Urinary citrate excretion in patients with renal calculi

Urinary citrate excretion was measured with a specific enzymatic technique in normal subjects and in an unselected group of patients with recurrent calcium oxalate stones. Hypocitraturia (citrate levels less than those present in 95 per cent of the normal population) was detected in 7 of 46 patients with stones (15 per cent). Hypocitraturia was the only metabolic abnormality in 6 patients.     

Urinary citrate excretion in stone-formers and normal controls.

A specific method was used for the estimation of citrate in 24-hour urine collections from 108 young adult controls, 158 patient controls and 164 stone-formers. Stone-formers excreted significantly less citrate in 24 hours than either patient controls or young adult controls. Stone-formers had a lower concentration of citrate in their urine than either of the control groups. The young adult females exhibited a much greater excretion of citrate relative to calcium than the young males. Because of the ability of citrate to complex with calcium ions and keep them in solution, the relatively low incidence of calcium-containing stones in females under 50 years of age could well be the result of their high excretion of citrate and their increased excretion of this substance relative to calcium.     

Urinary excretion of endothelin-1 in normal subjects and patients with renal disease

To elucidate the pathophysiological significance of urinary endothelin-1 (ET-1), we measured urinary excretion of ET-1-like immunoreactivity (L1) in 17 patients with renal disease and 9 normal subjects. Twenty-four hour urinary ET-1-L1 excretion in patients with renal disease (358 +/- 68 ng, mean +/- SE) was significantly (P less than 0.005) greater than that of normal subjects (77 +/- 5 ng). In patients with renal disease. ET-1-L1 clearance (CET) exceeded creatinine clearance (CCR); CET/CCR (305 +/- 81%) was significantly (P less than 0.005) greater than that of normal subjects (43 +/- 13%). The 24-hour urinary excretion of ET-1-L1 in patients with renal disease showed significant correlation with that of N-acetyl-beta-D-glucosaminidase (r = 0.587, P less than 0.05), beta 2-microglobulin (r = 0.614, P less than 0.01) and albumin (r = 0.484, P less than 0.05). Intravenous infusion of saline (500 ml) in seven normal subjects did not affect urinary ET-1 excretion rate. These data suggest that urinary excretion of ET-1 derives mainly from renal tubular secretion at least in patients with renal disease, and that degradation and/or reabsorption of ET-1 at the tubular site may also contribute to the renal handling of ET-1. Therefore, urinary excretion of ET-1 should serve as a potential marker for renal injury.     

Urinary excretion of glycosaminoglycans in normal and stone forming subjects

There is evidence suggesting that glycosaminoglycans (GAG) are potent inhibitors of growth and aggregation of calcium oxalate crystals in vitro. This finding raises the possibility that the urinary GAG could play an inhibitory role in the urolithiasis. To investigate this hypothesis, a study on the urinary excretion of GAG in normal and stone forming adults and children was undertaken. Different methods were compared, and the best results were obtained when the GAG were measured by densitometry after agarose gel electrophoresis. Although the GAG concentration was increased in the morning urine compared to the 24-hour urine samples, and in males compared to females, the GAG/creatinine ratio was independent of period of urine collection and of sex. So, it was advantageous to express the amounts of urinary GAG as mg/g of creatinine. Children excreted more GAG than adults, with a higher proportion of chondroitin sulfate. We have shown that the stone forming subjects, both adults and children, excreted lower levels of urinary GAG as compared to normal subjects, independently of the metabolic disorder. The proportions between chondroitin sulfate and heparan sulfate and the structures of these GAG were unaltered in the stone formers. These results indicate that there is a definite difference in terms of levels of GAG between normal and stone forming urines, and suggest a correlation between the urinary GAG concentration and urolithiasis.     

