Saoussen Krid

Pharmacokinetics of Enoxaparin After Renal Transplantation in Pediatric Patients

Enoxaparin is commonly used in the prevention of renal allograft vascular thrombosis but off‐label in children, and no consensus exists regarding the optimal dosing and dose adjustment. In this retrospective study, 444 anti‐Xa levels were obtained from 30 pediatric renal transplant recipients in order to investigate enoxaparin population pharmacokinetics. The main results were (1) 25% of children achieved the target anti‐Xa activity 36 hours after initiation of treatment, (2) anti‐Xa time courses were best described by a 1‐compartment open model with first‐order absorption, (3) body weight but not renal function was the sole covariate influencing clearance and volume of distribution, and (4) large between‐subject and between‐occasion variabilities in anti‐Xa activity were observed. However, creatinine‐based estimated glomerular filtration rate in the first post–renal transplantation hours may not reliably reflect the actual renal function of the children. Based on the final population model, a Bayesian‐based program was developed in order to estimate the individual pharmacokinetic parameters on a single anti‐Xa measurement, allowing determination of the next enoxaparin dose that will quickly achieve an appropriate anti‐Xa activity (targeting 0.3‐0.5 IU/mL) and anticoagulation. Finally, these results should help standardize practices that remain to date largely heterogeneous in pediatric intensive care units.

Pulmonary hypertension in an adolescent with end-stage-renal disease—a diagnostic challenge: Questions

Our patient was diagnosed at 13 months old for congenital nephrotic syndrome with diffuse mesangial sclerosis on the kidney biopsy secondary to PLCE1mutation. He quickly progressed to ESRD and underwent bilateral nephrectomy because of severe hypertension. Following an initial period of hemodialysis on a jugular catheter, he underwent a first renal transplantation in 2001. Four years later, he had acute renal failure, nephrotic syndrome,andclinicaland laboratoryfeaturesofsystemic thrombotic microangiopathy. He progressed rapidly to ESRD and initiated dialysis. Multiple hemodialysis catheter changes severely impaired jugular and sub clavicular venous accesses precluding arteriovenous (A-V) fistula creation on the upper limbs. Thus, a femoralarteriovenous(A-V)fistulawascreatedin2005.Asecond renal transplantationwasperformed in2007.Fifteenmonths later, he had acute antibody-mediated rejection with deterioration of graft function. During follow-up, hedidnot have systemichypertension.An echocardiography performed in 2008 only showed a dilated left ventricle (LV) and normal systolic pulmonary pressure. In August 2012, at 16years of age, hewas admitted to the intensive careunit for rapidlyprogressingdyspnea.B-typenatriureticpeptide was increased at 1462 ng/mL. Chest X-ray and a chest CT scan showed pulmonary edema. The echocardiography showed a dilated LV (LVEDD 56 mm, z score + 2.76) with normal systolic function and an ejection fraction of 65%. The maximum tricuspid regurgitation velocity showed an elevated systolic pulmonary pressure of 60mmHg and signs of increased right atrial pressure above 10mmHg. He improved with diuretics. The patient’s nephrologist asked the cardiologist to perform heart catheterization. Right heart catheterization confirmed PH with a mean pulmonary artery pressure of 50 mmHg and a pulmonary wedge pressure of 21 mmHg, while systemic pressure was 149/80 (mean 108) mmHg. Oxygen saturation in the inferior vena cava was 96% and cardiac index was at 10 L/min/m. Pulmonary vascular resistance (PVRi) was 2.8 WoodU*m. Acute vasoreactivity testing was performed by oxygen and NO inhalation and showed a drop in PVRi to 1.6 WoodU/m.

Syndrome de Goodpasture et maladie des anticorps anti-membrane basale chez l’enfant : revue de la littérature

Antiglomerular basement membrane glomerulonephritis is a rare autoimmune disease characterized by rapidly progressive glomerulonephritis that may be associated with pulmonary hemorrhage (Goodpasture syndrome). The disease is caused by autoantibodies (classically IgGs) directed against the α3 subunit of type IV collagen. This is a rare disease in the adult population and extremely rare in children, with a reported cumulative annual incidence at 1/106 people/year. Among scarce reported pediatric cases (n=31), most are girls (M/F sex ratio, 1:4), and the mean age at diagnoses is 9.2±4.6 years. A medical diagnosis is an emergency and is based on the identification of specific antibodies in the serum, and pathognomonic linear fixation of IgGs along the glomerular basement membrane. Without appropriate treatment, the disease is generally fulminant, and patient and kidney survival is poor. Indeed, glomerular function strongly correlates with histological lesions. The current guidelines recommend the use of plasma exchanges and immunosuppressive drugs. For the past few years, alternative therapeutics such as specific anti-B-cell antibodies (rituximab) or specific extrarenal cleansing such as immunoadsorption have been successfully used in adults. Immunoadsorptions (IAs) can remove pathogenic IgGs from the circulation and do not require plasma infusions, contrary to plasma exchanges. In this review, we discuss the key points of antiglomerular basement membrane glomerulonephritis diagnosis and conventional or alternative therapeutics.