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: A 70-year-old woman on furosemide and lisinopril takes naproxen for three days for knee pain, and her creatinine rises f · Answer
- W2: A 58-year-old man with type 2 diabetes and a urine albumin-to-creatinine ratio of 420 mg/g starts lisinopril 10 mg daily · Answer
- W3: A 72-year-old man with CKD (eGFR 40 mL/min/1.73 m²) has taken colchicine 0.6 mg daily for a year to prevent gout flares. · Answer
- Q4: The lab calls while she is still in the room: creatinine 2.0 mg/dL (1.2 four weeks ago), potassium 5.8 mEq/L. She has a · Answer
- Q5: Before the full panel is back you already have: a new fine tremor, evening headaches, creatinine 2.0 (from 1.2), potassi · Answer
- Q6: Her tacrolimus dose has not changed in fourteen months, and she has not missed or doubled a dose. If the level has risen · Answer
- Q7: Sodium 137, chloride 107, bicarbonate 19, potassium 5.8, albumin 4.0, urine pH 5.5. Which interpretation is correct? · Answer
- Q8: It is 2 p.m. The tacrolimus level will report at about 4:30 p.m., and the transplant nephrologist will call you once it · Answer
- Q9: If you were thinking tacrolimus toxicity — not the ibuprofen-and-diarrhea story alone — is driving her creatinine rise , · Answer
- Q10: The transplant nephrologist reviews the level of 18.2 and recommends ending the unplanned diltiazem interaction. Which p · Answer
- Q11: Diltiazem is stopped. Her blood pressure will drift back toward 150/90 over the next week, and with one kidney that matt · Answer
- Q12: She calls your nurse line in February: twenty-four hours of vomiting, a temperature of 38.3 °C, and a cough. Urgent care · Answer
Session S5 · 2026-11-03 · in-session · 37 min Anchor: Integrative review — AKI in a kidney-transplant recipient, the hemodynamic-AKI frame in new dress · Integrates: CYP3A4 pharmacology, safe antihypertensive choice, hyperkalemia with type-4-RTA physiology, hypomagnesemia, hyperglycemia, outpatient creatinine-bump triage, the primary-care transplant checklist, the sick-day rule One-line hook: A transplant patient will walk into your primary-care clinic within your first year of practice. You will not manage her tacrolimus. You will be the clinician who sees her first when her creatinine moves — and who has to decide which parts of the problem are yours.
Learning Objectives
Answers for this section: W1 · W2 · W3 · Q4 · Q5 · Q6 · Q7 · Q8 · Q9 · Q10 · Q11 · Q12
- Triage an unexpected creatinine rise in a kidney-transplant recipient in clinic — same-day evaluation versus a 48–72-hour recheck — from the potassium, the symptoms, the trajectory and the fact that she has one kidney that is not hers.
- Recognize which findings in a cluster of tremor, hyperkalemia with a mild normal-gap acidosis, hypomagnesemia, hyperglycemia and a creatinine rise point beyond an NSAID, read a calcineurin-inhibitor trough by its clock, and name the CYP3A4 interaction that raises it.
- Place calcineurin-inhibitor toxicity and NSAID injury inside the prerenal / intrinsic / post-renal frame as hemodynamic AKI, and state the first-line moves: hold the NSAID, rehydrate, recheck, stop the interacting drug you started, and call the transplant center today — never holding or adjusting the transplant drugs yourself.
- Choose a safe antihypertensive for a transplant recipient whose potassium is 5.8, and recite the primary-care transplant checklist: interacting drugs, NSAID avoidance, non-live vaccines coordinated with the transplant center, skin and cervical cancer screening, and the "call the center when" list.
- Apply a written, individualized sick-day and restart plan: patients contact the transplant center urgently and do not independently change immunosuppression; the center may intentionally adjust the regimen during illness.
Warm-Up (individual commit before the case)
Answers for this section: W1 · W2 · W3
W1The NSAID and the filter
A 70-year-old woman on furosemide and lisinopril takes naproxen for three days for knee pain, and her creatinine rises from 1.1 to 1.8 mg/dL. Which statement best explains why the NSAID hurt her kidney?
