14.1 Nephrotic Syndrome

Nephrotic Syndrome

Nephrotic syndrome is one of the most frequently tested renal topics on the ABHS Pediatrics Part 1 written paper, with examiners favoring vignettes that separate a classic steroid-responsive minimal change presentation from atypical features that demand biopsy or a nephritic work-up.

Definition and the Classic Tetrad

Nephrotic syndrome is a clinical disorder caused by increased glomerular permeability to protein, producing a characteristic tetrad:

The proteinuria is the primary event: podocyte (visceral epithelial cell) injury damages the glomerular filtration barrier, protein spills into the urine, serum albumin falls, plasma oncotic pressure drops, and fluid shifts into the interstitium, producing edema. The liver responds to the low oncotic pressure by upregulating lipoprotein production, producing the hyperlipidemia.

An important exam distinction is nephrotic vs. nephritic presentation. Nephrotic syndrome is dominated by heavy proteinuria and edema, with blood pressure and renal function usually preserved; a nephritic process (such as post-streptococcal glomerulonephritis, covered in the next section) is instead dominated by hematuria, hypertension, and a falling glomerular filtration rate, with proteinuria present but rarely at nephrotic-range levels. Some children show overlap features, but recognizing which picture predominates is often the fastest route to the correct diagnosis on a timed exam.

Minimal Change Disease: The Classic Pediatric Cause

Minimal change disease (MCD) accounts for roughly 80-90% of nephrotic syndrome in children between 1 and 10 years old, with a peak incidence between ages 2 and 6 and a mild male predominance. The name reflects the histology: light microscopy is essentially normal, immunofluorescence is negative for immune deposits, and the only abnormality is diffuse foot process effacement on electron microscopy.

Typical presentation: a preschool-age child develops periorbital edema (often mistaken for allergies), which spreads to generalized edema over days, frequently following a viral upper respiratory infection. Urine is frothy from heavy proteinuria. Blood pressure and renal function are usually normal, and — critically for the exam — serum complement (C3) is normal in MCD. A low C3 in a child with edema and proteinuria should redirect the differential toward a glomerulonephritis, not MCD.

Steroid-Responsive vs. Steroid-Resistant Disease

First-line treatment for a child with new-onset nephrotic syndrome (without atypical features such as gross hematuria, hypertension, low complement, or age outside 1-10 years) is empiric oral corticosteroids — prednisone/prednisolone, typically around 60 mg/m2/day (maximum roughly 60 mg/day) for 4-6 weeks, followed by a tapering course — without biopsy, because MCD is by far the most likely diagnosis at this age.

Some initial responders go on to relapse repeatedly (frequent relapsers) or become steroid-dependent, which changes long-term management (steroid-sparing agents) but does not change the initial diagnosis. A child who fails to respond to an adequate steroid trial is labeled steroid-resistant and needs a biopsy — this is the single biggest exam trigger for moving beyond "just give steroids."

Complications

Two complications recur as exam themes because they are directly explained by what nephrotic children lose in the urine:

• Infection risk. Nephrotic children lose immunoglobulin G (IgG) and complement factor B in the urine, and steroid therapy adds iatrogenic immunosuppression on top of that. The classic complication is spontaneous bacterial peritonitis (SBP), most often caused by Streptococcus pneumoniae; cellulitis and sepsis are also more common. This is why pneumococcal vaccination is emphasized in nephrotic syndrome management.
• Thrombosis. Nephrotic syndrome is a hypercoagulable state: urinary loss of antithrombin III, hemoconcentration from intravascular volume depletion, increased hepatic synthesis of clotting factors (fibrinogen, factors V and VIII), and reactive thrombocytosis all contribute. Renal vein thrombosis, deep vein thrombosis, and even cerebral venous sinus thrombosis or pulmonary embolism can occur; risk rises with severe hypoalbuminemia and with aggressive diuresis.

Additional exam-relevant points: children can also develop acute kidney injury from intravascular volume depletion, especially with overly aggressive diuretic use, and they remain at risk for relapse triggered by intercurrent viral illness.

Worked scenario: A 3-year-old boy presents with periorbital swelling that started after a cold, now with abdominal and scrotal swelling. Urine dipstick shows 3+ protein, serum albumin is 1.9 g/dL, cholesterol is elevated, blood pressure is normal, and C3 is normal. This is the textbook presentation of minimal change disease — start empiric corticosteroids without biopsy.

Exam trap: age matters. A well-appearing 3-year-old with the picture above almost certainly has minimal change disease. Nephrotic-range proteinuria and edema presenting in the first 3 months of life, by contrast, should raise concern for congenital nephrotic syndrome (classically the Finnish type, caused by NPHS1 mutations affecting the podocyte protein nephrin), which does not respond to steroids and behaves very differently from typical childhood MCD — a reminder that the age of onset itself carries diagnostic weight.