Hyperuricemia: an unrecognized risk factor for kidney-related sequelae in children with hemolytic uremic syndrome.

BACKGROUND: Chronic kidney-related sequelae after STEC-HUS occur in 20-40% of patients. Hyperuricemia (HU) may cause acute and chronic toxicity involving the kidneys. We retrospectively assessed if there was an association between the presence of HU during the acute illness and that of kidney-related sequelae in children with STEC-HUS. METHODS: Children with STEC-HUS who had clinical and laboratory data at 2 years of follow-up were included in this case-control study. Univariate and multivariate analyses were performed between patients with (cases) or without (controls) kidney-related sequelae to identify factors associated with outcomes, including different measures of serum uric acid (sUA) (baseline level, peak, and duration of HU). HU was defined as sUA > 8 mg/dL. RESULTS: Of 86 patients included, 77.9% had HU. Patients with sequelae (n = 41) had a higher prevalence of HU (41/41 vs. 26/45, p < 0.01), higher baseline leukocyte count, serum creatinine (sCr), and sUA levels as well as lower sodium than controls. During hospitalization, cases also had higher sCr peak, sUA peak and duration of HU, requirement and duration of dialysis, extrarenal complications, and hypertension. By multivariate analysis, after adjusting for length of dialysis, only duration of HU (p = 0.0005; OR 1.7, 95% CI 1.27-2.36) remained as an independent predictor of sequelae, with a best cutoff of 5.5 days (AUC 0.95, specificity 80%, sensitivity 100%). CONCLUSIONS: The presence of HU is a common finding in children with STEC-HUS and its duration during the acute stage was associated with kidney-related sequelae, regardless of the duration of dialysis. A higher resolution version of the Graphical abstract is available as Supplementary Information.

Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial.

BACKGROUND: The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. METHODS: We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. RESULTS: Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. CONCLUSION: In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prodromal Phase of Hemolytic Uremic Syndrome Related to Shiga Toxin-Producing Escherichia coli: The Wasted Time.

OBJECTIVES: This study aimed to evaluate practice patterns during prodromal phase of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS). METHODS: Trajectories of children from first symptoms until STEC-HUS admitted consecutively at our center (period 2000-2017) were retrospectively reviewed. Early recommended practices include identification of STEC infections, antibiotics and antiperistaltic avoidance, and administration of anticipatory intravenous fluids; therefore, implementation and changes over time (before and after 2011) of such interventions were assessed. In addition, early management was correlated with acute disease outcomes. RESULTS: Of 172 patients, 98 (57%) had early consults, 75 of them visit the pediatric emergency department. Those seen with watery diarrhea (n = 74) were managed as outpatients, whereas 27 of the 45 assisted with bloody diarrhea were hospitalized for diagnosis other than STEC-HUS. Stool cultures were performed in 13.4% (23/172), 18% (31/172) received antibiotics, and 12.8% (22/172) received endovenous fluids; none received antiperistaltic agents. Shiga toxin-producing E. coli infection was proven in 4% (7/172) before HUS. Rate of cultured patients and treated with intravenous fluids remained unchanged over time (P = 0.13 and P = 0.48, respectively), whereas antibiotic prescription decreased from 42.8% to 16.6% (P = 0.005). Main acute outcomes (need for dialysis, pancreatic compromise, central nervous system involvement, and death) were similar (P > 0.05) regardless of whether they received antibiotics or intravenous fluids. CONCLUSIONS: During the diarrheal phase, 57% of patients consulted; three-quarters of them consulted to the pediatric emergency department. Shiga toxin-producing E. coli detection was poor, antibiotic use remained high, and anticipatory volume expansion was underused. These findings outline the critical need to improve the early management of STEC-HUS.

Rasburicase in hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli: a report of nine cases.