Urinary glycosaminoglycans in normal subjects and patients with stones

Urinary glycosaminoglycans are thought to be macromolecular inhibitors of calcium stone formation. The 24-hour excretion of urinary glycosaminoglycans was measured quantitatively in 24 normal subjects and 206 patients with different etiologies of stone disease. In both groups a positive correlation was found between urinary glycosaminoglycans and total urinary volume and urinary sulfate. In normal subjects total urinary volume was r equals 0.716, p less than 0.001 and urinary sulfate was r equals 0.813, p less than 0.001, while in patients with stones these values were r equals 0.338, p less than 0.001 and r equals 0.326, p less than 0.001, respectively. The only significant difference in excretion of urinary glycosaminoglycans between the groups was found in the subgroup of patients with type I absorptive hypercalciuria. The type I absorptive hypercalciuria value of 33.4 +/- 14.9 mg. per day in patients with stones was significantly higher than the 25.8 +/- 8.3 mg. per day detected in normal subjects (p less than 0.05). Urinary glycosaminoglycan excretion in all other subgroups of nephrolithiasis as well as in a combined group of all patients with stones showed no significant difference when compared to that of normal subjects. Thus, no major quantitative relationship could be demonstrated between urinary glycosaminoglycan excretion and calcium stone formation in this study.     

Urinary excretion substances in patients with cystic fibrosis: risk of urolithiasis?

Patients with cystic fibrosis (CF) have an increased risk of urolithiasis/nephrocalcinosis. To determine potential mechanisms responsible, we studied the urinary excretion of lithogenic and stone-inhibitory substances and calculated the urinary saturation for calcium-oxalate (CaOx), brushite (CaHPO₄), and uric acid (UA). We examined 24-h urines in 63 patients with CF (34 female, 29 male) aged 5 months to 36 years. Renal ultrasonography was performed at the time of urine collection. Hyperoxaluria was found in 25 patients (range 0.51 – 1.71 mmol/1.73 m² per 24 h). Urinary Ca was increased in 13 patients (4.1 – 8.22 mg/kg per 24 h). Hyperuricosuria was found in 16 patients (5.2 – 18.0 mmol/1.73 m² per 24 h) and hypocitraturia in 14 patients (0.07 – 1.14 mmol/1.73 m² per 24 h). CaOx saturation was elevated in 26 patients, related to hyperoxaluria in 19 patients. CaHPO₄ saturation was increased in 19 patients and UA saturation in 11 patients. Urolithiasis in situ was diagnosed in 1 patient; 3 patients previously had renal stones; 4 patients had present nephrocalcinosis. Elevated excretion of lithogenic substances and urinary supersaturation might lead to the higher risk of urolithiasis/nephrocalcinosis in patients with CF. Received March 5, 1997; received in revised form September 19, 1997; accepted September 24, 1997     

Urinary cytology in patients with urolithiasis

Urinary cytological examination was performed on 1032 patients of urolithiasis at the Department of Urology, Chiba University Hospital between 1980 and 1990. Seven hundred twenty-four were male and 308 were female, and the mean age was 44 years. The results of cytological examination of I-II and IV-V were classified as negative and positive, respectively. Eleven patients (1.1%) were positive, 2 of whom were found to be with renal pelvic tumor. False-positive findings were noticed in 9 cases (0.9%), and the abnormal cytologic changes in these cases disappeared after the calculi were removed. In negative cytological cases, 2 cases of renal pelvic tumor were found, one at nephrectomy and the other at percutaneous nephrolithotripsy. These cases were with staghorn calculi with hydronephrosis. The significance of cytological examination in management of calculous diseases were discussed.     

The relation between orthophosphate and pyrophosphate in normal subjects and in patients with urolithiasis

Summary In calcium lithiasis, inhibitors have a significant effect in reducing the crystallization process. This work evaluated orthophosphate in a group of patients with calcium oxalate lithaisis, and in a control group. The study of orthophosphate and pyrophosphate, showed differences between stone formers and the control group. These results could be attributed to a failure in the renal transformation of orthophosphate into pyrophosphate.     

Urinary excretion of citrate, glycosaminoglycans, magnesium and zinc in relation to age and sex in normal subjects and in patients who form calcium stones.

One hundred and ninety-seven healthy subjects and 104 patients with idiopathic calcium stone disease had their urinary excretion of citrate, glycosaminoglycans, magnesium, and zinc measured and the results correlated with sex and age. In normal subjects the daily excretion of citrate, magnesium, and zinc increased with age to a maximum during the fifth decade and remained relatively constant until the eighth decade when they decreased. The daily excretion of magnesium and zinc were higher in men than in women, which was attributed to the higher body weights of the men. The urinary excretion of citrate, magnesium, and zinc related to creatinine remained relatively constant with age in adult life; analyses of magnesium and zinc excretion rates divided by urine creatinine did not distinguish men from women. There was no significant difference between men and women for citrate excretion in 24 hour urine, but the citrate:creatinine ratio was significantly higher in women than men. The higher citrate excretion in women may explain the lower incidence of calcium stones in women. The highest glycosaminoglycan excretion rates were seen during the first two decades which is why children and teenagers are less prone to develop calcium stones in spite of high urinary calcium concentrations. Urinary citrate and magnesium excretion were lower, and glycosaminoglycan and zinc excretion were higher, in stone formers than in controls. It seems that a decreased excretion of citrate and magnesium together with an increased excretion of calcium, may contribute to the formation of calcium stones. The role of urinary glycosaminoglycans and zinc in the formation of calcium stones remains uncertain.     

