Nephrotic syndrome

Pathophysiology - Leaky Kidney Chaos

Primary Insult: Damage to glomerular basement membrane (GBM) & podocyte foot processes.
Core Defect: Loss of negative charge & size barrier → massive leakage of plasma proteins.

Normal vs. Nephrotic Syndrome Glomerular Barrier

Consequences:
- Edema: Periorbital, pitting, can lead to anasarca.
- Hyperlipidemia: ↑ liver production of lipids.
  - Lipiduria: Oval fat bodies in urine (Maltese cross sign).
- Thrombosis Risk: ↑ loss of Antithrombin III in urine.

⭐ The hypercoagulable state, particularly renal vein thrombosis, is a classic and dangerous complication due to urinary loss of anticoagulant factors.

Etiology - The Usual Suspects

Primary Glomerular Disease (Idiopathic)
- Minimal Change Disease (MCD): Most common cause in children.
- Focal Segmental Glomerulosclerosis (FSGS): Most common cause in adults of African ancestry; associated with HIV, heroin use, obesity.
- Membranous Nephropathy: Most common cause in Caucasian adults.
- Membranoproliferative Glomerulonephritis (MPGN): Mixed nephrotic-nephritic picture.
Secondary Causes
- Systemic Disease: Diabetes Mellitus (most common secondary cause), SLE, Amyloidosis.
- Infection: Hepatitis B & C, HIV.
- Drugs: NSAIDs, penicillamine, gold salts.
- Malignancy: Lymphoma (MCD), solid tumors (Membranous).

⭐ In an older patient (>60 yrs) with new-onset nephrotic syndrome, suspect Membranous Nephropathy and screen for an underlying solid tumor (e.g., lung, colon).

Electron microscopy of minimal change disease

Diagnosis - Puffy Patient Puzzle

Urinalysis: Initial screen shows proteinuria. Key finding is heavy proteinuria: >3.5 g/24h or urine protein/creatinine ratio (UPCR) >3.5.
Blood Tests:
- Hypoalbuminemia: Serum albumin <3 g/dL.
- Hyperlipidemia: ↑ LDL, ↑ cholesterol.
Microscopy: Lipiduria with oval fat bodies.

⭐ Under polarized light, oval fat bodies containing cholesterol esters appear as classic “Maltese crosses.”

Kidney Biopsy: Gold standard to identify the specific underlying glomerular disease (e.g., MCD, FSGS, MN).

Management & Complications - Damage Control Duty

General Management
- Diet: Salt restriction (<2 g/day), fluid restriction.
- Proteinuria: ACE inhibitors or ARBs.
Specific Therapy
- Edema: Loop diuretics (furosemide).
- Hyperlipidemia: HMG-CoA reductase inhibitors (statins).
- Thrombosis Prophylaxis: Consider anticoagulation if albumin is <2.5 g/dL or with other risk factors.
Key Complications
- Thromboembolism: Due to loss of antithrombin III. Most common is renal vein thrombosis.
- Infection: Loss of immunoglobulins (IgG) increases risk from encapsulated bacteria (e.g., S. pneumoniae).

⭐ In a patient with nephrotic syndrome, the sudden onset of flank pain, hematuria, and fever should raise high suspicion for renal vein thrombosis.

Nephrotic syndrome is defined by massive proteinuria (>3.5 g/day), hypoalbuminemia, generalized edema, and hyperlipidemia/lipiduria.

The core pathology is podocyte injury, which compromises the glomerular filtration barrier, leading to protein loss.

Minimal Change Disease is the most common cause in children and shows effacement of foot processes on EM.

Membranous Nephropathy is the most common primary cause in white adults.

FSGS is the most frequent cause in African American and Hispanic adults.

Major complications include thromboembolism and increased susceptibility to infections.

Nephrotic syndrome US Medical PG Practice Questions and MCQs

Practice US Medical PG questions for Nephrotic syndrome. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.

