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Around 1.7 billion cases of childhood diarrhoea occur annually. Since the introduction of Oral Rehydration Solution (ORS) in 1978 many lives have been saved, but around 525 000 children still die from diarrhoeal illnesses each year. Dehydration significantly contributes to mortality and the kidney is highly sensitive to dehydration. Diarrhoea is a common cause of acute kidney injury (AKI), and may therefore be an important contributor to deaths associated with diarrhoeal illness in children globally. In addition, shiga toxin-producing E. Coli (STEC)and other pathogens can cause hemolytic uremic syndrome (HUS), a severe condition characterized by diarrhea, hemolysis, thrombocytopenia and AKI (STEC+/D+-HUS). Due to the lack of standardized classification systems, the clinical variability and partially mild symptoms of AKI in children, it is likely that AKI is significantly underdiagnosed. Children with AKI have an increased mortality and are at risk of developing long-term complications, such as chronic kidney disease (CKD), hypertension and proteinuria. This systematic review aims to better understand the impact of diarrhoeal diseases on AKI incidence and outcomes.
We performed a systematic literature review evaluating studies on AKI and diarrhoea in children. Articles were categorized into 3 groups: studies reporting on the proportion of AKI in children hospitalized with diarrhoea (Diarrhoea/AKI); studies analyzing diarrheal disease in patients hospitalized with AKI (AKI/Diarrhoea); and studies on D+-HUS patients. Papers were identified through MEDLINE, Web of Science, African Index Medicus, and the WHO library. We included studies published in English, performed in pediatric patients and published after the year 2000.
After screening titles and abstracts of 1896 articles, 228 full text articles were evaluated and 97 articles were included for analysis. Papers were stratified into 3 categories: Diarrhoea/AKI (n=8, 8.5%), AKI/Diarrhoea (n=15, 16.5%), D+-HUS (n=74, 75%). Across all 3 subgroups, single-center, retrospective studies predominated. A high proportion of studies (50%) originated from HICs, whereas MICs and LICs contributed 25% each. The mean proportion of patients with AKI following diarrheal disease (Diarrhoea/AKI), is higher in LICs 43.2% (range from 10-86%) compared to 12.5% (range from 0.8-24.6%) in HICs. In patients with AKI, the mean proportion with diarrheal disease (AKI/Diarrhoea) was similar across different income countries (HICs 16.15%, range from 12-20% vs. LICs 23.8%, range from 10-43%). In patients with HUS, the mean proportion requiring dialysis ranged between 45-56% and peritoneal dialysis was the predominant dialysis modality. While the proportion of patients progressing to CKD was comparable among the different countries, the mortality was highest in LICs (mean proportion 31.5%, range from 17-52%). Laboratory parameters purporting a poorer prognosis in D+-HUS, regardless of country income, were an elevated hematocrit and serum creatinine levels, and a decreased albumin, sodium, platelet and WBC count. The most important clinical risk factors were anuria/oliguria, as well as duration of dialysis.
Diarrhea is a significant cause of AKI in children and yet literature investigating the relationship of AKI and diarrhea is scarce. The lack of prospective, long-term follow-up studies may account for the substantial number of unresolved CKD cases.