Parathyroidectomy and the Development of New Depression Among Adults With Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with neuropsychiatric symptoms. Although parathyroidectomy has been associated with improvement of preexisting depression among adults with PHPT, the effect of parathyroidectomy on the development of new depression is unknown. Objective: To determine the effect of early parathyroidectomy on the incidence of new depression among adults with PHPT compared with nonoperative management. Design, Setting, and Participants: Analyzed data included observational national Veterans Affairs data from adults with a new diagnosis of PHPT from 2000 through 2019 using target trial emulation with cloning, a biostatistical method that uses observational data to emulate a randomized clinical trial. New depression rates were compared between those treated with early parathyroidectomy vs nonoperative management using an extended Cox model with time-varying inverse probability censoring weighting, adjusted for patient demographics, comorbidities, and depression risk factors. Eligible adults with a new biochemical diagnosis of PHPT, excluding those with past depression diagnoses, residing in an assisted living/nursing facility, or with Charlson Comorbidity Index score higher than 4 were included. These data were analyzed January 4, 2023, through June 15, 2023. Exposure: Early parathyroidectomy (within 1 year of PHPT diagnosis) vs nonoperative management. Main Outcome: New depression, including among subgroups according to patient age (65 years or older; younger than 65 years) and baseline serum calcium (11.3 mg/dL or higher; less than 11.3 mg/dL). Results: The study team identified 40 231 adults with PHPT and no history of depression of whom 35896 were male (89%) and the mean (SD) age was 67 (11.3) years. A total of 3294 patients underwent early parathyroidectomy (8.2%). The weighted cumulative incidence of depression was 11% at 5 years and 18% at 10 years among patients who underwent parathyroidectomy, compared with 9% and 18%, respectively, among nonoperative patients. Those treated with early parathyroidectomy experienced no difference in the adjusted rate of new depression compared with nonoperative management (hazard ratio, 1.05; 95% CI, 0.94-1.17). There was also no estimated effect of early parathyroidectomy on new depression in subgroup analyses based on patient age or serum calcium. Conclusions: In this study, there was no difference in the incidence of new depression among adults with PHPT treated with early parathyroidectomy vs nonoperative management, which is relevant to preoperative discussions about the benefits and risks of operative treatment.

Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure : A Target Trial Emulation Study.

BACKGROUND: For older adults with kidney failure who are not referred for transplant, medical management is an alternative to dialysis. OBJECTIVE: To compare survival and home time between older adults who started dialysis at an estimated glomerular filtration rate (eGFR) less than 12 mL/min/1.73 m2 and those who continued medical management. DESIGN: Observational cohort study using target trial emulation. SETTING: U.S. Department of Veterans Affairs, 2010 to 2018. PARTICIPANTS: Adults aged 65 years or older with chronic kidney failure and eGFR below 12 mL/min/1.73 m2 who were not referred for transplant. INTERVENTION: Starting dialysis within 30 days versus continuing medical management. MEASUREMENTS: Mean survival and number of days at home. RESULTS: Among 20 440 adults (mean age, 77.9 years [SD, 8.8]), the median time to dialysis start was 8.0 days in the group starting dialysis and 3.0 years in the group continuing medical management. Over a 3-year horizon, the group starting dialysis survived 770 days and the group continuing medical management survived 761 days (difference, 9.3 days [95% CI, -17.4 to 30.1 days]). Compared with the group continuing medical management, the group starting dialysis had 13.6 fewer days at home (CI, 7.7 to 20.5 fewer days at home). Compared with the group continuing medical management and forgoing dialysis completely, the group starting dialysis had longer survival by 77.6 days (CI, 62.8 to 91.1 days) and 14.7 fewer days at home (CI, 11.2 to 16.5 fewer days at home). LIMITATION: Potential for unmeasured confounding due to lack of symptom assessments at eligibility; limited generalizability to women and nonveterans. CONCLUSION: Older adults starting dialysis when their eGFR fell below 12 mL/min/1.73 m2 who were not referred for transplant had modest gains in life expectancy and less time at home. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs and National Institutes of Health.

