Evidence-based clinical practice guidelines for nephrotic syndrome 2014

Nephrotic syndrome is a clinical syndrome showing specific features of heavy proteinuria and hypoalbuminemia or hypoproteinemia as its consequence. It is caused by increased permeability of serum protein through the damaged basement membrane in the renal glomerulus. The definition of nephrotic syndrome includes both massive proteinuria (≥3.5 g/day) and hypoalbuminemia (serum albumin ≤3.0 g/dL) (Tables 1, 4). Primary nephrotic syndrome has no background diseases, whereas secondary nephrotic syndrome has any background diseases. As a result of massive proteinuria and hypoalbuminemia, this syndrome is frequently accompanied by edema, dyslipidemia, abnormalities in coagulation/fibrinolysis, reduced renal function, and immunological disorders. The effect of treatment is determined by the urinary protein level after treatment (Tables 2, 3). Table 1 Clinical definition of adult nephrotic syndrome 1. Proteinuria: ≥3.5 g/day and continuous (comparable to ≥3.5 g/gCr at spot urine) 2. Hypoalbuminemia: Serum albumin ≤ 3.0 g/dL Serum total protein ≤ 6.0 g/dL is helpful 3. Edema 4. Dyslipidemia (Hyper LDL cholesterolemia) The above urine protein and hypoalbuminemia are indispensable prerequisites for the clinical diagnosis of nephrotic syndrome Edema is not an indispensable prerequisite but an important finding for nephrotic syndrome Dyslipidemia is not an indispensable prerequisite for nephrotic syndrome Oval fat body is helpful for diagnosis of nephrotic syndrome Table 2 Therapeutic evaluation for nephrotic syndrome The therapeutic evaluation is done by the amount of urine protein at 1 and 6 months after the initiation of treatment Complete remission: urine protein <3.0 g/day Incomplete remission I: 0.3 g/day ≤ urine protein <1.0 g/day Incomplete remission II: 1.0 g/day ≤ urine protein <3.5 g/day Non-response: urine protein ≥3.5 g/day The diagnosis of nephrotic syndrome and therapeutic evaluation should be done by 24-hour urine collection. If to collect 24-hour urine is impossible, the ratio of urine protein and urine creatinine (g/gCr) at spot urine is available for the diagnosis of nephrotic syndrome and therapeutic evaluation In principle, the evaluation of complete remission or incomplete remission at 6 months after the initiation of treatment includes the improvement of clinical finings and serum albumin The evaluation of relapse is the condition that urine protein ≥ 1 g/gCr (1g/gCr) runs or ≥(2+) continues 2–3 times in a row In Europe and the United States partial remission defines 50% or more of the reduction of urine protein, while the Japanese evaluation does not use this definition Table 3 The classification by the response to treatment of nephrotic syndrome Steroid resistant nephrotic syndrome: The enough dose of steroid treatment fails to achieve complete remission or incomplete remission I at 1 month after the initiation of treatment Refractory nephrotic syndrome: The various treatments including steroid and immunosuppressive agents fail to achieve complete remission or incomplete remission I at 6 months after the initiation of treatment Steroid dependent nephrotic syndrome: Steroid treatment is impossible to discontinue, because repeated over 2 times relapses appear after the reduction or discontinuation of steroid Frequent relapse nephrotic syndrome: Over 2 times relapses appear in 6 months Nephrotic syndrome requiring chronic treatment: Nephrotic syndrome to be treated by steroid or immunosuppressive agents over 2 years Table 4 The definition of nephrotic syndrome in children 1. Nephrotic syndrome: Massive proteinuria (40 ≥ mg/h/m2) + hypoalbuminemia (serum albumin ≤ 2.5 g/dL) 2. Steroid sensitive nephrotic syndrome: Daily administrated prednisolone treatment attains the remission within 4 weeks 3. Relapse: After the remission urine protein of 40 ≥ mg/h/m2 or morning urine 100 mg/dL or more by dip stick continues for 3 days