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Aims Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). Methods and results The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9–3.3], 2.0 (1.9–2.1), 4.5 (4.2–4.9), 2.8 (2.7–3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43–50) within 3 months] after adjustment for other CVD subtype incidence. Conclusion Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.

OBJECTIVE To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or RESULTS There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

Aims The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an ‘Add-on’ to incorporate CKD measures into these algorithms, using a validated approach. Methods In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. Results In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004–0.008) and 0.016 (0.010–0.023), respectively, for SCORE2 and 0.012 (0.009–0.015) and 0.024 (0.014–0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062–0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. Conclusion Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

Living a healthy lifestyle is one of the safest and most cost-effective ways to improve one’s quality of life and prevent and/or manage chronic disease. As such, current CKD management guidelines recommend that patients adhere to a healthy diet, perform ≥150 minutes per week of physical activity, manage their body weight, abstain from tobacco use, and limit alcohol. However, there are limited studies that investigate the relationship between these lifestyle factors and the progression of CKD among people with established CKD. In this narrative review, we examine the reported frequencies of health lifestyle behavior engagement among individuals with non–dialysis-dependent CKD and the existing literature that examines the influences of diet, physical activity, weight management, alcohol consumption, and tobacco use on the progression of CKD, as measured by decline in GFR, incident ESKD, or elevated proteinuria or albuminuria in individuals with CKD. Many of the available studies are limited by length of follow-up and small sample sizes, and meta-analyses were limited because the studies were sparse and had heterogeneous classifications of behaviors and/or referent groups and of CKD progression. Further research should be done to determine optimal methods to assess behaviors to better understand the levels at which healthy lifestyle behaviors are needed to slow CKD progression, to investigate the effect of combining multiple lifestyle behaviors on important clinical outcomes in CKD, and to develop effective techniques for behavior change. Despite the lack of evidence of efficacy from large trials on the ability of lifestyle behaviors to slow CKD progression, maintaining a healthy lifestyle remains a cornerstone of CKD management given the undisputed benefits of healthy lifestyle behaviors on cardiovascular health, BP control, and survival.

Background: Landmark trials of direct oral anticoagulants (DOACs) versus warfarin for non-valvular atrial fibrillation (NVAF) excluded patients with severe chronic kidney disease (CKD). Real-world data on safety and effectiveness of DOACs in severe CKD is limited. Methods: New users of DOACs (apixaban, rivaroxaban, and dabigatran) or warfarin with NVAF and severe CKD between 2010 and 2020 were identified using the de-identified electronic health records form the Optum Labs Data Warehouse. We estimated the risks of bleeding, ischemic stroke, and death for apixaban and rivaroxaban separately (vs. warfarin) using Cox regression models. Incidence rate (IR) and hazard ratio (HR) were adjusted for baseline characteristics by inverse probability of treatment weighting (IPTW). Dabigatran users were not included for the analysis due to small sample size (n=318). Results: Compared with warfarin users (n=7548), apixaban users (n=3719) were older (mean age 77 vs. 76 years) and had more hypertension (94% vs. 90%). In IPTW analysis, apixaban was associated with a lower risk of any bleeding (HR [95% CI], 0.71 [0.56, 0.89]), as well as major bleeding (HR [95% CI], 0.61 [0.46, 0.81]). There were no significant differences in ischemic stroke and death between apixaban and warfarin users ( Figure A ). Rivaroxaban users (n=920) were older (mean age 76 vs. 75 years) and had higher estimated glomerular filtration rate than warfarin users (mean: 25 vs. 23 ml/min/1.73 m 2 ). In IPTW analysis, risks of bleeding were higher among rivaroxaban users than warfarin users (any bleeding: HR [95% CI], 1.43 [1.05, 1.95]; major bleeding: HR [95% CI], 1.54 [1.09, 2.17]), with no significant differences in ischemic stroke and death ( Figure B ). Conclusion: Apixaban was associated with a lower risk of bleeding, but rivaroxaban was associated with a higher risk of bleeding, compared with warfarin in patients with NVAF and severe CKD. Risks of ischemic stroke and death were similar between agents. Apixaban may be a preferable oral anticoagulant in this population.

Objective Obesity is a global public health challenge and strongly associated with type 2 diabetes (T2D), but its burden and effects are not well understood in people with type 1 diabetes (T1D). Particularly, the link between obesity and chronic kidney disease (CKD) in T1D is poorly characterized. Research Design and Methods We included all T1D and, for comparison, T2D in the Geisinger Health System from 2004 to 2018. We evaluated trends in obesity (body mass index ≥ 30 kg/m2), low estimated glomerular filtration rate (eGFR) (≤60 mL/min/1.73m2), and albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g). We used multivariable logistic regression to evaluate the independent association of obesity with CKD in 2018. Results People with T1D were younger than T2D (median age 39 vs 62 years). Obesity increased in T1D over time (32.6% in 2004 to 36.8% in 2018), while obesity in T2D was stable at ~60%. The crude prevalence of low eGFR was higher in T2D than in T1D in all years (eg, 30.6% vs 16.1% in 2018), but after adjusting for age differences, prevalence was higher in T1D than T2D in all years (eg, 16.2% vs 9.3% in 2018). Obesity was associated with increased odds of low eGFR in T1D [adjusted odds ratio (AOR) = 1.52, 95% CI 1.12-2.08] and T2D (AOR = 1.29, 95% CI 1.23-1.35). Conclusions Obesity is increasing in people with T1D and is associated with increased risk of CKD. After accounting for age, the burden of CKD in T1D exceeded the burden in T2D, suggesting the need for increased vigilance and assessment of kidney-protective medications in T1D.

