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[Studies on urolithiasis. The histochemistry of the kidney tissues and stones from patients with urolithiasis].

In this study, 17 kidney tissue specimens and 29 renal stones were obtained from patients with urolithiasis. Control kidney specimens were dissected from 7 individuals not suffering from urolithiasis. The tissue specimens were fixed with 1% cetylpiridinium chloride (CPC) in 10% formalin (for 24 hours at room temperature). Then the kidney tissue specimens were embedded in paraffin and stained with hematoxylin-eosin for general observation as well as histochemically for demonstration of complex carbohydrates. Also, stone specimens were embedded in epon and thin sections made by the mineral polishing specimen preparation, and stained along with the kidney tissues. For identifying individual acidic and neutral carbohydrates, the enzyme digestion was performed for some tissue sections prior to histochemical staining. The stone-forming kidney tissues, normal kidney tissues and urinary stones (calcium oxalate, mixed, struvite) contained some glycosaminoglycans and neutral glycoproteins, but uric acid stones and cystine stones did not. The results of digestion with enzymes indicated that calcium oxalate stone-forming kidney tissue contains heparitin (heparan) sulfate; mixed stone-forming tissue contains sialic acid, hyaluronic acid, chondroitin sulfate A, B, C and heparitin (heparan) sulfate; struvite stone-forming tissue contains sialic acid, hyaluronic acid, chondroitin sulfate A, C and heparitin (heparan) sulfate; and cystine stone-forming tissue contains sialic acid, chondroitin sulfate A, C and heparitin (heparan) sulfate. The stone organic matrix is classified into the amorphous and stratiform types. The amorphous type matrix contains chondroitin sulfate A, B, C and heparitin (heparan) sulfate, and the stratiform type matrix also contains sialic acid and hyaluronic acid. The stone-forming kidney tissues, normal kidney tissues and stones (calcium oxalate, mixed, struvite) contain an appreciable amount of alpha-D-glucose, alpha-D-mannose and beta-D-galactose, but the uric acid stones and cystine stones do not contain sugar residues. Since the specific glycosaminoglycan composition differed for kidneys of different mineral content and stones of different morphological type, we believe that some glycosaminoglycans in kidneys and amorphous type matrix might play the role of a nucleating agent, and that a stratiform type matrix encourages stone enlargement.

Adult

[Clinical analysis of urolithiasis in Poh Ai Hospital of I-Lan, Taiwan, R.O.C.--a comparative study with urolithiasis in Japan].

Between August 1987 and December 1990, 546 patients were admitted to the department of Urology at the Poh Ai Hospital of I-Lan, Taiwan, R.O.C. for the treatment of urinary stones. These urinary stone cases accounted for 50 to 60% of all urology patients admitted. The incidence of urolithiasis in I-Lan was estimated at 147/100,000 population in 1990. There were 402 male patients and 144 female patients, The male to female ratio was 2.8: 1. There were 450 upper urinary tract stones (kidney, ureter) in 314 males and 136 females, and 79 lower urinary tract stones (bladder, urethra) in 72 males and 7 females. The ratio of upper to lower urinary tract stones was 6:1. Endourological treatments such as percutaneous nephrolithotripsy and transurethral ureterolithotripsy have increased rapidly in recent years. A summary of the present analysis for composition of 365 stones follows. The most frequent type was calcium-containing stone (92.3%), followed by infection stone (4.7%), then uric acid (UA) stone (3.0%). There were no UA stones found in the female patients. According to urinalysis criteria of more than 10 WBC/HPF (x 400), pyuria was found in 67 cases of 334 metabolic stones (20.1%), and 11 cases of 17 infection stones (67.7%). There were neither pediatric case of stone formation nor cystine stones.

Adolescent

[Clinical studies on recurrence of urolithiasis. (2) Hypercalciuria and recurrence of urolithiasis].

