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Background: Statins have uncertain benefits in persons with chronic kidney disease (CKD) because individual trials may have insufficient power to determine whether treatment effects differ with severity of CKD.Purpose: To summarize the benefits and harms of statin therapy for adults with CKD and examine whether effects of statins vary by stage of kidney disease.Data Sources: Cochrane and EMBASE databases (inception to February 2012).Study Selection: Randomized trials comparing the effects of statins with placebo, no treatment, or another statin on mortality and cardiovascular outcomes.Data Extraction: Two independent reviewers extracted data and assessed risk of bias.Data Synthesis: Eighty trials comprising 51099 participants compared statin with placebo or no treatment. Treatment effects varied with stage of CKD. Moderate- to high-quality evidence indicated that statins reduced all-cause mortality (relative risk [RR], 0.81 [95% CI, 0.74 to 0.88]), cardiovascular mortality (RR, 0.78 [CI, 0.68 to 0.89]), and cardiovascular events (RR, 0.76 [CI, 0.73 to 0.80]) in persons not receiving dialysis. Moderate- to high-quality evidence indicated that statins had little or no effect on all-cause mortality (RR, 0.96 [CI, 0.88 to 1.04]), cardiovascular mortality (RR, 0.94 [CI, 0.82 to 1.07]), or cardiovascular events (RR, 0.95 [CI, 0.87 to 1.03]) in persons receiving dialysis. Effects of statins in kidney transplant recipients were uncertain. Statins had little or no effect on cancer, myalgia, liver function, or withdrawal from treatment, although adverse events were evaluated systematically in fewer than half of the trials.Limitation: There was a reliance on post hoc subgroup data for earlier stages of CKD.Conclusion: Statins decrease mortality and cardiovascular events in persons with early stages of CKD, have little or no effect in persons receiving dialysis, and have uncertain effects in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease (CKD). We analyzed the effects of phosphate binders on biochemical and patient-level end points in patients with CKD. Study Design: Systematic review and meta-analysis by searching MEDLINE (1966 to April 2009), EMBASE (1980 to April 2009), and the Cochrane Renal Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL). Setting& Population: Patients with CKD. Selection Criteria For Studies: Randomized controlled trials. Intervention: Phosphate binders. Outcomes: Serum phosphorus, calcium, and parathyroid hormone levels; incidence of hypercalcemia; all-cause mortality; adverse effects. Results: 40 trials (6,406 patients) were included. There was no significant decrease in all-cause mortality (10 randomized controlled trials; 3,079 patients; relative risk [RR], 0.73; 95% confidence interval [CI], 0.46 to 1.16), hospitalization, or end-of-treatment serum calcium-phosphorus product levels with sevelamer compared with calcium-based agents. There was a significant decrease in end-of-treatment phosphorus and parathyroid hormone levels with calcium salts compared with sevelamer and a significant decrease in risk of hypercalcemia (RR, 0.47; 95% CI, 0.36 to 0.62) with sevelamer compared with calcium-based agents. There was a significant increase in risk of gastrointestinal adverse events with sevelamer in comparison to calcium salts (RR, 1.39; 95% CI, 1.04 to 1.87). Compared with calcium-based agents, lanthanum significantly decreased end-of-treatment serum calcium and calcium-phosphorus product levels, but with similar end-of-treatment phosphorus levels. Effects of calcium acetate on biochemical end points were similar to those of calcium carbonate. Existing data are insufficient to conclude for a differential impact of any phosphate binder on cardiovascular mortality or other patient-level outcome. Limitations: Few long-term studies of the efficacy of phosphate binders on mortality and musculoskeletal morbidity, significant heterogeneity for many surrogate outcomes, and suboptimal reporting of study methods to determine trial quality. Conclusion: Currently, there are insufficient data to establish the comparative superiority of non-calcium-binding agents over calcium-containing phosphate binders for such important patient-level outcomes as all-cause mortality and cardiovascular end points. Additional trials are still required to examine the differential effects of phosphate-binding agents on these end points and the mineral homeostasis pathway. [ABSTRACT FROM AUTHOR]

Background: Optimal hydration measures to prevent contrast-induced nephropathy are controversial.Study Design: We conducted a systematic review and meta-analysis using the MEDLINE database (1966 to January 2008), EMBASE (January 2008), and abstracts from conference proceedings.Setting& Population: Adult patients undergoing contrast procedures.Selection Criteria For Studies: Randomized controlled trials comparing intravenous hydration with sodium bicarbonate with hydration with intravenous normal saline for prevention of contrast-induced nephropathy.Intervention: Hydration with intravenous sodium bicarbonate with or without N-acetylcysteine versus hydration with normal saline with or without N-acetylcysteine.Outcomes: Contrast-induced nephropathy, need for renal replacement therapy, and worsening of heart failure.Results: Twelve trials (1,854 participants) were included. Sodium bicarbonate significantly decreased the risk of contrast-induced nephropathy (12 trials, 1,652 patients; odds ratio [OR], 0.46; 95% confidence interval [CI], 0.26 to 0.82; I2 = 55.9%) without a significant difference in need for renal replacement therapy (9 trials, 1,215 patients; OR, 0.50; 95% CI, 0.16 to 1.53; I2 = 0%), in-hospital mortality (11 trials, 1,640 patients; OR, 0.51; 95% CI, 0.15 to 1.69), or congestive heart failure compared with controls. Similar results were seen for the risk of contrast-induced nephropathy when sodium bicarbonate was compared with normal saline alone (OR, 0.39; 95% CI, 0.20 to 0.77), but not when sodium bicarbonate/N-acetylcysteine combination was compared with N-acetylcysteine/normal saline combination (OR, 0.68; 95% CI, 0.34 to 1.37). A subgroup analysis limited to published trials showed similar results (OR, 0.26; 95% CI, 0.10 to 0.64; I2 = 63.3%), whereas unpublished studies showed a nonsignificant decrease (OR, 0.85; 95% CI, 0.46 to 1.57; I2 = 25.9%) in risk of contrast-induced nephropathy.Limitation: Publication bias and heterogeneity.Conclusion: Hydration with sodium bicarbonate decreases the incidence of contrast-induced nephropathy in comparison to hydration with normal saline without a significant difference in need for renal replacement therapy and in-hospital mortality. Larger studies analyzing patient-centered outcomes are needed. [ABSTRACT FROM AUTHOR]

Fibrillary glomerulonephritis belongs to a group of disorders characterized by pathogenic deposition of fibrils in glomeruli. This glomerulopathy tends to progress to end-stage kidney disease, and there currently are no treatments of proven benefit, including corticosteroids and cytotoxic agents. Because the glomerular deposits contain an immunoglobulin component, it was postulated that anti-B-cell therapy with rituximab, an anti-CD20 monoclonal antibody, may be effective in the treatment of patients with fibrillary glomerulonephritis. We describe 3 patients with fibrillary glomerulonephritis who were treated with rituximab for nephrotic-range proteinuria. Each patient also received standard antiproteinuria therapy, including blockade of the renin-angiotensin system and strict blood pressure control. All patients showed a decrease in proteinuria to less than 1.5 g/d of protein by 27 months, and kidney function was preserved throughout the duration of therapy and follow-up. No adverse effects were seen with rituximab. These outcomes suggest that treatment with rituximab may be a promising approach to the management of fibrillary glomerulonephritis, an entity previously considered refractory to therapy. [ABSTRACT FROM AUTHOR]

