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Drug-Induced Kidney Stones and Crystalline Nephropathy: Pathophysiology, Prevention and Treatment

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Abstract

Drug-induced calculi represent 1–2% of all renal calculi. The drugs reported to produce calculi may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favour crystallisation in the urine. Among them, drugs used for the treatment of patients with human immunodeficiency, namely atazanavir and other protease inhibitors, and sulphadiazine used for the treatment of cerebral toxoplasmosis, are the most frequent causes. Besides these drugs, about 20 other molecules may induce nephrolithiasis, such as ceftriaxone or ephedrine-containing preparations in subjects receiving high doses or long-term treatment. Calculi analysis by physical methods including infrared spectroscopy or X-ray diffraction is needed to demonstrate the presence of the drug or its metabolites within the calculi. Some drugs may also provoke heavy intra-tubular crystal precipitation causing acute renal failure. Here, the identification of crystalluria or crystals within the kidney tissue in the case of renal biopsy is of major diagnostic value. The second group includes drugs that provoke the formation of urinary calculi as a consequence of their metabolic effects on urinary pH and/or the excretion of calcium, phosphate, oxalate, citrate, uric acid or other purines. Among such metabolically induced calculi are those formed in patients taking uncontrolled calcium/vitamin D supplements, or being treated with carbonic anhydrase inhibitors such as acetazolamide or topiramate. Here, diagnosis relies on a careful clinical inquiry to differentiate between common calculi and metabolically induced calculi, of which the incidence is probably underestimated. Specific patient-dependent risk factors also exist in relation to urine pH, volume of diuresis and other factors, thus providing a basis for preventive or curative measures against stone formation.

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Authors and Affiliations

  1. CRISTAL Laboratory, Tenon Hospital, Paris, France

    Michel Daudon

  2. Laboratoire des Lithiases, Service des Explorations Fonctionnelles Multidisciplinaires, AP-HP, Hôpital Tenon, 4, rue de la Chine, 75020, Paris, France

    Michel Daudon & Vincent Frochot

  3. INSERM, UMRS 1155 UPMC, Tenon Hospital, Paris, France

    Michel Daudon & Vincent Frochot

  4. CNRS, UPMC, Paris, France

    Dominique Bazin

  5. Laboratoire de Chimie de la Matière Condensée de Paris, UPMC, Paris, France

    Dominique Bazin

  6. Department of Nephrology, Necker Hospital, AP-HP, Paris, France

    Paul Jungers

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  1. Michel Daudon
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Daudon, M., Frochot, V., Bazin, D. et al. Drug-Induced Kidney Stones and Crystalline Nephropathy: Pathophysiology, Prevention and Treatment. Drugs 78, 163–201 (2018). https://doi.org/10.1007/s40265-017-0853-7

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