Ismael Toledo

Impact of platelet transfusions in children with post-diarrheal hemolytic uremic syndrome

BackgroundPlatelet transfusions should be avoided in children with post-diarrheal hemolytic uremic syndrome (D + HUS) because they might increase microthrombi formation, thereby aggravating the disease. As this possibility has not yet been explored, we investigated whether platelet transfusion in patients with D + HUS would lead to a worse disease course compared to that in patients who did not receive platelet transfusion.MethodsThis was a case–control study in which data from D + HUS children who received platelet transfusions (cases, n  =  23) and those who did not (controls, n  =  54) were retrospectively reviewed and compared.ResultsBoth patient groups were similar in age (p = 0.3), gender (p  =  0.53), weight (p  =  0.86), height (p  =  0.45), prior use of non-steroidal anti-inflammatory drugs (p  =  0.59) or antibiotics (p  =  0.45) and presence of dehydration at admission (p  =  0.79). The two groups also did not differ in initial leukocyte count (p  =  0.98), hematocrit (p  =  0.44) and sodium (p  =  0.11) and alanine aminotransferase levels (p  =  0.11). During hospitalization, dialysis duration (p  =  0.08), number of erythrocyte transfusions (p  =  0.2), serum creatinine peak (p  =  0.22), presence of severe bowel (p  =  0.43) or neurologic (p  =  0.97) injury, arterial hypertension (p  =  0.71), need for intensive care (p  =  0.33) and death (p  =  1.00) were also comparable.ConclusionOur findings suggest that platelet transfusion does not aggravate the course of the disease. Conversely, no hemorrhagic complications were observed in the group of patients who did not receive a platelet transfusion. Until these observations are confirmed by further studies, the benefits and risk of platelet transfusion should be thoughtfully balanced on an individual case basis.

Laboratory predictors of acute dialysis in hemolytic uremic syndrome

Strict guidelines on use of dialysis in children with post‐diarrheal hemolytic uremic syndrome (D + HUS) are lacking. This study investigated laboratory predictors of acute dialysis because they are more objective than clinical features. Added to this, given that urine output is also an objective parameter, its ability to predict dialysis requirements was also investigated.

Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case–control study

BackgroundAlthough erythropoietin (EPO) deficiency has been reported in children with post-diarrheal hemolytic uremic syndrome (D + HUS), very limited clinical data on EPO use in this disease are currently available. In this case–control study we examined whether EPO administration would reduce the number of red blood cell (RBC) transfusions in D + HUS patients under our care.MethodsData from children treated exclusively with RBC transfusions (controls; n = 21) were retrospectively compared with data on those who also received EPO for the treatment of anemia (cases; n = 21).ResultsBoth patient groups were similar in age (p = 0.9), gender (p = 0.12), weight (p = 1.00) and height (p = 0.66). Acute phase severity was also comparable, as inferred by the need for dialysis (p = 0.74), the duration of dialysis (p = 0.3), length of hospitalization (p = 0.81), presence of severe bowel (p = 1.00) or neurological injury (p = 0.69), arterial hypertension (p = 1.00) and death (p = 1.00). No differences in the hemoglobin level at admission (p = 0.51) and discharge (p = 0.28) were noted. Three children treated with EPO and two controls did not require any RBC transfusion (p = 1.00). Median number of RBC transfusions needed by cases and controls was 2 (p = 0.52).ConclusionTreatment with EPO did not reduce the number of RBC transfusions in D + HUS children. Assessment of EPO efficacy in D + HUS merits further studies.

Hemoconcentration in hemolytic uremic syndrome: time to review the standard case definition?

Sirs, Hemoconcentration at disease onset has been postulated as a factor of worse prognosis in children with postdiarrheal hemolytic uremic syndrome (D + HUS). Previous studies have demonstrated a significant association between hemoconcentration and severe bowel injury, the need for and longer duration of dialysis, and acute phase death [1, 2]. In their recent paper published in Pediatric Nephrology, Ardissino and colleagues found in a cohort of 61 patients that hemoconcentration at admission also correlated with major neurological involvement [3]. Of particular importance, given that anemia is a hallmark of the disease but that the more severe cases in their study were associated with little or no anemia, the authors postulate that anemia, based on hematocrit or hemoglobin level, should no longer be considered an absolute diagnostic criterion of D + HUS. Rather, they propose that signs of hemolysis (high lactate dehydrogenase levels, schistocytes, and haptoglobin consumption) should be considered to be equally important indicators for diagnosis, even if anemia is not present at disease onset [3]. In line with their statement, our data provides further support to this notion. Analysis of 154 patients with D + HUS treated in our institution revealed that, regardless of the severity of the disease, a considerable proportion of these patients did not have marked anemia at presentation. Thirty-five patients presented with an initial hematocrit level of ≥30 % (23 %), of whom 24 (16 %) had hematocrit values ranging from 30 to 35 % and the remaining 11 (7 %) presented with initial hematocrit levels of >35 %. Remarkably, three patients presented hematocrit levels as high as 44, 45 and 49 %, respectively. Because patients with hemoconcentration at admission are at increased risk of severe forms of the disease, early diagnosis is mandatory to provide them with the best therapeutic treatment and to promptly determine whether the child should be transferred to a tertiary care center. However, given that anemia is an absolute diagnosis criterion, diagnosis of D + HUS may be delayed when there is little or no apparent anemia. Consequently, we believe that the revision of the standard case definition of D + HUS proposed by Ardissino et al. [3] should be carefully considered.

Hyperuricemia in children with post-diarrheal hemolytic uremic syndrome

Sirs, We read with great interest the article by Acosta and Hogg recently published in Pediatric Nephrology, which described a marked reduction of uricemia associated with improvement of renal function in a child with postdiarrheal hemolytic uremic syndrome (D+HUS) after rasburicase administration [1]. Although urate nephropathy has been postulated as an additional factor of acute kidney injury in D+HUS children [2], there is limited information about its treatment. Recently, we reviewed our experience treating with allopurinol hyperuricemic D+HUS patients and we wish to share it to further address this issue. During the past 5 years, uric acid (UA) levels were investigated in 29 children admitted with D+HUS diagnosis (median age, 1.9 years; range, 0.5–10 years; 15 boys, 14 girls). At baseline, the dialyzed patients (n019, all received peritoneal dialysis) had higher UA levels [(median 14 (range 10.5–28) versus median 5.4 (range 4.1–18.7) mg/dL, p00.003] and creatinine [(median 3.9 (range 1.26–11) versus median 1.04 (range 0.3–3.49) mg/dL, p00.0001] than those who did not undergo dialysis (n010). The dialyzed group presented with anuria while the other showed diuresis ranging from 1.4 to 3.3 mL/kg/h. Twenty-two (19 on dialysis and 3 with normal diuresis) of the 29 patients evaluated had hyperuricemia (UA level >8 mg/dL) [3] and received oral allopurinol at usual doses according to the degree of renal failure. Satisfactory response to treatment was considered if the patient reached uricemia <8 mg/dL, evaluated as follows: 1) In non dialyzed patients: the UA level before allopurinol administration was compared with the minimum value obtained during treatment. 2) In dialyzed patients: the UA level before allopurinol administration was compared with the value obtained prior to recovery of a minimum diuresis of 1 mL/kg/h. Complementarily, if normalization of UA levels occurred after the end of dialysis, the time of its occurrence as well as changes in urine output and creatinine were also analyzed. Continuous variables were compared using the Wilcoxon signed rank test considering a p value <0.05 as statistically significant. After a median of 6 (range 2–18) days of therapy a significant reduction of UA levels was observed, from 14.8 to 10 mg/dL (p00.001). However, the small sample size studied needed a close examination of individual responses: 5 patients (2 on dialysis and the 3 non-oliguric) achieved normal UA levels, 13 dialyzed patients improved levels without reaching normal values and the remaining 4 had even higher levels, despite treatment. In conclusion, just 5 patients achieved normal uricemia [(median 5 (range 2.6– 5.9) mg/dL] during allopurinol treatment, and this response included the 3 non-oliguric children. It is not possible to elucidate from these data whether this improvement of the UA levels depends on the allopurinol therapy, the improvement of the renal failure or both. Furthermore, in the dialyzed patients part of the reduction of the UA levels could be secondary to its transperitoneal clearance. However, since a greater decrease in the uricemia was achieved throughout the days following the recovery of renal function, it seems more probable that this was the major cause of UA levels normalization. In fact, a median A. Balestracci (*) Nephrology Unit, Hospital General de Niños Pedro de Elizalde, Montes de Oca 40, 1270, Ciudad Autónoma de Buenos Aires, Argentina e-mail: abalestracci@yahoo.com.ar

Diagnosis of vesicoureteral reflux according to the 1999 and 2011 guidelines of the Subcommittee on Urinary Tract Infection of the American Academy of Pediatrics.

