Proteinuria: diagnostic approach — viva

Stage 1 — The asymptomatic adolescent

Examiner: A 14-year-old girl is found to have 1+ protein on a dipstick at a school sports screen. She is well. Take me through your diagnostic approach. [6]

Expected thread: Resist the single-dipstick diagnosis. Confirm the proteinuria on two to three repeat first-morning urine samples taken weeks apart when she is well, because a single reading during activity is most likely transient (functional) proteinuria. State that the first-morning sample is the test because it is passed after overnight recumbency and a normal value excludes orthostatic proteinuria. If the daytime dipsticks remain positive but the first-morning UPr/Cr is normal, classify the pattern as orthostatic (postural) proteinuria. Measure her blood pressure against paediatric centiles and examine for oedema and growth failure before deciding between monitoring and referral. [2]

Stage 2 — The orthostatic pattern and its long-term outlook

Examiner: Her first-morning UPr/Cr is 0.1 mg/mg, her blood pressure is normal, and her renal function is normal. You diagnose orthostatic proteinuria. Is this benign, and what do you tell the family? [4]

Expected thread: The traditional teaching is that orthostatic proteinuria is uniformly benign, but recent long-term follow-up data show that a minority of affected individuals develop sustained proteinuria, hypertension or renal functional change over decades. Tell the family that the great majority do well, but that monitoring rather than discharge is the modern stance. Arrange periodic measurement of blood pressure, urinalysis and renal function, lengthening the interval if the values stay normal, and refer to nephrology if the pattern, the blood pressure or the function changes. [5]

Stage 3 — The dipstick blind spot

Examiner: A different child. A 4-year-old boy has growth failure, hypercalciuria and nephrocalcinosis, but his dipstick protein is only trace, while a spot total protein is markedly raised. Why, and what does it mean for your workup? [5]

Expected thread: The dipstick uses a tetrabromophenol indicator that detects albumin and does not detect non-albumin proteins. The child has tubular proteinuria, with low-molecular-weight proteins such as beta-2-microglobulin, alpha-1-microglobulin and retinol-binding protein that the dipstick misses, so the dipstick reads trace or negative despite heavy total protein. The clinical picture (a boy with hypercalciuria, nephrocalcinosis and growth failure) points to Dent disease. Request the low-molecular-weight protein assays and the total protein or sulfosalicylic acid test, and refer to paediatric nephrology. The general lesson is to reach for these assays whenever the dipstick and the clinical picture disagree. [5]

Examiner probes (held in reserve)

• State the paediatric threshold for proteinuria and the nephrotic-range threshold. (Proteinuria over 100 mg per square metre per day or a first-morning UPr/Cr over 0.2 mg/mg over two years; nephrotic range over 1000 mg per square metre per day or a UPr/Cr over 2 mg/mg.) [1]
• Name the KDIGO albuminuria categories. (A1 under 30 mg per gram, A2 at 30 to 300, A3 over 300.) [1]
• When would you start an angiotensin-converting-enzyme inhibitor in a child with proteinuria? (Only after the diagnosis of persistent glomerular disease is established and under nephrology supervision, with monitoring of blood pressure, creatinine and potassium — never before the cause is known.) [1]
• Give two features that convert a routine proteinuria workup into an urgent nephrology referral. (Proteinuria with haematuria or hypertension, a falling eGFR, or nephrotic-range proteinuria with oedema.) [2]