Nephrotic syndrome US Medical PG Question 1: A 43-year-old man comes to the physician for a 1-week history of swelling around his eyes and decreased urination. His pulse is 87/min, and blood pressure is 152/95 mm Hg. Physical examination shows 1+ periorbital and pretibial edema. Serum studies show a urea nitrogen concentration of 21 mg/dL and a creatinine concentration of 1.4 mg/dL. Urinalysis shows 3+ blood and 1+ protein. Further evaluation of this patient is most likely to show which of the following?

A. Urinary rhomboid crystals
B. Renal interstitial inflammation
C. Hypoalbuminemia
D. Detached renal tubular epithelial cells
E. Red blood cell casts (Correct Answer)

Nephrotic syndrome Explanation: ***Red blood cell casts*** - The patient's presentation with **periorbital and pretibial edema**, **hypertension**, elevated **creatinine**, **hematuria** (3+ blood), and mild **proteinuria** (1+ protein) is highly suggestive of **acute glomerulonephritis**. - **Red blood cell casts** are pathognomonic for **glomerulonephritis**, indicating that red blood cells are leaking from the glomeruli and congealing in the renal tubules. *Urinary rhomboid crystals* - **Urinary rhomboid crystals** are typically associated with conditions like **uric acid nephrolithiasis** or gout, which are not suggested by the patient's symptoms or lab findings. - Their presence would indicate a risk for **kidney stones**, not evidence of glomerular inflammation. *Renal interstitial inflammation* - **Renal interstitial inflammation** is characteristic of **acute interstitial nephritis**, which often presents with fever, rash, eosinophilia, and flank pain, usually due to drug reactions or infections. - While kidney injury can occur, the primary findings of **hematuria** and **proteinuria** in this context strongly point away from an interstitial process as the initial diagnosis. *Hypoalbuminemia* - **Hypoalbuminemia** is a hallmark of **nephrotic syndrome**, characterized by severe proteinuria (>3.5 g/day), significant edema, and hyperlipidemia. - This patient has only 1+ proteinuria, which is not severe enough to cause significant hypoalbuminemia or the full nephrotic picture. *Detached renal tubular epithelial cells* - **Detached renal tubular epithelial cells** and **tubular cell casts** are characteristic findings in **acute tubular necrosis (ATN)**, usually resulting from ischemia or nephrotoxins. - While ATN can cause acute kidney injury, the prominent **hematuria** and **hypertension** in this case are more indicative of a glomerular process than tubular damage.

Nephrotic syndrome US Medical PG Question 2: A 44-year-old man comes to the physician because of a 2-week history of lower extremity swelling and frothy urine. He has a history of chronic hepatitis C infection. Physical examination shows 3+ pitting edema of the lower legs and ankles. Further evaluation of this patient is most likely to show which of the following?

A. Decreased cholesterol
B. Decreased blood urea nitrogen
C. Increased antithrombin III
D. Decreased cystatin C
E. Increased lipoproteins (Correct Answer)

Nephrotic syndrome Explanation: ***Increased lipoproteins*** - The patient's symptoms (**lower extremity swelling**, **frothy urine**) and history of **hepatitis C infection** are highly suggestive of **nephrotic syndrome**. - **Nephrotic syndrome** is characterized by severe proteinuria, leading to **hypoalbuminemia**, edema, and often **compensatory hyperlipidemia** (increased lipoproteins) due to increased hepatic synthesis of lipids. *Decreased cholesterol* - **Nephrotic syndrome** typically leads to **hyperlipidemia**, including **elevated cholesterol levels**, not decreased, as the liver compensates for protein loss by increasing lipid synthesis. - This is a key diagnostic feature differentiating nephrotic syndrome from other conditions that might cause edema. *Decreased blood urea nitrogen* - In **nephrotic syndrome**, kidney function might initially be preserved, or kidney injury could lead to **increased BUN** if glomerular filtration rate (GFR) significantly declines. - **Decreased BUN** is usually seen in conditions like liver failure, overhydration, or low protein diet, which are not suggested by the clinical picture. *Increased antithrombin III* - Patients with **nephrotic syndrome** typically have **decreased levels of antithrombin III** due to urinary loss of this anticoagulant protein, increasing their risk of **thrombosis**. - Therefore, an increase in antithrombin III would be highly unlikely and is contrary to the pathophysiology of nephrotic syndrome. *Decreased cystatin C* - **Cystatin C** is an endogenous marker of **renal function** (similar to creatinine), and its levels usually **increase** when glomerular filtration rate (GFR) decreases, indicating kidney impairment. - A decrease in cystatin C would suggest improved or hyper-filtration, which is not consistent with the signs of kidney damage seen in nephrotic syndrome.

