Combined renin angiotensin blockade in childhood steroid‐resistant nephrotic syndrome

Background: Reduced proteinuria results in delayed deterioration of renal function and remission of proteinuria predicts a good long‐term prognosis in steroid‐resistant nephrotic syndrome (SRNS). The aim of this study was to analyze the effects of the combined angiotensin‐converting enzyme inhibitor and angiotensin II receptor blocker in reducing proteinuria in SRNS. Methods: A prospective study of eight patients with SRNS was conducted at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University from September 2003 to December 2007. Enalapril was given at 0.1 mg/kg/day and was increased by 0.1 mg/kg/day every 4 weeks up to 0.6 mg/kg/day (maximum 40 mg/day) and 1 mg/kg/day of losartan was added for 4 weeks and stepped up to 2 mg/kg/day (maximum 100 mg/day) for another 4 weeks. Results: There were five boys (62.5%) and three girls (37.5%). The mean age at diagnosis was 8.3 ± 4.1 years (range 2.05–13 years) and age at enrollment was 11.7 ± 3.8 years (range 6–16 years). Renal histology revealed seven focal segmental glomerulosclerosis and one immunoglobulin M nephropathy. The results showed significant reduction on mean spot urine protein : creatinine ratio from 9.6 ± 2.3 to 3.6 ± 1.6 (P < 0.05) and 24‐h urine protein from 182.8 ± 59.6 to 28.7 ± 8.2 mg/m²/h (P < 0.05). Urine protein reduction ratio at the end of the study was 50% (P= 0.08). Serum cholesterol, albumin, potassium, blood pressure and renal function had no significant change. No clinical and laboratory side‐effects were reported. Conclusion: Combined high‐dose angiotensin II receptor blocker to high‐dose angiotensin‐converting enzyme inhibitor therapy is safe and effective in reducing proteinuria in childhood SRNS. However a large‐scale study should be conducted to validate this result.     

Ofatumumab in post‐transplantation recurrence of a pediatric steroid‐resistant idiopathic nephrotic syndrome

Treatment of SRNS is a challenge. Antiproliferative agents and depleting antibodies have been reported to be effective. However, these agents are not always successful, and use of ofatumumab could provide a different treatment option. Our patient was diagnosed with a SRNS at 5 years of age. She developed ESRD, with FSGS. This was cause for a first renal transplantation. The NS relapsed, leading to loss of the graft, and a second renal transplantation was performed. Due to the recurrence of the NS, IAds were initiated and led to a complete remission. Our patient remained dependent on IAds, however, despite treatments with calcineurin inhibitors, corticosteroids, rituximab, and abatacept. Ofatumumab was introduced and led to a remission, thus allowing cessation of the IAd treatment. Another infusion of ofatumumab was administered 8 months after the last one, due to the recurrence of the NS and a renewed increase in B cells. Although it did not result in a complete remission, the proteinuria was stabilized in the absence of IAds. Ofatumumab may be an alternative treatment for post‐transplantation rituximab‐resistant SRNS, although this needs to be confirmed by further studies.     

Elevated serum interleukin‐7 level in idiopathic steroid‐sensitive nephrotic syndrome

Background: Several cytokines have a pathological association with idiopathic steroid‐sensitive nephrotic syndrome (ISSNS) in inducing proteinuria or regulating T cells. Because interleukin (IL)‐7 plays important roles in regulating T‐cell proliferation and sustaining naïve or memory T cells, IL‐7 is one of the candidate cytokines in the pathogenesis of ISSNS. Very little is known, however, about the association of IL‐7 with ISSNS. To clarify the IL‐7 dynamics in children with ISSNS, serum IL‐7 level was investigated, from the nephrotic phase before steroid treatment (STx; group A1) to the remission phase with STx (group A2) and without STx (group A3). Methods: Eighteen children with ISSNS were included in the present study. A total of 25 paired samples were analyzed for groups A1 and A2, and a total of 10 paired samples for groups A1, A2, and A3 due to recurrence. Two control groups (with normal urinalysis, group B; or with nephrotic syndrome other than ISSNS, group C), matched for age and gender, were also included. Serum cytokine level was measured on bead‐based assay. Results: Each serum IL‐7 level in groups A1 and A3 was higher than each serum IL‐7 level of groups C and B, respectively. The group A2 serum IL‐7 level was higher than that of group A1. There was no statistical significance of serum IL‐7 level between group A1 and group A3. Conclusion: Serum IL‐7 level was elevated in children with ISSNS regardless of the status of the disease. This brings us one step closer to a better understanding of the pathophysiology of ISSNS in children.     

