A 15-year-old girl is brought to the clinic for evaluation of swelling around her eyes that developed over the past week. The patient is a cheerleader, and she had been taking ibuprofen daily for the last 3 months for various sprains and aches after practice. She has no chronic medical conditions. Vital signs are normal. On physical examination, there is moderate periorbital edema with bilateral lower extremity pitting edema. Serum creatinine is 0.5 mg/dL and serum albumin is 2.1 g/dL. Urinalysis shows 4+ protein and negative blood. Multiple regions of the kidney are biopsied, and a representative image is shown below:
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Which of the following is the most likely diagnosis?
Minimal change disease | |
Epidemiology |
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Pathogenesis |
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Clinical features |
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Diagnosis |
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EM = electron microscopy; IM = immunofluorescence microscopy; LM = light microscopy. | |
This patient with edema, proteinuria, and hypoalbuminemia has nephrotic syndrome. The normal glomeruli on light microscopy (LM) suggest a diagnosis of minimal change disease (MCD), the most common cause of nephrotic syndrome in children. It is often idiopathic but may be triggered by drugs (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], as in this patient), immunizations, or malignancy (eg, Hodgkin lymphoma).
Pathogenesis involves T cell dysfunction with production of a glomerular permeability factor (possibly IL-13), which damages podocytes and decreases the anionic charge of the glomerular basement membrane (GBM), allowing for selective loss of albumin in the urine.
Clinical features include acute weight gain, diffuse edema, and frothy urine due to heavy proteinuria. Renal biopsy demonstrates normal glomeruli on LM, with no immunoglobulin or complement deposits visible on immunofluorescent microscopy. However, electron microscopy shows diffuse effacement and fusion of podocyte foot process.
(Choice A) Acute interstitial nephritis often occurs after initiation of new drugs (eg, NSAIDS, diuretics) but causes acute kidney injury with white blood cell casts on urinalysis; heavy proteinuria is unexpected. Although the glomeruli are often normal, inflammation involving the interstitium and tubules will be seen on LM.
(Choices B and F) Crescentic glomerulonephritis and poststreptococcal glomerulonephritis cause nephritic syndrome (eg, hematuria, red blood cell casts, hypertension). Crescentic glomerulonephritis occurs in multiple renal diseases (eg, Goodpasture disease, microscopic polyangiitis) and demonstrates hypercellular crescents composed of parietal and inflammatory cells. Poststreptococcal glomerulonephritis, which occurs 2-4 weeks after a group A streptococcal infection, demonstrates hypercellular glomeruli on LM.
(Choice C) Focal segmental glomerulosclerosis causes nephrotic syndrome and also demonstrates similar podocyte foot process effacement on electron microscopy; however, LM demonstrates sclerotic foci within the glomerulus. This disease is more common in adults and typically has a slower onset of edema and weight gain.
(Choice D) Membranous nephropathy causes nephrotic syndrome, and is associated with NSAID use, but is more common in adults. LM demonstrates glomeruli with diffuse GBM thickening.
Educational objective:
Minimal change disease is the most common cause of nephrotic syndrome in children. It is often idiopathic but may be triggered by drugs, immunizations, or malignancy. Light microscopy shows normal glomeruli, with no immunoglobulin or complement deposits on immunofluorescent staining. However, electron microscopy shows diffuse podocyte foot process effacement and fusion.