Differential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic in utero

Mercury and arsenic are known developmental toxicants. Prenatal exposures are associated with adverse childhood health outcomes that could be in part mediated by epigenetic alterations that may also contribute to altered immune profiles. In this study, we examined the association between prenatal mercury exposure on both DNA methylation and white blood cell composition of cord blood, and evaluated the interaction with prenatal arsenic exposure. A total of 138 mother-infant pairs with postpartum maternal toenail mercury, prenatal urinary arsenic concentrations, and newborn cord blood were assessed using the Illumina Infinium Methylation450 array. White blood cell composition was inferred from DNA methylation measurements. A doubling in toenail mercury concentration was associated with a 2.5% decrease (95% CI: 5.0%, 1.0%) in the estimated monocyte proportion. An increase of 3.5% (95% CI: 1.0, 7.0) in B-cell proportion was observed for females only. Among the top 100 CpGs associated with toenail mercury levels (ranked on P-value), there was a significant enrichment of loci located in North shore regions of CpG islands (P = 0.049), and the majority of these loci were hypermethylated (85%). Among the top 100 CpGs for the interaction between arsenic and mercury, there was a greater than expected proportion of loci located in CpG islands (P = 0.045) and in South shore regions (P = 0.009) and all of these loci were hypermethylated. This work supports the hypothesis that mercury may be contributing to epigenetic variability and immune cell proportion changes, and suggests that in utero exposure to mercury and arsenic, even at low levels, may interact to impact the epigenome.     

Global DNA methylation (LINE-1) associated with exposure to arsenic-contaminated environment and with type of arsenical skin lesions in Thailand

The effects of chronic arsenic exposure mode on DNA methylation and skin lesion type are unclear. These relationships were investigated in an arsenic-contaminated area of southern Thailand. Cases with arsenical skin lesions (n = 131) and lesion-free controls (n = 163) were selected from an arsenic-contaminated sub-district, as well as 105 controls from a non-contaminated area. Type and severity of skin lesions and salivary global DNA methylation (LINE-1) were determined. Arsenic exposure was characterized as occupational, domestic and current (toe-nail arsenic). Associations were explored using logistic regression. Cases and controls had lower LINE-1 methylation and higher toenail arsenic than external controls (74.65% and 74.61% vs 76.05%, p < 0.001 for each). Cases were more likely to have been exposed domestically (OR_total 1.76, 95% ci 1.00, 3.11; and 2.22, 95% ci 1.22, 4.03; P_trend = 0.005 for exposure <36 and ≥36 years). More severe spotty hyperpigmentation was related to higher LINE-1 methylation (P_trend=0.006). LINE-1 methylation was positively associated with toenail arsenic only among non-symptomatic exposed subjects (OR 1.31, 95% ci 1.06, 1.64; p = 0.014). Exposure to an arsenic-contaminated environment results in global DNA hypomethylation. However, among symptomatic subjects, increased global DNA methylation was associated with increased severity of spotty hyperpigmentation.     

Association between toenail zinc concentrations and incidence of asthma among American young adults: The CARDIA study

BackgroundAs an essential micronutrient, zinc plays an important role in modulating the immune system. However, data on the association between zinc concentrations and asthma incidence are sparse, especially in adults.MethodsWe prospectively followed up 3682 individuals aged 20–32 years without history of asthma or current asthma at baseline from 1987–1988 to 2015–2016. Zinc concentrations were measured in toenail clippings collected at Exam Year 2 using inductively-coupled-plasma mass spectroscopy. Asthma was diagnosed by a physician and/or reported medication use for asthma control with verification. Cox regression was used to model the association between toenail zinc concentrations and asthma incidence.ResultsOver an average of 22.5 years of follow-up, 508 incident cases of asthma were identified. After adjustment for potential confounders, no statistically significant association was found between zinc concentration and asthma incidence (HR = 0.81; 95% CI: 0.62, 1.07; P_{linear trend} = 0.26). The observed association was not materially modified by sex, body mass index, smoking or atopic status. When stratifying data by race, a significant inverse linear association was found among African Americans (per 1 standard deviation increment in toenail zinc concentrations: HR = 0.86; 95% CI: 0.75, 0.99; P_{linear trend} = 0.03), but not in Caucasians (HR = 1.07; 95% CI: 0.91, 1.25; P_{linear trend} = 0.42), though the test for interaction was not statistically significant (P_interaction = 0.099).ConclusionsFindings from this prospective cohort study do not support a significant longitudinal association between toenail zinc concentrations and incidence of asthma among American young adults. Future studies are needed to confirm our findings.     

Angiopoietin-2 as a Prognostic Biomarker of Major Adverse Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease

Background

Chronic kidney disease (CKD) patients have higher prevalence of major adverse cardiovascular events (MACE) and all-cause mortality. Endothelial damage and dysfunction have been regarded as early portents of MACE in CKD patients. Angiopoietin-2 (Ang-2) impairs endothelial function and promotes aberrant neovascularization. The aim of the study was to assess the relationship between circulating Ang-2 and MACE or all-cause mortality in a CKD cohort.

Methods

A total of 621 pre-dialysis stage 3–5 CKD patients were enrolled from January 2006 to December 2011 and were followed up till October 2014. Plasma Ang-2 was measured in duplicate using commercial enzyme-linked immunosorbent assays (ELISA). Clinical outcomes included MACE or all-cause mortality

Results

Of all patients, 122 (19.8%) reached MACE or all-cause mortality. Seventy-two had MACE, 79 died, and 29 had both MACE and all-cause mortality during the follow-up period of 41.5±28.3 months. Ang-2 quintile was divided at 1405.0, 1730.0, 2160.9, and 2829.9 pg/ml. The adjusted HR of MACE or all-cause mortality for every single higher log Ang-2 was 5.69 (95% CI: 2.00–16.20, P = 0.001). The adjusted HR of MACE or all-cause mortality was 2.48 (95% CI: 1.25–4.90) for patients of quintile 5 compared with those of quintile 1. A longitudinal association between MACE or all-cause mortality and stepwise increases in Ang-2 levels was found (P-trend = 0.008).

Conclusions

Ang-2 is an independent predictor of MACE or all-cause mortality in CKD patients. Additional study is necessary in order to explore the mechanism of the association of Ang-2 with adverse outcomes in patients with CKD.     

Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m²/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.     

Association between Blood Dioxin Level and Chronic Kidney Disease in an Endemic Area of Exposure

Background

Dioxin is an industrial pollutant related to various diseases, but epidemiological data on its effects on the kidney are limited. Therefore, we conducted a study to evaluate the association between dioxin exposure and chronic kidney disease (CKD) and identify the related factors.

Methods

We conducted a community-based cross-sectional study and recruited participants from an area where the residents were exposed to dioxin released from a factory. We defined a “high dioxin level” as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) ≥ 20 pg WHO₉₈-TEQ_DF/g lipid in the serum and defined CKD as having an estimated glomerular filtration rate (e-GFR) ≤ 60 mL/min/1.73m² or a diagnosis of CKD by a physician. The renal function was assessed between 2005 and 2010, and we excluded those who had had kidney diseases before the study started. Comparisons between patients of CKD and those who did not have CKD were made to identify the risk factors for CKD.

Results

Of the 2898 participants, 1427 had high dioxin levels, and 156 had CKD. In the univariate analyses, CKD was associated with high dioxin levels, age, gender, metabolic syndrome, diabetes mellitus, hypertension, and high insulin and uric acid levels. After adjusting for other factors, we found high dioxin levels (adjusted odds ratio [AOR] = 1.76, 95% confidence interval [CI]: 1.04–2.99), female gender (AOR = 1.74, 95%CI: 1.20–2.53), hypertension (AOR = 1.68, 95%CI: 1.17–2.42), high insulin levels (AOR = 2.14, 95% CI: 1.26–3.61), high uric acid levels (AOR = 4.25, 95% CI: 2.92–6.20), and older age (AOR = 4.66, 95% CI: 1.87–11.62 for 40–64 year and AOR = 26.66, 95% CI: 10.51–67.62 for age ≥ 65 year) were independent predictors of CKD.

Conclusion

A high dioxin level was associated with an increased prevalence of CKD. Therefore, the kidney function of populations with exposure to dioxin should be monitored.     

慢性肾脏病患者血清GDF-15的水平及临床意义

目的:探讨慢性肾脏病(Chronic Kidney Disease,CKD)患者血清生长分化因子-15(Growth Differentiation Factor-15,GDF-15)的表达及与其他肾功能相关临床指标的相关性。方法:选取西南医科大学附属医院2017年3月至2017年7月健康体检中心30例健康体检者对照组及肾病内科、内分泌科、心内科住院病房各期CKD患者150例,采用ELISA法测试验检其血清GDF-15水平。结果:除去CKD1期外,各期CKD患者eGFR及血清SCr、BUN、GDF-15水平均明显高于健康对照组,差异具有统计学意义(P0.05);随着CKD分期的增加,患者血清SCr、BUN、GDF-15浓度逐渐增加,且各组之间差异具有统计学意义(P0.05)。CKD3组患者血清UA浓度明显高于健康对照组、CKD1组(P0.05),CKD4组、CKD5组血清UA浓度明显高于健康对照组、CKD1组及CKD2组(P0.05)。GDF-15水平与eGFR水平呈负相关(r=-0.768,P0.01),与SCr水平呈正相关(r=0.751,P0.01),与BUN水平呈正相关(r=0.764,P0.01),与UA水平呈正相关(r=0.470,P0.01)。结论:GDF-15与慢性肾脏病的发生与发展密切相关。     

Plasma-transforming growth factor-alpha expression in residents of an arseniasis area in Taiwan

Abstract

Epidemiological studies have demonstrated an association between long-term exposure to inorganic arsenic and the related adverse effects such as cancers, skin lesions, and vascular diseases. Although several hypotheses have been proposed for the mechanism of arsenic-induced pathogenesis, it remains imperfectly understood. Recent studies have suggested that alterations in growth signal transduction pathways, particularly involving transforming growth factor-alpha (TGF-alpha), may be important. Immunoassays were used to determine the plasma levels of TGF-alpha and epidermal growth factor receptor (EGFR), which is the receptor for TGF-alpha, in residents of an arseniasis area of Taiwan in relation to their estimated cumulative arsenic exposure from drinking water. No relationship between arsenic exposure and EGFR was found. However, among the high cumulative exposure group (>6 ppm-years), levels of plasma TGF-alpha (25.5±38.2 pg ml^?1) and the proportion of individuals with TGF-alpha over-expression (29.4%) were significantly higher (p<0.05) than normal, healthy unexposed controls (8.1±5.6 pg ml^?1, 8.6%, respectively). There was a significant linear trend between cumulative arsenic exposure and the prevalence of plasma TGF-alpha over-expression after adjusting for age and sex (p=0.019). The results suggest that plasma TGF-alpha expression may be a useful biomarker when detecting adverse effects on arsenic exposed population.     

Toenail mercury levels positively correlate with obesity and abdominal obesity among Korean adults

