Dynamic evolution of kidney function in patients with STEC-hemolytic uremic syndrome followed for more than 15 years: unexpected changes.

BACKGROUND: Most studies regarding kidney outcomes in patients with Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome (STEC-HUS) focus on kidney status at last assessment. We aimed to describe patterns of changes in kidney function during follow-up and investigate associations between kidney function at 1st, 5th, and 10th year after onset and long-term kidney outcomes. METHODS: Data of patients with STEC-HUS followed for at least 15 years were analyzed. Kidney function patterns were constructed considering kidney status at 1st, 5th, 10th, and ≥ 15 years and defined as (1) progressive, if patients changed from complete recovery to any chronic kidney disease (CKD) stage or if CKD worsened; (2) improvement, if they shifted from any CKD stage to complete recovery or to a milder stage; and (3) stable, if remained unchanged. RESULTS: Of 152 patients included, after 1 year of follow-up, 47% had complete recovery, 22% CKD1, and 32% CKD2-5. At last assessment, 46% had complete recovery, 34% CKD1, and 19% CKD2-5. Despite percentages seeming similar, patients differed: 48% were stable, 27% improved, and 25% worsened. Further, 62% of patients with CKD2-4 in the 1st year normalized their glomerular filtration rate (GFR) thereafter. Comparison of kidney function between 1st, 5th, and 10th year to last assessment shows a stable pattern in 48, 59, and 69% respectively. CONCLUSIONS: Changes in kidney function showed a dynamic and complex behavior, with patients moving from one group to another. Consistently, kidney function neither at the 1st, 5th, or 10th year was representative of final outcome. Unexpectedly, two-thirds of patients with CKD2-4 after 1 year achieved normal eGFR later during follow-up.

Kidney sequelae in 281 Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome patients after a median follow-up of 12 years.

BACKGROUND: A substantial proportion of patients with Escherichia coli-hemolytic uremic syndrome (STEC-HUS) evolve to chronic kidney disease (CKD). The objectives of this study were to evaluate long-term kidney outcomes and to identify CKD predictors. METHODS: In this single-center retrospective study, long-term outcomes of patients were analyzed according to the presence of complete recovery (CR) or CKD at last visit. Then, they were grouped into favorable (CR + CKD1) or poor (CKD2-5) outcome to compare predictors at diagnosis (sex, age, leukocytes, creatinine, hemoglobin, HUS severity score), dialysis duration, and follow-up time between them. RESULTS: Of 281 patients followed up for a median of 12 years, 139 (49%) had CR, 104 (37%) CKD1, 27 (10%) CKD2-4, and 11 (4%) CKD5. Thirty-eight patients progressed to CKD2-5 after a median of 4.8 years, 7% in the first 5 years, increasing to 8%, 10%, and 14% after 5-10 years, 10-15 years, and > 15 years, respectively. They were younger, had higher baseline hemoglobin and leukocytes, and required longer dialysis and follow-up than those with favorable outcome. By multivariate analysis, days of dialysis and follow-up time remained as independent predictors of poor outcome. The best cutoff for days of dialysis was 10 days. After 5 years, 20% of those dialyzed ≥ 10 days evolved to CKD2-5 versus 1% of those non-dialyzed or dialyzed < 10 days. CONCLUSIONS: Fifty-one percent of patients evolved to CKD after 12 years of follow-up and 14% to CKD2-5. Ten days of dialysis was the best cutoff to recognize outcomes. In some cases, kidney damage was evident after 15 years of surveillance, highlighting the need for follow-up until adulthood in all STEC-HUS patients.

Long-term kidney outcomes in non-dialyzed children with Shiga-toxin Escherichia coli associated hemolytic uremic syndrome.

BACKGROUND: Long-term kidney outcomes of non-dialyzed children with Shiga-toxin Escherichia Coli hemolytic uremic syndrome (STEC-HUS) have been scantily studied. Therefore, we aimed to evaluate kidney outcomes and prognostic markers in these patients. METHODS: Non-dialyzed STEC-HUS patients followed for at least 5 years were included. They were grouped and compared according to kidney status at last visit: complete recovery (CR) or chronic kidney disease (CKD). Predictors of CKD evaluated at diagnosis were sex, age, leukocytes, hematocrit, hemoglobin (Hb), and serum creatinine (sCr). Peak sCr and time of follow-up were also analyzed. RESULTS: A total of 122 patients (62 female, median age at diagnosis 1.6 years) with a median follow-up of 11.3 years were included. At last visit, 82 (67%) had CR, 36 (30%) had CKD stage 1, and 4 (3%) had stage 2. No patient developed CKD stage 3-5. Median time to CKD was 5 years (IQR 3.1-8.76 years). Of the 122 patients, 18% evolved to CKD in the first 5 years, increasing to 28% at 10 and 33% at 20 years of follow-up. Serum Cr at diagnosis and peak sCr were significantly higher in patients with CKD than in those with CR. CONCLUSIONS: One third of non-dialyzed STEC-HUS patients evolved to CKD after a median time of 5 years. However, CKD may appear even after 15 years of CR. Serum Cr was significantly higher among patients who evolved to CKD. These data reinforce that all non-dialyzed patients should be followed until adulthood. A higher resolution version of the Graphical abstract is available as Supplementary information.

Tiempo de excreción fecal de Escherichia coliproductora de toxina Shiga en niños con síndrome urémico hemolítico / Duration of fecal shedding of Shiga toxin-producing Escherichia coli among children with hemolytic uremic syndrome

Introducción. Conocer el tiempo de excreción fecal de Escherichia coli productora de toxina Shiga (Shiga toxin-producing Escherichia coli; STEC, por sus siglas en inglés) en pacientes con síndrome urémico hemolítico sería útil para controlar la transmisión de la enfermedad.Objetivos. 1) Analizar las características del tiempo de excreción de STEC. 2) Evaluar la asociación con las variables sexo, edad, necesidad de diálisis, antibióticos y serotipos de STEC.Población y métodos. Estudio prospectivo, observacional, longitudinal y analítico. Período 2013-2019. Se realizaron coprocultivos al ingresar y cada 5-7 días hasta obtener 2 negativos. Se definió tiempo de excreción desde el inicio de la diarrea hasta el primer negativo. Se confirmó STEC por detección de los genes stx1, stx2 y rfbO157 por reacción en cadena de la polimerasa. Se calculó la media (IC 95 %) y percentilos del tiempo de excreción de STEC, y se compararon las variables estudiadas mediante el test de t.Resultados. Se incluyeron 43 pacientes. La media de tiempo de excreción fue 10,2 días (IC 95 %: 8,92-11,59), rango: 3-22 días. El 90 % de los pacientes negativizaron el coprocultivo a los 15 días. No hubo diferencias según sexo (p = 0,419), edad (p = 0,937), necesidad de diálisis (p = 0,917), antibióticos (p = 0,147) ni serotipos (p = 0,231).Conclusión. El 90 % de los pacientes negativizó el coprocultivo a los 15 días del inicio de la diarrea, y todos, al día 22. No se encontró asociación entre el tiempo de excreción y las variables estudiadas.

Introduction. Knowing the duration of fecal shedding of Shiga toxin-producing Escherichia coli(STEC) among patients with hemolytic uremic syndrome would be useful to control disease transmission.Objectives. 1) To analyze the characteristics of STEC shedding duration. 2) To assess the association with sex, age, need of dialysis, antibiotics, and STEC serotypes.Population and methods. Prospective, observational, longitudinal, and analytical study in the 2013-2019 period. Stool cultures were done upon admission and every 5-7 days until 2 negative results were obtained. Shedding duration was defined as the period from diarrhea onset to the first negative result. STEC was confirmed with polymerase chain reaction detection of stx1, stx2, and rfbO157 genes. The mean (95 % CI) and percentile values of the STEC shedding duration were estimated, and the studied outcome measures were compared using the t test.Results. A total of 43 patients were included. The mean duration of shedding was 10.2 days (95 % CI: 8.92-11.59), range: 3-22 days. After 15 days, 90 % of patients had a negative stool culture. There were no differences in terms of sex (p = 0.419), age (p = 0.937), need of dialysis (p = 0.917), antibiotics (p = 0.147) or serotype (p = 0.231).Conclusion. Fifteen days after the onset of diarrhea, 90 % of patients had a negative stool culture, and all patients had one after 22 days. No association was observed between the duration of shedding and studied outcome measures.

Duration of fecal shedding of Shiga toxin-producing Escherichia coli among children with hemolytic uremic syndrome. / Tiempo de excreción fecal de Escherichia coli productora de toxina Shiga en niños con síndrome urémico hemolítico.

INTRODUCTION: Knowing the duration of fecal shedding of Shiga toxin-producing Escherichia coli (STEC) among patients with hemolytic uremic syndrome would be useful to control disease transmission. OBJECTIVES: 1) To analyze the characteristics of STEC shedding duration. 2) To assess the association with sex, age, need of dialysis, antibiotics, and STEC serotypes. POPULATION AND METHODS: Prospective, observational, longitudinal, and analytical study in the 2013-2019 period. Stool cultures were done upon admission and every 5-7 days until 2 negative results were obtained. Shedding duration was defined as the period from diarrhea onset to the first negative result. STEC was confirmed with polymerase chain reaction detection of stx1, stx2, and rfbO157 genes. The mean (95 % CI) and percentile values of the STEC shedding duration were estimated, and the studied outcome measures were compared using the t test. RESULTS: A total of 43 patients were included. The mean duration of shedding was 10.2 days (95 % CI: 8.92-11.59), range: 3-22 days. After 15 days, 90 % of patients had a negative stool culture. There were no differences in terms of sex (p = 0.419), age (p = 0.937), need of dialysis (p = 0.917), antibiotics (p = 0.147) or serotype (p = 0.231). CONCLUSION: Fifteen days after the onset of diarrhea, 90 % of patients had a negative stool culture, and all patients had one after 22 days. No association was observed between the duration of shedding and studied outcome measures.

