Background
Black individuals have been disproportionately affected by the coronavirus disease 2019 (COVID-19). However, it remains unclear whether there are any biological factors that predispose ...Black patients to COVID-19-related morbidity and mortality.
Objective
To compare in-hospital morbidity, mortality, and inflammatory marker levels between Black and White hospitalized COVID-19 patients.
Design and Participants
This single-center retrospective cohort study analyzed data for Black and White patients aged ≥18 years hospitalized with a positive SARS-CoV-2 PCR test between March 1, 2020, and August 4, 2020.
Main Measures
The exposure was self-identified race documented in the medical record. The primary outcome of was in-hospital death. Secondary outcomes included intensive care unit admission, hospital morbidities, and inflammatory marker levels.
Key Results
A total of 1,424 Black and White patients were identified. The mean ± SD age was 56.1 ± 17.4 years, and 663 (44.5%) were female. There were 683 (48.0%) Black and 741 (52.0%) White patients. In the univariate analysis, Black patients had longer hospital stays (8.1 ± 10.2 vs. 6.7 ± 8.3 days, p = 0.011) and tended to have higher rates of in-hospital death (11.0% vs. 7.3%), myocardial infarction (6.9% vs. 4.5%), pulmonary embolism (PE; 5.0% vs. 2.3%), and acute kidney injury (AKI; 39.4% vs. 23.1%) than White patients (p <0.05). However, after adjusting for potential confounders, only PE (adjusted odds ratio aOR 2.07, 95% CI, 1.13–3.79) and AKI (aOR 2.16, 95% CI, 1.57–2.97) were statistically significantly associated with Black race. In comparison with White patients, Black patients had statistically significantly higher peak plasma D-dimer (standardized β = 0.10), erythrocyte sedimentation rate (standardized β = 0.13), ferritin (standardized β = 0.09), and lactate dehydrogenase (standardized β = 0.11), after adjusting for potential confounders (p<0.05).
Conclusions
Black hospitalized COVID-19 patients had increased risks of developing PE and AKI and higher inflammatory marker levels compared with White patients. This observation may be explained by differences in the prevalence and severity of underlying comorbidities and other unmeasured biologic risk factors between Black and White patients. Future research is needed to investigate the mechanism of these observed differences in outcomes of severe COVID-19 infection in Black versus White patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abnormalities in calcium metabolism are common in chronic kidney disease (CKD). Diminished urinary calcium excretion may promote vascular calcification and increased urinary calcium excretion may ...lead to nephrolithiasis and nephrocalcinosis, conditions associated with CKD.
To study predictors of urinary calcium excretion and its association with adverse clinical outcomes in CKD.
This study assessed 3768 nondialysis participants in the Chronic Renal Insufficiency Cohort study from April 2003 to September 2008. Participants were followed up to October 2018.
Clinically plausible predictors of urinary calcium excretion and 24-h urinary calcium excretion at baseline.
Urinary calcium excretion; incident end stage kidney disease (ESKD), CKD progression 50% estimated glomerular filtration rate (eGFR) decline or incident ESKD, all-cause mortality, and atherosclerotic cardiovascular disease events.
eGFR was positive correlated with 24-h urinary calcium excretion. The variables most strongly associated with 24-h urinary calcium excretion in males and females were 24-h urinary sodium (β = 0.19 and 0.28, respectively), serum parathyroid hormone (β = -0.22 and -0.20, respectively), loop diuretics (β = 0.36 and 0.26, respectively), thiazide diuretics (β = -0.49 and -0.53, respectively), and self-identified black race (β = -0.23 and -0.27, respectively). Lower urinary calcium excretion was associated with greater risks of adverse outcomes, but these associations were greatly attenuated or nullified after adjustment for baseline eGFR.
Urinary calcium excretion is markedly lower in individuals with CKD compared to the general population. Determinants of urinary calcium excretion differed between sexes and levels of CKD. Associations between urinary calcium excretion and adverse clinical events were substantially confounded by eGFR.
Vasopressin triggers the phosphorylation and apical plasma membrane accumulation of aquaporin 2 (AQP2), and it plays an essential role in urine concentration. Vasopressin, acting through protein ...kinase A, phosphorylates AQP2. However, the phosphorylation state of AQP2 could also be affected by the action of protein phosphatases (PPs). Rat inner medullas (IM) were incubated with calyculin (PP1 and PP2A inhibitor, 50 nM) or tacrolimus (PP2B inhibitor, 100 nM). Calyculin did not affect total AQP2 protein abundance (by Western blot) but did significantly increase the abundances of pS256-AQP2 and pS264-AQP2. It did not change pS261-AQP2 or pS269-AQP2. Calyculin significantly enhanced the membrane accumulation (by biotinylation) of total AQP2, pS256-AQP2, and pS264-AQP2. Likewise, immunohistochemistry showed an increase in the apical plasma membrane association of pS256-AQP2 and pS264-AQP2 in calyculin-treated rat IM. Tacrolimus also did not change total AQP2 abundance but significantly increased the abundances of pS261-AQP2 and pS264-AQP2. In contrast to calyculin, tacrolimus did not change the amount of total AQP2 in the plasma membrane (by biotinylation and immunohistochemistry). Tacrolimus did increase the expression of pS264-AQP2 in the apical plasma membrane (by immunohistochemistry). In conclusion, PP1/PP2A regulates the phosphorylation and apical plasma membrane accumulation of AQP2 differently than PP2B. Serine-264 of AQP2 is a phosphorylation site that is regulated by both PP1/PP2A and PP2B. This dual regulatory pathway may suggest a previously unappreciated role for multiple phosphatases in the regulation of urine concentration.
