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Uremic symptoms are common in patients with advanced chronic kidney disease, but the toxins that cause these symptoms are unknown. To evaluate this, we performed a cross-sectional study of the 12 month post-randomization follow-up visit of Modification of Diet in Renal Disease (MDRD) participants reporting uremic symptoms who also had available stored serum. We quantified 1,163 metabolites by liquid chromatography-tandem mass spectrometry. For each uremic symptom, we calculated a score as the severity multiplied by the number of days the symptom was experienced. We analyzed the associations of the individual symptom scores with metabolites using linear models with empirical Bayesian inference, adjusted for multiple comparisons. Among 695 participants, the mean measured glomerular filtration rate (mGFR) was 28 mL/min/1.73 m(2). Uremic symptoms were more common in the subgroup of 214 patients with an mGFR under 20 mL/min/1.73 m(2) (mGFR under 20 subgroup) than in the full group. For all metabolites with significant associations, the direction of the association was concordant in the full group and the subgroup. For gastrointestinal symptoms (bad taste, loss of appetite, nausea, and vomiting), eleven metabolites were associated with symptoms. For neurologic symptoms (decreased alertness, falling asleep during the day, forgetfulness, lack of pep and energy, tiring easily/weakness), seven metabolites were associated with symptoms. Associations were consistent across sensitivity analyses. Thus, our proof of principle study demonstrates the potential for metabolomics to understand metabolic pathways associated with uremic symptoms. Larger, prospective studies with external validation are needed.

Diabetes and prediabetes are growing concerns among US youth. Fasting glucose (FG) and HbA1c are standard diabetes screening tests, but HbA1c may be unreliable in some settings and fasting is burdensome in children. Glycated albumin (GA) is a non-fasting test that was recently cleared for clinical use in the US, but studies in youth without diabetes are limited. We conducted a cross-sectional analysis in 6826 youth without diabetes aged 8-19 years in the 1999-2004 National Health and Nutrition Examination Survey (NHANES). We evaluated the associations of GA with HbA1c, FG, and cardiometabolic risk factors. Glycated albumin was poorly correlated with HbA1c (ρ = 0.074) and FG (ρ = -0.047) and was negatively associated with BMI and cardiometabolic risk factors. Compared to youth in the highest tertile of GA (≥13.5%), those in the lowest GA tertile (

Background: Genome-wide association studies (GWAS) have revealed numerous loci for kidney function (estimated glomerular filtration rate, eGFR). The relationship of polygenic predictors of eGFR, risk of incident adverse kidney outcomes, and the plasma proteome is not known. Methods: We developed a genome-wide polygenic risk score (PRS) for eGFR by applying the LDpred algorithm to summary statistics generated from a multiethnic meta-analysis of CKDGen Consortium GWAS (N=765,348) and UK Biobank GWAS (90% of the cohort; N=451,508), followed by best parameter selection using the remaining 10% of UK Biobank (N=45,158). We then tested the association of the PRS in the Atherosclerosis Risk in Communities (ARIC) study (N=8,866) with incident chronic kidney disease, kidney failure, and acute kidney injury. We also examined associations between the PRS and 4,877 plasma proteins measured at at middle age and older adulthood and evaluated mediation of PRS associations by eGFR. Results: The developed PRS showed significant associations with all outcomes with hazard ratios (95% CI) per 1 SD lower PRS ranged from 1.06 (1.01, 1.11) to 1.33 (1.28, 1.37). The PRS was significantly associated with 132 proteins at both time points. The strongest associations were with cystatin-C, collagen alpha-1(XV) chain, and desmocollin-2. Most proteins were higher at lower kidney function, except for 5 proteins including testican-2. Most correlations of the genetic PRS with proteins were mediated by eGFR. Conclusions: A PRS for eGFR is now sufficiently strong to capture risk for a spectrum of incident kidney diseases and broadly influences the plasma proteome, primarily mediated by eGFR.

New Equations for Estimating GFR without Race Equations for estimating GFR with serum creatinine overestimate measured GFR in Blacks. The authors report new equations, without race as an inflation factor, using cystatin C and creatinine that reduced errors in estimation between Black participants and non-Black participants.Background Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct. Methods We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations. Results In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m(2) of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m(2); 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m(2); 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m(2); 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m(2); 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks. Conclusions New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)

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

OBJECTIVE To characterize national trends and characteristics of adults with diabetes receiving American Diabetes Association (ADA) guideline-recommended care. RESEARCH DESIGN AND METHODS We performed serial cross-sectional analyses of 4,069 adults aged ≥20 years with diabetes who participated in the 2005–2018 National Health and Nutrition Examination Survey (NHANES). RESULTS Overall, the proportion of U.S. adults with diabetes receiving ADA guideline-recommended care meeting all five criteria by self-report in the past year (having a primary doctor for diabetes and one or more visits for this doctor, HbA1c testing, an eye examination, a foot examination, and cholesterol testing) increased from 25.0% in 2005–2006 to 34.1% in 2017–2018 (P-trend = 0.004). For participants with age ≥65 years, it increased from 29.3% in 2005–2006 to 44.2% in 2017–2018 (P-trend = 0.001), whereas for participants with age 40–64 and 20–39 years, it did not change significantly during the same time period: 25.2% to 25.8% (P-trend = 0.457) and 9.9% to 26.0% (P-trend = 0.401), respectively. Those who were not receiving ADA guideline-recommended care were more likely to be younger, of lower socioeconomic status, uninsured, newly diagnosed with diabetes, not on diabetes medication, and free of hypercholesterolemia. CONCLUSIONS Receipt of ADA guideline-recommended care increased only among adults with diabetes aged ≥65 years in the past decade. In 2017–2018, only one of three U.S. adults with diabetes reported receiving ADA guideline-recommended care, with even a lower receipt of care among those

Rationale & Objective Obesity has been related to risk for chronic kidney disease. However, the associations of different measures of midlife obesity with long-term kidney function trajectories and whether they differ by sex and race are unknown. Study Design Observational study. Setting & Participants 13,496 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Predictors Midlife obesity status as measured by body mass index (BMI), waist-to-hip ratio, and predicted percent fat at baseline. Outcomes Estimated glomerular filtration rate (eGFR) calculated using serum creatinine level measured at 5 study visits, and incident kidney failure with replacement therapy (KFRT). Analytical Approach Mixed models with random intercepts and random slopes for eGFR. Cox proportional hazards models for KFRT. Results Baseline mean age was 54 years, median eGFR was 103 mL/min/1.73 m2, and median BMI was 27 kg/m2. Over 30 years of follow-up, midlife obesity measures were associated with eGFR decline in White and Black women but not consistently in men. Adjusted for age, center, smoking, and coronary heart disease, the differences in eGFR slope per 1-SD higher BMI, waist-to-hip ratio, and predicted percent fat were 0.09 (95% CI, −0.18 to 0.36), −0.25 (95% CI, −0.50 to 0.01), and −0.14 (95% CI, −0.41 to 0.13) mL/min/1.73 m2 per decade for White men; −0.91 (95% CI, −1.15 to −0.67), −0.82 (95% CI, −1.06 to −0.58), and −1.02 (95% CI, −1.26 to −0.78) mL/min/1.73 m2 per decade for White women; −0.70 (95% CI, −1.54 to 0.14), −1.60 (95% CI, −2.42 to −0.78), and −1.24 (95% CI, −2.08 to −0.40) mL/min/1.73 m2 per decade for Black men; and −1.24 (95% CI, −2.08 to −0.40), −1.50 (95% CI, −2.05 to −0.95), and −1.43 (95% CI, −2.00 to −0.86) mL/min/1.73 m2 per decade for Black women. Obesity indicators were independently associated with risk for KFRT for all sex-race groups except White men. Limitations Loss to follow-up during 3 decades of follow-up with 5 eGFR assessments. Conclusions Obesity status is a risk factor for future decline in kidney function and development of KFRT in Black and White women, with less consistent associations among men.

