Evaluation of Racial, Ethnic, and Socioeconomic Disparities in Initiation of Kidney Failure Treatment During the First 4 Months of the COVID-19 Pandemic.

Importance: Persons with kidney failure require treatment (ie, dialysis or transplantation) for survival. The burden of the COVID-19 pandemic and pandemic-related disruptions in care have disproportionately affected racial and ethnic minority and socially disadvantaged populations, raising the importance of understanding disparities in treatment initiation for kidney failure during the pandemic. Objective: To examine changes in the number and demographic characteristics of patients initiating treatment for incident kidney failure following the COVID-19 pandemic by race and ethnicity, county-level COVID-19 mortality rate, and neighborhood-level social disadvantage. Design, Setting, and Participants: This cross-sectional time-trend study used data from US patients who developed kidney failure between January 1, 2018, and June 30, 2020. Data were analyzed between January and July 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Number of patients initiating treatment for incident kidney failure and mean estimated glomerular filtration rate (eGFR) at treatment initiation. Results: The study population included 127 149 patients with incident kidney failure between January 1, 2018, and June 30, 2020 (mean [SD] age, 62.8 [15.3] years; 53 021 [41.7%] female, 32 932 [25.9%] non-Hispanic Black, and 19 835 [15.6%] Hispanic/Latino patients). Compared with the pre-COVID-19 period, in the first 4 months of the pandemic (ie, March 1 through June 30, 2020), there were significant decreases in the proportion of patients with incident kidney failure receiving preemptive transplantation (1805 [2.1%] pre-COVID-19 vs 551 [1.4%] during COVID-19; P < .001) and initiating hemodialysis treatment with an arteriovenous fistula (2430 [15.8%] pre-COVID-19 vs 914 [13.4%] during COVID-19; P < .001). The mean (SD) eGFR at initiation declined from 9.6 (5.0) mL/min/1.73 m2 to 9.5 (4.9) mL/min/1.73 m2 during the pandemic (P < .001). In stratified analyses by race/ethnicity, these declines were exclusively observed among non-Hispanic Black patients (mean [SD] eGFR: 8.4 [4.6] mL/min/1.73 m2 pre-COVID-19 vs 8.1 [4.5] mL/min/1.73 m2 during COVID-19; P < .001). There were significant declines in eGFR at initiation for patients residing in counties in the highest quintile of COVID-19 mortality rates (9.5 [5.0] mL/min/1.73 m2 pre-COVID-19 vs 9.2 [5.0] mL/min/1.73 m2 during COVID-19; P < .001), but not for patients residing in other counties. The number of patients initiating treatment for incident kidney failure was approximately 30% lower than projected in April 2020. Conclusions and Relevance: In this cross-sectional study of US adults, the COVID-19 pandemic was associated with a substantially lower number of patients initiating treatment for incident kidney failure and treatment initiation at lower levels of kidney function during the first 4 months, particularly for Black patients and people living in counties with high COVID-19 mortality rates.

Twenty-four-hour versus clinic blood pressure levels as predictors of long-term cardiovascular and renal disease outcomes among African Americans.

In Caucasian and Asian populations, evidence suggests that 24-h blood pressures (BP) are more predictive of long-term cardiovascular events than clinic BP. However, few long-term studies have evaluated the predictive value of 24-h BP phenotypes (24-h, daytime, nighttime) among African Americans (AA). The purpose of this study is to evaluate the added value of 24-h BP phenotypes compared to clinic BP in predicting the subsequent fatal and non-fatal cardiovascular/renal disease events in AA subjects. AA subjects (n = 270) were initially studied between 1994 and 2006 and standardized clinic BP measurements were obtained during screening procedures for a 3-day inpatient clinical study during which 24-h BP measurements were obtained. To assess the subsequent incidence of cardiovascular and renal disease events, follow-up information was obtained and confirmed by review of paper and electronic medical records between 2015 and 2017. During a mean follow-up of 14 ± 4 years, 50 subjects had one or more fatal or non-fatal cardiovascular/renal disease events. After adjustment for covariates, clinic systolic and diastolic BP were strongly associated with cardiovascular/renal disease events and all-cause mortality (p < 0.0001). Twenty-four-hour BP phenotypes conferred a small incremental advantage over clinic BP in predicting cardiovascular/renal events, which was limited to making a difference of one predicted event in 250-1,000 predictions depending on the 24-h BP phenotype. Nocturnal BP was no more predictive than the other 24-h BP phenotypes. In AA, 24-h BP monitoring provides limited added value as a predictor of cardiovascular/renal disease events. Larger studies are needed in AA to confirm these findings.