According to the dynamics of the urinary calcium excretion mechanism, we have classified the patients with urolithiasis into 4 groups, namely group I (normocalciuria; urinary calcium excretion of 270 mg/day or less for male patients and 210 mg/day or less for female patients), group II (absorptive hypercalciuria; hypercalciuric with urinary calcium excretion of 200 mg/day or less under the low calcium diet), group III (renal hypercalciuria; hypercalciuric with urinary calcium excretion exceeds 200 mg/day even under a low calcium diet), and group IV (hyperparathyroidism; hypercalciuric patients as in group III with high serum calcium). Of the 97 stone formers, 77 were classified into group I, 9 into group II, 8 into group III and 3 into group IV. Both under the restricted diet and under the ambulatory free diet, urinary calcium excretion of groups II, III and IV was significantly higher than that of the group I patients. It was noteworthy, however, that some of the patients in group I excreted much calcium without restriction of their diet. Although no difference in excretion of oxalate, magnesium and phosphate was observed between the 4 groups, the patients in groups II, and III excreted more uric acid into their urine than group I patients. As for stone recurrence rate, no difference was noted between group I and group II, III or IV. Based on these findings, we conclude that hypercalciuria has no significant role in the stone forming mechanism. However, lowering of urinary calcium and other stone forming constituents is mandatory in preventing stone recurrence until the mechanism of stone formation is elucidated more precisely.

Calcium

[Experimental and clinical studies on calcium urolithiasis: (I) Animal model for calcium oxalate urolithiasis using ethylene glycol and 1-alpha (OH) D3].

As calcium oxalate stones are the most important component in urolithiasis, an experimental model has to be designed to clarify the pathogenesis and aid in their prevention. Hyperoxaluria as well as hypercalciuria were produced in rats by administering ethylene glycol (0.5%, in drinking water administered ad libitum) and 1-alpha (OH) D3 (0.5 micrograms/rat given every other day), respectively, for three to four weeks. Neither drug alone produced stones efficiently as did the combination regimen of these two compounds. The occurrence of stones was 77.3%, and with only a moderate degree of renal functional impairment. Biochemical and histological data were obtained using this model.

Animals

Risk relationship between inflammatory bowel disease and urolithiasis: A two-sample Mendelian randomization study.

BACKGROUND: The causal genetic relationship between common parenteral manifestations of inflammatory bowel disease (IBD) and urolithiasis remains unclear because their timing is difficult to determine. This study investigated the causal genetic association between IBD and urolithiasis using Mendelian randomization (MR) based on data from large population-based genome-wide association studies (GWASs). METHODS: A two-sample MR analysis was performed to assess the potential relationship between IBD and urolithiasis. Specific single nucleotide polymorphism data were obtained from GWASs, including IBD (n = 59957) and its main subtypes, Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data on urolithiasis (n = 218792) were obtained from different GWAS studies. A random-effects model was analyzed using inverse-variance weighting, MR-Egger, and weighted medians. RESULTS: Genetic predisposition to IBD and the risk of urolithiasis were significantly associated [odds ratio (OR), 1.04 (95% confidence interval [CI], 1.00-.08), P = 0.01]. Consistently, the weighted median method yielded similar results [OR, 1.06 (95% CI, 1.00-1.12), P = 0.02]. The MR-Egger method also demonstrated comparable findings [OR, 1.02 (95% CI, 0.96-1.08), P = 0.45]. Both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and urolithiasis. CD was strongly associated with it in its subtype analysis [OR, 1.04 (95% CI, 1.01-1.07), P = 0.01], and UC was also causally associated with urolithiasis, although the association was not significant [OR, 0.99 (95% CI, 0.95-1.03), P = 0.71]. CONCLUSION: A unidirectional positive causal correlation was identified between IBD and urolithiasis, with varying degrees of association observed among the different subtypes of IBD. Recognizing the increased incidence of urolithiasis in patients with IBD is crucial in clinical practice. Early detection and surveillance of IBD, improved patient awareness, adoption of preventive strategies, and promotion of collaborative efforts among healthcare providers regarding treatment methodologies are vital for improving patient outcomes.

Humans

Induction of urolithiasis in single comb white Leghorn pullets: effect on glomerular number.

Urolithiasis was induced in an experimental group of Single Comb White Leghorn pullets by feeding them layer ration and exposing them to nephrotrophic Gray strain infectious bronchitis virus (IBV). Gray strain IBV was recovered from kidney and cloacal swabs for up to 26 days after exposure to the virus. Control pullets fed pullet grower ration and not exposed to Gray strain IBV did not develop urolithiasis. The experimental design did not allow differentiation between the roles of layer ration and IBV in triggering urolithiasis. Urolithiasis was associated with asymmetry in left vs. right kidney weight comparisons for individual pullets. Pullets from the urolithiasis group had 43,800 +/- 4,500 glomeruli/gram kidney weight, whereas control pullets had 68,770 +/- 3,500 glomeruli/gram kidney weight. This difference was significant (P less than .01). Total kidney weights did not differ significantly when the experimental and control pullets were compared. Comparisons of glomeruli size distributions indicated that the number of intermediate sized glomeruli (.15 to .22 mm in circumference) was significantly reduced in pullets from the urolithiasis treatment group. These observations indicate that a significant reduction in nephron number can be masked by compensatory hypertrophy of the remaining kidney tissue in pullets with urolithiasis.

Animals

Formation of calcium oxalate urolithiasis in experiment and its inhibition by pyridoxine and magnesium.

Possibility of application of experimental model of calcium oxalate urolithiasis to the study of some medicament actions useful in prevention of calcium oxalate urolithiasis in men has been examined in animal experiments. Inhibition effects of pyridoxine and magnesium in formation of calcium oxalate stone formation have been proved. Administration of pyridoxine and/or magnesium to experimental animals inhibited formation of incrustations on renal papillae. Administration of nothing but magnesium lowered considerably also frequency of nephrocalcinosis occurrence. Good reproducibility of applied model of calcium oxalate urolithiasis creates conditions for further experimental study of this kind of urolithiasis. In the previous series of experiments (4) we tiped out an experimental model of calcium oxalate urolithiasis in animals well reproducible in our conditions. In the following period we were interested, whether the created model can be applied to verification of efficiency and further study of some medicaments affecting this kind of urolithiasis. At present, pyridoxine and magnesium are mode widely used for prevention of calcium oxalate urolithiasis in the clinical practice. Therefore, we decided to use the possibilities of the evaluated experimental model for the study of their inhibition effects. The results of experiments are presented in this paper.

Animals

Uric acid excretion in children with urolithiasis.

Urinary uric acid excretion was assessed in 38 children to determine whether hyperuricuria was a risk factor in children with urolithiasis. Uric acid excretion (measured per deciliter glomerular filtration rate), and fractional excretion of uric acid were similar in 27 children with hypercalciuria and calcium oxalate urinary stones, in six children with idiopathic calcium oxalate urolithiasis, and in five with uric acid urolithiasis, of whom four were white boys and one was an Asian girl. One boy with a urate stone had cystinosis. Serum uric acid concentrations exceeded 6.0 mg/dl (360 mumol/L) in two children with hypercalciuria and in two patients with idiopathic calcium oxalate urolithiasis. None of the children with calcium urolithiasis had excessive urinary excretion of uric acid. In children with hypercalciuria, uric acid excretion did not change significantly when dietary sodium was increased from 1.0 to 5.0 gm/1.73 m2. We conclude that excessive urinary uric acid excretion is seldom an additional risk factor in children with calcium urolithiasis and that dietary sodium chloride does not have a strong influence on urinary excretion of uric acid in children with hypercalciuria.

Adolescent

[The frequency and mechanisms of urolithiasis in acromegaly].

It is generally accepted that acromegaly is often associated with hypercalciuria, but there are few reports on the frequency and the mechanisms of urolithiasis. Recently we consecutively experienced 2 cases of acromegaly with urolithiasis, and these experiences made us investigate the association between urolithiasis and acromegaly. Among 18 acromegalies from 1977 to March 1990 (10 males, 8 females, 24-64 years old), 13 cases (72%) fulfilled the criteria of hypercalciuria (urinary calcium (u-Ca) greater than or equal to 200 mg/day or u-Ca/urinary creatinine (u-Ca/u-Cr) greater than or equal to 0.15), and 7 cases (39%) suffered from urolithiasis that was diagnosed by KUB (4 cases) or X-ray computed tomography (CT) (3 cases). Especially in the last 2 years, 5 out of 7 cases (71%) were complicated with urolithiasis and all 7 cases were associated with hypercalciuria. These results suggest that hypercalciuria and urolithiasis are both much more frequent than previously reported. In 6 cases who were treated by pituitary adenomectomy from 1988-1989 (4 males, 2 females, 24-59 years old), we examined Ca metabolism before and after operation. Before operation, the levels of serum growth hormone (GH), u-Ca (mg/day), u-Ca/u-Cr (in all cases) and plasma somatomedin-C (Sm-C) (in 4 cases) were increased above the normal range. To determine the etiology of hypercalciuria, we performed the oral Ca load test under restriction of Ca (400 mg/day) and P (650 mg/day) intake. The results suggested that the hypercalciuria might be mainly due to the increased absorption of Ca from the intestine (so-called "Absorptive hypercalciuria"). However, the levels of serum vitamin D (Vit. D) metabolites were all within the normal range before operation. After operation, GH and u-Ca/u-Cr (in 5 cases) and u-Ca (mg/day) (in all cases) decreased significantly compared with before operation, and the levels of Sm-C (in all cases), serum 25-(OH)D3, 1 alpha, 25-(OH)2D3 (in 4 cases) and 24,25-(OH)2D3 (in 3 cases) were also reduced after operation. Surprisingly, u-Ca and u-Ca/u-Cr normalized only in 4 cases who showed a reduction in 1 alpha, 25-(OH)2D3 levels after operation, although there were no correlations between u-Ca (mg/day) or u-Ca/u-Cr and 1 alpha, 25-(OH)2D3. Significant correlations were found between u-Ca (mg/day) or u-Ca/u-Cr and Sm-C. The parathyroid function evaluated by the rapid Ca infusion test or nephrogenous cyclic adenosine monophosphate (NcAMP) was normal before and after operation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly

Oxalate measurement in the picomol range by ion chromatography: values in fasting plasma and urine of controls and patients with idiopathic calcium urolithiasis.

Oxalate was measured by ion chromatography in the ultrafiltrate of heparinized plasma from peripheral venous blood, using a membrane with a cut-off molecular weight (Mr). The following criteria were established: sensitivity 0.7 mumol.l-1; intra- and inter-assay coefficients of variation 4% and 12%, respectively; precision of duplicate determinations (expressed as standard deviation) 0.08 mumol.l-1; overall recovery (oxalate added and diluted, respectively) 100.7%. These qualified the method for assessment of plasma oxalate in healthy human controls (males: n = 12) as well as patients with idiopathic renal calcium urolithiasis (males: n = 22; females: n = 16). Renal calcium urolithiasis patients were subclassified into those with normocalciuria and idiopathic hypercalciuria. In male and female controls the mean values (and range) of plasma oxalate were 1.98 (1.4-2.5) and 1.78 (0.7-2.9) mumol.l-1, respectively. In male controls ultrafiltration (membrane cut off Mr 10,000) revealed that 11-16% plasma oxalate was bound to constituents having an apparent Mr above 10,000, and that with use of membranes with smaller pore size, the ultrafilterability of oxalate decreases further. In renal calcium urolithiasis the following values were elicited (mumol.l-1): male normocalciuria 1.78 (0.8-4.0), idiopathic hypercalciuria 1.58 (1.2-2.2); female normocalciuria 1.69 (0.8-3.6), idiopathic hypercalciuria 1.21 (0.8-2.1). The difference from controls is significant in idiopathic hypercalciuria (males and females). In contrast, in fasting urine of renal calcium urolithiasis the oxalate excretion rate (5-45 mumol per 120 min) and oxalate clearance (21-328 ml per min) resemble those in controls, whereas in renal calcium urolithiasis the fractional oxalate clearance (30-357% of creatinine clearance) tended to higher values (p less than 0.01, in male idiopathic hypercalciuria versus controls). It is suggested that 1) ion chromatography allows the reliable assessment of ultrafiltrable plasma oxalate in health and disease states, 2) in renal calcium urolithiasis this technique may help to elucidate oxalate pathophysiology, especially the mode of renal handling of oxalate.

Adult

Urolithiasis in chronic inflammatory bowel disease.

In a selected material of 228 patients with chronic inflammatory bowel disease (CIBD) the incidence of urolithiasis was 15% (95% confidence limit 11-21). The tendency to urolithiasis is significantly correlated to small-bowel resection and its extent and to obstruction in the urinary tract. On the other hand, there is no definite correlation to the duration or extent of the bowel disease. The significant correlation between urolithiasis and ileal resection is in agreement with the hyperabsorption of oxalate as an important cause of stone formation demonstrated by others. That local factors too play an essential role in the formation of urinary calculi is apparent from the increased incidence of urolithiasis in obstruction of the urinary tract. The incidence of urolithiasis was particularly high (22-25%) among patients with ileostomies. The few and negligible symptoms of and sequelae to, urolithiasis in CIBD encourage a conservative attitude.

Adolescent

Urinary volume in children with urolithiasis.