Urinary function in patients with corticobasal degeneration; comparison with normal subjects

AIMS: Corticobasal degeneration (CBD) is a rare neurodegenerative disorder affecting cerebral cortex and basal ganglia, both of which are crucial for regulating the lower urinary tract function. However, urinary function of this disorder has not been fully delineated. We investigated urinary function in patients with CBD. METHODS: A questionnaire for storage and voiding urinary symptoms was performed in all 10 patients with CBD (four men, six women; mean age, 67.3 years; mean duration of disease, 3.9 years) and 11 age-matched control subjects (four men and seven women; mean age, 73.0 years). Urodynamic studies were performed in six of the patients and all control subjects, including electromyography (EMG)-cystometry and analysis of motor unit potentials of the external sphincter. RESULTS: As compared to the control subjects (27%), patients with CBD had more common urinary symptoms (80%, P < 0.05). The urinary symptoms appeared 1-3 years after the onset of the disease, and were more common in patients with longer disease duration (>5 years) and in patients with forced grasp reflex. Nocturnal frequency was the most common and tended to be the initial urinary symptom (seven), followed by urinary incontinence (six), urinary urgency (six), diurnal frequency (five), and difficulty in voiding (five). None was in a state of urinary retention. While, one asymptomatic patient showed normal urodynamic finding, all five symptomatic patients showed various abnormalities, including decreased bladder capacity (four), detrusor overactivity (DO) (three), which was noted only in one of the control subjects, detrusor hypocontractility on voiding (three), and low compliance detrusor (one). None of the patients had post-void residuals, detrusor-sphincter dyssynergia, or neurogenic motor unit potentials of the external sphincter muscles. CONCLUSION: Although the number of our patients was small, the present study suggests that urinary dysfunction is a common feature in patients with CBD. Since decreased bladder capacity and DO were common in the symptomatic patients, lesions in the supranuclear parasympathetic system are mainly responsible for their dysfunction.     

Urinary glycosaminoglycan excretion in normal and stone-forming subjects: significant disturbance in recurrent stone formers

The overnight (12 h) urinary excretion of glycosaminoglycans, citrate, magnesium, calcium and uric acid were measured in 82 normal subjects and 63 outpatients who had formed at least one urinary stone. No significant difference could be found between the two groups of unselected subjects with respect to any of the urinary parameters. Nonetheless, recurrent stone formers had significantly lower glycosaminoglycans and predictive risk index than normal controls.     

Estrogen replacement increased the citrate and calcium excretion rates in postmenopausal women with recurrent urolithiasis.

PURPOSE: Epidemiological data indicate a sharp increase in urinary calcium stone formation after menopause. We investigated the role of menopausal estrogen replacement therapy on the urinary constituents and characteristics that may influence recurrent calcium oxalate stone disease. MATERIALS AND METHODS: Urinary constituents in 28 postmenopausal women on estrogen replacement therapy for more than 6 months were compared with those in 41 women who had never been exposed to estrogen after menopause. These 2 groups had a history of recurrent calcium oxalate urolithiasis. A group of age matched, nonstone forming volunteers who were and were not on estrogen served as controls. RESULTS: The 24-hour urine collection revealed significantly higher mean calcium plus or minus standard deviation (188.8 +/- 101.5 versus 129.2 +/- 80.9 mg./24 hours, p <0.01), citrate (576.6 +/- 237.9 versus 306.2 +/- 209.9 mg./24 hours, p <0.001) and agglomeration inhibition (203 +/- 106 versus 159 +/- 81 minutes, p <0.05) in stone forming women who were versus were not on estrogen. CONCLUSIONS: Higher urinary citrate and higher agglomeration inhibition in women exposed to estrogen may decrease the risk of subsequent calcium stone formation.     