NSAIDs remove the prostaglandins holding the afferent arteriole open, the support her two other drugs left her relying on
NSAIDs constrict the efferent arteriole, so adding one to an ACE inhibitor evens out the pressure inside each filter
NSAID kidney injury is an allergic interstitial nephritis, so her urine will show white cells and white-cell casts
Topical NSAIDs carry the same kidney risk as tablets, so a gel instead of naproxen would not have protected her
Show answer and explanation · Link to this question
Correct answer: A
Learning point: Prostaglandins hold the afferent arteriole — the small artery feeding each filter (glomerulus) — open. Her diuretic shrinks her volume and her ACE inhibitor removes the efferent squeeze that props up filtration pressure, so that dilation is the last support left; take it away and filtration falls within a day or two, with a bland urine, and recovers when the drug stops. Diuretic + RAAS blocker + NSAID is the "triple whammy" , and its risk is highest in the first 30 days. Why not the others: B reverses the anatomy — the efferent arteriole belongs to angiotensin II, and the ACE inhibitor is what makes the combination dangerous; C is the rarer NSAID mechanism — the common one is hemodynamic, with a bland urinalysis; D is wrong — topical NSAIDs generally have less systemic absorption, though risk is not zero and are the alternative the handouts recommend. Course reading: Evidence for this case
W2The creatinine that is allowed to rise
A 58-year-old man with type 2 diabetes and a urine albumin-to-creatinine ratio of 420 mg/g starts lisinopril 10 mg daily. At two weeks his creatinine is 1.2 mg/dL (baseline 1.0) and potassium 4.8 mEq/L. He feels well. What is the right move?
Stop lisinopril — any creatinine rise on an ACE inhibitor means the kidney is being injured
Order a renal artery duplex today, because a rise this early suggests bilateral renal artery stenosis
Continue lisinopril and recheck the BMP in about two weeks — a 20% rise is the expected effect
Halve the lisinopril and add an ARB so the two drugs protect the kidney from both directions
Show answer and explanation · Link to this question
Correct answer: C
Learning point: A small early creatinine rise can follow reduced intraglomerular pressure with ACE inhibition. In this well patient, 1.0 to 1.2 is 20%, so continue and recheck creatinine and potassium. KDIGO 2024 advises reassessment when creatinine rises more than 30% within 4 weeks: look for volume depletion, interacting drugs and renovascular disease, and reduce or stop if the problem cannot be corrected. Symptomatic hypotension or uncontrolled hyperkalemia can also require adjustment. A rise is not required to prove benefit. Why not the others: A throws away the one drug that slows his diabetic kidney disease over an expected number; B is the work-up for a rise above 30%, not 20%; D is dual RAAS blockade — the trials found more hyperkalemia and AKI and no benefit. Course reading: Evidence for this case
W3The antibiotic and the gout pill
A 72-year-old man with CKD (eGFR 40 mL/min/1.73 m²) has taken colchicine 0.6 mg daily for a year to prevent gout flares. Urgent care prescribes clarithromycin for bronchitis. Five days later he has diarrhea, muscle weakness and a low white-cell count. What is the best explanation?
The antibiotic caused the diarrhea, and his weakness and low white count come from the bronchitis itself
Clarithromycin blocks the enzyme and the pump that clear colchicine, so it builds up on the same dose
Clarithromycin speeds colchicine's breakdown into a toxic product that his kidneys cannot excrete
His eGFR of 40 alone let colchicine accumulate, and the antibiotic is a coincidence of timing
Show answer and explanation · Link to this question
Correct answer: B
Learning point: Colchicine is cleared by CYP3A4 — a drug-metabolizing enzyme in the liver and the gut wall — and pumped out of cells by P-glycoprotein, and clarithromycin blocks both. On an unchanged dose the level climbs, and colchicine has a narrow window: diarrhea, muscle injury and a falling blood count are its toxicity, worse when kidney function is reduced. This combination is contraindicated in renal impairment: stop the interacting drugs and arrange urgent toxicity assessment. The rule travels: when a narrow-window drug is cleared by CYP3A4, a new inhibitor raises its level and a new inducer lowers it. Why not the others: A blames the infection for a toxicity pattern that began after the new drug; C has the direction backwards — clarithromycin slows clearance, it does not speed it; D ignores a year on the same dose at the same eGFR without trouble. Course reading: Evidence for this case
Part 1 — Presentation
Answers for this section: Q4 · Q5 · Q6
Ms. R. is 46. Three years ago her sister gave her a kidney. The cause of her own kidney failure was IgA nephropathy, diagnosed in her twenties. The transplant has gone well: at the transplant center's last visit three months ago her creatinine was 1.2 mg/dL (eGFR about 57 mL/min/1.73 m² by CKD-EPI 2021 — a transplant kidney is one kidney doing the work of two, so this is a good number for her), her tacrolimus trough was 7.1 ng/mL against a center target of 6–8, and her A1c was 6.1% (the center tracks it because tacrolimus and prednisone both cause post-transplant diabetes ). A dental hygienist who does not smoke or drink, she lives ninety minutes from the center with her husband and two teenagers. Her primary care lives with you.
A trough is the lowest blood level of a drug, drawn just before the next dose. Tacrolimus is a calcineurin inhibitor — the drug that holds her immune system back from attacking the kidney — and it has a narrow window: too low and the kidney is rejected; too high and the drug itself becomes toxic. That is why her center checks a trough every three months and asks to be told about any new medicine.
