Kidney Stone Disease With Special Regard to Drug-Induced Kidney Stones – A Contemporary Synopsis

Abstract

Kidney stone disease (nephrolithiasis; urolithiasis) is a clinical entity with long-term course and recurrence, primarily affecting mature and ageing men, involving the formation and presence of urinary stones in the kidneys and urinary tract. The pathogenesis of this disorder is complex and still not fully understood. A rare, potentially modifiable, form of kidney stone disease takes the form of drug-induced urinary stones. The aim of the review was a brief description of the classification and pathophysiology of kidney stone disease, along with the short characteristics of drug-induced urinary stones. This type of stones is formed as a result of crystallisation in the kidneys and urinary tract of sparingly soluble drugs and their metabolites, or as a result of metabolic changes caused by drugs, predestinating the development of stones containing endogenous compounds. Conclusion: Therefore, during treatment with the use of drugs with high lithogenic potential, the safety of pharmacotherapy should be monitored in the context of its increased risk of developing urinary stones.

A Synopsis of Current Theories on Drug-Induced Nephrotoxicity

“…Drugs regarded as being associated with an increased risk of the ability to form intrarenal crystal deposition mostly include sulphonamides, triamterene, antiretroviral drugs used in HAART therapy (delavirdine, efavirenz, nevirapine, and rilpivirine), antacids (magnesium trisilicate, aluminum hydroxide), methotrexate, quinolones (ciprofloxacin, norfloxacin), and some antibiotics (e.g., ampicillin, amoxicillin) [ 10 , 17 , 18 , 19 , 20 , 21 ]. Detailed information on the etiopathogenesis of drug-related nephrolithiasis, with particular emphasis on the specific types of drug-induced stones, is beyond the scope of this study and can be found in the detailed reviews on this subject [ 59 , 60 , 61 ]. It should be emphasized that apart from drug-induced kidney stones, developing as a result of the direct precipitation of drugs and their metabolites in the urinary tract, other indirect “metabolic, drug-related stones” may be distinguished.…”

“…It should be emphasized that apart from drug-induced kidney stones, developing as a result of the direct precipitation of drugs and their metabolites in the urinary tract, other indirect “metabolic, drug-related stones” may be distinguished. The pathogenesis of the latter is associated with the induction of metabolic changes promoting lithogenesis caused by some drugs, and maybe a consequence of loop diuretics or laxatives that cause electrolyte changes, high doses of vitamin C that significantly acidify the urine, or xanthine oxidase inhibitors (allopurinol), and uricosuric compounds that cause hyperuricemia [ 60 ]. From a clinical perspective, crystal nephropathies are associated with abnormal urinalysis and urinary sediment findings, tubulopathies, and chronic kidney disease.…”

Lower Urinary Tract Disorders as Adverse Drug Reactions—A Literature Review

“…Kidney stone pain is a severe cramping pain evoked by the movement of a stone through the urinary tract, which is augmented by the ureteral spasm and possible obstruction. The pain is usually not related to body position and is accompanied by nausea, vomiting and macro- or at least micro-hematuria and often bladder overactivity symptoms (sensation of urinary frequency and urgency) [ 52 ]. The detailed description of the pathophysiology and symptomatology of urolithiasis is out of the scope of this paper and can be found in other reviews [ 51 , 53 , 54 , 55 , 56 ].…”

“…According to general aetiology, one can distinguish infectious and non-infectious stones, those caused by genetic defects and those induced as a result of adverse drug reactions. On the other hand, based on the above-mentioned chemical composition, five main types of stones can be classified: calcium, struvite or magnesium ammonium phosphate, uric acid or urate, cystine and rare stones (including drug-induced ones) [ 52 , 57 ].…”

“…The second group of drug-induced urinary stones are those classified as a sub-type of “metabolic stones”, due to the fact that treatment with these drugs contributes to the development of metabolic disturbances that facilitate the crystallisation of endogenous lithogenic substances. Many drugs may induce urinary stone development by affecting the pH of urine (in such a way that the solubility of many endogenous substances decreases), the alternation of the glomerular filtration and tubular secretion/reabsorption of the endogenous substances, or impairing the balance and action of crystallisation promoters/inhibitors [ 52 , 58 , 59 , 60 ]. The drugs contributing to drug-induced kidney stone development are listed in Table 4 .…”