Association of race and ethnicity with initial surgical hemodialysis access type in a safety net system.

OBJECTIVES: Prior studies have found lower arteriovenous fistula (AVF) creation rates in Black and Hispanic patients. Whether this is due to health care disparities or other differences is unclear. Our objective was to evaluate the racial/ethnic differences in initial surgical access type within a high-volume, safety net system with predominantly Black and Hispanic populations. METHODS: A retrospective review of initial hemodialysis (HD) access in consecutive cases between 2014 and 2019 was conducted from all five safety net hospitals in a health care system that primarily treats underserved patients. Patient data collected included race, ethnicity, sex, comorbidities, and initial arteriovenous (AV) access type (AV fistula [AVF] vs AV graft [AVG]). The rates of cephalic vein-based AVF (CAVF; radiocephalic, brachiocephalic) were compared with basilic and brachial vein AVF (BAVF), because the latter are performed as two stages. Bivariate and multivariate logistic regression models were adjusted for demographic and clinical variables to evaluate the relationship between race/ethnicity, surgical access type, and comorbid conditions. RESULTS: We included 1334 patients (74% Hispanic, 9% Black, 7% Asian, 2% White, 8% other) who underwent first-time surgical HD access creation. The majority were male (818 [63%]). Medical comorbidities were equal among groups, except for chronic obstructive pulmonary disease and stroke, which were higher in Black patients (P < .005 and P = .005, respectively). Overall, 1303 patients (98%) underwent AVF creation and 31 AVG creation (2%), with no difference between race/ethnicity in AVF vs AVG creation. Of the AVF cohort, 991 (76%) had a CAVF and 312 (24%) had a BAVF. Males were more likely than females to get a CAVF (65% vs 35%; P = .002). CONCLUSIONS: Within our safety net health system, where most patients are under-represented minorities, nearly all patients undergoing HD access had an AVF as their initial surgery with no difference in race/ethnicity. AVF type received differed by race, with Black patients twice as likely to undergo BAVF, which required two stages. Further studies are needed to identify the reasons for these differences.

Validation of the international IgA nephropathy prediction tool in a French cohort beyond 10 years after diagnosis.

INTRODUCTION: The International IgA Nephropathy Network developed a tool (IINN-PT) for predicting the risk of end-stage renal disease (ESRD) or a 50% decline in the estimated glomerular filtration rate (eGFR). We aimed to validate this tool in a French cohort with longer follow-up than previously published validation studies. METHODS: The predicted survival of patients with biopsy-proven immunoglobulin A nephropathy (IgAN) from the Saint Etienne University Hospital cohort was computed with IINN-PT models with or without ethnicity. The primary outcome was the occurrence of either ESRD or a 50% decline in eGFR. The models' performances were evaluated through c-statistics, discrimination and calibration analysis. RESULTS: There were 473 patients with biopsy-proven IgAN, with a median follow-up of 12.4 years. Models with and without ethnicity showed areas under the curve (95% confidence interval) of 0.817 (0.765; 0.869) and 0.833 (0.791; 0.875) and R2D of 0.28 and 0.29, respectively, and an excellent discrimination of groups of increasing predicted risk (P < .001). The calibration analysis was good for both models up to 15 years after diagnosis. The model without ethnicity exhibited a mathematical issue of survival function after 15 years. DISCUSSION: The IINN-PT provided good performances even after 10 years post-biopsy as showed by our study based on a cohort with a longer follow-up than previous cohorts (12.4 versus <6 years). The model without ethnicity exhibited better performances up to 15 years but became aberrant beyond this point due to a mathematical issue affecting the survival function. Our study sheds light on the usefulness of integrating ethnicity as a covariable for prediction of IgAN course.

Healthful dietary patterns and risk of end-stage kidney disease: the Singapore Chinese Health Study.

BACKGROUND: Although adherence to healthful dietary patterns has been associated with a lower risk of kidney function decline in Western populations, evidence in Asian populations remains scanty. OBJECTIVES: We examined predefined dietary patterns, namely, the Alternate Healthy Eating Index-2010 (AHEI-2010), the Dietary Approaches to Stop Hypertension (DASH), and the alternate Mediterranean diet (aMED), in relation to risk of end-stage kidney disease (ESKD). METHODS: We included 56,985 Chinese adults (aged 45-74 y) in the Singapore Chinese Health Study who were free of cancer, stroke, coronary artery disease, and ESKD at recruitment (1993-1998). Dietary pattern scores were calculated based on a validated 165-item FFQ. AHEI-2010 and aMED scores were modified by excluding the alcohol intake component because daily drinking has been associated with a higher risk of ESKD in our study population. We identified 1026 ESKD cases over a median follow-up of 17.5 y via linkage with the nationwide Singapore Renal Registry. Multivariable Cox regression models were used to compute HRs and their 95% CIs. RESULTS: Higher scores of all 3 dietary patterns were associated with lower ESKD risk in a dose-dependent manner. Compared with the lowest quintiles, the multivariable-adjusted HRs (95% CIs) of ESKD were 0.75 (0.61, 0.92) for the highest quintile of AHEI-2010, 0.67 (0.54, 0.84) for DASH, and 0.73 (0.59, 0.91) for aMED (all P-trend ≤ 0.004). These inverse associations were stronger with increasing BMI (in kg/m2), and the HRs for the diet-ESKD association were lowest in the obese (BMI ≥ 27.5), followed by the overweight (BMI = 25 to <27.5) participants, compared with those in lower BMI categories; the P-interaction values between BMI and diet scores were 0.03 for AHEI-2010, 0.004 for aMED, and 0.06 for DASH. CONCLUSIONS: Adherence to healthful dietary patterns was associated with a lower ESKD risk in an Asian population, especially in overweight or obese individuals.

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.

Allograft and Patient Outcomes Between Indigenous and Nonindigenous Kidney Transplant Recipients.

BACKGROUND: Kidney transplant outcomes of indigenous Australians are poorer compared with nonindigenous Australians, but it is unknown whether the type of acute rejection differs between these patient groups or whether rejection mediates the effect between ethnicity, death-censored graft failure (DCGF), and death with a functioning graft (DWFG). METHODS: Biopsy-proven acute rejection (BPAR) rates and types were compared between indigenous and nonindigenous recipients. The associations between ethnicity, BPAR, DCGF, and DWFG were examined using adjusted competing risk analyses, and mediation analysis was conducted to determine whether BPAR mediated the adverse effects between ethnicity and outcomes. RESULTS: Fifty-seven (9.3%) of 616 patients who have received kidney-only transplants between 2000 and 2010 in Western Australia were indigenous. Compared with nonindigenous recipients, BPAR rates were higher in indigenous recipients (42 versus 74 episodes/100 recipients, P < 0.01), with an excess of antibody-mediated rejections. During a median follow-up of 8 years, indigenous recipients were more likely to experience BPAR, DCGF, and DWFG compared with nonindigenous recipients, with adjusted subdistribution hazard ratio of 1.94 (1.39-2.70), 1.53 (0.85-2.76; P = 0.159), and 2.14 (1.13-4.06; P = 0.020), respectively. Although 70% of the effect between ethnicity and DCGF was mediated by BPAR, no similar association was found for DWFG. CONCLUSIONS: Indigenous recipients experienced poorer allograft and patient outcomes compared with nonindigenous recipients, with BPAR an important determinant for DCGF. Future research identifying other risk factors and mediators associated with patient survival in indigenous recipients should be considered a priority.

Association of African-American ethnicity and smoking status with total and individual damage index in systemic lupus erythematosus.

INTRODUCTION: Smoking has been associated with increased incidence, severity of cutaneous lupus, and lupus activity. We looked at the association of both smoking and ethnicity with the individual damage items from the SLICC/ACR Damage Index. METHODS: Poisson regression was used to model the total SLICC/ACR Damage Index score against ever smoking. Cox regression was used to assess the relationship between time to individual damage items and ever smoking. Furthermore, we compared SLICC/ACR Damage Index items among African-American and Caucasian ever smokers. RESULTS: The study included 2629 patients, 52.6% Caucasian and 39.3% African-American. The prevalence of ever smokers was 35.8%. There was no significant difference in total SLICC/ACR Damage Index score between ever smokers and never smokers after adjustment for ethnicity, gender, age at diagnosis, and years of education. Ever smokers had more atherosclerotic cardiovascular damage and skin damage compared to non-smokers. Caucasian SLE patients who ever smoked were more likely to have muscle atrophy and atherosclerosis compared to Caucasian non-smokers. African-American patients who ever smoked were more likely to have skin damage compared to African-American non-smokers. African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked. CONCLUSION: Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Surprisingly, cardiovascular damage items had higher hazard ratios in Caucasian smokers than non-smokers while skin damage items hazard ratios were higher in African-American smokers compared to non-smokers.Key Points• This study is the largest cohort study to date evaluating the effect of smoking on the cumulative SLICC/ACR Damage Index and its individual damage items.• It is the only study that examined the effect of smoking on individual items of the SLICC/ACR Damage Index in terms of Caucasians vs. African-American ethnicity.• Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Compared to non-smokers, Caucasian smokers had higher risk of cardiovascular damage while African-American smokers had more skin damage.• African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked.

Survival after major lower extremity amputation in patients with end-stage renal disease.

OBJECTIVE: This study evaluates survival of patients with end-stage renal disease (ESRD) after major lower extremity amputation (MLEA), given the burden of peripheral arterial disease in patients with ESRD, the hindrance posed by cardiovascular disease on their survival, and the national investment in ESRD-related care. METHODS: A retrospective review of all hemodialysis patients (HD) and renal transplant (RT) recipients who underwent MLEA between January 2007 and December 2011 in the United States Renal Data System was performed. Univariable, Kaplan-Meier, multivariable logistic, and Cox regression analyses were used to evaluate patient survival among HD patients and RT recipients overall; and within strata of amputation level, gender, and race. RESULTS: There were 32,540 MLEAs (HD, 92%; RT, 8%). Among HD patients, the median survival was 6 months for above knee amputation (AKA) and 16 months for below knee amputation (BKA). The risk-adjusted mortality was higher for AKA compared with BKA (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.44-1.52; P < .001), females compared with males (aHR, 1.04; 95% CI, 1.01-1.08; P = .004), but lower for blacks (aHR, 0.78 95% CI, 0.76-0.81; P < .001) and Hispanics (aHR, 0.74; 95% CI, 0.70-0.79; P < .001) compared with white HD patients. Among RT recipients, the median survival was 16 months for AKA and 47 months for BKA. Mortality was significantly higher for above knee amputees compared with below knee amputees (aHR, 1.83; 95% CI, 1.60-2.10; P < .001). However, there was no difference in mortality between the gender and racial categories of RT recipients. There was a twofold increase in the 30-day mortality (adjusted odd ratio, 1.94; 95% CI, 1.66-2.25; P < .001) and long-term mortality (aHR, 2.18; 95% CI, 2.05-2.32; P < .001) for HD patients relative to RT recipients. CONCLUSIONS: Survival after MLEA is limited in patients with ESRD. It is relatively better for RT recipients compared with HD patients. Mortality was higher for females compared with males, but lower for blacks and Hispanics compared with white HD patients. There were no gender- or race-specific difference in mortality among RT recipients. These estimates of life expectancy should guide the informed decision- making process for patients and their healthcare providers when the need for intervention arises after MLEA in these unique categories of patients.

Racial Differences and Factors Associated with Pregnancy in ESKD Patients on Dialysis in the United States.

