Aim: To describe incidence and outcome of acute kidney injury (AKI) in infants with hypothermia‐treated hypoxic‐ischaemic encephalopathy (HIE).Methods: This observational population‐based study included all term and near‐term infants with hypothermia‐treated HIE born between 2007 and 2009 in greater Stockholm. The KDIGO definition modified for neonatal patients was used to identify infants with AKI. We analysed association between AKI and neonatal morbidity/mortality. Furthermore, we calculated estimated glomerular filtration rate (eGFR) at the age of 10–12 years.Results: Out of 83,939 live births in the Stockholm region, 66 infants underwent hypothermia treatment due to HIE. Out of 65 included infants, 45% suffered AKI. Degree of AKI correlated with HIE severity. One infant needed kidney replacement therapy; others were treated conservatively. AKI was associated with increased mortality and need for blood products (p < 0.05). eGFR at age 10–12 years was available for 72% of survivors. Nine children (21%) had subnormal eGFR, with no difference between those with and without a history of neonatal AKI.Conclusion: Despite therapeutic hypothermia, AKI remains a common complication in infants with HIE and is associated with increased neonatal mortality. Twenty‐one per cent of children had subnormal eGFR at 10–12 years, highlighting the need for long‐term follow‐up of renal function.

Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may exacerbate renal manifestations. In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-associated hemolytic uremic syndrome. The role of the terminal complement complex, and its blockade as a therapeutic modality, was investigated in a mouse model of E. coli O157:H7 infection. BALB/c mice were treated with monoclonal anti-C5 i.p. on day 3 or 6 after intragastric inoculation and monitored for clinical signs of disease and weight loss for 14 d. All infected untreated mice (15 of 15) or those treated with an irrelevant Ab (8 of 8) developed severe illness. In contrast, only few infected mice treated with anti-C5 on day 3 developed symptoms (three of eight, p < 0.01 compared with mice treated with the irrelevant Ab on day 3) whereas most mice treated with anti-C5 on day 6 developed symptoms (six of eight). C6-deficient C57BL/6 mice were also inoculated with E. coli O157:H7 and only 1 of 14 developed disease, whereas 10 of 16 wild-type mice developed weight loss and severe disease (p < 0.01). Complement activation via the terminal pathway is thus involved in the development of disease in murine EHEC infection. Early blockade of the terminal complement pathway, before the development of symptoms, was largely protective, whereas late blockade was not. Likewise, lack of C6, and thereby deficient terminal complement complex, was protective in murine E. coli O157:H7 infection.

Shiga toxin (Stx)-producing Escherichia coli (STEC) is an important foodborne pathogen with the ability to cause bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Little is known about enterohemolysin-encoded by ehxA. Here we investigated the prevalence and diversity of ehxA in 239 STEC isolates from human clinical samples. In total, 199 out of 239 isolates (83.26%) were ehxA positive, and ehxA was significantly overrepresented in isolates carrying stx_2a + stx_2c (p < 0.001) and eae (p < 0.001). The presence of ehxA was significantly associated with BD and serotype O157:H7. Five ehxA subtypes were identified, among which, ehxA subtypes B, C, and F were overrepresented in eae-positive isolates. All O157:H7 isolates carried ehxA subtype B, which was related to BD and HUS. Three ehxA groups were observed in the phylogenetic analysis, namely, group Ⅰ (ehxA subtype A), group Ⅱ (ehxA subtype B, C, and F), and group Ⅲ (ehxA subtype D). Most BD- and HUS-associated isolates were clustered into ehxA group Ⅱ, while ehxA group Ⅰ was associated with non-bloody stool and individuals ≥10 years of age. The presence of ehxA + eae and ehxA + eae + stx₂ was significantly associated with HUS and O157:H7 isolates. In summary, this study showed a high prevalence and the considerable genetic diversity of ehxA among clinical STEC isolates. The ehxA genotypes (subtype B and phylogenetic group Ⅱ) could be used as risk predictors, as they were associated with severe clinical symptoms, such as BD and HUS. Furthermore, ehxA, together with stx and eae, can be used as a risk predictor for HUS in STEC infections.

Circulating cell-free DNA (cfDNA) has diverse applications in oncological, prenatal, toxicological, cardiovascular, and autoimmune diseases, diagnostics, and organ transplantation. In particular, mitochondrial cfDNA (mt-cfDNA) is associated with inflammation and linked to early vascular ageing (EVA) in end-stage kidney failure (ESKF), which could be a noninvasive marker for graft rejection and organ damage. Plasma samples from 44 ESKF patients, of whom half (n = 22) underwent either conservative therapy (non-HD) or hemodialysis (HD) before kidney transplantation (KT). These samples were analyzed at baseline and two years after KT. cfDNA was extracted from plasma and quantified using the fluorometric method. qPCR was used to quantify and differentiate the fractions of mt-cfDNA and nuclear cfDNA (nc-cfDNA). mt-cfDNA levels in KT patients decreased significantly from baseline to two years post-KT (p < 0.0268), while levels of total cfDNA and nc-cfDNA did not differ. Depending on therapy modality (HD vs. non-HD) before KT, total cfDNA levels were higher in HD patients at both baseline (p = 0.0133) and two years post-KT (p = 0.0421), while nc-cfDNA levels were higher in HD only at baseline (p = 0.0079). Males showed a nonsignificant trend of higher cfDNA levels. Patients with assessed vascular fibrosis (p = 0.0068), either alone or in combination with calcification plus fibrosis, showed reduced mt-cfDNA post-KT (p = 0.0195). Changes in mt-cfDNA levels suggests the impact of KT on the inflammatory state of ESKF, as evidenced via its correlation with high sensitivity C-reactive protein after KT. Further studies are warranted to assess if cfDNA could serve as a noninvasive method for monitoring the response to organ transplantation and even for amelioration of EVA status per se.

Chronic kidney disease (CKD) is associated with chronic low-grade inflammation, but the primary factors triggering this inflammation remain unclear. Extracellular or cell-free DNA (exDNA) originates from virtually all tissues, being released during cell death, and stimulates the innate immune system. Our study was designed as an observational, cross-sectional cohort study of children with CKD (both before and after kidney transplantation) and controls to analyze associations between exDNA, markers of inflammation, and cardiovascular health. Extracellular DNA (total, nuclear, and mitochondrial) was analyzed in plasma using fluorometry and real-time PCR. We found that children with CKD after kidney transplantation had higher concentrations of total and nuclear extracellular DNA (total exDNA and nc_exDNA) in plasma compared to controls. In univariate analysis, levels of interleukin-6 (IL-6), antimicrobial peptide cathelicidin (LL-37), soluble vascular cell adhesion molecule-1 (VCAM-1) and left ventricular mass index (LVMI) were positively correlated with total exDNA and nc_exDNA concentrations. Multivariate analysis revealed LVMI as the only independent variable associated with high levels of both total exDNA and nc_exDNA. We believe that our results contribute new knowledge to the pathogenesis of CKD and its complications and may help identify new treatment targets.