Current literature is lacking a comprehensive review of data on dietary interventions in blood pressure (BP) management in sub-Saharan African countries. We assessed the association of dietary and ...other lifestyle interventions with BP-lowering effects in populations within sub-Saharan Africa.
We performed a systematic review and random-effects meta-analysis to determine the impact of dietary and lifestyle interventions on SBP and DBP in sub-Saharan Africa. We searched the MEDLINE, EMBASE, and Web of Science databases. We included intervention studies that were randomized and nonrandomized conducted in Africans residing in sub-Saharan Africa investigating diet and other lifestyle, physical activity, weight loss, tobacco, and alcohol cessation modifications. We determined the effect of diet and other lifestyle interventions on SBP and DBP. We expressed effect size as weighted mean difference and 95% confidence interval (CI).
: We identified six studies with a total of 1412 individuals, 38% males, mean age of 52.8 years (SD = 11.5). The weighted mean difference of dietary and other lifestyle interventions on SBP and DBP was -7.33 mmHg, (95% CI: -9.90 to -4.76, P < 0.001) and -2.98 mmHg, (95% CI: -4.28 to -1.69, P < 0.001), respectively. In the metaregression analyses, the duration of the interventions did not have any effect on changes in SBP and DBP.
: Dietary modifications showed a beneficial overall improvement in SBP and DBP in Africans. However, aside from low-salt interventions, studies on dietary potassium, healthy dietary patterns, and lifestyle modifications have not been investigated extensively in Africans and are in critical need. In addition, researchers will need to consider the settings (rural, urban, or semiurban) and the predominant existing dietary habits while designing studies on dietary interventions in sub-Saharan Africa.
CRD42020207923.
Background Pregnancy complications are risk factors for cardiovascular disease (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in ...combination with pregnancy complications, in predicting subsequent severe maternal CVD. Methods and Results This study included 566 mothers of diverse races and ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and CysC (cystatin C) were measured 1 to 3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models. During an average of 10.3±3.2 years of follow-up, 30 mothers developed 1 or more CVDs. Only a modest association was observed between creatinine and risk of CVD. In comparison, we found that per 0.1 mg/L increase of CysC was associated with a hazard ratio (HR) of 1.2 (95% CI, 1.1-1.4) for CVD after adjusting for covariates. Compared with those without preeclampsia and with normal CysC level (≤75th percentile), mothers with preeclampsia and elevated CysC (>75th percentile) had the highest risk of CVD (HR, 4.6 95% CI, 1.7-17.7), whereas mothers with preeclampsia only or with elevated CysC only did not have significantly increased CVD risk. Similar synergistic effects for CVD were observed between CysC and preterm delivery. Conclusions In this sample of US, traditionally underrepresented multiracial and multiethnic high-risk mothers, elevated maternal plasma CysC, independently and jointly with pregnancy complications, increased risk of CVD later in life. These findings warrant further investigation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03228875.
Lupus nephritis (LN) is a serious organ manifestation of systemic lupus erythematosus. Histologic overlap is relatively common in the six pathologic classes (I to VI) of LN. For example, mixed ...proliferative LN (MPLN) often includes features of classes III & V or classes IV & V combined. We performed a comparative evaluation of renal outcomes in patients with MPLN to patients with pure proliferative LN (PPLN) against pre-specified renal outcomes, and we also identified predictor of clinical outcomes among those with PPLN and MPLN.
Individuals with MPLN will have worse short-term renal outcomes compared to those with PPLN.
We retrospectively reviewed 278 adult LN patients (≥18 years old) identified from an Emory University Hospital registry of native renal biopsies performed between January 2000 and December 2011. The final analytic sample consisted of individuals with a diagnosis of PPLN (n = 60) and MPLN (n = 96). We analyzed differences in clinical and laboratory characteristics at baseline. We also assessed associations between LN category and renal outcomes (complete remission and time to ESRD) with logistic and Cox proportional hazards models within two years of baseline.
The study population was predominantly female (83.97%) and African American (71.8%) with a mean age of 33.4 years at baseline. Over a median follow up of 1.02 years, we did not find any statistically significant associations between MPLN and the development of ESRD or remission when compared to patients with PPLN (adjusted HR = 0.30, 95% CI = 0.07, 1.26).
