Drug-induced urolithiasis.

Diagnostic and therapeutic drugs may enhance urolithiasis in one or a combination of ways, including: (1) alteration of urine pH in such fashion as to create an environment that increases the solubility of some lithogenic substances, (2) alteration of glomerular filtration rate, tubular reabsorption, and tubular secretion of drugs of endogenous substances so as to enhance promoters or impair inhibitors of urolithiasis, and (3) precipitation (e.g., drugs or their metabolites) to form a portion or all of a urolith.

Urolithiasis as a hazard of sulfonamide therapy.

We identified 40 patients (25 men and 15 women) who developed calculi composed totally or partially of sulfonamides (acetylsulfamethoxazole, sulfadiazine, and acetylsulfisoxazole) between 1980 and 1987. The incidence of sulfonamide stones is less than 1% of stones. Patient characteristics were determined from questionnaires sent to the patients and attending physicians. The majority of patients developed symptoms 1 to 4 weeks after beginning sulfonamide therapy. The bladder was the most common stone location. Obstruction of the urinary system by the acetyl derivatives of the drug is the most serious consequence of sulfonamide therapy. Early recognition of drug-related stones is essential to protect patients from recurrences, reduce the risk of renal complications, and avoid continuing ineffective therapeutic regimens.

Dissolution of calcified gallstones. Part I. Correlation of in vitro dissolution kinetics in methyl tert-butyl ether with patterns of calcification by computed tomography.

RATIONALE AND OBJECTIVES: The authors evaluated the relationship between stone computed tomography (CT) attenuation patterns and the kinetics of dissolution with methyl tertbutyl ether (MTBE). METHODS: Single moderately and heavily calcified gallstones from 40 patients were selected from a gallstone library and classified for pattern of calcification by in vitro CT scan (dense, rim, core, and laminated). Each stone was placed in a 10-mL aliquot of MTBE for 24 hours. Stone residue was blotted dry and weighted at 8, 16, and 24 hours. Results were normalized with respect to stone size. RESULTS: Only 1 of 40 (4%) specimens dissolved to particulate matter that was smaller than 2 mm. All (6 of 6) stones that were densely calcified showed virtually no dissolution. The rate of gallstone dissolution varied temporally within the rim, core, and laminated stone categories and was related to the composition of the layer exposed to the solvent at any given time. CONCLUSION: The success and rate of dissolution may be predicted by the pattern of calcification as determined by computed tomography (CT).

Dissolution of calcified gallstones. Part II. Evaluation of edetic acid preparations for dissolution of residue after in vitro methyl tert-butyl ether treatment.

RATIONALE AND OBJECTIVES: The authors assessed the potential of edetic acid (EDTA) preparations to dissolve the residue of calcified gallstones partially treated with methyl tert-butyl ether (MTBE). METHODS: Nineteen triplets (57 gallstones) were submitted to dissolution in EDTA, urea-EDTA, and an MTBE control for 48 hours after initial partial dissolution in MTBE for 24 hours. Results were compared with findings at specimen computed tomography and crystallographic analysis. All data were corrected for differences in stone size. RESULTS: In all three treatment groups (EDTA, urea-EDTA, MTBE), almost identical dissolution outcomes were observed within each triplet. Most triplets that dissolved displayed a laminated or a core-calcification pattern and consisted primarily of cholesterol. Specimens that dissolved poorly in all three groups displayed dense calcifications or thick calcified rims and were classified as pigment stones. CONCLUSION: Because no statistically significant differences in dissolution were found among the EDTA, urea-EDTA, and MTBE treatments, we conclude that EDTA preparations are not superior to the continued use of MTBE for dissolution of residue after initial MTBE treatment.

Prediction of gallstone composition: synthesis of CT and radiographic features in vitro.

