Management of steroid resistant nephrotic syndrome.

JUSTIFICATION: There is a lack of evidence based guidelines for management of children with steroid resistant nephrotic syndrome (SRNS). PROCESS: Experts of the Indian Society of Pediatric Nephrology were involved in a two-stage process, the Delphi method followed by a structured face to face meeting, to formulate guidelines, based on current practices and available evidence, on management of these children. Agreement of at least 80% participants formed an opinion. OBJECTIVES: To develop specific, realistic, evidence based criteria for management of children with idiopathic SRNS. RECOMMENDATIONS: The Expert Group emphasized that while all patients with SRNS should initially be referred to a pediatric nephrologist for evaluation, the subsequent care might be collaborative involving the primary pediatrician and the nephrologist. Following the diagnosis of SRNS (lack of remission despite treatment with prednisolone at 2 mg/kg/day for 4 weeks), all patients (with initial or late resistance) should undergo a renal biopsy, before instituting specific treatment. Patients with idiopathic SRNS secondary to minimal change disease or focal segmental glomerulosclerosis should receive similar therapy. Effective regimens include treatment with calcineurin inhibitors (tacrolimus, cyclosporine), intra-venous cyclophosphamide or a combination of pulse corticosteroids with oral cyclophosphamide, and tapering doses of alternate day corticosteroids. Supportive management comprises of, when indicated, therapy with angiotensin converting enzyme inhibitors and statins. It is expected that these guidelines shall enable standardization of care for patients with SRNS in the country.

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.

Dialysis therapy in children.

Acute dialysis can be life saving for children suffering from acute emergencies due to acute renal failure, poisoning or inborn errors of metabolism causing severe organic acidaemia and hyperammonaemia. Chronic dialysis is life sustaining for children with chronic renal failure or end stage renal disease till renal transplantation is performed. The basic principles, indications, procedures, equipment, complications of acute and chronic dialysis in children are same as in adults. Dialysis can be performed in children at any age from newborn to adolescent period. In newborn, infants and preschool children (0-5 years age) haemodialysis is difficult due to technical problems associated with vascular access and haemodynamic instability. Peritoneal dialysis is simple, efficient, easy to perform, does not require highly sophisticated equipment or personnel and with low complication rate. For successful dialysis appropriate sizes of catheters, tubings, dialysers, small volume dialysate bags, etc, are required. These are now available in our country, although the cost of peritoneal dialysis fluid and catheters, etc, is 2-3 times higher than equipment for haemodialysis. Hence, continuous ambulatory peritoneal dialysis for chronic renal failure/end stage renal disease has not taken off yet in India. A team of experts including specially trained paediatric nephrologists, urologists, nurses, dieticians, technicians and social workers are needed to organise dialysis programme for children with end stage renal disease. Acute peritoneal dialysis should be made available in each paediatric department offering emergency services to children.

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.

Renal parameters during infancy.

In a prospective study we estimated common renal parameters in 48 full term normal neonates, of which 15 were also tested at 6 months and 12 months of age. The mean levels of serum creatinine, were high at birth (0.73 mg/dl) but normal for age at 6 and 12 months; uric acid followed a similar trend. The blood pH and bicarbonate were low at birth (7.28 and 20.36 mEq/L, respectively) reached normal adult values by 12 months; chloride levels were high at birth (110 +/- 5 mEq/L) and normal at 6 months. The plasma renin activity was higher than normal all throughout the first year (27.1, 416.8, 64.8 ng/ml/hr by RIA). Plasma aldosterone values were high at birth (1387.5 pg/ml) and reached normal level (301.6) at 12 months. Renal length and volume as assessed by ultrasonography compared well with American standards. Urinary constituents were variable due to breast feeding up to 6 months and varied diet during the weaning period. This study shows that mild metabolic acidosis and hyperchloremia due to immaturity of renal acidification mechanism and high renin and aldosterone levels due to partial nonresponsiveness of distal tubules are normal variables in babies from birth to 6 months. The levels of serum creatinine and uric acid are high at birth and in assessing renal functions this should be borne in mind.

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.