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This child with volume overload (eg, facial puffiness, edema) and nephrotic-range proteinuria consisting mainly of albumin most likely has minimal change disease, the most common cause of nephrotic syndrome in children.

Renal filtration of macromolecules is mediated by the glomerular filtration barrier, which consists of fenestrated endothelium, the glomerular basement membrane (GBM), and podocytes.  This barrier has selective permeability based on molecular size and charge.  Size selectivity is dependent on pores in the GBM and the thin membrane between the foot processes of podocytes (slit diaphragm).  Charge selectively is reliant on polyanions (eg, heparan sulfate) on the GBM and endothelial cells, which repel negatively charged molecules such as albumin.

Albumin is small enough to fit through pores in the GBM and slit diaphragms, but it is not normally filtered through the glomerular filtration barrier due to its negative charge.  In patients with minimal change disease, systemic T-cell dysfunction leads to the production of glomerular permeability factor, a cytokine that causes podocyte foot process fusion and decreases the anionic properties of the GBM.  Loss of negative charge leads to increased filtration of negatively charged plasma proteins and selective loss of albumin in the urine (selective albuminuria).

(Choice A)  Low-molecular-weight proteins (eg, beta-2 microglobulin, immunoglobulin light chains) are normally filtered by the glomerulus and almost completely reabsorbed in the proximal tubule.  Tubular proteinuria occurs when proximal tubular function is disrupted (eg, tubulointerstitial nephritis).

(Choice C)  Inflammation of the urinary tract (eg, due to infection) causes production of a proteinaceous inflammatory exudate that can leak into the urine.  However, the proteinuria is generally mild (non-nephrotic range) and often accompanied by leukocyturia.

(Choices D and E)  Overflow proteinuria can occur if a particular protein is produced in excess amounts, leading to increased glomerular filtration and excretion of that protein.  This can occur with excess light chain production in multiple myeloma or in rhabdomyolysis, in which necrosis of the skeletal muscle leads to increased excretion of myoglobin in the urine.

Educational objective:
Minimal change disease is the most common cause of nephrotic syndrome in children.  Systemic T-cell dysfunction leads to the production of glomerular permeability factor, which causes podocyte foot process fusion and decreases the anionic properties of the glomerular basement membrane.  The loss of negative charge leads to selective albuminuria.