Prospective Study on Kidney Dysfunction Markers and Risk for Mortality among South Asians.

Introduction: Associations between markers of impaired kidney function and adverse outcomes among South Asians is understudied and could differ from existing data derived mostly from North American or European cohorts. Methods: We conducted a prospective analysis of 9797 participants from the ongoing cardiometabolic risk reduction study in South Asia, India. We examined the associations between baseline spot urine albumin-to-creatinine (UACR) ratio and creatinine-based estimated glomerular filtration rate (eGFR) estimating equations with all-cause mortality using Cox proportional hazards regression, adjusting for baseline age, sex, diabetes, systolic blood pressure, tobacco, history of cardiovascular disease, and cholesterol. Additionally, we calculated population attributable fraction (PAF) for both markers. Results: Over a median 7-year follow-up, with 66,909 person-years, 791 deaths occurred. At baseline, the weighted prevalence of UACR ≥ 30 mg/g and eGFRCKD-EPI 2009 <60 ml/min per 1.73 m2 was 6.6% and 1.6%, respectively. The risk for mortality was increased with higher UACR (10-30 hazard ratio [HR]: 1.6 [1.2-2.1]), 30-300 HR: 2.4 [1.8-3.1]), and ≥300 (HR: 6.0 [3.8-9.4] relative to UACR <10 mg/g). Risk for mortality was also higher with lower eGFRCKD-EPI 2009 (44-30; HR: 4.5 [2.5-8.3] and <30 HR: 7.0 [3.7-13.0], relative to 90-104 ml/min per 1.73 m2). PAF for mortality because of UACR ≥30 mg/g and eGFRCKD-EPI 2009 <45 ml/min per 1.73 m2 were 24.4% and 13.4%, respectively. Conclusion: Single-time point assessment of UACR ≥30 mg/g or eGFRCKD-EPI 2009 <45 ml/min per 1.73 m2 portends higher mortality risk among urban South Asians. Because albuminuria is common and associated with accelerated decline in GFR, screening and targeted efforts to reduce albuminuria are warranted.

MyPlate Awareness and Engagement and Perceived and Objective Diet Quality in US Adults With Chronic Kidney Disease.

OBJECTIVE: Awareness of federal dietary guidelines has been associated with better perceived and objective diet quality. Little is known about the awareness of federal dietary recommendations among persons with chronic kidney disease (CKD) and the associations between recognition of guidelines, perception of diet quality, and objective quality of the diet in this population. DESIGN AND METHODS: We compared awareness of, and engagement with, MyPlate (a representation of 5 food groups from the US Department of Agriculture) along with perceived and objective diet quality, the latter assessed via Dietary Approaches to Stop Hypertension index scores, among US adults with and without CKD during 2017-2020. RESULTS: Among noninstitutionalized adults in the United States, 8.3% had albuminuria with normal or near-normal kidney function, 4.0% had estimated glomerular filtration rate 45-59 mL/minute/1.73 m2 (CKD stage G3a) and 1.6% had estimated glomerular filtration rate <45 mL/minute/1.73 m2 (CKD stages G3b/G4/G5). MyPlate awareness was lower among persons with CKD compared with those without CKD (19.6% vs. 26.4%, P < .001) and was lower among persons with more advanced CKD stages: 20.8%, 18.2%, and 16.3% in persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend P < .001). Among persons aware of MyPlate, a numerically higher proportion with CKD attempted to follow MyPlate recommendations (43.9% vs. 32.3%, P = .10); the proportion was highest among persons with moderate-to-advanced CKD (41.9%, 42.9%, and 56.9% among persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend P < .001)). Perceived and objective dietary quality (the latter based on concordance with the Dietary Approaches to Stop Hypertension diet) were slightly higher among persons with CKD relative to those without CKD. CONCLUSIONS: Adults with CKD have lower MyPlate awareness than adults without CKD. Enhancing diet education to persons with CKD could improve diet quality and potentially ameliorate CKD-associated complications.

Representation of Real-World Adults With Chronic Kidney Disease in Clinical Trials Supporting Blood Pressure Treatment Targets.