Mortality and Recovery Associated with Kidney Failure due to Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: AKI requiring dialysis is a contributor to the growing burden of kidney failure, yet little is known about the frequency and patterns of recovery of AKI and its effect on outcomes in patients on incident dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the US Renal Data System, we evaluated a cohort of 1,045,540 patients on incident dialysis from January 1, 2005 to December 31, 2014, retrospectively. We examined the association of kidney failure due to AKI with the outcome of all-cause mortality and the associations of sex and race with kidney recovery. RESULTS: Mean age was 63±15 years, and 32,598 (3%) patients on incident dialysis had kidney failure due to AKI. Compared with kidney failure due to diabetes mellitus, kidney failure attributed to AKI was associated with a higher mortality in the first 0-3 months following dialysis initiation (adjusted hazard ratio, 1.28; 95% confidence interval, 1.24 to 1.32) and 3-6 months (adjusted hazard ratio, 1.16; 95% confidence interval, 1.11 to 1.20). Of the patients with kidney failure due to AKI, 11,498 (35%) eventually recovered their kidney function, 95% of those within 12 months. Women had a lower likelihood of kidney recovery than men (adjusted hazard ratio, 0.86; 95% confidence interval, 0.83 to 0.90). Compared with whites, blacks (adjusted hazard ratio, 0.68; 95% confidence interval, 0.64 to 0.72), Asians (adjusted hazard ratio, 0.82; 95% confidence interval, 0.69 to 0.96), Hispanics (adjusted hazard ratio, 0.82; 95% confidence interval, 0.76 to 0.89), and Native Americans (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.95) had lower likelihoods of kidney recovery. CONCLUSIONS: Kidney failure due to AKI confers a higher risk of mortality in the first 6 months compared with kidney failure due to diabetes or other causes. Recovery within 12 months is common, although less so among women than men and among black, Asian, Hispanic, and Native American patients than white patients.

Association of Socioeconomic Status and Comorbidities with Racial Disparities during Kidney Transplant Evaluation.

BACKGROUND AND OBJECTIVES: Black patients referred for kidney transplantation have surpassed many obstacles but likely face continued racial disparities before transplant. The mechanisms that underlie these disparities are unclear. We determined the contributions of socioeconomic status (SES) and comorbidities as mediators to disparities in listing and transplant. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a cohort (n=1452 black; n=1561 white) of patients with kidney failure who were referred for and started the transplant process (2009-2018). We estimated the direct and indirect effects of SES (self-reported income, education, and employment) and medical comorbidities (self-reported and chart-abstracted) as mediators of racial disparities in listing using Cox proportional hazards analysis with inverse odds ratio weighting. Among the 983 black and 1085 white candidates actively listed, we estimated the direct and indirect effects of SES and comorbidities as mediators of racial disparities on receipt of transplant using Poisson regression with inverse odds ratio weighting. RESULTS: Within the first year, 876 (60%) black and 1028 (66%) white patients were waitlisted. The relative risk of listing for black compared with white patients was 0.76 (95% confidence interval [95% CI], 0.69 to 0.83); after adjustment for SES and comorbidity, the relative risk was 0.90 (95% CI, 0.83 to 0.97). The proportion of the racial disparity in listing was explained by SES by 36% (95% CI, 26% to 57%), comorbidity by 44% (95% CI, 35% to 61%), and SES with comorbidity by 58% (95% CI, 44% to 85%). There were 409 (42%) black and 496 (45%) white listed candidates transplanted, with a median duration of follow-up of 3.9 (interquartile range, 1.2-7.1) and 2.8 (interquartile range, 0.8-6.3) years, respectively. The incidence rate ratio for black versus white candidates was 0.87 (95% CI, 0.79 to 0.96); SES and comorbidity did not explain the racial disparity. CONCLUSIONS: SES and comorbidity partially mediated racial disparities in listing but not for transplant.

