Urinary Calcium Oxalate Stone Formation Research Articles

Circadian clock gene BMAL1 reduces urinary calcium oxalate stones formation by regulating NRF2/HO-1 pathway

Calcium oxalate stones are closely related to oxalate metabolism and oxidative stress injury. Normal metabolism homeostasis and tissue repair are often affected by the biological rhythm, which plays an indispensable role in maintaining the homeostasis of the organism. Nuclear factor erythroid 2-related factor/heme oxygenase-1 (NRF2/HO-1) is one pathway related to oxidative stress injury in human body. Normal operation of this pathway is conducive to the resistance against oxidative stress-related injury. This study was mainly aimed to explore whether the rhythm gene “brain and muscle ARNT-like 1” (BMAL1) was involved in regulating oxidative stress-related NRF2/HO-1 pathway to reduce the formation of urinary calcium oxalate stones. In vitro experiment found that the activation of NRF2/HO-1 can significantly reduce the oxalate-induced oxidative damage and urinary calcium oxalate stone formation, and the relative expression of BMAL1 was increased. Then overexpression of circadian gene BMAL1 can activate the NRF2/HO-1 pathway and reduce the oxalate-induced oxidative damage. In the hyperoxaluria animal model, the BMAL1 expression level decreased obviously, and the production of calcium oxalate stones was significantly reduced after activating NRF2/HO-1. Finally, we further verified the BMAL1 expression in blood samples from the patients, and analysis of several single nucleotide polymorphisms showed BMAL1 was related to calcium oxalate stones. Therefore, maintaining normal biorhythms and appropriately intervening related rhythm genes and their downstream antioxidant pathways may play an important role in the prevention and postoperative recurrence of urinary calcium oxalate calculi, which may open up new directions for the treatment of urinary calculi.

Assessment of Lithogenic Risk in Children Based on a Morning Spot Urine Sample

The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on 24-hour urine collection. We studied whether the Bonn Risk Index could be measured in spot urine samples and which part of the day is most suitable for this purpose. We collected total and fractionated 24-hour urine (in a 6-hour nocturnal portion and 9 consecutive 2-hour diurnal samples) in 42 children and adolescents with calcium oxalate urolithiasis and 46 controls. Bonn Risk Index values determined from each of the urine fractions were compared to those obtained from related 24-hour urine collections. Both groups exhibited similar circadian patterns of Bonn Risk Index values. Median Bonn Risk Index for the nighttime portion of urine in the stone group was 1.4 times higher than that obtained from the total 24-hour urine. The morning hours between 08:00 and 10:00 showed the peak lithogenic risk, and this fraction had the highest sensitivity and selectivity regarding discrimination between stone formers and healthy subjects. The afternoon hours demonstrated lower and less fluctuating crystallization risk. Despite diurnal fluctuations in Bonn Risk Index, there was still a well-defined cutoff between the groups. Bonn Risk Index determined from urine samples collected between 08:00 and 10:00 appears optimal in separating stone formers from healthy subjects, and appears as useful as the value determined from 24-hour urine collection. Investigation of this diurnal sample simplifies diagnosis in pediatric stone disease without loss of clinical information.

Bonn Risk Index Based Micromethod for Assessing Risk of Urinary Calcium Oxalate Stone Formation

The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on a 200 ml urine sample taken from a 24-hour collection. We evaluated whether the Bonn Risk Index can also be effectively determined in small urine samples. We studied 190 children and adolescents with nocturia and calcium oxalate urolithiasis. Initially Bonn Risk Index was determined according to the original method of Laube. Subsequently Bonn Risk Index was calculated using a computer program controlling a specially designed system to define the time point of induced crystallization based on consecutive urine samples of 1.5, 2.0 and 3.0 ml. No significant differences were found in Bonn Risk Index between values obtained from 200 ml samples and those based on the micromethod with urine samples of 2 and 3 ml. Assessment of risk of urinary calcium oxalate stone formation with Bonn Risk Index in small urine volumes, based on prototype equipment controlled by specialized computer software, is comparable to the original method. This finding facilitates the procedure and improves Bonn Risk Index determination in children.