Nephrotic syndrome US Medical PG Question 3: A 57-year-old immigrant from Nigeria presents to the emergency department for sudden, severe pain and swelling in her lower extremity. She was at a rehabilitation hospital when her symptoms became apparent. The patient has a past medical history of obesity, diabetes, bipolar disorder, and tonic-clonic seizures. Her current medications include metformin, insulin, lisinopril, and valproic acid. The patient is a prominent IV drug and alcohol user who has presented to the ED many times for intoxication. On physical exam you note anasarca and asymmetric lower extremity swelling. Based on the results of a doppler ultrasound of her swollen lower extremity, heparin is started. The patient is then transferred to the general medicine floor for continued management. Laboratory studies are shown below. Serum: Na+: 137 mEq/L K+: 5.5 mEq/L Cl-: 100 mEq/L HCO3-: 24 mEq/L Urea nitrogen: 22 mg/dL Ca2+: 5.7 mg/dL Creatinine: 1.7 mg/dL Glucose: 70 mg/dL The patient's presentation includes generalized edema (anasarca) along with laboratory abnormalities. What is the most likely underlying diagnosis that explains her overall clinical presentation?

A. Liver failure
B. Nephrotic syndrome (Correct Answer)
C. Antithrombin III deficiency
D. Prothrombin gene mutation
E. Factor V Leiden

Nephrotic syndrome Explanation: ***Nephrotic syndrome*** - The patient presents with **anasarca** (generalized edema), **asymmetric lower extremity swelling**, and laboratory findings consistent with **nephrotic syndrome**. - Classic features present: **anasarca** (from hypoalbuminemia and fluid retention), **hypercoagulable state** leading to DVT (loss of antithrombin III in urine), and **renal dysfunction** (elevated creatinine 1.7 mg/dL). - The **hypocalcemia (5.7 mg/dL)** is explained by low albumin—total calcium appears low because ~40% of serum calcium is albumin-bound; ionized calcium is likely normal. - Nephrotic syndrome is characterized by: heavy proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edema—this patient's presentation fits this diagnosis. - Risk factors include diabetes (diabetic nephropathy is a common cause of nephrotic syndrome in adults). *Liver failure* - Although **anasarca** and **edema** can occur in liver failure due to decreased albumin synthesis and portal hypertension, the laboratory values do not show typical signs of severe hepatic dysfunction (e.g., elevated transaminases, bilirubin, or prolonged INR). - The **elevated creatinine** and **hypercoagulable state with DVT** point more towards a primary renal issue rather than liver failure. - Liver failure typically causes **hypocoagulability**, not the hypercoagulability seen here. *Antithrombin III deficiency* - This is a **hereditary thrombophilia** that increases the risk of **venous thromboembolism**, which could explain the DVT. - However, it does **not explain** the patient's **anasarca**, **hypocalcemia**, **elevated creatinine**, or generalized fluid retention. - This would be a complication of nephrotic syndrome (acquired AT-III deficiency from urinary loss), not the primary diagnosis. *Prothrombin gene mutation* - This is another **genetic thrombophilia** (G20210A mutation) that increases the risk of **blood clots**. - Similar to Antithrombin III deficiency, it accounts for DVT risk but **fails to explain** the widespread edema, electrolyte abnormalities, and renal dysfunction. *Factor V Leiden* - The **Factor V Leiden mutation** is the most common inherited cause of **thrombophilia**, predisposing individuals to venous thromboembolism. - While relevant to explaining DVT in isolation, it does **not explain** the patient's severe generalized edema, hypocalcemia, or renal impairment—all of which are key to this clinical presentation.

