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The inhibitory effect of human urine on urease-induced crystallization in vitro.

To study whether human urine contains inhibitors against urease-induced crystallization, Jackbean urease and human urine, in amounts small enough (0.5 to 10 per cent) not to influence the ion concentration, buffering capacity or pH, were added to synthetic urine. The ammonia production and alkalinization that followed were independent of the amounts of human urine added. The addition of human urine gave a dose-related decrease in the amount of calcium phosphate and struvite precipitated on glass rods immersed in the synthetic urine, however. Addition of only 0.5 per cent human urine gave a reproducible decrease and when 10 per cent human urine was added to the synthetic urine the precipitation of calcium phosphate was reduced by 50 per cent and that of struvite by 75 per cent. The results thus indicate that human urine contains components with the ability to reduce the urease-induced crystallization.

Adult↗

Combined percutaneous and extracorporeal shock wave lithotripsy for staghorn calculi: an alternative to anatrophic nephrolithotomy.

Combinations of percutaneous and extracorporeal shock wave lithotripsy were performed on 46 patients with 52 staghorn calculi. Of the renal units 15 per cent had minute residual fragments but only 9.7 per cent with struvite had residual stones. The morbidity of this combined approach is less than that of anatrophic nephrolithotomy. We believe that the majority of staghorn calculi can be removed in this manner. Nephrostolithotomy should be the initial procedure in most instances. This less invasive approach is especially advantageous in patients at high risk for recurrence.

Adolescent↗

Identification of urinary stone and sediment crystals by scanning electron microscopy and x-ray microanalysis.

A procedure based on scanning electron microscopic techniques is described for the identification of crystals in urinary sediments and stones. The crystals are identified by their morphology and elemental composition using scanning electron microscopy and x-ray microanalysis. The procedure has a number of advantages over conventional methods. It is easy to use. It is non-destructive so that both the exterior and interior of the same stone can be separately analyzed. It is the only technique in which information about spatial relationships between various crystals in a stone can be obtained easily. Scanning electron microscopic techniques can detect minor components, and analysis of a wide variety of materials ranging from amorphous substances to microcrystals to macroscopic stones is possible.

Animals↗

Glycosaminoglycans content of stone matrix.

The role of urinary glycosaminoglycans (GAGs) in lithogenesis is a topic of current interest in urologic research. One GAG, chondroitin sulfate, has previously been shown to inhibit calcium oxalate crystal formation. It has long been known that the chemical components of GAGs are present in the matrix of urinary concretions, but it has not been determined whether these components exist in free form or as constituents of GAG. This study was undertaken to determine whether GAGs are present in urinary stone matrices and, if so, to characterize them. Matrices of nine single urinary stones of various compositions and of three stone pools (calcium oxalate, magnesium ammonium phosphate) were isolated by exhaustive dialysis. The techniques of cellulose acetate electrophoresis, Alcian blue staining and enzymatic degradation were used to identify various GAGs. Material that stained Alcain blue was present in eleven of twelve samples. GAG was detected as this material in ten samples. The GAGs identified are heparan sulfate, hyaluronic acid and possibly keratan sulfate. The most prominent urinary GAG, chondroitin sulfate, was notably absent from urinary stone matrix. GAG seems to be incorporated into matrix on a selective basis. This finding may be due to differences in the affinities of different GAG species for the crystals which comprise the calculi. It has been proposed that the inhibitory activity of GAGs lies in their ability to bind to (and therefore block) the growth sites of crystals. It is apparent from this study that certain GAG species are incorporated into the structure of the stone and they may be intimately related to stone development and growth.

Calcium Oxalate↗

Graphic display of urinary risk factors for renal stone formation.

From the analysis of various urinary constituents and the estimation of urinary saturation of stone-forming salts, it is now possible to identify risk factors responsible for or contributing to stone formation. Metabolic factors included calcium, oxalate, uric acid, citrate and pH. Environmental factors were total volume, sodium, sulfate, phosphate and magnesium. Physicochemical factors represented saturation of calcium oxalate, brushite, monosodium urate, struvite and uric acid. A scheme for graphic display of risk factors was developed to allow ready visual recognition of important risk factors presumed to cause stone formation. This graphic display had diagnostic use as well as practical value in following response to treatment. For example, a low urinary pH and high urinary concentration of undissociated uric acid could be discerned readily in cases of uric acid lithiasis, as were high urinary pH and exaggerated urinary supersaturation of struvite in cases of infection lithiasis. In a patient with absorptive hypercalciuria and hypocitraturia treatment with thiazide and potassium citrate could be shown to abolish high risks (hypercalciuria, hypocitraturia and relative supersaturation of calcium oxalate) displayed before treatment.

Calcium↗

Percutaneous removal of kidney stones: review of 1,000 cases.

We report the results of 1,000 consecutive patients who underwent percutaneous removal of renal and ureteral stones. Removal was successful for 98.3 per cent of the targeted renal stones and 88.2 per cent of the ureteral stones. Complications, evolution and technique are discussed. Percutaneous techniques are an effective way to handle the majority of renal calculi and these techniques will continue to be important as shock wave lithotripsy becomes more widespread in the United States.

Blood Transfusion↗

Urease-induced crystallization in synthetic urine.

The urease-induced crystallization of magnesium ammonium phosphate and calcium phosphate was studied at different alkalinization degrees by incubating synthetic urine with increasing Jack Bean urease concentrations. The crystallization was studied as precipitation on glass rods immersed in synthetic urine. The calcium phosphate precipitation on the glass rods occurred when the pH reached 6.8. Magnesium ammonium phosphate precipitation occurred when the pH reached 7.0. The maximal crystallization occurred at a pH between 7.5 and 8.0; at higher pHs the precipitation was considerably lower. The possible mechanisms and clinical implications behind this narrow pH optimum for urease-induced crystallization, which also have important implications for future experimental studies, are discussed.