BackgroundAlthough previous studies have shown that short-term exposure to mercury is associated with obesity, it should be noted that mercury is not easily released and that it constantly accumulates in the body. However, few studies have explored the association between chronic mercury exposure and obesity. This study aimed to examine the association between chronic mercury exposure and obesity in Korean adults.MethodsThe study used baseline data from the Trace Element Study of Korean Adults in Yeungnam area. A total of 495 participants aged 40–69 years who provided the required information (demographic, diet, lifestyle, toenail mercury levels, and health examination results) were included. Toenail mercury levels were measured using neutron-activation analysis. Body mass index and waist circumference were obtained from medical examination. Multivariable-adjusted logistic regression and restricted cubic spline regression were used in the analysis.ResultsIn the fully adjusted logistic regression models, participants with the highest toenail mercury levels had a higher prevalence of obesity (odds ratio [OR]: 3.26, 95 % confidence interval [CI]: 1.79–5.93) and abdominal obesity (OR: 2.30, 95 % CI: 1.15–4.59). In the cubic spline regression model, linear relationships were confirmed between increased toenail mercury levels and higher prevalence of obesity and abdominal obesity (all p > 0.05 for nonlinearity).ConclusionsIn summary, chronic mercury exposure was associated with higher prevalence of obesity and abdominal obesity in Korean adults. Therefore, the development of public health interventions against environmental exposure of foods is required to manage and prevent obesity.     

Level of trace elements in serum and toenail samples of patients with onychocryptosis (ingrown toenail) and onychomycosis

BackgroundOnychocryptosis (ingrown toenail) and onychomycosis are common pathologies of the toenail and affecting many people. Since levels of trace elements have been shown to vary in certain diseases, in the presented work, chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se), and zinc (Zn) levels of toenail and serum samples of healthy individuals and patients with onychocryptosis and onychomycosis were compared.MethodsSerum and toenail samples of 88 voluntary subjects (healthy n = 24; onychomycosis n = 24; onychocryptosis n = 40) aged between 19–80 years were collected. Levels of trace elements in the samples were analyzed by using an inductively coupled plasma-optical emission spectrophotometer (ICP-OES Thermo iCAP - 6000). The differences in medians between the groups for elements were evaluated with Kruskal -Wallis H test with post hoc for pairwise comparisons in SPSS 18.ResultsMg (p < 0.001) and Mn (p = 0.002) levels were significantly increased whereas Zn (p = 0.011) level was decreased in toenails of patients with onychomycosis compared to healthy subjects. Although Mg and Mn levels were higher in female subjects with onychomycosis (p = 0.001; p = 0.019), Mn was only increased in male subjects (p = 0.015). Mg was the only trace element found to be independent of sex, age, and smoking status in patients with onychomycosis. However, no significant difference has been found in serum trace element levels neither between any groups nor toenail trace element levels of patients with onychocryptosis and healthy subjects.ConclusionAs a response of the human body to pathogens like fungi in toenails, Mg, Mn and Zn levels vary. Especially the role of Mg ions in onychomycosis needs to be investigated more specifically.     

Relationships between serum iron and liver diseases in nutrition intervention trials: A nested case-control study

BackgroundSerum iron is associated with the risk of several diseases. However, limited prospective studies have been performed between serum iron and the subsequent risk of chronic liver disease (CLD) and primary liver cancer (PLC) incidence.MethodsWe performed a nested case-control study using data from the Linxian Nutrition Intervention Trials among participants who developed PLC incidence or died from CLD over 22-years of follow-up. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of PLC incidence or CLD death in different quintile of baseline serum iron using logistic regression.ResultsIndividuals with serum iron in the highest quintile, compared to those in the second quintile (the reference), had an increased risk of CLD mortality (OR=2.02, 95% CI=1.27–3.27, P_trend=0.011). The association was stronger among HCV-positive participants (P_interaction=0.005). For PLC incidence, the risk estimates were above one, but not statistically significant (all P > 0.05).ConclusionsA significant positive association was found between serum iron and the risk of CLD-related mortality, especially in HCV-positive subjects. Our results suggest that serum iron plays a risk role in CLD death but not in PLC incidence.     

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients

ObjectiveNondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.MethodsThis case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).ResultsThe HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL).ConclusionCKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.     