OBJECTIVES: Less than half of US adults with hypertension have controlled blood pressure (BP). Higher body mass index (BMI) is associated with an increased risk for hypertension, but the association between BMI and BP control is not well characterized. We examined hypertension awareness, antihypertensive medication use, and BP control, by BMI category. METHODS: Data for 3,568 US adults aged ≥18 years with hypertension (BP ≥140/90 mmHg or taking antihypertensive medication) from the 2015–2018 National Health and Nutrition Examination Survey were analyzed. BMI was categorized as normal (

OBJECTIVE: To examine the effect of a telehealth intervention that used a dietary app, educational website, and weekly dietitian tele-counseling) on sodium intake, diet quality, blood pressure and albuminuria among individuals with diabetes and early stage chronic kidney disease. DESIGN AND METHODS: We examined the effects of a dietary app-supported tele-counseling intervention in a single center, single arm study of 44 participants with type 2 diabetes and stage 1–3a chronic kidney disease. Participants recorded and shared dietary data via MyFitnessPal with registered dietitians, who used motivational interviewing to provide telephone counseling weekly for 8 weeks. After the 8-week intensive intervention, participants were followed at 6 months and 12 months. Outcomes included 24-hour urine sodium (2 collections per timepoint), Healthy Eating Index (HEI) 2015 score (three 24-hour dietary recalls per timepoint), 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), and 24-hour urine albumin excretion. RESULTS: Out of 44 consented participants (mean age 60.3 +/− 11.9 years, 43% female, 89% white, median eGFR was 78.5 ml/min/1.73m(2), median urine albumin excretion 52.9 mg/day, 84% hypertension), 32 (73%) completed 8-week follow-up, 27 (61%) completed 6-month follow up, and 25 (57%) completed 12-month follow up. Among participants who completed 12-month follow up, reported sodium intake decreased by 638 mg/day from baseline of 2919 mg/day (p-value

Abstract Objectives To characterize and compare glucose-lowering medication use in type 2 diabetes in the US, Sweden, and Israel, including adoption of newer medications and prescribing patterns. Research Design and Methods We used data from the National Health and Nutrition Examination Survey (NHANES) from the US, Stockholm CREAtinine Measurements project (SCREAM) from Sweden, and Maccabi Healthcare Services from Israel. Specific pharmacotherapy for type 2 diabetes between 2007 and 2018 were examined. Results Use of glucose-lowering medications among patients with type 2 diabetes was substantially lower in the US and SCREAM than in Maccabi (66.0% in NHANES, 68.4% in SCREAM, and 88.1% in Maccabi in 2017-2018). Among patients who took at least one glucose-lowering medication in 2017-2018, metformin use was also lower in the US and SCREAM (74.1% in NHANES, 75.9% in SCREAM, and 92.6% in Maccabi) whereas sulfonylureas use was greater in the US (31.5% in NHANES, 16.0% in SCREAM, and 14.9% in Maccabi). Adoption of DPP4i and SGLT2i were slower in the US and SCREAM than Maccabi. History of atherosclerotic cardiovascular disease, heart failure, reduced kidney function, and albuminuria were not consistently associated with greater use of SGLT2i or GLP1RA across the three countries. Conclusions There were substantial differences in real-world use of glucose-lowering medications across the US, Sweden, and Israel, with more optimal pharmacologic management in Israel. Variation in access to care and medication cost across countries may have contributed to these differences. SGLT2i and GLP1RA use in high-risk patients was limited in all three countries during this time period.

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%–74.5%) in diabetes and 4.1% (1.3%–20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42–1.60]; in hypertension, 1.36 [1.28–1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR

The Endocrine Society Clinical Practice Guidelines recommend the avoidance of medications that may cause weight gain (i.e., obesogenic medications) in individuals with overweight or obesity. Obesity disproportionately affects people with lower socioeconomic status (SES); however, it is unknown whether the use of obesogenic medications differs by SES.We included adults with overweight or obesity and used prescription medications from 2009-2018 of the US National Health and Nutrition Examination Survey. We examined the associations between a composite measure of SES and use of obesogenic medications and anti-obesity medications. The composite SES includedhigh school education (1 point), household income below federal poverty level (1 point), no insurance (2 points), and public health insurance only (1 point). We defined 3 composite SES groups (0 [high], 1 [intermediate], and ≥2 points [low]).Among 10,673 US adults with overweight or obesity, 20.0% had low SES. Use of obesogenic medications was common (37.7%). Low (vs. high) SES was associated with greater obesogenic medication use, independent of demographic characteristics, prescription medication burden, and comorbidities (OR 1.3 [1.2-1.5]). Among 12,133 eligible participants, utilization of anti-obesity medications was very low overall (0.5%) and within all SES groups (low 0.27%, intermediate 0.71, and high 0.65%).Our findings highlight common and modifiable risk factors for obesity. Clinicians should screen patient medications for those that may cause weight gain and increase adoption of anti-obesity medications, especially among adults living in low SES.The National Institute of Diabetes and Digestive and Kidney Disease (R01DK115534, K24HL155861, and K01DK121825).

Background The DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown. Objectives The purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation. Methods DASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro–B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period. Results Of the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: −27% to −7%) and hs-CRP by 13% (95% CI: −24% to −1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: −24% to −14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: −31% to −7%) and NT-proBNP by 23% (95% CI: −32% to −12%), whereas hs-CRP was not significantly changed (−7%; 95% CI: −22% to 9%) compared with the high sodium-control diet. Conclusions Combining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH – Sodium]; NCT00000608 )

Obesity prevalence continues to increase worldwide, accompanied by a rising tide of hypertension, diabetes, and chronic kidney disease (CKD). Although body mass index is typically used to assess obesity in clinical practice, altered body composition (eg, reduced muscle mass and increased visceral adiposity) are common among patients with CKD. Weight loss achieved through behavioral modification or medications reduces albuminuria and in some cases slows the decline in estimated glomerular filtration rate. Use of medications that promote weight loss with favorable cardiovascular risk profiles should be promoted, particularly in patients with type 2 diabetes, obesity, and CKD. For those who fail to achieve weight loss through lifestyle modification, bariatric surgery should be considered because observational studies have shown reductions in risk for estimated glomerular filtration rate decline and kidney failure. Uncertainty persists on the risk to benefit ratio of intentional weight loss in patients with kidney failure due to the lack of prospective trials and limitations of observational data. Regardless, sleeve gastrectomy is increasingly being used for patients with kidney failure and severe obesity, with success in achieving sustained weight loss, improved access to kidney transplantation, and favorable posttransplantation outcomes. More research is needed assessing long-term cardiovascular and kidney outcomes of most weight loss medications.