Effect of three compounds extracted from Aiisma Orientalis ( Sam. ) juzep, on urinary calcium oxalate stones formation

Objective To study the effect of three compounds extracted from Alisma Orientalis on urinary calcium oxalate stones formation and identify the effective constituents.Methods Three com-pounds were extracted from Alisma Orientalis.In the in vivo experiment, 50 adult healthy male Wistar strain rats,weighing 180-220 g,were randomly divided into 5 groups (n=10 each) :group A (normal con-trol group), group B (oxalate calcium stone formation group), group C (compound Ⅰ-treated group), group D (compound Ⅱ -treated group),group D (compound Ⅲ-treated group).After feeding for 4 weeks under the same conditions,24 h urine was collected and the levels of 24-h OX, and Ca2+ were determined.All kidneys were resected,and crystal/stone location, renal tubular dilation and the total of Ca2+ contents in the renal tissues of all rats were examined.Results The result of the in vivo experiment showed that in group C, renal tissue calcium content (10.35±6.45) and crystals deposition were significantly lower than those in group B except for 24 h urinary Ox excretion,but the 24-h urinary calcium excretion (61.49±2.06) was increased.Conclusion The compound I extracted from Alisma Orientalis seems to decrease renal tissue calcium content, tubular dilatation and crystals deposition but increase 24-h urinary calcium excretion in renal tissues in vivo, therefore to be the effective constituent of Alisma Orientalis to prevent calcium oxalate stone formation. Key words: Urinary calculi; Oriental Waterplantain Rhizome; Calcium oxalate; Pharmacology

Association of absence of intestinal oxalate degrading bacteria with urinary calcium oxalate stone formation.

Urinary concentration of oxalate is considered an important factor in the formation of renal stones. Dietary oxalate is a major contributor to urinary oxalate excretion in most individuals. Furthermore, oxalate degrading bacteria have been isolated from human feces. We investigated the significance of oxalate degrading bacteria for urinary oxalate excretion and urinary stone formation. Twenty-two known calcium oxalate stone-forming patients (stone formers) and 34 healthy volunteers (non-stone formers) were included in the study. Stool specimens were inoculated into pepton yeast glucose (PYG) medium supplemented with oxalate under anaerobic condition at 37 C for one week. After the incubation period, each colony was checked for the loss of oxalate from the culture medium. A 24-h urine sample was collected in 43 individuals and analyzed for oxalate excretion. Twenty-eight of 34 (82%) healthy volunteers and 10 of 22 (45%) calcium oxalate stone formers were colonized with oxalate degrading bacteria. Calcium oxalate stone formers were more frequently free of oxalate degrading bacteria (P < 0.01). Urinary excretion of oxalate in those with oxalate degrading bacteria was significantly less than in those without oxalate degrading bacteria (P < 0.05). Hyperoxaluria (> 40 mg/day) was found in four of 27 individuals (15%) with oxalate degrading bacteria compared to seven of 16 (44%) without oxalate degrading bacteria (P < 0.05), suggesting an association between the absence of oxalate degrading bacteria and the presence of hyperoxaluria. The absence of oxalate degrading bacteria in the gut could promote the absorption of oxalate, thereby increasing the level of urinary oxalate excretion. The absence of oxalate degrading bacteria from the gut appears to be a risk factor for the presence of absorptive hyperoxaluria and an increased likelihood of urolithiasis.

Risk Factors in Urinary Calcium Oxalate Stone Formation and their Relation to Urinary Calcium Oxalate Supersaturation

We studied the effect of potential risk factors of urinary calcium oxalate saturation on calcium oxalate stone formation. Using the Equil2 program, the DG values of calcium oxalate in 390 clinical urine specimens were estimated in 5 healthy male individuals with and without citrate therapy. Critical calcium-oxalate supersaturation (DG value, > 2.8) was noted in 15 out of 390 urine specimens. Of the 15, 14 late night or morning specimens had critical calcium oxalate supersaturation, while only 1 afternoon specimen was supersaturated. Critical calcium oxalate supersaturation was often associated with hyperoxaluria and hypercalciuria, while undersaturation was often associated with hypomagnesiuria, a high Ca/Mg ratio, and hypocitraturia. Hypomagnesiuria, hypocitraturia, and a high Ca/Mg ratio appear to be poor indicators of calcium-oxalate supersaturation, and it is hard to predict the level of calcium-oxalate saturation using single parameters.

Circadian variations in the risk of urinary calcium oxalate stone formation.

To evaluate the circadian fluctuations in the risk of urinary calcium oxalate stone formation with regard to critical periods of crystallization. Over a given time period, the Tiselius index depends on urine volume and urinary excretion of oxalate, calcium, citrate and magnesium. This crystallization potential was evaluated during three successive periods spread over 24 h for 25 recurrent stone-formers aged 16-76 years (mean 50) and 25 control subjects aged 27-71 years (mean 44). There was no significant difference in the value of the Tiselius index for all equivalent time periods in both groups of patients. The minimum value was recorded in the afternoon and the circadian pattern of the index illustrated the predominant importance of urinary output in its determination. Morning urinary concentrations and excretions of citrate, and nocturnal levels of magnesium were significantly higher in the stone-formers when compared with the control subjects. The lithogenic risk for calcium oxalate stones was maximal at the end of the night or during the early morning, when urinary output was minimal. This circadian study revealed abnormalities that are not apparent from non-fractionated 24 h urine samples, and which were potentially relevant to therapy.