Uric Acid Level Has a U-Shaped Association with Loss of Kidney Function in Healthy People: A Prospective Cohort Study

BackgroundThe relationship between hyperuricemia and chronic kidney disease (CKD) has been found in various observational studies. Although hypouricemia is associated with cardiovascular events, it has not been established as a risk factor for CKD. We investigated the relationship between serum uric acid level and the loss of kidney function and incident CKD in healthy people.ResultsThe following data was obtained: mean±SD age, male, 39.6±10.4 years, female 38.4±10.8 years; eGFR, male, 81.9±16.4 ml/min/1.73m2, female, 82.1±17.5 ml/min/1.73m2; serum uric acid level, male, 5.8±1.2 mg/dl, female, 4.1±0.9 mg/dl. Both low and high serum uric acid levels were associated with the outcome and eGFR decline in males (multivariate logistic additional additive models, linear p = 0.0001, spline p = 0.043; generalized additive models, linear p = 0.0001, spline p = 0.012). In subjects with low serum uric acid levels (male, <5 mg/dl; female, <3.6 mg/dl), multivariate linear mixed models showed that low serum uric acid levels were associated with eGFR decline in a time-dependent manner (male, p = 0.0001; female, p = 0.045).ConclusionThis study showed that low as well as high levels of uric acid are associated with the loss of kidney function. Hypouricemia is a candidate predictor of kidney function decline in healthy people.     

Plasma Free Metanephrine and Normetanephrine Levels are Increased in Patients with Chronic Kidney Disease

ObjectivePatients with impaired renal function, particularly those on dialysis, frequently exhibit high blood pressure and hemodynamic instability, which often lead to pheochromocytoma assessment. Our objective was to assess plasma free metanephrine (MN) and normetanephrine (NMN) in chronic kidney disease patients (CKD) with or without dialysis.MethodsIn this prospective observational study we performed enzyme-linked immunosorbent assays (ELISAs) to evaluate plasma free MN and NMN in 48 CKD patients (15 with stage 3-5 CKD without dialysis, 26 on hemodialysis [HD], and 7 continuous ambulatory peritoneal dialysis [CAPD]), 30 patients with histologically proven pheochromocytoma, and 43 hypertensive patients. Adrenal masses were ruled out by abdominal computed tomography (CT) scans in all CKD and control hypertensive patients.ResultsAll 3 CKD groups (HD, CAPD, and CKD without dialysis) had significantly higher plasma free MN and NMN levels than the control hypertensive group (P < .0055). HD and CAPD patients had significantly lower plasma free NMN (P < .0055), but free MN levels were not significantly different than those observed in pheochromocytoma patients. In patients with HD, CAPD, and CKD without dialysis, plasma free MN and NMN were higher than manufacturer’s upper limits of normal in 57.7% and 28.5%, 13.3% and 61.5%, and 85.7% and 26.6%, respectively. Regression models showed that the number of dialysis years was significantly correlated with plasma free MN (r = 0.615, P < .001) but not free NMN.ConclusionPlasma free MN and NMN levels are frequently elevated in CKD patients, particularly in those on dialysis. Plasma free MN levels significantly overlap with the range in pheochromocytoma patients and correlate with the number of years on dialysis. (Endocr Pract. 2014;20:139-144)     

Arsenic Exposure and Outcomes of Antimonial Treatment in Visceral Leishmaniasis Patients in Bihar,India: A Retrospective Cohort Study