The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Management of Blood Pressure in Chronic Kidney Disease (CKD) recommends a target systolic blood pressure under 120 mmHg based on standardized office blood pressure measurement. Here, we examined the potential implications of this new guideline for blood pressure lowering with antihypertensive medication among adults in the United States with CKD compared to the 2012 KDIGO guideline (target blood pressure 130/80 mmHg or under with albuminuria or 140/90 mmHg or under without albuminuria) and the 2017 American College of Cardiology/American Heart Association (target blood pressure under 130/80 mmHg) guideline. Additionally, we determined implications of the 2021 KDIGO guideline for angiotensin converting enzyme inhibitor (ACEi) or angiotensin II-receptor blocker (ARB) use for those with albuminuria (recommended at systolic blood pressure of 120 mmHg or over) compared to the 2012 KDIGO guideline (recommended at blood pressures over 130/80 mmHg). Data were analyzed from 1,699 adults with CKD (estimated glomerular filtration rate 15–59 ml/min/1.73m(2) or a urinary albumin-to-creatinine ratio of 30 mg/g or more) in the 2015–2018 National Health and Nutrition Examination Survey and averaged up to three standardized blood pressure measurements. Among adults with CKD, 69.5% were eligible for blood pressure lowering according to the 2021 KDIGO guideline, compared with 49.8% as per 2012 KDIGO or 55.6% as per 2017 American College of Cardiology/American Heart Association guidelines. Among those with albuminuria, 78.2% were eligible for ACEi/ARB use by the 2021 KDIGO guideline compared with 71.0% by the 2012 KDIGO guideline. However, only 39.1% were taking an ACEi/ARB. Thus, our findings highlight opportunities to improve blood pressure management and reduce cardiovascular risk among adults in the United States with CKD.

OBJECTIVE To characterize and compare glucose-lowering medication use in type 2 diabetes in the U.S., Sweden, and Israel, including adoption of newer medications and prescribing patterns. RESEARCH DESIGN AND METHODS We used data from the National Health and Nutrition Examination Survey (NHANES) from the U.S., the Stockholm CREAtinine Measurements (SCREAM) project from Sweden, and Maccabi Healthcare Services (Maccabi) from Israel. Specific pharmacotherapy for type 2 diabetes between 2007 and 2018 was examined. RESULTS Use of glucose-lowering medications among patients with type 2 diabetes was substantially lower in NHANES and SCREAM than in Maccabi (66.0% in NHANES, 68.4% in SCREAM, and 88.1% in Maccabi in 2017–2018). Among patients who took at least one glucose-lowering medication in 2017–2018, metformin use was also lower in NHANES and SCREAM (74.1% in NHANES, 75.9% in SCREAM, and 92.6% in Maccabi) whereas sulfonylureas use was greater in NHANES (31.5% in NHANES, 16.0% in SCREAM, and 14.9% in Maccabi). Adoption of dipeptidyl peptidase 4 inhibitors and sodium–glucose cotransporter 2 inhibitors (SGLT2i) was slower in NHANES and SCREAM than in Maccabi. History of atherosclerotic cardiovascular disease, heart failure, reduced kidney function, or albuminuria was not consistently associated with greater use of SGLT2i or glucagon-like peptide 1 receptor agonists (GLP1RA) across the three countries. CONCLUSIONS There were substantial differences in real-world use of glucose-lowering medications across the U.S., Sweden, and Israel, with more optimal pharmacologic management in Israel. Variation in access to care and medication cost across countries may have contributed to these differences. SGLT2i and GLP1RA use in patients at high risk was limited in all three countries during this time period.

Transplant patients have poor outcomes in coronavirus-disease 2019 (COVID-19). The pandemic's effects on rural patients' overall care experience, attitudes to telemedicine, and vaccination are poorly understood.We administered a cross-sectional survey to adult kidney transplant recipients in central Pennsylvania across four clinical sites between March 29, 2021 and June 2, 2021. We assessed the pandemic's impact on care access, telemedicine experience, attitudes toward preventive measures, vaccination, and variation by sociodemographic variables.Survey completion rate was 51% (303/594). Of these, 52.8% were rural residents. The most common impact was use of telemedicine (79.2%). Predominant barriers to telemedicine were lack of video devices (10.9%), perceived complexity (5.6%), and technical issues (5.3%). On a 0-10 Likert scale, the mean positive impression for telemedicine was 7.7; lower for patients with telephone-only versus video visits (7.0 vs. 8.2; p .001), and age ≥60 years (7.4 vs. 8.1; p = .01) on univariate analyses. Time/travel savings were commonly identified (115/241, 47.7%) best parts of telemedicine and lack of personal connection (70/166, 42.2%) the worst. Only 68.9% had received any dose of COVID vaccination. The vaccinated group members were older (58.4 vs. 53.5 years; p = .007), and less likely rural (47.8% vs. 65.2%; p = .005). Common themes associated with vaccine hesitancy included concerns about safety (27/59, 46%), perceived lack of data (19/59, 32%), and distrust (17/59, 29%). At least one misconception about the vaccines or COVID-19 was quoted by 29% of vaccine-hesitant patients.Among respondents, the pandemic significantly impacted healthcare experience, especially in older patients in underserved communities. COVID-19 vaccination rate was relatively low, driven by misconceptions and lack of trust.

Multiple clinical guidelines recommend an ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker (ARB) in patients with elevated albuminuria, which can be measured through urine albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, or dipstick. However, how albuminuria test results relate to the prescription of ACE inhibitor/ARB is uncertain. We identified individuals with an ACR measurement between January 1, 2004, and June 30, 2018, and no contraindications or allergy to ACE inhibitor/ARB. We performed multivariable logistic regression analyses to evaluate the association between ACR level and prescription of ACE inhibitor/ARB within 6 months after the test. We applied similar methods to investigate the association of protein-to-creatinine ratio and dipstick measurement results with the prescription of ACE inhibitor/ARB. Among 67 237 individuals with an ACR measurement, 47.7% were already taking an ACE inhibitor or ARB at the time of first ACR measurement. Among the 35 138 individuals who were not on ACE inhibitor/ARB, those with higher ACR levels were more likely to be prescribed ACE inhibitor/ARB in the following 6 months, with steep increases in prescriptions until ACR 300 mg/g, after which the association plateaued. The majority (80.9%) of ACE inhibitor/ARB prescriptions were made by family medicine and internal medicine. A similar pattern held in the cohorts tested by protein-to-creatinine ratio and dipstick measurement. Our study provides evidence that albuminuria test results change patient care, suggesting that adherence to albuminuria testing is a key step in optimal medical management.