Nephrotic syndrome US Medical PG Question 4: A 36-year-old man comes to the physician for a 4-week history of swollen legs. He has difficulty putting on socks because of the swelling. Two years ago, he was diagnosed with sleep apnea. He takes no medications. He emigrated from Guatemala with his family when he was a child. He is 171 cm (5 ft 6 in) tall and weighs 115 kg (253 lb); BMI is 39 kg/m2. His pulse is 91/min and blood pressure is 135/82 mm Hg. Examination shows periorbital and bilateral lower extremity edema. Serum Albumin 3.1 g/dL Total cholesterol 312 mg/dL Urine Blood negative Protein +4 RBC 1-2/hpf RBC cast negative Fatty casts numerous A renal biopsy is obtained. Which of the following is most likely to be seen under light microscopy of the patient's renal biopsy specimen?

A. Diffuse thickening of glomerular capillaries
B. Amyloid deposition in the mesangium
C. Eosinophilic nodules within the glomeruli
D. Fibrin crescents within the glomerular space
E. Segmental sclerosis of the glomeruli (Correct Answer)

Nephrotic syndrome Explanation: ***Segmental sclerosis of the glomeruli*** - The patient presents with **nephrotic syndrome** (edema, proteinuria, hypoalbuminemia, hypercholesterolemia) and **obesity** (BMI 39 kg/m2), which are strong risk factors for **focal segmental glomerulosclerosis (FSGS)**. - **FSGS** is characterized by **segmental sclerosis** within some glomeruli, often affecting juxtamedullary glomeruli initially. *Diffuse thickening of glomerular capillaries* - **Diffuse thickening of glomerular capillaries** (due to subepithelial immune complex deposition causing SPIKES on silver stain) is characteristic of **membranous nephropathy**, which typically presents with nephrotic syndrome but is not directly linked to obesity in the way FSGS is. - While membranous nephropathy could cause nephrotic syndrome, the association with **morbid obesity** makes FSGS a stronger consideration. *Amyloid deposition in the mesangium* - **Amyloid deposition** typically presents with nephrotic syndrome and is associated with chronic inflammatory conditions or plasma cell dyscrasias, not primarily with obesity or the specific presentation described. - On light microscopy, amyloid appears as **acellular, eosinophilic congophilic deposits** in the mesangium and capillary walls, showing apple-green birefringence under polarized light, which is not suggested by the clinical picture. *Eosinophilic nodules within the glomeruli* - **Eosinophilic nodules within the glomeruli** (Kimmelstiel-Wilson lesions) are characteristic of **diabetic nephropathy**, which commonly causes nephrotic syndrome. - While the patient is obese, there is no information about diabetes or hyperglycemia to suggest diabetic nephropathy as the primary cause. *Fibrin crescents within the glomerular space* - **Fibrin crescents within the glomerular space** are indicative of **rapidly progressive glomerulonephritis (RPGN)**, which typically presents as nephritic syndrome (hematuria, hypertension, azotemia) rather than pure nephrotic syndrome. - The patient's urine microscopic findings show only 1-2 RBC/hpf and no RBC casts, making RPGN unlikely.

Nephrotic syndrome US Medical PG Question 5: A 12-year-old boy is brought to the physician for a well-child examination. He feels well. He has no history of serious illness. He has received all age-appropriate screenings and immunizations. His 7-year-old brother was treated for nephrotic syndrome 1 year ago. He is at 50th percentile for height and 60th percentile for weight. His temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 96/54 mm Hg. Physical examination shows no abnormalities. Urine dipstick shows 1+ protein. A subsequent urinalysis of an early morning sample shows: Blood negative Glucose negative Protein trace Leukocyte esterase negative Nitrite negative RBC none WBC 0–1/hpf Protein/creatinine ratio 0.2 (N ≤ 0.2) Which of the following is the most appropriate next step in management?

