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

BACKGROUND: Acute 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 FINDINGS: Patients 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. CONCLUSIONS: This 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.

Diagnostic performance of a point-of-care saliva urea nitrogen dipstick to screen for kidney disease in low-resource settings where serum creatinine is unavailable.

BACKGROUND: Kidney disease is prevalent in low-resource settings worldwide, but tests for its diagnosis are often unavailable. The saliva urea nitrogen (SUN) dipstick is a laboratory and electricity independent tool, which may be used for the detection of kidney disease. We investigated the feasibility and performance of its use in diagnosing kidney disease in community settings in Africa. METHODS: Adult patients at increased risk of kidney disease presenting to three community health centres, a rural district hospital and a central hospital in Malawi were recruited between October 2016 and September 2017. Patients underwent concurrent SUN and creatinine testing at enrolment, and at 1 week, 1 month, 3 months and 6 months thereafter. RESULTS: Of 710 patients who presented at increased risk of kidney disease, 655 (92.3%) underwent SUN testing at enrolment, and were included (aged 38 (29-52) years, 367 (56%) female and 333 (50.8%) with HIV). Kidney disease was present in 482 (73.6%) patients and 1479 SUN measurements were made overall. Estimated glomerular filtration rate (eGFR) correlated with SUN (r=-0.39; p<0.0001). The area under the receiver operating characteristics curve was 0.61 for presenting SUN to detect acute or chronic kidney disease, and 0.87 to detect severe (eGFR <15 mL/min/1.73 m2) kidney disease (p<0.0001; sensitivity 82.3%, specificity 81.8%, test accuracy 81.8%). In-hospital mortality was greater if enrolment SUN was elevated (>test pad #1) compared with patients with non-elevated SUN (p<0.0001; HR 3.3 (95% CI 1.7 to 6.1). CONCLUSIONS: SUN, measured by dipstick, is feasible and may be used to screen for kidney disease in low resource settings where creatinine tests are unavailable.

Incidence, Etiology, and Outcomes of Community-Acquired Acute Kidney Injury in Pediatric Admissions in Malawi.

INTRODUCTION: The epidemiology of acute kidney injury (AKI) in children in sub-Sahara Africa (SSA) is poorly described. The aim of this study was to establish the incidence, etiology, and outcomes of community-acquired AKI in pediatric admissions in Southern Malawi. METHODS: We conducted a prospective observational study of pediatric admissions to a tertiary hospital in Blantyre between 5 February and 30 April 2016. Children were screened for kidney disease on admission with measurement of serum creatinine and assessment of urine output. The clinical presentation, etiology, and management of children with AKI were documented. RESULTS: A total of 412 patients (median age 4 years, 52.6% male, and 7.5% human immunodeficiency virus [HIV] infected) were included in the study. Forty-five patients (10.9%) had AKI (Kidney Disease: Improving Global Outcomes [KDIGO] criteria), which was stage 3 in 16 (35.6%) patients. Sepsis and hypoperfusion, most commonly due to malaria (n = 19; 42.2%), were the causes of AKI in 38 cases (84.4%). Three patients (6.7%) underwent peritoneal dialysis (PD) for AKI: 2 of them recovered kidney function, and the other one died. In-hospital mortality was 20.5% in AKI and 2.9% if no kidney disease was present (p < 0.0001). Seventeen (47.2%) patients with kidney disease had persistent kidney injury on hospital discharge. CONCLUSION: Acute kidney injury occurs in 10.9% of pediatric admissions in Malawi and is primarily due to infections, particularly malaria. Acute kidney injury results in significantly increased in-hospital mortality. Urgent interventions are required to eliminate preventable causes of death in this region.

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.

Diagnostic Performance of a Saliva Urea Nitrogen Dipstick to Detect Kidney Disease in Malawi.