PURPOSE: Management of hypertension in patients with diabetes should address both renal and cardiovascular protection. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for control of hypertension in patients with diabetic nephropathy is widely advocated by various international guidelines. Use of any agent that provides tight control of blood pressure is indicated in patients with diabetes but without nephropathy. METHODS: In this article, the authors present a clinical case scenario and review current clinical evidence supporting the use of ACE inhibitors and ARBs in patients with diabetic nephropathy. In addition, the use of ACE and ARBs in patients with diabetes but without nephropathy will be discussed. RESULTS: Available trial evidence confirms the survival benefits of patients taking ACE inhibitors with diabetic nephropathy. However, the efficacy of ARB inhibitors on survival is unknown. In patients with diabetes without nephropathy, only ACE inhibitors have been found to reduce the risk of onset of microalbuminuria, while all agents affect survival provided a tight control of blood pressure is monitored. CONCLUSIONS: Dose of ACE inhibitors should be titrated appropriately to obtain proven benefits. In summary, current evidence supports the use of ACE inhibitors in patients with and without nephropathy because of renal and cardiovascular benefits. [ABSTRACT FROM AUTHOR]

Background: To identify patient and health system characteristics associated with late referral of patients with chronic kidney disease to nephrologists.Methods: MEDLINE, CENTRAL, and CINAHL were searched using the appropriate MESH terms in March 2007. Two reviewers individually and in duplicate reviewed the abstracts of 256 articles and selected 18 observational studies for inclusion. The reasons for late referral were categorized into patient or health system characteristics. Data extraction and content appraisal were done using a prespecified protocol.Results: Older age, the existence of multiple comorbidities, race other than Caucasian, lack of insurance, lower socioeconomic status and educational levels were patient characteristics associated with late referral of patients with chronic kidney disease. Lack of referring physician knowledge about the appropriate timing of referral, absence of communication between referring physicians and nephrologists, and dialysis care delivered at tertiary medical centers were health system characteristics associated with late referral of patients with chronic kidney disease. Most studies identified multiple factors associated with late referral, although the relative importance and the combined effect of these factors were not systematically evaluated.Conclusion: A combination of patient and health system characteristics is associated with late referral of patients with chronic kidney disease. Overall, being older, belonging to a minority group, being less educated, being uninsured, suffering from multiple comorbidities, and the lack of communication between primary care physicians and nephrologists contribute to late referral of patients with chronic kidney disease. Both primary care physicians and nephrologists need to engage in multisectoral collaborative efforts that ensure patient education and enhance physician awareness to improve the care of patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: Pulmonary hypertension is a common comorbidity in patients with chronic kidney disease (CKD), but therapeutic options are limited. We discuss the epidemiology of pulmonary hypertension in patients with CKD and review therapies for pulmonary hypertension with a focus on emerging treatments for pulmonary arterial hypertension (PAH)., Recent Findings: The definition of pulmonary hypertension has been updated to a lower threshold of mean pulmonary artery pressures of more than 20 mmHg, potentially leading to more patients with CKD to qualify for the diagnosis of pulmonary hypertension. Endothelin receptor antagonists, a class of medications, which demonstrated efficacy in patients with PAH, have been shown to slow progression of CKD, but their efficacy in lowering pulmonary artery pressures and their effects on reducing cardiovascular mortality in this population remains unproven. Sotatercept, a novel activin signaling inhibitor, which was previously studied in dialysis patients has been shown to increase exercise capacity in patients with PAH. These studies may lead to new specific therapies for pulmonary hypertension in patients with CKD., Summary: Pulmonary hypertension is common in patients with CKD. Although our understanding of factors leading to pulmonary hypertension in this population have evolved, evidence supporting disease-specific therapy in CKD is limited arguing for larger, long-term studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Little is known about the association of discontinuation of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA) with outcomes in patients with chronic kidney disease (CKD)., Methods: We identified adults with CKD stages 3-4 from 2005-2022 in the Veterans Affairs healthcare system. Individuals with an incident prescription for SGLT2 inhibitors or GLP-1 RAs were included, with the first fill date considered the index date. Factors associated with time to first treatment discontinuation, defined as an interruption in SGLT2 inhibitor or GLP-1 RA prescription for ≥90 days, were studied using Cox proportional hazards regression models. Associations of discontinuation 90-179 days and ≥180 days with death, myocardial infarction, coronary revascularization, hospitalization for heart failure, and ischemic stroke were assessed using Cox proportional hazards regression., Results: Of 96,345 individuals who received an SGLT2 inhibitor and 60,020 who received a GLP-1 RA, at least one discontinuation occurred in 35,953 (37%) of SGLT2 inhibitor users and 28,407 (47%) of GLP-1 RA users. SGLT2 inhibitor users were 24% Black, 71% White, 71% age ≥70, and 84% with CKD stage 3a. GLP-1 RA users were 20% Black, 75% White, 63% age ≥70, and 81% with CKD stage 3a. Black race, Hispanic ethnicity, cerebrovascular disease, peripheral vascular disease, and ischemic heart disease were associated with discontinuation of both drug classes. Female sex and more advanced CKD stage were also associated with SGLT2 inhibitor discontinuation. SGLT2 inhibitor discontinuation ≥180 days was associated with death, (adjusted hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.58-1.77) and heart failure hospitalization, (adjusted HR 1.26, 95% CI 1.13-1.40). GLP-1 RA discontinuation ≥180 days was associated with death, (adjusted HR 1.97, 95% CI 1.87-2.07), myocardial infarction (adjusted HR 1.23, 95% CI 1.11-1.36), heart failure hospitalization (adjusted HR 1.48, 95% CI 1.33-1.64), and ischemic stroke (adjusted HR 1.24, 95% CI 1.14-1.35)., Conclusions: SGLT2 inhibitor and GLP-1 RA discontinuation was common and associated with harmful outcomes in adults with CKD., (Copyright © 2024 by the American Society of Nephrology.)

