Commit to an answer before revealing the explanation. Use the section menu to navigate; each question and answer has its own link. Five-option evidence updates ask for the most defensible direction of change; discuss a justified adjacent response.
Save and export your first responses
First choices and optional confidence stay in this browser and are not sent to the website. Opening an explanation first is recorded. Revisiting an unchanged case preserves the first response; revised cases receive a new version. Website visit analytics are separate. On a shared device, export and clear the history when finished.
Sections in this case
Question and answer links
- W1: Which set of findings defines nephrotic syndrome? · Answer
- W2: Which drug–kidney lesion pairing is correct? · Answer
- Q3: Mr. Kessler, 66, has gained 10 kg, has periorbital and thigh-high pitting edema, a jugular venous pressure of 6 cm, clea · Answer
- Q4: If you were thinking "diuretic-resistant heart failure," and you then learn that his BNP is 42 pg/mL — drawn this mornin · Answer
- Q5: Mr. Kessler's sodium is 131 mEq/L with a measured serum osmolality of 274 and urine osmolality of 420; he has thigh-high · Answer
- Q6: Day 7, nephrology clinic. The screen is back: A1c 5.5%; HIV, hepatitis B surface antigen, hepatitis C antibody, RPR and · Answer
- Q7: Day 18. Mr. Kessler, with membranous nephropathy and albumin 1.8, has new left flank pain and gross hematuria; creatinin · Answer
Session S3 · 2026-10-28 · supplementary · 20 min Anchor: Nephrotic syndrome in an adult (membranous nephropathy) presenting as "diuretic-resistant heart failure" · Integrates: edema evaluation (cardiac vs renal), drug-induced glomerular disease (NSAIDs), thrombosis as a complication, the AKI framework when a nephrotic patient's creatinine jumps, nephrotic diuretics, hypervolemic hyponatremia One-line hook: Two emergency visits, two furosemide prescriptions and a cardiology referral later, he is still swelling — and nobody has asked why.
Self-study case. Commit to an answer before you open each folded callout. The Session 5 readiness quiz samples one item from this case.
Learning Objectives
Answers for this section: W1 · W2 · Q3 · Q4 · Q5 · Q6 · Q7
- Sort generalized edema into cardiac, hepatic and renal causes from the neck veins, the albumin and the urine, and order the tests that separate them before escalating a diuretic.
- Define nephrotic syndrome, quantify proteinuria with a spot protein-to-creatinine ratio, and manage hypervolemic hyponatremia without saline.
- Run the adult secondary-cause screen for new nephrotic syndrome, interpret a positive anti-PLA2R antibody, and stop the drugs linked to glomerular disease.
- Prescribe nephrotic diuresis — sodium restriction, a loop diuretic at the right dose and frequency, a weight target — and know why "resistance" happens.
- When a nephrotic patient's creatinine jumps, sort prerenal, intrinsic and postrenal causes, recognize renal vein thrombosis, and know which decisions belong to nephrology.
Warm-Up (individual commit before the case)
Answers for this section: W1 · W2
W1The definition
Which set of findings defines nephrotic syndrome?
Hematuria with red-cell casts, hypertension, oliguria and a rising creatinine
Proteinuria of 0.5–3.5 g/day with dysmorphic red cells and a normal albumin
Proteinuria over 3.5 g/day, albumin under 3.0 g/dL, edema and high cholesterol
A 4+ dipstick protein on any single urine sample, whatever the albumin or the edema
Show answer and explanation · Link to this question
Correct answer: C
Learning point: Nephrotic syndrome is a leak: the glomerular filter loses so much protein (more than 3.5 g a day) that serum albumin falls below 3.0 g/dL, oncotic pressure falls and edema follows, while the liver's response drives cholesterol up. Oval fat bodies and fatty casts are its urine signature. Nephritic syndrome is inflammation: hematuria with red-cell casts, hypertension and a falling GFR, with less protein. Why not the others: A is nephritic syndrome; B is sub-nephrotic glomerular bleeding; D — a dipstick reads concentration, not grams a day, and one sample is not a syndrome. Course reading: Evidence for this case
W2Drug and lesion
Which drug–kidney lesion pairing is correct?