Background and objectives Patients with sickle cell disease-associated kidney failure have high mortality, which might be lowered by kidney transplantation. However, because they show higher post-transplant mortality compared with patients with other kidney failure etiologies, kidney transplantation remains controversial in this population, potentially limiting their chance of receiving transplantation. We aimed to quantify the decrease in mortality associated with transplantation in this population and determine the chance of receiving transplantation with sickle cell disease as the cause of kidney failure as compared with other etiologies of kidney failure. Design, setting, participants, & measurements Using a national registry, we studied all adults with kidney failure who began maintenance dialysis or were added to the kidney transplant waiting list in 1998-2017. To quantify the decrease in mortality associated with transplantation, we measured the absolute risk difference and hazard ratio for mortality in matched pairs of transplant recipients versus waitlisted candidates in the sickle cell and control groups. To compare the chance of receiving transplantation, we estimated hazard ratios for receiving transplantation in the sickle cell and control groups, treating death as a competing risk. Results Compared with their matched waitlisted candidates, 189 transplant recipients with sickle cell disease and 220,251 control recipients showed significantly lower mortality. The absolute risk difference at 10 years post-transplant was 20.3 (98.75% confidence interval, 0.9 to 39.8) and 19.8 (98.75% confidence interval, 19.2 to 20.4) percentage points in the sickle cell and control groups, respectively. The hazard ratio was also similar in the sickle cell (0.57; 95% confidence interval, 0.36 to 0.91) and control (0.54; 95% confidence interval, 0.53 to 0.55) groups (interaction P=0.8). Nonetheless, the sickle cell group was less likely to receive transplantation than the controls (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.61 to 0.87). Similar disparities were found among waitlisted candidates (subdistribution hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72). Conclusions Patients with sickle cell disease-associated kidney failure exhibited similar decreases in mortality associated with kidney transplantation as compared with those with other kidney failure etiologies. Nonetheless, the sickle cell population was less likely to receive transplantation, even after waitlist registration.

Introduction Low serum 25-hydroxyvitamin D levels have been identified as a risk factor for acute kidney injury (AKI) among critically ill patients. Whether low 25-hydroxyvitamin D levels are associated with long-term incidence of hospitalization with AKI in the general population is unknown. Methods Among 12,380 participants (mean age, 57 years; 24% black) in the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 2 (1990–1992), we explored the association of serum 25-hydroxyvitamin D with incident hospitalization with AKI. Multivariable Cox models were used to estimate hazard ratios (HRs). We also examined the association of serum fibroblast growth factor 23 (FGF23) with AKI. Results During a median follow-up of 24.3 years, 2145 participants had incident hospitalization with AKI (crude incidence rate: 8.3; 95% confidence interval [CI]: 8.0–8.7, per 1,000 person-years). In multivariable Cox models (including adjustment for kidney function), lower 25-hydroxyvitamin D and higher FGF23 levels were each significantly associated with an increased risk of AKI (HR: 1.35; 95% CI: 1.17–1.54, for lowest vs. highest quartile for 25-hydroxyvitamin D, and HR: 1.19; 95% CI: 1.05–1.36, for highest vs. lowest quartile for FGF23). The association was consistent across demographic and clinical subgroups, regardless of whether AKI was the primary diagnosis for hospitalization, and when adjusting for incident chronic kidney disease (CKD) or cardiovascular disease (CVD) as a time-varying covariate. Conclusion Among middle- to older-age adults in the community, low 25-hydroxyvitamin D and high FGF23 levels were independently associated with an increased risk of AKI. Future studies should explore underlying mechanisms linking these bone mineral metabolism markers with kidney injury., Graphical abstract

RATIONALE & OBJECTIVE: Current dietary guidelines recommend that chronic kidney disease (CKD) patients restrict individual nutrients, such as sodium, potassium, phosphorus and protein. This approach can be difficult for patients to implement and ignores important nutrient interactions. Dietary patterns are an alternative method to intervene on diet. Our objective was to define the associations of four healthy dietary patterns with risk of CKD progression and all-cause mortality among people with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,403 participants aged 21–74 years with an estimated glomerular filtration rate (eGFR) of 20–70 mL/min/1.73 m(2) and dietary data in the Chronic Renal Insufficiency Cohort (CRIC) study. EXPOSURES: Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean diet (aMed), and Dietary Approaches to Stop Hypertension (DASH) diet scores were calculated from food frequency questionnaires. OUTCOMES: 1) CKD progression defined as ≥50% eGFR decline, kidney transplantation, or dialysis and 2) all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards regression models adjusted for demographic, lifestyle, and clinical covariates to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: There were 855 cases of CKD progression and 773 deaths over a maximum of 14 years. Compared with participants with the lowest adherence, the most highly adherent tertile of AHEI-2010, aMed, and DASH had lower adjusted risk of CKD progression with the strongest results for aMed (HR: 0.75, 95% CI: 0.62–0.90). Compared with participants with the lowest adherence, the highest adherence tertiles for all scores had lower adjusted risk of all-cause mortality for each index (24–31% lower risk). LIMITATIONS: Self-reported dietary intake. CONCLUSIONS: Greater adherence to several healthy dietary patterns is associated with a lower risk of CKD progression and all-cause mortality among people with CKD. Guidance to adopt healthy dietary patterns can be considered as a strategy for managing CKD. INDEX WORDS: dietary patterns, nutrition, kidney disease, renal, mortality

BACKGROUND AND OBJECTIVES: Genetic variants in NAT8, a liver- and kidney-specific acetyltransferase encoding gene, have been associated with eGFR and CKD in European populations. Higher circulating levels of two NAT8-associated metabolites, N-δ-acetylornithine and N-acetyl-1-methylhistidine, have been linked to lower eGFR and higher risk of incident CKD in the Black population. We aimed to expand upon prior studies to investigate associations between rs13538, a missense variant in NAT8, N-acetylated amino acids, and kidney failure in multiple, well-characterized cohorts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted analyses among participants with genetic and/or serum metabolomic data in the African American Study of Kidney Disease and Hypertension (AASK; n=962), the Atherosclerosis Risk in Communities (ARIC) study (n=1050), and BioMe, an electronic health record–linked biorepository (n=680). Separately, we evaluated associations between rs13538, urinary N-acetylated amino acids, and kidney failure in participants in the German CKD (GCKD) study (n=1624). RESULTS: Of 31 N-acetylated amino acids evaluated, the circulating and urinary levels of 14 were associated with rs13538 (P

Background Patients with chronic kidney disease (CKD) face risks of not only end-stage kidney disease (ESKD), cardiovascular disease (CVD) and death, but also decline in kidney function, quality of life (QOL) and mental and physical well-being. This study describes the multidimensional trajectories of CKD using clinical events, kidney function and patient-reported outcome measures (PROMs). We hypothesized that more advanced CKD stages would associate with more rapid decline in each outcome. Methods Among 3939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, we evaluated multidimensional disease trajectories by G- and A-stages of enrollment estimated glomerular filtration rate (eGFR) and albuminuria, respectively. These trajectories included clinical events (ESKD, CVD, heart failure and death), eGFR decline and PROMs [kidney disease QOL (KDQOL) burden, effects and symptoms questionnaires, as well as the 12-item short form mental and physical component summaries]. We also evaluated a group-based multitrajectory model to group participants on the basis of longitudinal PROMs and compared group assignments by enrollment G- and A-stage. Results The mean participant age was 58 years, 45% were women, mean baseline eGFR was 44 mL/min/1.73 m2 and median urine albumin:creatinine ratio was 52 mg/g. The incidence of all clinical events was greater and eGFR decline was faster with more advanced G- and A-stages. While baseline KDQOL and physical component measures were lower with more advanced G- and A-stage of CKD, changes in PROMs were inconsistently related to the baseline CKD stage. Groups formed on PROM trajectories were fairly distinct from existing CKD staging (observed agreement 60.6%) and were associated with the risk of ESKD, CVD, heart failure and death. Conclusions More advanced baseline CKD stage was associated with a higher risk of clinical events and faster eGFR decline, and was only weakly related to changes in patient-reported metrics over time.

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.

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

Background Cardiac markers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B natriuretic peptide (NTproBNP) are predictors of developing acute kidney injury (AKI) during hospitalization for surgery or revascularization. However, their associations with the long-term risk of AKI in the general population are uncharacterized. Methods We conducted a prospective cohort study in 10 669 participants of the Atherosclerosis Risk in Communities Study (visit 4, 1996–1998, mean age, 63 years, 56% female, 22% black race) to examine the association of plasma concentrations of hs-cTnT and NTproBNP with the incident hospitalization with AKI. We used multivariable Cox regression analysis to estimate hazard ratios (HRs). Results During follow-up, 1907 participants had an incident hospitalization with AKI. Participants with higher concentrations of hs-cTnT had a higher risk of hospitalization with AKI in a graded fashion (adjusted HR, 1.88 [95%CI , 1.59–2.21] for ≥14 ng/L, 1.36 [1.18–1.57] for 9–13 ng/L, and 1.16 [1.03–1.30] for 5-8 ng/L compared to Conclusions In middle-aged to older black and white adults in the community, higher concentrations of hs-cTnT and NTproBNP were robustly associated with an increased risk of hospitalization with AKI. These results suggest the usefulness of hs-cTnT and NT-proBNP to identify people at risk of AKI in the general population.

Introduction South Africa has the highest prevalence of HIV in the world. The epidemiology of kidney disease among people with HIV infections is well-described in the United States. However, there are limited data coming from South Africa, particularly that involve kidney biopsies. The purpose of this study was to determine what, if any, patient factors are predictive of HIV-associated nephropathy (HIVAN) on kidney biopsy in a South African kidney biopsy cohort. Methods This study prospectively collected data of all patients infected with HIV referred to the Groote Schuur Hospital (GSH) renal unit for a kidney biopsy from 2002 to 2018. Results There were 419 patients included in the study. Mean age was 36.5 years (SD, 9.4); 219 (52.3%) were women; and all were black. Seventy-nine patients (18.9%) were on dialysis at the time of biopsy; the mean estimated glomerular filtration rate among the remainder was 41.4 ml/min per 1.73 m2 (SD, 39.2). Only 163 patients (47.1%) were known to be taking antiretroviral therapy (ART) at the time of biopsy. There were 246 (58.7%) cases of HIVAN detected, and they were comparable on age, sex, kidney function, and kidney size to those with kidney disease of other causes but were less likely to be taking ART (P < 0.001). Biopsy confirmed HIVAN was associated with mortality (adjusted hazard ratio, 1.77; 95% confidence interval [CI]: 1.07–2.91; P = 0.025), and the use of ART at biopsy was protective (adjusted hazard ratio, 0.52; 95% CI, 0.32–0.84, P = 0.008). The proportion of HIVAN on biopsy decreased and the proportion taking ART increased from 2002 to 2018 (P for trend for both < 0.001). Conclusion In summary, HIVAN was the most common etiology of kidney disease in this biopsy cohort from South Africa; however, the proportion with biopsy-proven HIVAN declined over time, perhaps in the setting of greater ART availability., Graphical abstract

Objective To evaluate whether the incidence of infectious diseases increases the long-term risk for incident end-stage renal disease (ESRD) in the general population. Patients and Methods In 10,290 participants of the Atherosclerosis Risk in Communities Study who attended visit 4 (1996-1998), we evaluated the association of incident hospitalization with major infections (pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis) with subsequent risk for ESRD through September 30, 2015. Hospitalization with major infection was entered into multivariable Cox models as a time-varying exposure to estimate the hazard ratios. Results Mean age was 63 years, and of 10,290 individuals, 56% (n=5781) were women, 22% (n=2252) were black, and 7% (n=666) had an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. During a median follow-up of 17.4 years, there were 2642 incident hospitalizations with major infection and 281 cases of ESRD (132 cases after hospitalization with major infection). The risk for ESRD was higher following major infection compared with while free of major infection (crude incidence rate, 10.9 vs 1.0 per 1000 person-years). In multivariable time-varying Cox analysis, hospitalization with major infection was associated with a 3.3-fold increased risk for ESRD (hazard ratio, 3.34; 95% CI, 2.56-4.37). The association was similar across pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis, and remained significant across subgroups of age, sex, race, diabetes, history of cardiovascular disease, and chronic kidney disease. Conclusion Hospitalization with major infection was independently and robustly associated with subsequent risk for ESRD. Whether preventive approaches against infection have beneficial effects on kidney outcomes may deserve future investigations.

Blood pressure and kidney function have a bidirectional relation. Hypertension has long been considered as a risk factor for kidney function decline. However, whether intensive blood pressure control could promote kidney health has been uncertain. The kidney is known to have a major role in affecting blood pressure through sodium extraction and regulating electrolyte balance. This bidirectional relation makes causal inference between these two traits difficult. Therefore, to examine the causal relations between these two traits, we performed two-sample Mendelian randomization analyses using summary statistics of large-scale genome-wide association studies. We selected genetic instruments more likely to be specific for kidney function using meta-analyses of complementary kidney function biomarkers (glomerular filtration rate estimated from serum creatinine [eGFRcr], and blood urea nitrogen from the CKDGen Consortium). Systolic and diastolic blood pressure summary statistics were from the International Consortium for Blood Pressure and UK Biobank. Significant evidence supported the causal effects of higher kidney function on lower blood pressure. Based on the mode-based Mendelian randomization method, the effect estimates for one standard deviation (SD) higher in log-transformed eGFRcr was -0.17 SD unit (95 % confidence interval: -0.09 to -0.24) in systolic blood pressure and -0.15 SD unit (95% confidence interval: -0.07 to -0.22) in diastolic blood pressure. In contrast, the causal effects of blood pressure on kidney function were not statistically significant. Thus, our results support causal effects of higher kidney function on lower blood pressure and suggest preventing kidney function decline can reduce the public health burden of hypertension.