PURPOSE: To test a morphoradiographic algorithm designed to predict the composition of gallstones with use of computed tomography (CT) to define calcification patterns. MATERIALS AND METHODS: Two reviewers retrospectively evaluated the radiographic features of 120 separate in vitro specimens (59 radiopaque and 61 radiolucent), then classified the stones into several categories of composition with the algorithm. RESULTS: The most useful features for prediction of cholesterol composition were, in order of decreasing importance, stone shape, absence of dense calcification on plain radiographs, overall CT attenuation not higher than that of water, presence of a second generation of smaller stones, and a peripheral cover of calcification detected on CT scans of aging cholesterol stones. The greatest error occurred in distinction between stones with mixed composition (50%-79% cholesterol) and older stones with higher cholesterol content (80%-95% cholesterol). CONCLUSION: The range of qualitative CT appearances advances the possibility of predicting gallstone composition and potential outcome of nonsurgical treatment.

Triamterene nephrolithiasis: renewed attention is warranted.

Although triamterene has been known to contribute to urinary calculus formation, it has been presumed to be a rare phenomenon. Our review of stone analyses performed during the last decade by a single laboratory reveals an increasing incidence of triamterene stones. Awareness of the calculogenic potential of triamterene-containing medications should be re-emphasized.

Cystine calculi--rough and smooth: a new clinical distinction.

Four stones each from 2 populations of cystine calculi, 1 with a rough external surface (cystine-R) and the other smooth (cystine-S), were studied for their crystal structure with stereoscopic and scanning electron microscopy. Two stones each of cystine-R and cystine-S, calcium oxalate monohydrate, calcium oxalate dihydrate, struvite plus apatite and brushite were fragmented with extracorporeal shock wave lithotripsy and the fragmentability was compared. Fragments resulting from cystine-R and cystine-S extracorporeal shock wave lithotripsy were examined under the stereoscope to assess the plane of cleavage or fracture. Results show that cystine-R stones are comprised of well formed blocks of hexagonal crystals, whereas cystine-S calculi have small, irregular and poorly formed interlacing crystals. The center of cystine-R stones was similar to that of the periphery but the center of cystine-S stones was formed of blocks of hexagons similar to but smaller than the cystine-R calculi. Fragmentation with extracorporeal shock wave lithotripsy revealed that cystine-S stones are the least fragile, calcium oxalate dihydrate and struvite plus apatite were the most fragile, and cystine-R, brushite and calcium oxalate monohydrate calculi were in the intermediate fragility range. The possibility of the patient having a cystine-R calculus should be considered during therapeutic procedures.

Physical characteristics of gallstones removed at cholecystectomy: implications for extracorporeal shock-wave lithotripsy.

The criteria by which patients are selected for new, nonsurgical forms of gallstone therapy will influence the use of these techniques. We estimated the number of patients with gallbladder stones who are potentially suitable for extracorporeal shock-wave lithotripsy according to the current Food and Drug Administration protocol for the United States trials of the Dornier gallbladder lithotriptor. Exclusion criteria include patients with (1) more than three stones, (2) stones less than 0.5 cm or more than 3.0 cm in diameter, (3) radiopaque stones, and (4) a nonfunctioning gallbladder. The gallbladder contents in 100 consecutive patients undergoing cholecystectomy were analyzed according to the number, size, and calcium content of the stones as determined by specimen radiographs. Because none of these patients underwent preoperative oral cholecystography, an estimated percentage of functioning gallbladders was taken from the literature. Preoperative symptoms were not considered in determining a patient's eligibility for gallbladder lithotripsy. On the basis of these criteria, we estimated that 85% of our surgical patients would have been excluded from extracorporeal shock-wave lithotripsy according to the current Food and Drug Administration protocol for the Dornier gallbladder lithotriptor.

Computed tomographic analysis of urinary calculi.

Excised urinary calculi were subjected to computed tomographic (CT) scanning in an attempt to determine whether CT attenuation values would allow accurate analysis of stone composition. The mean, maximum, and modal pixel densities of the calculi were recorded and compared; the resulting values reflected considerable heterogeneity in stone density. Although uric acid and cystine calculi could be identified by their discrete ranges on one or more of these criteria, calcium-containing stones of various compositions, including struvite, could not be distinguished reliably. CT analysis of stone density is not likely to be more accurate than standard radiography in characterizing stone composition in vivo.

Percutaneous catheter dissolution of cystine calculi.

In 11 kidneys with presumed cystine stones that were symptomatic and obstructing, percutaneous nephrostomy and stone lavage with either acetylcysteine-bicarbonate solution or tromethamine-E were performed. There were 7 complete stone dissolutions: 2 of 6 attempts with acetylcysteine-bicarbonate alone, 3 of 5 with tromethamine-E, 1 partial with acetylcysteine-bicarbonate, which was completed with tromethamine-E, and 1 proved mixed stone (cystine and calcium phosphate) that required acetylcysteine-bicarbonate and hemiacidrin. In 1 case tromethamine-E irrigation was 97 per cent complete but a few tiny caliceal fragments remained. There were 3 failures of chemolysis: 2 pure cystine stones (1 each acetylcysteine-bicarbonate and tromethamine-E) and 1 mixed calculus with a surface shell of calcium oxalate. Irrigation time was 6 to 42 days for the 7 unoperated kidneys. Tromethamine-E appears to be a more effective agent for cystine stone dissolution. Percutaneous nephrostomy and dissolution are an alternative to an operation in patients with cystine calculous disease.

Determination of the chemical composition of urinary calculi by computerized tomography.

The clinical management of renal calculi would be aided if a direct in vivo determination of stone chemical composition could be made. We investigated the possibility of obtaining this information by a quantitative analysis of the computerized tomography scan images of 80 urinary calculi. Our results show that by using an appropriately calibrated computerized tomography scanner the differentiation of stone chemical composition can be made on the basis of 3 parameters, namely, absolute computerized tomography value at a single x-ray energy, the difference between computerized tomography values measured at 2 different x-ray energies, and computerized tomography value-frequency histograms (pixel patterns) of the stones. Uric acid stones were differentiated from all other stones at a significance level of p less than 0.001. Cystine was differentiated from calcium oxalate and brushite at the same significance level. Using pixel patterns cystine and struvite were separated from each other correctly with 70 per cent accuracy. Struvite stones of low or moderate calcium phosphate content were identified correctly with 80 per cent accuracy. Struvite stones of high calcium phosphate content could not be differentiated from calcium oxalate or brushite. Calcium oxalate and brushite could not be separated. The minimum stone size that allowed chemical identification was established for each stone type. In addition, we demonstrated that all the urinary calculi examined were visible on computerized tomography scan regardless of chemical composition or size.

A repeated dose-response study of methazolamide in glaucoma.

Twenty-two patients with open-angle glaucoma were given weekly courses of methazolamide at different dosages. Mean intraocular pressure reductions of 3.3, 4.3, and 5.6 mm Hg were achieved at dosages of 25 mg, 50 mg, and 100 mg of methazolamide every eight hours, respectively. Maximal intraocular pressure lowering was still present nine to ten hours after administration. The mean reduction in outflow pressure for all eyes receiving a daily dosage of 300 mg was only 31%, but this included eyes (17% of the total) that demonstrated less than 13% reduction in outflow pressure, despite similar methazolamide serum levels. Eight patients subsequently received acetazolamide, 250 mg four times a day for a week. The effect of this dosage of acetazolamide on pressure was between the effects of 50 and 100 mg of methazolamide three times daily.

Trace elements in kidney stones from three areas in the United States.