There was no association between mixed or pure histopathologic features of LN at presentation and rate of complete or partial remission but higher baseline eGFR was associated with a lower probability of complete remission among patients with lupus nephritis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Progressive CKD in Black individuals is strongly associated with polymorphisms in the
gene, but it is unknown whether dietary risk factors for CKD progression vary in high- versus low-risk
genotypes. ...We investigated if
genotypes modify associations of dietary potassium and sodium with CKD progression and death.
We analyzed 1399 self-identified Black participants enrolled in the Chronic Renal Insufficiency Cohort from April 2003 to September 2008. Exposures were calibrated 24-hour urine potassium and sodium excretion. The primary outcome was CKD progression defined as the time to 50% decline in eGFR or kidney failure. The secondary outcome was CKD progression or death. We tested for an interaction between urinary potassium and sodium excretion and
genotypes.
Median 24-hour urinary sodium and potassium excretions in Black participants were 150 mmol (interquartile range, 118-188) and 43 mmol (interquartile range, 35-54), respectively. Individuals with high- and low-risk
genotypes numbered 276 (20%) and 1104 (79%), respectively. After a median follow-up of 5.23 years, CKD progression events equaled 605, and after 7.29 years, CKD progression and death events equaled 868. There was significant interaction between
genotypes and urinary potassium excretion with CKD progression and CKD progression or death (
=0.003 and
=0.03, respectively). In those with high-risk
genotypes, higher urinary potassium excretion was associated with a lower risk of CKD progression (quartiles 2-4 versus 1: hazard ratio, 0.83; 95% confidence interval, 0.50 to 1.39; hazard ratio, 0.54; 95% confidence interval, 0.31 to 0.93; and hazard ratio, 0.50; 95% confidence interval, 0.27 to 0.93, respectively). In the low-risk
genotypes, higher urinary potassium excretion was associated with a higher risk of CKD progression (quartiles 2-4 versus 1: hazard ratio, 1.01; 95% confidence interval, 0.75 to 1.36; hazard ratio, 1.23; 95% confidence interval, 0.91 to 1.66; and hazard ratio, 1.53; 95% confidence interval, 1.12 to 2.09, respectively). We found no interaction between
genotypes and urinary sodium excretion with CKD outcomes.
Higher urinary potassium excretion was associated with lower versus higher risk of CKD progression in
high-risk and low-risk genotypes, respectively.
Clinical trials and cohort studies are required to meet target recruitment of study participants within stipulated timelines, especially when the priority is to include populations traditionally ...unrepresented in biomedical research. By the third quarter of 2019, the University of Arizona‐Banner Health Provider Organization (UA‐Banner HPO) has enrolled > 30,000 core participants into the All of Us Research Program (AoURP), the research cohort of the Precision Medicine Initiative. The majority of enrolled participants meet the criteria for individuals under‐represented in biomedical research. The enrollment goals were calculated based on a target of 20,000 as set by the National Institutes of Health and our health provider organization achieved enrollment numbers between 17% and 86% above the targeted daily enrollment. We evaluated enrollment methods and challenges to enrollments encountered by the UA‐Banner Health Provider Organization into the AoURP. Challenges to enrollment centered around the need for high‐touch engagement methods, time investment necessary for stakeholder inclusion, and the use of purely digital enrollment methods especially in populations under‐represented in biomedical research. These challenges occurred at the level of the individual, provider, institutions, and community, and cumulatively impacted participant enrollment. Successful strategies for engagement and enrollment leveraged provider partners as advocates for the program. For high‐volume enrollment in clinical research, it is important to engage leaders in the healthcare setting, patient providers, and tailor engagement and enrollment to potential participant needs. We emphasize the need for precision engagement and enrollment methods tailored to individual needs.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives
To investigate racial and ethnic differences in graft and recipient survival in elderly kidney transplant recipients.
Design
Retrospective cohort.
Setting
First‐time, kidney‐only ...transplant recipients aged 60 and older of age at transplantation transplanted between July 1996 and October 2010 (N = 44,013).
Participants
United Network for Organ Sharing (UNOS) database.
Measurements
Time to graft failure and death obtained from the UNOS database and linkage to the Social Security Death Index. Neighborhood poverty from 2000 U.S. Census geographic data.
Results
Of the 44,013 recipients in the sample, 20% were black, 63% non‐Hispanic white, 11% Hispanic, 5% Asian, and the rest “other racial groups.” In adjusted Cox models, blacks were more likely than whites to experience graft failure (hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.15–1.32), whereas Hispanics (HR = 0.77, 95% CI = 0.70–0.85) and Asians (HR = 0.70, 95% CI = 0.61–0.81) were less likely to experience graft failure. Blacks (HR = 0.84, 95% CI = 0.80–0.88), Hispanics (HR = 0.68, 95% CI = 0.64–0.72), and Asians (HR = 0.62, 95% CI = 0.57–0.68) were less likely than whites to die after renal transplantation.
Conclusion
Elderly blacks are at greater risk of graft failure than white transplant recipients but survive longer after transplantation. Asians have the highest recipient and graft survival, followed by Hispanics. Further studies are needed to assess additional factors affecting graft and recipient survival in elderly adults and to investigate outcomes such as quality of life.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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