Ocular complications in children with nephrotic syndrome on long term oral steroids.

OBJECTIVES: To estimate the burden of ocular complications like posterior subcapsular cataract (PSCC) and raised intra ocular pressure (IOP) in children with nephrotic syndrome on long term steroid therapy and to assess the correlation of cumulative dosage and duration of consumption of steroids with these ocular complications. METHODS: Children between 4-18 y with nephrotic syndrome, who received steroids for at least six months, were included in this cross sectional study. Demographic, clinical and treatment details were obtained from case records. Detailed ocular evaluation was performed to detect PSCC and to measure IOP. RESULTS: One hundred and eighteen children were screened and 82 with a median (IQR=Interquartile range) follow up of 4.2 y (2.4, 6.3 y) were included in the final analysis. The median (IQR) age of children was 9.3 y (6, 12.5 y) at recruitment. The proportion of children with PSCC and raised IOP were 22/82 (26.8 %) and 9/82 (10.97 %) respectively. PSCC was associated with older age (p = 0.009). The median cumulative dose of steroids in those with and without cataract was 338.4 mg/kg and 343.2 mg/kg respectively (p = 0.58). The median duration of steroid theraphy was 58 wk and 59 wk in the two groups respectively (p = 0.73). Of children with PSCC, 9 (42.8 %) had mild diminution of vision. CONCLUSIONS: One in 4 and 1 in 9 children with nephrotic syndrome in the present study had PSCC and raised IOP respectively. Cumulative dose and duration of steroid therapy were not significantly associated with PSCC or raised IOP. The present study emphasizes the need for regular ocular evaluation and also to explore additional factors in causation of steroid induced ocular complications.

Cyclosporine/ketoconazole reduces treatment costs for nephrotic syndrome.

Cyclosporine A (CyA) is an effective agent for the treatment of glucocorticoid-dependent idiopathic nephrotic syndrome (GCDNS), but costs are prohibitive in resource-poor societies. The objectives of this study were to evaluate the efficacy and safety of reducing the dose of CyA by co-administering ketoconazole. A prospective study targeting children 2-18 years of age with GCDNS in remission with CyA monotherapy was conducted. CyA dose was reduced by 50% and ketoconazole was added at 25% of the recommended therapeutic dose, and the drug levels and therapeutic and adverse effects (AE) were monitored. Continued combined therapy after completion of the 4-week trial period was offered. Ten patients (median age 9.5 years, range 3.0-16.0 years) were enrolled in the study. At week 4, the CyA dose was 2.2 ± 0.7 mg/kg/day compared with 5.6 ± 0.9 mg/kg/day at enrolment (P < 0.0001). No AE were noted. All patients continued ketoconazole treatment for at least 3 months. CyA drug cost savings were 61%, and approximately 60% with ketoconazole cost included. The combination of an expensive immunosuppressive drug with a cheap metabolic inhibitor reduced the treatment costs by> 50% without increased adverse events or drug monitoring needs. This intervention demonstrates how access of patients with limited resources to needed drugs can be improved by interference with physiological drug elimination.

Urinary indices during relapse of childhood nephrotic syndrome.

Sodium retention is the hallmark of idiopathic nephrotic syndrome (INS). Sodium retention could be secondary to activation of renin-angiotensin-aldosterone axis or due to an intrinsic activation of Na(+)K(+) ATPase in the cortical collecting duct. Urine potassium/urine potassium + urine sodium (UK(+)/UK(+) + UNa(+)) is a surrogate marker for aldosterone activity and can be useful in differentiating primary sodium retention from secondary sodium retention in children with INS. This was a cross-sectional study of children with INS, presenting to our center from June 2007 to June 2008. Children were categorized into those with steroid responsive and steroid nonresponsive nephrotic syndrome. One hundred and thirty-four children with nephrotic syndrome were analyzed. The FeNa(+) was significantly lower during relapse than in remission but no such difference was observed with UK(+)/UK(+) + UNa(+). The values of FeNa(+) and UK(+)/UK(+) + UNa(+) across various categories of nephrotic syndrome were similar. Correlating FeNa(+) and UK(+)/UK(+) + UNa(+) with cut-off of 0.5 and 60%, respectively, we found 50% of steroid responsive children and 36% of steroid nonresponders having a corresponding UK(+)/UK(+) + UNa(+) of <60% along with low FeNa(+) of <0.5%, favoring primary sodium retention. Urinary indices did not vary with the type of steroid response. In early relapse, the urinary indices revealed an overlap of both primary and secondary sodium retention in most stable edematous children with nephrotic syndrome.

Steroid sensitive nephrotic syndrome.

Nephrotic syndrome in children is a common recurrent disease. Most of the cases are due to minimal change disease with a favourable outcome. More than 90% of children with minimal change disease respond to corticosteroid therapy (steroid sensitive nephrotic syndrome). 40-60% experience frequent relapses or have steroid dependence. These children require frequent corticosteroid therapy and/or immunomodulators or treatment with immunosuppressants, and are at high risk of cumulative steroid toxicity and side effects of cytotoxic therapy. Children with frequent relapses or steroid dependence should be managed in consultation with a pediatric nephrologist. Despite relapsing course, progression of minimal change nephrotic syndrome to end stage renal disease is extremely rare.