A. Anti-nuclear antibody level
B. Repeat urine dipstick in 1 year (Correct Answer)
C. Measure serum creatinine and urea nitrogen
D. 24-hour urine protein collection
E. Lipid profile

Nephrotic syndrome Explanation: ***Repeat urine dipstick in 1 year*** - The initial 1+ protein on a random dipstick with a normal early morning protein/creatinine ratio (0.2, which is ≤0.2) is consistent with **benign orthostatic (postural) proteinuria** in an otherwise healthy adolescent. - **Orthostatic proteinuria** is a common, benign finding in adolescents where protein appears in upright position but resolves when supine (hence the trace protein in early morning sample). - Given the patient is asymptomatic, has normal vital signs, no edema, and a normal protein/creatinine ratio, this represents a benign condition requiring only monitoring with annual urine dipstick to ensure no progression. - The family history of nephrotic syndrome in his brother does not change management in this asymptomatic patient with normal findings. *Anti-nuclear antibody level* - An **ANA level** is used to screen for **systemic lupus erythematosus** (SLE) and other autoimmune diseases that can cause glomerulonephritis. - The patient has no symptoms or signs (e.g., rash, joint pain, serositis, hematuria) suggestive of an autoimmune condition, and the normal protein/creatinine ratio makes significant renal pathology unlikely. *Measure serum creatinine and urea nitrogen* - This would be appropriate if there was evidence of **renal dysfunction**, such as persistent abnormal proteinuria (protein/creatinine ratio >0.2), elevated blood pressure, or other signs of kidney disease. - The patient has normal blood pressure, no edema, and a normal protein/creatinine ratio indicating no impaired kidney function. *24-hour urine protein collection* - A **24-hour urine collection** is indicated when there is sustained, significant proteinuria that needs quantification (e.g., to confirm nephrotic syndrome with >3.5 g/day or to monitor chronic kidney disease). - The patient's normal protein/creatinine ratio (0.2) already provides adequate quantification and confirms the initial 1+ protein was transient orthostatic proteinuria, making 24-hour collection unnecessary. *Lipid profile* - A **lipid profile** is typically ordered in cases of suspected or confirmed **nephrotic syndrome**, as dyslipidemia is a common complication. - This patient does not have nephrotic syndrome, which requires proteinuria >3.5 g/day (protein/creatinine ratio >3.5), hypoalbuminemia, edema, and hyperlipidemia—none of which are present.

Nephrotic syndrome US Medical PG Question 6: A 65-year-old man comes to the physician because of increasing swelling of the legs and face over the past 2 months. He has a history of diastolic heart dysfunction. The liver and spleen are palpable 4 cm below the costal margin. On physical examination, both lower limbs show significant pitting edema extending above the knees and to the pelvic area. Laboratory studies show: Serum Cholesterol 350 mg/dL (<200 mg/dL) Triglycerides 290 mg/dL (35–160 mg/dL) Calcium 8 mg/dL Albumin 2.8 g/dL Urea nitrogen 54 mg/dL Creatinine 2.5 mg/dL Urine Blood 3+ Protein 4+ RBC 15–17/hpf WBC 1–2/hpf RBC casts Many Echocardiography shows concentrically thickened ventricles with diastolic dysfunction. Skeletal survey shows no osteolytic lesions. Which of the following best explains these findings?

A. Smoldering multiple myeloma
B. Monoclonal gammopathy of undetermined significance
C. Waldenstrom’s macroglobulinemia
D. AL amyloidosis (Correct Answer)
E. Symptomatic multiple myeloma

Nephrotic syndrome Explanation: ***AL amyloidosis*** - The combination of **nephrotic syndrome** (edema, proteinuria, hypoalbuminemia, hyperlipidemia) with **renal failure** (elevated BUN and creatinine, RBC casts) and **restrictive cardiomyopathy** (diastolic dysfunction, concentrically thickened ventricles) is highly suggestive of **AL (light chain) amyloidosis**. - **Hepatomegaly** (palpable liver) further supports the diagnosis of systemic amyloidosis due to amyloid deposition in the liver. *Smoldering multiple myeloma* - Characterized by high levels of **monoclonal protein** and **plasma cells in the bone marrow** but **without CRAB features** (HyperCalcemia, Renal failure, Anemia, Bone lesions). - This patient presents with **renal failure** and **cardiac involvement**, which are symptomatic and thus inconsistent with smoldering multiple myeloma. *Monoclonal gammopathy of undetermined significance* - Defined by the presence of a **monoclonal protein** in the serum or urine but **without evidence of multiple myeloma, amyloidosis, or related disorders**. - This patient exhibits significant **organ damage** indicative of systemic disease, ruling out MGUS. *Waldenstrom's macroglobulinemia* - A low-grade lymphoma characterized by **IgM monoclonal gammopathy** and **lymphoplasmacytic infiltration of the bone marrow**. - It often causes **hyperviscosity syndrome**, lymphadenopathy, and peripheral neuropathy, which are not the primary features in this case. *Symptomatic multiple myeloma* - Requires evidence of **CRAB features** (HyperCalcemia, Renal failure, Anemia, Bone lesions) in addition to monoclonal protein and bone marrow plasma cells. - While **renal failure** is present, the prominent **cardiac involvement** (restrictive cardiomyopathy) and the specific nature of the renal disease (nephrotic range proteinuria, RBC casts suggesting glomerular involvement) are more characteristic of AL amyloidosis rather than typical multiple myeloma kidney.

Nephrotic syndrome US Medical PG Question 7: A 48-year-old man comes to the emergency department because of sudden right flank pain that began 3 hours ago. He also noticed blood in his urine. Over the past two weeks, he has developed progressive lower extremity swelling and a 4-kg (9-lb) weight gain. Examination shows bilateral 2+ pitting edema of the lower extremities. Urinalysis with dipstick shows 4+ protein, positive glucose, and multiple red cell and fatty casts. Abdominal CT shows a large right kidney with abundant collateral vessels and a filling defect in the right renal vein. Which of the following is the most likely underlying cause of this patient's symptoms?

A. Factor V Leiden
B. Malignant erythropoietin production
C. Antiphospholipid antibodies
D. Increased lipoprotein synthesis
E. Loss of antithrombin III (Correct Answer)

Nephrotic syndrome Explanation: ***Loss of antithrombin III*** - The patient presents with **nephrotic syndrome** (lower extremity edema, weight gain, 4+ proteinuria, fatty casts), which causes massive urinary loss of proteins, including **antithrombin III**, a critical inhibitor of coagulation. - Loss of **antithrombin III** creates a **hypercoagulable state**, predisposing to **renal vein thrombosis** (RVT), which explains the acute flank pain, hematuria, enlarged kidney, and filling defect on CT. - This is the underlying mechanism linking the nephrotic syndrome to the thrombotic complication. *Factor V Leiden* - This is a **genetic mutation** causing Factor V resistance to activated protein C, leading to hypercoagulability. - While it can cause venous thrombosis, it does **not cause nephrotic syndrome** with massive proteinuria and fatty casts as seen in this patient. - This would be a predisposing factor, not the underlying cause of the nephrotic syndrome itself. *Antiphospholipid antibodies* - These antibodies cause a **hypercoagulable state** and can lead to both arterial and venous thromboses, including RVT. - However, they do **not directly cause nephrotic syndrome** with the massive proteinuria and fatty casts seen here. - Like Factor V Leiden, this would predispose to thrombosis but doesn't explain the primary renal pathology. *Increased lipoprotein synthesis* - This is a **consequence** of nephrotic syndrome, where hepatic compensation for albumin loss leads to increased synthesis of all proteins, including lipoproteins, causing hyperlipidemia. - It is a **secondary effect**, not the mechanism causing the hypercoagulable state and renal vein thrombosis. *Malignant erythropoietin production* - This would cause **polycythemia** (increased RBC count) and potentially thrombotic events due to hyperviscosity. - It does **not explain** the profound nephrotic syndrome with massive proteinuria, edema, and fatty casts. - There is no evidence of polycythemia in this clinical presentation.