BACKGROUND: Hyperuricemia might induce additional renal damage in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS). A few case reports have shown rasburicase to be effective in decreasing serum uric acid (UA) and improving renal function. However, there is only one report on the use of rasburicase in a child with STEC-HUS, which shows satisfactory results. We describe here the safety and efficacy of rasburicase in nine additional cases. CASE-DIAGNOSIS/TREATMENT: Data from 9 children (5 females, median age 2 years) who received rasburicase were reviewed. At admission, 6 were dehydrated and 3 euvolemic. Dehydrated patients received saline solution and afterwards, as well as for those initially euvolemic, we aimed to keep a neutral fluid balance. Despite this, urine output did not increase. Baseline creatinine was 3.35 mg/dL (1.47-9.1) and UA 11.4 mg/dL (8.3-19.2). A single dose of rasburicase (0.2 mg/kg) was given 6-8 h after admission, which reduced UA levels to 1.8 mg/dL (0.3-5, p = 0.009) on the next day. However, renal parameters worsen and dialysis had to be initiated. Then, while still on dialysis, a UA rebound occurred in all cases reaching a peak of 8.9 mg/dL (4.5-13.8). Just after a steady increase in urine output, a sustained decline in UA levels concomitantly occurred with an improvement in renal function. At discharge, all patients reached normal UA levels. No side effects were recorded. CONCLUSIONS: Administration of rasburicase in children with STEC-HUS was safe but failed to provide any significant benefit despite fall in serum UA levels.

C3 levels and acute outcomes in Shiga toxin-related hemolytic uremic syndrome.

BACKGROUND: The correlation between complement activation and severity of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) has been examined in few studies, with conflicting results. We investigated whether C3 levels on admission are associated with worse acute outcomes. METHODS: Demographic, clinical, and laboratory variables were compared between dialyzed and non-dialyzed patients and between those with or without extrarenal complications. Univariate and multivariate analyses were performed; odds ratio (OR) and 95% confidence interval (95%CI) were calculated. C3 concentrations were correlated with dialysis length (Spearman test) and ROC curves with area under the curves (AUC) were calculated to identify C3 concentrations able to discriminate patients with dialysis requirements and complicated course. RESULTS: Among 49 children, 33 had normal and 16 had decreased C3 concentrations. Higher hemoglobin, lactic dehydrogenase, urea and creatinine and lower albumin, sodium, and C3 and C4 concentrations at admission were associated with dialysis requirement; only creatinine remained significant (p = 0.03, OR 2.1, 95%CI 1.34-2.7) by multivariate analysis. Patients with a complicated course presented higher leukocyte count, hemoglobin and lactic dehydrogenase and lower albumin, sodium, and C3 and C4. In the multivariate analysis, leukocyte count (p = 0.02, OR 2.6, 95%CI 1.4-4.3) and C3 concentration (p = 0.039, OR 1.7, 95%CI 1.1-2.73) were independently associated with a complicated disease. C3 levels correlated with dialysis length (r = - 0.42, p = 0.002); nevertheless, they were unable to discriminate dialysis requirement (AUC = 0.25, 95%CI 0.11-0.38) and extrarenal complications (AUC = 0.24, 95%CI 0.11-0.4). CONCLUSIONS: Our study suggests that decreased C3 levels at admission are associated with a more complicated STEC-HUS episode.

Correction to: C3 levels and acute outcomes in Shiga toxin-related hemolytic uremic syndrome.

Due to an unfortunate error during the processing of the article, the spelling of the second author name was incorrect.

The Influence of Chloride for the Interpretation of Plasma Bicarbonate During the Treatment of Diabetic Ketoacidosis.

INTRODUCTION: Hyperchloremic metabolic acidosis can occur in diabetic ketoacidosis (DKA) and may affect the acid-base interpretation during treatment. OBJECTIVES: This study aims to describe the prevalence of hyperchloremia during the treatment of DKA and its effect on the interpretation of bicarbonate value. METHODS: A cross-sectional study, including all cases of DKA in patients aged 1 to 18 years old admitted from 2010 to 2015, was performed. Laboratory tests were performed on admission (baseline), 2 and 6 hours after admission, and when resolution of DKA was achieved. Adjusted bicarbonate value was calculated using regression equations. RESULTS: Seventy-nine DKA episodes were included. The average age was 13.3 ± 3.8 years. Baseline levels were as follows: plasma glucose, 479 ± 133 mg/dL; pH 7.1 ± 0.083; bicarbonate, 9.65 ± 2.9; and anion gap, 23.9 ± 7.5. The time to achieve resolution of DKA was 12.2 ± 4.4 hours, and the decrease in capillary glucose was 25.5 (19.7-38.2) mg/dL per hour. After 6 hours of treatment, the proportion of patients presenting hyperchloremia increased from 23% to 77%. By using adjusted bicarbonate, the percentage of patients achieving resolution of DKA after 6 hours of treatment would have been 35.4% (confidence interval 95%, 28-49), in comparison with 24.1% (confidence interval 95%, 18-37) using observed bicarbonate (P = 0.004). CONCLUSIONS: The hyperchloremia developed during the treatment of DKA could modify the value of measured plasma bicarbonate concentration and unnecessarily prolong the initial phase of treatment.

[Prevalence of Arterial Hypertension in a neonatal intensive care unit]. / Prevalencia de Hipertensión Arterial en una unidad de cuidados intensivos neonatales.

INTRODUCTION: The prevalence of neonatal hypertension in neonatal intensive care units (NICU) ranges between 3 and 9%. However, there is no current data on Latin America. OBJECTIVE: To estimate the prevalence of neonatal hypertension and to assess its association with causes previously related to this condi tion. PATIENTS AND METHOD: cross-sectional study. All patients admitted to the NICU during one year were included, excluding those transferred to the cardiovascular NICU. The following maternal and neonatal variables were registered: maternal arterial hypertension, type of delivery, gestational age, age, sex, birth weight, Apgar score, history of pulmonary maturation with corticosteroids, and umbilical vessel catheterization as well as the reason for admission to the NICU, medications, and complications during hospitalization. Blood pressure was measured with an automated oscillometric device, defining neonatal hypertension according to standards in gestational age. Prevalence was ex pressed as percentage (confidence interval 95%, CI95%). Descriptive data were reported as median (range) and frequency of presentation (percentage). Finally, we used the Wilcoxon, Chi2 o Fisher exact test to identify factors related to NH as applicable (p < 0.05). RESULTS: 169 patients were in cluded (60% males). Gestational age was 38 weeks (range 26-42 weeks), 38% were preterm. Birth weight was 3000 g (range 545-4950 g) and 32% presented low birth weight. Eight patients presented hypertension during hospitalization (4.7% prevalence, CI95% 2.4-9). The presence of hypertension was associated with prematurity (p = 0.0003), low birth weight (p = 0.01), prenatal corticosteroid treatment (p = 0.002), umbilical catheterization (p = 0.03), administration of ὅ 2 nephrotoxic drugs (p = 0.02), caffeine treatment (p = 0.0001), acute kidney injury (p = 0.02), and intracranial hyper tension (p = 0.04). Only one patient required antihypertensive pharmacologic treatment and in all cases, hypertension was resolved during follow-up. CONCLUSION: Prevalence of neonatal hypertension in our NICU was 4.7% and in all cases occurred in preterm newborns with previously recognized factors associated with this condition.

Blood urea nitrogen to serum creatinine ratio as a prognostic factor in diarrhea-associated hemolytic uremic syndrome: a validation study.

Identifying those children with complicated forms of diarrhea-associated hemolytic uremic syndrome (D+HUS) on admission can optimize their management. Recently, the blood urea nitrogen to serum creatinine ratio (BCR) at admission has been proposed as a novel and accurate predictor of complicated clinical outcome in D+HUS; therefore, we performed this retrospective study aimed to validate such observation in a larger series of patients. A complicated course was defined as developing one or more of the following: severe neurological or bowel injury, pancreatitis, cardiac or pulmonary involvement, hemodynamic instability, hemorrhage, and death. Data from 161 children were reviewed, 50 of them with a complicated disease including five deaths. Those with worse evolution presented a lower admission BCR than those with good outcome (22.5 vs. 30.8; p = 0.005). BCR at admission showed a limited ability to identify children at risk of a complicated course, with an AUC of 0.63 (95% CI 0.58-0.71) and an optimal cutoff point of ≤ 26.7, which achieves a sensitivity of 70% (95% CI 55.2-81.7) and a specificity of 56.7% (95% CI 47-66). CONCLUSION: In this validation study, the BCR at admission provided a limited value to predict severe forms of D+HUS. What is Known: • BCR at admission has been proposed as an accurate predictor of complicated clinical course in children with D+HUS. What is New: • In a larger series of children with D+HUS, we were unable to confirm the usefulness of the admission BCR to early identify those at risk of complicated forms of the disease. • Further research is warranted to improve the optimal detection of these high-risk patients.

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

BACKGROUND: Although 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. METHODS: Data 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). RESULTS: Both 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). CONCLUSION: Treatment with EPO did not reduce the number of RBC transfusions in D + HUS children. Assessment of EPO efficacy in D + HUS merits further studies.

