Aicha Merouani

Plasma homocysteine concentration in children with chronic renal failure

Abstract. Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 µmol/l vs 6.8 µmol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 µmol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 µmol/l) than nondialyzed patients with the mutation (10.7 µmol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l.Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients.

Hyperlipidemic profiles during remission in childhood idiopathic nephrotic syndrome

Hyperlipidemia, an important characteristic of idiopathic nephrotic syndrome in children (NS), is usually observed during the active phase of the disease and disappears with the resolution of the proteinuria. However, persisting lipid anomalies during remission have been reported in a few studies and raise the question of the later development of atherosclerosis. Plasma lipid profiles in 25 children with NS at remission, with or without active prednisone treatment, were compared with those of an age-matched population. The results indicate that plasma total and LDL-cholesterol levels were above the 95(th) percentile for age and sex in 12 of the 25 patients (48%) with 7 of them having apolipoprotein B and triglyceride concentrations above the 95(th) percentile. Moreover, frequently relapsing children were more likely to have abnormal lipid profile during the remission. We conclude that close monitoring of lipid levels during the remission of the NS especially in those with frequent relapses, is necessary to select the high-risk patients.

Fluid balance of pediatric hematopoietic stem cell transplant recipients and intensive care unit admission

Fluid administration is essential in patients undergoing hematopoietic stem cell transplant (HSCT). Admission to pediatric intensive care unit (PICU) is required for 11–29% of pediatric HSCT recipients and is associated with high mortality. The objective of this study was to determine if a positive fluid balance acquired during the HSCT procedure is a risk factor for PICU admission. The medical records of 87 consecutive children who underwent a first HSCT were reviewed retrospectively for the following periods: from admission for HSCT to PICU admission for the first group (PICU group), and from admission for HSCT to hospital discharge for the second group (non-PICU group). Fluid balance was determined on the basis of weight gain (WG) and fluid overload (FO). PICU group consisted of 19 patients (21.8%). Among these, 13 (68.4%) developed ≥10% WG prior to PICU admission compared with 15 (22.1%) in the non-PICU group (p < 0.001). Thirteen patients (68.4%) developed ≥10% FO prior to PICU admission compared with 31 (45.6%) in the non-PICU group (p = 0.075). Following multivariate analysis, ≥10% WG (p = 0.018) and cardiac dysfunction on admission for HSCT (p = 0.036) remained independent risk factors for PICU admission. Smaller children (p = 0.033) and patients with a twofold increase in serum creatinine (p = 0.026) were at risk of developing ≥10% WG. This study shows that WG is a risk factor for PICU admission in pediatric HSCT recipients. Further research is needed to better understand the pathophysiology of WG in these patients and to determine the impact of WG prevention on PICU admission.

Impact of blood volume monitoring on fluid removal during intermittent hemodialysis of critically ill children with acute kidney injury

BACKGROUND In chronic pediatric patients treated with intermittent hemodialysis (IHD), blood volume monitoring (BVM) is commonly used to assess and manage volume status during the dialysis session. Minimal data exists on its use during IHD in critically ill children with acute kidney injury (AKI). In these cases, fluid removal may be limited by hemodynamic instability. METHODS We present a retrospective study conducted in our pediatric intensive care unit. For eligible patients, demographic data and IHD treatment characteristics were recorded including BVM use, ultrafiltration (UF) volume per session, hypotensive episodes and intradialysis interventions. Hypotensive episodes and UF per IHD session were compared between IHD sessions with BVM (BVM group) and IHD sessions without BVM (control group). RESULTS Twenty-three AKI patients with a median age of 11 years (1.8-18) and body weight of 36 kg (10-85) received 134 IHD sessions (70 with BVM and 64 without BVM). Hypotensive episodes occurred in 34% of all sessions with no significant difference between the BVM group and the control group: (95% CI: 22%, 44%) and 36% (95% CI: 24%, 48%), respectively, but UF per session was higher in the BVM group as compared to control (48 ± 27 mL/kg and 33 ± 26 mL/kg, respectively, P = 0.0001). The mean decrease in BVM did not exceed 13% over an entire dialysis session in patients without hypotension. CONCLUSION In conclusion, in our experience of IHD sessions in critically ill children with AKI, the use of BVM allowed a higher UF in those with BVM without influencing the frequency of hypotensive episodes. Applying specific guidelines on BVM use may decrease hypotensive episodes during IHD treatment in critically ill patients.

