in significant improvement in survival as well as quality of life when compared with maintenance dialysis. The burden of cardiovascular disease (CVD) in ESKD is reduced after KT; however, it still remains the leading cause of premature patient and allograft loss, as well as a source of significant morbidity and healthcare costs. All major phenotypes of CVD including coronary artery disease, heart failure, valvular heart disease, arrhythmias and pulmonary hypertension are represented in the KT recipient population. Pre-existing risk factors for CVD in the KT recipient are amplified by superimposed cardio-metabolic derangements after transplantation such as the metabolic effects of immunosuppressive regimens, obesity, posttransplant diabetes, hypertension, dyslipidemia and allograft dysfunction. This review summarizes the major risk factors for CVD in KT recipients and describes the individual phenotypes of overt CVD in this population. It highlights gaps in the existing literature to emphasize the need for future studies in those areas and optimize cardiovascular outcomes after KT. Finally, it outlines the need for a joint 'cardio-nephrology' clinical care model to ensure continuity, multidisciplinary collaboration and implementation of best clinical practices toward reducing CVD after KT.
Subject(s)
Cardiovascular Diseases , Disease Management , Kidney Transplantation/adverse effects , Transplant Recipients , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/therapy , Global Health , Humans , Incidence , Kidney Failure, Chronic/surgery , Survival Rate/trendsABSTRACT
In this systematic review, we sought to summarize the 3 recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials (Dapagliflozin Effect on CardiovasculAR Events (DECLARE-TIMI 58), Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, and Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME)) and to explore the potential causes for their different results. We found that the major adverse cardiovascular event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14% for DECLARE-TIMI 58, CANVAS, and EMPA-REG OUTCOME, respectively. DECLARETIMI 58 had the fewest cardiorenal events (across treatment and control arms) and EMPA-REG OUTCOME the most. DECLARE-TIMI 58 used alternative inclusion criterion for baseline renal function (creatinine clearance ⧠60 mL/min) compared to the other trials (estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 bodysurface area). Therefore, the DECLARE-TIMI 58 study cohort had higher eGFR (mean eGFR 85.2 mL/min/1.73 m2 compared to 76.5 and 74 in CANVAS and EMPAREG OUTCOME, respectively); this may have caused the difference in results. Additionally contributing to the high event rate in EMPA-REG OUTCOME was the requirement of prior confirmed cardiovascular disease (CVD), resulting in 99.2% of patients with CVD compared to only 65.6% and 40.6% in CANVAS and DECLARE-TIMI 58, respectively (which did not require CVD). In conclusion, there is a need for large-scale studies of SGLT2i with matching inclusion/exclusion criteria and appropriate endpoints to ensure a truly direct comparison of the drugs.
Subject(s)
Benzhydryl Compounds/therapeutic use , Canagliflozin/therapeutic use , Cardiovascular Diseases/physiopathology , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Kidney Diseases/physiopathology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/adverse effects , Biomarkers , Blood Glucose/drug effects , Blood Glucose/metabolism , Canagliflozin/adverse effects , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Glucosides/adverse effects , Health Status , Humans , Kidney Diseases/diagnosis , Kidney Diseases/mortality , Randomized Controlled Trials as Topic , Research Design , Risk Factors , Sodium-Glucose Transporter 2/drug effects , Sodium-Glucose Transporter 2/metabolism , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Treatment OutcomeABSTRACT
Clinical trials of sodium glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and comorbid cardiovascular and kidney disease have shown reductions in major adverse cardiovascular events, heart failure hospitalizations, and attenuation of the progression of kidney disease. The magnitude of benefit appears to be greater than expected due to glycemic control, reduced blood pressure, and loss of adiposity. This impact is also independent from reduced renal function and lesser degrees of natriuresis and glycosuria. However, these agents have also been associated with limb amputation, Fournier's gangrene, diabetic ketoacidosis, metabolic bone disease, and increased hematopoiesis. A strong off-target effect of SGLT2i on the sodium-proton antiporter (exchanger) on the cell surface and intracellular organelles explains the wide-ranging effects of these agents. By slowing the restoration of pH within cells, SGLT2i activate secondary processes that mimic ischemic preconditioning in the heart and kidney and increased hematopoiesis in bone marrow which would explain salutary effects. Conversely, the inability to rapidly recover pH in ischemic peripheral tissues explains the progression of diabetic extremity ulcers, gangrene, propensity for metabolic bone disease, and diabetic ketoacidosis in patients who are predisposed. This paper will review the evidence for the strong off-target effect of SGLT2i on the sodium-proton exchanger and its potential effect on the organ systems and processes in which SGLT2i appear to have activity.
Subject(s)
Cardiovascular Diseases/metabolism , Cardiovascular System/drug effects , Diabetes Mellitus, Type 2/drug therapy , Kidney Diseases/metabolism , Kidney/drug effects , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Hydrogen Exchangers/antagonists & inhibitors , Animals , Biomarkers , Blood Glucose/drug effects , Blood Glucose/metabolism , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cardiovascular Diseases/physiopathology , Cardiovascular System/metabolism , Cardiovascular System/physiopathology , Comorbidity , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Health Status , Humans , Hydrogen-Ion Concentration , Kidney/metabolism , Kidney/physiopathology , Kidney Diseases/diagnosis , Kidney Diseases/mortality , Kidney Diseases/physiopathology , Risk Factors , Sodium-Glucose Transporter 2/drug effects , Sodium-Glucose Transporter 2/metabolism , Sodium-Hydrogen Exchangers/metabolism , Treatment OutcomeABSTRACT
BACKGROUND: There are no guidelines for transitioning patients from chronic kidney disease stage 5 to hemodialysis. We conducted this study to determine if there are uniform patterns in how nephrologists transition patients to dialysis. METHODS: We designed an electronic survey with 39 questions and sent it to a database of practicing nephrologists at the National Kidney Foundation. Factors that were important for transitioning a patient to hemodialysis were evaluated, including medication changes on dialysis initiation, dry weight and dialysis prescription. RESULTS: 160 US Nephrologists replied to the survey; 18% (29/160) of the responses were completed via social media sites. Prior to dialysis, 74% (118/160), prescribed furosemide and 67% (107/160) used furosemide with metolazone. Once dialysis started, only 46% (74/160) of the responders continued patients on diuretics daily. Hypertension medications prescribed in dialysis were calcium channel blockers 69% (112/160), beta blockers 36% (58/160), angiotensin converting enzyme inhibitor 32% (53/160), angiotensin receptor blocker 29% (46/160) and diuretics 25% (42/160). Once dialysis started, 68% (109/160) routinely changed medications. Most, 67% (107/160) ordered patients to avoid anti-hypertensive medications on dialysis days to allow for ultrafiltration. Dry weight was determined in the first week by 29% (46/160) and in the first month by 53% (85/160). Most, 59% (94/160) felt that multiple causes lead to hypertension. Most nephrologists would prescribe small dialyzers and a shorter period of time for the first dialysis session. CONCLUSION: The transition period to chronic hemodialysis has variations in practice patterns and may benefit from further studies to optimize clinical practice.