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

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

Background Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium–PAD relationship is independent of or modified by kidney function. Methods A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990–92) was studied. We investigated the association of serum magnesium and other bone–mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression. Results Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40–2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR 65 pg/mL was significantly related to PAD only in those with eGFR Conclusions Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population.

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas.

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently willing to consider a 30% to 40% glomerular filtration rate (GFR) decline as a surrogate end point for kidney failure for clinical trials of kidney disease progression under appropriate conditions. However, these end points may not be practical for early stages of kidney disease. In March 2018, the National Kidney Foundation sponsored a scientific workshop in collaboration with the FDA and EMA to evaluate changes in albuminuria or GFR as candidate surrogate end points. Three parallel efforts were presented: meta-analyses of observational studies (cohorts), meta-analyses of clinical trials, and simulations of trial design. In cohorts, after accounting for measurement error, relationships between change in urinary albumin-creatinine ratio (UACR) or estimated GFR (eGFR) slope and the clinical outcome of kidney disease progression were strong and consistent. In trials, the posterior median R2 of treatment effects on the candidate surrogates with the clinical outcome was 0.47 (95% Bayesian credible interval [BCI], 0.02-0.96) for early change in UACR and 0.72 (95% BCI, 0.05-0.99) when restricted to baseline UACR > 30 mg/g, and 0.97 (95% BCI, 0.78-1.00) for total eGFR slope at 3 years and 0.96 (95% BCI, 0.63-1.00) for chronic eGFR slope (ie, the slope excluding the first 3 months from baseline, when there might be acute changes in eGFR). The magnitude of the relationships of changes in the candidate surrogates with risk for clinical outcome was consistent across cohorts and trials: a UACR reduction of 30% or eGFR slope reduction by 0.5 to 1.0 mL/min/1.73 m2 per year were associated with an HR of ∼0.7 for the clinical outcome in cohorts and trials. In simulations, using GFR slope as an end point substantially reduced the required sample size and duration of follow-up compared with the clinical end point when baseline eGFR was high, treatment effects were uniform, and there was no acute effect of the treatment. We conclude that both early change in albuminuria and GFR slope fulfill criteria for surrogacy for use as end points in clinical trials for chronic kidney disease progression under certain conditions, with stronger support for change in GFR than albuminuria. Implementation requires understanding conditions under which each surrogate is likely to perform well and restricting its use to those settings.

BACKGROUND: Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD. METHODS: We quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years. We performed separate analyses for these proteins in a subset of 4378 participants (visit 5), who were followed at a later time point, for a median of 4.4 years. For validation, we evaluated proteins with significant associations (false discovery rate

Introduction: Clinical trials have shown cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, adoption of SGLT2i in clinical practice has been slow, perhaps in part due to safety concerns. We aimed to assess the association between SGLT2i and risk of all-cause hospitalization as the totality of severe adverse events and benefits, comparing to risks associated with DPP4 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1RA). Methods: We identified patients with type 2 diabetes who initiated SGLT2i (n=2492), DPP4i (n=4762) or GLP1RA (n=1982) between 2015 and 2018 in Geisinger and performed 1:1 propensity score matching on SGLT2i (n=2171) vs. DPP4i (n=2171) and SGLT2i (n=1605) vs. GLP1RA (n=1605). We examined all-cause hospitalization as the main outcome. We also considered two positive controls (major adverse cardiovascular event [MACE] defined as cardiovascular death, myocardial infarction, and stroke; and heart failure [HF] hospitalization), and a negative control (hospitalization due to major bleeding). Results: Mean (SD) age was 58 (13) and 56 (13) years and 46% and 53% were women in the SGLT2i-DPP4i and SGLT2i-GLP1RA matched sample, respectively. During a median follow-up of 14 months, SGLT2i had similar risk of all-cause hospitalization compared with DPP4i (HR [95% CI] 0.85 [0.72-1.01]) or GLP1RA (HR 0.93 [0.77-1.13]). SGLT2i was associated with significantly lower risk of MACE and HF hospitalization compared with DPP4i (MACE: HR 0.70 [0.37, 0.98]; HF: HR 0.61 [0.38, 0.97]) but not with GLP1RA (MACE: HR 1.02 [0.50, 2.08]; HF: HR 0.72 [0.42, 1.23]). Risk of hospitalization due to bleeding was similar between SGLT2i vs. DPP4i or SGLT2i vs. GLP1RA. Conclusions: In this real-world comparison of antidiabetes medications, SGLT2i may be as safe as DPP4i with significant cardiac benefits and have comparable risk-benefit profiles compared with GLP1RA. These results further encourage SGLT2i use in routine diabetes care, particularly among patients at high risk of MACE. Disclosure B. Lyu: None. M. Grams: None. A. R. Chang: Advisory Panel; Self; Reata Pharmaceuticals, Inc., Relypsa Inc., Research Support; Self; Novo Nordisk Inc. L. A. Inker: None. J. Coresh: Consultant; Self; Healthy. io, Research Support; Self; National Institutes of Health, National Kidney Foundation. J. Shin: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K01DK121825)

Background GSTM1 encodes glutathione S-transferase μ-1 (GSTM1), which belongs to a superfamily of phase 2 antioxidant enzymes. The highly prevalent GSTM1 deletion variant is associated with kidney disease progression in human cohorts: the African American Study of Kidney Disease and Hypertension and the Atherosclerosis Risk in Communities (ARIC) Study. Methods We generated a Gstm1 knockout mouse line to study its role in a CKD model (involving subtotal nephrectomy) and a hypertension model (induced by angiotensin II). We examined the effect of intake of cruciferous vegetables and GSTM1 genotypes on kidney disease in mice as well as in human ARIC study participants. We also examined the importance of superoxide in the mediating pathways and of hematopoietic GSTM1 on renal inflammation. Results Gstm1 knockout mice displayed increased oxidative stress, kidney injury, and inflammation in both models. The central mechanism for kidney injury is likely mediated by oxidative stress, because treatment with Tempol, an superoxide dismutase mimetic, rescued kidney injury in knockout mice without lowering BP. Bone marrow crosstransplantation revealed that Gstm1 deletion in the parenchyma, and not in bone marrow-derived cells, drives renal inflammation. Furthermore, supplementation with cruciferous broccoli powder rich in the precursor to antioxidant-activating sulforaphane significantly ameliorated kidney injury in Gstm1 knockout, but not wild-type mice. Similarly, among humans (ARIC study participants), high consumption of cruciferous vegetables was associated with fewer kidney failure events compared with low consumption, but this association was observed primarily in participants homozygous for the GSTM1 deletion variant. Conclusions Our data support a role for the GSTM1 enzyme in the modulation of oxidative stress, inflammation, and protective metabolites in CKD.

