Publications by authors named "Katherine Tuttle"

Of the nearly 600,000 people in the U.S. who receive dialysis for chronic kidney failure, >60% have diabetes.

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Background And Aim: Kidney transplant recipients frequently experience a wide range of metabolic complications, including weight changes, which significantly impact patient outcomes and graft function, yet the relationship between weight gain and transplant outcomes remains poorly understood. This systematic review and meta-analysis aimed to synthesise existing evidence on the influence of weight gain on patient and graft outcomes following kidney transplantation to enhance clinical practice and optimise post-transplant care strategies.

Materials And Methods: A literature search was conducted across databases such as PubMed and Scopus for peer-reviewed studies published up to 8 August 2024.

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Background: GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials.

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Article Synopsis
  • * The KDOQI Work Group generally agrees with KDIGO's suggestions for CKD evaluation, management options, and the use of new medications such as SGLT2 inhibitors for various CKD types, particularly in patients with diabetes.
  • * The guidelines stress team-based care as essential in addressing CKD challenges, and the work group has identified barriers and opportunities for implementing these new recommendations while continuing research on early CKD detection and treatment.
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Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do.

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Patients with chronic kidney disease (CKD) are at risk of progressive loss of kidney function, heart failure, and cardiovascular death despite current proven therapies, including renin-angiotensin system inhibitors (RASi), sodium glucose co-transporter-2 inhibitors (SGLT2i), and statin-based regimens. RASi and SGLT2i reduce risk of CKD progression irrespective of primary cause of kidney disease, suggesting they target final common pathways. Targeting aldosterone overactivity with a nonsteroidal mineralocorticoid receptor antagonist (MRA) also reduces cardiorenal risk in patients with albuminuric diabetic kidney disease already treated with RASi.

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  • The EMPA-KIDNEY trial examined the effects of empagliflozin, an SGLT2 inhibitor, on patients with chronic kidney disease at risk for progression, assessing outcomes during and after the trial.
  • A total of 6609 patients were randomized, with 4891 participating in a follow-up period after the trial where they were observed for an additional 2 years, without trial medication but allowed to use other SGLT2 inhibitors.
  • Results showed that fewer primary outcome events (like kidney disease progression or cardiovascular death) occurred in the empagliflozin group (26.2%) compared to the placebo group (30.3%), suggesting lasting benefits of the drug even after the trial ended. *
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Article Synopsis
  • - The study investigates the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular outcomes specifically in patients with type 2 diabetes and low-to-normal body mass index (BMI), addressing a gap in previous research.
  • - Researchers analyzed data from over 30 million citizens in Japan, comparing outcomes between SGLT2 inhibitors and dipeptidyl peptidase (DPP) 4 inhibitors across various BMI categories while tracking a range of cardiovascular events.
  • - Results showed that while SGLT2 inhibitors generally reduced the risk of major cardiovascular outcomes for the overall population, they did not demonstrate the same protective effect in patients with low-to-normal BMI.
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In contrast to inborn errors of immunity (IEI), which are inherited disorders of the immune system that predispose to infections, malignancy, atopy, and immune dysregulation, secondary immunodeficiencies and immune dysregulation states (SID) are acquired impairments in immune cell function and/or regulation, and may be transient, reversible, or permanent. SIDs can derive from a variety of medical comorbidities, including protein-losing conditions, malnutrition, malignancy, certain genetic syndromes, prematurity, and chronic infections. Medications, including immunosuppressive and chemotherapeutic drugs, can have profound effects on immunity and biologic agents used in rheumatology, neurology, and hematology/oncology practice are increasingly common causes of SID.

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Mechanisms underlying the cardiovascular-kidney-metabolic (CKM) syndrome are unknown, although key small molecule metabolites may be involved. Bulk and spatial metabolomics identified adenine to be upregulated and specifically enriched in coronary blood vessels in hearts from patients with diabetes and left ventricular hypertrophy. Single nucleus gene expression studies revealed that endothelial methylthioadenosine phosphorylase (MTAP) was increased in human hearts with hypertrophic cardiomyopathy.

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Background: People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m, kidney replacement therapy, and kidney or CV death) by 24%.

