- Browse by Author
Browsing by Author "Tuttle, Katherine R."
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item Molecular mechanisms and therapeutic targets for diabetic kidney disease(Elsevier, 2022) Tuttle, Katherine R.; Agarwal, Rajiv; Alpers, Charles E.; Bakris, George L.; Brosius, Frank C.; Kolkhof, Peter; Uribarri, Jaime; Medicine, School of MedicineDiabetic kidney disease has a high global disease burden and substantially increases the risk of kidney failure and cardiovascular events. Despite treatment, there is substantial residual risk of disease progression with existing therapies. Therefore, there is an urgent need to better understand the molecular mechanisms driving diabetic kidney disease to help identify new therapies that slow progression and reduce associated risks. Diabetic kidney disease is initiated by diabetes-related disturbances in glucose metabolism, which then trigger other metabolic, hemodynamic, inflammatory, and fibrotic processes that contribute to disease progression. This review summarizes existing evidence on the molecular drivers of diabetic kidney disease onset and progression, focusing on inflammatory and fibrotic mediators—factors that are largely unaddressed as primary treatment targets and for which there is increasing evidence supporting key roles in the pathophysiology of diabetic kidney disease. Results from recent clinical trials highlight promising new drug therapies, as well as a role for dietary strategies, in treating diabetic kidney diseaseItem Obstacles and Opportunities in Managing Coexisting Obesity and CKD: Report of a Scientific Workshop Cosponsored by the National Kidney Foundation and The Obesity Society(Wiley, 2022-12) Friedman, Allon N.; Schauer, Philip R.; Beddhu, Srinivasan; Kramer, Holly; le Roux, Carel W.; Purnell, Jonathan Q.; Sunwold, Duane; Tuttle, Katherine R.; Jastreboff, Ania M.; Kaplan, Lee M.; Medicine, School of MedicineThe National Kidney Foundation (NKF) and The Obesity Society (TOS) cosponsored a multispecialty international workshop in April 2021 to advance the understanding and management of obesity in adults with chronic kidney disease (CKD). The underlying rationale for the workshop was the accumulating evidence that obesity is a major contributor to CKD and adverse outcomes in individuals with CKD, and that effective treatment of obesity, including lifestyle intervention, weight loss medications, and metabolic surgery, can have beneficial effects. The attendees included a range of experts in the areas of kidney disease, obesity medicine, endocrinology, diabetes, bariatric/metabolic surgery, endoscopy, transplant surgery, and nutrition, as well as patients with obesity and CKD. The group identified strategies to increase patient and provider engagement in obesity management, outlined a collaborative action plan to engage nephrologists and obesity medicine experts in obesity management, and identified research opportunities to address gaps in knowledge about the interaction between obesity and kidney disease. The workshop's conclusions help lay the groundwork for development of an effective, scientifically based, and multidisciplinary approach to the management of obesity in people with CKD.Item Racial-Ethnic Differences in Health-Related Quality of Life among Adults and Children with Glomerular Disease(Karger, 2021) Krissberg, Jill R.; Helmuth, Margaret E.; Almaani, Salem; Cai, Yi; Cattran, Daniel; Chatterjee, Debanjana; Gbadegesin, Rasheed A.; Gibson, Keisha L.; Glenn, Dorey A.; Greenbaum, Laurence A.; Iragorri, Sandra; Jain, Koyal; Khalid, Myda; Kidd, Jason M.; Kopp, Jeffrey B.; Lafayette, Richard; Nestor, Jordan G.; Parekh, Rulan S.; Reidy, Kimberly J.; Selewski, David T.; Sperati, C. John; Tuttle, Katherine R.; Twombley, Katherine; Vasylyeva, Tetyana L.; Weaver, Donald Jack; Wenderfer, Scott E.; O’Shaughnessy, Michelle M.; Pediatrics, School of MedicineIntroduction: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships between race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease. Methods: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: 1. Missed school or work due to kidney disease; 2. Responses to Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression. Results: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than White or Asian participants. Black adults missed work or school most frequently due to kidney disease (30% versus 16-23% in the other three groups, p=0.04), and had the worst self-reported global physical health (median score 44.1 versus 48.0-48.2, p<0.001) and fatigue (53.8 versus 48.5-51.1, p=0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status were associated with HRQOL. Conclusions: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by Black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.Item Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials(American Diabetes Association, 2022) Tuttle, Katherine R.; Levin, Adeera; Nangaku, Masaomi; Kadowaki, Takashi; Agarwal, Rajiv; Hauske, Sibylle J.; Elsäßer, Amelie; Ritter, Ivana; Steubl, Dominik; Wanner, Christoph; Wheeler, David C.; Medicine, School of MedicineObjective: To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3-4) enrolled in clinical trials. Research design and methods: This analysis pooled data from 19 randomized, placebo-controlled, phase 1-4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models. Results: Among a total of 15,081 patients who received at least one study drug dose, 1,522, 722, and 123 were classified as having G3A, G3B, and G4 CKD, respectively, at baseline. Demographic and clinical characteristics were similar between treatment groups across CKD categories. Rates of serious AEs, AEs leading to discontinuation, and events of special interest (including lower limb amputations and acute renal failure [ARF]) were also similar between empagliflozin and placebo across CKD subgroups. In adjusted Cox regression analyses, risks for volume depletion and ARF were similar for empagliflozin and placebo in the combined group with CKD categories G3B and G4 and the G3A group. Notably lower risks were observed in both groups for hyperkalemia (hazard ratio 0.59 [95% CI 0.37-0.96, P = 0.0323] and 0.48 [0.26-0.91, P = 0.0243], respectively) and edema (0.47 [0.33-0.68, P < 0.0001] and 0.44 [0.28-0.68, P = 0.0002], respectively). Conclusions: Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema.