Heavy proteinuria (>3.5 g/day) with hypoalbuminemia, edema, and hyperlipidemia.
Also known as: nephrotic syndrome, minimal change disease, FSGS, membranous nephropathy, diabetic nephropathy
Overview
A glomerular disorder characterized by proteinuria >3.5 g/day (or UPCR >3.5 g/g), hypoalbuminemia (<3.0 g/dL), peripheral edema, and hyperlipidemia. Reflects increased glomerular basement membrane permeability to plasma proteins.
Epidemiology
Annual incidence ~3 per 100,000 adults. Minimal change disease is the most common cause in children; FSGS and membranous nephropathy dominate in adults. Diabetic nephropathy is the most common secondary cause overall.
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Question 1RenalMedium
A 60-year-old man with type 2 diabetes is seen for routine follow-up. Blood pressure is 148/92 mm Hg on repeated measurements. Laboratory studies show eGFR 52 mL/min/1.73 m^2 and a urine albumin-to-creatinine ratio of 320 mg/g. He is not currently on antihypertensive therapy. Which of the following is the most appropriate first-line antihypertensive agent?
AHydrochlorothiazide
BAmlodipine
CLisinopril
DMetoprolol
Reveal answer & full explanation
Correct answer: C — Lisinopril
AHydrochlorothiazide
BAmlodipine
CLisinopril✓
DMetoprolol
Why Lisinopril is correct
This patient has diabetic nephropathy with albuminuria (urine albumin-to-creatinine ratio 320 mg/g) and hypertension
ACE inhibitors (or ARBs) are first-line because they reduce intraglomerular pressure and proteinuria, slow CKD progression, and lower BP
Target BP is <130/80 mm Hg
Monitor potassium and creatinine after initiation
Why the others are wrong
Hydrochlorothiazide — a reasonable add-on for blood pressure but lacks the albuminuria-lowering renoprotection of RAAS blockade needed first-line here
Amlodipine — effective for blood pressure but does not reduce intraglomerular pressure or proteinuria, so it is not first-line in albuminuric diabetic kidney disease
Metoprolol — a beta-blocker without specific renoprotective or antiproteinuric benefit, reserved for a compelling cardiac indication
Additional high-yield points
SGLT2 inhibitors (e.g., dapagliflozin) and finerenone add further renoprotection in this population
Question 2RenalMedium
A 55-year-old man with type 2 diabetes presents for annual lab review. Urinalysis shows microalbuminuria (urine albumin:creatinine ratio 65 mg/g). Creatinine 1.1, eGFR 72. BP 138/86. He is on metformin only. Which of the following is the most appropriate first-line antihypertensive and antiproteinuric agent to add?
ASGLT-2 inhibitor
BAmlodipine
CFurosemide
DACE inhibitor
Reveal answer & full explanation
Correct answer: D — ACE inhibitor
ASGLT-2 inhibitor
BAmlodipine
CFurosemide
DACE inhibitor✓
Why ACE inhibitor is correct
Diabetic kidney disease (DKD) with microalbuminuria: angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are first-line renoprotective therapy regardless of blood pressure level.
They reduce intraglomerular pressure and slow progression of diabetic nephropathy.
ACE/ARB remains the foundational initial therapy.
Why the others are wrong
SGLT-2 inhibitor — Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (empagliflozin, dapagliflozin) also have strong renoprotective evidence and are recommended by American Diabetes Association (ADA)/Kidney Disease: Improving Global Outcomes (KDIGO) as add-on therapy, especially with eGFR >20 and albuminuria, but ACE/ARB is the foundational initial therapy.
Amlodipine — Amlodipine treats hypertension but lacks renoprotective effects in DKD.
Furosemide — Furosemide does not protect kidneys.
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Damage to the glomerular filtration barrier (podocytes, GBM, endothelium) increases permeability to albumin and larger proteins. Proteinuria drives hypoalbuminemia → reduced oncotic pressure → edema. Hepatic compensatory synthesis raises lipoproteins (hyperlipidemia). Loss of antithrombin III, protein C/S, and immunoglobulins predisposes to thrombosis and infection.
Clinical presentation
Symptoms
Insidious or rapid-onset peripheral edema — periorbital in morning, dependent later
Foamy or frothy urine (proteinuria)
Weight gain, abdominal distention (ascites)
Dyspnea (pleural effusions), fatigue
Symptoms of underlying cause: rash, joint pain (SLE), polyuria/polydipsia (diabetes)
Muehrcke lines (transverse white nail bands), xanthelasma
Classic findings
Periorbital edema in a child = consider minimal change disease until proven otherwise.
Differential diagnosis
Minimal change disease — Most common in children; abrupt nephrotic onset; normal light microscopy; podocyte effacement on EM; steroid-responsive
Focal segmental glomerulosclerosis (FSGS) — Common in adults, especially Black patients (APOL1); HIV, obesity, heroin; segmental sclerosis on biopsy
Membranous nephropathy — Most common primary nephrotic syndrome in white adults; anti-PLA2R antibody positive in ~70% primary; subepithelial deposits, 'spike and dome'
Nephrotic syndrome diagnosed by: proteinuria >3.5 g/day, hypoalbuminemia <3.0 g/dL, edema, hyperlipidemia. Kidney biopsy is standard in adults to determine specific pathology and guide therapy (excepting clear diabetic nephropathy).
Labs
24-h urine protein OR spot UPCR (>3.5 g/g diagnostic)
Urinalysis with microscopy — oval fat bodies, fatty casts, 'Maltese cross' under polarized light
Serum albumin (<3.0 g/dL), lipid panel (elevated), creatinine, BMP
Hep B, Hep C, HIV serologies
ANA, complement (C3, C4), SPEP/UPEP with free light chains
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.