Four weeks ago she came to your clinic for a routine visit. Blood pressure was 152/92, repeated 149/90, and her home cuff had been averaging 148/90 for a month. Her labs that day were unremarkable for her: creatinine 1.2, potassium 4.6, bicarbonate 24, fasting glucose 118. The clinic started diltiazem ER 180 mg daily — "gentle, kidney-friendly, no cough" — and booked a four-week follow-up. Nobody called the transplant center.
Today she is back for that follow-up, and her blood pressure is 128/78. She is pleased about the number and nothing else. For two weeks her hands have shaken — a fine, fast tremor she first noticed holding a coffee cup, and her charting at work has become hard to read. She has had a headache most evenings for a week and is sleeping badly. Last week she and her husband had two days of watery diarrhea — five or six stools a day, no fever, no blood — which she managed with over-the-counter loperamide and did not report to anyone. Yesterday the headache was bad enough that she took ibuprofen 400 mg twice, at two in the afternoon and at ten at night. She has not missed or doubled a transplant dose; she stores them in a dated pill organizer and takes tacrolimus at 8 a.m. and 8 p.m. Urine output seems normal to her.
Her fasting labs for today's visit were drawn at 7:45 this morning.
Vitals: BP 128/78 seated, 118/76 standing · Pulse 64 seated, 78 standing · T 36.9 °C · Respiratory rate 14 · Weight 68.0 kg (69.5 kg four weeks ago) · Height 165 cm.
Exam: Alert, anxious about her hands. Fine, fast tremor of both hands when held outstretched; no rigidity, normal gait. Mucous membranes slightly dry; no jugular venous distension; lungs clear; heart regular without murmur. Abdomen soft; the transplant kidney in the right lower quadrant is non-tender with no bruit. No edema. Skin: a few rough, scaly patches on both forearms (actinic keratoses). No rash, no lymphadenopathy.
| Drug | Dose | Route | Frequency | Indication |
|---|---|---|---|---|
| Tacrolimus (immediate-release) | 3 mg | PO | every 12 h (8 a.m. / 8 p.m.) | Prevent rejection of the kidney transplant (calcineurin inhibitor); dose unchanged for 14 months |
| Mycophenolate mofetil | 750 mg | PO | every 12 h | Prevent rejection (antimetabolite) |
| Prednisone | 5 mg | PO | daily | Prevent rejection (maintenance steroid) |
| Diltiazem ER | 180 mg | PO | daily | Hypertension — started 4 weeks ago by this clinic |
| Atorvastatin | 20 mg | PO | nightly | Hyperlipidemia |
| Cholecalciferol (vitamin D₃) | 1,000 IU | PO | daily | Bone health after transplant |
| Levonorgestrel IUD | — | intrauterine | in place | Contraception (required while on mycophenolate, which causes birth defects) |
| Ibuprofen (OTC) | 400 mg | PO | two doses yesterday (14:00, 22:00) | Headache — self-directed |
| Loperamide (OTC) | 2 mg | PO | two doses last week | Diarrhea — self-directed |
Pause — commit before the reveal
Q4Same day or seventy-two hours?
The lab calls while she is still in the room: creatinine 2.0 mg/dL (1.2 four weeks ago), potassium 5.8 mEq/L. She has a new tremor, a mild orthostatic drop, and one working kidney — the transplant. What is the right disposition today?
Stop the ibuprofen, push oral fluids and recheck a BMP in 48–72 hours — the classic bump after an NSAID and a stomach bug
Order a CT of the abdomen and pelvis with IV contrast today to look for obstruction or a collection around the transplant
Same-day work-up: ECG, urinalysis, bladder scan and ultrasound, magnesium and a tacrolimus level, and a call to the center
Ask the center to book a transplant biopsy first — a creatinine rise in a transplant is rejection until proven otherwise
Show answer and explanation · Link to this question
Correct answer: C
Learning point: Three things take her out of the 48–72-hour lane: a potassium of 5.8 that needs an ECG today; a creatinine 1.67 times her baseline — the size of a KDIGO stage 1 rise, although with the last value four weeks old the 7-day clock cannot be applied ; and new symptoms in a patient whose only working kidney is a transplant. The outpatient creatinine-bump work-up is the usual one — confirm the change, review the medications, check the urine and the bladder, assess volume — and in a transplant recipient it adds a tacrolimus level and a same-day call to the center. Why not the others: A is the right recheck on the wrong clock for a transplant kidney with a potassium of 5.8, and it leaves the center out; B gives iodinated contrast to an injured kidney when a bladder scan and an ultrasound answer the obstruction question without it; D is biopsy before the bladder scan — rejection is a center diagnosis, and it would not explain the tremor. Course reading: Evidence for this case
Q5Five findings, two stories
Before the full panel is back you already have: a new fine tremor, evening headaches, creatinine 2.0 (from 1.2), potassium 5.8, and a fasting point-of-care glucose of 238 mg/dL. Yesterday's ibuprofen and last week's diarrhea are one story. Which two findings does that story fail to explain?
