Drug Dosing in Kidney Disease — Viva

Q1: Foundational principles (2 min)

Examiner: "Why is drug dosing a separate discipline in kidney disease, and what is the single framework you would use to prescribe safely?" [1]

Model answer: The kidney is the principal organ of elimination for many drugs and their water-soluble metabolites, so a falling GFR causes predictable accumulation and toxicity unless doses are adjusted — while a separate set of drugs directly injure the kidney. I use the five-step systematic approach: estimate kidney function (Cockcroft-Gault for dosing, eGFR CKD-EPI for staging), review every drug (renal-cleared, nephrotoxic, TDM, interactions), adjust the dose or interval (loading unchanged), monitor levels and renal function, and reassess at every high-risk moment — AKI, declining GFR, polypharmacy, new drugs, contrast, transitions of care. [1]

Examiner: "Name the two errors that most drug-dosing-in-CKD questions are testing." [1]

Model answer: (1) Not adjusting a renally-cleared drug — causing accumulation and toxicity (vancomycin, gabapentin, digoxin, DOACs, metformin). (2) Missing a nephrotoxin — NSAIDs, contrast, ACEi/ARB in volume depletion, vancomycin + piperacillin-tazobactam — that worsens kidney function. [1]

Q2: Estimating kidney function (2 min)

Examiner: "Reproduce the Cockcroft-Gault formula and explain why it is preferred over eGFR for drug dosing." [1]

Model answer: CrCl (mL/min) = [(140 − age) × weight in kg] / [72 × serum creatinine in mg/dL], then × 0.85 for women. Cockcroft-Gault is preferred for drug dosing because most drug labels and TDM nomograms were originally validated against it (Stevens 2009, AJKD). eGFR (CKD-EPI) is preferred for staging CKD and following progression. The two estimates usually agree within one dosing band but reclassify roughly 20 to 40 percent of patients, especially at extremes of body size and in the elderly. [1]

Examiner: "When would you NOT trust either formula?" [1]

Model answer: In AKI (non-steady-state creatinine — formulae overestimate GFR), in amputees, body-builders, cirrhosis, pregnancy (abnormal muscle mass or body composition — use measured 24-h creatinine clearance or cystatin C-based eGFR), and in extreme obesity (use an adjusted body weight). [1]

Q3: Dose-adjust, avoid, monitor (3 min)

Examiner: "Give me three drugs from each of the three categories." [1]

Model answer:

• Dose-adjust (renal clearance): vancomycin (AUC-guided), aminoglycosides (Hartford nomogram, extended interval), gabapentin/pregabalin (halve under GFR 30), digoxin (reduce + monitor), allopurinol (reduce under GFR 30).
• Avoid/caution: nitrofurantoin (under eGFR 30), metformin (under eGFR 30 — do not initiate, stop), NSAIDs (under 60 if possible; contraindicated in AKI), lithium, bisphosphonates (under 30 to 35).
• TDM: vancomycin AUC/MIC 400 to 600 (trough 15 to 20), aminoglycoside peak/trough, digoxin trough 0.5 to 0.9 ng/mL in CKD (lower target), lithium 12 h post-dose 0.4 to 1.0 mEq/L, tacrolimus trough, methotrexate at 24/48/72 h. [1]

Examiner: "What is the nephrotoxicity concern with vancomycin and piperacillin-tazobactam together, and what would you do?" [1]

Model answer: The combination causes synergistic AKI at two to four times the rate of either alone (ASHP/IDSA 2020 consensus), especially in CKD. I would switch piperacillin-tazobactam to cefepime, monitor vancomycin AUC closely, and reassess renal function daily. [1]

Q4: Special scenarios (2 min)

Examiner: "How would you adjust the DOACs in CKD?" [1]

Model answer: Dabigatran (80 % renally cleared) is avoided if CrCl under 30 mL/min. Apixaban is dose-reduced from 5 mg BD to 2.5 mg BD when two of three criteria are met: age over 80, weight under 60 kg, creatinine over 1.5 mg/dL. Rivaroxaban is reduced by CrCl band for some indications (e.g. 20 mg OD if CrCl over 50, 15 mg OD if 15 to 50 for AF). For severe CKD or dialysis, warfarin (with careful INR control) or apixaban are often preferred. [1]

Examiner: "What drugs are removed by haemodialysis and need a post-dialysis top-up?" [1]

Model answer: Water-soluble, low-molecular-weight, low-protein-binding, small-Vd drugs — aminoglycosides, most beta-lactams, vancomycin (less well, but still tracked), metformin, lithium, salicylate, methotrexate. Drugs NOT meaningfully removed — highly protein-bound or large Vd (digoxin, amiodarone, warfarin, phenytoin) — need no top-up. CRRT actively clears drugs and often requires higher-than-standard renal-failure doses because the filter clearance mimics a GFR of 20 to 40 mL/min. [1]

Q5: Pitfalls and exam pearls (1 min)

Examiner: "Give me one pitfall that catches candidates out." [1]

Model answer: Trimethoprim falsely raises serum creatinine by inhibiting tubular creatinine secretion (without changing true GFR), AND causes real hyperkalaemia by blocking the epithelial sodium channel (ENaC) in the distal tubule. A patient on trimethoprim with a rising creatinine and hyperkalaemia needs the drug stopped and the picture rechecked — the creatinine may partly normalise, but the hyperkalaemia was real and must be treated. [1]

Examiner: "Final one-liner." [1]

Model answer: "Estimate GFR, review every drug, adjust or avoid, monitor, reassess — at every visit and during AKI." [1]

References

1. [1]Lea-Henry TN, et al. Clinical Pharmacokinetics in Kidney Disease: Fundamental Principles. CJASN, 2018.PMID 29934432