INTRODUCTION In 1999, the American Academy of Pediatrics (AAP) recommended perform a renal ultrasonography and avoiding cystourethrography to all infants between 2 and 24 months of age after their first urinary tract infection (UTI). In 2011, the AAP restricted voiding cystourethrography to children with a pathological ultrasonography, recurrent and/ or atypical infections. Our objective was to compare, in patients with vesicoureteral reflux (VUR) and normal renal ultrasonography, the prevalence of a relevant pathology as if patients had been studied as per the 1999 guidelines (for first UTI) or the 2011 guidelines (for recurrent and/or atypical UTI). POPULATION AND METHODS We conducted a retrospective analysis of patients with UTI, aged between 2 and 24 months old, seen at our department between January 2010 and August 2014 and who had a normal renal ultrasonography and VUR. A relevant pathology was defined as a finding of grade III VUR or higher and/or pathological renal scintigraphy. RESULTS Forty-five patients (31 girls) were included and were grouped as if they had been treated as per the 1999 or 2011 guidelines. The prevalence of a relevant pathology among patients studied as per the 1999 guidelines (9 out of 24 cases, 3 with atypical UTI) or as per the 2011 guidelines (11 out of 21 cases) was similar (37.5% versus 52%, respectively; p= 0.31). Six patients (25%) with a relevant pathology diagnosed as per the 1999 guidelines would not have been identified in a timely manner with the 2011 version. CONCLUSIONS The prevalence of a relevant pathology identified in children with VUR and normal renal ultrasonography was similar with both guidelines. However, considering the present guidelines, one out of four patients would have been exposed to a delayed or potentially missed diagnosis if recurrence would have been expected to complete the assessment.

Comment to: “A simple prognostic index for Shigatoxin-related hemolytic uremic syndrome at onset: data from the ItalKid-HUS network” by Ardissino et al. Eur J Pediatr. 2018 Aug 10. doi: 10.1007/s00431-018-3198-7

Dear Sir, We have read with great interest the paper by Ardissino et al. [4] on the usefulness of a prognostic index for Shigatoxin-related hemolytic uremic syndrome (STEC-HUS) recently published on the European Journal of Pediatrics. Between 2000 and 2016, we treated 162 cases; 29 of them were lost to follow-up. The remaining 132 were categorized, similarly to the original series, according to whether they coursed a complicated acute disease/long-term sequels (n = 70) or not (n = 62). Then, the score was applied, and the receiver operating characteristic (ROC) curve was calculated. The area under the curve (AUC) was 0.66 (95% CI 0.57–0.74), and the optimal cutoff point was > 12.6 yielding 75.7% (95% CI 63.7–84.8) sensitivity and 56.4% (95% CI 43.3–68.7) specificity. This cutoff, which was almost the same obtained by Ardissino et al., was used to compare the outcomes (chi-square or Fisher’s test as appropriate; level of significance p < 0.05) (Table 1). Although the AUC was quite low, the index worked well to identify patients with severe acute renal and central nervous system (CNS) injury and also for renal or systemic sequel; disappointingly, it did not show utility for death. Creatinine levels of both death patients presenting low score were not so high, which consequently reduced the equation results. Given that these fatal cases had encephalopathy, other factors not addressed by the index formula, such as electrolyte disturbances and/or Shigatoxin direct brain injury, might have alternatively contributed to death [1, 6]. As there is no previous accurate prognostic index for STEC-HUS [3, 5, 7] and given the proper rationale of this novel one [2], further validation is encouraged, especially for death outcome. Communicated by Mario Bianchetti

