Incidence, aetiology and outcomes of obstetric-related acute kidney injury in Malawi: a prospective observational study.

BACKGROUND: Obstetric-related acute kidney injury (AKI) is thought to be a key contributor to the overall burden of AKI in low resource settings, causing significant and preventable morbidity and mortality. However, epidemiological data to corroborate these hypotheses is sparse. This prospective observational study aims to determine the incidence, aetiology and maternal-fetal outcomes of obstetric-related AKI in Malawi. METHODS: Women greater than 20 weeks gestation or less than 6 weeks postpartum admitted to obstetric wards at a tertiary hospital in Blantyre, Malawi, and at high-risk of AKI were recruited between 21st September and 11th December 2015. All participants had serum creatinine tested at enrolment; those with creatinine above normal range (> 82 µmol/L) underwent serial measurement, investigations to determine cause of kidney injury, and were managed by obstetric and nephrology teams. AKI was diagnosed and staged by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Primary outcomes were the incidence proportion and aetiology of AKI. Secondary outcomes were in-hospital maternal mortality, need for dialysis, renal recovery and length of stay; in-hospital perinatal mortality, gestational age at delivery, birthweight and Apgar score. RESULTS: 354 patients were identified at risk of AKI from the approximate 2300 deliveries that occurred during the study period. Three hundred twenty-two were enrolled and 26 (8.1%) had AKI (median age 27 years; HIV 3.9%). The most common primary causes of AKI were preeclampsia/eclampsia (n = 19, 73.1%), antepartum haemorrhage (n = 3, 11.5%), and sepsis (n = 3, 11.5%). There was an association between preeclampsia spectrum and AKI (12.2% AKI incidence in preeclampsia spectrum vs. 4.3% in other patients, p = 0.015). No women with AKI died or required dialysis and complete renal recovery occurred in 22 (84.6%) cases. The perinatal mortality rate across all high-risk admissions was 13.8%. AKI did not impact on maternal or fetal outcomes. CONCLUSIONS: The incidence of AKI in high-risk obstetric admissions in Malawi is 8.1% and preeclampsia was the commonest cause. With tertiary nephrology and obstetric care the majority of AKI resolved with no effect on maternal-fetal outcomes. Maternal-fetal outcomes in Sub-Saharan Africa may be improved with earlier detection of hypertensive disease in pregnancy.

A Salivary Urea Nitrogen Dipstick to Detect Obstetric-Related Acute Kidney Disease in Malawi.

INTRODUCTION: Obstetric-related acute kidney injury (AKI) is associated with adverse outcomes for mother and fetus, particularly in low-income countries. However, laboratory-independent tools to facilitate diagnosis are lacking. We assessed the diagnostic performance of a salivary urea nitrogen (SUN) dipstick to detect obstetric-related acute kidney disease in Malawi. METHODS: Women at high risk for AKI admitted to an obstetric unit in Blantyre, Malawi, were recruited between 21 September and 11 December 2015. Patients underwent serum creatinine (SCr) testing alongside measurement of SUN using a dipstick on admission, and every 48 hours thereafter if evidence of kidney disease was found. RESULTS: A total of 301 patients were included (mean age 25.9 years, 11% HIV positive). Of the patients, 23 (7.6%) had AKI, stage 1 in 47.8%, most commonly due to preeclampsia/eclampsia. Mean presenting SCr values were 108.8 ± 21.8 µmol/l (1.23 ± 0.25 mg/dl), 118 ± 34.45 µmol/l (1.33 ± 0.39 mg/dl), and 136.1 ± 30.4 µmol/l (1.54 ± 0.34 mg/dl) in AKI stages 1 to 3 respectively. SUN > 14 mg/dl had a sensitivity of 12.82% and a specificity of 97.33% to detect acute kidney disease; the area under the receiver operating characteristic curve was 0.551. In patients with normal SUN on admission, perinatal mortality was 11.8%, and was 25.0% if SUN was > 14 mg/dl (P = 0.18). CONCLUSION: The SUN dipstick was specific but insensitive when used to diagnose obstetric-related AKI. Limited biochemical derangement and low salivary urea concentrations due to physiological changes in pregnancy, as opposed to a technical limitation of the dipstick itself, are the likely reason for the lack of sensitivity in this study.

Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial.

BACKGROUND: Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy, and alternative regimens need to be identified. With the return of chloroquine efficacy in southern Africa, we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes. METHODS: We did an open-label, single-centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in southern Malawi. We enrolled pregnant women (first or second pregnancy) at 20-28 weeks' gestation who were HIV negative. Participants were randomly assigned in a 1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine-pyrimethamine (two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2, and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg every week). The primary endpoint was placental malaria in the modified intent-to-treat population, which consisted of participants who contributed placental histopathology data at birth. Secondary outcomes included clinical malaria, maternal anaemia, low birthweight, and safety. This trial is registered with ClinicalTrials.gov, number NCT01443130. FINDINGS: Between February, 2012, and May, 2014, we enrolled and randomly allocated 900 women, of whom 765 contributed histopathological data and were included in the primary analysis. 108 (14%) women had placental malaria, which was lower than the anticipated prevalence of placental malaria infection. Protection from placental malaria was not improved by chloroquine as either prophylaxis (30 [12%] of 259 had positive histopathology; relative risk [RR] 0·75, 95% CI 0·48-1·17) or intermittent therapy (39 [15%] of 253; RR 1·00, 0·67-1·50) compared with intermittent sulfadoxine-pyrimethamine (39 [15%] of 253). In protocol-specified analyses adjusted for maternal age, gestational age at enrolment, bednet use the night before enrolment, anaemia at enrolment, and malaria infection at enrolment, women taking chloroquine as prophylaxis had 34% lower placental infections than did those allocated intermittent sulfadoxine-pyrimethamine (RR 0·66, 95% CI 0·46-0·95). Clinical malaria was reported in nine women assigned intermittent sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0·26), and two allocated chloroquine prophylaxis (p=0·063). Maternal anaemia was noted in five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated intermittent chloroquine (p=0·038), and six assigned chloroquine prophylaxis (p>0·99). Low birthweight was recorded for 31 babies born to women allocated intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine (p=0·78), and 41 allocated chloroquine prophylaxis (p=0·28). Four women assigned intermittent sulfadoxine-pyrimethamine had adverse events possibly related to study product compared with 94 women allocated intermittent chloroquine (p<0·0001) and 26 allocated chloroquine prophylaxis (p<0·0001). Three women had severe or life-threatening adverse events related to study product, of whom all were assigned intermittent chloroquine (p=0·25). INTERPRETATION: Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine. Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy, but studies with larger sample sizes are needed to confirm these results. FUNDING: US National Institutes of Health.