BACKGROUND: Pregnancy in women with ESKD undergoing dialysis is uncommon due to impaired fertility. Data on pregnancy in women on dialysis in the United States is scarce. METHODS: We evaluated a retrospective cohort of 47,555 women aged 15-44 years on dialysis between January 1, 2005 and December 31, 2013 using data from the United States Renal Data System with Medicare as primary payer. We calculated pregnancy rates and identified factors associated with pregnancy. RESULTS: In 47,555 women on dialysis, 2352 pregnancies were identified. Pregnancy rate was 17.8 per thousand person years (PTPY) with the highest rate in women aged 20-24 (40.9 PTPY). In the adjusted time-to-event analysis, a higher likelihood of pregnancy was seen in Native American (HR, 1.77; 95% CI, 1.33 to 2.36), Hispanic (HR, 1.51; 95% CI, 1.32 to 1.73), and black (HR, 1.33; 95% CI, 1.18 to 1.49) women than in white women. A higher rate of pregnancy was seen in women with ESKD due to malignancy (HR, 1.64; 95% CI, 1.27 to 2.12), GN (HR, 1.38; 95% CI, 1.21 to 1.58), hypertension (HR, 1.32; 95% CI, 1.16 to 1.51), and secondary GN/vasculitis (HR, 1.18; 95% CI, 1.02 to 1.37) than ESKD due to diabetes. A lower likelihood of pregnancy was seen among women on peritoneal dialysis than on hemodialysis (HR, 0.47; 95% CI, 0.41 to 0.55). CONCLUSIONS: The pregnancy rate is higher in women on dialysis than previous reports indicate. A higher likelihood of pregnancy was associated with race/ethnicity, ESKD cause, and dialysis modality.

Is immunoglobulin A nephropathy different in different ethnic populations?

Immunoglobulin A nephropathy (IgAN) is one of the commonest global patterns of primary glomerulonephritis and remains a leading cause of chronic kidney disease and end-stage renal disease. The sole diagnostic criterion of IgAN remains the presence of dominant mesangial immunoglobulin A deposits on kidney biopsy. Beyond this defining feature, there is significant heterogeneity in the epidemiology, clinical presentation, renal progression and long-term outcomes of IgAN in different ethnic populations. Mirroring this heterogeneity in clinical phenotypes, there is also marked ethnic variation in the extent of histopathological lesions observed on kidney biopsy, which may partly explain the well-documented differences in response to immunomodulatory agents reported in different regions of the world. In parallel, disparities have been identified in genetic association studies and key pathogenic pathways in different ethnic populations. Understanding the basis for these differences in IgAN has important implications for both clinical care and future research. In this review, we will examine the impact of ethnicity on the epidemiology, clinical presentation and outcomes, pathogenesis and genetic associations in IgAN.

Kidney disease in Africans with HIV and tuberculosis.

OBJECTIVE: To describe the spectrum of kidney disease in African patients with HIV and tuberculosis (TB). METHODS: We used data from three cohorts: consecutive patients with HIV/TB in South London (UK, 2004-2016; n = 95), consecutive patients with HIV/TB who underwent kidney biopsy in Cape Town (South Africa, 2014-2017; n = 70), and consecutive patients found to have HIV/TB on autopsy in Abidjan (Cote d'Ivoire, 1991; n = 100). Acute kidney injury (AKI) was ascertained using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In the Cape Town cohort, predictors of recovery of kidney function at 6 months were assessed using Cox regression. RESULTS: In the London cohort, the incidence of moderate/severe AKI at 12 months was 15.1 (95% CI 8.6-26.5) per 100 person-years, and the prevalence of chronic and end-stage kidney disease (ESKD) 13.7 and 5.7%, respectively. HIV-associated nephropathy (HIVAN) was diagnosed in 6% of patients in London, and in 6% of autopsy cases in Abidjan. Evidence of renal TB was present in 60% of autopsies in Abidjan and 61% of kidney biopsies in Cape Town. HIVAN and acute tubular necrosis (ATN) were also common biopsy findings in Cape Town. In Cape Town, 40 patients were dialyzed, of whom 28 (70%) were able to successfully discontinue renal replacement therapy. Antiretroviral therapy status, CD4 cell count, estimated glomerular filtration rate (eGFR) at biopsy and renal histology, other than ATN, were not predictive of eGFR recovery. CONCLUSION: Kidney disease was common in Africans with HIV/TB. Monitoring of kidney function, and provision of acute dialysis to those with severe kidney failure, is warranted.

Association of Racial Disparities With Access to Kidney Transplant After the Implementation of the New Kidney Allocation System.

Importance: Inactive patients on the kidney transplant wait-list have a higher mortality. The implications of this status change on transplant outcomes between racial/ethnic groups are unknown. Objectives: To determine if activity status changes differ among races/ethnicities and levels of sensitization, and if these differences are associated with transplant probability after implementation of the Kidney Allocation System. Design, Setting, and Participants: A multistate model was constructed from the Organ Procurement and Transplantation Network kidney transplant database (December 4, 2014, to September 8, 2016). The time interval followed Kidney Allocation System implementation and provided at least 1-year follow-up for all patients. The model calculated probabilities between active and inactive status and the following competing risk outcomes: living donor transplant, deceased donor transplant, and death/other. This retrospective cohort study included 42 558 patients on the Organ Procurement and Transplantation Network kidney transplant wait-list following Kidney Allocation System implementation. To rule out time-varying confounding from relisting, analysis was limited to first-time registrants. Owing to variations in listing practices, primary center listing data were used for dually listed patients. Individuals listed for another organ or pancreatic islets were excluded. Analysis began July 2017. Main Outcome and Measures: Probabilities were determined for transitions between active and inactive status and the following outcome states: active to living donor transplant, active to deceased donor transplant, active to death/other, inactive to living donor transplant, inactive to deceased donor transplant, and inactive to death/other. Results: The median (interquartile range) age at listing was 55.0 (18.0-89.0) years, and 26 535 of 42 558 (62.4%) were men. White individuals were 43.3% (n = 18 417) of wait-listed patients, while black and Hispanic individuals made up 27.8% (n = 11 837) and 19.5% (n = 8296), respectively. Patients in the calculated plasma reactive antibody categories of 0% or 1% to 79% showed no statistically significant difference in transplant probability among races/ethnicities. White individuals had an advantage in transplant probability over black individuals in calculated plasma reactive antibody categories of 80% to 89% (hazard ratio [HR], 1.8 [95% CI, 1.4-2.2]) and 90% or higher (HR, 2.4 [95% CI, 2.1-2.6]), while Hispanic individuals had an advantage over black individuals in the calculated plasma reactive antibody group of 90% or higher (HR, 2.5 [95% CI, 2.1-2.8]). Once on the inactive list, white individuals were more likely than Hispanic individuals (HR, 1.2 [95% CI, 1.17-1.3]) or black individuals (HR, 1.4 [95% CI, 1.3-1.4]) to resolve issues for inactivity resulting in activation. Conclusions and Relevance: For patients who are highly sensitized, there continues to be less access to kidney transplant in the black population after the implementation of the Kidney Allocation System. Health disparities continue after listing where individuals from minority groups have greater difficulty in resolving issues of inactivity.

Female preterm indigenous Australian infants have lower renal volumes than males: A predisposing factor for end-stage renal disease?

AIM: Indigenous Australians have an increased risk of developing chronic kidney disease (CKD). Indigenous women have a higher rate of CKD than men. In a cohort of Indigenous and non-Indigenous preterm neonates, we assessed total renal volume (TRV) (a proxy indicator for nephron number). We hypothesized that there would be no difference in renal volume between these two groups at term corrected (37 weeks gestation). METHODS: Normally grown preterm neonates less than 32 weeks of gestation were recruited and at term corrected dates, the neonates underwent renal ultrasonography (TRV measurements), urine microalbumin-creatinine ratio and serum analysis for Cystatin C measurement for estimated glomerular filtration rate (eGFR) calculation. RESULTS: One hundred and five neonates (38 Indigenous; 67 non-Indigenous) were recruited. Indigenous neonates were significantly more premature and of lower birth weight. At term corrected age, Indigenous neonates had a significantly smaller TRV (18.5 (4.2) vs 21.4 (5.1) cm3 ; P = 0.027) despite no significant difference in body weight. Despite having a smaller TRV, there was no significant difference in eGFR between Indigenous and Non-indigenous neonates (47.8 [43.2-50.4] vs 46.2 [42.6-53.3] ml/min per 1.73 m2 ; P = 0.986). These infants achieve similar eGFR through hyperfiltration, which likely increases their future risk of CKD. There was no difference in microalbumin-creatinine ratio. Female Indigenous neonates, however, had significantly smaller TRV compared with Indigenous male neonates (15.9 (3.6) vs 20.6 (3.6) cm3 ; P = 0.006), despite no difference in eGFR, birth weight, gestational age, and weight at term corrected. CONCLUSION: The difference in TRV is likely to be an important risk factor for the difference in morbidity and mortality from renal disease reported between male and female Indigenous adults.