BackgroundIn the late twentieth century, emergence of high rates of treatment failure with antimonial compounds (SSG) for visceral leishmaniasis (VL) caused a public health crisis in Bihar, India. We hypothesize that exposure to arsenic through drinking contaminated groundwater may be associated with SSG treatment failure due to the development of antimony-resistant parasites.MethodsA retrospective cohort design was employed, as antimony treatment is no longer in routine use. The study was performed on patients treated with SSG between 2006 and 2010. Outcomes of treatment were assessed through a field questionnaire and treatment failure used as a proxy for parasite resistance. Arsenic exposure was quantified through analysis of 5 water samples from within and surrounding the patient’s home. A logistic regression model was used to evaluate the association between arsenic exposure and treatment failure. In a secondary analysis survival curves and Cox regression models were applied to assess the risk of mortality in VL patients exposed to arsenic.ResultsOne hundred and ten VL patients treated with SSG were analysed. The failure rate with SSG was 59%. Patients with high mean local arsenic level had a non-statistically significant higher risk of treatment failure (OR = 1.78, 95% CI: 0.7–4.6, p = 0.23) than patients using wells with arsenic concentration <10 μg/L. Twenty one patients died in our cohort, 16 directly as a result of VL. Arsenic levels ≥ 10 μg/L increased the risk of all-cause (HR 3.27; 95% CI: 1.4–8.1) and VL related (HR 2.65; 95% CI: 0.96–7.65) deaths. This was time dependent: 3 months post VL symptom development, elevated risks of all-cause mortality (HR 8.56; 95% CI: 2.5–29.1) and of VL related mortality (HR 9.27; 95% CI: 1.8–49.0) were detected.Discussion/ConclusionThis study indicates a trend towards increased treatment failure in arsenic exposed patients. The limitations of the retrospective study design may have masked a strong association between arsenic exposure and selection for antimonial resistance in the field. The unanticipated strong correlation between arsenic exposure and VL mortality warrants further investigation.     

Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study

BackgroundAcute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries.Methods and findingsPatients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27–62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily.ConclusionsThis multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.

Etienne Macedo and colleagues report on a point-of-care testing program for acute kidney injury and disease in high-risk primary care patients.     

Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study

BackgroundVisceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients.MethodsIn this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient’s house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development.ResultsOut of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1–200 μg/L and 200.1–432.0 μg/L were 1.85 (1.13–3.03) and 2.31 (1.39–3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02–2.7; p = 0.04).ConclusionOur findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.     

Five-Year Incidence of Chronic Kidney Disease (Stage 3-5) and Associated Risk Factors in a Spanish Cohort: The MADIABETES Study

Objective

To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m²) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use.

Design

The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).

Results

The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12–11.44) and the incidence density was 2.07 (95% CI = 1.83–2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19–2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13–4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42–2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25–2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30–2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02–2.24).

Conclusions

After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.     

Income differences in COVID-19 incidence and severity in Finland among people with foreign and native background: A population-based cohort study of individuals nested within households

BackgroundAlthough intrahousehold transmission is a key source of Coronavirus Disease 2019 (COVID-19) infections, studies to date have not analysed socioeconomic risk factors on the household level or household clustering of severe COVID-19. We quantify household income differences and household clustering of COVID-19 incidence and severity.Methods and findingsWe used register-based cohort data with individual-level linkage across various administrative registers for the total Finnish population living in working-age private households (N = 4,315,342). Incident COVID-19 cases (N = 38,467) were identified from the National Infectious Diseases Register from 1 July 2020 to 22 February 2021. Severe cases (N = 625) were defined as having at least 3 consecutive days of inpatient care with a COVID-19 diagnosis and identified from the Care Register for Health Care between 1 July 2020 and 31 December 2020. We used 2-level logistic regression with individuals nested within households to estimate COVID-19 incidence and case severity among those infected.Adjusted for age, sex, and regional characteristics, the incidence of COVID-19 was higher (odds ratio [OR] 1.67, 95% CI 1.58 to 1.77, p < 0.001, 28.4% of infections) among individuals in the lowest household income quintile than among those in the highest quintile (18.9%). The difference attenuated (OR 1.23, 1.16 to 1.30, p < 0.001) when controlling for foreign background but not when controlling for other household-level risk factors. In fact, we found a clear income gradient in incidence only among people with foreign background but none among those with native background. The odds of severe illness among those infected were also higher in the lowest income quintile (OR 1.97, 1.52 to 2.56, p < 0.001, 28.0% versus 21.6% in the highest quintile), but this difference was fully attenuated (OR 1.08, 0.77 to 1.52, p = 0.64) when controlling for other individual-level risk factors—comorbidities, occupational status, and foreign background. Both incidence and severity were strongly clustered within households: Around 77% of the variation in incidence and 20% in severity were attributable to differences between households. The main limitation of our study was that the test uptake for COVID-19 may have differed between population subgroups.ConclusionsLow household income appears to be a strong risk factor for both COVID-19 incidence and case severity, but the income differences are largely driven by having foreign background. The strong household clustering of incidence and severity highlights the importance of household context in the prevention and mitigation of COVID-19 outcomes.

