A Randomized Controlled Trial of Intravenous versus Oral Cyclophosphamide in Steroid-resistant Nephrotic Syndrome in Children.

This is a randomized, parallel group, active-controlled trial to compare the efficacy of intravenous cyclophosphamide (IVCP) with oral cyclophosphamide (OCP) in patients with steroid-resistant nephrotic syndrome (SRNS) in children. Fifty consecutive children with idiopathic SRNS were biopsied and then randomized to receive either OCP at a dose of 2 mg/kg/day for 12 weeks or IVCP at a dose of 500 mg/m2/month for 6 months. Both groups received tapering doses of oral steroids. The response was evaluated in terms of induction of complete remission (CR) or partial remission (PR), time to remit, and side effects. The groups were followed up to determine the duration of remission, percentage of patients who remain in sustained remission for more than 1 year after completion of therapy, change in steroid response status, progression to chronic kidney disease stage 3 or more. Of the fifty patients, OCP was given to 25 children and IVCP to 25 children. The demographic data, histopathology, biochemical profile, and duration of follow-up in the two groups were comparable. The rates of induction of CR were 52% versus 44% and of PR were 8% versus 8% in the intravenous (IV) and oral group, respectively. Time to remit was shorter with OCP than IVCP (53 days vs. 84.4 days). Incidence of side effects (both major and minor) was 36% in IVCP versus 20% in OCP group. The actuarial cumulative sustained remission in our study was 12% in IVCP compared with 16% in OCP at 1 year after completion of therapy. Twelve percent children in both the groups exhibited restoration of steroid sensitivity. Thus, in our study, overall, more than half of SRNS patients showed initial response to cyclophosphamide, but only one-fourth patients had sustained remission on follow-up. OCP and IVCP were equally efficacious and safe in idiopathic SRNS in children.

Deep vein thrombosis associated with osteomyelitis.

Three children developed deep vein thrombosis (DVT) along with osteomyelitis of the femur. Although DVT was recognized early, the diagnosis of associated osteomyelitis was delayed due to overlapping clinical signs and the absence of radiological changes in the initial X-rays.

Treatment of neonatal candidiasis with liposomal amphotericin B(L-AMP-LRC-1): phase II study.

A liposomal amphotericin B preparation (L-AMP-LRC-1) has been developed and tested successfully in adults by us. This preparation was administered to 23 neonates with candidiasis in an open phase II study. All the 14 assessable patients responded completely to the L-AMP-LRC-1 therapy given at 1 mg/kg for 28 days. Compared to AmBisome, another liposomal formulation of amphotericin B, L-AMP-LRC-1 was effective at lower dose in neonatal candidiasis. Thus L-AMP-LRC-1 appears to be an effective and low cost drug for the treatment of candidiasis.

Renal dysfunction detected by beta-2 microglobulinuria in sick neonates.

OBJECTIVE: To assess renal involvement in sick neonates referred to Neonatal Intensive Care Unit (NICU) using standard renal parameters and urinary beta 2 microglobulin (B2M) excretion. DESIGN: Descriptive study. SETTING: Level II NICU and Nephrology Division of Pediatric Tertiary hospital. SUBJECTS: Forty six term sick neonates transferred for neonatal care and forty healthy term neonates who served as normal controls for urinary B2M excretion. METHODS: Standard tests including estimation of BUN, serum creatinine, blood pH, serum bicarbonate, serum and urinary electrolytes, urine output, and urinalysis. Urinary B2M levels were estimated from urine collected on day 1 (D1) and day 3 (D3) in all and 18 neonates were tested on day 7 (D7) by radio-immunoassay method. RESULTS: Statistically significant elevation of mean values of urinary B2M were noted when sick neonates were compared with normal controls irrespective of primary disease, indicating tubular dysfunction (41/46 = 90%), whilst only 7 of these (17%) had abnormalities indicating renal involvement when judged by standard tests. Very high levels of urinary B2M were noted with birth asphyxia (n = 9), sepsis (n = 8) and renal disease (n = 7). Transient elevation of urinary B2M was noted in meconium aspiration syndrome (n = 4). Ten surgical cases with non renal congenital malformations showed high urinary B2M and 12/18 tested on D7 had persistently high urinary B2M due to multiple factors. CONCLUSIONS: Elevated urinary B2M in 90% sick neonates with apparently normal renal parameters in majority (34/41) indicates subclinical proximal tubular dysfunction especially in neonates with asphyxia, sepsis and congenital malformations. Persistent elevation of urinary B2M appear to be a sensitive diagnostic indicator for defining a group of neonates with subtle renal tubular dysfunction, the clinical relevance of which on long term basis is a subject for future study.

Superior sagittal sinus thrombosis in a child with nephrotic syndrome.

A 3-year-old male with steroid-responsive nephrotic syndrome developed a rare complication, sagittal sinus thrombosis during an episode of gastroenteritis, while on steroid therapy. Anticoagulation, as assessed by partial thromboplastin time, was difficult to maintain, despite administering high doses of heparin, infusions of fresh-frozen plasma to provide antithrombin III, and, subsequently, maximum doses of warfarin (0.3 mg/kg per day). Despite these problems the child made a complete neurological recovery.

Glomerular basement membrane abnormalities in infants with heavy proteinuria.

Two Indian male children with infantile-onset heavy proteinuria (with nephrotic syndrome in 1) had thickening of the glomerular basement membrane with splitting and basket-weave appearance of lamina densa on electron microscopic evaluation of kidney tissue (like Alport's syndrome), with normal light microscopic findings and negative immunofluorescence. The proteinuria was non-familial and was not associated with microhaematuria in patient 1; transient microhaematuria, perhaps associated with urinary tract infection, was noted in patient 2. There was no neurosensory deafness in the patients or their parents. The nephrotic syndrome remitted totally in one patient over a 7-month period. The proteinuria, as well as the renal disease, was non-progressive in the second patient over a 27-month period. The significance of these basement membrane abnormalities (classically described in Alport's syndrome) in early-onset nephrotic syndrome/heavy proteinuria that is non-familial and non-progressive needs to be evaluated.

Systemic lupus erythematosus in Indian children.

Twenty cases of systemic lupus erythematosus (SLE) in prepubertal children (less than 14 years of age) were seen over a period of 14 years. The male:female ratio was 1:2.3, and the mean age at onset was 9.37 years. Fever with joint involvement was the commonest presenting manifestation (60%), followed by nephrotic syndrome (25%). Notable clinical features included a high incidence of renal involvement (75%), significant hypertension (45%) and reversibility of acute renal failure (2 cases). The other organs and systems involved included: mucocutaneous manifestations (60%), cardiovascular system (30%), respiratory system (25%), neuropsychiatric manifestations (45%), and anemia (75%). Raynaud's phenomenon and thrombocytopenia were rare while leucopenia was not seen in a single patient. Immunological abnormalities noted were 100% positivity for antinuclear antibodies, and 87.5 and 75% positivity for antibodies to double-stranded and single-stranded DNA, respectively. Hypocomplementemia was seen in 75% of patients tested.