Racial differences in utilization and outcomes of hemodialysis access in the Unites States.

OBJECTIVE: To evaluate patterns of use and outcomes of arteriovenous fistulas and prosthetic grafts within racial categories in a large population based cohort of hemodialysis (HD) patients in the United States. METHODS: A retrospective analysis of white, black, and Hispanic patients in the prospectively maintained United States Renal Database System who had an autogenous fistula or prosthetic graft placed for HD access between January 2007 and December 2014 was performed. Analysis of variance, χ2, t-tests, Kaplan-Meier, log-rank tests, multivariable logistic, and Cox regression analyses were used to evaluate maturation, patency, infection, and mortality. RESULTS: This study of 359,942 patients, composed of 285,781 autogenous fistulas (79.4%) and 74,161 prosthetic grafts (20.6%) placed in 213,877 white (59.4%), 115,727 black (32.2%), and 30,338 Hispanic (8.4%) patients. There was a 11% increase in the risk-adjusted odds of HD catheter use as bridge to autogenous fistula placement in blacks (adjusted odds ratio, 1.11; 95% confidence interval [CI], 1.08-1.14; P < .001) and a 9% increase in Hispanics (adjusted odds ratio, 1.09; 95% CI, 1.05-1.14; P < .001) compared with whites. Fistula maturation for HD access for whites vs blacks vs Hispanics was 77.0% vs 76.3% vs 77.8% (P = .35). After adjusting for covariates, fistula maturation was higher for blacks (adjusted hazard ratio, 1.09; 95% CI, 1.06-1.13; P < .001) and Hispanics (adjusted hazard ratio, 1.13; 95% CI, 1.06-1.20; P < .001) compared with whites. There was no significant difference in prosthetic graft maturation for blacks and Hispanics compared with whites. Primary, primary-assisted, and secondary patency were highest for Hispanic and least for black autogenous fistula recipients. Primary, primary-assisted, and secondary patency was also highest for Hispanic patients who received prosthetic grafts. Prosthetic grafts were associated with a decrease in patency and patient survival compared with fistulas in all racial categories. Mortality was lower for blacks and Hispanics relative to white patients. Initiation of HD with a catheter and conversion to autogenous fistula was associated with decrease in patency and patient survival compared with initiation with a fistula in all racial groups. CONCLUSIONS: Autogenous fistulas are associated with better patency and patient survival compared with prosthetic grafts for all races studied. The use of HD catheter before fistula placement is more prevalent in Hispanic and black patients and is associated with worse patency and patient survival irrespective of race. Fistula and graft patency is highest for Hispanic patients. Patient survival is higher for Hispanic and black patients relative to whites. These associations suggest potential benefit with initiation of HD via autogenous fistula and minimizing temporizing catheter use, irrespective of race.

Perspectives of African-American Family Members about Kidney Failure Treatment.

Understanding African-American families' experiences with treatment for kidney failure is necessary for informing the delivery of family-centered care and the design of appropriate interventions. This qualitative study explored treatment-related questions, concerns, and family impacts among African-American family members of patients with pre-kidney failure and kidney failure. Thirty-five family members participated in focus groups stratified by patients' treatment experiences (pre-kidney failure, in-center hemodialysis, peritoneal dialysis, awaiting living-donor kidney transplantation, or post-transplantation). Family members raised questions and concerns about the psychological, lifestyle, and practical aspects of treatment. Similarly, discussions about family impacts emphasized psychosocial effects, lifestyle consequences, and the provision and receipt of support. Efforts to address these questions, concerns, and perceived family impacts through additional research, early and tailored education, and supportive interventions are needed.

Single-Dose Pharmacokinetics, Safety, and Tolerability of Avadomide (CC-122) in Subjects With Mild, Moderate, or Severe Renal Impairment.