Pamidronate — primary membranous nephropathy
Hydralazine — ANCA-associated vasculitis
Lithium — anti-glomerular basement membrane disease
Naproxen — immunoglobulin A nephropathy
Show answer and explanation · Link to this question
Correct answer: B
Learning point: Hydralazine, like propylthiouracil and levamisole-cut cocaine, can trigger ANCA vasculitis, and stopping the drug is part of the treatment. The rest of the student table: NSAIDs → minimal change disease, membranous nephropathy and interstitial nephritis; lithium → FSGS or minimal change disease (and nephrogenic diabetes insipidus); pamidronate → FSGS, often the collapsing form. Why not the others: A — pamidronate's lesion is FSGS; C — lithium's are FSGS, minimal change disease and diabetes insipidus, not anti-GBM disease; D — NSAIDs cause minimal change, membranous and interstitial disease, not IgA nephropathy. Course reading: Evidence for this case
Part 1 — Presentation
Answers for this section: Q3 · Q4
Mr. Roy Kessler, 66, a retired county highway-crew foreman, comes to his primary care clinic after his second emergency visit in six weeks. The first visit's note says "CHF exacerbation" and started furosemide 40 mg daily; the second, ten days ago, says "diuretic-resistant heart failure," doubled the furosemide and placed a cardiology referral. An echocardiogram is booked for later this week. "The water pills aren't working," he says, "and my wife says my eyes are swollen shut every morning."
He has gained 10 kg in two months. His legs swell to the thighs by evening. His urine has been foamy "like a beer." He has no orthopnea, no waking breathless at night, no chest pain, and can walk his usual mile slowly because his legs feel heavy. Four months ago a gout flare in his right great toe was treated with naproxen, and he has taken it twice a day ever since "to keep the gout away." Before these visits he had never been told he had heart, kidney or liver disease. He has never smoked and drinks a beer a week. A screening colonoscopy at 62 was normal. The emergency department's chest X-ray, read ten days ago, showed a normal heart size and no pulmonary edema.
Vitals. BP 152/90 · Pulse 76, regular · Resp 16 · SpO₂ 97% on room air · T 36.7 °C · Weight 88 kg (78 kg two months ago) · Height 180 cm.
Exam. Puffy eyelids and face. Jugular venous pressure 6 cm H₂O at 45°, no hepatojugular reflux. Lungs clear. Heart regular, no S3, no murmur. Abdomen soft, no shifting dullness, liver not enlarged; no spider angiomas, no jaundice. Pitting edema 3+ to the mid-thighs and over the sacrum.
Medications
| Drug | Dose | Route | Frequency | Indication |
|---|---|---|---|---|
| Furosemide | 80 mg | PO | daily (40 mg until 10 days ago) | "Heart failure" (emergency department) |
| Naproxen | 500 mg | PO | twice daily, every day for 4 months | Gout prevention |
Q3Before the next diuretic
Mr. Kessler, 66, has gained 10 kg, has periorbital and thigh-high pitting edema, a jugular venous pressure of 6 cm, clear lungs and no S3, and a "diuretic-resistant heart failure" label on furosemide 80 mg daily. What is the most useful next step?
Add metolazone 2.5 mg daily to the furosemide to break the diuretic resistance
Keep the current furosemide dose and wait for this week's echocardiogram first
Order bilateral leg venous duplex scans to look for deep-vein thrombosis first
Urinalysis with microscopy, urine protein-to-creatinine ratio, albumin and BNP
Show answer and explanation · Link to this question
Correct answer: D
Learning point: Before a third diuretic, find the cause of the edema. Generalized edema comes from high capillary pressure (a failing heart or blocked veins) or low oncotic pressure (albumin lost through the kidney or not made by the liver), and the bedside already leans away from the heart: normal neck veins, clear lungs, no S3, periorbital swelling that is worst in the morning. A urinalysis with microscopy, a protein-to-creatinine ratio and a serum albumin test the kidney; a BNP tests the heart. A basic metabolic panel does not include albumin, which is how this gets missed. Why not the others: A — sequential nephron blockade escalates treatment for a diagnosis nobody has made; B — waits days on a heart test while the cheap test that answers the question goes undone; C — symmetric edema reaching the face is a systemic process, not two clots. Course reading: Evidence for this case
Q4Evidence update
Concordance-style practice: there is no expert panel behind this key, the teaching explanation. "Unchanged" means the finding does not move the hypothesis — not "I'm not sure."
If you were thinking "diuretic-resistant heart failure," and you then learn that his BNP is 42 pg/mL — drawn this morning, while he is 10 kg above his usual weight and swollen to the thighs — and his spot urine protein-to-creatinine ratio is 9.1 g/g, this hypothesis becomes:
Much less likely
Less likely
Unchanged
More likely
Much more likely
Show answer and explanation · Link to this question
Correct answer: A
Learning point: The very heavy proteinuria provides a compelling renal explanation for edema, while the low BNP reduces the likelihood of decompensated heart failure. BNP is influenced by treatment and patient factors and does not independently exclude heart failure; the subsequent echocardiogram adds information. The combination shifts the leading diagnosis toward nephrotic disease. Why not the others: B is defensible with a clear explanation of BNP limitations; C misses the strong alternative mechanism; D and E move toward the less-supported cause. The verbal degree is formative. Course reading: Evidence for this case
Part 2 — Data
Answers for this section: Q5 · Q6
Day 0, with the emergency department value from six weeks ago
| Test | Day 0 | 6 weeks ago | Reference range |
|---|---|---|---|
| Sodium | 131 | 137 | 135–145 mEq/L |
| Potassium | 4.3 | 4.4 | 3.5–5.0 mEq/L |
| Chloride | 100 | 103 | 98–107 mEq/L |
| Bicarbonate | 25 | 24 | 22–29 mEq/L |
| BUN | 22 | 18 | 7–20 mg/dL |
| Creatinine | 1.2 | 1.1 | 0.7–1.3 mg/dL |
| eGFR (CKD-EPI 2021) | 67 | 74 | ≥60 mL/min/1.73 m² |
| Glucose | 96 | 101 | 70–99 mg/dL |
| Albumin | 1.9 | — | 3.5–5.0 g/dL |
| Total cholesterol | 348 | — | <200 mg/dL |
| LDL cholesterol | 238 | — | <100 mg/dL |
| Serum osmolality (measured) | 274 | — | 275–295 mOsm/kg |
| Urine osmolality | 420 | — | 50–1,200 mOsm/kg (varies with intake) |
| BNP | 42 | — | <100 pg/mL |
| Urine protein-to-creatinine ratio | 9.1 | — | <0.2 g/g |
| Hemoglobin | 13.1 | 13.4 | 13.5–17.5 g/dL |
A note on the anion gap: 131 − (100 + 25) = 6. Albumin is the main unmeasured anion, so the gap falls 2.5 for every 1 g/dL of albumin below 4: corrected, 6 + 2.5 × 2.1 = 11, which is normal.
Urinalysis (fresh, clean-catch): specific gravity 1.018; protein 4+; blood 1+; glucose, leukocyte esterase and nitrite negative. Microscopy: oval fat bodies and fatty casts (Maltese crosses under polarized light), 3–5 RBC/hpf, no red-cell casts, 0–2 WBC/hpf.
Echocardiogram (day 3): left ventricular ejection fraction 60%, normal wall thickness and diastolic function, normal right ventricle, no valve disease.
Q5The sodium and the swelling
Mr. Kessler's sodium is 131 mEq/L with a measured serum osmolality of 274 and urine osmolality of 420; he has thigh-high edema, albumin 1.9, a UPCR of 9.1 g/g, eGFR 67, and takes furosemide 80 mg daily and naproxen 500 mg twice daily. Which plan fits him?
