Nephrotic Range Proteinuria in Children
Nephrotic-range proteinuria in children is defined as a first morning spot urine protein-to-creatinine ratio (UPCR) ≥2 g/g (or ≥200 mg/mmol), which correlates with the traditional 24-hour urine collection threshold of ≥40 mg/m²/hour. 1
Measurement Methods and Practical Application
The spot UPCR has replaced 24-hour urine collections as the standard of care for quantifying proteinuria in children due to excellent correlation between methods and the practical difficulty of obtaining accurate timed collections in pediatric patients 1
First morning urine specimens are preferred because they minimize the impact of orthostatic proteinuria and provide the most reliable assessment 2
The traditional definition from the International Study of Kidney Disease in Children established proteinuria ≥40 mg/m²/hour as nephrotic-range, which has been validated over 50 years of clinical trials 1
Relationship to Nephrotic Syndrome
Nephrotic-range proteinuria alone does not equal nephrotic syndrome. The complete syndrome requires three components:
Important Distinction
The 2021 KDIGO guideline suggested changing the albumin threshold to <3 g/dL, but the KDOQI US Commentary (2023) explicitly recommends maintaining the traditional cutoff of ≤2.5 g/dL for children, as there is no evidence that children with albumin 2.6-2.9 g/dL respond similarly to treatment 1
Changing this 50-year standard definition would complicate comparison with historical clinical trials and lacks supporting evidence 1
Alternative Measurement Units
Nephrotic-range proteinuria can be expressed in multiple equivalent ways:
- UPCR ≥2 g/g (or ≥2000 mg/g) 1, 2
- Timed collection ≥40 mg/m²/hour 1, 3
- 24-hour protein excretion >3.5 g/day (in older children approaching adult size) 4
- Urine dipstick showing 3+ or 4+ protein (less precise but suggestive) 3
Clinical Significance and Referral Thresholds
Any child with UPCR ≥2 g/g requires prompt nephrology referral, especially when accompanied by hypoalbuminemia, edema, or hematuria 2, 4
The presence of nephrotic-range proteinuria with hematuria strongly suggests glomerular disease and mandates urgent subspecialty evaluation 2, 5
Children with confirmed nephrotic syndrome (proteinuria + hypoalbuminemia + edema) should begin corticosteroid therapy with prednisone 60 mg/m²/day, with renal biopsy reserved for steroid-resistant cases after 4 weeks 2
Common Pitfalls to Avoid
Do not rely on random dipstick testing alone for quantification—it has poor sensitivity and specificity except at extreme values 6
Do not use 24-hour collections routinely in children due to high collection error rates (57% of samples in one study had significant creatinine variation) 6
Do not confuse nephrotic-range proteinuria with nephrotic syndrome—the former is a laboratory finding while the latter is a clinical syndrome requiring all three diagnostic criteria 1, 3
Be aware that the albumin assay method matters: bromocresol green (BCG) overestimates serum albumin in nephrotic syndrome compared to bromocresol purple (BCP) 1