Rationale & Objective The relationship between hypertension, antihypertension medication use, and change in glomerular filtration rate (GFR) over time among individuals with preserved GFR requires investigation. Study Design Observational study. Setting & Participants 14,854 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Predictors Baseline hypertension status (1987-1989) was categorized according to the 2017 American College of Cardiology/American Heart Association Clinical Practice Guideline as normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication. Outcomes Slope of estimated GFR (eGFR) at 5 study visits over 30 years. Analytical Approach Mixed models with random intercepts and random slopes were fit to evaluate the association between baseline hypertension status and slope of eGFR. Results At baseline, 13.2%, 7.3%, and 19.4% of whites and 15.8%, 14.9%, and 39.9% of African Americans had stage 1 hypertension, stage 2 hypertension without medication, and stage 2 hypertension with medication. Compared with those with normal blood pressure, the annual eGFR decline was greater in people with higher blood pressure (whites: elevated blood pressure, −0.11mL/min/1.73m2; stage 1 hypertension, −0.15mL/min/1.73m2; stage 2 hypertension without medication, −0.36mL/min/1.73m2; stage 2 hypertension with medication, −0.17mL/min/1.73m2; African Americans: elevated blood pressure, −0.21mL/min/1.73m2; stage 1 hypertension, −0.16mL/min/1.73m2; stage 2 hypertension without medication, −0.50mL/min/1.73m2; stage 2 hypertension with medication, −0.16mL/min/1.73m2). The 30-year predicted probabilities of developing chronic kidney disease stage G3a+with normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication among whites were 54.4%, 61.6%, 64.7%, 78.1%, and 70.9%, respectively, and 55.4%, 62.8%, 60.9%, 76.1%, and 66.6% among African Americans. Limitations Slope estimated using a maximum of 5 eGFR assessments; differential loss to follow-up. Conclusions Compared to normotension, baseline hypertension status was associated with faster kidney function decline over 30-year follow-up in a general population cohort. This difference was attenuated among people using antihypertensive medications.

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.

BACKGROUND AND OBJECTIVES: The association between plant-based diets, incident CKD, and kidney function decline has not been examined in the general population. We prospectively investigated this relationship in a population-based study, and evaluated if risk varied by different types of plant-based diets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Analyses were conducted in a sample of 14,686 middle-aged adults enrolled in the Atherosclerosis Risk in Communities study. Diets were characterized using four plant-based diet indices. In the overall plant-based diet index, all plant foods were positively scored; in the healthy plant-based diet index, only healthful plant foods were positively scored; in the provegetarian diet, selected plant foods were positively scored. In the less healthy plant-based diet index, only less healthful plant foods were positively scored. All indices negatively scored animal foods. We used Cox proportional hazards models to study the association with incident CKD and linear mixed models to examine decline in eGFR, adjusting for confounders. RESULTS: During a median follow-up of 24 years, 4343 incident CKD cases occurred. Higher adherence to a healthy plant-based diet (HR comparing quintile 5 versus quintile 1 [HR(Q5 versus Q1)], 0.86; 95% confidence interval [95% CI], 0.78 to 0.96; P for trend =0.001) and a provegetarian diet (HR(Q5 versus Q1), 0.90; 95% CI, 0.82 to 0.99; P for trend =0.03) were associated with a lower risk of CKD, whereas higher adherence to a less healthy plant-based diet (HR(Q5 versus Q1), 1.11; 95% CI, 1.01 to 1.21; P for trend =0.04) was associated with an elevated risk. Higher adherence to an overall plant-based diet and a healthy plant-based diet was associated with slower eGFR decline. The proportion of CKD attributable to lower adherence to healthy plant-based diets was 4.1% (95% CI, 0.6% to 8.3%). CONCLUSIONS: Higher adherence to healthy plant-based diets and a vegetarian diet was associated with favorable kidney disease outcomes.

BackgroundThere is strong evidence of an association between socioeconomic status (SES) and end-stage renal disease (ESRD). However, the association of SES with the risk of chronic kidney disease (CKD) and the rate of change in kidney function is unclear.MethodsA cohort of 14 086 participants with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at baseline in the Atherosclerosis Risk in Communities study (1987–89) were studied. The association of annual household income, educational attainment and neighborhood deprivation with incident ESRD, incident CKD and change in eGFR using four measurements over ∼23 years was assessed.ResultsA total of 432 participants developed ESRD and 3510 developed CKD over a median follow-up time of ∼23 years. After adjustment for demographics and baseline eGFR, the hazard ratio (HR) for incident ESRD compared with the high-income group was 1.56 [95% confidence interval (CI) 1.22–1.99 in the medium-income group and 2.30 (95% CI 1.75–3.02) in the low-income group (P-trend ConclusionsSES (annual household income, educational attainment or neighborhood deprivation) was associated not only with ESRD risk but also with eGFR decline, although the association with CKD appeared weaker.

Introduction: In individuals with chronic kidney disease (CKD), healthy dietary patterns are inversely associated with CKD progression. Metabolomics, an approach which measures many small molecules in biofluids, can identify biomarkers of healthy dietary patterns and elucidate metabolic pathways underlying diet-disease associations. Hypothesis: We hypothesized that adherence to 4 healthy dietary patterns would be associated with a set of known metabolites in CKD patients. Methods: We examined associations between 634 plasma metabolites assessed using the Broad platform at year 1 and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and alternate Mediterranean diet (aMED), and their food components in 1,117 participants in the CRIC Study. Usual dietary intakes were assessed using a food frequency questionnaire at baseline and year 2. We conducted multivariable linear regression models to study associations between diet scores and individual plasma metabolites, adjusting for sociodemographic characteristics, health behaviors, and clinical factors. Results: After Bonferroni correction, we identified a total of 362 diet-metabolite associations (HEI=78; AHEI=127; DASH=97; aMED=60), and 101 metabolites were associated with more than 1 dietary pattern. The most common metabolite categories were triacylglycerols and diacylglycerols. Most lipids were negatively associated with healthy dietary patterns, except for cholesterols esters and triacylglycerols with ≥7 double bonds. Triacylglycerols with high number of double bonds were positively associated with healthy fat intake (e.g., higher monounsaturated and polyunsaturated fatty acid, omega-3 fatty acid, fish) within HEI, AHEI, and aMED ( Table ). Conclusions: We identified many metabolites associated with healthy dietary patterns, indicative of food consumption. If replicated, they may be considered biomarkers of healthy dietary patterns in CKD patients.

