A 5-year-old boy is brought to the office due to a weeklong history of generalized edema and fatigue. Otherwise, he has been well, and his medical history is significant only for obesity. The patient takes a daily multivitamin and no other medications. BMI is at the 98th percentile for age. Blood pressure is 92/55 mm Hg and pulse is 90/min. Periorbital edema and 1+ pretibial edema are found on examination. The scrotum is mildly swollen but nontender. Abdominal examination is unremarkable. Urinalysis results are as follows: Which of the following is the most likely underlying pathogenesis for this patient's condition?

Question

A 5-year-old boy is brought to the office due to a weeklong history of generalized edema and fatigue.  Otherwise, he has been well, and his medical history is significant only for obesity.  The patient takes a daily multivitamin and no other medications.  BMI is at the 98th percentile for age.  Blood pressure is 92/55 mm Hg and pulse is 90/min.  Periorbital edema and 1+ pretibial edema are found on examination.  The scrotum is mildly swollen but nontender.  Abdominal examination is unremarkable.  Urinalysis results are as follows:  Which of the following is the most likely underlying pathogenesis for this patient's condition?

Quizplus · Accepted Answer

11ec25c8_d72b_791a_bc81_9741924b8b92_MD0003_00 This patient has generalized edema and isolated, marked proteinuria, findings consistent with nephrotic syndrome. The most likely cause in a child is minimal change disease (MCD), which accounts for 80% of pediatric cases of nephrotic syndrome. The pathogenesis of MCD begins with dysregulation of T-cell subpopulations. Dysfunctional T cells release cytokines (eg, IL-13) that damage the capillary wall of the glomerulus, leading to epithelial podocyte injury and loss of charge selectivity across the glomerular basement membrane. This allows for urinary loss of anions (eg, albumin), causing marked proteinuria. The resulting hypoalbuminemia leads to decreased plasma oncotic pressure and acute-onset, gravity-dependent edema (eg, periorbital, scrotal, tibial). Rapid fluid accumulation may result in generalized edema (ie, anasarca) with ascites and pleural effusions. Children with MCD often have nonspecific symptoms (eg, fatigue, headache), as seen in this patient. podocyte injury Diagnosis of MCD is clinical with kidney biopsy reserved for atypical cases. If performed, light microscopy demonstrates normal kidney architecture, and immunofluorescence staining of the glomeruli is negative. Diffuse effacement of foot processes of podocytes on electron microscopy confirms the diagnosis. (Choice B) Renal amyloidosis can cause nephrotic syndrome due to glomerular amyloid deposition. This condition is exceedingly rare in children and typically associated with progressive, chronic disease. (Choice C) Alport syndrome (hereditary nephritis) is characterized by a glomerular collagen abnormality that causes hematuria, not severe proteinuria, in childhood. Moreover, patients frequently have a positive family history, which is not seen in this child. (Choice D) Glomerulosclerosis is seen in focal segmental glomerulosclerosis (FSGS), which also causes nephrotic syndrome in children. However, in addition to being much less common than MCD in this age group, FSGS also commonly causes hematuria and hypertension, making this diagnosis less likely in this patient. (Choice E) Immune complex deposition occurs in several pediatric nephropathies (eg, acute poststreptococcal and membranoproliferative glomerulonephritis) and can lead to edema from proteinuria. However, these syndromes also present with hematuria, which is not seen in this patient. Educational objective: Minimal change disease is the most common cause of nephrotic syndrome in children. Pathogenesis involves cytokine-induced glomerular injury, which damages epithelial podocytes, leading to a massive urinary loss of protein, hypoalbuminemia, and edema. References: Minimal change disease. (http://www.ncbi.nlm.nih.gov/pubmed/27940460)

A 5-Year-Old Boy Is Brought to the Office Due to a Weeklong