Nephrotic syndrome US Medical PG Question 8: A 10-year-old boy presents to your office with puffy eyes. The patient's mother states that his eyes seem abnormally puffy and thinks he may have an eye infection. Additionally, he had a sore throat a week ago which resolved with over the counter medications. The mother also thought that his urine was darker than usual and is concerned that blood may be present. His temperature is 99.5°F (37.5°C), blood pressure is 107/62 mmHg, pulse is 100/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for bilateral periorbital edema. Cranial nerves are grossly intact bilaterally. Which of the following is the most likely finding on renal biopsy for this patient?

A. Sub-epithelial electron dense deposits on electron microscopy (Correct Answer)
B. Linear Ig deposits along the basement membrane
C. Podocyte fusion on electron microscopy
D. Alternating thickening and thinning of basement membrane with splitting of the lamina densa
E. No abnormalities

Nephrotic syndrome Explanation: ***Sub-epithelial electron dense deposits on electron microscopy*** - The patient's presentation with periorbital edema, dark urine (suggesting hematuria), and a recent history of pharyngitis strongly points towards **post-streptococcal glomerulonephritis (PSGN)**. - Renal biopsy in PSGN characteristically shows **sub-epithelial humps** (electron-dense deposits) primarily composed of IgG and C3, which are best visualized on electron microscopy. *Linear Ig deposits along the basement membrane* - **Linear immunoglobulin G (IgG) deposits** along the glomerular basement membrane (GBM) are characteristic of **Goodpasture syndrome (anti-GBM disease)**. - This condition presents with rapidly progressive glomerulonephritis and often pulmonary hemorrhage, which is not suggested by this patient's symptoms. *Podocyte fusion on electron microscopy* - **Podocyte effacement** (fusion of foot processes) is the hallmark finding in **minimal change disease**. - Minimal change disease typically presents with **nephrotic syndrome** (heavy proteinuria, hypoalbuminemia, severe edema) without significant hematuria or a history of recent infection. *Alternating thickening and thinning of basement membrane with splitting of the lamina densa* - This description is characteristic of **Alport syndrome**, an inherited disorder affecting collagen IV. - Alport syndrome presents with progressive hematuria, sensorineural hearing loss, and ocular abnormalities, which are not mentioned in this acute presentation. *No abnormalities* - Given the patient's clear symptoms of **nephritic syndrome** (edema, hematuria following infection), it is highly unlikely that a renal biopsy would show no abnormalities. - A significant pathological process is indicated by the clinical picture.

Nephrotic syndrome US Medical PG Question 9: A 43-year-old man is referred by his family physician because his urine dipstick reveals 3+ protein and urinalysis reveals 1-2 red cells/high power field, but is otherwise negative. He does not have any current complaints. His family history is irrelevant. He denies smoking and alcohol use. His temperature is 36.7°C (98.06°F), blood pressure is 130/82 mm Hg, and pulse is 78/min. Physical examination is unremarkable. Which of the following is the best next step in the management of this patient’s condition?

A. Reassurance
B. Repeat the urine dipstick test
C. 24-hour urine collection (Correct Answer)
D. Start captopril
E. Urine culture