Purpose of Review: Diabetic kidney disease continues to increase, and several novel therapeutic agents have been shown to slow the progression of chronic kidney disease in those with diabetes. This review summarizes more recent data on the role of glucagon-like peptide-1 (GLP-1) receptor agonists and kidney outcomes., Recent Findings: Posthoc analysis of cardiovascular outcome trials, as well as several retrospective studies, demonstrate benefits of GLP-1 receptor agonist therapy for chronic kidney disease progression in diabetics. Although limited randomized clinical trials evidence assessing the effects of GLP-1 receptor agonists on kidney outcomes in diabetic chronic kidney disease patients have been published, FLOW-CKD trial was halted based on interim data for efficacy, and results are awaited., Summary: GLP-1 receptor agonism is a promising therapy for slowing the progression of diabetic chronic kidney disease. Recent studies support kidney benefits GLP-1 receptor agonists over insulin and dipeptidyl peptidase-4-inhibitors, and the FLOW-CKD trial would inform the potential benefits for reducing the need for dialysis and kidney-disease related mortality in those with kidney disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale & Objective: Studies have shown that generally healthy individuals who consume diets rich in plant foods have a lower risk of incident chronic kidney disease (CKD) and cardiovascular disease. This study investigated the prospective associations of plant-based diets with the risk of CKD progression and all-cause mortality in individuals with CKD., Study Design: Prospective cohort study., Setting & Participants: 2,539 participants with CKD recruited between 2003-2008 into the Chronic Renal Insufficiency Cohort (CRIC) Study., Exposure: Responses on the Diet History Questionnaire were used to calculate scores for the overall plant-based diet index, healthy plant-based diet index, and unhealthy plant-based diet index., Outcome: (1) CKD progression defined as≥50% estimated glomerular filtration rate decline from baseline or kidney replacement therapy (dialysis, transplant) and (2) all-cause mortality., Analytical Approach: Cox proportional hazards models to compute hazard ratios and 95% confidence intervals adjusting for lifestyle, socioeconomic, and clinical covariates., Results: There were 977 CKD progression events and 836 deaths during a median follow-up period of 7 and 12 years, respectively. Participants with the highest versus lowest adherence to overall plant-based diets and healthy plant-based diets had 26% (HR, 0.74 [95% CI, 0.62-0.88], P trend<0.001) and 21% (HR, 0.79 [95% CI, 0.66-0.95], P trend=0.03) lower risks of all-cause mortality, respectively. Each 10-point higher score of unhealthy plant-based diets was modestly associated with a higher risk of CKD progression (HR, 1.14 [95% CI, 1.03-1.25) and all-cause mortality (HR, 1.11 [95% CI, 1.00-1.23)., Limitations: Self-reported diet may be subject to measurement error., Conclusions: Adherence to an overall plant-based diet and a healthy plant-based diet is associated with a reduced risk of all-cause mortality among individuals with CKD. An unhealthy plant-based was associated with an elevated risk of CKD progression and all-cause mortality., Plain-Language Summary: Plant-based diets are healthful dietary patterns that have been linked to a lower risk of chronic diseases. However, the impact of plant-based diets on clinical outcomes in patients with chronic kidney disease (CKD) is not well established. In 2,539 individuals with CKD, we examined the associations of adherence to 3 different types of plant-based diets with the risks of CKD progression and all-cause mortality. We found that following an overall plant-based diet and a healthy plant-based diet was associated with a lower risk of all-cause mortality. By contrast, following an unhealthy plant-based diet was associated with a higher risk of CKD progression and all-cause mortality. These results suggest that the quality of plant-based diets may be important for CKD management., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines suggest that adults with diabetes and kidney disease receive treatment with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). This is an update of a Cochrane review published in 2006., Objectives: We compared the efficacy and safety of ACEi and ARB therapy (either as monotherapy or in combination) on cardiovascular and kidney outcomes in adults with diabetes and kidney disease., Search Methods: We searched the Cochrane Kidney and Transplants Register of Studies to 17 March 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov., Selection Criteria: We included studies evaluating ACEi or ARB alone or in combination, compared to each other, placebo or no treatment in people with diabetes and kidney disease., Data Collection and Analysis: Two authors independently assessed the risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Main Results: One hundred and nine studies (28,341 randomised participants) were eligible for inclusion. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi may make little or no difference to all-cause death (24 studies, 7413 participants: RR 0.91, 95% CI 0.73 to 1.15; I 2 = 23%; low certainty) and with similar withdrawals from treatment (7 studies, 5306 participants: RR 1.03, 95% CI 0.90 to 1.19; I 2 = 0%; low certainty). ACEi may prevent kidney failure (8 studies, 6643 participants: RR 0.61, 95% CI 0.39 to 0.94; I 2 = 0%; low certainty). Compared to placebo or no treatment, ARB may make little or no difference to all-cause death (11 studies, 4260 participants: RR 0.99, 95% CI 0.85 to 1.16; I 2 = 0%; low certainty). ARB have uncertain effects on withdrawal from treatment (3 studies, 721 participants: RR 0.85, 95% CI 0.58 to 1.26; I 2 = 2%; low certainty) and cardiovascular death (6 studies, 878 participants: RR 3.36, 95% CI 0.93 to 12.07; low certainty). ARB may prevent kidney failure (3 studies, 3227 participants: RR 0.82, 95% CI 0.72 to 0.94; I 2 = 0%; low certainty), doubling of serum creatinine (SCr) (4 studies, 3280 participants: RR 0.84, 95% CI 0.72 to 0.97; I 2 = 32%; low certainty), and the progression from microalbuminuria to macroalbuminuria (5 studies, 815 participants: RR 0.44, 95% CI 0.23 to 0.85; I 2 = 74%; low certainty). Compared to ACEi, ARB had uncertain effects on all-cause death (15 studies, 1739 participants: RR 1.13, 95% CI 0.68 to 1.88; I 2 = 0%; low certainty), withdrawal from treatment (6 studies, 612 participants: RR 0.91, 95% CI 0.65 to 1.28; I 2 = 0%; low certainty), cardiovascular death (13 studies, 1606 participants: RR 1.15, 95% CI 0.45 to 2.98; I 2 = 0%; low certainty), kidney failure (3 studies, 837 participants: RR 0.56, 95% CI 0.29 to 1.07; I 2 = 0%; low certainty), and doubling of SCr (2 studies, 767 participants: RR 0.88, 95% CI 0.52 to 1.48; I 2 = 0%; low certainty). Compared to ACEi plus ARB, ACEi alone has uncertain effects on all-cause death (6 studies, 1166 participants: RR 1.08, 95% CI 0.49 to 2.40; I 2 = 20%; low certainty), withdrawal from treatment (2 studies, 172 participants: RR 0.78, 95% CI 0.33 to 1.86; I 2 = 0%; low certainty), cardiovascular death (4 studies, 994 participants: RR 3.02, 95% CI 0.61 to 14.85; low certainty), kidney failure (3 studies, 880 participants: RR 1.36, 95% CI 0.79 to 2.32; I 2 = 0%; low certainty), and doubling of SCr (2 studies, 813 participants: RR 1.14, 95% CI 0.70 to 1.85; I 2 = 0%; low certainty). Compared to ACEi plus ARB, ARB alone has uncertain effects on all-cause death (7 studies, 2607 participants: RR 1.02, 95% CI 0.76 to 1.37; I 2 = 0%; low certainty), withdrawn from treatment (3 studies, 1615 participants: RR 0.81, 95% CI 0.53 to 1.24; I 2 = 0%; low certainty), cardiovascular death (4 studies, 992 participants: RR 3.03, 95% CI 0.62 to 14.93; low certainty), kidney failure (4 studies, 2321 participants: RR 1.15, 95% CI 0.67 to 1.95; I 2 = 29%; low certainty), and doubling of SCr (3 studies, 2252 participants: RR 1.18, 95% CI 0.85 to 1.64; I 2 = 0%; low certainty). Comparative effects of different ACEi or ARB and low-dose versus high-dose ARB were rarely evaluated. No study compared different doses of ACEi. Adverse events of ACEi and ARB were rarely reported., Authors' Conclusions: ACEi or ARB may make little or no difference to all-cause and cardiovascular death compared to placebo or no treatment in people with diabetes and kidney disease but may prevent kidney failure. ARB may prevent the doubling of SCr and the progression from microalbuminuria to macroalbuminuria compared with a placebo or no treatment. Despite the international guidelines suggesting not combining ACEi and ARB treatment, the effects of ACEi or ARB monotherapy compared to dual therapy have not been adequately assessed. The limited data availability and the low quality of the included studies prevented the assessment of the benefits and harms of ACEi or ARB in people with diabetes and kidney disease. Low and very low certainty evidence indicates that it is possible that further studies might provide different results., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Rationale & Objective: The measurement of cystatin C has been recommended to enhance chronic kidney disease (CKD) detection and risk stratification in clinical practice. This study gathered insights into the perceptions and experiences of clinical staff regarding the use of cystatin C in CKD detection within the Veterans Health Administration (VHA) system., Study Design: A qualitative approach was employed to explore barriers and facilitators of clinical staff regarding the use of cystatin C in CKD detection within the VHA system. The Organizational Theory of Implementation Effectiveness informed the development of a semistructured interview guide., Setting & Participants: Health care providers, nurses, and clinical pharmacists from the VHA systems in San Francisco, San Diego, and Houston were interviewed between October 2021 and May 2022., Exposures: Participants' experiences with cystatin C testing., Outcomes: Perceived barriers and facilitators to cystatin C testing., Analytical Approach: Participant responses from individual interviews were analyzed by a multidisciplinary team using rapid qualitative analysis methods., Results: Fourteen in-depth interviews were conducted across the 3 VHA systems. Ten of 11 providers worked in primary care. Five key barriers to using cystatin C for CKD detection were identified. These included lack of patient awareness of CKD testing, lack of provider awareness about cystatin C, knowledge barriers about cystatin C testing, unclear roles and ownership of CKD detection, and lack of clinic support to enhance CKD detection. Suggested interventions to overcome these barriers included educational and training programs, improved clinic workflows, and electronic health record aids to support CKD detection and use of cystatin C., Limitations: The results may not be generalizable to other health care systems outside the VHA., Conclusions: The findings indicate a need for targeted interventions such as educational and training programs, improved clinical workflows, and electronic health record aids to address barriers limiting the use of cystatin C in clinical practice for enhanced CKD detection., (© 2024 The Authors.)

