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 citrate excretion in patients with urolithiasis and normal subjects

Citrate is a normal constituent of urine which combines with calcium to form a soluble salt. Urinary citrate excretion was examined in patients with urolithiasis and normal subjects by a specific enzymatic technique. There was a considerable overlap in the urinary citrate excretion between normal subjects and stone-formers, but the citrate-creatinine ratio, the citrate-calcium ratio and the citrate-magnesium-calcium ratio, which were all highly significantly lower (p less than 0.001) in stone-formers than in controls, proved most reliable in discriminating between these groups.     

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 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.     

Fasting urine excretion of magnesium,calcium, and sodium in patients with renal calcium stones

Urine excretion of magnesium (Mg), calcium (Ca) and sodium(Na) was studied in patients with renal Ca stones having normal kidney function (n= 60), and in matched controls (n= 60), on a free diet following an overnight fasting period. In some formers, Mg was lower than in normals, whereas Ca was unusually high resulting in a significantly higher molar Ca/Mg ratio (p less than 0.001). 2. In 3 out of 4 stone groups Na excretion was significantly elevated because of reduced tubular reabsorption. In normals, fractional Na excretion varied between 0.44 and 0.54% of endogenous creatinine clearance, whereas it exceeded 1% in the stone patients. Conversely, the molar ratio Na/Ca was equal in all groups. 3. Fasting urinary cyclic AMP was comparable in both populations supporting the assumption that in the majority of patients Ca- or Mg- wasting via urine may not be responsible for secondary hyperparathyroidism. In small selected groups, losses of divalent cations may act in concert, leading to stimulation of the parathyroid glands. 4. Correlations between minerals and Na reveal a close relationship between Na, Ca and Mg in terms of clearance and excretion rate in patients and controls. Fractional Na and Ca excretion are correlated in patients but not in normals. This suggests that in the absence of phosphaturia, factors other than extracellular volume expansion and/or hyperparathyroidism are operative in stone disease. 5. The origin of fasting natriuresis and relative hypercalciuria may be ascribed to a change, as yet not causally identified, in distal tubular Na reabsorption.     

On the relation between citrate and calcium in normal and stone-former subjects

The aim of this work is to evaluate citrate in a group of patients with calcium oxalate urolithiasis and in a control group for detecting possible differences between the two groups. The mean urinary concentration in the stone-formers was found significantly lower than in the controls. Particularly interesting was the correlation study between citrate and calcium. It was found that patients with hypocitraturia have hypercalciuria. Thus, it is particularly interesting to point out the importance of citrate in preventing the risk of lithiasis in the group of stone-formers studied by us.     

On the relation between citrate and calcium in normal and stone-former subjects

The aim of this work is to evaluate citrate in a group of patients with calcium oxalate urolithiasis and in a control group for detecting possible differences between the two groups. The mean urinary concentration in groups of stone-formers was found significantly lower than in the control group. Particularly interesting was the correlation study between citrate and calcium. It was found that patients with hypocitraturia have hypercalciuria. Thus, it is particularly interesting to point out the importance of citrate in preventing the risk of lithiasis in stone-formers studied by us.     

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 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.     

Noninvasive three-dimensional analysis of cervical spine motion in normal subjects in relation to age and sex. An experimental examination

STUDY DESIGN: Experimental examination in vivo. OBJECTIVES: To determine the precision of the ultrasound-based Coordinate Measuring System (CMS 50; Zebris Medizintechnik GmbH, D-88316, Isny, Germany) and then to establish a reference range for the active range of motion of the cervical spine in normal test subjects grouped according to age and sex. SUMMARY OF BACKGROUND DATA: Many different devices such as inclinometers, goniometers, potentiometers, computer-aided devices, and radiographic procedures have been developed to examine the range of motion of the cervical spine. All of them have more or less inherent limitations. METHODS: To assess the precision of this examination method, preliminary experiments were performed including intraobserver retest and two-observer repeatability, intraindividual variability, a daily profile, and a comparison between active and passive motions. In the subsequent main experiment 157 persons (86 women and 71 men) were examined during active motion. The sex groups were further subdivided into age groups of 10 years each. A comparison of weight and athletic activity was also performed. RESULTS: The range of motion decreased with increasing age, increasing body weight, and decreasing athletic activity. The rotation in the upper cervical spine increases with age to compensate for the reduced range of motion in the lower levels. Women showed significantly better mobility than men of the same age, only above the age of 70. CONCLUSIONS: The CMS 50 device provides precise reproducible measurements of the active range of motion of the cervical spine in all three planes. Criteria such as age, sex, body weight, and athletic activity influence the range of motion of the cervical spine.     

Pathophysiology and therapy of hypercalciuria in patients who form recurrent stones.

