The relation of C - reactive protein to chronic kidney disease in African Americans: the Jackson Heart Study

<p>Abstract</p> <p>Background</p> <p>African Americans have an increased incidence and worse prognosis with chronic kidney disease (CKD - estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m²) than their counterparts of European-descent. Inflammation has been related to renal disease in non-Hispanic whites, but there are limited data on the role of inflammation in renal dysfunction in African Americans in the community.</p> <p>Methods</p> <p>We examined the cross-sectional relation of log transformed C-reactive protein (CRP) to renal function (eGFR by Modification of Diet and Renal Disease equation) in African American participants of the community-based Jackson Heart Study's first examination (2000 to 2004). We conducted multivariable linear regression relating CRP to eGFR adjusting for age, sex, body mass index, systolic and diastolic blood pressure, diabetes, total/HDL cholesterol, triglycerides, smoking, antihypertensive therapy, lipid lowering therapy, hormone replacement therapy, and prevalent cardiovascular disease events. In a secondary analysis we assessed the association of CRP with albuminuria (defined as albumin-to-creatinine ratio > 30 mg/g).</p> <p>Results</p> <p>Participants (n = 4320, 63.2% women) had a mean age ± SD of 54.0 ± 12.8 years. The prevalence of CKD was 5.2% (n = 228 cases). In multivariable regression, CRP concentrations were higher in those with CKD compared to those without CKD (mean CRP 3.2 ± 1.1 mg/L vs. 2.4 ± 1.0 mg/L, respectively p < 0.0001). CRP was significantly associated with albuminuria in sex and age adjusted model however not in the multivariable adjusted model (p > 0.05).</p> <p>Conclusion</p> <p>CRP was associated with CKD however not albuminuria in multivariable-adjusted analyses. The study of inflammation in the progression of renal disease in African Americans merits further investigation.</p

Smoking patterns and chronic kidney disease in US Hispanics: Hispanic Community Health Study/Study of Latinos

Intermittent smoking is prevalent among Hispanics, but little is known about whether this smoking pattern associates with increased chronic kidney disease (CKD) risk in this population. The objective of the present study is to identify patterns of exposure associated with CKD in US Hispanics

Acculturation and chronic kidney disease in the Hispanic community health study/study of Latinos (HCHS/SOL)

Hispanics/Latinos are burdened by chronic kidney disease (CKD). The role of acculturation in this population has not been explored. We studied the association of acculturation with CKD and cardiovascular risk factor control. We performed cross-sectional analyses of 13,164 U.S. Hispanics/Latinos enrolled in the HCHS/SOL Study between 2008 and 2011. Acculturation was measured using the language and ethnic social relations subscales of the Short Acculturation Scale for Hispanics, and proxies of acculturation (language preference, place of birth and duration of residence in U.S.). CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or urine albumin-to-creatinine ratio ≥ 30 mg/g. On multivariable analyses stratified by age, lower language subscale score was associated with higher odds of CKD among those older than 65 (OR 1.29, 95% CI, 1.03, 1.63). No significant association was found between proxies of acculturation and CKD in this age strata. Among individuals aged 18–44, a lower language subscale score was associated with lower eGFR (β = −0.77 ml/min/1.73 m2, 95% CI −1.43, −0.10 per 1 SD increase) and a similar pattern was observed for ethnic social relations. Among those older than 65, lower language subscale score was associated with higher log-albuminuria (β = 0.12, 95% CI 0.03, 0.22). Among individuals with CKD, acculturation measures were not associated with control of cardiovascular risk factors. In conclusion, lower language acculturation was associated with a higher prevalence of CKD in individuals older than 65. These findings suggest that older individuals with lower language acculturation represent a high risk group for CKD

Seed-shattering phenology at soybean harvest of economically important weeds in multiple regions of the United States. Part 1: Broadleaf species