Background: Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after post-LVAD RHF are uncertain, so we investigated this., Methods and Results: We identified individuals who received primary continuous-flow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of baseline kidney function with RHF risk at the different time points, were assessed. We identified 8076 LVAD recipients who met inclusion criteria. Incident RHF was present at 1 month in 26.4%. There were 4850 individuals with follow-up at 3 months, with incident RHF in 4.2%. Kidney function trajectories differed from pre-LVAD implantation to 1-month follow-up by RHF category, with those developing persistent RHF having no improvement in baseline kidney function. For trajectories before the 3-month RHF ascertainment time, the shape was similar for those with and without RHF, with lower estimated glomerular filtration rate levels among those who developed RHF. Baseline estimated glomerular filtration rate levels below the normal range were associated with higher risk of RHF at 1 and 3 months., Conclusions: In LVAD recipients, preimplantation kidney function and subsequent kidney function trajectories differed substantially by RHF at 1 and 3 months postimplantation, even after adjustment for several confounders. This may demonstrate bidirectional associations between kidney function and right ventricular function in LVAD recipients.

Background: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs)., Methods: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains., Results: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics., Conclusions: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improve outcomes but are underutilized in patients with chronic kidney disease (CKD). Little is known about reasons for discontinuation and lack of reinitiating these medications. We aimed to explore clinicians' and patients' experiences and perceptions of ACEI/ARB use in CKD., Methods: A multi-profession sample of health care clinicians and patients with documented ACEI/ARB-associated side effects in the past 6 months. Participants were recruited from 2 Veterans Affairs healthcare systems in Texas and Tennessee. A total of 15 clinicians and 10 patients completed interviews. We used inductive and deductive qualitative data analysis approaches to identify themes related to clinician and patient experiences with ACEI/ARB. Thematic analysis focused on prescribing decisions and practices, clinical guidelines, and perception of side effects. Data were analyzed as they amassed, and recruitment was stopped at the point of thematic saturation., Results: Clinicians prescribe ACEI/ARB for blood pressure control and kidney protection and underscored the importance of these medications in patients with diabetes. While clinicians described providing comprehensive patient education about ACEI/ARB in CKD, patient interviews revealed significant knowledge gaps about CKD and ACEI/ARB use. Many patients were unaware of their CKD status, and some did not know why they were prescribed ACEI/ARB. Clinicians' drug management strategies varied widely, as did their understanding of prescribing guidelines. They identified structural and patient-level barriers to prescribing and many endorsed the development of a decision support tool to facilitate ACEI/ARB prescribing and management., Discussion/conclusion: Our qualitative study of clinicians and providers identified key target areas for improvement to increase ACEI/ARB utilization in patients with CKD with the goal to improve long-term outcomes in high-risk patients. These findings will also inform the development of a decision support tool to assist with prescribing ACEI/ARBs for patients with CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Rationale & Objective: Heart-kidney crosstalk is recognized as the cardiorenal syndrome. We examined the association of cardiac function and structure with the risk of kidney failure with replacement therapy (KFRT) in a chronic kidney disease (CKD) population., Study Design: Prospective observational cohort study., Setting & Participants: 3,027 participants from the Chronic Renal Insufficiency Cohort Study., Exposure: Five preselected variables that assess different aspects of cardiac structure and function: left ventricular mass index (LVMI), LV volume, left atrial (LA) area, peak tricuspid regurgitation (TR) velocity, and left ventricular ejection fraction (EF) as assessed by echocardiography., Outcome: Incident KFRT (primary outcome), and annual estimated glomerular filtration rate (eGFR) slope (secondary outcome)., Analytical Approach: Multivariable Cox models and mixed-effects models., Results: The mean age of the participants was 59±11 SD years, 54% were men, and mean eGFR was 43±17mL/min/1.73m 2 . Between 2003 and 2018 (median follow-up, 9.9 years), 883 participants developed KFRT. Higher LVMI, LV volume, LA area, peak TR velocity, and lower EF were each statistically significantly associated with an increased risk of KFRT, with corresponding HRs for the highest versus lowest quartiles (lowest vs highest for EF) of 1.70 (95% CI, 1.27-2.26), 1.50 (95% CI, 1.19-1.90), 1.43 (95% CI, 1.11-1.84), 1.45 (95% CI, 1.06-1.96), and 1.26 (95% CI, 1.03-1.56), respectively. For the secondary outcome, participants in the highest versus lowest quartiles (lowest vs highest for EF) had a statistically significantly faster eGFR decline, except for LA area (ΔeGFR slope per year, -0.57 [95% CI, -0.68 to-0.46] mL/min/1.73m 2 for LVMI, -0.25 [95% CI, -0.35 to-0.15] mL/min/1.73m 2 for LV volume, -0.01 [95% CI, -0.12 to-0.01] mL/min/1.73m 2 for LA area, -0.42 [95% CI, -0.56 to-0.28] mL/min/1.73m 2 for peak TR velocity, and -0.11 [95% CI, -0.20 to-0.01] mL/min/1.73m 2 for EF, respectively)., Limitations: The possibility of residual confounding., Conclusions: Multiple aspects of cardiac structure and function were statistically significantly associated with the risk of KFRT. These findings suggest that cardiac abnormalities and incidence of KFRT are potentially on the same causal pathway related to the interaction between hypertension, heart failure, and coronary artery diseases., Plain-Language Summary: Heart disease and kidney disease are known to interact with each other. In this study, we examined whether cardiac abnormalities, as assessed by echocardiography, were linked to the subsequent progression of kidney disease among people living with chronic kidney disease (CKD). We found that people with abnormalities in heart structure and function had a greater risk of progression to advanced CKD that required kidney replacement therapy and had a faster rate of decline in kidney function. Our study indicates the potential role of abnormal heart structure and function in the progression of kidney disease among people living with CKD., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Multiple clinical trials have demonstrated significant cardiovascular benefit with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2DM) and heart failure (HF) irrespective of ejection fraction. There are limited data evaluating real-world prescription and practice patterns of SGLT2 inhibitors., Objectives: The authors sought to assess utilization rates and facility-level variation in the use among patients with established atherosclerotic cardiovascular disease (ASCVD), HF, and T2DM using data from the nationwide Veterans Affairs health care system., Methods: The authors included patients with established ASCVD, HF, and T2DM seen by a primary care provider between January 1, 2020, and December 31, 2020. They assessed the use of SGLT2 inhibitors and the facility-level variation in their use. Facility-level variation was computed using median rate ratios, a measure of likelihood that 2 random facilities differ in use of SGLT2 inhibitors., Results: Among 105,799 patients with ASCVD, HF, and T2DM across 130 Veterans Affairs facilities, 14.6% received SGLT2 inhibitors. Patients receiving SGLT2 inhibitors were younger men with higher hemoglobin A1c and estimated glomerular filtration rate and were more likely to have HF with reduced ejection fraction and ischemic heart disease. There was significant facility-level variation of SGLT2 inhibitor use, with an adjusted median rate ratio of 1.55 (95% CI: 1.46-1.64), indicating a 55% residual difference in SGLT2 inhibitor use among similar patients with ASCVD, HF, and T2DM receiving care at 2 random facilities., Conclusions: Utilization rates of SGLT2 inhibitors are low in patients with ASCVD, HF, and T2DM, with high residual facility-level variation. These findings suggest opportunities to optimize SGLT2 inhibitor use to prevent future adverse cardiovascular events., Competing Interests: Funding Support and Author Disclosures This work was supported by a Department of Veterans Affairs (VA) Health Services Research and Development Service Investigator Initiated grants (IIR 16-072, IIR 19-069) and the Houston VA Health Services Research and Development Center for Innovations grant (CIN13-413). Support for VA/Centers for Medicare and Medicaid Services data was provided by the Department of Veterans Affairs, VA Health Services Research and Development Service, VA Information Resource Center (Project Numbers SDR 02-237 and 98-004). Dr Nambi was the site primary investigator for the study sponsored by Merck and Amgen. Dr Ballantyne has received grant/research support (to his institution) from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostic; and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Dr Slipczuk has received consulting honoraria from Amgen, Regeneron, and Phillips and grant support from Amgen. Dr Bozkurt has received consulting fees from Amgen, scPharmaceuticals, Baxter, Sanofi-Aventis, Relypsa, Vifor, Roche, Boehringer Ingelheim, the Clinical Event Committee for Abbott Vascular, the Data Safety Monitoring Committees of Liva Nova and Cardurion, and the Steering Committee of Renovocor. Dr Virani has received research funding from the Department of Veterans Affairs, National Institutes of Health, World Heart Federation, and Tahir and Jooma Family; and has received an honorarium from American College of Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Rationale & Objective: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are recommended for type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease (CKD) or atherosclerotic cardiovascular disease (ASCVD). We evaluated factors associated with SGLT2 inhibitor prescription, disparities by race and sex, and facility-level variation in prescription patterns., Study Design: Retrospective cohort., Setting & Participants: A national sample of US veterans with comorbid T2DM, CKD, and ASCVD with a primary care visit between January 1 and December 31, 2020., Exposure: Race, sex, and individual Veterans Affairs (VA) location., Outcome: SGLT2 inhibitor prescription., Analytical Approach: Multivariable logistic regression assessed associations of race and sex with SGLT2 inhibitor prescription. Facility-level variation in SGLT2i prescription was quantified by median rate ratios (MRR), which express the likelihood that 2 randomly selected facilities differ in their use of SGLT2 inhibitor among similar patients., Results: Of 174,443 patients with CKD, T2DM, and ASCVD, 20,024 (11.5%) were prescribed an SGLT2 inhibitor. Lower odds of SGLT2 inhibitor prescription were seen in Black or African American patients compared with White patients (OR, 0.87 [95% CI, 0.83-0.91]) and among women compared with men (OR, 0.59 [95% CI 0.52-0.67]). The adjusted MRR for SGLT2 inhibitor prescription was 1.58 (95% CI 1.48-1.67) in the total cohort, indicating an unexplained 58% variation in treatment between VA facilities, independent of patient and facility characteristics. Facility-level variation was evaluated among Black or African American patients (MRR, 1.55 [95% CI 1.41-1.68]), White patients (MRR, 1.57 [95% CI 1.47-1.66]), women (MRR, 1.40 [95% CI 1.28-1.51]), and men (MRR, 1.57 [95% CI 1.48-1.67])., Limitations: Albuminuria was not assessed., Conclusions: Prescription for SGLT2 inhibitors was low among likely eligible patients, with evident disparities by sex and race and between individual VA facilities. Efforts are needed to study and address the reasons for these disparities to improve equitable adoption of these important medications., (Published by Elsevier Inc.)