Urinary citrate excretion in healthy children depends on age and gender

Background

Hypocitraturia is considered a major risk factor for calcium stone formation. However, there is no widely accepted reference database of urinary citrate excretion in children. The aim of our study was to determine the amount of citrate eliminated in the urine over a 24-h period in a pediatric cohort and to determine an optimal unit reflecting excretion.

Methods

The study cohort comprised 2,334 healthy boys and girls aged 2–18 years. The levels of urinary citrate were assessed by an enzymatic method in 24-hour urine and expressed in absolute values, as urinary concentration, citrate/creatinine ratio, per kilogram of body weight, in relation to 1.73 m², and as the calcium/citrate index.

Results

Similar incremental age-related citraturia rates were observed in both male and female subjects until puberty during which time citrate excretion became significantly higher in girls. Urinary citrate adjusted for creatinine and for body weight showed a significantly decreasing trend with increasing age in both sexes. Urinary citrate corrected for body surface was weakly correlated with age. Thus, the assumption of 180 mg/1.73 m²/24 h for males and 250 mg/1.73 m²/24 h for females as lower cut-off values appeared to be reliable from a practical perspective.

Conclusions

We found distinct sex-dependent differences in citraturia at the start of puberty, with significantly higher values of urinary citrate in girls than in boys. Further prospective studies are warranted to elucidate whether this difference represents a differentiated risk of urolithiasis.     

Urinary porphyrin excretion in normal children and adults

The relationship of random urinary porphyrin and creatinine values as functions of age and sex was examined in a normal population. Total urinary porphyrin was measured by a solvent extraction technique, while urinary creatinine was evaluated by an alkaline picrate method. Random urine specimens from 120 healthy patients (81 children and 39 adults) were evaluated. In both pediatric and adult populations, a strong correlation was found between urinary concentrations of porphyrin and creatinine (r = 0.7, P less than 0.0001). Urinary porphyrin excretion in mumol/mol creatinine (micrograms/g) was inversely related to both age (r = -0.59, P less than 0.0001) and weight (r = -0.61, P less than 0.0001) until approximately 9 years of age or 30 kg. Urinary porphyrin excretion in children 9 to 18 years of age was lower than that of younger children (P less than 0.0001) and approached adult values. Sex was not found to be a factor until 9 to 18 years of age, when females had higher urinary creatinine concentrations (P less than 0.05), but lower urinary porphyrin excretions (P less than 0.05) than similarly aged males. The converse was observed when similar values of adult women were compared with those of adult men. Men also had higher urinary porphyrin concentrations than women (P less than 0.01). Men had increased urinary creatinine concentration (P less than 0.05) and decreased porphyrin excretion ratios (P less than 0.05) when compared with males 9 to 18 years of age. Women had significantly lower urinary creatinine (P less than 0.001) and porphyrin (P less than 0.001) concentrations than females 9 to 18 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary chemokines/cytokines are elevated in patients with urolithiasis

The prevalence of urolithiasis in the general population has been increasing recently. The inflammatory responses may play an important role in the development of urolithiasis. We aimed to investigate whether the urine inflammatory cytokine and chemokine profiles from patients with urolithiasis can be used as prognostic markers for urolithiasis. Multiplex immunoassays were used to simultaneously detect five inflammatory cytokines and five inflammatory chemokines in urine collected from 29 patients and 38 sex and age-matched healthy volunteers. After adjusting for urinary creatinine, urinary levels of interleukin-8 (IL-8), regulated on activation, normal T cell expressed and secreted, monocyte chemoattractant protein-1, interferon-gamma (IFN-γ)-inducible 10-kDa protein, monokine induced by IFN-γ and IL-6 were significantly increased in patients compared with healthy controls. However, concentrations of urinary IL-1β, IL-10, IL-12, and tumor necrosis factor-alpha were not significantly different between those of patients and healthy controls. Using receiver operating characteristics curve analysis, we found that the adjusted IL-8 level of 6.2 pg/mg creatinine can reach a sensitivity of 90% and specificity of 68% to detect urolithiasis. Our data showed that urinary stones are associated with a cascade of inflammatory responses, including chemokine secretion, and urinary IL-8 levels. In addition, the elevation of urinary IL-8 could be a useful biomarker in healthy screening and clinical follow-up of urolithiasis.