The new tremor and the fasting glucose of 238
The creatinine of 2.0 and the potassium of 5.8
The potassium of 5.8 and the fasting glucose
The new tremor and the creatinine rise of 0.8
Show answer and explanation · Link to this question
Correct answer: A
Learning point: Ibuprofen on top of lost volume explains a creatinine rise (W1's afferent squeeze) and can raise the potassium, because NSAIDs lower renin and with it aldosterone. That explanation does not adequately account for the new tremor and worsening glucose on an unchanged prednisone dose; stress can raise glucose, so these are supporting clues rather than proof; the headaches could belong to either story. Two findings outside the first story mean a second process — in a tacrolimus patient, what a level above range looks like, which is why a level was added to this morning's sample. Whether it is high, and whether it also explains the creatinine, the result will say. Why not the others: B — both fit the first story: the afferent squeeze, and an NSAID's hold on aldosterone; C — the potassium fits the NSAID even though diarrhea alone would lower it; D — the creatinine needs nothing beyond the NSAID and the lost volume. Course reading: Evidence for this case
Q6Read the medication list by date
Her tacrolimus dose has not changed in fourteen months, and she has not missed or doubled a dose. If the level has risen, which drug on her list is the most likely reason?
Atorvastatin — CYP3A4 also breaks it down, so it competes with tacrolimus and slows its clearance
Ibuprofen, taken yesterday — NSAIDs slow the liver's breakdown of tacrolimus within hours
Prednisone — steroids slow tacrolimus breakdown, and she has taken hers for three years
Diltiazem, started four weeks ago — it blocks CYP3A4 and P-glycoprotein, which clear tacrolimus
Show answer and explanation · Link to this question
Correct answer: D
Learning point: When a stable patient destabilizes on an unchanged dose, look for the new drug that changed how the old one is cleared — read the medication list by start date. Tacrolimus is broken down by CYP3A4 in the liver and gut wall and pumped back out of gut cells by P-glycoprotein; diltiazem and verapamil, the heart-rate-slowing (non-dihydropyridine) calcium-channel blockers, block both, so the same 3 mg gives a higher level. Azole antifungals, clarithromycin and erythromycin, and grapefruit juice do the same; the inducers rifampin, phenytoin, carbamazepine and St John's wort push the level down and risk rejection. Why not the others: A confuses a substrate (a drug the enzyme works on) with an inhibitor (a drug that blocks it), and atorvastatin has sat on her list for years without moving her trough; B adds its own afferent squeeze but does not slow tacrolimus clearance, and two doses yesterday cannot explain a tremor that began two weeks ago; C is a long-standing drug at an unchanged dose — nothing new happened on that line. Course reading: Evidence for this case
Part 2 — Data
Answers for this section: Q7 · Q8 · Q9
The same-day work-up comes back over the next ninety minutes. Walk the table — kidney numbers, electrolytes, urine, pictures — asking what each result excludes before what it proves.
Serum chemistry and blood counts (drawn 07:45, fasting)
| Test | Result | Reference range |
|---|---|---|
| Sodium | 137 mEq/L | 135–145 |
| Potassium | 5.8 mEq/L | 3.5–5.0 |
| Chloride | 107 mEq/L | 98–107 |
| Bicarbonate | 19 mEq/L | 22–28 |
| Anion gap (Na − [Cl + HCO₃]) | 137 − (107 + 19) = 11 | 8–12 (this lab) |
| BUN | 36 mg/dL | 7–20 |
| Creatinine | 2.0 mg/dL | 0.6–1.1 (her baseline 1.2) |
| BUN:creatinine | 18:1 | — (below 20; a ratio alone cannot assign the mechanism) |
| eGFR | not valid — creatinine is moving (baseline about 57 mL/min/1.73 m² at Cr 1.2, CKD-EPI 2021, 46-year-old woman) | ≥60 |
| Glucose (fasting) | 238 mg/dL | 70–99 |
| Hemoglobin A1c | 6.9% | <5.7% (hers was 6.1% three months ago) |
| Calcium | 9.0 mg/dL | 8.5–10.5 |
| Albumin | 4.0 g/dL | 3.5–5.0 |
| Phosphorus | 3.9 mg/dL | 2.5–4.5 |
| Magnesium | 1.3 mg/dL | 1.8–2.4 |
| WBC | 5.8 ×10³/µL | 4.0–11.0 |
| Hemoglobin | 12.6 g/dL | 12.0–16.0 |
| Platelets | 212 ×10³/µL | 150–400 |
| Tacrolimus level (added to the 07:45 sample) | pending — hospital lab reports about 4:30 p.m. | center target 6–8 ng/mL (trough) |
Urinalysis
| Component | Result | Reference |
|---|---|---|
| Color / clarity | yellow, clear | — |
| Specific gravity | 1.020 | 1.005–1.030 |
| pH | 5.5 | 4.5–8.0 |
| Protein | trace | negative |
| Glucose | 2+ | negative |
| Ketones | negative | negative |
| Blood (heme) | negative | negative |
| Leukocyte esterase / nitrite | negative / negative | negative |
| Microscopy | RBC 0–2/hpf; WBC 0–2/hpf; occasional hyaline casts; no granular, cellular or red-cell casts; no crystals | — |
Bedside and imaging: Post-void residual 30 mL. Transplant kidney ultrasound (same afternoon): normal size, no hydronephrosis, no fluid collection around the kidney. ECG: sinus rhythm 66/min, PR 160 ms, QRS 88 ms, QTc 430 ms, normal T waves — no peaking.
