Hypertension and mild chronic kidney disease persist following severe haemolytic uraemic syndrome caused by Shiga toxin-producingEscherichia coliO104:H4 in adults
Abstract:Although shiga toxin-producing Escherichia coli (STEC)-HUS induced by O104:H4 was a life-threatening acute disease, follow-up showed a good recovery of organ function in all patients. Whereas kidney function recovered even after longer duration of dialysis, chronic hypertension developed after severe HUS with neurological symptoms and could not be prevented by the extended therapy.
“…As in our patients, it has been previously observed that the GFR can improve or deteriorate over time after HUS [20,21]. Similar to the results of Rosales et al and our results, 2 of 45 (4%) adult patients from the 2011 outbreak from a single center had increased creatinine after 1 year of follow-up [22]. However, decreased eGFR < 90 mL/min calculated from cystatin C was found in Figure 3.…”
Section: Discussionsupporting
confidence: 91%
“…Substantial variation between the different studies might also be due to the different definitions of proteinuria applied. Again adults affected during the outbreak showed similar results, with albuminuria in 27% of the cases at 1-year follow-up [22]. Although proteinuria in patients after HUS is more common compared with the normal population and proteinuria is associated with impaired kidney function, it is not necessarily a measure for poor outcome.…”
Section: Discussionmentioning
confidence: 59%
“…This was associated with older age (mean age 60 years [eGFR < 90 mL/min] vs 43 years [eGFR > 90 mL/min]) [22].…”
Background. In 2011 Escherichia coli O104:H4 caused an outbreak with >800 cases of hemolytic uremic syndrome (HUS) in Germany, including 90 children. Data on the intermediate outcome in children after HUS due to E. coli O104:H4 have been lacking.Methods. Follow-up data were gathered retrospectively from the medical records of patients who had been included in the German Pediatric HUS Registry during the 2011 outbreak.Results. Seventy-two of the 89 (81%) patients were included after a median follow-up of 3.0 (0.9-4.7) years. Hypertension and proteinuria were present in 19% and 28% of these patients, respectively. Of 4 patients with chronic kidney disease (CKD) > stage 2 at short-term follow-up, 1 had a normalized estimated glomerular filtration rate, and 3 (4%) had persistent CKD > stage 2. In 1 of these patients, CKD improved from stage 4 to 3; 1 who had CKD stage 5 at presentation received kidney transplantation; and 1 patient required further hemodialysis during follow-up. One patient (1.4%) still had major neurological symptoms at the latest follow-up. Dialysis during the acute phase (P = .01), dialysis duration (P = .01), and the duration of oligo-/anuria (P = .005) were associated with the development of renal sequelae. Patients treated with eculizumab (n = 11) and/or plasmapheresis (n = 13) during the acute phase of HUS had comparable outcomes.Conclusions. The overall outcome of pediatric patients after HUS due to E. coli O104:H4 was equivalent to previous reports on HUS due to other types of Shiga toxin-producing E. coli (STEC). Regular follow-up visits in patients are recommended after STEC-HUS.
“…As in our patients, it has been previously observed that the GFR can improve or deteriorate over time after HUS [20,21]. Similar to the results of Rosales et al and our results, 2 of 45 (4%) adult patients from the 2011 outbreak from a single center had increased creatinine after 1 year of follow-up [22]. However, decreased eGFR < 90 mL/min calculated from cystatin C was found in Figure 3.…”
Section: Discussionsupporting
confidence: 91%
“…Substantial variation between the different studies might also be due to the different definitions of proteinuria applied. Again adults affected during the outbreak showed similar results, with albuminuria in 27% of the cases at 1-year follow-up [22]. Although proteinuria in patients after HUS is more common compared with the normal population and proteinuria is associated with impaired kidney function, it is not necessarily a measure for poor outcome.…”
Section: Discussionmentioning
confidence: 59%
“…This was associated with older age (mean age 60 years [eGFR < 90 mL/min] vs 43 years [eGFR > 90 mL/min]) [22].…”
Background. In 2011 Escherichia coli O104:H4 caused an outbreak with >800 cases of hemolytic uremic syndrome (HUS) in Germany, including 90 children. Data on the intermediate outcome in children after HUS due to E. coli O104:H4 have been lacking.Methods. Follow-up data were gathered retrospectively from the medical records of patients who had been included in the German Pediatric HUS Registry during the 2011 outbreak.Results. Seventy-two of the 89 (81%) patients were included after a median follow-up of 3.0 (0.9-4.7) years. Hypertension and proteinuria were present in 19% and 28% of these patients, respectively. Of 4 patients with chronic kidney disease (CKD) > stage 2 at short-term follow-up, 1 had a normalized estimated glomerular filtration rate, and 3 (4%) had persistent CKD > stage 2. In 1 of these patients, CKD improved from stage 4 to 3; 1 who had CKD stage 5 at presentation received kidney transplantation; and 1 patient required further hemodialysis during follow-up. One patient (1.4%) still had major neurological symptoms at the latest follow-up. Dialysis during the acute phase (P = .01), dialysis duration (P = .01), and the duration of oligo-/anuria (P = .005) were associated with the development of renal sequelae. Patients treated with eculizumab (n = 11) and/or plasmapheresis (n = 13) during the acute phase of HUS had comparable outcomes.Conclusions. The overall outcome of pediatric patients after HUS due to E. coli O104:H4 was equivalent to previous reports on HUS due to other types of Shiga toxin-producing E. coli (STEC). Regular follow-up visits in patients are recommended after STEC-HUS.
“…The overall increased systolic and diastolic blood pressure places the PNA animals in the range of uncomplicated stage I hypertension (between 140/90 to 150/99 mmHg). 71 , 72
10.1080/19490976.2018.1441664-F0004Figure 4.Radiotelemetry Blood Pressure, Heart Rate, and Locomotor Activity. Radiotelemetry analysis was performed for moving averages every hour for 28 hours with standard error calculated for each hour.…”
Section: Resultsmentioning
confidence: 99%
“…38 , 39 Bacteria from the family Enterobacteriaceae , particularly Escherichia coli , have been associated with increased systemic lipopolysaccharides 136 , increased risk of obesity, inflammation, reduced glomerular filtration rate, increased serum cystatin C and insulin resistance. 71 , 137 , 138
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Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring.
Results: The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs).
Conclusions: We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.
Enterohemorrhagic Escherichia coli (EHEC) are Shiga toxin (Stx) producing bacteria causing a disease characterized by bloody (or non-bloody) diarrhea, which might progress to hemolytic uremic syndrome (HUS). EHEC O104:H4 caused the largest ever recorded EHEC outbreak in Germany in 2011, which in addition showed the so far highest incidence rate of EHEC-related HUS worldwide. The aggressive outbreak strain carries an unusual combination of virulence traits characteristic to both EHEC-a chromosomally integrated Stx-encoding bacteriophage, and enteroaggregative Escherichia coli-pAA plasmid-encoded aggregative adherence fimbriae mediating its tight adhesion to epithelia cells. There are currently still open questions regarding the 2011 EHEC outbreak, e.g., with respect to the exact molecular mechanisms resulting in the hypervirulence of the strain, the natural reservoir of EHEC O104:H4, and suitable therapeutic strategies. Nevertheless, our knowledge on these issues has substantially expanded since 2011. Here, we present an overview of the epidemiological, clinical, microbiological, and molecular biological data available on the 2011 German EHEC O104:H4 outbreak.
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