Browsing by Subject "End-stage kidney disease"
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Item A prespecified exploratory analysis from FIDELITY examined finerenone use and kidney outcomes in patients with chronic kidney disease and type 2 diabetes(Elsevier, 2023) Bakris, George L.; Ruilope, Luis M.; Anker, Stefan D.; Filippatos, Gerasimos; Pitt, Bertram; Rossing, Peter; Fried, Linda; Roy-Chaudhury, Prabir; Sarafidis, Pantelis; Ahlers, Christiane; Brinker, Meike; Joseph, Amer; Lawatscheck, Robert; Agarwal, Rajiv; FIDELIO-DKD and FIGARO-DKD Investigators; Medicine, School of MedicineIn FIDELITY, a prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD studies, finerenone was found to improve cardiorenal outcomes in patients with type 2 diabetes, a urine albumin-to-creatinine ratio of 30-5000 mg/g, an estimated glomerular filtration rate (eGFR) of 25 ml/min per 1.73 m2 or more and also receiving optimized renin-angiotensin system blockade treatment. This present analysis focused on the efficacy and safety of finerenone on kidney outcomes. Among 13,026 patients with a median follow-up of three years, finerenone significantly reduced the hazard of a kidney composite outcome (time to kidney failure, sustained 57% or more decrease in eGFR from baseline, or kidney death) by 23% versus placebo (hazard ratio, 0.77; 95% confidence interval, 0.67-0.88), with a three-year absolute between-group difference of 1.7% (95% confidence interval, 0.7-2.6). Hazard ratios were directionally consistent for a prespecified baseline eGFR and urine albumin-to-creatinine ratio categories (Pinteraction = 0.62 and Pinteraction = 0.67, respectively), although there was a high degree of uncertainty in the 30-300 mg/g subgroup. Finerenone significantly reduced the hazard of end-stage kidney disease (ESKD) by 20% versus placebo (0.80; 0.64-0.99). Adverse events were similar between treatment arms, although hyperkalemia leading to treatment discontinuation occurred significantly more frequently with finerenone versus placebo (2.4% vs 0.8% and 0.6% vs 0.3% in patients with eGFR less than 60 vs. greater than or equal to 60 ml/min per 1.73 m2, respectively). Thus, finerenone improved kidney outcomes, reduced the hazard of ESKD, and is well tolerated in patients with chronic kidney disease and type 2 diabetes.Item Age-based risk of end-stage kidney disease in patients with myelomeningocele(Elsevier, 2023-04) Adams, Cyrus M.; Misseri, Rosalia; Roth, Joshua D.; Whittam, Benjamin M.; Guckien, Zoe E.; King, Shelly J.; Kaefer, Martin; Rink, Richard C.; Szymanski, Konrad M.; Urology, School of MedicineObjective We aimed to quantify end-stage kidney disease (ESKD) risk after infancy in individuals with myelomeningocele (MMC) followed by urology in the modern medical era and to assess if ESKD risk was higher after surgery related to a hostile bladder. Methods We retrospectively reviewed patients with MMC followed by urology at our institution born ≥ 1972 (when clean intermittent catheterization was introduced) past 1 year of age (when mortality is highest, sometimes before establishing urology care). ESKD was defined as requiring permanent peritoneal/hemodialysis or renal transplantation. Early surgery related to hostile bladder included incontinent vesicostomy, bladder augmentation, detrusor Botulinum A toxin injection, ureteral reimplantation, or nephrectomy for recurrent urinary tract infections. Survival analysis and proportional hazards regression were used. Sensitivity analyses included: risk factor analysis with only vesicostomy, timing of surgery, including the entire population without minimal follow-up (n = 1054) and only patients with ≥ 5 years of follow-up (n = 925). Results Overall, 1029 patients with MMC were followed for a median of 17.0 years (49% female, 76% shunted). Seven patients (0.7%) developed ESKD at a median 24.3 years old (5 hemodialysis, 1 peritoneal dialysis, 1 transplantation). On survival analysis, the ESKD risk was 0.3% at 20 years old and 2.1% at 30 years old (Figure). This was ∼100 times higher than the general population (0.003% by 21 years old, p < 0.001). Patients who underwent early surgery for hostile bladder had higher ESKD risk (HR 8.3, p = 0.001, 6% vs. 1.5% at 30 years). On exploratory analyses, gender, birth year, shunt status and wheelchair use were not associated with ESKD risk (p ≥ 0.16). Thirty-year ESKD risk was 10% after early vesicostomy vs. 1.4% among children without one (p = 0.001). Children undergoing bladder surgery between 1.5 and 5 years old had a higher risk of ESKD. No other statistically/clinically significant differences were noted. Comment Patients with MMC remain at risk of progressive renal damage throughout life. We relied on the final binary ESKD outcome to quantify this risk, rather than imprecise glomerular filtration rate formulas. Analysis was limited by few people developing ESKD, inconsistent documentation of early urodynamic findings and indications for bladder-related surgery. Conclusions While ESKD is relatively uncommon in the MMC population receiving routine urological care, affecting 2.1% of individuals in the first 3 decades, it is significantly higher than the general population. Children with poor