BACKGROUND: Little is known about how well trial participants with chronic kidney disease (CKD) represent real-world adults with CKD. We assessed the population representativeness of clinical trials supporting the 2021 Kidney Disease: Improving Global Outcomes blood pressure (BP) guidelines in real-world adults with CKD. METHODS AND RESULTS: Using a cross-sectional analysis, we identified patients with CKD who met the guideline definition of hypertension based on use of antihypertensive medications or sustained systolic BP ≥120 mm Hg in 2019 in the Veterans Affairs and Kaiser Permanente of Southern California. We applied the eligibility criteria from 3 BP target trials, SPRINT (Systolic Pressure Intervention Trial), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and AASK (African American Study of Kidney Disease), to estimate the proportion of adults with a systolic BP above the guideline-recommended target and the proportion who met eligibility criteria for ≥1 trial. We identified 503 480 adults in the Veterans Affairs and 73 412 adults in Kaiser Permanente of Southern California with CKD and hypertension in 2019. We estimated 79.7% in the Veterans Affairs and 87.3% in the Kaiser Permanente of Southern California populations had a systolic BP ≥120 mm Hg; only 23.8% [23.7%-24.0%] in the Veterans Affairs and 20.8% [20.5%-21.1%] in Kaiser Permanente of Southern California were trial-eligible. Among trial-ineligible patients, >50% met >1 exclusion criteria. CONCLUSIONS: Major BP target trials were representative of fewer than 1 in 4 real-world adults with CKD and hypertension. A large proportion of adults who are at risk for cardiovascular morbidity from hypertension and susceptible to adverse treatment effects lack relevant treatment information.

Defining systolic blood pressure normative values in hospitalized pediatric patients: a single center experience.

BACKGROUND: Normative blood pressure (BP) values and definition of hypertension (HTN) in children in outpatient setting cannot be reliably used for inpatient therapy initiation. No normative exists to describe HTN in hospitalized pediatric populations. We aimed to study the prevalence of hypertension and produce normative BP values in hospitalized children. METHODS: Cross sectional observational study of all children hospitalized on acute care floors, ≥2 and <18 years age, at Stanford Children's Hospital, from Jan-01-2014 to Dec-31-2018. Cohort included 7468 hospital encounters with a total of 118,423 automated, oscillometric, BPs measured in the upper extremity during a hospitalization of >24 hours. RESULTS: Overall prevalence of HTN, defined by outpatient guidelines, was 12-48% in boys and 6-39% in girls, stage 1 systolic HTN in 12-38% of boys and 6-31% of girls, stage 2 systolic HTN in 3-10% of boys and 1-8% of girls. Centile curves were derived demonstrating overall higher BP reading for hospitalized patients compared to the outpatient setting. CONCLUSION: Higher blood pressures are anticipated during hospitalization. Thresholds provided by the centile curves generated in this study may provide the clinician with some guidance on how to manage hospitalized pediatric patients based on clinical circumstances. IMPACT: Hospitalized children have higher blood pressures compared to patients in the ambulatory setting, hence outpatient normative blood pressure values cannot be reliably used for inpatient therapy initiation. No normative exists to describe hypertension in hospitalized pediatric populations. The thresholds provided by the centile curves generated in this study may provide the clinician with some guidance on how to manage hospitalized pediatric patients based on clinical circumstances.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Active Kidney Involvement in the United States: 2016-2020.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its subtypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA), frequently present with acute kidney injury and can often lead to kidney failure, even with successful induction therapy. Few contemporary, nationally representative studies have described hospital complications of AAV. Methods: Using data from the 2016-2020 National Inpatient Sample, a nationally representative database, we identified hospitalizations from adults with a new diagnosis of AAV (subtype or unspecified) and an inpatient kidney biopsy during the index hospitalization. We described baseline characteristics, associated inpatient procedures and complications, and compared lengths of stay and costs by geographic region, hospital characteristics, and AAV subtype. Results: We identified an average of 1,329 cases of hospitalized AAV with a concurrent kidney biopsy per year over the 5-year period. More than 50% were not designated as having a specific subtype, likely owing to delays in documentation of histopathology. Kidney involvement was severe as the majority of patients developed acute kidney injury, and the proportion of patients who required inpatient dialysis was approximately 24%. Approximately 20% of patients developed hypoxia. Inpatient plasmapheresis was delivered to 20.4% and 20.6% of patients with GPA and MPA, respectively. There were no clinically meaningful or statistically significant differences in adjusted length of stay or inpatient costs among AAV subtypes. Admission in the Midwest region was associated with shorter hospital stays and lower costs than that in the Northeast, South, or West regions of the USA (adjusted p = 0.007 and <0.001, respectively). Conclusion: AAV with acute kidney involvement remains a challenging, high-risk condition. Maintaining a high index of suspicion and a low threshold for kidney biopsy should help ameliorate short- and long-term complications.