Introducción. Conocer el tiempo de excreción fecal de Escherichia coli productora de toxina Shiga (Shiga toxin-producing Escherichia coli; STEC, por sus siglas en inglés) en pacientes con síndrome urémico hemolítico sería útil para controlar la transmisión de la enfermedad. Objetivos. 1) Analizar las características del tiempo de excreción de STEC. 2) Evaluar la asociación con las variables sexo, edad, necesidad de diálisis, antibióticos y serotipos de STEC. Población y métodos. Estudio prospectivo, observacional, longitudinal y analítico. Período 2013-2019. Se realizaron coprocultivos al ingresar y cada 5-7 días hasta obtener 2 negativos. Se definió tiempo de excreción desde el inicio de la diarrea hasta el primer negativo. Se confirmó STEC por detección de los genes stx1, stx2 y rfbO157 por reacción en cadena de la polimerasa. Se calculó la media (IC 95 %) y percentilos del tiempo de excreción de STEC, y se compararon las variables estudiadas mediante el test de t. Resultados. Se incluyeron 43 pacientes. La media de tiempo de excreción fue 10,2 días (IC 95 %: 8,92- 11,59), rango: 3-22 días. El 90 % de los pacientes negativizaron el coprocultivo a los 15 días. No hubo diferencias según sexo (p = 0,419), edad (p = 0,937), necesidad de diálisis (p = 0,917), antibióticos (p = 0,147) ni serotipos (p = 0,231). Conclusión. El 90 % de los pacientes negativizó el coprocultivo a los 15 días del inicio de la diarrea, y todos, al día 22. No se encontró asociación entre el tiempo de excreción y las variables estudiadas.

Enfermedad invasiva asociada a neumococo y síndrome urémico hemolítico, nuevo serotipo / Invasive pneumococcal disease and hemolytic uremic syndrome: new serotype

El síndrome urémico hemolítico asociado a Streptococcus pneumoniae (SUH-Sp) se define como anemia hemolítica microangiopática, plaquetopenia y lesión renal aguda, en un paciente con infección invasiva por Streptococcus pneumoniae (Sp). Varón de 2 años, con neumonía con derrame pleural por Sp aislado en hemocultivos y líquido pleural. A las 72 h, presentó palidez, decaimiento, quejido respiratorio y oliguria. En el análisis de laboratorio se encontró anemia, plaquetopenia, aumento de la urea, la creatinina y la lactato deshidrogenasa en sangre; coombs directa +; esquistocitos en frotis; fibrinógeno; coagulograma normal; dímero D aumentado. Orina con proteinuria y hematuria. En Terapia Intensiva requirió asistencia respiratoria mecánica y transfusión con glóbulos rojos lavados; se recuperó progresivamente. El Instituto Malbrán informó serotipo 38 de Sp. Es el primer paciente comunicado con este serotipo

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury, in a patient with Streptococcus pneumoniae (Sp) invasive infection. A 2-year-old boy was admitted with pneumonia and empyema. Sp was isolated from blood and pleural fluid cultures. After 72 h, the patient showed paleness, asthenia, respiratory whining and oliguria. Laboratory showed anemia, low platelets, increased blood urea, creatirnina, lactate dehdrogenase, direct Coombs +, schistocytes, fibrinogen, normal coagulogram and increased D-dimer. Proteinuria and hematuria were detected in urine. Mechanical ventilatory assistance and transfusions of washed red blood cells were required. The patient recovered progressively. Sp serotype 38 was isolated in the National Reference Laboratory "Malbran". This is the first report associated to this serotype

[Invasive pneumococcal disease and hemolytic uremic syndrome: new serotype]. / Enfermedad invasiva asociada a neumococo y síndrome urémico hemolítico, nuevo serotipo.

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury, in a patient with Streptococcus pneumoniae (Sp) invasive infection. A 2-year-old boy was admitted with pneumonia and empyema. Sp was isolated from blood and pleural fluid cultures. After 72 h, the patient showed paleness, asthenia, respiratory whining and oliguria. Laboratory showed anemia, low platelets, increased blood urea, creatirnina, lactate dehdrogenase, direct Coombs +, schistocytes, fibrinogen, normal coagulogram and increased D-dimer. Proteinuria and hematuria were detected in urine. Mechanical ventilatory assistance and transfusions of washed red blood cells were required. The patient recovered progressively. Sp serotype 38 was isolated in the National Reference Laboratory "Malbran". This is the first report associated to this serotype.

