Progression of chronic kidney disease among black patients attending a tertiary hospital in Johannesburg, South Africa.

BACKGROUND: Chronic kidney disease (CKD) is a major public health issue worldwide and is an important contributor to the overall non-communicable disease burden. Chronic kidney disease is usually asymptomatic, and insidiously and silently progresses to advanced stages in resource limited settings. METHODOLOGY: A prospective longitudinal study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2022. Demographic and clinical data were extracted from the ongoing continuous clinic records, as well as measurements of vital signs and interviews at baseline and at follow up. Patients provided urine and blood samples for laboratory investigations as standard of care at study entry (0) and at 24 months, and were followed up prospectively for two (2) years. Data were descriptively and inferentially entered into REDcap and analysed using STATA version 17, and multivariable logistic regression analysis was used to identify predictors of CKD progression. RESULTS: A total of 312 patients were enrolled into the study, 297 (95.2%) patients completed the study, 10 (3.2%) patients were lost to follow and 5 (1.6%) patients died during the study period. The prevalence of CKD progression was 49.5%, while that of CKD remission was 33% and CKD regression was 17.5%. For patients with CKD progression the median age at baseline was 58 (46-67) years, the median eGFR was 37 (32-51) mL/min/1.73 m2, median urine protein creatinine ratio (uPCR) was 0.038 (0.016-0.82) g/mmol and the median haemoglobin (Hb) was 13.1 (11.7-14.4) g/dl; 95.2% had hypertension, 40.1% patients had diabetes mellitus and 39.5% had both hypertension and diabetes mellitus. Almost half (48.3%) of patients with CKD progression had severely increased proteinuria and 45.6% had anaemia. Variables associated with higher odds for CKD progression after multivariable logistic regression analysis were severely increased proteinuria (OR 32.3, 95% CI 2.8-368.6, P = 0.005), moderately increased proteinuria (OR 23.3, 95% CI 2.6-230.1, P = 0.007), hypocalcaemia (OR 3.8, 95% CI 1.0-14.8, P = 0.047), hyponatraemia (OR 4.5, 95% CI 0.8-23.6, P = 0.042), anaemia (OR 2.1, 95% CI 1.0-4.3, P = 0.048), diabetes mellitus (OR 1.8, 95% CI 0.9-3.6, P = 0.047), elevated HbA1c (OR 1.8, 95% CI 1.2-2.8, P = 0.007) and current smoking (OR 2.8, 95% CI 0.9-8.6, P = 0.049). CONCLUSION: Our study identified a higher prevalence of CKD progression in a prospective longitudinal study of black patients with CKD compared with literature reports. CKD Progression was associated with proteinuria, diabetes mellitus, elevated HbA1c, anaemia, hypocalcaemia, hyponatraemia and current smoking in a cohort of black patients with CKD who had controlled hypertension and diabetes mellitus at baseline.

Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex.

BACKGROUND: The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown. METHODS: We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex. RESULTS: On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone. CONCLUSIONS: The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.).

Disparities in absolute cardiovascular risk, metabolic syndrome, hypertension, and other risk factors by income within racial/ethnic groups among middle-aged and older US people.

This cross-sectional study determined income disparities in age-adjusted prevalence and trends of 10-year high absolute cardiovascular disease (CVD) risk, metabolic syndrome, hypertension, diabetes, obesity, chronic kidney disease (CKD), leisure-time physical activity (LTPA), and current tobacco smoking within racial/ethnic groups in the US. National Health and Nutrition Examination Survey 2001-2016 data of 40-79-year-old people were analyzed. Survey periods were grouped as 2001-2006, 2007-2012, and 2013-2016. Race/ethnicity was grouped as non-Hispanic whites, non-Hispanic blacks, and other races/ethnicities. Three equal-sized strata (low-, middle-, and high income) were made from the family income-to-poverty ratio. Of the 25,777 participants (mean age: 55.6 years, 48% males), a majority of the studied prevalence was higher in most survey years among non-Hispanic blacks compared to non-Hispanic whites. Most studied prevalence was also higher among low-income people than middle-/high-income people. Within racial/ethnic groups, the prevalence also differed by income for high CVD risk, metabolic syndrome, hypertension, diabetes, obesity, CKD, LTPA, and tobacco smoking (P < 0.05) in most survey periods. After stratifying by race/ethnicity, the prevalence of many conditions remained disproportionately higher among low- and middle-income people, compared to those with high income during most survey periods in all racial/ethnic groups. These results reveal income in addition to race/ethnicity to be an important correlate of cardiovascular health and underscore the need to consider each when controlling for risk factors.