Sanni Saarinen and colleagues explore the association between income differences and COVID-19 incidence and severity among people with foreign and native background in Finland.     

Symptom burden and health-related quality of life in chronic kidney disease: A global systematic review and meta-analysis

BackgroundThe importance of patient-reported outcome measurement in chronic kidney disease (CKD) populations has been established. However, there remains a lack of research that has synthesised data around CKD-specific symptom and health-related quality of life (HRQOL) burden globally, to inform focused measurement of the most relevant patient-important information in a way that minimises patient burden. The aim of this review was to synthesise symptom prevalence/severity and HRQOL data across the following CKD clinical groups globally: (1) stage 1–5 and not on renal replacement therapy (RRT), (2) receiving dialysis, or (3) in receipt of a kidney transplant.Methods and findingsMEDLINE, PsycINFO, and CINAHL were searched for English-language cross-sectional/longitudinal studies reporting prevalence and/or severity of symptoms and/or HRQOL in CKD, published between January 2000 and September 2021, including adult patients with CKD, and measuring symptom prevalence/severity and/or HRQOL using a patient-reported outcome measure (PROM). Random effects meta-analyses were used to pool data, stratified by CKD group: not on RRT, receiving dialysis, or in receipt of a kidney transplant. Methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, and an exploration of publication bias performed. The search identified 1,529 studies, of which 449, with 199,147 participants from 62 countries, were included in the analysis. Studies used 67 different symptom and HRQOL outcome measures, which provided data on 68 reported symptoms. Random effects meta-analyses highlighted the considerable symptom and HRQOL burden associated with CKD, with fatigue particularly prevalent, both in patients not on RRT (14 studies, 4,139 participants: 70%, 95% CI 60%–79%) and those receiving dialysis (21 studies, 2,943 participants: 70%, 95% CI 64%–76%). A number of symptoms were significantly (p < 0.05 after adjustment for multiple testing) less prevalent and/or less severe within the post-transplantation population, which may suggest attribution to CKD (fatigue, depression, itching, poor mobility, poor sleep, and dry mouth). Quality of life was commonly lower in patients on dialysis (36-Item Short Form Health Survey [SF-36] Mental Component Summary [MCS] 45.7 [95% CI 45.5–45.8]; SF-36 Physical Component Summary [PCS] 35.5 [95% CI 35.3–35.6]; 91 studies, 32,105 participants for MCS and PCS) than in other CKD populations (patients not on RRT: SF-36 MCS 66.6 [95% CI 66.5–66.6], p = 0.002; PCS 66.3 [95% CI 66.2–66.4], p = 0.002; 39 studies, 24,600 participants; transplant: MCS 50.0 [95% CI 49.9–50.1], p = 0.002; PCS 48.0 [95% CI 47.9–48.1], p = 0.002; 39 studies, 9,664 participants). Limitations of the analysis are the relatively few studies contributing to symptom severity estimates and inconsistent use of PROMs (different measures and time points) across the included literature, which hindered interpretation.ConclusionsThe main findings highlight the considerable symptom and HRQOL burden associated with CKD. The synthesis provides a detailed overview of the symptom/HRQOL profile across clinical groups, which may support healthcare professionals when discussing, measuring, and managing the potential treatment burden associated with CKD.Protocol registrationPROSPERO CRD42020164737.

In a systematic review and meta analysis, Benjamin R. Fletcher and colleagues study patient-reported symptom prevalence, severity, and health related quality of life among individuals with different stages of chronic kidney disease in 62 countries.