El síndrome urémico hemolítico asociado a Streptococcus pneumoniae (SUH-Sp) se define como anemia hemolítica microangiopática, plaquetopenia y lesión renal aguda, en un paciente con infección invasiva por Streptococcus pneumoniae (Sp). Varón de 2 años, con neumonía con derrame pleural por Sp aislado en hemocultivos y líquido pleural. A las 72 h, presentó palidez, decaimiento, quejido respiratorio y oliguria. En el análisis de laboratorio se encontró anemia, plaquetopenia, aumento de la urea, la creatinina y la lactato deshidrogenasa en sangre; coombs directa +; esquistocitos en frotis; fibrinógeno; coagulograma normal; dímero D aumentado. Orina con proteinuria y hematuria. En Terapia Intensiva requirió asistencia respiratoria mecánica y transfusión con glóbulos rojos lavados; se recuperó progresivamente. El Instituto Malbrán informó serotipo 38 de Sp. Es el primer paciente comunicado con este serotipo.

Factores de riesgo asociados a infección en pacientes con hidronefrosis antenatal de alto grado / Risk factors associated to urinary infection in patients with high grade antenatal hydronephrosis

Introducción: la elevada incidencia de infección urinaria en pacientes con hidronefrosis antenatal de alto grado ha llevado a la recomendación de profilaxis antibiótica. Objetivos: Determinar la incidencia de infección urinaria en pacientes con hidronefrosis antenatal aislada de alto grado y posibles factores de riesgo asociados. Material y métodos: Diseño observacional, analítico, retrospectivo. Criterios de inclusión: recién nacidos con hidronefrosis antenatal de alto grado aislada (moderadas y severas, diámetro antero-posterior de la pelvis >15 mm) con más de 12 meses de seguimiento en aquellos tratados conservadoramente y hasta la cirugía en los que la requirieron. No se incluyeron recién nacidos con hidronefrosis de alto grado debida a reflujo vesicoureteral, mega uréteres, válvula de uretra posterior, ureterocele. Se realizó análisis de regresión logística múltiple, variables independientes: género, grado de hidronefrosis y profilaxis antibiótica. Se aplicó prueba exacta de Fisher, p≤0,05 fue considerada significativa. Resultados: Se evaluaron 68 pacientes, 51 con hidronefrosis antenatal moderada (parénquima normal) y 17 con severa (parénquima afinado). Dieciséis pacientes (23,5%) tuvieron infección urinaria. Ni el género, ni el grado de hidronefrosis fueron factores de riesgo para infección urinaria. El 57% (12/21) de los pacientes con profilaxis presentaron IU, contra el 8,5% (4/47) sin profilaxis. La profilaxis incrementó el riesgo de IU (OR crudo 14,3; IC 95% 3,7-54,7; y ajustado por género y grado de hidronefrosis 25; IC 95% 5- 125; p<0.001). Conclusiones: La incidencia de infección urinaria fue 23,5%. Nuestro estudio muestra un mayor riesgo de infección urinaria en pacientes con profilaxis antibiótica.

Introduction: the high incidence of urinary infection in patients with high-grade antenatal hydronephrosis has led us to recommend antibiotic prophylaxis. Objectives: To determine the incidence of urinary infection in patients with high grade isolated antenatal hydronephrosis and its possible associated risk factors. Methods: Observational retrospective analytic design. Inclusion criteria: new born with isolated high grade antenatal hydronephrosis (moderate and severe, anterior-posterior pelvis diameter >15mm) monitored for more than 12 months, conservatively treated until surgical intervention on those that required it. New born with high-grade hydronephrosis due to vesicoureteral reflux, megaureters, posterior urethral valve, ureterocele, were not included. Multiple logistic regression analyses were performed, independent variables: gender, grade of hydronephrosis and antibiotic prophylaxis. FisherÆs exact test was used, p<0.05 was considered significant. Results: 68 patients were evaluated, 51 with moderate antenatal hydronephrosis (normal parenchyma) and 17 with severe antenatal hydroneprohosis (thin parenchyma). Sixteen patients (23.5%) had urinary infection. Neither gender nor hydronephrosis grade were risk factors for urinary infection. 57% (12/21) of the patients with prophylaxis presented UI, compared to 8.5% (4/47) in those without prophylaxis. Prophylaxis increased risk of IU: OR crude 14.3 (CI 95% 3.7-54.7) and adjusted by gender and hydronephrosis grade OR 25 (CI 95%5-125; p<0.001). Conclusions: Urinary infection incidence was 23.5%. Our study shows a major risk of urinary infection in patients with antibiotic prophylaxis.