There are two alternative mechanisms that might be responsible for idiopathic hypercalciuria in recurrent stone formers: increased intestinal absorption of calcium with parathyroid suppression and overflow hypercalciuria (primary intestinal hyperabsorption) or renal calcium leak with compensatory hyperparathyroidism and intestinal hyperabsorption (primary renal-tubular hypercalciuria). In this study, urinary excretion of cAMP, the intracellular effector substance synthetised under parathyroid hormone stimulation, was found to be in the normal range. This finding would argue against intestinal hyperabsorption of calcium as the primary cause of hypercalciuria.     

Effects of magnesium citrate and phytin on reducing urinary calcium excretion in rats

Summary The aim of this study was to determine and compare the effects of both magnesium citrate and phytin on reducing urinary calcium excretion under high-calcium-diet conditions during single and combined treatments. An animal experiment was carried out over a period of 4 weeks in 35 male rats. Urinary calcium excretion was reduced significantly by magnesium citrate and/or phytin in rats fed on high-calcium diets. The hypocalciuric effect of magnesium citrate was more evident than that of phytin. Urinary magnesium excretion was high in all experimental groups. However, the urinary magnesium/calcium ratios showed a consistent increase only in the groups treated with magnesium citrate. Urinary citrate excretion showed a relative increase with the introduction of magnesium citrate plus phytin; however, in both the high-calcium-diet group and the magnesium-citrate group this was found to be reduced. Urinary phosphate excretion was slightly higher in the groups treated with phytin. There was no definite difference in urinary oxalate concentration between the groups. No significant change was noted in the serum concentration of calcium, magnesium, or phosphate.     

Urinary excretion of calcium,magnesium, phosphate,citrate, oxalate,and uric acid by healthy schoolchildren using a 12-h collection protocol

Although we do not have reliable data for the true prevalence of urolithiasis during childhood, the number of patients seen in outpatient clinics and admitted for stone-related problems is steadily increasing worldwide. As for most pediatric patients a metabolic disease is the reason for stone development, because a high number of patients have severely recurrent urolithiasis, early and proper diagnostic evaluation is necessary to begin adequate and preventive treatment. However, diagnostic evaluation, especially in infants and younger children, is not always easy, and frequently a diagnosis is made late. Diagnostic evaluation should start with repeated urine analysis; but how and which urine should be collected and analyzed? What is the best and most accurate method for urine collection? In a paper published in a recent issue of Pediatric Nephrology, Torres and colleagues describe a more simplified method of urine collection. They propose analysis of late-afternoon spot-urine samples as well as an overnight collection of urine as the most appropriate to evaluate patient-specific urinary risk factors. Is this truly the case?     

Uromucoid excretion in normal subjects,calcium stone formers and in patients with chronic renal failure

Summary Using an electroimmunoassay technique for uromucoid in urine, the excretion of this protein has been studied in normal subjects, calcium stone formers and in patients with chronic renal failure. In the normal subjects there was no significant difference in daily excretion between males and females, but a positive correlation with urine volume was demonstrated for this group. No significant difference in daily uromucoid excretion was found between normal and stone forming subjects. In the presence of chronic renal failure uromucoid excretion was found to be reduced and correlated with overall renal function as assessed by creatinine clearance.     

Urinary excretion of calcium,magnesium, phosphate,citrate, oxalate,and uric acid by healthy schoolchildren using a 12-h collection protocol

Background

Improving knowledge about normal urine composition in children is important for early prevention of lithiasis. We describe urinary excretion values of calcium (Ca), magnesium (Mg), phosphate (P), citrate (Cit), uric acid (Ur), and oxalate (Ox) in healthy children with and without a family history of lithiasis, using a 12-h urine collection protocol.

Methods

Urine samples were obtained from 184 children (5?12 years): a spot sample collected in the afternoon, and a 12-h overnight sample. Solute/creatinine (Cr) and 12-h solute excretion was calculated.

Results

Urinary excretion values of the studied solutes are presented as percentile values, separately for each type of sample. Due to age-related differences in the solute/creatinine ratios, except for Ca and Cit, results are described according to the child’s age. The presence of excretion values related to an increased risk of lithiasis was more common in children with a family history.

Conclusions

We report data from urine samples collected by using a simplified collection protocol. The observed differences between children with and without a family history of lithiasis could justify that in population studies aimed at setting reference values, the former are excluded.     

Tamm-Horsfall protein excretion and its relation to citrate in urine of stone-forming patients

OBJECTIVES: To evaluate the relation of Tamm-Horsfall protein (THP) and citrate, both potent actors in the urinary stone forming process. METHODS: Quantitative determination of THP in calcium oxalate (CaOx) stone-forming patients and healthy subjects was carried out according to the enzyme-linked immunosorbent assay method. RESULTS: THP excretion in 24-hour urine samples of CaOx stone-forming patients was significantly reduced compared with healthy subjects. A significant correlation exists between the concentration of THP and citrate in the stone-forming group, as well as in the group of healthy subjects, and for the 24-hour excretion, this correlation persists in the group of CaOx stone-forming patients. CONCLUSIONS: Decreased THP and citrate excretions were found in CaOx stone-forming patients. They indicate a tubular dysfunction of the distal section.