CC-122 (Avadomide) is a nonphthalimide analogue of thalidomide that has multiple pharmacological activities including immune modulation of several immune cell subsets, antigrowth activity, antiproliferative activity, and antiangiogenic activity. CC-122 as monotherapy and in combination with other agents is being evaluated for multiple indications including hematologic malignancies and advanced solid tumors. Given that renal clearance is one of the major routes of elimination for CC-122 and its clearance/exposure could be affected by renal impairment, a total of 50 subjects with various degrees of renal function were enrolled in an open-label, single-dose study to evaluate the impact of renal impairment on CC-122 pharmacokinetic disposition. The study showed that following administration of a single oral dose of 3 mg CC-122, renal impairment reduced both the apparent total plasma clearance and renal clearance of CC-122, but it had less impact on CC-122 absorption, as demonstrated by similar Tmax and Cmax among groups with various degrees of renal function. Compared with exposure in subjects with normal renal function, total plasma exposure to CC-122 increased by ∼20%, ∼50%, and ∼120% in subjects with mild, moderate, and severe renal insufficiency, respectively. Results from this study combined with modeling/simulation suggest that dose adjustments are necessary in patients with moderate or severe but not with mild renal impairment. Finally, a single dose of 3 mg CC-122 was safe and well tolerated by healthy subjects and subjects with mild, moderate, and severe renal impairment.

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm.

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), ß-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm.

First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis.

Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the PODXL gene encoding podocalyxin was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. However, this PODXL mutation appeared not to impair podocalyxin function, and it is necessary to identify new PODXL mutations and determine their causative role for FSGS. In the present study, we report the identification of a heterozygous nonsense PODXL mutation (c.C976T; p. Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared with those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British-Indian pedigree of AD-FSGS by WES. In vitro study showed that, human embryonic kidney 293T cells transfected with the pEGFP-PODXL-Arg326X or pEGFP-PODXL-Ser378X plasmid expressed significantly lower mRNA and PODXL protein compared with cells transfected with the wild-type plasmid. Blocking nonsense-mediated mRNA decay (NMD) significantly restored the amount of mutant mRNA and PODXL proteins, which indicated that the pathogenic effect of PODXL nonsense mutations is likely due to NMD, resulting in podocalyxin deficiency. Functional consequences caused by the PODXL nonsense mutations were inferred by siRNA knockdown in cultured podocytes and podocalyxin down-regulation by siRNA resulted in decreased RhoA and ezrin activities, cell migration and stress fiber formation. Our results provided new data implicating heterozygous PODXL nonsense mutations in the development of FSGS.

Mechanisms of Injury in APOL1-associated Kidney Disease.

BACKGROUND: An improved understanding of the pathogenesis in apolipoprotein L1 (APOL1) gene-associated chronic kidney disease (CKD) arose from observations in kidney transplantation. APOL1 genotyping could soon improve the safety of living kidney donation in individuals with recent African ancestry and alter the allocation of deceased donor kidneys. METHODS: This article reviews the potential mechanisms that underlie development of APOL1-associated nephropathy. Roles for circulating APOL1 protein versus intrinsic renal expression of APOL1 are discussed, as well as the requirement for modifying genetic and/or environmental factors. RESULTS: Abundant evidence supports local kidney production of APOL1 renal-risk variant protein in the development of nephropathy; this is true in both native kidney disease and after renal transplantation. Only a minority of kidneys from individuals with APOL1 high-risk genotypes will develop CKD or manifest shorter renal allograft survival after transplantation. Therefore, modifying factors that explain why only a subset of kidneys develops nephropathy remain critical to identify. It appears likely that environmental exposures, as opposed to major APOL1-second gene interactions, will prove to be stronger modifiers of the risk for nephropathy. CONCLUSIONS: The evolving understanding of the pathogenesis in APOL1-associated nephropathy will identify biomarkers predicting nephropathy in individuals at high genetic risk and lead to novel therapies to prevent or slow native CKD progression and prolong survival of transplanted kidneys. In the interim, the National Institutes of Health-sponsored "APOL1 Long-term Kidney Transplantation Outcomes" Network will determine whether APOL1 genotyping in individuals with recent African ancestry improves outcomes and safety in kidney transplantation.

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation.

