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These data suggest that a substantial number of children with SCD in Malawi have renal disease and could be at risk for worsening nephropathy and ESRD as they age. Our data suggest that urinary nephrin could be utilized as an early marker of glomerular disease in SCD.

Background Malnutrition is highly prevalent in HIV-exposed perinatally uninfected infants (HEUs) increasing the risk of morbidity and mortality throughout the life course. We set out to compare the effect of postnatal exposure to maternal antiretroviral therapy (mART) in breastmilk versus infant Nevirapine prophylaxis (iNVP) on somatic growth of HEUs in the randomized PROMISE trial. Methods and findings We randomized 2431 mothers with HIV and their 2444 HEUs from six African countries and India 6–14 days after delivery to mART or iNVP for prevention of breastmilk HIV transmission. The mART regimen contained tenofovir/emtricitabine (99%) plus lopinavir/ritonavir. Infant growth parameters were compared at postnatal week 10, 26, 74 and 104 using World Health Organization (WHO) z-scores for length-for-age (LAZ), weight-for-age (WAZ), and head circumference-for-age (HCAZ). Week 26 LAZ was the primary endpoint measure. Student T-tests compared mean LAZ, WAZ, and HCAZ; estimated mean and 95% confidence interval (CI) are presented. Maternal and infant baseline characteristics were comparable between study arms. The estimated median breastfeeding duration was 70 weeks. After a mean follow-up of 88 weeks, mean LAZ and WAZ were below the WHO reference population mean at all timepoints, whereas mean HCAZ was not. The mART and iNVP arms did not differ for the primary outcome measure of LAZ at week 26 (p-value = 0.39; estimated mean difference (95%CI) of -0.05 (-0.18, 0.07)) or any of the other secondary growth outcome measures or timepoints (all p-values≥0.16). Secondary analyses of the primary outcome measure adjusting for week 0 LAZ and other covariates did not change these results (all p-values≥0.09). However, infants assigned to mART were more likely to have stunting compared to iNVP infants at week 26 (odds ratio (95% CI): 1.28 (1.05, 1.57)). Conclusions In HEUs, growth effects from postnatal exposure to mART compared to iNVP were comparable for measures on length, weight and head circumference with no clinically relevant differences between the groups. Despite breastfeeding into the second year of life, length and weight were below reference population means at all ages in both arms. Further investment is needed to optimize postnatal growth of infants born to women with HIV. Clinical trial registration ClinicalTrials.gov number NCT01061151.