Background: Few studies have examined the natural history of prediabetes, specifically, regression to normoglycemia as well as progression to clinical diabetes. Furthermore, there are several definitions of prediabetes in current use. Methods: We conducted a prospective cohort analysis of 8214 participants without diabetes who attended visit 2 (1990-1992) and visit 4 (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study. We used multinomial logistic regression to compare cumulative incidence of diabetes and regression to normoglycemia among persons meeting different definitions of prediabetes (American Diabetes Association criteria): fasting glucose (FG) 100-125 mg/dL; A1C 5.7-6.4%; or elevations in both tests (single-sample confirmatory). Incident diabetes was defined as a self-reported diagnosis, medication use, or both FG ≥ 126 mg/dL and A1C ≥ 6.5%; normoglycemia was defined as both FG < 100mg/dL and A1C < 5.7% and no diabetes diagnosis or medication use. Analyses were adjusted for age, sex, and race-center. Results: The prevalence of prediabetes at visit 2 (age range, 46-69; 57% female; 17% black) was 37.6% (n=3089) based on FG criteria, 17.4% (n=1427) based on A1C criteria, and 10.6% (N=867) by both FG and A1C criteria. The 6-year cumulative incidence of diabetes was 7.2% in participants with FG-defined prediabetes, 17.1% in participants with A1C-defined prediabetes, and 22.4% in participants meeting both criteria. Among participants with prediabetes by FG criteria, regression to normoglycemia was 1.9 times as likely as progression to diabetes (14.0% vs. 7.2%). However, when prediabetes was defined by A1C and by confirmatory criteria, progression to diabetes was 1.5 times and 3.5 times more likely than regression to normoglycemia, respectively. Conclusions: Risks of progression to diabetes and regression to normoglycemia differed by prediabetes definition. Prediabetes identified by A1C criteria and single-sample confirmatory criteria identified people at highest risk for diabetes.

Introduction: Statin-induced rhabdomyolysis is a rare, but potentially life-threatening condition. It is unknown whether specific statins carry a greater risk of rhabdomyolysis and whether the risk differs between patients with and without chronic kidney disease (CKD). The objective of this study was to investigate the association of rosuvastatin use vs. atorvastatin use with the risk of rhabdomyolysis across CKD status. Hypothesis: Rosuvastatin use is associated with a higher risk of rhabdomyolysis as compared to atorvastatin use and the risk is greater among those with CKD than those without CKD. Methods: We identified adult patients who initiated rosuvastatin or atorvastatin between January 1, 2004 and December 31, 2018 and were free of end-stage kidney disease at the time of prescription in the Geisinger Health System. The association between rosuvastatin use and rhabdomyolysis was assessed using Cox proportional hazards regression models with an interaction between rosuvastatin use and CKD (i.e., estimated glomerular filtration rate 2 ) in an inverse probability of treatment weighted (IPTW) sample. Results: Of 8,748 rosuvastatin users (mean [SD] age, 59.7 [12.6] years; 49.8% female; 11.8% CKD) and 31,770 atorvastatin users (mean [SD] age, 59.1 [12.6] years; 48.2% female; 11.9% CKD), 0.7% and 0.4% patients developed rhabdomyolysis, respectively, during a median follow-up of 5.1 years. Rosuvastatin use was associated with a higher risk of rhabdomyolysis in patients with CKD (hazard ratio [HR], 3.29; 95% CI, 1.53-7.09), but not in those without CKD (HR, 1.29; 95% CI, 0.82-2.03; p-interaction=0.04). A higher risk of rhabdomyolysis associated with rosuvastatin use in lower eGFR was also observed in the analysis with continuous eGFR ( Figure ). Conclusions: The findings suggest that rosuvastatin use in patients with CKD may be associated with excess risk of rhabdomyolysis as compared to atorvastatin.

OBJECTIVE The 2021 American Diabetes Association (ADA) guidelines recommend different A1C targets in older adults that are based on comorbid health status. We assessed risk of mortality and hospitalizations in older adults with diabetes across glycemic control (A1C RESEARCH DESIGN AND METHODS Prospective cohort analysis of older adults aged 66–90 years with diagnosed diabetes in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS Of the 1,841 participants (56% women, 29% Black), 32% were classified as healthy, 42% as complex/intermediate, and 27% as very complex/poor health. Over a median 6-year follow-up, there were 409 (22%) deaths and 4,130 hospitalizations (median [25th–75th percentile] 1 per person [0–3]). In the very complex/poor category, individuals with A1C ≥8% (vs. CONCLUSIONS There were substantial differences in mortality and hospitalizations across ADA health status categories, but older adults with A1C

Background and Aims Many adverse drug events are preventable, such as those potentially resulting from the prescription of nephrotoxic drugs to persons with chronic kidney disease (CKD). We here quantify the extent of contemporary nephrotoxic medication use in patients with CKD. Method In two observational cohorts of Swedish (Stockholm CREAtinine Measurements [SCREAM] project, Stockholm, Sweden) and U.S. (Geisinger Health System, Pennsylvania) adults with confirmed CKD stages G3-G5 undergoing routine care during 2016-2018, we explored the prescription (in U.S.) and dispensation (in Sweden) of 115 different ambulatory drugs with proven or purported nephrotoxicity during the 12 months following study inclusion. We evaluated the proportion of participants receiving nephrotoxic drugs, ranked main contributors and identified clinical predictors. Results In the Swedish cohort, there were 57880 patients (54.6% women) with median age of 80.00 (inter-quartile range [IQR]: 73.0-86.0) years and eGFR 48.9 ([IQR]: 39.9-55.0) mL/min/1.73 m2. In the U.S. cohort, there were 16255 patients (59% women) with median age of 76 years and eGFR 44 mL/min/1.73 m2. During observation, 20% (Sweden) and 17% (U.S.) of patients received at least one nephrotoxic drug. The top 3 potentially inappropriate nephrotoxic drugs identified were NSAIDs (9% and 11% of participants in U.S. and Sweden received it), antivirals (2.0% and 2.5%) and immunosuppressants (1.5% and 2.7%). Bisphosphonate use was common in Sweden (3.3% of participants), but not in U.S. (0.5%). Conversely, fenofibrates were common in U.S. (3.6%), but not in Sweden (0.13%). In adjusted analyses, patients with young age (0.05 for all). Notably, patients aware of their CKD (identified either by issued diagnosis or recent visit to a nephrologist), were at lower risk of nephrotoxic drug use (OR 0.87, 95% CI 0.82-0.92 in Sweden and 0.89, 95% CI 0.81-1.01 in U.S.). Conclusion In two geographically distinct health systems, one in five patients with CKD received potentially inappropriate nephrotoxic medications, mainly NSAIDs. Strategies to increase CKD awareness and physician’s knowledge of drug nephrotoxicity may reduce inappropriate ambulatory prescriptions and prevent iatrogenic kidney injury.

OBJECTIVES To determine whether lower serum albumin in community-dwelling, older adults is associated with increased risk of hospitalization and death independent of pre-existing disease. DESIGN Prospective cohort study of participants in the fifth visit of the Atherosclerosis Risk in Communities (ARIC) study. Baseline data were collected from 2011 to 2013. Follow-up was available to December 31, 2017. Replication was performed in Geisinger, a health system in rural Pennsylvania. SETTING For ARIC, four US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota. PARTICIPANTS A total of 4947 community-dwelling men and women aged 66 to 90 years. EXPOSURE Serum albumin. MAIN OUTCOMES Incident all-cause hospitalization and death. RESULTS Among the 4947 participants, mean age was 75.5 years (SD: 5.12) and mean baseline serum albumin concentration was 4.05 g/dL (SD: 0.30). Over a median follow-up period of 4.42 years (interquartile interval: 4.16-5.05), 553 participants (11.2%) died and 2457 participants (49.7%) were hospitalized at least once. The total number of hospitalizations was 5725. In analyses adjusted for demographics and numerous clinical characteristics, including tobacco use, obesity, frailty, cardiovascular disease, kidney disease, diabetes C-reactive protein (CRP), cognitive status, alcohol use, medication use, respiratory disease, and systolic blood pressure, 1 g/dL lower baseline serum albumin concentration was associated with higher risk of both hospitalization (incidence rate ratio [IRR]: 1.58; 95% confidence interval [CI]: 1.36-1.82; p

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research., The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI.