Give a liter of 0.9% saline for the sodium first, then furosemide 80 mg twice daily
Stop the furosemide, since it lowered his sodium, and restrict fluid to 1 L a day
Stop naproxen; sodium under 2 g and a fluid limit; furosemide 80 mg twice daily
Add hydrochlorothiazide 25 mg to the current furosemide today to break the resistance
Show answer and explanation · Link to this question
Correct answer: C
Learning point: His hyponatremia is hypervolemic — water held by ADH (urine osmolality 420) in a body already overloaded with salt and water — so it is treated with the edema: sodium restriction, a modest fluid limit and a loop diuretic dosed for a nephrotic kidney. Low albumin delivers less furosemide to the tubule and a swollen gut absorbs less, so the dose rises and is split; naproxen goes because it blunts the diuretic and is contraindicated in nephrotic syndrome. A proposed loss of 0.5–1 kg/day requires daily weights, perfusion assessment and electrolyte/creatinine checks; the rate must slow if underfilling develops. Why not the others: A — saline adds salt and water to an edematous patient, and can worsen overload; B — he is overloaded, not dry, and stopping the loop lets him gain; D — a thiazide is the second step after an adequate loop dose, and it deepens hyponatremia. Course reading: Evidence for this case
Atorvastatin 40 mg was started for the nephrotic hyperlipidemia, and the adult secondary-cause screen was sent the same day. His gout flares will be treated with a short prednisone course or colchicine, not an NSAID.
Q6What the antibody settles
Day 7, nephrology clinic. The screen is back: A1c 5.5%; HIV, hepatitis B surface antigen, hepatitis C antibody, RPR and ANA negative; C3 and C4 normal; serum protein electrophoresis with immunofixation and the free light chain ratio normal. Anti-PLA2R antibody is positive. Mr. Kessler asks whether "the gout pills did this." Which statement is correct?
It proves the naproxen caused his disease, so stopping the naproxen is the whole treatment
It supports PLA2R-associated membranous disease; review associated causes and the biopsy need
It excludes an underlying cancer, so his age-appropriate cancer screening can now stop
It means immunosuppression should start in primary care this week to protect his kidney
Show answer and explanation · Link to this question
Correct answer: B
Learning point: Anti-PLA2R with this nephrotic presentation supports PLA2R-associated membranous nephropathy and may allow diagnosis without biopsy. KDIGO still calls for evaluation of associated conditions regardless of antibody status; a positive result does not exclude cancer, infection or a coincident drug contribution. Stop naproxen and let nephrology assess disease risk, biopsy value and treatment. Why not the others: A claims an unproven drug cause and cure; C incorrectly ends cancer screening; D starts specialist immunosuppression before risk assessment. Course reading: Evidence for this case
Part 3 — Course and Decisions
Answers for this section: Q7
At the same visit he received the pneumococcal vaccine, because a nephrotic patient loses immunoglobulins in the urine. Losartan 25 mg was started on day 10, once his weight and creatinine were moving the right way. By day 14 he weighed 80 kg (8 kg in 14 days, about 0.6 kg a day); creatinine 1.3 mg/dL, potassium 4.6, sodium 134.
Day 18. He calls at 07:00 with sharp left flank pain since waking and urine "the color of cola." In clinic: BP 138/84 seated and 136/82 standing, pulse 80, weight 80 kg (unchanged since day 14), 1+ ankle edema.
| Test | Day 14 | Day 18 | Reference range |
|---|---|---|---|
| Creatinine | 1.3 | 2.1 | 0.7–1.3 mg/dL |
| eGFR (CKD-EPI 2021) | 61 | not valid — creatinine is moving | ≥60 mL/min/1.73 m² |
| Potassium | 4.6 | 4.9 | 3.5–5.0 mEq/L |
| Albumin | — | 1.8 | 3.5–5.0 g/dL |
| Urine dipstick blood | 1+ | Large | Negative |
| Urine microscopy | 3–5 RBC/hpf | >50 RBC/hpf, 0–2 WBC/hpf, no WBC casts | 0–3 RBC, 0–5 WBC/hpf |
| Bladder scan (post-void residual) | — | 30 mL | <100 mL |
The creatinine is 1.6 times the day-14 value within four days: KDIGO stage 1 acute kidney injury.
Q7Why did the creatinine jump?
Day 18. Mr. Kessler, with membranous nephropathy and albumin 1.8, has new left flank pain and gross hematuria; creatinine 2.1 from 1.3 four days ago; stable weight, no orthostatic change, residual edema; bladder scan 30 mL; no pyuria; naproxen stopped 18 days ago; losartan started 8 days ago. What is the most likely cause, and the right action?