BACKGROUND: Low tacrolimus concentrations have been associated with higher risk of acute rejection, particularly within African American (AA) kidney transplant recipients; little is known about intrapatient tacrolimus variabilities impact on racial disparities. METHODS: Ten year, single-center, longitudinal cohort study of kidney recipients. Intrapatient tacrolimus variability was assessed using the coefficient of variation (CV) measured between 1 month posttransplant and the clinical event, with a comparable period assessed in those without events. Pediatrics, nontacrolimus/mycophenolate regimens, and nonrenal transplants were excluded. Multivariable Cox regression models were used to analyze data. RESULTS: One thousand four hundred eleven recipients were included (54.4% AA) with 39 521 concentrations used to assess intrapatient tacrolimus CV. Overall, intrapatient tacrolimus CV was higher in AAs versus non-AAs (39.9 ± 19.8 % vs 34.8 ± 15.8% P < 0.001). Tacrolimus variability was a significant risk factor for deleterious clinical outcomes. A 10% increase in tacrolimus CV augmented the risk of acute rejection by 20% (adjusted hazard ratio, 1.20, 1.13-1.28; P < 0.001) and the risk of graft loss by 30% (adjusted hazard ratio, 1.30, 1.23-1.37; P < 0.001), with significant effect modification by race for acute rejection, but not graft loss. High tacrolimus variability (CV >40%) was a significant explanatory variable for disparities in AAs; the crude relative risk of acute rejection in AAs was reduced by 46% when including tacrolimus variability in modeling and reduced by 40% for graft loss. CONCLUSIONS: These data demonstrate that intrapatient tacrolimus variability is strongly associated with acute rejection in AAs and graft loss in all patients. Tacrolimus variability is a significant explanatory variable for disparities in AA recipients.

Clinical Course of Hemodialysis Access After Initial Endovascular Intervention for Stenosis in Asian Renal Failure Patients.

BACKGROUND: Arteriovenous fistula (AVF) and arteriovenous fistula graft (AVG) access for hemodialysis can develop stenosis, eventually leading to thrombosis and access failure. Prompt endovascular intervention can salvage the access but restenosis does occur. Clinical course, restenosis pattern, and risk factors associated with initial stenosis of AVFs/AVGs in Asian hemodialysis patients were studied. METHOD: A retrospective study was conducted (January 2009-June 2012) on consecutive patients with renal failure who developed the first-time stenosis in the vascular access and were managed with endovascular intervention. One hundred fourteen patients (54 AVFs and 60 AVGs) were studied, and all clinical outcomes were recorded until October 2013. RESULTS: The mean time from access creation to endovascular intervention for the first-time stenosis for patients with AVF and AVG was 23.5 (32.7 standard deviation [SD]) months and 12.5 (11.0) months, respectively. An average of 1.7 (range, 1-5) interventions were performed for AVFs, whereas 2.4 (range, 1-11) for AVGs ( P = .008). Upon conclusion of the study, 23 patients with AVF survived with functional index access, whereas 10 passed away with a functional original access. The remaining 21 patients with AVFs failed, requiring new access, tunneled catheter, or peritoneal dialysis. Of the 60 patients with AVG, 6 survived and 8 died with functional index access; 46 required new access or other forms of dialysis ( P = .000). Kaplan-Meier estimated that access patency and survival with functional access were significantly lower for AVGs than for AVFs after the first salvage intervention. Female patients had an increased risk of restenosis with both univariate ( P = .016) and multivariate ( P = .013) analysis. With univariate analysis ( P = .039), patients with hyperlipidemia had a higher risk of developing restenosis in the vascular access. CONCLUSION: The clinical course and prognosis of failing AVFs and AVGs are distinct. The information on access prognosis and stenosis recurrence patterns will be helpful for patient counseling and planning of follow-up intervals, after the first-time intervention for access stenosis.

Race, Genomics and Chronic Disease: What Patients with African Ancestry Have to Say.

