Drugs and the Kidney / Toxic Nephropathies
• Many drugs require dose adjustment in CKD to avoid toxicity due to reduced clearance:
o Aminoglycosides – nephrotoxic, require careful therapeutic monitoring
o Lithium – narrow therapeutic window; accumulates in CKD, ↑ risk of toxicity
o Digoxin – renally cleared; monitor levels in CKD and with hypokalaemia
1. Aminoglycosides (e.g. gentamicin)
• Cause acute tubular necrosis (ATN) via direct toxicity to proximal tubule cells
• Risk factors: dehydration, prolonged use, other nephrotoxins
• Monitor drug levels and renal function closely
2. Amphotericin B
• Causes renal vasoconstriction and tubular damage, leading to AKI and electrolyte disturbances (↓ K⁺, ↓ Mg²⁺)
• Liposomal formulations are less nephrotoxic
3. NSAIDs
• Triple mechanism of nephrotoxicity:
o Pre-renal AKI (↓ prostaglandin-mediated afferent arteriolar dilation)
o AIN (hypersensitivity reaction)
o Papillary necrosis (long-term use)
4. Radiocontrast agents
• Cause contrast-induced nephropathy: ATN-like injury peaking ~48–72 hrs post-exposure
• Risk: pre-existing CKD, diabetes, dehydration
• Prevention: IV hydration, withhold nephrotoxins, consider N-acetylcysteine
• Cause dose-dependent vasoconstriction of afferent arterioles → ↓ GFR
• Long-term use leads to chronic interstitial fibrosis
• Monitor drug levels and renal function; nephrotoxicity may be indistinguishable from rejection
• Lead, mercury, cadmium → chronic tubulointerstitial nephritis
• Features: slowly progressive CKD, Fanconi syndrome (proximal tubule dysfunction)
• Diagnosis: exposure history, heavy metal levels
• Management: chelation therapy in selected cases
• Found in antifreeze; metabolised to oxalic acid → tubular damage
• Features:
o Severe metabolic acidosis, ↑ anion gap
o AKI with oxalate crystal deposition in renal tubules (envelope-shaped crystals)
• Diagnosis: osmolar gap, serum ethylene glycol (if available)
• Management: fomepizole or ethanol, haemodialysis
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Author & Educational Disclaimer
Author:
Dr Phillip Cockrell BM FRCP DipClinEd
Dr Phillip Cockrell is a UK Consultant Physician in Internal Medicine, currently working at Queen Alexandra Hospital, Portsmouth University Hospitals NHS Trust. He has previously worked as a registrar across Intensive Care Medicine, Gastroenterology, Cardiology, Stroke Medicine, Acute Medicine, and Respiratory Medicine.
He has held senior leadership roles including Associate Clinical Director of the Acute Medical Unit, Clinical Director of Internal Medicine, and Chief of Medicine. Dr Cockrell has over 15 years’ experience in postgraduate medical education, having lectured extensively across the MRCP syllabus and contributed to MRCP revision teaching and course development.
Dr Cockrell holds a Bachelor of Medicine (BM), Fellowship of the Royal College of Physicians (FRCP), and a Diploma in Clinical Education (DipClinEd). His teaching approach is based on structured consolidation of complex medical topics to support efficient and effective revision for postgraduate examinations.
Purpose of this content:
The material on this page is intended solely for educational purposes to support revision for the MRCP (UK) Part 1 examination. It reflects examination-relevant principles of internal medicine and is designed to aid learning and pattern recognition.
Medical disclaimer:
This content is designed for postgraduate medical examination revision and does not constitute medical advice, diagnosis, or treatment guidance and must not be used as a substitute for professional clinical judgement, local guidelines, or specialist consultation. Clinical decisions should always be made in the context of individual patient circumstances and current national guidance.
