Presentation
Which feature distinguishes nephrotic syndrome from nephritic syndrome?
A. Hematuria
B. Proteinuria >3.5 g/day
C. Hypertension
D. Oliguria
B. Proteinuria >3.5 g/day
A 50-year-old man presents with nephrotic syndrome. What is the most common secondary cause of nephrotic syndrome in adults?
A. Diabetes mellitus
B. Hypertension
C. HIV infection
D. Hepatitis C virus
A. Diabetes mellitus
A 30-year-old man presents with diffuse swelling that developed rapidly over the course of several days. He is diagnosed with the nephrotic syndrome, and a renal biopsy reveals features consistent with focal segmental glomerulosclerosis.
He is afebrile, and his blood pressure is 158/86 mm Hg. Other than the presence of anasarca, the physical examination is unremarkable.
Laboratory studies reveal a urinary protein level of 9600 mg/24 hr (reference range, <150). A test for HIV infection is negative, as is testing for APOL1 risk alleles.
In addition to initiating therapy with an angiotensin-converting-enzyme inhibitor, which one of the following treatments is most appropriate for this patient?
A. Tacrolimus
B. Cyclophosphamide
C. Prednisone
D. Cyclosporine
E. Mycophenolate mofetil
C. Prednisone
First-line therapy for primary focal segmental glomerulosclerosis (FSGS), along with an angiotensin-converting-enzyme inhibitor to reduce proteinuria. The clinical features of the nephrotic syndrome include hypoalbuminemia, edema, and nephrotic-range proteinuria (>3500 mg/24 hr). Hyperlipidemia is also commonly seen, as is lipiduria with fatty casts.
A 67-year-old man is admitted for evaluation of recurrent deep vein thrombosis (DVT). He has had 2 episodes in the past 6 months despite adherence to anticoagulation. He reports progressive fatigue but denies edema. Physical exam: normal vital signs, no obvious swelling of the legs, and no ascites.
Labs:
Serum creatinine: 1.1 mg/dL
Serum albumin: 1.7 g/dL
Total cholesterol: 385 mg/dL
Urinalysis: 3+ protein, no hematuria, oval fat bodies
24-hour urine protein: 5.2 g
Which of the following is the most likely underlying diagnosis?
A. Antithrombin III deficiency
B. Nephrotic syndrome with membranous nephropathy
C. Factor V Leiden mutation
D. Chronic liver disease
B. Nephrotic syndrome with membranous nephropathy
This patient presents not with edema (the usual hallmark), but with recurrent venous thromboembolism.
In nephrotic syndrome, loss of antithrombin III, protein C, and protein S in the urine creates a hypercoagulable state. Renal vein thrombosis and recurrent DVT/PE are well-known complications.
His labs show the other diagnostic hallmarks of nephrotic syndrome:
Heavy proteinuria (>3.5 g/day)
Hypoalbuminemia (<2.5 g/dL)
Hyperlipidemia (cholesterol 385 mg/dL)
A 60-year-old man with diabetes mellitus presents with proteinuria (>3.5 g/day). What finding on kidney biopsy is most characteristic?
A. Kimmelstiel–Wilson nodules
B. Spike and dome appearance
C. Segmental sclerosis
D. Minimal mesangial change
A. Kimmelstiel–Wilson nodules
A 60-year-old woman with nephrotic syndrome is found to have LDL 190 mg/dL. She asks if she should start a statin. What is the next best step?
A. Defer, as hyperlipidemia resolves with remission
B. Start statin now, as she meets standard indications for therapy
C. Begin niacin therapy
D. Start fibrate therapy only
B. Start statin now, as she meets standard indications for therapy
AAFP: Do not treat dyslipidemia solely due to NS, but if patient meets regular lipid guidelines (e.g., LDL >190), statins are indicated
A 22-year-old man presents with edema, foamy urine, and hypertension. UA: 4+ protein, RBC casts, dysmorphic RBCs. Which diagnosis is most likely?
A. Nephrotic syndrome
B. Nephritic-nephrotic syndrome overlap
C. Isolated nephritic syndrome
D. Isolated proteinuria without syndrome
B. Nephritic-nephrotic overlap
Proteinuria + hematuria with casts suggests mixed syndrome (e.g., lupus, membranoproliferative GN).
A 34-year-old woman presents with nephrotic syndrome. She reports heavy NSAID use for chronic migraines. What is the most likely cause?
A. Membranous nephropathy
B. Minimal change disease
C. Focal segmental glomerulosclerosis
D. IgA nephropathy
B. Minimal change disease
NSAIDs can cause drug-induced minimal change disease
A 50-year-old woman with long-standing rheumatoid arthritis reports a one-year history of gradually progressive lower-extremity edema despite treatment with furosemide and metolazone. Echocardiography shows no evidence of heart disease.