Race, Interleukin-6, TMPRSS6 Genotype, and Cardiovascular Disease in Patients With Chronic Kidney Disease.

Background Differences in death rate and cardiovascular disease (CVD) between Black and White patients with chronic kidney disease is attributed to sociocultural factors, comorbidities, genetics, and inflammation. Methods and Results We examined the interaction of race, plasma IL-6 (interleukin-6), and TMPRSS6 genotype as determinants of CVD and mortality in 3031 Chronic Renal Insufficiency Cohort study participants. The primary outcomes were all-cause mortality and a composite of incident myocardial infarction, peripheral artery disease, stroke, and heart failure. During the median follow-up of 10 years, Black patients with chronic kidney disease experienced a significantly higher mortality (34% versus 26%) and CVD composite (41% versus 28%) compared with White patients. After adjustment, TMPRSS6 genotype did not associate with the outcomes. The adjusted hazard ratio for mortality (4.11 [2.48-6.80], P<0.001) and CVD composite (2.52 [1.96-3.24], P<0.001) were higher for the highest versus lowest IL-6 quintile. The adjusted hazards for death per 1-quintile increase in IL-6 in White and Black individuals were 1.53 (1.42-1.64) versus 1.29 (1.20-1.38) (P<0.001), respectively. For CVD composite they were 1.61 (1.50-1.74) versus 1.30 (1.22-1.39) (P<0.001), respectively. In Cox proportional hazard models that included IL-6, there was no longer a racial disparity for death (1.01 [0.87-1.16], P=0.92), but significant unexplained mediation remained for CVD (1.24 [1.07-1.43]; P=0.004). Path models that included IL-6, diabetes, and urine albumin to creatinine ratio were able to identify variables responsible for racial disparity in mortality and CVD. Conclusions Racial differences in mortality and CVD among patients with chronic kidney disease could be explained by good-fitting path models that include selected mediator variables including diabetes and plasma IL-6.

Association of Estimated GFR Calculated Using Race-Free Equations With Kidney Failure and Mortality by Black vs Non-Black Race.

Importance: At a given estimated glomerular filtration rate (eGFR), individuals who are Black have higher rates of mortality and kidney failure with replacement therapy (KFRT) compared with those who are non-Black. Whether the recently adopted eGFR equations without race preserve racial differences in risk of mortality and KFRT at a given eGFR is unknown. Objective: To assess whether eGFR equations with and without race and cystatin C document racial differences in risk of KFRT and mortality in populations including Black and non-Black participants. Design, Setting, and Participants: Retrospective individual-level data analysis of 62 011 participants from 5 general population and 3 chronic kidney disease (CKD) US-based cohorts with serum creatinine, cystatin C, and follow-up for KFRT and mortality from 1988 to 2018. Exposures: Chronic Kidney Disease Epidemiology Collaboration equation with serum creatinine (eGFRcr with and without race), cystatin C (eGFRcys without race), or both markers (eGFRcr-cys without race). Main Outcomes and Measures: The prevalence of decreased eGFR at baseline and hazard ratios of KFRT and mortality in Black vs non-Black participants were calculated, adjusted for age and sex. Analyses were performed within each cohort and with random-effect meta-analyses of the models. Results: Among 62 011 participants (20 773 Black and 41 238 non-Black; mean age, 63 years; 53% women), the prevalence ratio (95% CI; percent prevalences) of eGFR less than 60 mL/min/1.73 m2 comparing Black with non-Black participants was 0.98 (95% CI, 0.93-1.03; 11% vs 12%) for eGFRcr with race, 0.95 (95% CI, 0.91-0.98; 17% vs 18%) for eGFRcys, and 1.2 (95% CI, 1.2-1.3; 13% vs 11%) for eGFRcr-cys but was 1.8 (95% CI, 1.7-1.8; 15% vs 9%) for eGFRcr without race. During a mean follow-up of 13 years, 8% and 4% of Black and non-Black participants experienced KFRT and 34% and 39% died, respectively. Decreased eGFR was associated with significantly greater risk of both outcomes for all equations. At an eGFR of 60 mL/min/1.73 m2, the hazard ratios for KFRT comparing Black with non-Black participants were 2.8 (95% CI, 1.6-4.9) for eGFRcr with race, 3.0 (95% CI, 1.5-5.8) for eGFRcys, and 2.8 (95% CI, 1.4-5.4) for eGFRcr-cys vs 1.3 (95% CI, 0.8-2.1) for eGFRcr without race. The 5-year absolute risk differences for KFRT comparing Black with non-Black participants were 1.4% (95% CI, 0.2%-2.6%) for eGFRcr with race, 1.1% (95% CI, 0.2%-1.9%) for eGFRcys, and 1.3% (95% CI, 0%-2.6%) for eGFRcr-cys vs 0.37% (95% CI, -0.32% to 1.05%) for eGFRcr without race. Similar patterns were observed for mortality. Conclusions and Relevance: In this retrospective analysis of 8 US cohorts including Black and non-Black individuals, the eGFR equation without race that included creatinine and cystatin C, but not the eGFR equation without race that included creatinine without cystatin C, demonstrated racial differences in the risk of KFRT and mortality throughout the range of eGFR. The eGFRcr-cys equation may be preferable to the eGFRcr equation without race for assessing racial differences in the risk of KFRT and mortality associated with low eGFR.

COVID-19 Survival and its impact on chronic kidney disease.

Up to 87% of patients hospitalized with coronavirus disease 2019 (COVID-19) experience chronic sequelae following infection. The long-term impact of COVID-19 infection on kidney function is largely unknown at this point in the COVID-19 pandemic. In this review, we highlight the current understanding of the pathophysiology of COVID-19-associated kidney injury and the impact COVID-19 may have on long-term kidney function. COVID-19-induced acute kidney injury may lead to tubular injury, endothelial injury, and glomerular injury. We highlight histopathologic correlates from large kidney biopsy and autopsy series. By conducting a comprehensive review of published literature to date, we summarize the rates of recovery from COVID-19-associated-AKI. Finally, we discuss how certain genetic differences, including APOL1 risk alleles (a risk factor for collapsing glomerulopathy), coupled with systemic healthcare disparities, may lead to a disproportionate burden of post-COVID-19-kidney function decline among racial and ethnic minority groups. We highlight the need for prospective studies to determine the true incidence of chronic kidney disease burden after COVID-19.

Association between Body Mass Index and Chronic Kidney Disease in Asian Populations: A Participant-level Meta-Analysis.