Ibuprofen-associated acute kidney injury in dehydrated children with acute gastroenteritis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) induce acute kidney injury (AKI) in volume-depleted patients; however the prevalence of this complication is likely underestimated. We assessed the impact of ibuprofen exposure on renal function among dehydrated children with acute gastroenteritis (AGE) to further characterize NSAID-associated AKI. METHODS: Over a 1-year period dehydrated children with AGE (n = 105) were prospectively enrolled and grouped as cases, presenting with AKI (n = 46) or controls, not presenting with AKI (n = 59). AKI was defined by pediatric RIFLE (pRIFLE) criteria. RESULTS: Among the children enrolled in the study, AKI prevalence was 44 %, and 34 (54 %) of the 63 patients who received ibuprofen developed renal impairment. Relative to the controls, children presenting with AKI were younger (median age 0.66 vs. 1.74 years; p < 0.001) and received ibuprofen more frequently (74 vs. 49 %, p = 0.01). After adjusting for the degree of dehydration, ibuprofen exposure remained an independent risk factor for AKI (p < 0.001, odds ratio 2.47, 95 % confidence interval 1.78-3.42). According to the pRIFLE criteria, 17 patients were at the 'risk' stage of AKI severity, 24 were at the 'injury' stage, and five were at the 'failure' stage; none required dialysis. Distribution of patients within categories was similar regardless of ibuprofen exposure. All cases fulled recovered from AKI. CONCLUSIONS: Ibuprofen-associated AKI was 54 % in our cohort of dehydrated children with AGE. Drug exposure increased the risk for developing AKI by more than twofold, independent of the magnitude of the dehydration.

Laboratory predictors of acute dialysis in hemolytic uremic syndrome.

BACKGROUND: 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. METHODS: Out of 153 D + HUS children reviewed, 88 received dialysis and 65 did not. Initial laboratory parameters and diuresis between both groups were analyzed. RESULTS: Dialyzed patients had higher creatinine, urea, alanine aminotransferase, hematocrit and leukocyte count; and lower sodium, bicarbonate, and pH compared to non-dialyzed ones. Serum creatinine was the only independent predictor (P = 0.003) of dialysis; therefore, its ability to predict dialysis was estimated on receiver operating characteristic (ROC) curve analysis and using the Acute Kidney Injury Network (AKIN) staging system. Area under the ROC curve was 0.92 (95% confidence interval [95%CI]: 0.83-1) with a creatinine cut-off of 1.25 mg/dL (sensitivity, 100%; specificity, 76.5%) for children <1 year, and 0.93 (95%CI: 0.88-0.98) with a threshold of 2 mg/dL (sensitivity, 91%; specificity, 87.5%) for older children. AKIN stage 3 at admission predicted dialysis with a sensitivity of 92% and specificity of 84.2%. Urine output had the highest accuracy for dialysis prediction (sensitivity, 100%; specificity, 95.3%). CONCLUSIONS: Initial serum creatinine concentration was the best laboratory predictor of dialysis, but the first 24 h diuresis was even better for this purpose. But, given that serum creatinine is an immediate available parameter, the cut-offs identified may label D + HUS children who will probably need dialysis, prompting early referral to centers able to provide dialysis.

Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression.

Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

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

BACKGROUND: Platelet 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. METHODS: This 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. RESULTS: Both 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. CONCLUSION: Our 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.

Dehydration at admission increased the need for dialysis in hemolytic uremic syndrome children.

BACKGROUND: Oligoanuric forms of postdiarrheal hemolytic uremic syndrome (D+ HUS) usually have more severe acute stage and higher risk of chronic sequelae than nonoligoanuric forms. During the diarrheal phase, gastrointestinal losses could lead to dehydration with pre-renal injury enhancing the risk of oligoanuric D+ HUS. Furthermore, it had been shown that intravenous volume expansion during the prodromal phase could decrease the frequency of oligoanuric renal failure. Thus, we performed this retrospective study to determine whether dehydration on admission is associated with increased need for dialysis in D+ HUS patients. CASE-DIAGNOSIS/TREATMENT: Data from 137 children was reviewed, which were divided into two groups according to their hydration status at admission: normohydrated (n = 86) and dehydrated (n = 51). Laboratory parameters of the dehydrated patients reflected expected deteriorations (higher urea, higher hematocrit and lower sodium, bicarbonate, and pH) than normohydrated ones. Likewise, the dehydrated group had a higher rate of vomiting and need for dialysis (70.6 versus 40.7 %, p = 0.0007). CONCLUSIONS: Our data suggests that dehydration at hospital admission might represent a concomitant factor aggravating the intrinsic renal disease in D+ HUS patients increasing the need for dialysis. Therefore, the early recognition of patients at risk of D+ HUS is encouraged to guarantee a well-hydrated status.