Potential effectiveness of harvest weed seed control (HWSC) systems depends upon seed shatter of the target weed species at crop maturity, enabling its collection and processing at crop harvest. However, seed retention likely is influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed-shatter phenology in 13 economically important broadleaf weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after physiological maturity at multiple sites spread across 14 states in the southern, northern, and mid-Atlantic United States. Greater proportions of seeds were retained by weeds in southern latitudes and shatter rate increased at northern latitudes. Amaranthus spp. seed shatter was low (0% to 2%), whereas shatter varied widely in common ragweed (Ambrosia artemisiifolia L.) (2% to 90%) over the weeks following soybean physiological maturity. Overall, the broadleaf species studied shattered less than 10% of their seeds by soybean harvest. Our results suggest that some of the broadleaf species with greater seed retention rates in the weeks following soybean physiological maturity may be good candidates for HWSC

Seed-shattering phenology at soybean harvest of economically important weeds in multiple regions of the United States. Part 2: Grass species

Seed shatter is an important weediness trait on which the efficacy of harvest weed seed control (HWSC) depends. The level of seed shatter in a species is likely influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed shatter of eight economically important grass weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after maturity at multiple sites spread across 11 states in the southern, northern, and mid-Atlantic United States. From soybean maturity to 4 wk after maturity, cumulative percent seed shatter was lowest in the southern U.S. regions and increased moving north through the states. At soybean maturity, the percent of seed shatter ranged from 1% to 70%. That range had shifted to 5% to 100% (mean: 42%) by 25 d after soybean maturity. There were considerable differences in seed-shatter onset and rate of progression between sites and years in some species that could impact their susceptibility to HWSC. Our results suggest that many summer annual grass species are likely not ideal candidates for HWSC, although HWSC could substantially reduce their seed output during certain years

Seed-shattering phenology at soybean harvest of economically important weeds in multiple regions of the United States. Part 3: Drivers of seed shatter

Seed retention, and ultimately seed shatter, are extremely important for the efficacy of harvest weed seed control (HWSC) and are likely influenced by various agroecological and environmental factors. Field studies investigated seed-shattering phenology of 22 weed species across three soybean [Glycine max (L.) Merr.]-producing regions in the United States. We further evaluated the potential drivers of seed shatter in terms of weather conditions, growing degree days, and plant biomass. Based on the results, weather conditions had no consistent impact on weed seed shatter. However, there was a positive correlation between individual weed plant biomass and delayed weed seed-shattering rates during harvest. This work demonstrates that HWSC can potentially reduce weed seedbank inputs of plants that have escaped early-season management practices and retained seed through harvest. However, smaller individuals of plants within the same population that shatter seed before harvest pose a risk of escaping early-season management and HWSC

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no effect. This decrease in Ovcar3 cell proliferation was due to a higher fraction of cells in the G(0)/G(1) stage of the cell cycle. CGZ and TGZ treatment increased apoptosis after 4 hours of treatment but not after 8 or 12 hours. Treatment with TGZ or CGZ increased PPARγ mRNA expression in Ovcar3 cells; however, protein levels were unchanged. Surprisingly, luciferase promoter assays revealed that none of the TZDs increased PPARγ activity. Overexpression of wild type PPARγ increased reporter activity. This was further augmented by TGZ, Rosi, and Pio indicating that these cells have the endogenous capacity to mediate PPARγ transactivation. To determine whether PPARγ mediates the TZD-induced decrease in proliferation, cells were treated with CGZ or TGZ in the absence or presence of a dominant negative (DN) or wild type overexpression PPARγ construct. Neither vector changed the TZD-mediated cell proliferation suggesting this effect of TZDs on ovarian cancer cells may be PPARγ independent.CGZ and TGZ cause a decrease in ovarian cancer cell proliferation that is PPARγ independent. This concept is supported by the finding that a DN or overexpression of the wild type PPARγ did not affect the changes in cell proliferation and cell cycle

Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function

Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m2), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10−7) and FNDC1 (p-value = 3.0×10−7) for UACR, and KCNQ1 with eGFR (p = 3.6×10−6). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy