Association of linear growth velocities between 0 and 6 years with kidney function and size at 10 years: A birth cohort study in Ethiopia.

BACKGROUND: Risk of noncommunicable diseases accrues from fetal life, with early childhood growth having an important role in adult disease risk. There is a need to understand how early-life growth relates to kidney function and size. OBJECTIVES: This study aimed to assess the association of linear growth velocities among children between 0 and 6 y with kidney function and size among children aged 10 y. METHODS: The Ethiopian Anthropometric and Body Composition birth cohort recruited infants born at term to mothers living in Jimma with a birth weight of ≥1500 g and without congenital malformations. Participants were followed up with 13 measurements between birth and 6 y of age. The latest follow-up was at ages 7-12 y with measurement of serum cystatin C as a marker of kidney function and ultrasound assessment of kidney dimensions. Kidney volume was computed using an ellipsoid formula. Linear-spline multilevel modeling was used to compute linear growth velocities between 0 and 6 y. Multiple linear regression modeling was used to examine the associations of linear growth velocities in selected age periods with cystatin C and kidney size. RESULTS: Data were captured from 355 children, at a mean age of 10 (range 7-12) y. The linear growth velocity was high between 0 and 3 mo and then decreased with age. There was no evidence of an association of growth velocity ≤24 mo with cystatin C at 10 y. Between 24 and 48 and 48 and 76 mo, serum cystatin C was higher by 2.3% [95% confidence interval (CI): 0.6, 4.2] and 2.1% (95% CI: 0.3, 4.0) for 1 SD higher linear growth velocity, respectively. We found a positive association between linear growth velocities at all intervals between 0 and 6 y and kidney volume. CONCLUSIONS: Greater linear growth between 0 and 6 y of development was positively associated with kidney size, and greater growth velocity after 2 y was associated with higher serum cystatin C concentrations.

Correlates of Iron, Cobalamin, Folate, and Vitamin A Status among Stunted Children: A Cross-Sectional Study in Uganda.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Correlates of Pancreatic Enzyme Replacement Therapy Intake in Adults with Cystic Fibrosis: Results of a Cross-Sectional Study.

Most people with cystic fibrosis (pwCF) develop pancreatic insufficiency and are treated with pancreatic enzyme replacement therapy (PERT). We aimed to describe the use of PERT and assess the correlates of PERT dose in adult pwCF. In a cross-sectional study at the Copenhagen CF Centre, the participants reported PERT intake, gastrointestinal (GI) symptoms and the use of concomitant treatments. Demographic and clinical characteristics were extracted from the Danish CF Registry. We used linear regression to assess the correlates of PERT dose per kg bodyweight (U-lipase/kg). We included 120 pwCF with a median age of 32.9 years, 46% women and 72% F508delta homozygote. The PERT dose ranged from 0 to 6160 U-lipase/kg per main meal (mean 1828; SD 1115). The PERT dose was associated with participants' sex (men vs. women: 661; 95% CI: 302; 1020 U-lipase/kg), age (-16; 95% CI: -31; -1 U-lipase/kg per year) and weight (-45; 95% CI: -58; -31 U-lipase/kg per kg). Having less frequent constipation and being lung transplanted were also associated with a higher PERT dose. A third of participants did not take PERT for snacks, and this was associated with the frequency of diarrhoea. These findings indicate that PERT intake may be improved to reduce GI symptoms.

Levels and correlates of physical activity and capacity among HIV-infected compared to HIV-uninfected individuals.