Nephrotic syndrome Explanation: ***24-hour urine collection*** - The presence of **3+ proteinuria on dipstick** (approximately ≥300 mg/dL) is significant and requires **quantification** to assess the degree of proteinuria and guide further management. - A **24-hour urine collection** is the traditional gold standard method to quantify total protein excretion and determine if the patient has clinically significant proteinuria (>150 mg/day is abnormal; >3.5 g/day indicates nephrotic-range proteinuria). - Alternatively, a **spot urine protein-to-creatinine ratio (PCR)** or **albumin-to-creatinine ratio (ACR)** can be used, but among the given options, 24-hour collection is the appropriate next step. - The concurrent finding of **microscopic hematuria (1-2 RBCs/hpf)** further supports the need for evaluation of possible **glomerular disease** or other renal pathology. *Repeat the urine dipstick test* - Repeating a dipstick is appropriate for **trace or 1+ proteinuria** to rule out transient causes (exercise, fever, orthostatic proteinuria, concentrated urine). - However, **3+ proteinuria is too significant** to simply repeat the dipstick; it requires quantification to determine the severity and guide further diagnostic workup (e.g., renal biopsy if nephrotic-range). *Urine culture* - While infection can cause proteinuria and hematuria, the urinalysis is described as "otherwise negative," suggesting an absence of **leukocytes, nitrites, or bacteria** typical of a urinary tract infection. - The patient is **asymptomatic** without dysuria, frequency, or fever, making infection unlikely. - A urine culture would be appropriate if there were clinical signs of UTI. *Reassurance* - Giving reassurance would be **inappropriate and potentially harmful** given the finding of **3+ proteinuria**, which is a significant indicator of potential renal pathology. - Proteinuria of this magnitude can indicate **glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis**, or other kidney diseases requiring further evaluation. - The presence of concurrent **microscopic hematuria** raises additional concern for glomerular disease. *Start captopril* - Captopril, an **ACE inhibitor**, is used to reduce proteinuria and provide renoprotection in patients with **confirmed chronic kidney disease**, particularly in the setting of **diabetes or hypertension**. - Initiating treatment is **premature** without first quantifying the proteinuria, establishing a diagnosis, and ruling out secondary causes. - The patient's blood pressure (130/82 mm Hg) is at the upper limit of normal but does not mandate immediate antihypertensive therapy before completing the diagnostic evaluation.

Nephrotic syndrome US Medical PG Question 10: A 21-year-old woman presents with malaise, joint pains, and a rash that worsens with sun exposure. Examination reveals an erythematous facial rash with edema. Her complete blood count shows lymphocytopenia. In addition to the most likely diagnosis, which of the following disorders can also cause lymphocytopenia? I. HIV II. Autoimmune disorders III. Tuberculosis IV. Lymphoma V. Hypersplenism

A. I, II, IV, V (Correct Answer)
B. III, V
C. I, II, III
D. III, IV
E. I, III, V

Nephrotic syndrome Explanation: ***I, II, IV, V*** - The patient's symptoms (malar rash, photosensitivity, joint pains, malaise, lymphocytopenia) are highly suggestive of **Systemic Lupus Erythematosus (SLE)**, an **autoimmune disorder** (II). - **HIV (I)** directly destroys CD4+ T lymphocytes, causing profound lymphocytopenia. - **Autoimmune disorders (II)** like SLE, rheumatoid arthritis, and Sjögren's syndrome cause lymphocytopenia via antibody-mediated destruction. - **Lymphoma (IV)** causes lymphocytopenia through bone marrow infiltration, increased consumption, or sequestration. - **Hypersplenism (V)** causes sequestration and destruction of lymphocytes along with other blood cells. - While disseminated tuberculosis can occasionally cause lymphocytopenia, **chronic tuberculosis typically causes lymphocytosis**, making it a less reliable answer. *III, V* - This option is incomplete as it correctly identifies hypersplenism but omits HIV, autoimmune disorders, and lymphoma, which are more consistent causes of lymphocytopenia. - **Tuberculosis (III)** in its chronic form typically causes **lymphocytosis**, not lymphocytopenia, though severe disseminated disease may cause lymphocytopenia. *I, II, III* - While HIV and autoimmune disorders are correct, including **tuberculosis (III)** is problematic as chronic TB typically causes **lymphocytosis**, not lymphocytopenia. - This option omits lymphoma and hypersplenism, both important causes. *III, IV* - **Tuberculosis (III)** in chronic form typically causes **lymphocytosis** rather than lymphocytopenia, making it an unreliable choice. - Although **lymphoma (IV)** is correct, this option excludes HIV, autoimmune disorders, and hypersplenism. *I, III, V* - **HIV (I)** and **hypersplenism (V)** are valid causes, but **tuberculosis (III)** is inconsistent as chronic TB typically causes lymphocytosis. - This option incorrectly includes tuberculosis while omitting autoimmune disorders and lymphoma.

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Nephrotic syndrome

On this page

Pathophysiology - Leaky Kidney Chaos

Etiology - The Usual Suspects

Diagnosis - Puffy Patient Puzzle

Management & Complications - Damage Control Duty

Practice Questions: Nephrotic syndrome

Flashcards: Nephrotic syndrome

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