What the table supports. The bladder scan and ultrasound show no obstruction, and the bland sediment supports a hemodynamic contribution from volume loss, ibuprofen and tacrolimus. A bland urine does not exclude tubular injury, interstitial nephritis or rejection. Glycosuria can occur at this serum glucose and is not by itself evidence of proximal tubular damage. Persistent dysfunction despite correction of volume and drug exposure needs transplant-center reassessment for rejection, infection and other intrinsic disease.
Q7Reading the gap and the potassium together
Sodium 137, chloride 107, bicarbonate 19, potassium 5.8, albumin 4.0, urine pH 5.5. Which interpretation is correct?
A high anion gap acidosis — the diarrhea left lactic acid behind and the injured kidney cannot clear it
A normal-gap (11) acidosis with high potassium — the type 4 RTA pattern, a duct ignoring aldosterone
A type 1 (distal) RTA — the kidney cannot acidify the urine, which is why her bicarbonate is low
A diarrhea acidosis — stool carried bicarbonate off last week, and the potassium rose along with it
Show answer and explanation · Link to this question
Correct answer: B
Learning point: Compute the gap before you name the acidosis: 137 − (107 + 19) = 11, inside this lab's 8–12, and an albumin of 4.0 needs no correction. A normal-gap acidosis with high potassium points to the collecting duct: aldosterone normally drives sodium in and potassium and acid out, and when the duct cannot respond — type 4 renal tubular acidosis (RTA) — both are retained, giving a mild acidosis (bicarbonate 17–24) with potassium 5.5–7.0 and a urine that can still acidify. High tacrolimus does this, NSAIDs add to it, and correcting the contributors may improve the bicarbonate. This is a type 4 pattern, not a definitive isolated RTA diagnosis from one BMP; the center directs any tacrolimus change. Why not the others: A — the calculated gap is normal. C — classic distal RTA usually has low potassium; a urine pH of 5.5 alone cannot establish normal acid excretion. D — diarrhea generally loses potassium and has ended, although mixed causes can coexist with reduced kidney function. Course reading: Evidence for this case
Pause — commit before the reveal
Q8What you do before the level is back
It is 2 p.m. The tacrolimus level will report at about 4:30 p.m., and the transplant nephrologist will call you once it does. Her ECG is normal. What is the right plan between now and tomorrow's recheck?
IV calcium gluconate, then insulin with dextrose, given here in clinic — her potassium is 5.8 and she has one kidney
Oral furosemide 40 mg now to push the potassium out, and a repeat BMP first thing tomorrow morning
Hold tonight's tacrolimus and mycophenolate to rest the kidney, and repeat her labs in 48 hours
Stop ibuprofen, rehydrate and repeat potassium today; use the transplant center's same-day plan for medication and follow-up
Show answer and explanation · Link to this question
Correct answer: D
Learning point: Remove ibuprofen, assess and correct volume loss, review potassium intake and repeat potassium promptly. A normal ECG does not exclude dangerous hyperkalemia. Discuss disposition with the transplant center now; outpatient follow-up is acceptable only if repeat results and the clinical assessment support it and rapid re-evaluation is reliable. Escalate to the ED if potassium rises, symptoms develop or timely reassessment is unavailable. The center directs any immunosuppression change. Why not the others: A — immediate calcium is not supported by the current ECG; severe hyperkalemia treatment requires a monitored setting. B — a loop may worsen volume depletion. C — independently holding immunosuppression and waiting 48 hours bypasses urgent transplant assessment. Normal ECG findings do not remove the need for same-day potassium reassessment. Course reading: Evidence for this case
At 4:30 p.m. the hospital lab reports the tacrolimus level from the 07:45 sample: 18.2 ng/mL (center target 6–8; her last three troughs 6.9, 7.4 and 7.1).