Rationale & Objective: Evaluation of glomerular filtration rate (GFR) is challenging in adults undergoing bariatric surgery because creatinine and cystatin C levels are influenced by changes in muscle and fat mass. Additionally, indexing of GFR by body surface area (BSA) may by affected by decreases in BSA. Study Design: Prospective observational study. Setting & Participants: 27 adults with body mass index (BMI) ≥ 35 kg/m2 who underwent measurement of GFR before and after bariatric surgery. Outcomes: Indexed and nonindexed GFRs measured (mGFRs) using plasma iohexol clearance, indexed and nonindexed estimated GFR (eGFR) based on levels of creatinine, cystatin C, or both from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Analytic Approach: Bias and percent of estimates within 20% and 30% of mGFR (P20 and P30) for estimating equations were examined. Results: Mean presurgery BMI was 49.5 (SD, 9.4) kg/m2, BSA was 2.42 (SD, 0.27) m2, nonindexed mGFR was 117.3 (SD, 34.1) mL/min, and indexed mGFR was 84.1 (SD, 22.0) mL/min/1.73 m2. After 6 months, mean BMI changed by –13.8 (95% CI, −15.9 to −11.8) kg/m2, BSA by −0.30 (95% CI, −0.33 to −0.27) m2, and nonindexed mGFR by −9.2 (95% CI, −17.2 to −1.1) mL/min, while indexed mGFR was unchanged at 5.1 (95% CI, −0.1 to 10.4) mL/min/1.73 m2. Nonindexed eGFRcr was unbiased (median bias, 5.0 [95% CI, −4.3 to 11.6] mL/min) before surgery, but overestimated mGFR (8.8 [95% CI, 1.8 to 16.9] mL/min) after surgery. Nonindexed eGFRcys underestimated mGFR before (median bias, −12.1 [95% CI, −21.4 to −1.2] mL/min) and after surgery (−11.2 [95% CI, −21.8 to −7.3] mL/min). Nonindexed eGFRcr-cys was unbiased before (median bias, −6.0 [95% CI, −11.0 to 1.0] mL/min) and after surgery (−2.0 [95% CI, −8.8 to 4.9] mL/min). Findings were similar for indexed eGFR compared with indexed mGFR. Limitations: Small, mostly white sample. Conclusions: Changes in indexed and nonindexed GFRs may be discordant after bariatric surgery in adults because of decreases in BSA. Indexed and nonindexed eGFRcr-cys may be less biased than indexed or nonindexed eGFRcr or eGFRcys because of opposite biases in estimating mGFR.

Identification and classification of leukemia cells in a rapid and label-free fashion is clinically challenging and thus presents a prime arena for implementing new diagnostic tools. Quantitative phase imaging, which maps optical path length delays introduced by the specimen, has been demonstrated to discern cellular phenotypes based on differential morphological attributes. Rapid acquisition capability and the availability of label-free images with high information content have enabled researchers to use machine learning (ML) to reveal latent features. We developed a set of ML classifiers, including convolutional neural networks, to discern healthy B cells from lymphoblasts and classify stages of B cell acute lymphoblastic leukemia. Here, we show that the average dry mass and volume of normal B cells are lower than those of cancerous cells and that these morphologic parameters increase further alongside disease progression. We find that the relaxed training requirements of a ML approach are conducive to the classification of cell type, with minimal space, training time, and memory requirements. Our findings pave the way for a larger study on clinical samples of acute lymphoblastic leukemia, with the overarching goal of its broader use in hematopathology, where the prospect of objective diagnoses with minimal sample preparation remains highly desirable.

Background and objectives It is unclear whether the presence of albuminuria modifies the effects of intensive systolic BP control on risk of eGFR decline, cardiovascular events, or mortality. Design, setting, participants, & measurements The Systolic Blood Pressure Intervention Trial randomized nondiabetic adults ≥50 years of age at high cardiovascular risk to a systolic BP target of Results Over a median follow-up of 3.1 years, 69 of 1723 (4%) participants with baseline albuminuria developed ≥40% eGFR decline compared with 61 of 7162 (1%) participants without albuminuria. Incidence rates of ≥40% eGFR decline were higher in participants with albuminuria (intensive, 1.74 per 100 person-years; standard, 1.17 per 100 person-years) than in participants without albuminuria (intensive, 0.48 per 100 person-years; standard, 0.11 per 100 person-years). Although effects of intensive BP lowering on ≥40% eGFR decline varied by albuminuria on the relative scale (hazard ratio, 1.48; 95% confidence interval, 0.91 to 2.39 for albumin-creatinine ratio ≥30 mg/g; hazard ratio, 4.55; 95% confidence interval, 2.37 to 8.75 for albumin-creatinine ratio Conclusions Albuminuria did not modify the absolute benefits and risks of intensive systolic BP lowering.

BACKGROUND In 2016, the Food and Drug Administration (FDA) changed labeling regarding metformin contraindications in patients with diabetes and CKD from using serum creatinine-based thresholds to using eGFR-based thresholds. Because race and sex affect serum creatinine levels independently of GFR, the earlier creatinine-based contraindication may have inadvertently caused racial and sex disparities in metformin prescription among patients with low eGFR. METHODS In an analysis of 15,946 Black and White primary care patients with diabetes and eGFR≥30 ml/min per 1.73 m2 in a large health system (the primary cohort), we assessed the association of race and sex with metformin prescription across eGFR level before and after the FDA label change. For a replication cohort, we meta-analyzed data from 36 cohorts with 1,051,723 patients from OptumLabs Data Warehouse. RESULTS In the primary cohort, before the label change, Black patients with eGFR of 30-44 ml/min per 1.73 m2 were prescribed metformin less often than White counterparts (adjusted prevalence ratio [aPR], 0.65; 95% confidence interval [95% CI], 0.52 to 0.82); this disparity was significantly attenuated after the label change (aPR, 0.90; 95% CI, 0.74 to 1.09; P value for interaction by period =0.04). Results were consistent in the replication cohorts. Men with eGFR of 30-44 ml/min per 1.73 m2 received metformin prescriptions less often than women counterparts before the label change; this was nonsignificantly attenuated after the label change, but we found significant attenuation in the replication cohorts (aPRpre-label change, 0.76; 95% CI, 0.73 to 0.79; aPRpost-label change, 0.85; 95% CI, 0.83 to 0.88; P value for interaction by period

