Diagnostic Approach to Nephrotic Range Proteinuria
Initial Evaluation and Diagnosis
- The American College of Rheumatology recommends performing kidney biopsy in all adults with nephrotic-range proteinuria to establish the underlying diagnosis, except when serum anti-phospholipase A2 receptor antibodies are positive, which is diagnostic of membranous nephropathy 1
- The International Society of Nephrology recommends complete metabolic panel, including serum creatinine and estimated GFR, to assess renal function in patients with nephrotic-range proteinuria 2
- Urinalysis with microscopic examination should be performed to evaluate for hematuria, pyuria, and cellular casts, which suggests glomerulonephritis 2
- Hepatitis B and C serology should be tested to exclude viral-associated glomerular disease 2
- HIV testing should be performed to exclude HIV-associated nephropathy 2
- Antinuclear antibody (ANA) should be screened to evaluate for systemic lupus erythematosus 2
- Complement levels (C3, C4) should be evaluated to assess for complement-mediated glomerular disease 2
- Renal ultrasound should be performed to evaluate kidney size, structural abnormalities, and exclude obstruction 2
Kidney Biopsy and Pathological Assessment
- The International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification should be used for lupus nephritis 1
- Activity and chronicity indices should be assessed to guide treatment decisions 1
- Evaluation for thrombotic and vascular lesions should be performed, particularly if antiphospholipid antibodies are present 1
Genetic Testing and Specialized Care
- Massively parallel sequencing (whole-exome sequencing preferred) should be performed as first-line diagnostic in infants with congenital nephrotic syndrome (onset within first 3 months of life) 3
- Genetic screening establishes etiology, informs management regarding potential Wilms tumor or neurological involvement, and enables family counseling 3
- Infants with congenital nephrotic syndrome must be referred to specialized tertiary pediatric nephrology centers with multidisciplinary teams including neonatologists, pediatric nephrologists, dieticians, and surgeons 3
- Early introduction to transplant center is recommended for children with congenital nephrotic syndrome to minimize dialysis time 3