The nephrotic syndrome (NS) is caused by renal diseases that increase the permeability across the glomerular filtration barrier. It is classically characterized by four clinical features, but the first two are used diagnostically because the last two may not be seen in all patients:
- Nephrotic range proteinuria: Urine protein excretion >50 mg/kg per day.
- Hypoalbuminemia: Serum albumin <3 g/dL (30 g/L).
- Edema.
- Hyperlipidemia.
Idiopathic NS is the most common form of NS in children, representing more than 90 percent of cases before 10 years of age and 50 percent after 10 years of age. Idiopathic NS is characterized by diffuse foot process effacement on electron microscopy and minimal changes (called minimal change disease [MCD]), focal segmental glomerulosclerosis (FSGS), or mesangial proliferation on light microscopy.
Children's Nephrotic Syndrome Consensus
In 2009, the Children's Nephrotic Syndrome Consensus Conference, which included pediatric nephrologists from the southeast and midwest sections of the United States, developed the following guidelines for the treatment of children with nephrotic syndrome.
- Initial therapy — Initial prednisone therapy of 2 mg/kg per day for six weeks, followed by alternate day prednisone of 1.5 mg/kg for an additional six weeks.
- First relapse / Infrequent relapse — Prednisone therapy of 2 mg/kg per day until the urine protein tests are negative or trace for three consecutive days, followed by alternate day prednisone of 1.5 mg/kg for four weeks.
- Frequent relapses — Prednisone therapy of 2 mg/kg per day until the urine protein tests are negative or trace for three consecutive days, followed by alternate day prednisone of 1.5 mg/kg for four weeks, which is than tapered over two months by 0.5 mg/kg every other day. Steroid-sparing agents may be used to sustain remission and thereby reduce cumulative steroid doses and toxicity. These agents include oral cyclophosphamide, cyclosporine, and mycophenolate mofetil.
- Steroid-dependent disease — Prednisone remains the preferred therapy in the absence of significant steroid toxicity. Steroid-sparing agents, such as cyclosporine, tacrolimus, and mycophenolate, may be helpful in reducing steroid dosing. However, there are no data based upon controlled trials in helping to chose among these agents, and drug selection is based upon the risk/benefit ratio of each agent as determined by the clinician.
- Steroid-resistant disease — Therapy is based upon the histologic findings found on renal biopsy. Additional treatment includes angiotensin antagonism and supportive care focused on managing the complications of nephrotic syndrome (edema, hypertension, infection, dyslipidemia, thromboembolism).
References:
Gipson DS, Massengill SF, Yao L, et al. Management of childhood onset nephrotic syndrome. Pediatrics 2009; 124:747.