Alejandro Balestracci

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.

Acute dialysis-associated peritonitis in children with D+ hemolytic uremic syndrome

Acute peritoneal dialysis (PD) is the preferred therapy for renal replacement in children with post-diarrheal hemolytic uremic syndrome (D+ HUS), but peritonitis remains a frequent complication of this procedure. We reviewed data from 149 patients with D+ HUS who had undergone acute PD with the aim of determining the prevalence and risk factors for the development of peritonitis. A total of 36 patients (24.2%) presented peritonitis. The median onset of peritonitis manifestations was 6 (range 2–18) days after the initiation of dialysis treatment, and Gram-positive microorganisms were the predominant bacterial type isolated (15/36 patients). The patients were divided into two groups: with or without peritonitis, respectively. Univariate analysis revealed that a longer duration of the oligoanuric period, more days of dialysis, catheter replacement, stay in the intensive care unit, and hypoalbuminemia were significantly associated to the development of peritonitis. The multivariate analysis, controlled by duration of PD, identified the following independent risk factors for peritonitis: catheter replacement [p = 0.037, odds ratio (OR) 1.33, 95% confidence interval (CI) 1.02–1.73], stay in intensive care unit (p = 0.0001, OR 2.62, 95% CI 1.65–4.19), and hypoalbuminemia (p = 0.0076, OR 1.45, 95% CI 1.10–1.91). Based on these findings, we conclude that the optimization of the aseptic technique during catheter manipulation and early nutritional support are targets for the prevention of peritonitis, especially in critically ill patients.

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

A case of Menkes' disease with nephrocalcinosis and chronic renal failure.

Sirs, Renal tubule disorders have been reported in Menkes’ disease (MNK) [1–5]. Among others, hypercalciuria has been observed [3, 5]. We report the details of a child with MNK and nephrocalcinosis due to hypercalciuria. A 35-day-old boy was referred to our hospital with a diagnosis of MNK. He was the third child of an unrelated couple, and a previous son had died at 11 months of age from the same disease. The diagnosis of MNK was made on the basis of the following findings: hypotonia, seizures, sparse hypopigmented hair, low serum levels of copper (Cu) (30 μg/dl, normal range 70–140 μg/dl) and caeruloplasmin (7 mg/dl, normal range 15–54mg/dl). Light microscopy of his hair showed pili torti. Subcutaneous Cu histidine therapy (350 μg/day) was initiated. With this treatment, Cu and caeruloplasmin levels were maintained within the normal ranges. When he was 7 months of age renal ultrasonography revealed multiple bladder diverticula and marked bilateral medullary hyperechogenicity suggestive of nephrocalcinosis. He had no history of calcium or vitamin D supplementation or other drugs linked to hypercalciuria. Malabsorption was ruled out. Because of the nephrocalcinosis, his renal function was investigated. On initial evaluation his blood laboratory parameters were as follows: urea 32 mg/dl, creatinine 0.46 mg/dl, sodium (Na) 140 mEq/l, potassium (K) 4.2 mEq/l, chloride (Cl) 105 mEq/l, pH 7.34, bicarbonate 22 mEq/l, calcium (Ca) 9.3 mg/dl, phosphate (P) 4.5 mg/dl, alkaline phosphatase 440 IU/l, intact parathyroid hormone (iPTH) 26 pg/ml, magnesium (Mg) 1.95 mg/dl, uric acid 1.6 mg/dl. Urinary parameters were: urine flow 4.1 ml/kg body weight per hour, specific gravity 1.015 g/l, calciuria 8.2 mg/kg per day (normal < 4 mg/kg per day), magnesiuria 1.9 mg/kg per day (normal < 2.5 mg/kg per day), uricosuria 15.5 mg/kg per day (normal < 18 mg/kg per day), tubular reabsorption of phosphate (TRP) 94.4% (normal 80–95%), proteinuria 12 mg/kg per day (normal <5 mg/kg per day), microalbumin 8 μg/min (normal <20 μg/min), β-2 microglobulin 1,575 μg/l (normal <137 μg/l), uroproteinogram tubular pattern, citraturia 267 mg/day (normal 140–900 mg/day), oxaluria 22.2 mg/day (normal 13–38 mg/day), and results for glucose and aminoaciduria were negative. Blood pressure was always within the normal ranges. Restriction of sodium intake up to 1 g/day, hydrochlorothiazide 2 mg/kg per day and potassium citrate 2 mEq K/kg per day were indicated to reduce the hypercalciuria. During 4 years of follow-up, his urinary β2-microglobulin levels rose to 8,040 μg/l and microalbumin to 188 μg/min; hypercalciuria persisted, despite treatment, and creatinine clearance decreased from 81 ml/min per 1.73 m body surface area to 58.7 ml/min per 1.73 m body surface area. An excessive amount of Cu accumulates in the proximal convoluted tubular cells of patients with MNK, and increased Cu was found in the form of Cu-metallothionein (Cu-MT) [2, 3]. Metallothioneins are low molecular weight heavy metal-binding proteins, and Cu-MT overproduction is thought to contribute to cell necrosis [6]. Proximal tubule dysfunction has previously been reported in children with MNK. Two patients in the original observation of Menkes et al. were found to have albuminuria and aminoaciduria, respectively [1]. Ozawa et al. demonstrated a high rate of excretion of urinary β2Pediatr Nephrol (2009) 24:1255–1256 DOI 10.1007/s00467-008-1104-7

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.