Urinary volume in 24-hour urine collections was examined in 50 children with hypercalciuria and urolithiasis or hematuria, 12 with idiopathic calcium oxalate urolithiasis and 36 healthy children. Urinary volume was 22.2 +/- 2.0 ml. per kg. per day in healthy children and 25.4 +/- 2.0 ml. per kg. per day in children with hypercalciuria, and it was similar in children with absorptive and renal hypercalciuria, and significantly lower in children with idiopathic calcium oxalate urolithiasis (12.2 +/- 1.4 ml. per kg. per day, p less than 0.001 from controls and children with hypercalciuria). Volume was not statistically different in hypercalciuric children with and without urolithiasis. Urinary sodium excretion in children with idiopathic calculi was not statistically different from controls. Urine osmolality was similar among the groups. Urinary volume represents a risk factor in children with idiopathic calcium oxalate urolithiasis, and increased fluid intake should be emphasized in such patients.

Calcium

A possible synergism of dietary phosphate and urine-acidifying salts in preventing silica urolithiasis in a rat model.

Using an animal model involving rats fed tetraethylorthosilicate, the minimal effective dietary concentration of ammonium chloride for reduction of silica urolithiasis was determined to be approximately 0.10 equivalents/kg diet. Ammonium sulfate appeared to be only slightly less effective. The lower incidences of urolithiasis were associated with urinary pH less than 7. A subprophylactic concentration (0.067 equivalents/kg diet) of ammonium chloride was factored with three levels of supplemental phosphorus (0, 0.15 and 0.30%) from Na2HPO4 to determine whether the antiurolithic effects of dietary phosphate and urinary-acidifying salts are synergistic. Phosphate had no effect on urinary pH. A 50% urolith incidence occurred in controls; the incidence was 25% (P = 0.08) with 0.15 and 10% (P less than 0.01) with 0.30% phosphorus. Urinary pH was 7.5 in controls compared with approximately 7.2 in rats given the subprophylactic level of ammonium chloride, but ammonium chloride alone had no effect on urolithiasis. However, complete protection from urolithiasis was provided by each of the two levels of phosphorus in combination with ammonium chloride. It is concluded that supplemental dietary phosphorus is most effective for protection against silica urolithiasis under conditions contributing toward urinary acidification due to a possible synergism between dietary phosphorus and urinary acidifying salts.

Ammonium Chloride

Incidence of urolithiasis leading to hospitalization in Finland.

The study population consists of 2304 urolithiasis patients discharged from all hospitals in 21 central hospital districts in 1970. The incidence rate was 50 per 100 000 inhabitants per year, 74 for men and 27 for women. The age distribution resembles the Gaussian curve, with a peak between 45 and 49 years for men and between 50 and 54 years for women. The male/female ratio was 2.7 in the entire material, about 1 in the age group 0--24 years, about 3 in the age group 25--74 years and about 1.5 in patients 75 years or older. The standardized incidence was highest in Southeastern Finland and in the archipelago of Aland, and lowest in the coastal area of Southwestern Finland. In the area with high incidence, the age distribution of urolithiasis patients differed from that in the rest of the country: in the age groups over 40 the incidence of urolithiasis did not appear to decrease. This difference was attributed to some lifelong environmental exposure. The standardized incidence of urolithiasis leading to hospitalization was higher among urban than rural residents. Seasonal variation in the hospital admissions for urolithiasis was not evident, temporal patterns of admissions were, however, dissimilar in urban and rural areas, and might reflect differences in the physical activities of urban and rural populations.

Adolescent

Urinary Tamm-Horsfall glycoprotein concentrations in normal and urolithiasis-affected male cats determined by an ELISA.

A precise and reproducible enzyme-linked immunosorbent assay (ELISA) which measures urinary cat Tamm-Horsfall glycoprotein (cTHP) was developed in order to investigate the possible role of cTHP in the pathogenesis of feline urolithiasis. Reproducible quantification required that the cTHP be disaggregated with 2M urea and 0.05% Tween 20. It was necessary to standardize rigidly the handling of the samples prior to analysis, since the apparent cTHP concentration varied depending on the preanalysis protocols. Using the sample handling protocol of freezing urine at -70 degrees C before dialysis, urinary cTHP was quantified in male cats with no history of urolithiasis ("normal" cats) and in male cats with a history of urolith formation ("urolithiasis" cats). The mean cTHP concentration in adult, male "normal" cats of 49.2 +/- 35.5 micrograms/ml (N = 23) was significantly lower than the mean cTHP concentration of 95.4 +/- 34.1 micrograms/ml (N = 9) in "urolithiasis" cats (p < 0.01, Students' T-test). These findings indicate a correlation between urolithiasis and high urine cTHP concentrations in male cats which warrants further investigation.

Analysis of Variance