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet lowered blood pressure (BP) and low-density lipoprotein cholesterol. OBJECTIVE: To compare effects of diets rich in fruits and vegetables with a typical American diet on cardiovascular injury in middle-aged adults without known preexisting cardiovascular disease. DESIGN: Observational study based on a three-arm, parallel-design, randomized trial conducted in the U.S. from 1994 to 1996. (ClinicalTrials.gov:NCT00000544) SETTING: Three of the four original clinical trial centers. PARTICIPANTS: 326 of the original 459 trial participants with available stored specimens. INTERVENTIONS: Participants were randomized to 8 weeks of monitored feeding with: a control diet typical of what many Americans eat, a diet rich in fruit and vegetables but otherwise similar to control, or the DASH diet which was rich in fruit, vegetables, low-fat dairy, and fiber, and reduced in saturated fat and cholesterol. Weight was kept constant throughout feeding. MEASUREMENTS: Biomarkers collected at baseline and 8-weeks: high-sensitivity cardiac troponin I (hs-cTnI), N-terminal b-type pro natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). RESULTS: The mean age of participants was 45.2 years, 48% were women, 49% were black, and mean baseline BP was 131/85 mmHg. Compared to control, the fruits and vegetables diet reduced hs-cTnI by 0.5 ng/L (95% CI: −0.9 to −0.2) and NT-proBNP by 0.3 pg/mL (95% CI: −0.5 to −0.1). Compared to control, DASH reduced hs-cTnI by 0.5 ng/L (95% CI: −0.9 to −0.1) and NT-proBNP by 0.3 pg/mL (95% CI: −0.5 to −0.04). Hs-CRP did not differ between diets. None of the markers differed between the fruits and vegetables and DASH diets. LIMITATIONS: Short duration, missing specimens, inability to isolate effects of specific foods or micronutrients. CONCLUSION: Diets rich in fruits and vegetables given over an 8-week period were associated with lower markers of subclinical cardiac damage and strain in adults without preexisting cardiovascular disease.

Rationale & Objective Influenza vaccination is recommended for all adults but particularly for older adults and those with high-risk conditions. Reduced kidney function is an important high-risk condition, but the effectiveness of influenza vaccination across kidney function is uncharacterized. We assessed the effectiveness of influenza vaccination among older adults with and without reduced kidney function. Study Design Observational cohort study. Setting & Participants 454,634 person-seasons among 110,968 individuals 65 years or older in the Geisinger Health System between the 2005 and 2015 influenza seasons, with baseline characteristics matched between those with and without vaccination using inverse probability weighting. Exposures Status of influenza vaccination. Outcomes Incident hospitalization with pneumonia/influenza, coronary heart disease, and heart failure during influenza season stratified by estimated glomerular filtration rate (eGFR; ≥ 60, 30-59, and Analytical Approach Pooled logistic regression analysis to estimate adjusted ORs. Results In the 2014-2015 influenza season, the prevalence of influenza vaccination was 63.3% without evident difference across eGFR categories. The incidence of hospitalization was higher in lower eGFRs (eg, 2.2% per person-season among those not vaccinated with eGFR Limitations Possible unmeasured confounding. Conclusions Influenza vaccination was associated with lower risk for hospitalizations with pneumonia/influenza and major cardiac diseases in eGFR ≥ 30mL/min/1.73m2. Studies are needed to explore optimal vaccination strategies for eGFR

Two recent studies challenged traditional paradigms of mammalian sodium physiology, suggesting that sodium reduction might cause weight gain by altering metabolism. This new theory has important implications for population-wide dietary recommendations. However, these observations have not been confirmed. In the DASH (Dietary Approaches to Stop Hypertension)-Sodium trial, 412 adults with systolic blood pressure of 120 to 159 mm Hg and diastolic blood pressure of 80 to 95 mm Hg not taking antihypertensive medications were randomly assigned to the DASH diet or a control diet (parallel design). On their assigned diet, participants randomly consumed each of the 3 sodium levels for 4 weeks (crossover design). Participants were provided all meals but could drink noncaloric beverages (eg, water) freely. Throughout the trial, energy intake was adjusted to maintain weight constant. The 3 sodium levels (at 2100 kcal/day) were: low (1150 mg of Na/day), medium (2300 mg of Na/day), and high (3450 mg of Na/day). Energy intake, weight, self-reported thirst, and 24-hour urine volume were assessed after each period. Participants were 57% women and 57% black; mean age was 48 years [SD, 10]). Among those assigned the control, mean weight increased slightly with higher sodium but not among those assigned DASH. Energy intake did not vary across sodium levels in either diet ( P -trends ≥0.36). Higher sodium resulted in more thirst ( P -trends P -trend=0.007). Reducing sodium did not increase energy requirements to maintain stable weights but did decrease thirst and urine volume (control diet only), findings consistent with the traditional understanding of mammalian sodium physiology. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000608.

Introduction: Telehealth and web-based applications are increasingly available to promote healthy lifestyle behavior change. However, evidence that these approaches lower blood pressure is limited. Methods: We conducted a randomized controlled trial to compare the efficacy of a self-directed vs. a telehealth-delivered dietitian approach using web-based applications in 187 participants (mean age 54.6 y, 52% female) with 24-hour systolic blood pressure (BP) 120-160 mmHg. Participants were recruited in the Geisinger Health System from 1/2019 to 3/2021. Both study arms received personalized recommendations to improve dietary quality based on web-based food frequency questionnaire, and access to an online comprehensive weight management program. The telehealth arm additionally received weekly telephone calls with a dietitian who used motivational interviewing. The primary outcome was 3-month change in 24-hour systolic BP. Secondary outcomes included changes in awake and sleep BP, self-reported physical activity, healthy eating index (HEI)-2015 score, and weight. Results: Twenty-four hour systolic BP improved in both the telehealth-dietitian arm (-6.5 mmHg, 95% CI: -8.4, -4.6) and the self-directed arm (-4.9, 95% CI: -7.0, -2.8), with no difference between arms (p=0.3). Participants in the telehealth-dietitian arm had significantly greater decreases in sleep systolic BP (mean -6.9 mmHg vs. -1.5; p=0.004) and diastolic BP (-3.3 mmHg vs. 0.7; p=0.001). The telehealth-dietitian arm tended to have greater improvements in self-reported physical activity, weight loss, and HEI-2015 score (Figure). Participant satisfaction with the intervention was higher in the telehealth-dietitian arm (p=0.004). Conclusions: Among individuals with elevated BP, the telehealth-dietitian intervention did not lower 24-hour systolic BP compared to the self-directed arm over 3 months. However, there were encouraging changes in other outcomes, including reduced sleep systolic and diastolic BP and increased physical activity.

Background: Adherence to anticoagulants is critical for effective stroke prevention for patients with atrial fibrillation (AF). Whether adherence to direct oral anticoagulants (DOACs) differs by chronic kidney disease (CKD) status remains uncertain. Methods: Using data from the Geisinger, we identified patients with AF initiating a DOAC between 2010-2019 and had at least one-year engagement prior and 3-month after initiation. To assess medication adherence, we compared proportion of days covered (PDC) by DOAC at 3, 6, 9, 12, and 18-month between patients with and without CKD, defined as estimated glomerular filtration rate (eGFR) 2 . Poor adherence was defined as PDC Results: Among the 4082 patients who initiated dabigatran (n=574), rivaroxaban (n=1502), or apixaban (n=2006), the mean (SD) age was 72 (12) years, 1083 (44%) were female, and the average eGFR was 73 (21) mL/min/1.73 m 2 . Overall, patients with CKD had lower adherence to DOAC compared to those without CKD (mean PDC: 0.89 vs. 0.91 at 3-month [P=0.03]; 0.87 vs. 0.89 at 6-month [P=0.04]; 0.84 vs. 0.87 at 9-month [P=0.02]; 0.83 vs. 0.86 at 12-month [P=0.05]; and 0.80 vs. 0.83 at 18-month [P=0.04]). For individual DOAC, only adherence to rivaroxaban was significantly lower in patients with CKD compared to those without CKD ( Figure ). Poor adherence to rivaroxaban was more common in CKD, particularly in the long-term (31% vs. 24% at 18-month [P=0.04]). Adherence to apixaban was highest and did not differ by CKD (CKD vs. non-CKD, mean PDC: 0.88 vs. 0.88 at 6-month; 0.85 vs. 0.85 at 12-month; and 0.81 vs. 0.83 at 18-month). Adherence to dabigatran was lowest and did not differ by CKD (CKD vs. non-CKD, mean PDC: 0.83 vs. 0.83 at 6-month; 0.76 vs. 0.78 at 12-month; and 0.73 vs. 0.74 at 18-month). Conclusion: Medication adherence was highest in apixaban users, followed by rivaroxaban and dabigatran users. Patients with CKD had lower adherence to rivaroxaban compared to those without CKD.

Background: The DASH (Dietary Approaches to Stop Hypertension) diet has been shown to reduce high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of subclinical cardiac injury. However, the time course of the DASH diet’s effects on this biomarker has not been determined. Hypothesis: The DASH diet lowers hs-cTnI within 4 weeks and the effects gradually increase over time. Methods: We analyzed data from the DASH-Sodium trial, a randomized controlled feeding study of healthy adults with systolic blood pressure 120 to 159 mm Hg and diastolic blood pressure 80 to 95 mm Hg. Participants were randomly assigned to the DASH diet or a typical American diet (control). Within each arm of the study, participants were assigned three sodium levels, in random order, changed every 4 weeks. Hs-cTnI was measured from serum collected at baseline and at 4, 8, and 12 weeks of feeding. Energy intake was adjusted to maintain body weight throughout the trial. Results: Of the 411 participants included in the final analysis, their mean age was 48 years, 56% were women, and 56% were Black. The mean baseline systolic/diastolic blood pressure was 135/86 mm Hg. Compared with baseline, the control diet did not have a significant effect on hs-cTnI at any of the measured time points. In contrast, the DASH diet reduced hs-cTnI by 0.18 ng/l (95% CI: -0.32, -0.04) at 4 weeks, 0.14 ng/l (95% CI: -0.29, 0.00) at 8 weeks, and 0.33 ng/l (95% CI: -0.48, -0.18) at 12 weeks ( Figure ; P -trend = 0.025). The %-difference in mean change from baseline of hs-cTnI for DASH vs. control was -13.30% (95% CI: -25.34, 0.69), -10.47% (95% CI: -23.08, 4.21), and -17.78% (95% CI: -29.51, -4.09) at 4, 8, and 12 weeks, respectively. Conclusions: The DASH diet reduced hs-cTnI within 4 weeks of feeding with greater diet effects occurring at 12 weeks of feeding. These results suggest that the DASH diet has both early and cumulative effects on subclinical cardiac injury.

Despite reports of hematuria and proteinuria with rosuvastatin use at the time of its approval by the US Food and Drug Association (FDA), little postmarketing surveillance exists to assess real-world risk. Current labeling suggests dose reduction (maximum daily dose of 10 mg) for patients with severe CKD.Using deidentified electronic health record data, we analyzed 152,101 and 795,799 new users of rosuvastatin and atorvastatin, respectively, from 2011 to 2019. We estimated inverse probability of treatment-weighted hazard ratios (HRs) of hematuria, proteinuria, and kidney failure with replacement therapy (KFRT) associated with rosuvastatin. We reported the initial rosuvastatin dose across eGFR categories and evaluated for a dose effect on hematuria and proteinuria.Overall, we identified 2.9% of patients with hematuria and 1.0% with proteinuria during a median follow-up of 3.1 years. Compared with atorvastatin, rosuvastatin was associated with increased risk of hematuria (HR, 1.08; 95% confidence interval [95% CI], 1.04-1.11), proteinuria (HR, 1.17; 95% CI, 1.10-1.25), and KFRT (HR, 1.15; 1.02-1.30). A substantial share (44%) of patients with eGFR30 mL/min per 1.73 mCompared with atorvastatin, rosuvastatin was associated with increased risk of hematuria, proteinuria, and KFRT. Among patients with eGFR30 mL/min per 1.73 m