BACKGROUND: Variants of the APOL1 gene increase risk for kidney failure 10-fold, and are nearly exclusively found in people with African ancestry. To translate genomic discoveries into practice, we gathered information about effects and challenges incorporating genetic risk in clinical care. METHODS: An academic-community-clinical team tested 26 adults with self-reported African ancestry for APOL1 variants, conducting in-depth interviews about patients' beliefs and attitudes toward genetic testing- before, immediately, and 30 days after receiving test results. We used constant comparative analysis of interview transcripts to identify themes. RESULTS: Themes included: Knowledge of genetic risk for kidney failure may motivate providers and patients to take hypertension more seriously, rather than inspiring fatalism or anxiety. Having genetic risk for a disease may counter stereotypes of Blacks as non-adherent or low-literate, rather than exacerbate stereotypes. CONCLUSION: Populations most likely to benefit from genomic research can inform strategies for genetic testing and future research.

Lymphocyte-depleting induction therapy lowers the risk of acute rejection in African American pediatric kidney transplant recipients.

The use of lymphocyte-depleting induction immunosuppression has been associated with a reduction in risk of AR after KT among adult recipients, particularly among high-risk subgroups such as AAs. However, data on induction regimen and AR risk are lacking among pediatric KT recipients. We examined outcomes among 7884 first-time pediatric KT recipients using SRTR data (2000-2014). Characteristics were compared across race using Wilcoxon rank-sum tests for continuous and chi-square tests for categorical variables. Risk of AR was estimated using modified Poisson regression, stratified by recipient race, adjusting for recipient age, gender, BMI, primary diagnosis, number of HLA mismatches, maintenance immunosuppression, and donor type. Risk of AR within 1 year was lower in AA recipients receiving lymphocyte-depleting induction (ATG or alemtuzumab; RR, 0.66; 95% CI, 0.52-0.83 P < .001) compared to AA recipients receiving anti-IL-2 receptor antibody induction. This difference was not seen in non-AA recipients receiving lymphocyte-depleting induction (RR, 0.93; 95% CI, 0.81-1.06, P = .26) compared to IL-2 induction. These findings support a role for lymphocyte-depleting induction agents in AA pediatric patients undergoing KT and continued use of IL-2 inhibitor induction in non-AA pediatric KT recipients.

Hispanics/Latinos With Type 2 Diabetes Have Functional and Symptomatic Pulmonary Impairment Mirroring Kidney Microangiopathy: Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVE: Type 2 diabetes mellitus (DM) has been associated with lung dysfunction, but this association has not been explored in Hispanics/Latinos. The relation between diabetic nephropathy and lung function and symptoms has not been explored. RESEARCH DESIGN AND METHODS: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited 16,415 participants aged 18-74 years (14,455 with complete data on variables of interest), between 2008 and 2011 from four U.S. communities through a two-stage area household probability design. Baseline measurements were used for analyses. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and dyspnea score were compared between individuals with and without DM, overall, and stratified by albuminuria. The analyses were performed separately for those with and without preexisting lung disease (chronic bronchitis, emphysema, asthma). Linear regression with sampling weights was used for all analyses. RESULTS: Among Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC values and a higher mean dyspnea score than those without DM (mean [95% CI] FEV1 3.00 [2.96-3.04] vs. 3.10 [3.09-3.11] L, P < 0.01; FVC 3.62 [3.59-3.66] vs. 3.81 [3.79-3.83] L, P < 0.001; dyspnea score 0.60 [0.49-0.71] vs. 0.41 [0.34-0.49], P < 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P < 0.001), 6% lower FEV1 (P < 0.001), and 2.5-fold higher dyspnea score (P = 0.04) than those without DM and with normoalbuminuria. Similar findings but with higher impairment in FVC were found in Hispanics/Latinos with lung disease. CONCLUSIONS: Hispanics/Latinos with DM have functional and symptomatic pulmonary impairment that mirror kidney microangiopathy. The progression of pulmonary impairment in adults with DM needs to be investigated further.

Risk of post-transplantation diabetes mellitus is greater in South Asian versus Caucasian kidney allograft recipients.