Identification of a novel loss-of-function mutation of the GLA gene in a Chinese Han family with Fabry disease.

BACKGROUND: Fabry disease is an X-linked recessive lysosomal disorder caused by deficient enzymatic activity of α-galactosidase A (α-Gal A). The insufficient enzymatic activity leads to excessive accumulation of glycosphingolipids, the substrates of the enzyme, in lysosomes in organs and tissues. Mutations in the α-Gal A gene (GLA, Xq22) have been proven to be responsible for Fabry disease. METHODS: In this study, we report a four-generation pedigree with left ventricular hypertrophy and chronic renal failure that was diagnosed by sequencing the GLA gene. An over expression system was constructed to evaluate the function of the detected mutation. RESULTS: We identified a novel mutation in exon 6 of the GLA gene, p.Asn278Lys, which completely co-segregated with the disease phenotype. The protein level of α-Gal A was significantly lower in the variant group than in the wild-type group; additionally, the pharmacological chaperone 1-deoxy-galactonojirimycin (DGJ) effectively normalized the enzyme activity of α-Gal A and its decline at the protein level. CONCLUSIONS: This study is the first to report a novel loss-of-function mutation, p.Asn278Lys, in exon 6 of the GLA gene as a genetic aetiology for Fabry disease. In addition, we analysed the feasibility of DGJ as a therapeutic approach for this particular GLA mutation.

Raising awareness, screening and prevention of chronic kidney disease: It takes more than a village.

Chronic kidney disease (CKD) is a major public health problem worldwide. Its prevalence and incidence are increasing, particularly among the ethnic minority populations. Diabetes, hypertension and obesity have been the three major aetiologies for CKD in all developed countries. While diabetes and hypertension remain the major causes of CKD in developing countries, environmental pollution, pesticides, water, analgesic abuse and herbal medications are common causes in these regions. Rapid urbanization and globalization are thought to be the contributing factors to rising prevalence and incidents of CKD. Despite the rising prevalence of CKD, disease awareness remains profoundly low. Worldwide, only 6% of the general population and 10% of the high-risk population are aware of their CKD statuses. Health screenings have been shown to be effective in improving the incidence of ESRD. However, currently there is no effective tool to assess and evaluate the awareness objectively.

Plasma biomarkers are associated with renal outcomes in individuals with APOL1 risk variants.

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as improvement in area under curve. Among the 498 participants, the median age was 56 years, 67.7% were female, and the baseline eGFR was 83.3 ml/min/1.73 m2 with 80 reaching outcome over 5.9 years. TNFR1, TNFR2, and KIM1 at enrollment were independently associated with renal outcome continuously (adjusted hazard ratio 2.0 [95% confidence interval 1.3-3.1]; 1.5 [1.2-1.9]; and 1.6 [1.3-1.9] per doubling in levels, respectively) or by tertiles. The area under the curve significantly improved from 0.75 with the clinical model to 0.79 with the biomarker-enhanced model. The event rate was 40% with all 3 biomarkers elevated (adjusted odds ratio of 5.3 (2.3-12.0) vs. 17% (adjusted odds ratio 1.8 [0.9-3.6] with 1 or 2 elevated and 7% with no biomarkers elevated. Thus, plasma concentrations of TNFR1, TNFR2, and KIM1 are independently associated with renal outcome and improve discrimination or reclassification of African ancestry individuals with a high-risk APOL1 genotype and preserve renal function. Elevation of all markers had higher risk of outcome and can assist with better clinical prediction and improved clinical trial efficiency by enriching event rates.