INTRODUCTION: In the HIV-infected individuals, physical activity improves physical strength, quality of life and reduces the risk of developing non-communicable diseases. In Sub-Saharan Africa, HIV-infected patients report being less active compared to HIV-uninfected individuals. We assessed the levels and correlates of objectively measured physical activity and capacity among HIV-infected antiretroviral therapy (ART)-naive individuals compared to HIV-uninfected individuals in Mwanza, Tanzania. METHOD: We conducted a cross-sectional study among newly diagnosed HIV-infected ART-naive individuals and HIV-uninfected individuals frequency-matched for age and sex. Socio-demographic data, anthropometrics, CD4 counts, haemoglobin level, and C-reactive protein (CRP) were collected. Physical activity energy expenditure (PAEE) was assessed as measure of physical activity whereas sleeping heart rate (SHR) and grip strength were assessed as measures of physical capacity. Multivariable linear regression was used to assess the correlates associated with physical activity and capacity. RESULTS: A total of 272 HIV-infected and 119 HIV-uninfected individuals, mean age 39 years and 60% women participated in the study. Compared to HIV-uninfected individuals, HIV-infected had poorer physical activity and capacity: lower PAEE (-7.3 kj/kg/day, 95% CI: -11.2, -3.3), elevated SHR (7.7 beats/min, 95%CI: 10.1, 5.3) and reduced grip strength (-4.7 kg, 95%CI: -6.8, -2.8). In HIV-infected individuals, low body mass index, moderate-severe anaemia, low CD4 counts and high CRP were associated with lower physical activity and capacity. In HIV-uninfected individuals, abdominal obesity and moderate anaemia were associated with lower physical activity and capacity. CONCLUSION: HIV-infected participants had lower levels of physical activity and capacity than HIV-uninfected participants. Correlates of physical activity and capacity differed by HIV status. Management of HIV and related conditions needs to be provided effectively in health care facilities. Interventions promoting physical activity in these populations will be of importance to improve their health and reduce the risk of non-communicable diseases.

Association of schistosome infection with adiposity in Tanzania.

Background: Observational studies in humans have reported a link between schistosome infection and lower adiposity, but this may be explained by socioeconomic and demographic factors, intensity of infection, or common co-infections such as HIV. Methods: This was a cross-sectional study that investigated the relationship between schistosome infection and adiposity in a large, well-described cohort of Tanzanian adults living with and without HIV. Cross-sectional data were collected among adults living in Mwanza, Tanzania who were enrolled in the Chronic Infections, Co-morbidities and Diabetes in Africa (CICADA) cohort study. Schistosome circulating anodic antigen, secreted by both Schistosoma mansoni and haematobium which are endemic to Tanzania, was quantified from stored samples. Schistosome infection diagnosed by serum circulating anodic antigen levels. The primary outcome was fat mass measured by bioimpedance analysis. Secondary outcomes included fat-free mass, waist circumference, mid-upper arm circumference, and body mass index. Results: The study enrolled 1,947 adults, of whom 1,923 (98.8%) had serum available for schistosome testing. Of these, 873 (45.4%) had a serum circulating anodic antigen ≥30 pg/mL, indicating schistosome infection. Compared to uninfected individuals, those with schistosome infections had -1.1 kg [95% CI -1.9 to -0.3] lower fat mass after adjusting for age, sex, physical activity, tobacco use, education level, and socioeconomic status. Infected participants also had lower waist circumference, mid-upper arm circumference, and body mass index. Fat-free mass was not different between the two groups. Neither being HIV-infected, nor receiving antiretroviral therapy, modified associations between schistosome infection and adiposity. These associations were also not affected by Schistosoma worm burden. Conclusions: Schistosome infection was associated with lower fat mass and less central adiposity without a difference in muscle mass, irrespective of confounders, HIV status, or the intensity of schistosome infection. Future studies should adjust for socioeconomic and demographic factors that are associated with schistosome infection and adiposity. Identifying mechanistic pathways by which schistosome infection reduces adiposity while preserving muscle mass could yield new strategies for obesity control and cardiovascular disease prevention.

Serum creatinine and estimated glomerular filtration rates in HIV positive and negative adults in Ethiopia.

BACKGROUND: Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults. METHODS: Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR- 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance. RESULTS: A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (P<0.05). No difference was observed in eGFR between HIV positive and HIV negative adults. For all eGFR equations, the correlation between eGFR and 24-hr creatinine clearance was 0.45-0.53 and the accuracy within 30% of 24-hr creatinine clearance was 24-46%. Removing ethnic coefficient reduced the bias and improved accuracy of the CKD-EPI and the MDRD estimates. CONCLUSION: Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed.

Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia.

BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and <1000 copies/mL at 6 months). RESULTS: Two hundred sixty five patients had VL data available at baseline and at 6 months. Virological failure was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS: Our data confirm that the currently recommended first-line ART regimen is efficient in the vast majority of individuals initiating therapy in Jimma, Ethiopia eight years after the introduction of ART. However, the documented occurrence of transmitted resistance and accumulation of acquired HIVDR mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations.