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Corticosteroid therapy for nephrotic syndrome in children

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Abstract

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Background

In nephrotic syndrome (NS) protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While the majority of children with NS respond to corticosteroids, 70% experience a relapsing course. Corticosteroids have reduced the mortality rate to around 3%. However corticosteroids have well recognised potentially serious adverse effects such as obesity, poor growth, hypertension, diabetes mellitus and osteoporosis.

Objectives

To determine the benefits and harms of corticosteroid regimens in preventing relapse in children with steroid sensitive NS (SSNS).

Search methods

We searched CENTRAL, Cochrane Renal Group Specialised Register, MEDLINE and EMBASE without language restriction, reference lists of articles and contact with known investigators.

Selection criteria

Randomised controlled trials performed in children (three months to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent, with outcome data at six months or more.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. Results were expressed as risk ratio (RR) with 95% confidence intervals (CI) or mean difference (MD). Meta‐regression was used to explore potential between‐study differences due to baseline risk of relapse, study quality and interventions.

Main results

Twenty four trials were identified. Six trials comparing two months of prednisone or prednisolone with three months or more in the first episode showed longer duration significantly reduced the risk of relapse at 12 to 24 months (RR 0.70, 95% CI 0.58 to 0.84). There was an inverse linear relationship between treatment duration and risk of relapse (RR = 1.26 ‐ 0.112 duration; P = 0.03). Four trials showed that six months of prednisone was more effective than three months in reducing the risk for relapse (RR 0.57; 95% CI 0.45 to 0.71). Deflazacort was significantly more effective in maintaining remission than prednisone in children who frequently relapsed in a single study (RR 0.44, 95% CI 0.25 to 0.78). There were no increases in adverse events.

Authors' conclusions

Children in their first episode of SSNS should be treated for at least three months with an increase in benefit for up to seven months of treatment. For a baseline risk for relapse following the first episode of 60% with two months of therapy, daily prednisone or prednisolone given for four weeks followed by alternate‐day therapy for six months would reduce the number of children relapsing by 33%.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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Corticosteroid drugs for several months after a child has nephrotic syndrome can reduce repeat episodes

Nephrotic syndrome is a condition where the kidneys leak protein from the blood into the urine. Most children who experience this syndrome have repeat episodes. When it is untreated, children can often die from infections. Corticosteroid drugs (prednisone, prednisolone) are used to treat nephrotic syndrome and so reduce the risk of these infections, but the drugs can also have serious side effects. This review identified 24 trials evaluating 1726 children. Continuing to take corticosteroid medications for several months after the first episode of nephrotic syndrome has an increasing ability to reduce the risk of relapses, without an increase in serious side effects.