Background and objectives Metabolomics facilitates the discovery of biomarkers and potential therapeutic targets for CKD progression. Design, setting, participants, & measurements We evaluated an untargeted metabolomics quantification of stored plasma samples from 645 Chronic Kidney Disease in Children (CKiD) participants. Metabolites were standardized and logarithmically transformed. Cox proportional hazards regression examined the association between 825 nondrug metabolites and progression to the composite outcome of KRT or 50% reduction of eGFR, adjusting for age, sex, race, body mass index, hypertension, glomerular versus nonglomerular diagnosis, proteinuria, and baseline eGFR. Stratified analyses were performed within subgroups of glomerular/nonglomerular diagnosis and baseline eGFR. Results Baseline characteristics were 391 (61%) male; median age 12 years; median eGFR 54 ml/min per 1.73 m2; 448 (69%) nonglomerular diagnosis. Over a median follow-up of 4.8 years, 209 (32%) participants developed the composite outcome. Unique association signals were identified in subgroups of baseline eGFR. Among participants with baseline eGFR ≥60 ml/min per 1.73 m2, two-fold higher levels of seven metabolites were significantly associated with higher hazards of KRT/halving of eGFR events: three involved in purine and pyrimidine metabolism (N6-carbamoylthreonyladenosine, hazard ratio, 16; 95% confidence interval, 4 to 60; 5,6-dihydrouridine, hazard ratio, 17; 95% confidence interval, 5 to 55; pseudouridine, hazard ratio, 39; 95% confidence interval, 8 to 200); two amino acids, C-glycosyltryptophan, hazard ratio, 24; 95% confidence interval 6 to 95 and lanthionine, hazard ratio, 3; 95% confidence interval, 2 to 5; the tricarboxylic acid cycle intermediate 2-methylcitrate/homocitrate, hazard ratio, 4; 95% confidence interval, 2 to 7; and gulonate, hazard ratio, 10; 95% confidence interval, 3 to 29. Among those with baseline eGFR Conclusions Untargeted plasma metabolomic profiling facilitated discovery of novel metabolite associations with CKD progression in children that were independent of established clinical predictors and highlight the role of select biologic pathways.

International audience; Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

Chronic kidney disease (CKD) causes substantial global morbidity and increases cardiovascular and all-cause mortality. Unlike other chronic diseases with established strategies for screening, there has been no consensus on whether health systems and governments should prioritize early identification and intervention for CKD. Guidelines on evaluating and managing early CKD are available but have not been universally adopted in the absence of incentives or quality measures for prioritizing CKD care. The burden of CKD falls disproportionately upon persons with lower socioeconomic status, who have a higher prevalence of CKD, limited access to treatment, and poorer outcomes. Therefore, identifying and treating CKD at the earliest stages is an equity imperative. In 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a controversies conference entitled "Early Identification and Intervention in CKD." Participants identified strategies for screening, risk stratification, and treatment for early CKD and the key health system and economic factors for implementing these processes. A consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately for high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.

OBJECTIVE: To quantify the risk of hyperkalemia and acute kidney injury (AKI) when spironolactone use is added on to loop diuretic use among patients with heart failure, and to evaluate whether the risk is modified by level of kidney function. METHODS: We identified 17,110 patients with heart failure treated with loop diuretics between January 1, 2004, and December 31, 2016 within the Geisinger Health System. We estimated the incidence of hyperkalemia and AKI associated with spironolactone initiation, and used target trial emulation methods to minimize confounding by indication. RESULTS: During a mean follow-up of 134 mo, 3229 of 17,110 patients (18.9%) initiated spironolactone. Incidence rates of hyperkalemia and AKI in patients using spironolactone with a loop diuretic were 2.9 and 10.1 events per 1000 person-months, respectively. In propensity scoreematched analyses, spironolactone initiation was associated with higher hyperkalemia and AKI risk compared with loop alone (hazard ratio, 1.69; 95% CI, 1.35 to 2.10; P

BACKGROUND: The four-variable kidney failure risk equation (KFRE) is a well-validated tool for patients with GFR

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead.OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging.DESIGN: Individual participant-based meta-analysis.SETTING: 12 research and 21 clinical cohorts.PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein.MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g).RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR.LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample.CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis.PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Genome-wide association studies (GWAS) have revealed numerous loci for kidney function (estimated glomerular filtration rate, eGFR). The relationship of polygenic predictors of eGFR, risk of incident adverse kidney outcomes, and the plasma proteome is not known. We developed a genome-wide polygenic risk score (PRS) using a weighted average of 1.2 million SNPs for eGFR using the LDpred algorithm, summary statistics generated by a European-ancestry (EA) meta-analysis of the CKDGen Consortium (N=558,423) and UK Biobank GWAS for eGFR (90% of the cohort; N=289,432), followed by best parameter selection using data from the remaining 10% of the UK Biobank (N=32,159). We then tested the association of the PRS among 8,886 EA participants in the Atherosclerosis Risk in Communities (ARIC) study (mean age: 54±6 years, 53% female) with incident chronic kidney disease (CKD), end stage kidney disease (ESKD), kidney failure (KF), and acute kidney injury (AKI). We also examined 4,877 plasma proteins measured at two time points (visit 3 (1993-95) and visit 5 (2011-13)) in relation to the PRS and compared associations between the proteome and eGFR itself. All models were adjusted for age, sex, center, and the first 10 principal components of ancestry. The developed PRS had an R2for eGFR of 0.07 in ARIC. Over 30 years of follow up, the number of incident CKD, ESKD, KF, and AKI were 2,959, 137, 470, and 1,723, respectively. The PRS showed significant associations with all outcomes: hazard ratios (95% CI) per 1 SD lower PRS were 1.33 (1.28, 1.39), 1.20 (1.00, 1.42), 1.17 (1.06, 1.28), and 1.07 (1.02, 1.12) for incident CKD, ESKD, KF, and AKI respectively. The PRS was significantly associated (Bonferroni threshold P−5) with 108 proteins at both time points. The strongest associations were with cystatin-C (a marker of kidney function used in clinical practice), collagen alpha-1 (XV) chain, and desmocollin-2. All significant correlations with the PRS were negative, except those of testican-2 and angiostatin. Correlations of proteins with eGFR were much stronger than those with the PRS. Overall, we demonstrated that the PRS for eGFR is now sufficiently strong to capture risk for a spectrum of incident kidney diseases as well as broadly influence the plasma proteome.