Síndrome urémico hemolítico asociado a diarrea sin trombocitopenia

BACKGROUND Thrombocytopenia is a hallmark of postdiarrhoeal haemolytic uraemic syndrome (D+ HUS), although it can be transient and therefore undetected. There is scarce information regarding the prevalence and the course of the disease in children with D+ HUS without thrombocytopenia. OBJECTIVE To determine the prevalence of D+ HUS without thrombocytopenia and to describe the clinical characteristics of a series of children with this condition. PATIENTS AND METHODS The medical records of patients with D+ HUS hospitalised between 2000 and 2016 were reviewed to identify those without thrombocytopenia (>150,000mm3). Demographic, clinical and laboratory parameters of the selected cases were collected and descriptively analysed. RESULTS Nine cases (5.6%) without thrombocytopenia were identified among 161 patients hospitalised during the study period. Median age at diagnosis was 17 months (7-32) and median prodromal symptom duration was 15 days (7-21). Eight patients maintained normal urine output while the remaining one required dialysis. No patient presented with severe extrarenal compromise and/or hypertension. CONCLUSIONS The prevalence of non-thrombocytopenic D+ HUS was 5.6% and most cases occurred with mild forms of the disease; however, the need for dialysis in one of them indicated that normalisation of platelet count is not always an accurate marker for disease remittance. Our results also confirm that the time of onset of D+ HUS in patients without thrombocytopenia is usually delayed with respect to the initial intestinal symptoms; thus, heightened diagnostic suspicion is necessary.

Descripción del caso presentado en el numero anterior: Riñón ectópico intratorácico

Recibido: 24-4-2013 Aceptado: 18-5-2013 Caso ClíniCo Un niño eutrófico de 1 año y 7 meses fue derivado al Servicio de Neumotisiología por la persistencia de una opacidad radiológica en los campos medio e inferior del pulmón derecho luego de haber cursado una infección respiratoria interpretada como neumonía. Presentaba hemograma normal, prueba de tuberculina negativa y antecedentes de tres episodios de broncoespasmo. Dado que en el momento de la consulta a Neumotisiología se encontraba asintomático, pero con hallazgos auscultatorios y radiológicos similares a los previos al inicio del tratamiento antibiótico, se desestimó el diagnóstico de neumonía y se interpretó como un episodio de intercurrencia viral respiratoria alta. Por consiguiente, se plantearon otros diagnósticos de masa ocupante del tórax y se solicitó una tomografía computarizada con contraste. Ésta mostró un riñón ectópico intratorácico derecho con hernia hemidiafragmática asociada, sin ninguna otra víscera abdominal localizada en el tórax (Figura 1). En la ecografía se observó el riñón izquierdo ortotópico y el derecho intratorácico, ambos con ecoestructura conservada, tamaño normal y sin dilatación de la vía urinaria. La gammagrafía renal con DMSA evidenció una distribución heterogénea del trazador y contorno irregular del REI, en tanto que el riñón izquierdo era normal (función renal relativa: izquierda 46% y derecha 54%). Se completó el estudio con una angiorresonancia magnética, en la que se observó el riñón ectópico intratorácico derecho con su arteria emergente de la aorta abdominal (Figura 2).

Ectopic intrathoracic kidney

Recibido: 24-4-2013 Aceptado: 18-5-2013 Caso ClíniCo Un niño eutrófico de 1 año y 7 meses fue derivado al Servicio de Neumotisiología por la persistencia de una opacidad radiológica en los campos medio e inferior del pulmón derecho luego de haber cursado una infección respiratoria interpretada como neumonía. Presentaba hemograma normal, prueba de tuberculina negativa y antecedentes de tres episodios de broncoespasmo. Dado que en el momento de la consulta a Neumotisiología se encontraba asintomático, pero con hallazgos auscultatorios y radiológicos similares a los previos al inicio del tratamiento antibiótico, se desestimó el diagnóstico de neumonía y se interpretó como un episodio de intercurrencia viral respiratoria alta. Por consiguiente, se plantearon otros diagnósticos de masa ocupante del tórax y se solicitó una tomografía computarizada con contraste. Ésta mostró un riñón ectópico intratorácico derecho con hernia hemidiafragmática asociada, sin ninguna otra víscera abdominal localizada en el tórax (Figura 1). En la ecografía se observó el riñón izquierdo ortotópico y el derecho intratorácico, ambos con ecoestructura conservada, tamaño normal y sin dilatación de la vía urinaria. La gammagrafía renal con DMSA evidenció una distribución heterogénea del trazador y contorno irregular del REI, en tanto que el riñón izquierdo era normal (función renal relativa: izquierda 46% y derecha 54%). Se completó el estudio con una angiorresonancia magnética, en la que se observó el riñón ectópico intratorácico derecho con su arteria emergente de la aorta abdominal (Figura 2).