Calcium Phosphates↗

Ultrastructural microbial ecology of infection-induced urinary stones.

With advanced techniques of scanning and transmission electron microscopy we studied the ultrastructural ecology of bacteria associated with struvite calculi on catheter surfaces, and in the bladder, ureter and renal pelvis. These detailed morphological data indicate that the interstices, core and external surface of such struvite aggregates contain large numbers of bacterial cells that grow as microcolonies and thick biofilms within extensive fibrous organic matrices. These bacterial cells and their secreted products (glycocalyx or biofilm matrix) appear to provide initial foci for crystal development and aggregation of crystals to form macroscopic struvite stones. The protective glycocalyx-enclosed microcolonial mode of bacterial growth also may explain the relative resistance to antibiotics observed in bacteria associated with infection stones.

Bacterial Infections↗

Ureaplasma urealyticum-induced crystallization of magnesium ammonium phosphate and calcium phosphates in synthetic urine.

Crystallization of struvite and calcium phosphates was studied in vitro as encrustations on glass rods immersed in synthetic urine, to evaluate the crystallization capacity of Ureaplasma urealyticum and compare it with that of known urease and non-urease-producing bacteria. Inoculation of the synthetic urine with Ureaplasma urealyticum resulted in alkalinization of the synthetic urine and crystallization of struvite and brushite. Inoculation with Proteus mirabilis caused a faster and more pronounced alkalinization as well as crystallization of struvite and apatite. The alkalinization and crystallization caused by Ureaplasma urealyticum and Proteus mirabilis was completely prevented by acetohydroxamic acid, a potent urease inhibitor, linking the crystallization to the urease activity of the microorganisms. When the synthetic urine was inoculated with urease-negative Escherichia coli no alkalinization and no crystallization were seen.

Calcium Phosphates↗

A newly designed model for infection-induced bladder stone formation in the rat.

A newly designed urolithiasis model for rats, inducing a mild urinary tract infection, exhibiting reduced renal damage without pyelonephritis and causing reliable stone formation, was established. This was accomplished by implanting a zinc disc in the bladder and then performing transvesical inoculation of Proteus mirabilis into the bladder. Five days after challenge with 10(7) colony forming units (CFU) of P. mirabilis in each rat, the number of organisms in the bladder urine reached a level of over 10(5) colony forming units per ml. The infection was mostly restricted to the urinary tract organs. Infectious bladder stones were formed 5 days after infection and developed day by day, weighing 88.3 +/- 18.8 mg. on the 21st day. Blood urea nitrogen values stayed in the normal range in all test animals during this experiment. The main composition of the stones formed was shown to be struvite (MgNH4PO4 X 6H2O).

Animals↗

Bacteriology of branched renal calculi and accompanying urinary tract infection.

We determined the bacteriology of apparently infected renal calculi and accompanying urinary tract infections, and assessed the potential clinical value of the culture results. Twenty-two branched renal calculi from 16 patients were cultured. Fifteen calculi were infected with 1 or more urease-producing gram-negative enteric bacterium, 2 were infected with a urease-producing bacterium and a nonurease-producing organism, and 5 were sterile. Immersion of infected stones in antimicrobial solutions before culture reduced or eliminated surface bacteria but usually did not eradicate bacteria within the stone. The bacteriology of a stone or stones could be predicted on the basis of available urine culture results in only 2 of the 16 cases. These data suggest that branched renal calculi associated with bacteriuria usually are infected but that documentation of infection and identification of the infecting organism require culture of the stone.

Anti-Bacterial Agents↗

Primary dissolution therapy of struvite calculi.

Percutaneous nephrostomy and hemiacidrin were used as primary treatment of magnesium ammonium phosphate calculi in 32 surgical candidates. Of 28 patients who actually received hemiacidrin 24 (85 per cent) had successful treatment (no surgery necessary), including 19 (68 per cent) who had total stone dissolution. There were no significant complications. Patients have been followed for 3 months to 7 years. Percutaneous nephrostomy with hemiacidrin infusion is another possible treatment in the growing alternatives available for patients with urinary struvite calculi.

Citrates↗

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.

Calcium Oxalate↗

Hemiacidrin irrigation in the management of struvite calculi: long-term results.

Renacidin (10 per cent hemiacidrin) irrigation has been used in the management of renal struvite calculi in 25 patients. Of these patients 22 were free of stone after irrigation: 16 after dissolution of residual stone fragments postoperatively, 4 after prophylactic postoperative irrigation and 2 after primary, nonsurgical percutaneous dissolution. Recurrent urinary tract infections owing to the original urease-producing bacteria occurred in 14 per cent of these patients and recurrent nephrolithiasis occurred in 9 per cent during an average followup period of 66 months.

Adult↗

Urolithiasis in rats with diabetes insipidus (Brattleboro strain rats).

Brattleboro strain rats homozygous for hypothalamic diabetes insipidus (DI rat) excrete nearly their body weight per day in dilute urine and yet can form bladders stones composed of struvite and apatite. Studies were undertaken to investigate this apparent paradox. The results show that DI rat urine is indeed undersaturated with respect to struvite and apatite. However, chronic infection of DI rat urine with a urease-containing organism (Proteus mirabilis) results in the rapid formation of large struvite/apatite bladder stones. It is concluded that the Brattleboro strain DI rat, like man and unlike other rats, forms struvite/apatite calculi only in the presence at chronic urinary tract infection.

Animals↗