Over-diuresis: hold the furosemide and losartan and give a liter of saline today
Ureteral stone: non-contrast CT, tamsulosin, and urology follow-up next week
Naproxen interstitial nephritis: start prednisone and repeat the urinalysis in a week
Renal vein thrombosis: image the left renal vein today; same-day call to nephrology
Show answer and explanation · Link to this question
Correct answer: D
Learning point: The nephrotic state, marked hypoalbuminemia, flank pain, hematuria and acute creatinine rise make renal vein thrombosis an urgent concern. Arrange appropriate vascular imaging and contact nephrology the same day. An empty bladder argues against lower-tract retention but does not exclude upper-tract obstruction; no pyuria does not rule out AIN. Reassess perfusion, drugs and obstruction alongside the leading vascular diagnosis, rather than treating single negative findings as exclusions. Why not the others: A assumes underfilling without adequate supporting assessment; B delays evaluation of potentially serious obstruction or thrombosis; C starts steroids without establishing the cause. D addresses the leading time-sensitive complication. Course reading: Evidence for this case
Resolution and Teaching Points
Answers for this section: W1 · W2 · Q3 · Q4 · Q5 · Q6 · Q7
Imaging that afternoon showed a thrombus in the left renal vein. Nephrology admitted him and started anticoagulation, held the losartan until the creatinine settled, and — with a positive anti-PLA2R and a negative secondary screen — treated him as primary membranous nephropathy without a biopsy, beginning disease-specific therapy in their clinic. By week 8 his creatinine was 1.4 mg/dL, weight 77 kg, albumin 2.6 g/dL and UPCR 5.2 g/g; losartan was back. The cardiology referral was cancelled, and "heart failure" came off his problem list. His wife now checks his eyelids every morning, as she always did; the difference is that someone asked.
Clinical Pearl — Look at the urine before the third diuretic Normal neck veins, clear lungs and morning periorbital edema should prompt a renal and hepatic evaluation; they do not alone exclude cardiac disease. A urinalysis and a protein-to-creatinine ratio cost almost nothing; a basic metabolic panel does not include albumin.
Clinical Pearl — Quantify with a ratio A spot urine protein-to-creatinine ratio in g/g approximates grams a day; above 3.5 is nephrotic range. The dipstick reads concentration and is fooled by dilute urine; the UACR is the screening test; a timed collection may be useful when spot ratios are discordant or a treatment decision requires more reliable quantification.
Clinical Pearl — The adult nephrotic screen Glucose and A1c, HIV, hepatitis B and C, syphilis, ANA with C3 and C4, serum and urine electrophoresis with immunofixation and free light chains (particularly relevant in older adults or when monoclonal disease is suspected), a drug review, and age-appropriate cancer screening. Anti-PLA2R points to primary membranous nephropathy; it does not end the search for cancer.
Clinical Pearl — Nephrotic diuresis Sodium under 2 g a day, a loop diuretic twice daily at a higher dose (low albumin and gut edema both blunt furosemide), stop NSAIDs, aim for 0.5–1 kg a day, weigh daily and check a BMP within the first week. No saline for the low sodium.
Clinical Pearl — The complications travel together Clots (deep veins, lungs, renal veins — highest in membranous nephropathy with a very low albumin), infections (pneumococcal vaccine), lipids (statin) and over-diuresis AKI. Flank pain, new hematuria and a creatinine jump warrant urgent evaluation for renal vein thrombosis and competing causes.
Pitfall — Treating the label "Diuretic-resistant heart failure" earned two escalations and a referral without a urinalysis. When a diagnosis does not respond to its treatment, question the diagnosis before you add a drug.
Pitfall — Making nephrology's decisions alone Anticoagulation for a nephrotic patient, immunosuppression, and whether to biopsy are weighed specialist decisions: bleeding against clotting, a biopsy against an anticoagulant. Your job is to recognize, image, stop the harmful drugs and call the same day.
Concept Links
Answers for this section: W1 · W2 · Q3 · Q4 · Q5 · Q6 · Q7
Assigned reading: the explanations in this case and the question-linked course evidence guide. The objective map distinguishes tested decisions from concepts taught in explanations.
Concepts: aki-03, glom-04, glom-07, glom-10, glom-18, glom-19, glom-20, glom-21, glom-23, glom-24, lytes-07, structural-20.