INTRODUCTION: Kidney disease (KD), including acute kidney injury, is common, severe and leads to significant mortality in the developing world. However, simple tools to facilitate diagnosis and guide treatment are lacking. We studied the diagnostic performance of saliva urea nitrogen (SUN) measured by dipstick to diagnose KD in a low-resource setting. METHODS: Medical admissions to a tertiary hospital in Malawi had serum creatinine tested at presentation; SUN was measured using a dipstick. Patients with serum creatinine above normal range underwent serial measurements of SUN and blood urea nitrogen for up to 7 days. Hospital outcome was recorded in all patients. RESULTS: A total of 742 patients were included (age 41 ± 17·3 years, 56.1% male); 146 (19.7%) had KD, including 114 (15.4%) with acute kidney injury. SUN >14 mg/dl had a sensitivity of 0.72 and a specificity of 0.87 to diagnose KD; specificity increased to 0.97 when SUN levels were combined with self-reported urine output. The diagnostic performance of SUN was comparable with the one of blood urea nitrogen (SUN area under curve, 0.82; 95% confidence interval, 0.78-0.87; blood urea nitrogen area under curve, 0.82; 95% confidence interval, 0.59-1.0). SUN >14 mg/dl on admission was an independent predictor of all-cause mortality (hazard ratio = 2.43 [95% confidence interval, 1.63-3.62]). DISCUSSION: SUN measured by dipstick can be used to identify patients with KD in a low-resource setting. SUN is an independent predictor of mortality in this population.

Incidence, aetiology and outcome of community-acquired acute kidney injury in medical admissions in Malawi.

BACKGROUND: Epidemiological data on Acute Kidney Injury (AKI) from low-income countries is sparse. The aim of this study was to establish the incidence, severity, aetiology, and outcomes of community-acquired AKI in Malawi. METHODS: We conducted a prospective observational study of general medical admissions to a tertiary hospital in Blantyre between 27th April and 17th July 2015. All patients were screened on admission with a serum creatinine; those with creatinine above laboratory reference range were managed by the nephrology team. Hospital outcome was recorded in all patients. RESULTS: Eight hundred ninety-two patients were included; 188 (21 · 1%) had kidney disease on admission, including 153 (17 · 2%) with AKI (median age 41 years; 58 · 8% HIV seropositive). 60 · 8% of AKI was stage 3. The primary causes of AKI were sepsis and hypovolaemia in 133 (86 · 9%) cases, most commonly gastroenteritis (n = 29; 19 · 0%) and tuberculosis (n = 18; 11 · 8%). AKI was multifactorial in 117 (76 · 5%) patients; nephrotoxins were implicated in 110 (71 · 9%). Inpatient mortality was 44 · 4% in patients with AKI and 13 · 9% if no kidney disease (p <0.0001). 63 · 2% of patients who recovered kidney function left hospital with persistent kidney injury. CONCLUSION: AKI incidence is 17 · 2% in medical admissions in Malawi, the majority is severe, and AKI leads to significantly increased in-hospital mortality. The predominant causes are infection and toxin related, both potentially avoidable and treatable relatively simply. Effective interventions are urgently required to reduce preventable young deaths from AKI in this part of the world.

A 42-year-old woman with subacute reversible dementia: A cautionary tale.

A 42-year-old woman presented with a 6-month history of diffuse headache of moderate intensity and gradual onset of generalized weakness, imbalance, apathy, memory decline, hypophonia, dysphagia, constipation and urinary incontinence. Clinical examination revealed several elements of a frontal lobe dysfunction including apathy with motor impersistence, presence of primitive reflexes, generalized hyperreflexia with bilateral Hoffman sign and ankle clonus. The biological workup was unremarkable and a brain computed tomography scan identified a giant olfactory groove meningioma. A prompt neurosurgical intervention helped to reverse the symptoms. This case illustrates the benefits of actively looking for treatable conditions in young patients presenting with acute or subacute dementia and emphasizes the pivotal role of early brain imaging.

Adenine phosphoribosyltransferase deficiency as a rare cause of renal allograft dysfunction.

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in urine, yielding kidney injury and in some patients, kidney failure. Early recognition of the disease, institution of xanthine analog therapy to block the formation of 2,8-dihydroxyadenine, high fluid intake, and low purine diet prevent CKD. Because of symptom variability and lack of awareness, however, the diagnosis is sometimes extremely deferred. We describe a patient with adenine phosphoribosyltransferase deficiency who was diagnosed during evaluation of a poorly functioning second kidney allograft. This report highlights the risk of renal allograft loss in patients with undiagnosed adenine phosphoribosyltransferase deficiency and the need for improved early detection of this disease.