Q9Evidence 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 tacrolimus toxicity — not the ibuprofen-and-diarrhea story alone — is driving her creatinine rise, and you then learn that the tacrolimus level in this morning's 07:45 sample is 18.2 ng/mL, this hypothesis becomes:
Much less likely
Less likely
Unchanged
More likely
Much more likely
Show answer and explanation · Link to this question
Correct answer: E
Formative evidence update: The letter is a teaching anchor. Accept a justified adjacent response; this is not an expert-panel-validated score. Learning point: Notice the clock first: she takes tacrolimus at 8 a.m. and 8 p.m., so a 07:45 draw is a true trough — the same 18 drawn an hour after a dose would mean little. A true trough more than double her target, on a dose unchanged for fourteen months and four weeks after a CYP3A4 inhibitor started, explains the whole board (creatinine, tremor, potassium and acid, magnesium, glucose), where the ibuprofen-and-diarrhea story explains only the creatinine and the potassium. The two stories do not compete: persistent diarrhea can raise tacrolimus exposure, so it fed the same problem — the NSAID is demoted, not discarded, and it still had to go. Why not the others: D (More likely) undersells a true trough this high that accounts for every finding; C (Unchanged) would mean the level has no bearing on the cause, when it is the cause's fingerprint; A and B have no finding behind them. Course reading: Evidence for this case
Part 3 — Course and Decisions
Answers for this section: Q10 · Q11 · Q12
At 4:45 p.m. the transplant nephrologist calls back.
Pause — commit before the reveal
Q10What is yours to do today
The transplant nephrologist reviews the level of 18.2 and recommends ending the unplanned diltiazem interaction. Which plan carries that decision out safely?
Lower the tacrolimus dose yourself to bring the level back toward 6–8, and recheck the level in a week
Stop the diltiazem, leave the tacrolimus dose to the center, and recheck labs and troughs on its schedule
Keep the diltiazem — her pressure is finally at goal — and ask the center to lower the tacrolimus to match
Stop the diltiazem and skip further levels — without the inhibitor the trough will settle back to 6–8
Show answer and explanation · Link to this question
Correct answer: B
Learning point: Implement the center's plan: stop diltiazem, communicate the exact time and have the center adjust tacrolimus and schedule troughs. Exposure can change over the ensuing days, with variable timing. Continued creatinine elevation despite correction of exposure and volume requires reassessment for other allograft problems. Why not the others: A — changes the immunosuppressant outside the agreed monitoring plan. C — intentional diltiazem boosting can be used by a transplant team, but it contradicts the center's stated decision in this case. D — withdrawing an inhibitor still requires trough monitoring and dose adjustment. Course reading: Evidence for this case
The electrolyte and glucose plan, decided on the phone.
| Problem | What the clinic does today | What the center adds | What would send her to the ED |
|---|---|---|---|
| Potassium 5.8, normal ECG | Stop every contributor you own (the NSAID is already gone; no ACEi/ARB, no potassium-sparing diuretic, no TMP-SMX, no salt substitutes); low-potassium diet counseling; recheck in 24 h | The definitive fix is the tacrolimus reduction; a short course of a loop diuretic once she is rehydrated, or a potassium binder, if the number does not fall | Potassium at or above 6.0–6.5, any ECG change, weakness or palpitations |
| Magnesium 1.3, no arrhythmia or tetany | Oral magnesium selected and dosed by the transplant team, accounting for renal function and diarrhea tolerance | Tacrolimus wastes magnesium in the urine (last week's diarrhea added to the loss), so expect oral replacement until the trough is back in range; recheck with each BMP | Magnesium below 1.0, torsades or any arrhythmia, tetany or seizure, or inability to take oral — then IV magnesium sulfate in a monitored setting |
| Fasting glucose 238, A1c 6.9%, ketones negative (Transplant complications handout §IV — post-transplant diabetes) | Tacrolimus and prednisone may contribute; these results do not establish ketoacidosis; home fasting glucose checks; expect improvement as the trough falls; no metformin or SGLT2 inhibitor started during an AKI with an unsettled eGFR | Whether this is post-transplant diabetes is judged once the trough is back to 6–8; if glucose stays high, the center and primary care choose an agent together — dosed to the eGFR at that visit, not today's invalid number | Glucose above 300 with symptoms, or any ketones |
The headache gets acetaminophen (up to 3 g/day). Every NSAID is off her list permanently, with a note in the chart and a sentence to her: "Nothing from the pain aisle except acetaminophen, ever, without asking."
Q11The blood pressure
Diltiazem is stopped. Her blood pressure will drift back toward 150/90 over the next week, and with one kidney that matters. Potassium today is 5.8. Which replacement is the best choice once her home readings climb?
