Miscellaneous Stone Types

Abstract

Drug-induced calculi and other rare stone types, such as ammonium acid urate or protein matrix stones, represent only about 2% of all renal calculi. However, the chance to easily reverse stone formation risk by discontinuing the offending drug makes identification of these entities important for clinicians. Additionally, study of these rare stone types contributes to understanding the biochemistry of stone formation. Drug-induced calculi may be classified into two groups based on the mechanism of stone formation. The first group includes drugs that provoke calculi composed of principally the drug and its metabolites. These medications tend to be poorly soluble, highly excreted in urine, and required at high dosages for long durations of therapy. Historically, sulfonamides, triamterene, and the HIV protease inhibitor indinavir were leading causes of drug-induced calculi. Uses of novel agents within these drug classes or alternative therapies have reduced the incidence attributed to these drugs, although risk from newer, commonly used medications-notably ciprofloxacin, aminopenicillins, ceftriaxone, ephedrine, and guaifenesinare increasingly being recognized. Microscopic analysis for crystalluria or infrared spectroscopy of collected stones aid in recognition of calculi composed primarily of a drug and its metabolites. Understanding of drug metabolism and pharmacokinetics, particularly related to effects of urine pH on drug solubility and excretion, provides a rational basis for both prevention and treatment recommendations. When possible, clinicians should avoid or exercise great caution when prescribing these medications to patients with a prior history of stones. The second group of drug-induced calculi includes drugs that cause stones due to their metabolic effects, primarily on calcium or purine metabolism. Because these calculi are identical in physical composition to the more common nephrolithiasis types, careful medication history and high clinical suspicion are required for diagnosis of these drug-induced ''metabolic'' calculi. Most drugs in this class are readily expected based on their effects on urinary calcium excretion such as calcium/Vitamin D supplements and loop diuretics. Carbonic anhydrase inhibitors, including the antiepileptics topiramate and zonisamide, are also included in this group. Ammonium acid urate stones are endemic in developing countries due to dietary limitations and recurrent diarrheal illness, but rarely occur in developed countries. Identification of these stones should raise clinical suspicion of epidemiologic risk factors including recurrent urinary tract infections with urea-splitting organisms, inflammatory bowel disease, and laxative abuse. Interestingly, these unusual clinical scenarios can recapitulate a common biochemical pathway to stone formation. Protein matrix stones are another unusual stone type associated with specific epidemiologic factors, namely recurrent urinary infections and proteinuric end-stage renal disease. Although distinctly rare, protein matrix stones ...

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

“…Therefore, in accordance with the general, aforementioned pathophysiological premises, when the solubility equilibrium is exceeded, these drugs may undergo nucleation and crystallisation (both homogeneous and heterogeneous) in supersaturated urine. The second group of drug-induced urinary stones are those classified as a sub-type of "metabolic stones", due to the evoked metabolic effects of a drug, primarily on calcium or purine metabolism [25,26]. 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), alternation of the glomerular filtration and tubular secretion/reabsorption of the endogenous substances, or impairing the balance and action of crystallisation promoters/inhibitors (while enhancing the effects of the promoters of the phenomenon) [27].…”

“…To sum up, the physiological and biochemical disturbances, which form the basis for urinary stone development (nucleation, crystal growth, crystal aggregation) may be also drug-evoked. Since the chemical composition of drug-induced metabolic stones does not contain the drug itself, but appears identical to the non-drug dependent counterparts, the differential diagnosis of those drugs is particularly difficult and requires careful assessment [25][26][27][28].…”