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) impede glucose reabsorption in kidney proximal tubules, which in turn can stimulate osmotic diuresis, natriuresis, and the renin-angiotensin system. This mechanism may enhance potassium secretion via increased distal sodium and water delivery and

Family history of kidney disease increases risk of end-stage kidney disease (ESKD) in donors. Pre-donation genetic testing is recommended in evaluation guidelines and regulatory policy. Collaborating across several institutions, we describe cases to illustrate the utility as well as practical issues in incorporating genetic testing in transplant protocols. Case 1 is from 2009, before pervasive genetic testing. A healthy 27-year-old Caucasian male had an uneventful donor evaluation for his mother, who had early onset ESKD of unclear cause. He participated in paired-exchange kidney donation, but developed progressive kidney disease and gout over the next 10 years. A uromodulin gene mutation (NM_003361.3(UMOD):c.377 G>A p.C126Y) was detected and kidney biopsy showed tubulointerstitial kidney disease. The patient subsequently required kidney transplantation himself. Case 2 was a 36-year-old African American female who had an uneventful kidney donor evaluation. She underwent gene panel-based testing to rule out ApolipoproteinL1 risk variants, for which was negative. Incidentally, a sickle-cell trait (NM_000518.5(HBB):c.20A>T p.Glu7Val) was noted, and she was declined for kidney donation. This led to significant patient anguish. Case 3 was a 26-year-old Caucasian female who underwent panel-based testing because the potential recipient, her cousin, carried a variant of uncertain significance in the hepatocyte nuclear factor-1-β (HNF1B) gene. While the potential donor did not harbor this variant, she was found to have a likely pathogenic variant in complement factor I (NM_000204.4(CFI):c.1311dup:p.Asp438Argfs*8), precluding kidney donation. Our cases emphasize that while genetic testing can be invaluable in donor evaluation, transplant centers should utilize detailed informed consent, develop care pathways for secondary genetic findings, and share experience to develop best practices around genetic testing in donors.

CKD is increasingly prevalent and is often called a model of “accelerated aging”; even early stages of CKD add ≥5 years to the aging process, increasing the likelihood of experiencing physical dysfunction and cognitive decline (1). CKD has sequelae beyond ESKD and cardiovascular disease, including functional limitations and disability, which occur at higher rates in patients with CKD than age-matched controls, even after accounting for comorbidities, such as cardiovascular disease and diabetes. Functional status has long been recognized as an important outcome in chronic disease and geriatric populations and is also an important determinant for kidney transplantation selection and for adequate disease self-management. The impairment of functional status is important to consider because of its widespread prevalence and link to decreased quality of life; increased risk of disability, falls, fractures, and depression; and increased healthcare costs. However, much of the prior literature on functional decline has focused on individuals with ESKD or community-dwelling, older individuals. Less has been described about the functional status and burden of disability in patients with earlier-stage CKD. To prevent or mitigate functional limitations and disability, and to improve health outcomes in the CKD population, it is important to identify those at high risk of functional decline. In the process of trying to prevent functional decline, the first step is to effectively assess functional status and establish whether measures of functional status are associated with adverse outcomes among people with earlier stages of CKD. Then, interventions can be designed and tested in patients with poor functional status who may benefit from preventative interventions to prevent adverse outcomes. Researchers in gerontology have developed standardized, performance-based tests to assess physical function that are inexpensive, easy to use, reproducible, and …

Background Mutations in PKD1 or PKD2 cause typical autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic kidney disease. Dominantly inherited polycystic kidney and liver diseases on the ADPKD spectrum are also caused by mutations in at least six other genes required for protein biogenesis in the endoplasmic reticulum, the loss of which results in defective production of the PKD1 gene product, the membrane protein polycystin-1 (PC1). Methods We used whole-exome sequencing in a cohort of 122 patients with genetically unresolved clinical diagnosis of ADPKD or polycystic liver disease to identify a candidate gene, ALG9, and in vitro cell-based assays of PC1 protein maturation to functionally validate it. For further validation, we identified carriers of ALG9 loss-of-function mutations and noncarrier matched controls in a large exome-sequenced population-based cohort and evaluated the occurrence of polycystic phenotypes in both groups. Results Two patients in the clinically defined cohort had rare loss-of-function variants in ALG9, which encodes a protein required for addition of specific mannose molecules to the assembling N-glycan precursors in the endoplasmic reticulum lumen. In vitro assays showed that inactivation of Alg9 results in impaired maturation and defective glycosylation of PC1. Seven of the eight (88%) cases selected from the population-based cohort based on ALG9 mutation carrier state who had abdominal imaging after age 50; seven (88%) had at least four kidney cysts, compared with none in matched controls without ALG9 mutations. Conclusions ALG9 is a novel disease gene in the genetically heterogeneous ADPKD spectrum. This study supports the utility of phenotype characterization in genetically-defined cohorts to validate novel disease genes, and provide much-needed genotype-phenotype correlations.

Rationale & Objective: Pneumococcal vaccine is recommended for adults 65 years and older and those younger than 65 years with clinical indications (eg, diabetes, lung/heart disease, kidney failure, and nephrotic syndrome). Its cost-effectiveness in less severe chronic kidney disease (CKD) is uncharacterized.Study Design: Cost-effectiveness analysis.Setting & Population: US adults aged 50 to 64 and 65 to 79 years stratified by CKD risk status: no CKD (estimated glomerular filtration rate >= 60 mL/min/1.73 m(2) and urinary albumincreatinine ratio = 2,000 mg/g). Data sources were the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004, Centers for Disease Control and Prevention, and the Atherosclerosis Risk in Communities (ARIC) Study.Intervention(s): Vaccination compared to no vaccination.Outcomes: Incremental cost-effectiveness ratios based on US dollars per quality-adjusted life-year (QALY).Model, Perspective, & Timeframe: Markov model, US health sector perspective, and lifetime horizon.Results: The prevalence of pneumococcal vaccination in NHANES 1999 to 2004 was 56.6% (aged 65-79 years), 28.5% (aged 50-64 years with an indication), and 9.7% (aged 5064 years without an indication), with similar prevalences across CKD risk status. Pneumococcal vaccination was overall cost-effective (Limitations: Some model parameters were based on data from the general population. Analysis did not consider costs associated with kidney disease progression.Conclusions: Uptake of pneumococcal vaccination should be improved in general. Our results also suggest the cost-effectiveness of expanding its indication to younger adults with CKD less severe than kidney failure or nephrotic syndrome.