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Article Synopsis
  • The FLOW trial investigated the effects of semaglutide on cardiovascular (CV) events and death in individuals with type 2 diabetes and chronic kidney disease (CKD).
  • Results showed that semaglutide lowered the risk of CV death, non-fatal heart attacks, and strokes by 18%, and overall mortality by 20% across various levels of CKD severity.
  • The beneficial effects of semaglutide were consistent regardless of kidney function, protein levels in urine, or risk classification.
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Background: GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter 2) inhibitors both improve cardiovascular and kidney outcomes in people with type 2 diabetes. We conducted a systematic review and meta-analysis to assess the effects of GLP-1 receptor agonists on clinical outcomes with and without SGLT2 inhibitors.

Methods: We searched MEDLINE and Embase databases from inception until July 12, 2024, for randomized, double-blind, placebo-controlled outcome trials of GLP-1 receptor agonists in type 2 diabetes that reported treatment effects by baseline use of SGLT2 inhibitors, with findings supplemented by unpublished data.

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Background And Aim: Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion, and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies.

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Background And Aim: Sodium-glucose cotransporter (SGLT)-2 inhibitors are novel anti-diabetic medications with potential beneficial effects on cardiovascular and renal outcomes, metabolic parameters, and body weight. In addition to the beneficial effects on renal functions, including estimated glomerular filtration rate and reduction in proteinuria, recent studies have investigated the potential role of SGLT-2 inhibitor therapy on nephrolithiasis development. Nephrolithiasis, a condition affecting almost 10% of the general population at least once during a lifetime, is a common disorder with considerable risk for acute and chronic kidney injury and relatively few effective therapeutic options.

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Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended by Kidney Disease: Improving Global Outcomes (KDIGO) as risk-based treatment for hyperglycemia, weight management, and cardiovascular (CV) risk reduction in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). The aim of this analysis was to assess treatment effects of once weekly semaglutide on kidney disease outcomes by KDIGO risk category and on changes in KDIGO risk category, compared with placebo.

Methods: Participants with T2D and established CV disease or at high CV risk treated with once weekly semaglutide or placebo in SUSTAIN 6 (NCT01720446) were stratified by baseline KDIGO risk category (low [ = 1596], moderate [ = 831], high [ = 445], very high [ = 366]).

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Key Points: In a randomized, placebo-controlled, phase 2b study, we compared the effects of selonsertib with placebo on eGFR decline in people with type 2 diabetes and CKD. Patients taking selonsertib had slower eGFR decline but were more likely to reach a composite kidney outcome and report AKI. A larger trial with longer-term follow-up would more precisely assess the relative benefits and risks of selonsertib in this setting.

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Historically, it takes an average of 17 years for new treatments to move from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. Now is the time to narrow the gap between what we know and what we do.

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Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do.

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Background And Hypothesis: This post-hoc analysis explored the semaglutide effects on eGFR slope by baseline glycemic control, blood pressure (BP), body mass index (BMI), and albuminuria status in people with type 2 diabetes and high cardiovascular risk.

Methods: Pooled SUSTAIN 6 and PIONEER 6 data were analyzed for change in estimated glomerular filtration (eGFR) slope by baseline HbA1c (<8%/≥8%; <64 mmol/mol/≥64 mmol/mol), systolic BP (<140/90 mmHg/≥140/90 mmHg), and BMI (<30 kg/m2/≥30 kg/m2). SUSTAIN 6 data were analyzed by baseline urinary albumin: creatinine ratio (UACR; <30/30 - 300/>300 mg/g).

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Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recommended treatment for adults with chronic kidney disease (CKD), but uncertainty exists regarding their use in patients with frailty and/or multimorbidity, among whom polypharmacy is common. We derived a multivariable logistic regression model to predict hospitalization (reflecting frailty) and assessed empagliflozin's risk-benefit profile in a post-hoc analysis of the double-blind, placebo-controlled EMPA-KIDNEY trial.

Methods: The EMPA-KIDNEY trial randomized 6609 patients with CKD (estimated glomerular filtration rate [eGFR] ≥20<45 mL/min/1.

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Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do.

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