Introduction: The global distribution of sickle cell disease (SCD) overlaps with that of food scarcity and nutritional deficiencies. Chronic anemia secondary to SCD contributes to nutritional deficiencies, for example folic acid. Few studies have evaluated associations between malnutrition and SCD, nor effects of malnutrition on SCD outcomes. Moreover,hydroxyurea(HU), a disease modifying agent for SCD, has not been specifically evaluated in malnourished children although it is known to bind pharmacologically to human serum albumin. Methods: We conducted a cross-sectional nutritional assessment of children receiving chronic SCD care at a referral hospital in the capital city of Malawi, Lilongwe, between January and June 2016. Participants were measured for height, weight, and mid-upper arm circumference. Z-scores and percentiles for anthropomorphic indices were calculated using WHOAnthroSoftware. Nutritional measures of interest were BMI-for-age Z-score to assess wasting and height-for-age Z-score to assess stunting. We examined associations between nutritional status and clinical and laboratory data collected longitudinally at six-month intervals during routine care. Differences based on HU use were examined. Results: Fourteen of 99 (14.1%) participants had moderate-to-severe wasting and 36 of 101 (35.6%) moderate-to-severe stunting. The wasted group was significantly older than the non-wasted group but there was no significant difference in age between the stunted and non-stunted groups (Table 1). We observed significantly lower white blood cell (WBC) and lymphocyte counts in the wasted group when compared to the non-wasted group. The stunted group had significantly lower hemoglobin (Hb) than the non-stunted group. There was also a significantly higher prevalence of fevers in the stunted group than the non-stunted group. Forty-four of 151 (29.1%) participants were receiving HU for a median duration of 126 days (IQR 29 - 196 days). There were no significant differences in age or sex between the HU group and the non-HU group. We observed significantly lower Hb in the HU group when compared to the non-HU group, as expected as HU is typically prescribed for children with more severe SCD in Lilongwe. We also observed higher WBC, absolute neutrophil (ANC), and lymphocyte counts in the HU group. Again reflecting greater SCD severity, we observed a significantly more frequent history of fevers, upper respiratory tract infections, and splenomegaly in the HU group. There were no significant differences in the proportions of wasted participants by HU status [5/33 (15.2%) HUvs20/68 (29.4%) non-HU, p=0.84], and a trend toward more frequent stunting among HU users again likely reflecting growth effects of greater chronic SCD severity [16/33 (48.5%) HUvs9/66 (13.6%) non-HU, p=0.061]. Among HU users, peripheral blood counts were not significantly different in wastedvsnon-wasted children, nor stuntedvsnon-stunted children (Table 2). Conclusion: In a pediatric SCD cohort in Malawi we observed 14.1% of children with significant wasting and 35.6% with significant stunting, highlighting growth effects of chronic illness in this population even among children receiving regular SCD care. Among children prescribed HU, nutritional status did not seem to be associated with HU tolerability. Notably, HU was not associated with significantmyelosuppressionin our cohort including those children with wasting or stunting. More studies are needed to clarify interactions between nutritional status, SCD, and HU, but our data suggests wasting or stunting should not be contraindications to HU use when indicated for pediatric SCD in sub-Saharan Africa. Table 1 Table 1. Table 2 Table 2. Disclosures No relevant conflicts of interest to declare.

Sickle cell nephropathy (SCN) is a prevalent complication among adults with sickle cell disease (SCD) and has been observed in younger populations, suggesting potential early renal involvement in pediatric patients. Initial hyperfiltration and albuminuria followed by frank proteinuria, leading to declining GFR and eventual end stage renal disease is assumed to be the typical progression of SCN; however, few clinical biomarkers exist to identify early-stage renal disease. We describe the renal profile in 119 children with SCD at Kamuzu Central Hospital in Lilongwe, Malawi and propose a novel urinary biomarker for the identification of children with early renal disease. Among children with confirmed HbSS disease (females 47.9%; median age 9.0 years, IQR: 5, 11), 21.6% were found to have a urinary albumin to creatinine ratio (UACR) 30mg/g or above. Baseline laboratory and clinical parameters stratified by UACR are shown in Tables 1 and 2. Patients with increased levels of UACR were found to be significantly older, and have significantly elevated plasma levels of lactate dehydrogenase (LDH), total bilirubin, and indirect bilirubin when compared to those without albuminuria (p<0.05). No association was seen between albuminuria and either hemoglobin or plasma hemoglobin. Albuminuria was also significantly associated with elevated levels of nephrin, a urinary marker of glomerular injury (p<0.01). Multivariable logistic regression was used to investigate risk factors that are associated with albuminuria (UACR >= 30). Urine nephrin was significantly associated with albuminuria (regression coefficient estimate: 0.00188, SE: 0.000571, p = 0.0010). Additional analysis using a nephrin cut-point of 293 pg/mL, the median value in the cohort, revealed a 17.8 times greater odds of having albuminuria in children with nephrinuria above this value. These data taken together suggests that a significant proportion of children with SCD in Malawi exhibit renal involvement early in life and could be at risk for worsening nephropathy and end-stage renal disease as they grow older. Our data further indicates that urinary nephrin could be utilized as an early marker of glomerular disease in SCN and possibly prompt earlier intervention in these children. The discordant association of albuminuria with clinical markers of hemolysis suggests that hemolysis may not play a substantial role in the pathogenesis of albuminuria in this population. Increased surveillance of children with SCD for renal complications can ultimately inform management strategies to improve outcomes and increase life expectancy among children with SCD. Disclosures No relevant conflicts of interest to declare.