Genetic and environmental interactions predispose certain groups to lung cancer, including families. Families or caregiving units experience the disease interdependently. We have previously evaluated the concerns and preferences of patients in addressing the lung cancer experience and cancer risks in their families. This qualitative study evaluates the concerns and preferences of family members and caregivers of patients with lung cancer in the lung cancer experience and familial cancer risks. We held focus groups to discuss the format and timing of addressing these preferences and concerns. Qualitative data generated was analyzed using a grounded theory approach. Five focus groups totaling 19 participants were conducted. Seven themes were identified: (1) journey to lung cancer diagnosis has core dimensions for patient and family, (2) importance of communication between patients, families, and providers, (3) challenges for caregivers and family, (4) mixed perceptions of lung cancer causation among relatives, (5) discussion of cancer risk with relatives has complex dynamics, (6) impact of diagnosis on family health behaviors and screening, (7) role of genetic counseling. Family members of patients with lung cancer are interested in discussing risk factors, prevention, and diagnoses and also would like access to other supportive services do learn about and cope with some of the stresses and barriers they experience in the family lung cancer journey. The diagnosis represents a potential teachable moment with the opportunity to reduce the risk of LC development or improve early detection in LC patient’s family members.

Background: Hospitalization-associated acute kidney injury (AKI), affecting one-in-five inpatients, is associated with increased mortality and major adverse cardiac/kidney endpoints. Early AKI risk stratification may enable closer monitoring and prevention. Given the complexity and resource utilization of existing machine learning models, we aimed to develop a simpler prediction model. Methods: Models were trained and validated to predict risk of AKI using electronic health record (EHR) data available at 24 h of inpatient admission. Input variables included demographics, laboratory values, medications, and comorbidities. Missing values were imputed using multiple imputation by chained equations. Results: 26,410 of 209,300 (12.6%) inpatients developed AKI during admission between 13 July 2012 and 11 July 2018. The area under the receiver operating characteristic curve (AUROC) was 0.86 for Random Forest and 0.85 for LASSO. Based on Youden’s Index, a probability cutoff of >0.15 provided sensitivity and specificity of 0.80 and 0.79, respectively. AKI risk could be successfully predicted in 91% patients who required dialysis. The model predicted AKI an average of 2.3 days before it developed. Conclusions: The proposed simpler machine learning model utilizing data available at 24 h of admission is promising for early AKI risk stratification. It requires external validation and evaluation of effects of risk prediction on clinician behavior and patient outcomes.

To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care.We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}.One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.

Background Hospitalization-associated AKI is common and is associated with markedly increased mortality and morbidity. This prospective cohort study examined the feasibility and association of an AKI rehabilitation program with postdischarge outcomes. Methods Adult patients hospitalized from September 1, 2019 to February 29, 2020 in a large health system in Pennsylvania with stage 2–3 AKI who were alive and not on dialysis or hospice at discharge were evaluated for enrollment. The intervention included patient education, case manager services, and expedited nephrology appointments starting within 1–3 weeks of discharge. We examined the association between AKI rehabilitation program participation and risks of rehospitalization or mortality in logistic regression analyses adjusting for comorbidities, discharge disposition, and sociodemographic and kidney parameters. Sensitivity analysis was performed using propensity score matching. Results Among the high-risk patients with AKI who were evaluated, 77 of 183 were suitable for inclusion. Out of these, 52 (68%) patients were enrolled and compared with 400 contemporary, nonparticipant survivors of stage 2/3 AKI. Crude postdischarge rates of rehospitalization or death were lower for participants versus nonparticipants at 30 days (15% versus 34%; P=0.01) and at 90 days (31% versus 51%; P=0.01). After multivariable adjustment, participation in the AKI rehabilitation program was associated with lower risk of rehospitalization or mortality at 30 days (OR, 0.41; 95% CI, 0.16 to 0.93), with similar findings at 90 days (OR, 0.52; 95% CI, 0.25 to 1.05). Due to small sample size, propensity-matched analyses were limited. The participants’ rehospitalization or mortality was numerically lower but not statistically significant at 30 days (18% versus 31%; P=0.22) or at 90 days (47% versus 58%; P=0.4). Conclusions The AKI rehabilitation program was feasible and potentially associated with improved 30-day rehospitalization or mortality. Our interventions present a roadmap to improve enrollment in future randomized trials.

Objective: Clinical guidelines for people with diabetes recommend chronic kidney disease (CKD) testing at least annually using estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (uACR). We aimed to understand CKD testing among people with type 2 diabetes in the United States. Research Design and Methods: Electronic health record data were analyzed from 513,165 adults with type 2 diabetes, receiving primary care from 24 health care organizations and 1,164 clinical practice sites. We assessed the percentage of patients with both ≥1 eGFR and ≥1 uACR, and each test individually, in the 1, 2, and 3 years ending September 2019, by health care organization and clinical practice site. Elevated albuminuria was defined by uACR ≥30 mg/g. Results: The 1-year median testing rate across organizations was 51.6% for both uACR and eGFR, 89.5% for eGFR, and 52.9% for uACR. uACR testing varied (10th–90th percentile) from 44.7% to 63.3% across organizations and from 13.3% to 75.4% across sites. Over 3 years, the median testing rate for uACR across organizations was 73.7%. Overall, the prevalence of detected elevated albuminuria was 15%. The average prevalence of detected elevated albuminuria increased linearly with uACR testing rates at sites, with estimated prevalence of 6%, 15%, and 30%, at uACR testing rates of 20%, 50%, and 100%. Conclusions: While eGFR testing rates are uniformly high among people with type 2 diabetes, testing rates for uACR are suboptimal and highly variable across and within the organizations examined. Guideline-recommended uACR testing should increase detection of CKD.

Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures, reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): −1.5, −0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: −1.1, −0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: −0.04, 0.5), these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction, however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.