Lisinopril 10 mg daily — she has one kidney to protect and may have albuminuria
Losartan 50 mg daily — the same kidney protection without the ACE-inhibitor cough
Amlodipine 5 mg daily, cleared with the center and titrated to her home readings
Verapamil SR 180 mg daily — the drug class that just brought her pressure to goal
Show answer and explanation · Link to this question
Correct answer: C
Learning point: Match the agent to the patient: ACE inhibitors and ARBs raise potassium, and diltiazem and verapamil raise tacrolimus. Amlodipine, a dihydropyridine calcium-channel blocker (a different subclass from diltiazem), does not usually raise potassium and needs no renal dose adjustment, but can increase tacrolimus exposure; the center checks a trough after it starts, and ankle edema is the side effect to warn about. Her target is below 130/80 (2025 AHA/ACC); KDIGO's lower systolic target of 120 explicitly excludes transplant recipients . Why not the others: A is a RAAS blocker, which the RAAS handout says to avoid while potassium is above 5.0; B is a RAAS blocker too — once she is normokalemic an ARB is a reasonable conversation with the center, not a prescription today; D is diltiazem's sibling and inhibits CYP3A4 the same way. Course reading: Evidence for this case
The primary-care transplant checklist — what she should hear from you before she leaves, and what every transplant patient in your panel should have on a card:
| Checklist item | The rule in one line |
|---|---|
| Drugs that raise tacrolimus | Diltiazem and verapamil, azole antifungals (fluconazole, ketoconazole), clarithromycin and erythromycin, grapefruit juice → toxicity. Clear every new prescription with the center. |
| Drugs that lower tacrolimus | Rifampin, phenytoin, carbamazepine, St John's wort → rejection risk. The same phone call — and stopping a drug that raises the level makes it fall, so stopping needs the call too. |
| The azathioprine trap | If a transplant patient is on azathioprine instead of mycophenolate, allopurinol (and febuxostat) can cause fatal bone-marrow suppression. Do not start either without the center. |
| NSAIDs | Never — acetaminophen or topical agents instead . The same afferent arteriole tacrolimus already constricts. |
| Vaccines | Inactivated vaccines only (and encouraged): injected influenza, COVID-19, pneumococcal, recombinant zoster, Tdap, hepatitis B. No live vaccines — no nasal-spray influenza, MMR, varicella or yellow fever. Household contacts should be vaccinated. |
| Infection red flags | Fever is never "just a virus" in an immunosuppressed patient — same-day call. Dysuria, cough, diarrhea lasting more than a day, any new rash. Infection and rejection both show up as a rising creatinine; the center sorts them. |
| Cancer screening | Skin cancer is the most common cancer after transplant: sun protection, yearly skin exam by dermatology (her forearm keratoses get that referral today). Cervical screening on schedule. Age-appropriate colon and breast screening as for anyone else. |
| Call the center when | Fever; a creatinine that rises on any lab; less urine; vomiting or diarrhea; before starting or stopping any prescription or over-the-counter product; any hospital admission or procedure; a positive pregnancy test on mycophenolate. |
| Sick-day rule | Use a written, individualized plan for medicines during a dehydrating illness, including when to restart. Do not independently hold tacrolimus, mycophenolate or prednisone; contact the transplant center urgently because illness can change exposure and the center may need to adjust treatment. |
Q12Four months later, a phone call
She calls your nurse line in February: twenty-four hours of vomiting, a temperature of 38.3 °C, and a cough. Urgent care last night prescribed clarithromycin for "bronchitis" and offered the nasal-spray influenza vaccine. She asks whether to hold her transplant pills until she can keep food down, the way her neighbor holds his blood-pressure pills on sick days. Which instruction is correct?
Do not independently hold transplant drugs; defer clarithromycin and the live vaccine, and obtain urgent center advice today
Hold tacrolimus and mycophenolate until she can eat again, exactly as she would hold a SADMANS drug
Take the clarithromycin and accept the nasal vaccine — infection is the bigger danger after a transplant
Keep taking everything, use ibuprofen for the fever, and recheck her labs at the next routine visit
Show answer and explanation · Link to this question
Correct answer: A
Learning point: Three checklist items in one call. Patients should not independently interrupt immunosuppression: missed doses risk rejection and illness can alter exposure. The transplant center may intentionally hold or adjust a drug and directs the dose, route and monitoring. Clarithromycin is a CYP3A4 inhibitor that would do to her trough in days what diltiazem did in weeks; the nasal-spray influenza vaccine is live (she gets the injected inactivated one); and a fever in an immunosuppressed patient is a same-day call. Why not the others: B applies the right rule to the wrong drugs — the single most dangerous misreading of a sick-day card; C gets the infection risk right and every move wrong — a live vaccine and a drug that raises her tacrolimus; D puts an NSAID back on her list and waits weeks to learn what vomiting did to her level. Course reading: Evidence for this case
Resolution and Teaching Points
Answers for this section: W1 · W2 · W3 · Q4 · Q5 · Q6 · Q7 · Q8 · Q9 · Q10 · Q11 · Q12
Diltiazem stopped that afternoon. The center lowered her tacrolimus dose before the 8 p.m. dose and set troughs for day 4 and day 10. She left with oral magnesium, a low-potassium diet sheet, acetaminophen for the headache, a dermatology referral for the forearm keratoses, and a transplant card for her wallet.