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community., Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD., Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-421/coif). DCW reports honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Gilead, Janssen, Mundipharma, Merck Sharp and Dohme, Tricida, Vifor and Zydus. VWSW reports grants from Gilead Sciences; consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, TARGET PharmaSolutions; honoraria for lectures from Abbott, AbbVie, Gilead Sciences, Novo Nordisk and he is Chairman of Subspecialty Board of Gastroenterology and Hepatology, Hong Kong College of Physicians and Co-founder of Illuminatio Medical Technology Limited. CW reports consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, GSK, MSD, Sanofi; honoraria for lectures from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly. MTL reports research grants from Gilead Sciences and Echosens and he is on Advisory Board of Novo Nordisk. MHN reports research support from Pfizer, Enanta, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation, CurveBio and he is on consulting/advisory Board of Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine. SDN reports consulting fees from ACI clinical, Bayer, Lily, Vifor, Vertex and DSMB: AstraZeneca. JB reports grants from Echosens, Intercept, Inventiva, Siemens; consulting fees from Diafir, Echosens, Intercept, Siemens, BMS, Gilead, Intercept, Pfizer, MSD, Novo Nordisk; honoraria from Echosens, Gilead, Intercept, Siemens. LV reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, Viatris; honoraria from MSD, Gilead, AlfaSigma, AbbVie. YJW reports honoraria from AbbVie and Gilead Science. MEK reports honoraria from AstraZeneca, Roche, MSD, AbbVie, Eva, Mash Premier, Takeda, Organon, AUG, Inspire, HSO, Gilead, Janssen, Intercept, Rameda, Ipsen, Onxeo, MinaPharm, Pharco, Zeta, Alfa Cure, Bayer, Oncoustics, PDC, and Spimaco. SS serves as the unpaid editorial board member of Hepatobiliary Surgery and Nutrition. MP reports he is a shareholder in Perspectum Ltd. AGH reports grants from Novo Nordisk, Gilead, Co-lead PI LEGEND trial Inventiva; consulting fees from Novo Nordisk, Gilead, Echosens and Norgine and Julius Clinical. WKC reports consulting fees from Abbvie, Boehringer Ingelheim and Novo Nordisk; honoraria form Viatris and Hisky Medical. HCP reports honoraria from Intercept, Orphalan, Novo Nordisk, Roche Portugal and EISAI. MHZ reports honoraria from Hisky Medical and serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background: Mortality risk assessment before kidney transplantation (KT) is imperfect. An emerging risk factor for death in nontransplant populations is physiological age as determined by the application of artificial intelligence to the electrocardiogram (ECG). The aim of this study was to examine the relationship between ECG age and KT waitlist mortality., Methods: We applied a previously developed convolutional neural network to the ECGs of KT candidates evaluated 2014 to 2019 to determine ECG age. We used a Cox proportional hazard model to examine whether ECG age was associated with waitlist mortality., Results: Of the 2183 patients evaluated, 59.1% were male, 81.4% were white, and 11.4% died during follow-up. Mean ECG age was 59.0 ± 12.0 y and mean chronological age at ECG was 53.3 ± 13.6 y. After adjusting for chronological age, comorbidities, and other characteristics associated with mortality, each increase in ECG age of >10 y than the average ECG age for patients of a similar chronological age was associated with an increase in mortality risk (hazard ratio 3.59 per 10-y increase; 95% confidence interval, 2.06-5.72; P  < 0.0001)., Conclusions: ECG age is a risk factor for KT waitlist mortality. Determining ECG age through artificial intelligence may help guide risk-benefit assessment when evaluating candidates for KT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions in the lumen of the gastrointestinal tract to prevent the absorption of dietary potassium and increase potassium secretion. Several studies showed that potassium binders are effective compared with placebo for preventing hyperkalemia or steroidal MRA discontinuation, but none has evaluated whether this strategy impacts clinically important endpoints such as cardiovascular events. Due to this and other limitations related to cost, clinical availability, pill burden and patient selection, alternative potential strategies to mitigate hyperkalemia may be more practical. Conservative strategies include increased monitoring and use of loop or thiazide diuretics to increase urinary potassium excretion. Non-steroidal MRAs may have a lower risk of hyperkalemia than steroidal MRAs and have stronger anti-inflammatory and anti-fibrotic effects with resultant reduced risk of kidney disease progression. Sodium-glucose cotransporter-2 inhibitors also decrease hyperkalemia risk in patients on MRAs and decrease cardiovascular events and kidney disease progression. These may be better first-line interventions to obviate the need for potassium binders and offer additional benefits., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Japanese and US populations have similar chronic kidney disease prevalence but differing clinical outcomes. A secondary analysis compared cardiovascular outcomes in a Japanese- and a US-based chronic kidney disease cohort and found that the US cohort had markedly worse cardiovascular outcomes. Mediation analysis demonstrated that differences in left ventricular structure and function could explain most of the cardiovascular outcome difference. We examine and contextualize this finding and describe implications for precision nephrology and for population health., (Published by Elsevier Inc.)

Rationale & Objective: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting., Study Design: Prospective cohort study., Setting & Participants: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF., Predictors: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters., Outcome: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where<75 reflects clinically significant symptoms)., Analytical Approach: Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership., Results: Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms [average of 81] and clinically significant symptoms [average of 52], respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline), and group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of group 1 was male, without diabetes or obesity, and this group had higher baseline kidney function. A majority of groups 2 and 3 had diabetes and obesity. A majority of group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD)., Limitations: No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption., Conclusions: Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD., (Copyright © 2022 National Kidney Foundation, Inc. All rights reserved.)

Aims: Contemporary patterns of care of patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) and the adoption of finerenone are not known. The FINE-REAL study (NCT05348733) is a prospective observational study in patients with CKD and T2D to provide insights into the use of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in clinical practice., Methods: FINE-REAL is an international, prospective, multicenter, single-arm study enrolling approximately 5500 adults with CKD and T2D in an estimated 200 sites across 22 countries. The study is anticipated to be ongoing until 2027., Results: The primary objective is to describe treatment patterns in patients with CKD and T2D treated with finerenone in routine clinical practice. Secondary objectives include assessment of safety with finerenone. Other endpoints include characterization of healthcare resource utilization and occurrence of newly diagnosed diabetic retinopathy or its progression from baseline in patients with existing disease. A biobank is being organized for future explorative analyses with inclusion of participants from the United States., Conclusions: FINE-REAL is the first prospective observational study with a nonsteroidal MRA in a population with CKD and T2D and is expected to provide meaningful insights into the treatment of CKD associated with T2D. FINE-REAL will inform decision-making with respect to initiation of finerenone in patients with CKD and T2D., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Description: The KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease is an update of the 2020 guideline from Kidney Disease: Improving Global Outcomes (KDIGO)., Methods: The KDIGO Work Group updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the Work Group used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and expert judgment to develop consensus practice points. New evidence led to updating of recommendations in the chapters Comprehensive Care in Patients With Diabetes and CKD (Chapter 1) and Glucose-Lowering Therapies in Patients With T2D and CKD (Chapter 4). New evidence did not change recommendations in the chapters Glycemic Monitoring and Targets in Patients With Diabetes and CKD (Chapter 2), Lifestyle Interventions in Patients With Diabetes and CKD (Chapter 3), and Approaches to Management of Patients With Diabetes and CKD (Chapter 5)., Recommendations: The updated guideline includes 13 recommendations and 52 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). A focus on preserving kidney function and maintaining well-being is recommended using a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium-glucose cotransporter-2 inhibitors) demonstrated to improve clinical outcomes. To this are added additional drugs with heart and kidney protection, such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists, and interventions to control risk factors for CKD progression and cardiovascular events, such as blood pressure, glycemia, and lipids.

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs)., Methods: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains., Results: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics., Conclusions: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Introduction: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation., Methods: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented ADRs with treatment discontinuation., Results: There were 882,441 (73.0%) individuals in the current user group and 326,794 (27.0%) in the discontinued group. There were 26,434 documented ADRs, with at least one documented ADR in 7,520 (0.9%) current users and 9,569 (2.9%) of the discontinued group. ADR presence was associated with treatment discontinuation, aOR 4.16 (95% CI: 4.03, 4.29). The most common documented ADRs were cough (37.3%), angioedema (14.2%), and allergic reaction (10.4%). ADRs related to angioedema (aOR 3.81, 95% CI: 3.47, 4.17), hyperkalemia (aOR 2.03, 95% CI: 1.84, 2.24), peripheral edema (aOR 1.53, 95% CI: 1.33, 1.77), or acute kidney injury (aOR 1.32, 95% CI: 1.15, 1.51) were associated with treatment discontinuation., Conclusion: ADRs leading to drug discontinuation were infrequently documented. ADR types were differentially associated with treatment discontinuation. An understanding of which ADRs lead to treatment discontinuation provides an opportunity to address them at a healthcare system level., (© 2023 S. Karger AG, Basel.)

Background: The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured., Methods: We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among trajectory groups were investigated., Results: Among 4,615 LVAD implantations, 5 eGFR trajectory groups were identified. The 2 largest groups (Groups 1 and 2) made up >80% of the cohort, and were similar to group average trajectories previously reported, with early eGFR rise followed by decline and stabilization. Three novel trajectory groups were found: worsening followed by sustained low kidney function (Group 3, 10.1%), sustained improvement (Group 4, 3.3%), and worsening followed by variation (Group 5, 1.7%). These groups differed in baseline characteristics and outcomes. Group 4 was younger and had more cardiogenic shock and pre-implantation dialysis; Group 3 had higher rates of pre-existing chronic kidney disease, along with older age., Conclusions: Novel eGFR trajectories were identified in a national cohort, possibly representing distinct cardiorenal processes. Type 1 cardiorenal syndrome may have been predominant in Group 4, and parenchymal kidney disease may have been predominant in Group 3., (Copyright © 2022 International Society for Heart and Lung Transplantation. All rights reserved.)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: There are major gaps in the implementation of guideline-concordant care for persons with chronic kidney disease (CKD). The CKD Cascade of Care (C 3 ) initiative seeks to improve CKD care by improving detection and treatment of CKD in primary care., Methods: C 3 is a multi-modal initiative deployed in three major academic medical centers within the Department of Veterans Affairs (VA) Health Care System: San Francisco VA, San Diego VA, and Houston VA. The main objective of the first phase of C 3 described in this protocol is to establish the infrastructure for universal CKD detection among primary care patients at high-risk for CKD with a triple-marker screen comprising cystatin C, creatinine, and albuminuria. Across the three sites, a comprehensive educational intervention and the integration of primary care-based clinical champions will be employed with the goal of improving CKD detection and treatment. The San Francisco VA will also implement a practice-facilitation intervention leveraging telehealth and health informatics tools and capabilities for enhanced CKD detection. Parallel formative evaluation across the three sites will assess the feasibility and acceptability of integrating cystatin C as part of routine CKD detection in primary care practice. The effectiveness of the interventions will be assessed using a pre-post observational design for change in the proportion of patients tested annually for CKD. Secondary outcomes will assess change in the initiation of cardio-kidney protective therapies and in nephrology referrals of high-risk patients., Discussion: The first phase of C 3 is a multi-facility multi-modal initiative that aims to improve CKD care by implementing a triple-marker screen for enhanced CKD detection in primary care., (© 2022. The Author(s).)

Rationale & Objective: Dysnatremias have been associated with an increased risk of mortality in the chronic kidney disease (CKD) population. Our objective is to identify the prevalence of and risk factors associated with dysnatremias in a CKD population and assess the association of dysnatremias with kidney failure and mortality among patients with CKD enrolled in the Chronic Renal Insufficiency Cohort Study., Study Design: Analysis of prospective cohort study., Setting & Participants: Adult patients aged 21-74 years with CKD from the Chronic Renal Insufficiency Cohort study., Predictors: Baseline and time-dependent hyponatremia and hypernatremia., Outcomes: All-cause mortality and kidney failure., Analytical Approach: Baseline characteristics were compared using χ 2 tests for categorical variables, analysis of variance for age, and Kruskal-Wallis tests for laboratory variables. Cox proportional hazards models and competing risk models were used to evaluate the association between baseline sodium level and overall mortality., Results: Of a total of 5,444 patients with CKD, 486 (9%) had hyponatremia and 53 (1%) had hypernatremia. Altogether, 1,508 patients died and 1,206 reached kidney failure. In adjusted Cox models, time-dependent dysnatremias were strongly associated with mortality for both hyponatremia (HR, 1.38; 95% CI, 1.16-1.64) and hypernatremia (HR, 1.54; 95% CI, 1.04-2.29). Factors associated with hyponatremia included female sex, diabetes, and hypertension. Regardless of age, time-dependent hypernatremia was associated with an increased risk of kidney failure (HR, 1.64; 95% CI, 1.06-2.53). Baseline and time-dependent hyponatremia were associated with an increased risk of kidney failure in patients younger than 65 (baseline hyponatremia HR, 1.30; 95% CI, 1.03-1.64 and time-dependent hyponatremia HR, 1.36; 95% CI, 1.09-1.70) but not among patients aged >65 years., Limitations: Inability to establish causality and lack of generalizability to hospitalized patients., Conclusions: Dysnatremias are prevalent among ambulatory CKD patients and are associated with mortality and kidney failure. Time-dependent dysnatremias were significantly associated with mortality in patients with CKD. Time-dependent hypernatremia was associated with progression to kidney failure. Baseline and time-dependent hyponatremia were associated with an increased risk of progression to kidney failure in those younger than 65 years., (© 2022 The Authors.)

Rationale and Objective: Chronic kidney disease is a risk enhancing factor for cardiovascular disease (CVD) and mortality, and the role of aspirin use is unclear in this population. We investigated the risk and benefits of aspirin use in primary and secondary prevention of CVD in the Chronic Renal Insufficiency Cohort Study., Study Design: Prospective observational cohort., Setting & Participants: 3,664 Chronic Renal Insufficiency Cohort participants., Exposure: Aspirin use in patients with and without preexisting CVD., Outcomes: Mortality, composite and individual CVD events (myocardial infarction, stroke, and peripheral arterial disease), kidney failure (dialysis and transplant), and major bleeding., Analytical Approach: Intention-to-treat analysis and multivariable Cox proportional hazards model to examine associations of time varying aspirin use., Results: The primary prevention group was composed of 2,578 (70.3%) individuals. Mean age was 57 ± 11 years, 46% women, 42% Black, and 47% had diabetes. The mean estimated glomerular filtration rate was 45 mL/min/1.73 m 2 . Median follow-up was 11.5 (IQR, 7.4-13) years. Aspirin was not associated with all-cause mortality in those without preexisting cardiovascular disease (CVD) (HR, 0.84; 95% CI, 0.7-1.01; P  = 0.06) or those with CVD (HR, 0.88; 95% CI, 0.77-1.02, P  = 0.08). Aspirin was not associated with a reduction of the CVD composite in primary prevention (HR, 0.97; 95% CI, 0.77-1.23; P  = 0.79) and in secondary prevention because the original study design was not meant to study the effects of aspirin., Limitations: This is not a randomized controlled trial, and therefore, causality cannot be determined., Conclusions: Aspirin use in chronic kidney disease patients was not associated with reduction in primary or secondary CVD events, progression to kidney failure, or major bleeding., (© 2022 The Authors.)

Objectives: This analysis sought to determine factors (including adiposity-related factors) most associated with HF-type symptoms (fatigue, shortness of breath, and edema) in adults with chronic kidney disease (CKD)., Background: Symptom burden impairs quality of life in CKD, especially symptoms that overlap with HF. These symptoms are common regardless of clinical HF diagnosis, and may be affected by subtle cardiac dysfunction, kidney dysfunction, and other factors. We used machine learning to investigate cross-sectional relationships of clinical variables with symptom scores in a CKD cohort., Methods: Participants in the Chronic Renal Insufficiency Cohort (CRIC) with a baseline modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score were included, regardless of prior HF diagnosis. The primary outcome was Overall Summary Score as a continuous measure. Predictors were 99 clinical variables representing demographic, cardiac, kidney and other health dimensions. A correlation filter was applied. Random forest regression models were fitted. Variable importance scores and adjusted predicted outcomes are presented., Results: The cohort included 3426 individuals, 10.3% with prior HF diagnosis. BMI was the most important factor, with BMI 24.3 kg/m 2 associated with the least symptoms. Symptoms worsened with higher or lower BMIs, with a potentially clinically relevant 5 point score decline at 35.7 kg/m 2 and a 1-point decline at the threshold for low BMI, 18.5 kg/m 2 . The most important cardiac and kidney factors were heart rate and eGFR, the 4th and 5th most important variables, respectively. Results were similar for secondary analyses., Conclusions: In a CKD cohort, BMI was the most important feature for explaining HF-type symptoms regardless of clinical HF diagnosis, identifying an important focus for symptom directed investigations., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose of Review: Diabetic kidney disease is the most common cause of chronic kidney disease (CKD) and end-stage kidney disease in the world. Risk factor modification, glucose control, and renin-angiotensin-aldosterone system blockade have remained the standard of care for 2 decades. New therapeutic agents have emerged in recent years, demonstrating kidney and cardiovascular benefits, and herein we review recent clinical trials on this topic., Recent Findings: After the publication of several cardiovascular outcome trials for sodium-glucose cotransporter 2 inhibitors (SGLT-2i), new trials have focused ON primary kidney-specific outcomes demonstrating safety and benefits among patients with proteinuric CKD; patients with or without diabetes, and heart failure with preserved ejection fraction (HFpEF) respectively. Similarly, nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs) and glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) have improved cardiovascular and kidney outcomes. Recently, clinical practice guidelines have also been updated to reflect this new evidence., Summary: In summary, SGLT-2i, GLP-1 RAs, and ns-MRAs have demonstrated cardiovascular and kidney benefits, including all-cause and cardiovascular mortality, progression to end-stage kidney disease, and hospitalizations for heart failure exacerbation among diverse patient population., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Existing guidelines offer little direction about the use of thiazide and loop diuretics in patients with chronic kidney disease (CKD). This review summarizes recent studies impacting indications and safety considerations for these agents in patients with CKD., Recent Findings: Chlorthalidone reduces blood pressure compared to placebo in patients with advanced CKD, challenging the belief that thiazide diuretics lose efficacy at lower glomerular filtration rates (GFR). Existing studies show no clear impact of thiazide or loop diuretic use on kidney or cardiovascular outcomes in patients with CKD. Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have diuretic effects, but concomitant use of a diuretic does not diminish the preventive benefits of these agents against acute kidney injury (AKI). Despite theoretical concerns, thiazide diuretics likely do not worsen circulating vasopressin levels or cyst progression in polycystic kidney disease and may be useful for alleviating polyuria from tolvaptan. Diuretics cause multiple adverse effects, including electrolyte abnormalities, hemodynamic-mediated decrease in estimated GFR, and AKI., Summary: Recent evidence supports expanded indications for diuretics in patients with kidney disease, including chlorthalidone for hypertension in advanced CKD. Monitoring electrolytes and estimated GFR is critical to ensure patient safety when prescribing these agents for patients with CKD., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Natriuretic peptide levels are elevated in persons with chronic kidney disease (CKD) stages 1-3, but it remains unclear whether this is associated with extracellular volume excess or early cardiovascular changes. We hypothesized that patients with CKD stages 1-3 would have evidence of cardiovascular changes, which would associate with brain natriuretic peptide (BNP), amino-terminal-pro-BNP (NT-pro-BNP), and patient-reported symptoms.Outpatients with CKD stages 1-3 and non-CKD controls were enrolled. Cardiovascular parameters included extracellular water (ECW) normalized to body weight measured using whole-body multifrequency bioimpedance spectroscopy, and total peripheral resistance index (TPRI) and cardiac index measured by impedance cardiography. Dyspnea, fatigue, depression, and quality of life were quantified using questionnaires.Among 21 participants (13 with CKD), median (IQR) BNP was 47.0 (28.0-302.5) vs 19.0 (12.3-92.3) pg/mL, p=0.07, and NT-pro-BNP was 245.0 (52.0-976.8) vs 26.0 (14.5-225.8) pg/mL, p=0.08, in the CKD and control groups, respectively. Those with CKD had higher pulse pressure (79 (66-87) vs 64 (49-67) mm Hg, p=0.046) and TPRI (3721 (3283-4278) vs 2933 (2745-3198) dyn×s/cm 5 /m 2 , p=0.01) and lower cardiac index (2.28 (2.08-2.78) vs 3.08 (2.43-3.37) L/min/m 2 , p=0.02). In the overall cohort, natriuretic peptides correlated with pulse pressure (BNP r=0.59; NT-pro-BNP r=0.58), cardiac index (BNP r=-0.76; NT-pro-BNP r=-0.62), and TPRI (BNP r=0.48), p<0.05 for each, but not with ECW/weight. TPRI and blood pressure correlated moderately with symptoms.Elevated natriuretic peptides may coincide with low cardiac index and elevated peripheral resistance in patients with CKD stages 1-3. The role of these biomarkers to detect subclinical cardiovascular changes needs to be further explored., Competing Interests: Competing interests: PNVB is an associate editor for the Journal of Investigative Medicine. SN reports receiving personal fees from AstraZeneca (Data Safety Monitoring Board) Bayer, Boehringer Ingelheim, and Eli Lilly and Co and Vifor; receiving grants from Keryx and receiving research funding from the Department of Veterans Affairs Health Services Research & Development outside the submitted work. SV reports research funding from VA HSR&D, NIH, World Heart Federation, Tahir, and Jooma Family; and honoraria from the American College of Cardiology in his role as the Associate Editor for Innovations, acc.org, outside of this work. WW reports personal fees from Akebia/Otsuka, AstraZeneca, Bayer, Boehringer-Ingelheim/Lilly, GlaxoSmithKline, Janssen, Merck, Pharmacosmos, and Reata, outside of this work. The remaining authors have nothing to disclose., (The interpretation and reporting of these data are the responsibility of the authors and in no way should be viewed as official policy or interpretation of the Department of Veterans Affairs or the US government.Peter Van Buren is an Associate Editor; please add the disclosure to the competing interests statement.Final comment from a reviewer (please check with the authors at the galley stage):"In discussion there is just a sentence with typo that needs fixing: "Our exploratory results generate hypotheses that subclinical changes in cardiovascular parameters that may exist in patients with CKD stages 1-3."I believe extra word "that" should be removed.")

This study used data from the Veterans Affairs administrative and clinical dataset to evaluate determinants of glucagon-like peptide-1 receptor agonist (GLP-1 RA) use among patients with concomitant atherosclerotic cardiovascular disease and diabetes mellitus and an antecedent primary care provider visit. The prevalence of GLP-1 RA use was 8.0%. In multivariable-adjusted models, White race, hypertension, obesity, higher hemoglobin A1c, ischemic heart disease, chronic kidney disease, a higher number of primary care provider visits, and previous cardiology or endocrinology visits were directly associated with GLP-1 RA use. Older age, having a physician primary care provider, and receiving care at a teaching facility were inversely associated with GLP-1 RA use. Our data can help inform targeted interventions to promote equitable access to GLP-1 RA and incentivize the adoption of these disease-modifying agents in high-risk patient populations., Competing Interests: Disclosures Dr. Virani reports receiving honorarium from the American College of Cardiology (Associate Editor for Innovations, acc.org). Dr. Navaneethan reports receiving personal fees from Bayer, Boehringer Ingelheim, Eli Lilly, and Vifor and research grants from Keryx outside of the submitted work. The remaining authors have no conflicts of interest to declare., (Published by Elsevier Inc.)