Laboratory testing yields the following results:
Albumin 2.9
Total cholesterol 220
Creatinine 2
ESR 88
Anti-double-stranded DNA, complement C3, and complement C4 results are normal. A 24-hour urine collection reveals 5800 mg of protein (reference range, <150). Urine microscopy identifies 2 red cells per high-power field (0–2).
Which one of the following conditions is the most likely cause of this patient’s proteinuria and diminished kidney function?
A. Reactive systemic (AA) amyloidosis
B. Lupus nephritis
C. Immunoglobulin A nephropathy
D. Post-infectious glomerulonephritis
E. Chronic interstitial nephritis
A. Reactive systemic (AA) amyloidosis
Amyloidosis refers to the deposition of low-molecular-weight fibrils in extracellular tissue. The two most common forms of systemic amyloidosis are primary (AL) amyloidosis and secondary or reactive (AA) amyloidosis. Reactive systemic (AA) amyloidosis can complicate chronic inflammatory disorders that are associated with a sustained acute-phase response, such as rheumatoid arthritis, periodic fever syndromes, inflammatory bowel disease, and tuberculosis. The major sites of amyloid deposition are the kidneys, heart, and liver; however, in some conditions, amyloid deposition can be limited to one organ, such as the kidney.
This patient has nephrotic syndrome and a polyclonal gammopathy without an M spike in the setting of chronic inflammation or infection; this constellation of findings is characteristic of a secondary cause of amyloidosis (AA).
A 69-year-old white man comes to the physician because of a 15-day history of fatigue and lower leg swelling. Over the past 8 months, he has had a 3.8-kg (8.3-lb) weight loss. He has smoked one pack of cigarettes daily for 48 years. Vital signs are within normal limits. He appears thin. Examination shows 2+ pretibial edema bilaterally. An x-ray of the chest shows a right upper lobe density.
Laboratory studies show:
UA: Protein 4+
Light microscopic examination of a kidney biopsy shows thickening of glomerular capillary loops and the basal membrane.
Which of the following is the most likely diagnosis?
A. Granulomatosis with polyangiitis
B. Membranoproliferative glomerulonephritis
C. Focal segmental glomerulosclerosis
D. Rapidly progressive glomerulonephritis
E. Membranous nephropathy
E. Membranous nephropathy
Most common cause of nephrotic syndrome in White adults. Although the majority of cases are idiopathic, the condition can arise in association with solid malignancies, such as lung cancer, particularly in patients > 65 years. Deposition of antibodies between podocytes and the basal membrane causes thickening of glomerular capillary loops and the basal membrane, which in turn leads to nephrotic syndrome.
A 28-year-old woman comes to the emergency department 4 hours after the sudden onset of flank pain and nausea. Initially, the pain was limited to her left flank, but 1 hour ago, her right flank also started to hurt. During this time, she also noticed blood in her urine and gradually worsening swelling of her legs. She was diagnosed with membranous nephropathy 5 months ago, for which she takes enalapril and rituximab.
Her temperature is 37°C (98.6°F), pulse is 97/min, and blood pressure is 137/82 mm Hg. Physical examination shows a distended abdomen, bilateral flank tenderness, and 2+ pitting edema of both lower extremities.
Two weeks ago, her serum creatinine concentration and blood urea nitrogen were 1.5 mg/dL and 19 mg/dL, respectively.
Abdominal ultrasonography shows bilaterally enlarged kidneys. Which of the following is the most appropriate next step in diagnosis?
A. MR venography
B. 24-hour urine profile
C. CT angiography
D. Renal scintigraphyA. MR venography
A 7-year-old boy is brought to the physician by his parents because of persistent swelling of his face and legs. Two months ago, he was diagnosed with nephrotic syndrome, and high-dose oral prednisone was initiated. Physical examination shows periorbital and bilateral lower extremity edema.
Results of laboratory studies are shown:
Serum Albumin 1.7 g/dL
Creatinine 0.5 mg/dL
Urine
Blood negative
Protein 4+
Which of the following is the most appropriate next step in management?
A. Obtain renal ultrasound
B. Perform a renal biopsy
C. Start empiric intravenous cyclophosphamide
D. Continue high-dose oral prednisone
E. Check serum complement levels
B. Perform a renal biopsy
Nephrotic syndrome that does not resolve after 8 weeks of corticosteroid therapy is classified as steroid-resistant nephrotic syndrome (SRNS).
Distinguish minimal change disease (MCD) from other glomerulopathies (e.g., focal segmental glomerulosclerosis, membranous nephropathy), which are more likely to be steroid-resistant and may require alternative immunosuppressive therapies
MCD: 80–90% responding within 4 weeks.