Dialysis Modality, Transplant Characteristics, and Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using USRDS Data.

Rationale & Objective: Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied. Study Design: We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with atrial fibrillation. Setting & Participants: The study included 43,621 patients who were aged 18 years older when receiving a first kidney transplant between January 1, 2005, and September 30, 2012 and whose primary payer was Medicare (parts A and B) at the time of transplantation and the 6 months preceding it. Exposure: Dialysis modality used before transplant. Outcome: Time to incidence of atrial fibrillation up to 3 years posttransplant. Analytical Approach: Multivariable Cox regression was used to estimate HRs. Results: Of 43,621 patients, 84.9% received hemodialysis and 15.1% received peritoneal dialysis before transplant. The mean ± SD age was 51 ± 13.6 years; 60.8% were male, 55.6% White, and 35.8% Black race. The mean dialysis vintage was 4.3 ± 2.8 years. Newly diagnosed atrial fibrillation after kidney transplant occurred in 286 patients (during 15,363 person-years) who had received peritoneal dialysis and in 2,315 patients (during 83,536 person-years) who had received hemodialysis. After multivariable adjustment, atrial fibrillation was 20% (95% CI, 4%-38%) more likely in those who had been receiving hemodialysis versus peritoneal dialysis, regardless of whether death was considered a competing risk or a censoring event. Each year of pretransplant dialysis vintage increased the risk of posttransplant atrial fibrillation by 6% (95% CI, 3%-9%). Limitations: Residual confounding; data from billing claims does not specify the duration of atrial fibrillation or whether it is valvular. Conclusions: Pretransplant hemodialysis, as compared with peritoneal dialysis, was associated with higher risk of newly diagnosed atrial fibrillation after a first kidney transplant. Plain-Language Summary: New-onset atrial fibrillation (AF) occurs in 7% of kidney transplant recipients in the first 3 years posttransplantation. We conducted this study to determine whether pretransplant dialysis modality was associated with posttransplant AF. We identified 43,621 patients; 84.9% used hemodialysis and 15.1% used peritoneal dialysis pretransplant. Multivariable Cox regression was used to estimate hazard ratios. We found that patients receiving hemodialysis pretransplant were at 20% increased risk of developing posttransplant AF as compared with patients receiving peritoneal dialysis. As our understanding of transplant-specific risk factors for AF increases, we may be able to better risk-stratify transplant patients and develop monitoring and management strategies that can improve outcomes.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and mild/moderate chronic kidney disease.

AIM: To determine the comparative effectiveness regarding major cardiovascular events of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). MATERIALS AND METHODS: We assembled a cohort of commercially insured adult patients with T2DM in the United States (derived from Optum Clinformatics DataMart 2003-2021) who were new users of GLP-1 receptor agonists or SGLT-2 inhibitors. We compared risks of non-fatal myocardial infarction or stroke in patients with and without CKD, and further categorized by CKD stage: stages G1 or G2 [estimated glomerular filtration rate (eGFR) ≥60 ml/min] and A2 (urine albumin to creatinine ratio 30 to <300 mg/g) or A3 (urine albumin to creatinine ratio ≥300 mg/g), stage G3a (eGFR 45 to <60 ml/min/1.73 m2 ) and stage G3b (eGFR 30 to <45 ml/min/1.73 m2 ). We used proportional hazards regression after inverse probability of treatment weighting to compute hazard ratios and 95% confidence intervals. RESULTS: After accounting for the probability of treatment, patients with T2DM and CKD treated with SGLT-2 inhibitors experienced a 14% lower risk of non-fatal myocardial infarction or stroke (hazard ratio 0.86, 95% confidence interval 0.78-0.94) relative to those treated with GLP-1 receptor agonists. CONCLUSIONS: Recognizing the potential for residual confounding, selection bias and immortal time bias, commercially insured patients in the United States with T2DM and CKD treated with SGLT-2 inhibitors experienced significantly lower risks of non-fatal myocardial infarction or stroke relative to those treated with GLP-1 receptor agonists.