Transient early-childhood hyperkalaemia without salt wasting, pathophysiological approach of three cases.

Two types of early childhood hyperkalemia had been recognized, according to the presence or absence of urinary salt wasting. This condition was attributed to a maturation disorder of aldosterone receptors and is characterized by sustained hyperkalemia, hyperchloremic metabolic acidosis (MA) due to reduced ammonium urinary excretion and bicarbonate loss, and normal creatinine with growth delay. We present 3 patients of the type without salt wasting, which we will call transient early-childhood hyperkalemia (TECHH) without salt wasting, and discuss its physiopathology according to new insights into sodium and potassium handling by the aldosterone in distal nephron. In 3 children from 30 to 120-day-old admitted with bronchiolitis and growth delay hyperkalemia was found in routine laboratory. Further studies revealed a normal creatinine with inappropriately normal or low fractional excretion (FE) of potassium, accompanied by inadequately normal serum aldosterone and plasma renin activity for their higher plasma potassium levels, but without urine salt wasting. They also presented hyperchloremic MA with FE of bicarbonate 0.58%-2.2%, positive urinary anion gap during MA and normal ability to acidify the urine. Based on these findings a diagnosis of TECHH without salt wasting was made and they were treated sodium bicarbonate and hydrochlorothiazide with favorable response. The condition was transient in all cases leading to treatment discontinuation. Given that TECCH without salt wasting is a tubular disorder of transient nature with mild symptoms; it must be keep in mind in the differential diagnosis of hyperkalemia in young children.

Uncommon Presentation of Atypical Hemolytic Uremic Syndrome: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal damage. Its presentation as nephrotic syndrome (NS) during first year of life is uncommon; we describe a child with clinical and laboratory findings of NS whose renal biopsy revealed thrombotic microangiopathy (TMA). A previously healthy 4-month-old male was admitted with severe dehydration, diarrhea and anuria. Laboratory results showed electrolyte disturbances, increased serum creatinine, anemia without schistocytes, thrombocytosis, normal lactic dehydrogenase (LDH) levels, hypoalbuminemia hypercholesterolemia and decreased C3 levels. After rehydration hematuria and massive proteinuria were also documented and an initial diagnosis of NS of the first year was established. Studies seeking for infectious agents were negative. During hospitalization he continued to be oligo-anuric needing dialysis and a renal biopsy was performed, which showed TMA findings. We here considered the diagnosis of aHUS and started plasma infusions as a bridge until starting eculizumab. After two infusions urine output improved leading to discontinuation dialysis. The diagnoses of STEC infection and thrombocytopenic thrombotic purpura were ruled out. Factor B, H, I and properdin levels were normal. Antibodies against CFH negative were negative. Screening for genes causative of aHUS detected a heterozygous variant in CFHR3 of uncertain significance. On day 20, treatment was switched to eculizumab, which induced a progressive remission of the NS. This case outlines the need for a heightened diagnosis suspicion of this already rare disease since early initiation of eculizumab therapy improves its prognosis.

Transient early-childhood hyperkalemia without salt wasting, physiopathological approach of three cases. / Hiperpotasemia transitoria del lactante sin pérdida salina, enfoque fisiopatológico de tres casos.