A large number of trace elements has been found in calcium stones (whewellite, weddellite, and apatite) and in struvite. Significantly fewer elements, with lower abundances, are found in uric acid and cystine. With the exception of four trace elements (lead, silicon, strontium, and zine), the trace element assemblages are identical in the oxalates (whewellite and weddellite); struvite is also similar but with notable exceptions. In general, apatite contains approximately twice the level of trace element abundances as do the oxalates. This study is based on the distribution of 20 elements in 186 mimeralogically identified urinary calculi from three generalized areas of the United States (northeast, southeast, and midwest). In general, there is no statistical difference in the trace element assemblages of mineralogically identical stones from the three areas.

The presence of protein-bound gamma-carboxyglutamic acid in calcium-containing renal calculi.

The amino acid gamma-carboxyglutamic acid (Gla) is found in four blood-clotting proteins, in a bone protein, in kidney protein, and in the protein present in various ectopic calcifications. This paper reports the presence of Gla in the EDTA-soluble, nondialyzable proteins of calcium-containing renal calculi including calcium oxalate, hydroxyapatite, and mixed stores of apatite and struvite (MgNH4PO4). Calculi composed of pure struvite and those composed of only uric acid or cystine do not contain Gla. From calcium oxalate and hydroxyapatite stontes, a protein of about 17,000 daltons was obtained which contained about 40 residues of Gla per 1,000 amino acids. The amino acid composition of this protein had no apparent relationship to the Gla-containing bone protein or to the similarly-sized F1 fragment of prothrombin which contains about 64 residues of Gla per 1,000 amino acid residues. The Gla-rich protein in calcium-containing renal stones thus may be a different Gla-containing protein. These data as well as other studies demonstrating the presence of Gla in pathologically calcified tissues not normally containing Gla suggest that the Gla-containing proteins may be of considerable pathophysiological significance.

Degree of sulfation in mucopolysaccharide sulfates in normal and stone-forming urines.

Mucopolysaccharides were extracted from both normal and stone-forming urines, and those from the stone-forming samples showed a higher degree of sulfation than those from normal urines, as determined by sulfate analysis and electrophoretic measurement. The sulfated mucopolysaccharides from stone-forming urines formed insoluble calcium salts, whereas those from normal urines generally remained soluble in the presence of calcium ion. Rachitic rat cartilage was found to have more highly sulfated mucopolysaccharides than normal rat cartilage. Highly sulfated mucopolysaccharides appear to be a significant factor in calcium stone formations.

Kidney stone matrix. Differences in acidic protein composition.

Organic matrices from kidney stones of several mineral compositions (calcium oxalate, uric acid, and apatite-struvite) were isolated and found to contain an abundance of acidic amino acids. The calcium oxalate stones contained 50% aspartic and glutamic acid residues while the uric acid stones contained over 65%. The apatite-struvite stones had only 30% of these two amino acid residues and also contained 20% glycine residues. Since the specific amino acid composition differed for stones of different mineral content, it was felt that the organic matrix might play the role of a nucleating agent.

The riddle of Randall's plaques.

Randall described a pre-calculus lesion of the renal papilla in the 1930s and this was substantiated by others during the next decade and then largely ignored. This insignificant subepithelial calcification of the renal papilla. Randall's plaque type I, becomes the nucleus of at least 15% of calcium oxalate calculi, as demonstrated by apatite nuclei existing in papillary depression on the external stone surface. Cross section study of the stone demonstrates the peripheral nucleus with eccentric lamination postulating a mural origin. Contrariwise, study of the stone developing upon a nucleus originating in the papillary ducts (without producing obstruction) or out in the calix demonstrates a central nucleus surrounded by concentric laminations or lack of a mural origin, the more common type of calcium oxalate stone structure. Obstruction of the papillary ducts by hyperexcretion of stone salt may result in anemic infarction and sloughing of the apex of the papilla. Data concerning the prevalence of Randall's plaques in the population have been reviewed. Evidence of the incidence of calcium oxalate calculi that have developed upon Randall's plaques has been presented. A plea for further study of the pathology of the renal papilla has been voiced.