South Asians have increased risk for type 2 diabetes mellitus compared with Caucasians in the general population, but data for the development of post-transplantation diabetes mellitus (PTDM) is scarce. In this retrospective analysis, data was extracted from electronic patient records at a single centre (2004-2014). Caucasians were more likely to be male, with higher age and BMI than South Asians. Case-control matching was therefore undertaken to remove this bias, resulting in 102 recipient pairs. Median follow-up was 50 months (range 4-127 months). Matched groups had similar baseline characteristics, although South Asians compared with Caucasians received more deceased-donor kidneys (74% vs. 43%, respectively, P < 0.001) and were more likely to be CMV positive (77% vs. 43%, respectively, P < 0.001). PTDM incidence was significantly higher in South Asians versus Caucasians (35% vs. 10%, respectively, subhazard ratio 4.2 [95% CI: 2.1-8.5, P < 0.001]). Donor type had significant interaction with ethnicity, with the observed difference in PTDM rates between ethnicities most visible with receipt of deceased-donor kidneys. No significant difference was detected in allograft function, rejection episodes, adverse cardiovascular events or patient/graft survival. South Asians have increased risk of PTDM, especially recipients of deceased kidneys, and recognition of this allows appropriate patient counselling and development of targeted strategies.

Cardiovascular autonomic neuropathy associates with nephropathy lesions in American Indians with type 2 diabetes.

AIMS: Cardiovascular autonomic neuropathy (CAN) predicts clinical diabetic nephropathy (DN). We investigated the relationship between DN structural lesions and CAN. METHODS: Sixty three Pima Indians with type 2 diabetes underwent kidney biopsies following a 6-year clinical trial testing the renoprotective efficacy of losartan vs. placebo. CAN was assessed a median 9.2years later. CAN variables included expiration/inspiration ratio (E/I), standard deviation of the normal R-R interval (sdNN), and low and high frequency signal power and their ratio (LF, HF, LF/HF); lower values reflect more severe neuropathy. Associations of CAN with renal structural variables were assessed by linear regression adjusted for age, sex, diabetes duration, blood pressure, HbA1c, glomerular filtration rate, and treatment assignment during the trial. RESULTS: Global glomerular sclerosis was negatively associated with sdNN (partial r=-0.35, p=0.01) and LF (r=-0.32, p=0.02); glomerular basement membrane width was negatively associated with all measures of CAN except for LF/HF (r=-0.28 to -0.42, p<0.05); filtration surface density was positively associated with sdNN, LF, and HF (r=0.31 to 0.38, p<0.05); and cortical interstitial fractional volume was negatively associated with HF (r=-0.27, p=0.04). CONCLUSIONS: CAN associates with DN lesions.

Quantifying the Race Stratified Impact of Socioeconomics on Graft Outcomes in Kidney Transplant Recipients.

BACKGROUND: Socioeconomic status (SES) is a significant determinant of health outcomes and may be an important component of the causal chain surrounding racial disparities in kidney transplantation. The social adaptability index (SAI) is a validated and quantifiable measure of SES, with a lack of studies analyzing this measure longitudinally or between races. METHODS: Longitudinal cohort study in adult kidney transplantation transplanted at a single-center between 2005 and 2012. The SAI score includes 5 domains (employment, education, marital status, substance abuse and income), each with a minimum of 0 and maximum of 3 for an aggregate of 0 to 15 (higher score → better SES). RESULTS: One thousand one hundred seventy-one patients were included; 624 (53%) were African American (AA) and 547 were non-AA. African Americans had significantly lower mean baseline SAI scores (AAs 6.5 vs non-AAs 7.8; P < 0.001). Cox regression analysis demonstrated that there was no association between baseline SAI and acute rejection in non-AAs (hazard ratio [HR], 0.92; 95% confidence interval [95% CI], 0.81-1.05), whereas it was a significant predictor of acute rejection in AAs (HR, 0.89; 95% CI, 0.80-0.99). Similarly, a 2-stage approach to joint modelling of time to graft loss and longitudinal SAI did not predict graft loss in non-AAs (HR, 1.01; 95% CI, 0.28-3.62), whereas it was a significant predictor of graft loss in AAs (HR, 0.23; 95% CI, 0.06-0.93). CONCLUSIONS: After controlling for confounders, SAI scores were associated with a lower risk of acute rejection and graft loss in AA kidney transplant recipients, whereas neither baseline nor follow-up SAI predicted outcomes in non-AA kidney transplant recipients.