Heterogeneous Treatment Effects of Intensive Glycemic Control on Kidney Microvascular Outcomes and Mortality in ACCORD.

SIGNIFICANCE STATEMENT: Identifying and quantifying treatment effect variation across patients is the fundamental challenge of precision medicine. Here we quantify heterogeneous treatment effects of intensive glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, considering three outcomes of interest-a composite kidney outcome (driven by macroalbuminuria), all-cause mortality, and first assisted hypoglycemic event. We demonstrate that the effects of intensive glycemic control vary with risk of kidney failure, as predicted by the kidney failure risk equation (KFRE). Participants at highest risk of kidney failure gain the largest absolute kidney benefit of intensive glycemic control but also experience the largest absolute risk of death and hypoglycemic events. Our findings illustrate the value of identifying clinically meaningful treatment heterogeneity, particularly when treatments have different effects on multiple end points. OBJECTIVE: Clear criteria to individualize glycemic targets in patients with type II diabetes are lacking. In this post hoc analysis of the ACCORD, we evaluate whether the KFRE can identify patients for whom intensive glycemic control confers more benefit in preventing kidney microvascular outcomes. RESEARCH DESIGN AND METHODS: We divided the ACCORD trial population into quartiles on the basis of 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them with the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted mean survival time (RMST) differences between intensive and standard glycemic control arms on ( 1 ) time-to-first development of severely elevated albuminuria or kidney failure and ( 2 ) all-cause mortality. RESULTS: We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure derived the most from intensive glycemic control in reducing kidney microvascular outcomes (7-year RMST difference of 114.8 [95% confidence interval 58.1 to 176.4] versus 48.4 [25.3 to 69.6] days in the entire trial population) However, this same patient group also experienced a shorter time to death (7-year RMST difference of -56.7 [-100.2 to -17.5] v. -23.6 [-42.2 to -6.6] days). CONCLUSIONS: We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced reduction in kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

Predicting transfer to haemodialysis using the peritoneal dialysis surprise question.

BACKGROUND: People on peritoneal dialysis (PD) at risk of transfer to haemodialysis (HD) need support to remain on PD or ensure a safe transition to HD. Simple point-of-care risk stratification tools are needed to direct limited dialysis centre resources. In this study, we evaluated the utility of collecting clinicians' identification of patients at high risk of transfer to HD using a single point of care question. METHODS: In this prospective observational study, we included 1275 patients undergoing PD in 35 home dialysis programmes. We modified the palliative care 'surprise question' (SQ) by asking the registered nurse and treating nephrologist: 'Would you be surprised if this patient transferred to HD in the next six months?' A 'yes' or 'no' answer indicated low and high risk, respectively. We subsequently followed patient outcomes for 6 months. Cox regression model estimated the hazard ratio (HR) of transfer to HD. RESULTS: Patients' mean age was 59 ± 16 years, 41% were female and the median PD vintage was 20 months (interquartile range: 9-40). Responses were received from nurses for 1123 patients, indicating 169 (15%) as high risk and 954 (85%) as low risk. Over the next 6 months, transfer to HD occurred in 18 (11%) versus 29 (3%) of the high and low-risk groups, respectively (HR: 3.92, 95% confidence interval (CI): 2.17-7.05). Nephrologist responses were obtained for 692 patients, with 118 (17%) and 574 (83%) identified as high and low risk, respectively. Transfer to HD was observed in 14 (12%) of the high-risk group and 14 (2%) of the low-risk group (HR: 5.56, 95% CI: 2.65-11.67). Patients in the high-risk group experienced higher rates of death and hospitalisation than low-risk patients, with peritonitis events being similar between the two groups. CONCLUSIONS: The PDSQ is a simple point of care tool that can help identify patients at high risk of transfer to HD and other poor clinical outcomes.

