A 48-year-old woman with osteoarthritis has been taking ibuprofen 400 mg TDS for 6 months. She now complains of persistent ankle swelling, dyspnea on exertion, and a 3 kg weight gain over 2 weeks. On examination, she has bilateral ankle edema and elevated JVP. Which investigation would best confirm the suspected NSAID-induced adverse effect?

Explanation

## Investigation of Choice for NSAID-Induced Renal Toxicity with Fluid Retention **Key Point:** Serum creatinine and 24-hour urine protein are the most appropriate investigations to confirm NSAID-induced acute kidney injury (AKI) and nephrotic-range proteinuria, which are the underlying mechanisms of fluid retention and edema in this patient. ### Pathophysiology of NSAID-Induced Renal Injury 1. **Mechanism:** NSAIDs inhibit COX-1 and COX-2, reducing renal prostaglandin (PGE₂, PGI₂) synthesis 2. **Effect on renal hemodynamics:** Loss of afferent arteriole vasodilation → decreased glomerular filtration rate (GFR) 3. **Sodium and water retention:** Reduced renal perfusion activates RAAS → sodium reabsorption → fluid accumulation 4. **Proteinuria:** Direct glomerular injury can cause nephrotic-range proteinuria (>3.5 g/24 h) ### Clinical Presentation in This Case - **Bilateral ankle edema** — suggests systemic fluid retention - **Weight gain (3 kg in 2 weeks)** — rapid onset suggests acute kidney injury with fluid overload - **Dyspnea on exertion + elevated JVP** — signs of fluid overload, not primary cardiac dysfunction - **Risk factors:** Female, age >45, 6 months of continuous NSAID use **High-Yield:** NSAID-induced AKI typically presents with: - Serum creatinine elevation (often >50% from baseline) - Oliguria or non-oliguric presentation - Fractional excretion of sodium (FE~Na~) <1% (prerenal pattern) - Urinary sodium <20 mEq/L ### Why Serum Creatinine + 24-Hour Urine Protein? | Investigation | What it detects | Diagnostic value | |---|---|---| | **Serum creatinine** | GFR decline; degree of renal dysfunction | Confirms AKI; baseline for monitoring | | **24-hour urine protein** | Nephrotic-range proteinuria (>3.5 g/day) | Confirms glomerular injury from NSAID | | **Transthoracic echo** | Cardiac structure/function | Rules out primary cardiomyopathy, but not diagnostic for NSAID nephrotoxicity | | **Chest X-ray + BNP** | Pulmonary edema, cardiac strain | Non-specific; elevated in any cause of heart failure | | **Renal ultrasound + Doppler** | Renal artery stenosis, obstruction | Not indicated unless renovascular disease suspected | **Clinical Pearl:** NSAID-induced acute kidney injury is often reversible if the drug is discontinued early. Delayed diagnosis (relying on imaging alone) may result in progression to chronic kidney disease. Serum creatinine and proteinuria are the most direct markers of glomerular and tubular injury. **Mnemonic: NSAID Renal Injury — STOP:** - **S** — Serum creatinine elevation - **T** — Tubular dysfunction (oliguria, sodium retention) - **O** — Overload (fluid retention, edema, dyspnea) - **P** — Proteinuria (nephrotic range possible)