Congenital nephrotic syndrome with clinical hypothyroidism

A 15 month old boy with typical features of congenital nephrotic syndrome (CNS) is reported, who in addition to the renal pathology had an associated clinical hypothyroidism with low levels of total and free thyroxine and triiodothyronine and an elevated serum TSH. Improvement in the physical parameters and mental status from thyroid hormone replacement therapy is documented.     

Biochemical hypothyroidism in Nigerian children with nephrotic syndrome

The nephrotic syndrome in Nigerian children is known to be largely associated with the endemicity of quartan malaria. Routine thyroid function studies were carried out on 24 children with clinical and biochemical evidence of the nephrotic syndrome. The children, aged four to 14 years, were all in the active phase of their disease, presenting with facial and pedal oedema and ascites. There was severe hypoalbuninaemia [mean (S.E.); 19.2 (1.1) g/l], hypercholesterolaemia; 10.5 (1.0) mmol/l and severe albuminuria ranging from 1 to 10 g/l. There was no clinical evidence of thyroid disease. The results of thyroid function tests in these children were compared with those of 181 apparently healthy children of the same age range. The mean total serum thyroxine levels (S.E.) were 118.3 (2.6) and 50.0 (6.4) nmol/l in controls and patients, respectively; T3 resin uptake values were 29.8 (0.2)% and 33.1 (1.2)%; the free thyroxine index (FTI) was 34.7 (0.8) and 16.7 (1.9) while thyrotropin (TSH) levels were 4.8 (0.2) and 10.6 (1.0) mU/l (IRP. MRC 68/38), respectively. The findings of low levels of thyroxine and FTI in association with high levels of TSH suggest that a state of primary hypothyroidism exists in these nephrotic children.     

Involvement of CD5+CD19+Cell in steroid‐dependent nephrotic syndrome treated with B‐cell targeting therapy

We showed in this study the longitudinal changes of the B‐cell counts in patients with steroid‐dependent nephrotic syndrome (SDNS) treated with cyclophosphamide (CPM) and mycophenolate mofetil (MMF). In our case with SDNS, this combined therapy not only decreased B‐cell counts but also increased CD5⁺CD19⁺ (CD5⁺B)/ CD5^‐CD19⁺ (CD5‐B) cell ratio. Recurrence was not observed when an elevated CD5⁺B/CD5‐B cell ratio was maintained even after the B cells increased. Therefore, this ratio might be more important than the whole B‐cell counts. The changes of this ratio could be a good predictor of the clinical course of the patients treated with B‐cell targeting therapy.     

Neonatal autoimmune hypothyroidism: a patient report

BACKGROUND: Acquired primary hypothyroidism in neonates and infants under 3 years of age is very rare. Herein we report the case of an infant female affected by acquired autoimmune hypothyroidism. PATIENT REPORT: The infant was transferred to the Pediatric Clinic, University of Catania, Italy for evaluation of dysmorphic features, growth and motor retardation, and hypothyroidism on laboratory testing. Neonatal screening test for TSH and PKU was negative. An ultrasound scan showed a non-homogeneous thyroid gland which was increased in volume. Based on the laboratory results, the diagnosis of autoimmune hypothyroidism was made and L-thyroxine treatment was initiated at 50 microg/day. CONCLUSIONS: Autoimmune hypothyroidism in infancy is rare, but early recognition and therapy are essential to prevent neurologic damage and growth deficits. In this patient we would like to underline the early age of appearance of autoimmune thyroid disease and the possible onset of pathologic events before birth.     

Severe chemosis in a patient with nephrotic syndrome

Chemosis is a rare and reversible complication of nephrotic syndrome in children. However, it is not a threatening condition as there are no complications of its own. We report a 15-year-old girl with steroid-resistant nephrotic syndrome with bilateral chemosis recovering along with the disappearance of the anasarca.     

Fatal rituximab‐associated lung injury syndrome in a patient treated with rituximab for recurrence of post‐transplant nephrotic syndrome

Rituximab (anti‐B CD20 ab.) in recently widely used in renal transplantation. Case history: A 10‐yr‐old patient with end‐stage renal failure due to multidrug‐resistant NS was transplanted with renal graft from deceased donor and presented immediate recurrence of NS. PF was started on day 3 and patient received MP pulses, however with no effect. Rituximab (4 × 375 mg/m²) was administered. Chest radiographs taken at that time were normal. Partial remission was achieved and the patient was discharged in good condition. Sequential recurrence appeared two wk afterward. Twelve sessions of PF were performed and six pulses of MP were given, effecting a partial remission. Three months after the last dose of rituximab, patient was admitted with increasing respiratory failure, requiring mechanical ventilation. Infectious background, including CMV, BKV, mycoplasma, and pneumocystis, was not confirmed. The patient was treated with MP pulses, IVIG, and a variety of antibiotics. Ground‐glass opacity was confirmed on lung CT images. Respiratory failure worsened, despite aggressive ventilation and patient passed away after three wk at ICU. A destruction of alveolar epithelium and extended pulmonary fibrosis was confirmed in the autopsy report. The case represents a fatal RALI.     