Obesity and chronic kidney disease (CKD) are major public health problems worldwide. However, the association between body mass index (BMI) and CKD is inconclusive in Asians. In this meta-analysis, eight population-based studies, from China, India, Russia (Asian), Singapore and South Korea, provided individual-level data (n=50037). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. BMI was analyzed both as a continuous variable and in three categories: <25kg/m2, normal; 25-29.9kg/m2, overweight; and ≥30kg/m2, obese. The association between BMI and CKD was evaluated in each study using multivariable logistic regression models and individual estimates were pooled using random-effect meta-analysis to obtain the pooled odds ratio (OR) and 95% confidence interval (CI). Associations were also evaluated in subgroups of age, gender, smoking, diabetes, and hypertension status. Of 50037 adults, 4258 (8.5%) had CKD. 13328 (26.6%) individuals were overweight while 4440 (8.9%) were obese. The prevalence of any CKD ranged from 3.5% to 29.1% across studies. In pooled analysis, both overweight and obesity were associated with increased odds of CKD, with pooled OR (95% CI) of 1.15 (1.03-1.29) and 1.23 (1.06-1.42), respectively. In subgroup analyses, significant associations between BMI and CKD were observed in adult males, non-smokers, and those with diabetes and arterial hypertension (all p<0.05). When evaluated as a continuous variable, BMI was not significantly associated with CKD. If confirmed in longitudinal studies, these results may have clinical implications in risk stratification and preventive measures, given that obesity and CKD are two major chronic diseases with substantial public health burden worldwide.

Association of elevated serum aminotransferase levels with chronic kidney disease measures: hispanic community health study/study of latinos.

BACKGROUND: Previous studies have shown an association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), but it is unclear whether the association is independent of metabolic syndrome. METHODS: Data from 13,006 participants aged 18 to 74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) without viral hepatitis, excessive alcohol consumption, or high transferrin saturation levels were analyzed. Suspected NAFLD was defined as presence of sex-specific elevations in serum aminotransferase levels (aspartate aminotransferase (AST) > 37 U/L or alanine aminotransferase (ALT) > 40 U/L for men and AST or ALT > 31 U/L for women). Logistic regression was used to examine cross-sectional associations of elevated serum aminotransferase levels with low estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2 based on cystatin C), and with high urinary albumin-to-creatinine ratio (UACR) (> 17 mg/g in men and > 25 mg/ g in women) in separate models adjusting for demographic characteristics and metabolic syndrome. RESULTS: Mean (SD) age was 41 (0.27) years, and 45 % were male. Elevated serum aminotransferase levels were noted in 18.8 % of the population and were associated with greater odds of high UACR (OR = 1.31; 95 % CI = 1.10, 1.56) after adjusting for demographic characteristics; this association became non-significant after adjustment for metabolic syndrome (OR = 1.11, 95 % CI = 0.92, 1.33). In contrast, elevated serum aminotransferase levels were not associated with low eGFR (odds ratio (OR) = 0.73; 95 % confidence interval (CI) = 0.45, 1.18) after adjusting for covariates. CONCLUSIONS: In this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD.

New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.

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 m2 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 m2; 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 m2; 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 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 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.).

Race, Genetic Ancestry, and Estimating Kidney Function in CKD.

BACKGROUND: The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed. METHODS: In a large national study involving adults with chronic kidney disease, we conducted cross-sectional analyses of baseline data from 1248 participants for whom data, including the following, had been collected: race as reported by the participant, genetic ancestry markers, and the serum creatinine, serum cystatin C, and 24-hour urinary creatinine levels. RESULTS: Using current formulations of GFR estimating equations, we found that in participants who identified as Black, a model that omitted race resulted in more underestimation of the GFR (median difference between measured and estimated GFR, 3.99 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 2.17 to 5.62) and lower accuracy (percent of estimated GFR within 10% of measured GFR [P10], 31%; 95% CI, 24 to 39) than models that included race (median difference, 1.11 ml per minute per 1.73 m2; 95% CI, -0.29 to 2.54; P10, 42%; 95% CI, 34 to 50). The incorporation of genetic ancestry data instead of race resulted in similar estimates of the GFR (median difference, 1.33 ml per minute per 1.73 m2; 95% CI, -0.12 to 2.33; P10, 42%; 95% CI, 34 to 50). The inclusion of non-GFR determinants of the serum creatinine level (e.g., body-composition metrics and urinary excretion of creatinine) that differed according to race reported by the participants and genetic ancestry did not eliminate the misclassification introduced by removing race (or ancestry) from serum creatinine-based GFR estimating equations. In contrast, the incorporation of race or ancestry was not necessary to achieve similarly statistically unbiased (median difference, 0.33 ml per minute per 1.73 m2; 95% CI, -1.43 to 1.92) and accurate (P10, 41%; 95% CI, 34 to 49) estimates in Black participants when GFR was estimated with the use of cystatin C. CONCLUSIONS: The use of the serum creatinine level to estimate the GFR without race (or genetic ancestry) introduced systematic misclassification that could not be eliminated even when numerous non-GFR determinants of the serum creatinine level were accounted for. The estimation of GFR with the use of cystatin C generated similar results while eliminating the negative consequences of the current race-based approaches. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.

