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Proteinuria Questions for the Physician Assistant Exam

You should be familiar with proteinuria for the Physician Assistant Exam. Proteinuria, or protein in the urine, is the single most significant prognostic factor in determining the risk of future kidney disease. The cause of the proteinuria is important, as is the quantity of protein that the kidney excretes.

When evaluating a question concerning proteinuria, keep these points in mind:

  • In a test question, tipoffs that proteinuria may be present include the appearance of frothy or bubbly urine and/or presence of edema seen on the patient’s exam.

  • Proteinuria is present if a urinalysis dips positive for protein. If hematuria is also present, think about glomerulonephritis or vasculitis.

  • If a person has diabetes, screen for microalbuminuria by ordering an albumin/creatinine ratio. A normal level is 30 or less.

  • Along with the amount of protein, the age of the person and the kidney function (indicated by creatinine level) are clues to help you figure out what may be causing the proteinuria.

  • The first-line treatment for proteinuria of any cause is to use an angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin receptor blocker (ARB).

A test question about proteinuria typically concerns either what may be causing the proteinuria or what the first-line treatment should be.

Proteinuria

If proteinuria is present on urinalysis, the next step is quantifying the amount of protein in the urine through a 24-hour protein collection or random/spot urine to obtain a protein/creatinine ratio. Here’s how to classify the type of proteinuria:

  • A normal protein/creatinine ratio is 0.2 or less, corresponding to 200 mg or less of total protein in the urine.

  • More than 200 mg of total protein but less than 3,500 mg is considered tubular-range proteinuria.

    A cause of tubular-range proteinuria in teenagers and young adults is benign orthostatic proteinuria. This is tubular-range proteinuria in the range of 1 to 2 grams. It’s purely positional: The protein is elevated when the person is sitting or standing but goes away when the patient is lying down. There’s no definitive treatment for it — the proteinuria will go away as the person gets older.

  • More than 3.5 grams (3,500 mg) of protein in a 24-hour urinary collection is nephrotic-range proteinuria.

Tests may also tell you what the serum albumin is. A normal amount of albumin excreted in the urine in 24 hours is 150 mg or less. A normal albumin/creatinine level is 30 mg or less.

Nephrotic syndrome (NS)

Nephrotic syndrome is an important clinical condition that you need to be familiar with. Among other abnormalities, a significant amount of protein is being excreted. Here are the four components of nephrotic syndrome; they all need to be present for the diagnosis:

  • Greater than 3.5 grams of protein in a 24-hour urine collection (nephrotic-range proteinuria)

  • Hyperlipidemia

  • Edema

  • Low serum albumin (hypoalbuminemia)

In nephrotic syndrome, the urinalysis shows only proteinuria, not hematuria (blood in the urine). This point is important because for the most part, the various causes of nephrotic syndrome differ from the causes of glomerulonephritis.

For PANCE purposes, here are the four causes of nephrotic syndrome you need to know:

  • Minimal change disease (MCD): Minimal change disease is the most common cause of nephrotic syndrome in young children. Minimal change disease is also associated with certain cancers, particularly non-Hodgkin lymphoma, and with certain drugs like NSAIDs and lithium. The first-line treatment for minimal change disease is ACE inhibitors/ARBs and prednisone.

  • Focal segmental glomerulosclerosis (FSGS): You can divide this condition into primary and secondary causes. HIV and obstructive sleep apnea (OSA) are common secondary causes. Again, the first-line treatment is ACE inhibitors/ARBs and prednisone.

  • Membranous nephropathy: Membranous nephropathy is the most common cause of nephrotic syndrome in older adults. Membranous nephropathy can be divided into primary and secondary causes. Common secondary causes include lupus, hepatitis B, and solid organ cancers. On a test, a common complication of membranous nephropathy is renal vein thrombosis.

  • Diabetic nephropathy (DN): Diabetic nephropathy is the most common cause of proteinuria and chronic kidney disease (CKD) in the United States. Here are some points concerning diabetic nephropathy:

    • You screen for albumin in the urine by ordering an albumin/creatinine ratio. A normal level is 30 mg or less. Microalbuminuria is defined as an albumin level of 30 to 300 mg. A level greater than 300 mg is termed macroalbuminuria. You screen for microalbuminuria annually in anyone who has diabetes.

    • The first line of treatment for diabetic nephropathy is using an ACE inhibitor or ARB.

    • The goal blood pressure is < 125/75 mmHg for someone with more than 1 g total protein in the urine.

You are seeing a 5-year-old child in the office who presents with significant edema. The urinalysis shows 3+ protein but no blood. The serum albumin is 2.3 mg/dL. You order a 24-hour urine collection, and it shows 5 grams of protein. What is the most likely cause of proteinuria in this young child?

(A) Membranous nephropathy
(B) Focal segmental glomerulosclerosis (FSGS)
(C) Minimal change disease (MCD)
(D) Benign orthostatic proteinuria
(E) Transient proteinuria

The answer is Choice (C). Minimal change disease is the most common cause of nephrotic-range proteinuria in young children. Membranous nephropathy, Choice (A), and focal segmental glomerulosclerosis, Choice (B), represent common causes of idiopathic nephrotic-range proteinuria in older adults. Benign orthostatic proteinuria, Choice (D), is a distinct condition.

It usually occurs in teenagers, and the range of proteinuria is usually in tubular range, on the order of 1 to 2 g. The child in question has nephrotic-range proteinuria, not tubular-range proteinuria. Transient proteinuria, Choice (E), is a temporary type of proteinuria that can present during illness, stress, or exercise. It resolves when the aforementioned problems resolve and requires no treatment.

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