Building a strong collaborative biostatistics workforce: Strategies for effective intra-unit professional development activities.

Ongoing professional development is important for collaborative biostatisticians, as it enables them to remain current with the latest advances in statistical methodology and software, refine their analytical skills, and expand their domain knowledge, thereby facilitating their ability to contribute effectively to biomedical research. Although external opportunities for professional development, such as attending conferences and workshops, are widely recognized and valued in the field of biostatistics, there has been comparatively little attention given to internal opportunities for enhancing the skills and knowledge of biostatisticians which can be implemented with lower financial and time investment than external offerings. The purpose of this paper is to offer guidance for ongoing internal professional development activities that can be employed by collaborative biostatistics units in universities and academic medical centers to complement structured curricula and initial training. Specific examples of activities are provided so that collaborative biostatisticians and/or managers of biostatistical units can flexibly combine components to create an appropriately scaled, customized program that meets the needs of themselves or of the unit.

Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease.

Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24-hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24-hour urine citrate excretion (<200, 200-400, and >400 mg/d) and the time to osteoporosis or fracture according to 24-hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24-hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03-1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98-1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Treatment and Control of Hypertension Among Adults With Chronic Kidney Disease, 2011 to 2019.

BACKGROUND: Hypertension frequently accompanies chronic kidney disease (CKD) as etiology and sequela. We examined contemporary trends in hypertension treatment and control in a national sample of adults with CKD. METHODS: We evaluated 5% cross-sectional samples of adults with CKD between 2011 and 2019 in the Veterans Health Administration. We defined CKD as a sustained estimated glomerular filtration rate value <60 mL/min per 1.73 m2 or a urine albumin-to-creatinine ratio ≥30 mg/g. The main outcomes were blood pressure (BP) control, defined as a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg based on the mean of monthly BP measurements, and prescriptions for antihypertensive medications. RESULTS: The annual samples ranged between n=22 110 and n=33 039 individuals, with a mean age of 72 years, 96% of whom were men. Between 2011 and 2014, the age-adjusted proportion of adults with controlled BP declined from 78.0% to 72.2% (P value for linear trend, <0.001), reached a nadir of 71.0% in 2015, and then increased to 72.9% by 2019 (P value for linear trend, <0.001). Among adults with BP above goal, the age-adjusted proportion who did not receive antihypertensive treatment increased throughout the decade from 18.8% to 21.6%, and the age-adjusted proportion who received ≥3 antihypertensive medications decreased from 41.8% to 36.3%. Prescriptions for first-line antihypertensive agents also decreased. CONCLUSIONS: Among adults with CKD treated in the Veterans Health Administration, the proportion with controlled BP declined between 2011 and 2015 followed by a modest increase, coinciding with fewer prescriptions for antihypertensive medications.

Use of Wastewater Metrics to Track COVID-19 in the US.