bladder function are likely at high risk, underlining the need for routine urological care, particularly in adulthood.Item Balancing Nephrology Referrals With Nephrologist Capacity to Decrease Emergency Dialysis Starts(Elsevier, 2020-11-24) Jan, M. Yahya; Wish, Jay B.; Medicine, School of MedicineItem Evolution of Mineralocorticoid Receptor Antagonists in the Treatment of Chronic Kidney Disease Associated with Type 2 Diabetes Mellitus(Elsevier, 2022-10-15) Wish, Jay B.; Pergola, Pablo; Medicine, School of MedicineChronic kidney disease (CKD) is one of the most frequent complications associated with type 2 diabetes mellitus (T2DM) and is also an independent risk factor for cardiovascular disease. The mineralocorticoid receptor (MR) is a nuclear receptor expressed in many tissue types, including kidney and heart. Aberrant and long-term activation of MR by aldosterone in patients with T2DM triggers detrimental effects (eg, inflammation and fibrosis) in these tissues. The suppression of aldosterone at the early stage of T2DM has been a therapeutic strategy for patients with T2DM-associated CKD. Although patients have been treated with renin-angiotensin system (RAS) blockers for decades, RAS blockers alone are not sufficient to prevent CKD progression. Steroidal MR antagonists (MRAs) have been used in combination with RAS blockers; however, undesired adverse effects have restricted their usage, prompting the development of nonsteroidal MRAs with better target specificity and safety profiles. Recently conducted studies, Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD), have reported that finerenone, a nonsteroidal MRA, improves both renal and cardiovascular outcomes compared with placebo. In this article, we review the history of MRA development and discuss the possibility of its combination with other treatment options, such as sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and potassium binders for patients with T2DM-associated CKD.Item New Insights Into Dietary Approaches to Potassium Management in Chronic Kidney Disease(Elsevier, 2023) Sumida, Keiichi; Biruete, Annabel; Kistler, Brandon M.; Khor, Ban-Hock; Ebrahim, Zarina; Giannini, Rossella; Sussman-Dabach, Elizabeth J.; Avesani, Carla Maria; Chan, Maria; Lambert, Kelly; Wang, Angela Yee-Moon; Clegg, Deborah J.; Burrowes, Jerrilynn D.; Palmer, Biff F.; Carrero, Juan-Jesus; Kovesdy, Csaba P.; Nutrition and Dietetics, School of Health and Human SciencesPotassium disorders are one of the most common electrolyte abnormalities in patients with chronic kidney disease (CKD), contributing to poor clinical outcomes. Maintaining serum potassium levels within the physiologically normal range is critically important in these patients. Dietary potassium restriction has long been considered a core strategy for the management of chronic hyperkalemia in patients with CKD. However, this has been challenged by recent evidence suggesting a paradigm shift toward fostering more liberalized, plant-based dietary patterns. The advent of novel potassium binders and an improved understanding of gastrointestinal processes involved in potassium homeostasis (e.g., gastrointestinal potassium wasting) may facilitate a paradigm shift and incorporation of heart-healthy potassium-enriched food sources. Nevertheless, uncertainty regarding the risk-benefit of plant-based diets in the context of potassium management in CKD remains, requiring well-designed clinical trials to determine the efficacy of dietary potassium manipulation toward improvement of clinical outcomes in patients with CKD.Item Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized Trial(American Society of Nephrology, 2020-05) Jardine, Meg J.; Zhou, Zien; Mahaffey, Kenneth W.; Oshima, Megumi; Agarwal, Rajiv; Bakris, George; Bajaj, Harpreet S.; Bull, Scott; Cannon, Christopher P.; Charytan, David M.; de Zeeuw, Dick; Di Tanna, Gian Luca; Greene, Tom; Heerspink, Hiddo J.L.; Levin, Adeera; Neal, Bruce; Pollock, Carol; Qiu, Rose; Sun, Tao; Wheeler, David C.; Zhang, Hong; Zinman, Bernard; Rosenthal, Norman; Perkovic, Vlado; Medicine, School of MedicineBackground: Canagliflozin reduced renal and cardiovascular events in people with type 2 diabetes in the CREDENCE trial. We assessed efficacy and safety of canagliflozin by initial estimated glomerular filtration rate (eGFR). Methods: CREDENCE randomly assigned 4401 participants with an eGFR of 30 to <90 ml/min per 1.73 m2 and substantial albuminuria to canagliflozin 100 mg or placebo. We used Cox proportional hazards regression to analyze effects on renal and cardiovascular efficacy and safety outcomes within screening eGFR subgroups (30 to <45, 45 to <60, and 60 to <90 ml/min per 1.73 m2) and linear mixed effects models to analyze the effects on eGFR slope. Results: At screening, 1313 (30%), 1279 (29%), and 1809 (41%) participants had an eGFR of 30 to <45, 45 to <60, and 60 to <90 ml/min per 1.73 m2, respectively. The relative benefits of canagliflozin for renal and cardiovascular outcomes appeared consistent among eGFR subgroups (all P interaction >0.11). Subgroups with lower eGFRs, who were at greater risk, exhibited larger absolute benefits for renal outcomes. Canagliflozin's lack of effect on serious