Table 2.

Initial work-up for a child with nephrotic syndrome

Investigations	Comments
Clinical evaluation
Relevant patient history
Presence of gravity-dependent edema	(grade A, strong recommendation)
Fever episodes, pain, abdominal discomfort, fatigue
Search for risk factors for secondary causes (e.g., sickle cell disease, HIV,  systemic lupus erythematosus, hepatitis B, malaria, parvovirus B19, medications)    Screen for tuberculosis	Consider especially in patients from endemic areas before starting immunosuppressant medications (grade C, weak recommendation)
Physical examination
Blood pressure, assess volume status and extent of edema (ascites, pericardial and pleural effusions), lymphadenopathy    Signs of infection (respiratory tract, skin, peritonitis, urinary tract)	(grade A, strong recommendation)
Extrarenal features, e.g., dysmorphic features or ambiguous genitalia or eye abnormalities (microcoria, aniridia), rash, arthritis	Further work-up is recommended (grade A, strong recommendation)
Anthropometry
Growth chart: height/length, weight, and head circumference (< 2 years)	We recommend comparing data with appropriate national standards or WHO-MGRS charts (grade A, strong recommendation)
Vaccination status
Check/complete according to national standards esp., for encapsulated bacteria: pneumococcal, meningococcal, Haemophilus influenzae, Hep B, SARS-CoV2, influenza vaccine, and varicella	This is recommended before starting immunosuppressant medications other than PDN (grade B, moderate recommendation)
Family history
Kidney disease in family members    Extrarenal manifestations    HIV or tuberculosis in endemic regions    Consanguinity	(grade A, strong recommendation)
Biochemistry
Spot urine
Protein/creatinine ratio (in first morning void)	Recommended at least once before starting treatment of the first episode (grade B, moderate recommendation)
Urinalysis: including hematuria
Blood
Complete blood count, creatinine, eGFR, urea, electrolytes, albumin	eGFR (mL/min/1.73 m2) = k height (cm)/serum creatinine (mg/dl), where k is a constant = 0.413 or eGFR (mL/min/1.73 m2) = k height (cm)/serum creatinine (µmol/l), where k is a constant = 36.5 [300, 301]
Complement C3, C4, antinuclear and anti-streptococcal antibodies, and ANCA	Recommended in patients with macroscopic hematuria (grade A, strong recommendation)
Varicella and MMR specific IgG, in non-immunized children	Consider before start of PDN treatment (grade D, weak recommendation)
Imaging
Kidney ultrasound	Consider a kidney ultrasound in all children with INS to exclude kidney malformations and venous thrombosis and in patients with reduced eGFR, hematuria or abdominal pain and always before kidney biopsy (grade D, weak recommendation)
Chest X-ray	Recommended in case of suspected lymphoma (grade D, weak recommendation)
Histopathology
Kidney biopsy	Recommended in patients with atypical features including macroscopic hematuria, low C3 levels, AKI not related to hypovolemia, sustained hypertension, arthritis and/or rash (grade A, strong recommendation)
	Consider in patients with infantile onset NS if genetic screening is not available (age 3–12 months) (grade B, weak recommendation) (Fig. 2)
	Consider in patients > 12 years of age on a case-by-case basis (grade C, weak recommendation)
	Consider in patients with persistent microscopic hematuria in specific populations with a high incidence of glomerular diseases such as IgA nephropathy in East Asia (grade C, weak recommendation)
	Recommended in patients diagnosed with SRNS (grade A, strong recommendation)
Genetic testing	Recommended in patients with congenital NS, extrarenal features and/or family history suggesting syndromic/hereditary SRNS (grade A, strong recommendation)
	Consider in patients with infantile onset NS (age 3–12 months) (grade C, weak recommendation) (Fig. 2) Recommended in patients diagnosed with SRNS (grade A, strong recommendation)

AKI acute kidney injury, eGFR estimated glomerular filtration rate, ANCA antineutrophil cytoplasmic antibodies