The Québec NTBC Study

In this chapter we describe the current Quebec NTBC Study protocol. Quebecs unique characteristics have influenced the development of the protocol, including a high prevalence of hepatorenal tyrosinemia (HT1), universal newborn screening for HT1, availability of treatment with nitisinone (NTBC) and special diet, a large territory, where HT1 treatment is coordinated by a small number of centers. Screened newborns are seen within 3 weeks of birth. Patients with liver dysfunction (prolonged prothrombin time and/or international normalized ratio (INR) provide sensitive, rapidly available indicators) are treated by NTBC and special diet. The specific diagnosis is confirmed by diagnostic testing for succinylacetone (SA) in plasma and urine samples obtained before treatment. After an initial period of frequent surveillance, stable patients are followed every 3 months by assay of plasma amino acids and NTBC and plasma and urine SA. Abdominal ultrasound is done every 6 months. Patients have an annual visit to the coordinating center that includes multidisciplinary evaluations in metabolic genetics, hepatology, imaging (for abdominal ultrasound and magnetic resonance imaging) and other specialties as necessary. If hepatocellular carcinoma is suspected by imaging and/or because of progressive elevation of alphafetoprotein, liver transplantation is discussed. To date, no patient in whom treatment was started before 1 month of age has developed hepatocellular carcinoma, after surveillance for up to 20 years in some. This patient group is the largest in the world that has been treated rapidly following newborn screening. The protocol continues to evolve to adapt to the challenges of long term surveillance.

Severe Acute Kidney Injury and Multiple Organ Failure in a 17-Day-Old Newborn: When Pathology Makes the Difference

Rationale: Acute tubulointerstitial nephritis (ATIN) in children is most commonly due to allergic drug reactions. In neonates, diagnosis of ATIN is clinically suspected and a kidney biopsy is not routinely performed. Presenting concern: A 17-day-old newborn presented with vomiting and dehydration, along with anuric acute kidney injury, severe electrolyte disturbances, hypocomplementemia, and thrombocytopenia. Abdominal ultrasound revealed bilateral nephromegaly and hepatosplenomegaly. The patient was promptly started on intravenous (IV) fluid and broad-spectrum antibiotics. His electrolyte disturbances were corrected as per standard guidelines. The rapid progressive clinical deterioration despite maximal treatment and the unclear etiology influenced the decision to proceed to a kidney biopsy. Histopathological findings revealed diffuse interstitial edema with a massive polymorphic cellular infiltrate and destruction of tubular structures, consistent with severe ATIN. Elements of thrombotic microangiopathy (TMA) were observed. Diagnosis: The clinical presentation combined with imaging and histopathological findings was suggestive of ATIN caused by a severe acute bacterial pyelonephritis. Intervention: Methylprednisolone pulses followed by oral prednisolone were administered. Antibiotics were continued for 10 days. The patient was kept on invasive mechanical ventilation and on peritoneal dialysis for 12 days. Outcome: His condition stabilized following steroid pulses. His renal function progressively improved, and renal replacement therapy was weaned off. His renal ultrasound normalized. He has maintained a normal blood pressure, urinalysis, and renal function over the past 5 years. Novel finding: This case reports a severe presentation of acute bacterial pyelonephritis in a neonate. It highlighted the involvement of complement activation in severe infectious process. Histopathological findings of ATIN and TMA played a crucial role in understanding the physiopathology and severity of the disease.