Penicillin resistant pneumococcal peritonitis in nephrotic syndrome.

Two infants with nephrotic syndrome who developed penicillin resistant pneumococcal peritonitis while receiving penicillin chemoprophylaxis are reported and the problems associated with prophylaxis against pneumococcal infection discussed. It is suggested that penicillin prophylaxis may be hazardous in an environment in which penicillin resistant pneumococci are prevalent.     

Severe hypoglycemia secondary to methimazole‐induced insulin autoimmune syndrome in a 16 year old African‐American male

Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare disorder characterized by hypoglycemia secondary to insulin autoantibodies (IAb). Over 200 patients have been described from Japan with significantly less numbers being reported from outside the Orient. IAS is more common in patients older than 40 yr of age with reports in the pediatric age group being notably rarer. Exposure to sulfhydryl group containing medications is implicated in the pathogenesis of this syndrome. In this report, we describe a case of IAS in an African‐American adolescent. A 16‐yr‐old healthy African‐American male was diagnosed with Graves' disease and started on Methimazole. Four weeks later, he was found unconscious and hypoglycemic (blood sugar 1.5 mmol/L). Evaluation was negative for insulinoma. Insulin antibodies were positive. Oral glucose tolerance test revealed elevated free insulin concentrations with disproportionately elevated total insulin levels. The patient was started on prednisone, diazoxide, and propranolol for management of IAS and hyperthyroidism. Thyroid radio‐ablation was subsequently undertaken. The doses of prednisone and diazoxide were tapered and these medications discontinued after 9 months. The insulin antibody levels decreased gradually and became undetectable in 6 months with resolution of the hypoglycemia.     

Subsepsis allergica in a patient with type I polyglandular autoimmune syndrome

A 10.6 year old Turkish girl developed + the signs of a polyglandular autoimmune syndrome (PGA) type I since her first year of age. Apart from the endocrine and non-endocrine symptoms of PGA, she suffered from an acute state of illness with therapy-resistant fever and multiform exanthemas in the early course of disease. All included the criteria of Wissler-Fanconi syndrome became clear which has not yet been reported in association with PGA. Although this syndrome generally is considered an equivalent of Still's syndrome, rheumatoid symptoms could not be ascertained during the following 9-year-course of PGA.     

Tolvaptan in a pediatric patient with diuretic‐resistant heart and kidney failure

Despite conventional diuretic therapy, volume overload persists in many patients with decompensated heart failure. Adverse effects of diuretics are common, including worsening kidney function and electrolyte disturbance. Furthermore, decreased kidney function also affects the response to diuretics and is associated with an increased risk of mortality. A 10‐year‐old boy with congestive heart failure (CHF) complicated by advanced chronic kidney disease (CKD) presented with oliguria and generalized edema. He was being treated with furosemide and spironolactone, and these doses were increased to 3 mg/kg/day after admission. Although edema decreased temporarily, the symptoms worsened and furosemide resistance developed 2 months later. Tolvaptan (0.1 mg/kg/day) was started, resulting in a gradual increase in the plasma sodium level and adequate decongestion of the volume overload state. Cardiac function also improved. The use of tolvaptan should be considered in pediatric cases of conventional diuretic‐resistant CHF, even when complicated by advanced CKD.     

Successful treatment of non‐Hodgkin's lymphoma using R‐CHOP in a patient with Wiskott–Aldrich syndrome followed by a reduced‐intensity stem cell transplant

WAS is an X‐linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and increased incidence of autoimmunity and malignancy. HSCT is the only curative treatment for WAS. Herein, we report the case of a 17‐yr‐old boy with WAS who received an unrelated HSCT while in complete remission of diffuse large B‐cell lymphoma after chemotherapy. Pretransplant conditioning consisted of fludarabine, busulfan, and total body irradiation (4 Gy). GvHD prophylaxis consisted of tacrolimus and short‐course methotrexate. Following HSCT, rapid and stable engraftment was observed. Platelet count gradually increased, and the generalized eczema improved. The patient developed grade II acute GvHD and limited chronic GvHD on days 30 and 210, respectively, which resolved with immunosuppressive treatment. Symptoms caused by the reactivation of human herpes virus‐6, BK virus, and VZV were observed from days 21, 60, and 96, respectively; they were resolved after conservative treatment and acyclovir administration. No other regimen‐related toxicity was observed. Complete donor bone marrow chimerism was achieved one month after transplantation. RIST is an effective therapeutic option for older children with WAS accompanied by malignant lymphoma.