An estimated 8–16% of the world’s population has chronic kidney disease, defined by low glomerular filtration rate or albuminuria. Progression of chronic kidney disease is associated with adverse outcomes, including incident kidney failure with replacement therapy, accelerated cardiovascular disease, disability, and mortality. Therefore, slowing kidney function decline is paramount in the management of a patient with chronic kidney disease. Ascertaining the cause of kidney disease is an important first step and may compel specific therapies. Effective approaches that apply to the vast majority of patients with chronic kidney disease include the optimization of blood pressure and blockade of the renin-angiotensin aldosterone system, particularly if albuminuria is present. Recent studies suggest that sodium/glucose cotransporter 2 inhibitors are highly effective treatments in patients with diabetes and/or albuminuria. For patients with type 2 diabetes, glycemic control is important in preventing the development of microvascular complications, and glucagon-like peptide 1 receptor agonists may help reduce albuminuria levels. Other strategies include correction of metabolic acidosis, maintaining ideal body weight, following diets that are low in sodium and animal protein, and avoidance of potential nephrotoxins such as nonsteroidal anti-inflammatories, proton-pump inhibitors, and iodinated contrast.

Rationale & Objective Immune activation is fundamental to the pathogenesis of many kidney diseases. Innate immune molecules such as soluble urokinase-type plasminogen activator receptor (suPAR) have been linked to the incidence and progression of chronic kidney disease (CKD). Whether other biomarkers of immune activation are associated with incident kidney failure with replacement therapy (KFRT) in African Americans with nondiabetic kidney disease is unclear. Study Design Prospective cohort. Setting & Participants African American Study of Kidney Disease and Hypertension (AASK) participants with available baseline serum samples for biomarker measurement. Predictors Baseline serum levels of soluble tumor necrosis factor receptor 1 (sTNFR1), sTNFR2, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Outcomes Incident KFRT, all-cause mortality. Analytical Approach Cox proportional hazards models. Results Among 500 participants with available samples, mean glomerular filtration rate was 44.7 mL/min/1.73 m2, and median urinary protein-creatinine ratio was 0.09 g/g at baseline. Over a median follow up of 9.6 years, there were 161 (32%) KFRT and 113 (23%) death events. In models adjusted for demographic and clinical factors and baseline kidney function, each 2-fold higher baseline level of sTNFR1, sTNFR2, and TNF-α was associated with 3.66-fold (95% CI, 2.31-5.80), 2.29-fold (95% CI, 1.60-3.29), and 1.35-fold (95% CI, 1.07-1.71) greater risks of KFRT, respectively; in comparison, each doubling of baseline suPAR concentration was associated with 1.39-fold (95% CI, 1.04-1.86) greater risk of KFRT. sTNFR1, sTNFR2, and TNF-α were also significantly associated with death (up to 2.2-fold higher risks per 2-fold higher baseline levels; P ≤ 0.01). IFN-γ was not associated with either outcome. None of the biomarkers modified the association of APOL1 high-risk status (genetic risk factors for kidney disease among individuals of African ancestry) with KFRT (P > 0.05 for interaction). Limitations Limited generalizability to other ethnic groups or causes of CKD. Conclusions Among African Americans with CKD attributed to hypertension, baseline levels of sTNFR1, sTNFR2, and TNF-α but not IFN-γ were associated with KFRT and mortality.

Background and Aims Stopping mineralocorticoid receptor antagonists (MRAs) after an episode of hyperkalemia is common, particularly among patients with chronic kidney disease (CKD). This may involve therapeutic compromises, in that the cessation of MRAs deprives patients of their beneficial cardiovascular effects. The aim of this study is to determine the risks of adverse health outcomes in heart failure patients after an episode of hyperkalemia, comparing users of MRA who stop treatment to those who continue the drugs. Method Observational study from the Stockholm Creatinine Measurements (SCREAM) project. We identified patients with heart failure patients initiating MRAs and surviving a first-detected episode of hyperkalemia (plasma potassium >5.0 mmol/L). We used Cox regression, adjusting for multiple confounders, to estimate hazard ratios (HR) for adverse events following hyperkalemia. The primary outcome was the composite of hospital admission with heart failure, stroke, myocardial infarction or death. The secondary outcome was a new hyperkalemia event. We compared risks between people who stopped MRA treatment and those who continued MRA within 4 months from the hyperkalemia event (landmark analysis at month 4 after event). Results We identified 1,330 patients with heart failure that developed hyperkalemia after initiating MRA therapy. Their median age was 80 years, 46% were women and their median eGFR was 43 ml/min/1.73m2. Of those, 595 (45%) had discontinued MRA by 4 months after hyperkalemia. Patients who stopped MRA were more likely to have eGFR 5.5 mmol/L, 35% vs 21%), and had hyperkalemia occur earlier in the course of MRA therapy (within 3 months from MRA initiation, 66% vs 51%). During median 1.5 years of follow-up, a total of 846 patients (64%) experienced the primary composite outcome. Compared to patients who discontinued MRA, those who continued had a similar risk of the primary composite outcome (HR 0.95, 95% CI 0.82-1.10). A total of 569 patients (43%) developed a subsequent hyperkalemia event. Compared to patients who discontinued MRA, those who continued with the therapy were at higher risk of another hyperkalemia (HR 1.46, 95% CI 1.21-1.75). Results were consistent across age strata, sex and presence of CKD. Conclusion Continuing treatment with MRA after an episode of hyperkalemia was not associated with different medium-term cardiovascular risk compared to those who stopped the drugs.

Background: Quality health care delivery is critical to prevent diabetes-related complications. However, there is limited national information about the extent to which a diverse population of U.S. adults with diabetes receive the American Diabetes Association (ADA) recommended comprehensive diabetes care. Methods: We conducted a cross-sectional analysis of 4,114 adults aged ≥20 with self-reported diabetes from the National Health and Nutrition and Examination Survey (NHANES) 2005-2016. We estimated the prevalence and identified predictors of receipt of comprehensive diabetes care (i.e., meeting all 5 criteria in the past year: having a primary doctor for diabetes care and number of visits for this doctor ≥1, HbA1c testing, eye exam, foot exam, and cholesterol test). Results: Among adults with diabetes, 10.9% (95% CI, 9.3-12.6%) had received comprehensive care in the past year (all 5 criteria). Overall, 71.7% (95% CI, 69.6-73.7%) met ≥3 criteria. In a fully adjusted model, those less likely to receive comprehensive care were current smokers, and adults with lower socioeconomic status, lack of insurance, or depression (Table). Conclusions: Only 1 out of 10 U.S. adults with diabetes receive ADA recommended comprehensive diabetes care. Efforts are needed to improve health care delivery and equity in diabetes care. Insurance status and depression are important modifiable determinants of comprehensive care. Disclosure J. Shin: None. D. Wang: None. G. Fernandes: Employee; Spouse/Partner; Janssen Pharmaceuticals, Inc. Employee; Self; Merck Sharp & Dohme Corp. N.R. Daya: None. M. Grams: Other Relationship; Self; DCI. S. Golden: None. S. Rajpathak: Employee; Self; Menarini Group. E. Selvin: None.