School level of children carrying a HNF1B variant or a deletion.

The prevalence of neurological involvement in patients with a deletion of or a variant in the HNF1B gene remains discussed. The aim of this study was to investigate the neuropsychological outcomes in a large cohort of children carrying either a HNF1B whole-gene deletion or a disease-associated variant, revealed by the presence of kidney anomalies. The neuropsychological development-based on school level-of 223 children included in this prospective cohort was studied. Data from 180 children were available for analysis. Patients mean age was 9.6 years, with 39.9% of girls. Among these patients, 119 carried a HNF1B deletion and 61 a disease-associated variant. In the school-aged population, 12.7 and 3.6% of patients carrying a HNF1B deletion and a disease-associated variant had special educational needs, respectively. Therefore, the presence of a HNF1B deletion increases the risk to present with a neuropsychiatric involvement when compared with the general population. On the other hand, almost 90% of patients carrying a HNF1B disease-associated variant or deletion have a normal schooling in a general educational environment. Even if these findings do not predict the risk of neuropsychiatric disease at adulthood, most patients diagnosed secondary to kidney anomalies do not show a neurological outcome severe enough to impede standard schooling at elementary school. These results should be taken into account in prenatal counseling.

Prediction of high-degree steroid dependency in pediatric idiopathic nephrotic syndrome.

Most patients with idiopathic nephrotic syndrome are steroid-responsive, but about 50% relapse and often become steroid-dependent and exposed to long-term steroid complications. The aim of this study was to determine predictive risk factors for steroid and/or cyclosporine A (CyA) dependence. In France, steroid responsiveness is defined as remission after 1 month of oral prednisone (60 mg/m(2) per day) and-in the case of persistent proteinuria on day 30-three methylprednisolone pulses (MPP; 1 g/1.73 m(2) on days 1, 3, and 5). Thirty-five steroid-responsive children, followed between 1999 and 2006, were included in this study. Median age at diagnosis was 4.9 years. All patients initially received prednisone 60 mg/m(2) per day. Twenty-four of the 35 patients were steroid-dependent, with 12 requiring MPP. Of the latter 12 patients, 83.3% were treated with CyA during follow-up; in comparison, only 16.7% of the patients who did not receive MPP required CyA during follow-up (chi-square test, P = 0.001). T risk for steroid dependence was 100% in our cohort if remission was achieved after day 20. Patients who need MPP are at high risk to require CyA to achieve disease control. By identifying these children, we could use adequate immunosuppressive drugs earlier and reduce morbidity related to steroids and multiple relapses.

Acute pancreatitis in paediatric systemic lupus erythematosus.

Acute pancreatitis (AP) rarely complicates the clinical course of systemic lupus erythematosus (SLE). AP as the initial manifestation of SLE is exceptional, but its outcome is often fatal. Corticosteroids have been suspected to play a role in the development of AP, but the therapeutic benefit seems to be far above the risk of exacerbation of pancreatic lesions. We report a 13-y-old girl presenting with arthralgia and malaise, followed by abdominal pain, generalized oedema and haemodynamic instability. Increased CRP (325 ng/ml), serum amylase (14,000 IU/l) and lipase (2500 IU/l) levels suggested AP. Acute anuric renal failure required haemodialysis. Multiorgan involvement suggested SLE, which was confirmed 3 d later by increased anti-ds-DNA levels. Three methylprednisolone pulses were administered promptly, followed by oral prednisone (1.5 mg/kg/d) and six pulses of cyclophosphamide (500 mg/1.73 m2/2 wk). Mycophenolate mofetil was introduced for long-term disease control. Amylase and lipase levels decreased over 4 wk. Renal function was normal after 3 wk and proteinuria negative after 6 wk. This case suggests that steroid pulse therapy should be promptly administered if clinical and biochemical investigations suggest SLE to be responsible for AP. Aggressive treatment may be life saving.

Successful renal retransplantation after post-transplant lymphoproliferative disease.

Post-transplant lymphoproliferative disease (PTLD) is a rare but severe complication of renal transplantation. Reduction of immunosuppression is essential for controlling PTLD but may induce graft loss. Retransplantation after PTLD is considered dangerous, because immunosuppressive treatment resumption may trigger hematological relapse. We retrospectively report six patients (five adults, one child) who underwent a second renal transplantation after successfully treated PTLD. Epstein-Barr virus (EBV) serology was positive before the first transplantation in all patients except the child. Post-transplant lymphoproliferative disease was detected 6.6 months (range 4.5-9.4) after transplantation. Lymphoproliferation was always monomorphic, B-cell, and EBV-related. Post-transplant lymphoproliferative disease was confined to the renal allograft (n = 4), multilocular (n = 1) or cerebral (n = 1). Immunosuppression tapering (6/6) and transplantectomy (5/6) led to hematological remission in all patients. Retransplantation was performed 77 months (range 50-128) after PTLD diagnosis. Immunosuppression included steroids (n = 6), ATG (n = 2), anti-CD25 (n = 2), cyclosporine (n = 4), tacrolimus (n = 2), mycophenolate mofetil (n = 4) and azathioprine (n = 1). After a median follow up of 30 months (range 24-47) patient survival was 100%, with no recurrence of PTLD. In conclusion, renal retransplantation can be considered in patients with monomorphic PTLD history, without major risk of hematological recurrence.

Mesenteric thrombosis causing short bowel syndrome in nephrotic syndrome.

Nephrotic patients are at risk of developing venous and arterial thrombotic complications. Pulmonary embolism due to affected deep leg veins is by far the most common event. Renal or cerebral vein thromboses have been described. Thrombosis of arterial vessels is less frequent. Mesenteric infarction is a rare but severe complication in patients with nephrotic syndrome (NS). We report a 7-year-old boy with a steroid-dependent (SD) NS and a homozygous mutation of methylenetetrahydrofolate reductase, increasing the risk of thromboembolic events. He developed a thrombosis of his superior mesenteric artery during his ninth relapse, which was responsible for a necrosis of 240 cm of his small bowel, necessitating resection of necrotic parts and double external ostomy diversion. Remission was achieved with pulse prednisolone therapy. Corticoids were reduced over 4 months progressively. Oral cyclosporin A (CyA) was initiated for long-term treatment. Due to a short bowel syndrome with severe malabsorption, even oral administration of 22.5 mg/kg per day CyA did not lead to sufficient plasma levels. Intravenous cyclophosphamide pulse therapy over 6 months led to a complete remission. No relapse occurred over a period of more than 5 months after the last cyclophosphamide pulse. Anticoagulation and screening for increased susceptibility for thrombotic events are necessary in every nephrotic patient. Intravenous cyclophosphamide pulse therapy is a useful alternative in SDNS with impaired intestinal absorption of applied immunosuppressive drugs.