Impact of point-of-care screening for hypertension, diabetes and progression of chronic kidney disease in rural Manitoba Indigenous communities.

BACKGROUND: In 2013-2015, we conducted point-of-care screening for hypertension, diabetes and chronic kidney disease in rural and remote Indigenous communities in Manitoba, Canada. In this study, we aimed to determine whether optimal follow-up care was provided, defined as proportion of individuals with appropriate kidney disease laboratory testing, medication prescriptions and physician visits. METHODS: We linked screening data from participants to provincial administrative data sets to evaluate whether frequencies of laboratory testing, prescriptions of disease-modifying medications, and primary care and nephrology visits differed in the 18 months before and after screening. We also conducted a propensity score matching analysis to compare outcomes between screened and unscreened adults. RESULTS: Of 1353 adults who received the screening intervention and who had complete administrative data available, 44% were at risk of kidney failure at screening. Among these individuals, frequencies of comprehensive laboratory testing (estimated glomerular filtration rate and urine albumin to creatinine ratio) improved by 17.0% (95% confidence interval [CI] 11.5 to 22.5), anti-hyperglycemic medications improved by 4.4% (95% CI 1.0 to 7.8), and nephrology visits for participants meeting referral criteria improved by 5.9% (95% CI 3.4 to 8.5). We observed significant improvements in laboratory testing, antihyperglycemic medications and nephrology visits in the screened group compared with the 1:1 matched comparison group. INTERPRETATION: Point-of-care screening programs in rural and remote Indigenous communities are adaptable methods for increasing awareness, monitoring risk and treating chronic diseases. Interventions such as the development of a national screening program could improve chronic disease care in high-risk populations.

A randomized trial of race-related stress among African Americans with chronic kidney disease.

OBJECTIVE: African Americans progress from early to late-stage chronic kidney disease (CKD) at a rate that is three times that of Whites. Given research that implicates social stress in poor kidney outcomes, there is a need to examine whether race-related stress contributes to these disparities. Through experimental manipulation, this study sought to determine whether acute race-related stress was associated with autonomic arousal and an inflammatory marker, which are well-established pathways to poor kidney outcomes. Further we tested the hypothesis that expectations of racism may moderate this relationship. METHOD: Fifty-two African American patients along the CKD continuum were randomized to recall a general or race-related stressful experience. Before, during, and after the recall, patients' blood pressure and Interleukin-6 (IL-6) were monitored. Prior to the experimental manipulation, participants completed self-reported measures of expectations of racism. RESULTS: Across both study conditions, change in self-reported distress from baseline to stress was associated with both systolic and diastolic reactivity (both ps <.01), but not change in IL-6 responses (all ps > 0.05). A significant interaction revealed that those who were randomized to recall a race-related stressor demonstrated less diastolic blood pressure reactivity (F=4.80, p<.05) if they scored lower in expectations of racism as compared to those who scored high. Moreover, those who were randomized to the race-related stressor demonstrated greater increase in IL-6 from 45 to 90 min post-recall than those who recalled a general stressor (F=6.35, p<.05). CONCLUSIONS: Acute race-related stress may be associated with autonomic arousal and inflammatory response among African American patients along the CKD continuum, suggesting the need to further understand its role in racial disparities in CKD progression.

Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study.

BACKGROUND/OBJECTIVES: APOL1 high-risk genotypes confer an increased risk for kidney disease, but their clinical significance among older adults remains unclear. We aimed to determine whether APOL1 genotype status (high risk = 2 risk alleles; low risk = 0-1 risk alleles) and self-reported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality among older adults participating in a community-based cohort study. DESIGN: Observational longitudinal cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) study. PARTICIPANTS: Community-dwelling older adults (mean age = 75.8 years; range = 66-90 years). RESULTS: Among 5,564 ARIC participants (78.2% White, 19.1% APOL1 low-risk Black, and 2.7% APOL1 high-risk Black), the proportion with creatinine and cystatin C-based estimated glomerular filtration rate (eGFRCrCys ) below 60 mL/min/1.73 m2 at baseline was 40.6%, 34.8%, and 43.2%, respectively. Over a mean follow-up of 5.1 years, APOL1 high-risk Blacks had a 2.67-fold higher risk for ESRD compared with low-risk Blacks (95% confidence interval [CI] = 1.05-6.79) in models adjusted for age and sex. This association was no longer significant upon further adjustment for baseline eGFRCrCys and albuminuria (hazard ratio [HR] = 1.08; 95% CI = .39-2.96). Rate of hospitalizations and risks of mortality and incident CKD did not differ significantly by APOL1 genotype status. Compared with Whites, Blacks had 1.85-fold and 3.45-fold higher risks for incident CKD and ESRD, respectively, in models adjusted for age, sex, eGFRCrCys , and albuminuria. These associations persisted after additional adjustments for clinical/socioeconomic factors and APOL1 genotype (incident CKD: HR = 1.38; 95% CI = 1.06-1.81; ESRD: HR = 3.20; 95% CI = 1.16-8.86). CONCLUSION: Among older Black adults, APOL1 high-risk genotypes were associated with lower kidney function and therefore higher risk of ESRD. Racial disparities in incident kidney disease persisted in older age and were not fully explained by APOL1.

A New Panel-Estimated GFR, Including ß2-Microglobulin and ß-Trace Protein and Not Including Race, Developed in a Diverse Population.

RATIONALE AND OBJECTIVE: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. ß2-Microglobulin (B2M) and ß-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is. STUDY DESIGN: Study of diagnostic test accuracy. SETTING AND PARTICIPANTS: Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. TESTS COMPARED: Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. OUTCOMES: GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA. RESULTS: Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 - P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 - P30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups. LIMITATIONS: No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe. CONCLUSIONS: The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Prevalence and risk factors of chronic kidney disease among Palestinian type 2 diabetic patients: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health concern and diabetes is one of the main risk factors for its occurrence and progression. The aim of this research is to determine the prevalence of chronic kidney disease in a cross-sectional population of patients with type 2 diabetes in primary health centers in North West Bank. METHODS: Patient data including patient characteristics, creatinine level, blood pressure, HbA1c, and hypertension and period of diabetes were obtained from primary health care centers. The eGFR has been determined using the CKD-EPI equation. CKD was staged according to the 2012 Kidney Disease Improving Global Outcomes Framework (KDIGO) guideline. Both univariable and multivariable statistical analysis was conducted using SPSS. RESULTS: The prevalence of chronic kidney disease among diabetic adults in North West Bank was found to be 23.6% (95% CI: 19.4-28.1%) divided as follows: 19.7% had stage 3 CKD, 2.6% had stage 4 CKD and 1.3% had stage 5 CKD. In multivariable logistic regression, CKD was significantly associated with Age ≥ 60 years [adjusted OR: 3.2, 95% CI: 1.8-5.9], hypertension [adjusted OR: 5.7, 95% CI: 2.2-15.2], and smoking [adjusted OR: 2.3, 95% CI: 1.3-4.2]. CONCLUSIONS: CKD is very prevalent among diabetic adults in Palestine. Co-morbid hypertension, smoking and older age has been shown to increase the risk of developing CKD. Extensive screening for diabetic patients to diagnose CKD at an early stage and to follow more aggressive treatment methods for diabetes as well as other important risk factors, especially hypertension and smoking, is recommended.