adverse events, amputations, and fractures appeared consistent among eGFR subgroups. In all subgroups, canagliflozin use led to an acute eGFR drop followed by relative stabilization of eGFR loss. Among those with an eGFR of 30 to <45 ml/min per 1.73 m2, canagliflozin led to an initial drop of 2.03 ml/min per 1.73 m2. Thereafter, decline in eGFR was slower in the canagliflozin versus placebo group (-1.72 versus -4.33 ml/min per 1.73 m2; between-group difference 2.61 ml/min per 1.73 m2). Conclusions: Canagliflozin safely reduced the risk of renal and cardiovascular events, with consistent results across eGFR subgroups, including the subgroup initiating treatment with an eGFR of 30 to <45 ml/min per 1.73 m2. Absolute benefits for renal outcomes were greatest in subgroups with lower eGFR.Item Targeting the Gut Microbiota in Kidney Disease: The Future in Renal Nutrition and Metabolism(Elsevier, 2023) Lambert, Kelly; Rinninella, Emanuele; Biruete, Annabel; Sumida, Keiichi; Stanford, Jordan; Raoul, Pauline; Mele, Maria Cristina; Wang, Angela Yee-Moon; Mafra, Denise; Medicine, School of MedicineThere is increasing interest in the therapeutic potential of manipulating the gut microbiome of patients with chronic kidney disease (CKD). This is because there is a substantial deviation from a balanced gut microbiota profile in CKD, with many deleterious downstream effects. Nutritional interventions such as plant-based diets with reduced animal protein intake and the use of probiotics, prebiotics, and synbiotics may alter the microbiome. This article aims to briefly describe what is known about the gut microbiome in patients with CKD, factors contributing to gut dysbiosis, and outline important evidence gaps. Future potential therapies, including restoring the microbiota with food and microbiota-based and metabolomic-based therapies, are also discussed.Item The Importance of Transplant Nephrology to a Successful Kidney Transplant Program(Wolters Kluwer, 2022) Moe, Sharon M.; Brennan, Daniel C.; Doshi, Mona D.; Gaston, Robert S.; Gurley, Susan B.; Mujtaba, Muhammad A.; Schmidt, Rebecca J.; Segal, Mark S.; Tucker, J. Kevin; Wiseman, Alexander C.; Josephson, Michelle A.; Medicine, School of MedicineNephrologists are responsible for the care of patients with a diverse array of systemic diseases, comorbidities, and kidney issues across a variety of service locations (clinic, inpatient, dialysis unit). As the field of nephrology becomes increasingly complex, there has been a need for advanced training and subspecialization, similar to the transformation cardiology experienced with heart failure, electrophysiology, and interventional cardiology. As a result, the American Society of Nephrology (ASN) formed the ASN Task Force on Academic Nephrologist Compensation and Productivity to begin to understand the needed transformation, especially as it relates to assessing clinical productivity and compensation. Members of the task force included nephrology division chiefs, transplant program directors, and transplant nephrologists, representing academic and community transplant programs across the United States. The group met virtually throughout 2021 to discuss specific job functions, roles, responsibilities, and compensation models, and the discussion and conclusions follow. The flow of transplant funds from the hospital to the physician and transplant nephrology models of care are further discussed in a companion Perspective.Item VA-Based Peritoneal Dialysis Program Feasibility Considerations and Process Outline(Frontline Medical Communications, 2023) Wadhwa, Anuradha; Fried, Linda F.; Cavanaugh, Kerri; MacKichan, Karen; Sinha, Arjun D.; Adam, Sarah; Hippensteel, Laurie; Ruele, Scott; Crowley, Susan T.; Shukla, Ashutosh M.; Medicine, School of MedicineBackground: Home dialysis utilization is lower among veterans than in the general US population. Several sociodemographic factors and comorbidities contribute to peritoneal dialysis (PD) underutilization. In 2019, the Veterans Health Administration (VHA) Kidney Disease Program Office convened a PD workgroup to address this concern. Observations: The PD workgroup was explicitly concerned by the limited availability of PD within the VHA, which frequently requires veterans to transition kidney disease care from US Department of Veterans Affairs medical centers (VAMCs) to non-VHA facilities when they progress from chronic kidney disease to end-stage kidney disease, causing fragmentation of care. Since the administrative requirements and infrastructure of VAMCs vary, the workgroup focused its deliberations on synthesizing a standard process for evaluating the feasibility and establishing a new PD program within any individual VAMC. A 3-phased approach was envisioned, beginning with ascertainment of prerequisites, leading to an examination of the clinical and financial feasibility through the process of data gathering and synthesis, culminating in a business plan that translates the previous 2 steps into an administrative document necessary for obtaining VHA approvals. Conclusions: VAMCs can use the guide presented here to improve therapeutic options for veterans with kidney failure by establishing a new or restructured PD program.