Importance: Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence. Objective: To examine the association of county-level wastewater metrics with high case and hospitalization rates nationwide both before and after widespread use of at-home tests. Design, Setting, and Participants: This observational cohort study with a time series analysis was conducted from January to September 2022 in 268 US counties in 22 states participating in the US Centers for Disease Control and Prevention's National Wastewater Surveillance System. Participants included the populations of those US counties. Exposures: County level of circulating SARS-CoV-2 as determined by metrics based on viral wastewater concentration relative to the county maximum (ie, wastewater percentile) and 15-day percentage change in SARS-CoV-2 (ie, percentage change). Main Outcomes and Measures: High county incidence of COVID-19 as evidenced by dichotomized reported cases (current cases ≥200 per 100 000 population) and hospitalization (≥10 per 100 000 population lagged by 2 weeks) rates, stratified by calendar quarter. Results: In the first quarter of 2022, use of the wastewater percentile detected high reported case (area under the curve [AUC], 0.95; 95% CI, 0.94-0.96) and hospitalization (AUC, 0.86; 95% CI, 0.84-0.88) rates. The percentage change metric performed poorly, with AUCs ranging from 0.51 (95% CI, 0.50-0.53) to 0.57 (95% CI, 0.55-0.59) for reported new cases, and from 0.50 (95% CI, 0.48-0.52) to 0.55 (95% CI, 0.53-0.57) for hospitalizations across the first 3 quarters of 2022. The Youden index for detecting high case rates was wastewater percentile of 51% (sensitivity, 0.82; 95% CI, 0.80-0.84; specificity, 0.93; 95% CI, 0.92-0.95). A model inclusive of both metrics performed no better than using wastewater percentile alone. The performance of wastewater percentile declined over time for cases in the second quarter (AUC, 0.84; 95% CI, 0.82-0.86) and third quarter (AUC, 0.72; 95% CI, 0.70-0.75) of 2022. Conclusions and Relevance: In this study, nationwide, county wastewater levels relative to the county maximum were associated with high COVID-19 case and hospitalization rates in the first quarter of 2022, but there was increasing dissociation between wastewater and clinical metrics in subsequent quarters, which may reflect increasing underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments. This study offers a strategy to operationalize county wastewater percentile to improve the accurate assessment of community SARS-CoV-2 infection prevalence when reliability of conventional surveillance data is declining.

Describing Natural History and Exploring Risk Factors for Kidney Function Decline in Persons With CKD of Uncertain Etiology in Sri Lanka.

Introduction: Chronic kidney disease of uncertain etiology (CKDu) is a leading cause of death of adults in Sri Lanka's dry region. Methods: We initiated the Kidney Progression Project (KiPP) to prospectively follow 292 persons with Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) 20 to 60 ml/min per 1.73 m2 living in a CKDu endemic area. Using data from 3-year follow-up, we assessed kidney function decline (>30% from baseline eGFR), and the composite outcome of >30% eGFR decline, eGFR <15 ml/min or death, and explored the association of the 2 outcomes with baseline demographic, residential, and clinical parameters accounting for baseline eGFR. Results: Median eGFR at enrollment was 28 ml/min among 71 women; 30 ml/min among 221 men; 91% to 99% had trace or no proteinuria during follow-up. At enrollment, median serum sodium, uric acid, and potassium were 143 mmol/l, 6.3 mg/dl, 4.5 meq/l, respectively among women; and 143 mmol/l, 6.9 mg/dl, 4.3 meq/l among men. Mean slope of eGFR decline was -0.5 (SD 4.9) ml/min/yr. In exploratory analyses, men with greater years of education and those living in northern region of the study area experienced lower likelihood of disease progression (hazard ratios [HR] 0.87 [0.77-0.98] per additional year and 0.33 [0.12-0.89] for northern versus other subregions, respectively). There was a suggestion that men drinking well water had higher likelihood and men living further away from reservoirs had lower likelihood of >30% decline in eGFR (HR 2.07 [0.95-4.49] for drinking well water versus not, and HR 0.58 [0.32-1.05] per kilometer distance, respectively). Conclusions: The overall rate of kidney function decline was slow in this CKDu cohort, similar to other nonalbuminuric CKD, and event rates were similar among men and women. Further etiologic investigations could focus on specific residence locale and water use.

Heterogeneous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD.

Objective: Clear criteria to individualize glycemic targets are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients who disproportionately benefit from intensive glycemic control on kidney microvascular outcomes. Research design and methods: We divided the ACCORD trial population in quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality. Results: We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure benefitted the most from intensive glycemic control on kidney microvascular outcomes (7-year RMST difference of 115 v. 48 days in the entire trial population) However, this same patient group also experienced shorter times to death (7-year RMST difference of -57 v. -24 days). Conclusions: We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced benefits of treatment on kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.