Two types of early-childhood hyperkalemia had been recognized, according to the presence or absence of urinary salt wasting. This condition was attributed to a maturation disorder of aldosterone receptors and is characterized by sustained hyperkalemia, hyperchloremic metabolic acidosis due to reduced ammonium urinary excretion and bicarbonate loss, and normal creatinine with growth delay. We present three patients of the type without salt wasting, which we will call transient early-childhood hyperkalemia without salt wasting, and discuss its physiopathology according to new insights into sodium and potassium handling by the aldosterone in distal nephron. In three children from 30 to 120-day-old admitted with bronchiolitis and growth delay hyperkalemia was found in routine laboratory. Further studies revealed a normal creatinine with inappropriately normal or low fractional excretion of potassium, accompanied by inadequately normal serum aldosterone and plasma renin activity for their higher plasma potassium levels, but without urine salt wasting. They also presented hyperchloremic metabolic acidosis with fractional excretion of bicarbonate 0.58-2.2%, positive urinary anion gap during metabolic acidosis and normal ability to acidify the urine. Based on these findings a diagnosis of transient early-childhood hyperkalemia without salt wasting was made and they were treated sodium bicarbonate and hydrochlorothiazide with favorable response. The condition was transient in all cases leading to treatment discontinuation. Given that transient early-childhood hyperkalemia without salt wasting is a tubular disorder of transient nature with mild symptoms; it must be keep in mind in the differential diagnosis of hyperkalemia in young children.

Hemolytic uremic syndrome due to Shiga toxin­producing Escherichia coli and hypocomplementemia with favorable response to eculizumab: a case report / [Síndrome urémico hemolítico por Escherichia Coli e hipocomplementemia con respuesta favorable a eculizumab: comunicación de un caso]

Introduction: Neurologic involvement in hemolytic uremic syndrome related to Shiga toxin­producing Escherichia coli (STEC-HUS) is the main cause of death. In last years has been demonstrated that activation of complement alternative pathway also contributes to organ damage. This finding led to the recognition of decreased C3 levels at admission as a marker of poor prognosis as well as the evaluation of the use of eculizumab in cases with neurologic compromise. Objective: to report a patient with STEC-HUS and hypocomplementemia with neurological involvement treated with eculizumab. Clinical case: A 17-month-old male was admitted due to seizures and anuria for last 24 h with a history of 48 h of bloody diarrhea. He presented a laboratory profile compatible with STEC-HUS and severe hyponatremia, results of brain tomography were normal. Also there was complement activation: C3 73 mg/dl (normal > 90 mg/dL) and C5b-9 778.9 ng/ml (normal 135.8-385.3 ng/ml). Initial treatment includes normal saline solution and anticonvulsants drugs, sodium correction and peritoneal dialysis. On third day of hospitalization, because of progression of the neurologic involvement a dose of eculizumab (300 mg) was given, showing at 24 h a markedly neurologic improvement along with and increasing platelet count and a descending lactic dehydrogenase levels. He was discharged after 14 days in a good condition. Later a STEC O157:H7 infection was confirmed and he also normalized the C3 level. Conclusion: This case shows that decreased C3 level at admission was associated to neurologic involvement and suggests that eculizumab might be a favorable therapeutic option.

Introducción: En compromiso neurológico en el síndrome urémico hemolítico producido por Eschericha coli productor de Shiga toxina (STEC-SUH) es la primera causa de mortalidad. En los últimos años se ha demostrado que también contribuye al daño de órgano la activación de la vía alterna del complemento. Este hallazgo dio lugar al reconocimiento del descenso de C3 como marcador de mal pronóstico así como a la evaluación del uso de eculizumab ante compromiso neurológico severo. Objetivo: Comunicar un paciente con STEC-SUH e hipocomplementemia con compromiso neurológico tratado con eculizumab. Caso clínico: Varón de 17 meses que ingresa por síndrome convulsivo y 24 horas de anuria con antecedente de diarrea con sangre de 48 horas de evolución. Presentaba al ingreso laboratorio compatible con STEC-HUS e hiponatremia severa, con tomografía de cerebro normal. Además presentaba activación del complemento: C3 73 mg/dl (normal > 90 mg/dL) y C5b-9 778,9 ng/ml (normal 135,8-385,3 ng/ml). Se administró solución fisiológica y anticonvulsivantes, se corrigió la natremia y comenzó diálisis peritoneal. Al tercer día, por progresión del compromiso neurológico, se administró eculizumab (300 mg) experimentando una notable recuperación neurológica a las 24 horas junto a aumento de plaquetas y descenso de láctico deshidrogenasa. El paciente fue dado de alta luego de 14 días en buen estado general. Posteriormente se confirmó aislamiento de STEC O157:H7 y normalización de C3. Conclusión: este caso demuestra que el descenso de C3 al ingreso se asoció con daño neurológico y sugiere que la administración de eculizumab podría ser una alternativa terapéutica favorable.