Day 1: she drank about two liters overnight; potassium 5.6, creatinine 1.9, magnesium 1.4, fasting glucose 206 — fluids and no ibuprofen barely moved the creatinine, as expected while the level was still high. Day 2: potassium 5.3, creatinine 1.8. Day 3: her home average passed 130/80, and amlodipine 5 mg started with the center's agreement.
Two weeks later: creatinine 1.3 mg/dL, potassium 4.7, bicarbonate 23, magnesium 1.8 on oral replacement, fasting glucose 131, trough 7.4 ng/mL on the new dose. The tremor was gone by day 8 and the headaches with it — she realized afterward that the headache she took ibuprofen for was itself a symptom of the level. Blood pressure 134/84 on home readings; amlodipine increased to 10 mg daily.
Three months later: creatinine 1.2 (eGFR back to about 57), potassium 4.4, magnesium 1.9, A1c 6.4% (below the 6.5% diabetes threshold), trough 6.9, blood pressure 126/78. Dermatology treated two actinic keratoses and booked yearly skin checks. The chart now carries a banner — kidney transplant recipient on tacrolimus: check every new drug against the interaction list and notify the center — and the clinic added the same banner to its other four transplant patients.
Clinical Pearl — The med list by date When a stable patient destabilizes on an unchanged dose, the usual answer is a new drug changing how an old drug is cleared — not progression of disease. Read the medication list by start date before you read it by drug class.
Clinical Pearl — The high-tacrolimus cluster Tremor or headache, a creatinine rise, hyperkalemia with a mild normal-gap acidosis, low magnesium, high glucose, a blood pressure that climbs. Any two in a tacrolimus patient should buy a trough — drawn before the morning dose, with the clock time written on the requisition.
Clinical Pearl — Same arteriole, same urine NSAIDs and excess tacrolimus both injure the kidney by constricting the afferent arteriole, so both give a bland, concentrated urine. The urinalysis sorts out post-renal and structural intrinsic causes; it cannot choose between two hemodynamic ones — the trough can. Caught early, the tacrolimus injury reverses as the level falls; years of high levels scar the kidney for good.
Clinical Pearl — Whose drug is it? The interacting drug you started is yours to stop. The transplant drugs are the center's to adjust or hold. The electrolytes are yours to start treating and theirs to co-sign. Hand them clean numbers the same day.
Clinical Pearl — Why "call" is on the sick-day card, not "hold" Vomiting and diarrhea change tacrolimus levels — persistent diarrhea can raise them. That is the reason transplant drugs are never held by the patient and the center is called instead. SADMANS drugs are held; transplant drugs are reported.
Pitfall — Treating the cluster one organ at a time An ACE inhibitor for the pressure (the potassium climbs), insulin for the glucose, magnesium for the tremor, "watchful waiting" for the creatinine — four correct-looking moves and nobody asks why four things moved together. One trough answers all four.
Pitfall — "The blood pressure is finally controlled, so keep the diltiazem and lower the tacrolimus to match" This leaves the interaction in place and turns every future dose change into a guess — the same error as the paroxetine–metoprolol case (Course reading: site Case 31) with different drugs. Remove the inhibitor; let the center re-titrate the drug that matters.
Concept Links
Answers for this section: W1 · W2 · W3 · Q4 · Q5 · Q6 · Q7 · Q8 · Q9 · Q10 · Q11 · Q12
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, aki-13, aki-14, aki-27, ckd-18, ckd-19, ckd-20, htn-cardiorenal-07, htn-cardiorenal-08, lytes-14, lytes-18, structural-20, structural-27.
Source verification — 2026-10-12
Answers for this section: W1 · W2 · W3 · Q4 · Q5 · Q6 · Q7 · Q8 · Q9 · Q10 · Q11 · Q12
Lemahieu et al. (PMID 15888045) documented increased tacrolimus exposure in kidney-transplant recipients with persistent diarrhea. The direction is not guaranteed for every illness; check the trough and contact the transplant team. Do not independently change maintenance immunosuppression. The teaching checklist prompts contact and assessment; the receiving transplant center determines its own protocol.