Racial/Ethnic Differences in Early Detection and Screening for Chronic Kidney Disease Among Adults in Hawaii: A 10-Year Population Health Study.

INTRODUCTION: Native Hawaiian and Asian American populations are the most understudied racial/ethnic groups in chronic kidney disease (CKD) research. The objective of our study was to describe sociodemographic and comorbidity risk factors of chronic kidney disease among 2,944 community-dwelling Native Hawaiian, Filipino, Chinese, Japanese, and non-Hispanic white participants who attended the National Kidney Foundation of Hawaii Kidney Early Detection Screening program during 2006-2017. METHODS: We used multivariable logistic regression models to examine the association between age, sex, race/ethnicity, and the major risk factors for CKD (diabetes, hypertension, cardiovascular disease, hypercholesterolemia, overweight and obesity, and smoking) with elevated urine albumin to creatinine ratio (ACR) among adults aged 18 or older in 5 racial/ethnic groups in Hawaii: Native Hawaiian, Filipino, Chinese, Japanese, and non-Hispanic white. RESULTS: In the age- and sex-adjusted model, Native Hawaiian participants were significantly more likely than non-Hispanic white participants to have an ACR of 30.0 mg/g or more (odds ratio [OR] = 1.50; 95% CI, 1.15-1.95; P = .003). In the model that adjusted for CKD risk factors, the difference between Native Hawaiian and non-Hispanic white participants became nonsignificant (OR = 1.27; 95% CI, 0.96-1.69; P = .09]). The higher prevalence of chronic conditions among Native Hawaiians partially explained their higher risk of having an elevated ACR. Filipinos had significantly higher odds than non-Hispanic whites of elevated ACR in the age- and sex-adjusted model (OR = 1.44; 95% CI, 1.14-1.84; P = .003) and after adjustment for CKD risk factors (OR = 1.36; 95% CI, 1.06-1.74; P = .01). CONCLUSION: Culturally targeted interventions are needed to improve health outcomes among Native Hawaiians and Asian Americans, particularly Filipinos, with CKD. Such interventions should focus on early kidney disease management so that disease progression can be delayed.

Association of Race and Ethnicity with Vascular Access Type Selection and Outcomes.

BACKGROUND: Black patients with end-stage renal disease (ESRD) represent 30.5% of the prevalent ESRD population in the United States, despite only accounting for 18% of the total population. Black patients are less likely to have pre-ESRD care compared with their white counterparts and are 3-4 times more likely to progress from chronic kidney disease to ESRD than whites, suggesting that black patients are particularly vulnerable to disparities in outcomes related to hemodialysis and ESRD. The objective of this study is to examine the association of race with outcomes of hemodialysis access and selection of arteriovenous fistula (AVF) versus arteriovenous graft (AVG). METHODS: Patients with chronic kidney disease who initiated dialysis through a tunneled hemodialysis catheter (THC) were identified in the Optum's De-identified Clinformatics® Data Mart (OptumInsight, Eden Prairie, MN) claims database (2011-2017). The odds of AVF versus AVG creation and the odds of repeat vascular access creation were analyzed using logistic regression. Time from initial AVF/AVG to THC removal and time to repeat AVF/AVG were analyzed using Cox proportional hazards. RESULTS: About 7,584 vascular access patients met the inclusion criteria: 5,852 (77%) AVF and 1,732 (23%) AVG. Median follow-up was 583 days overall (range, 1-2,543), 589 days among AVF patients (range, 1-2,543), and 260 days among AVG patients (range, 1-2,529). Between races, there was no clinically significant variation in characteristics or comorbidities, with the exception of a much lower rate of obesity among Asians. Black patients had 36% lower odds of AVF index versus AVG index (P < 0.001). Patients 70 years or older and patients with diabetes had lower odds of AVF index, whereas men and obese patients had greater odds of receiving AVF. Overall, graft patients were 73% more likely to have a shorter time to THC removal than fistula patients, but Hispanic graft patients were 25% more likely to have a shorter time to THC removal than whites. Patients with diabetes, patients with cardiac arrhythmia, and obesity were more likely to have a longer time to THC removal. About 1,589 (21%) patients underwent a repeat vascular access creation during the follow-up period: 19% of whites (n = 802), 26% of blacks (n = 483), 19% of Hispanics (n = 250), and 19% of Asians (n = 54) (P < 0.001). Multivariate analysis demonstrated that black patients had 58% greater odds of requiring a second access than white patients (P < 0.001). Graft patients, patients 70 years or older, and men had lower odds of repeat access. Black patients were 45% more likely to have a shorter time until second access creation. Graft patients, patients aged 70 years or older, and men were more likely to have a longer time until second access. Patients with obesity were more likely to have a shorter time until second access. CONCLUSIONS: This study's findings suggest that after initial vascular access, compared with whites, blacks have no difference in time to index access success, but their access fails earlier and more frequently, independent of access type, age, and comorbidities. Given blacks constitute 30.5% of the hemodialysis population in the United States, it is imperative that future research investigate the root causes of these disparities.

Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Kidney Function in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Chronic kidney disease (CKD) is a common complication of type 2 diabetes that can lead to end-stage kidney disease and is associated with high cardiovascular risk. Few treatments are available to prevent CKD in type 2 diabetes. Objective: To test whether supplementation with vitamin D3 or omega-3 fatty acids prevents development or progression of CKD in type 2 diabetes. Design, Setting, and Participants: Randomized clinical trial with a 2 × 2 factorial design conducted among 1312 adults with type 2 diabetes recruited between November 2011 and March 2014 from all 50 US states as an ancillary study to the Vitamin D and Omega-3 Trial (VITAL), coordinated by a single center in Massachusetts. Follow-up was completed in December 2017. Interventions: Participants were randomized to receive vitamin D3 (2000 IU/d) and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid; 1 g/d) (n = 370), vitamin D3 and placebo (n = 333), placebo and omega-3 fatty acids (n = 289), or 2 placebos (n = 320) for 5 years. Main Outcomes and Measures: The primary outcome was change in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) from baseline to year 5. Results: Among 1312 participants randomized (mean age, 67.6 years; 46% women; 31% of racial or ethnic minority), 934 (71%) completed the study. Baseline mean eGFR was 85.8 (SD, 22.1) mL/min/1.73 m2. Mean change in eGFR from baseline to year 5 was -12.3 (95% CI, -13.4 to -11.2) mL/min/1.73 m2 with vitamin D3 vs -13.1 (95% CI, -14.2 to -11.9) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.5] mL/min/1.73 m2). Mean change in eGFR was -12.2 (95% CI, -13.3 to -11.1) mL/min/1.73 m2 with omega-3 fatty acids vs -13.1 (95% CI, -14.2 to -12.0) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.6] mL/min/1.73 m2). There was no significant interaction between the 2 interventions. Kidney stones occurred among 58 participants (n = 32 receiving vitamin D3 and n = 26 receiving placebo) and gastrointestinal bleeding among 45 (n = 28 receiving omega-3 fatty acids and n = 17 receiving placebo). Conclusions and Relevance: Among adults with type 2 diabetes, supplementation with vitamin D3 or omega-3 fatty acids, compared with placebo, resulted in no significant difference in change in eGFR at 5 years. The findings do not support the use of vitamin D or omega-3 fatty acid supplementation for preserving kidney function in patients with type 2 diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT01684722.