Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy

ABSTRACT Objective: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. Materials and Methods: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and probiotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats received Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. Findings: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) reduced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. Conclusion: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalate degrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

The Clinical Features and Prognosis of Nephrocalcinosis in Preterm Neonates: A Single Center Study in Korea

PURPOSE: Nephrocalcinosis (NC) is frequently observed in premature infants. Small-scale studies have suggested that NC adversely affects renal function; however, the etiologic factors are still unclear. This prospective observational study aimed to identify the factors that influence the development of NC, through urine analysis. METHODS: In total, 99 preterm infants (gestational age 0.51]). The follow-up rate was 52% (27/52) and symptoms in none of the infants had progressed to nephrolithiasis. In the infants that were followed up, NC was resolved at a mean age of 7.7 (range: 2-32) months. CONCLUSION: Our results suggest that hyperoxaluria is a significant risk factor for the development of NC.

Bone Marrow Oxalosis in a Patient With Pancytopenia Following Bilateral Nephrectomy

No abstract available.

A rare case of hyperoxaluria presenting with acute liver injury and stone-free kidney injury

A 49-year-old woman visited the clinic because of acute hepatitis and acute kidney injury with decreased urine output presenting microscopic hematuria and proteinuria. An abdominal computed tomography revealed a localized, hypoattenuated lesion in a hepatic lateral segment, and kidney biopsy showed oxalate crystal deposition with tubular necrosis. In addition, the patient's 24-hour urinary excretion of oxalate was increased. Her kidney and liver injury improved after sessions of hemodialysis, and urinary oxalate excretion was normalized. Major mutations in primary hyperoxaluria have not been proven. A full sequencing of target genes may be helpful to diagnose a rare form of primary hyperoxaluria.

Nutritional Management of Kidney Stones (Nephrolithiasis)

The incidence of kidney stones is common in the United States and treatments for them are very costly. This review article provides information about epidemiology, mechanism, diagnosis, and pathophysiology of kidney stone formation, and methods for the evaluation of stone risks for new and follow-up patients. Adequate evaluation and management can prevent recurrence of stones. Kidney stone prevention should be individualized in both its medical and dietary management, keeping in mind the specific risks involved for each type of stones. Recognition of these risk factors and development of long-term management strategies for dealing with them are the most effective ways to prevent recurrence of kidney stones.

Therapeutic effect of inulin on enteric hyperoxaluria in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the therapeutic effect of inulin on enteric hyperoxaluria in rats.</p><p><b>METHODS</b>In experimental A, 24 healthy male Sprague-Dawley rats received an oxalate-free diet on day 1, a high-oxalate diet (oxalate, 74.82 mg/100 g feed stuffs) on days 2 and 3, and plus 2 g inulin to each rat on day 3. The 24-hour urinary volume, concentrations of urinary oxalate and urine creatinine were measured, and 24-hour urinary oxalate excretion was calculated. In experimental B, 24 healthy male Sprague-Dawley rats were equally randomized into control group and inulin group, Each rat received a high oxalate diet (oxalate, 74.82 mg/100 g feedstuffs), and plus 2 g inulin in inulin group. The 24-hour urinary oxalate excretion was calculated in both two groups.</p><p><b>RESULTS</b>In experimental A, the 24-hour urinary oxalate excretion varied with time (F=11.481, P=0.035). The 24-hour urinary oxalate excretion significantly increased on day 2 compared with that on day 1 (P=0.026) and day 3 (P=0.037); it significantly increased on day 3 compared with day 1 (P=0.004). In experimental B, the 24-hour urinary oxalate excretion significantly decreased in inulin group compared with the control (P=0.011).</p><p><b>CONCLUSION</b>Inulin may have potential therapeutic effect on enteric hyperoxaluria in rats.</p>

Nephrocalcinosis induced by hyperoxaluria in rats

PURPOSE: To investigate nephrocalcinosis due to hyperoxaluria induced by two different inducing agents in rats. METHODS: Forty Sprague-Dawley male rats were randomly distributed into four groups: Group1 (Clinical control, n = 10); Group 2 (0.5% Ethylene Glycol + Vitamin D3, n = 10); Group 3 (1.25% Ethylene Glycol, n = 10); and Group 4 (5%Hydroxy L-proline, n = 10). Five animals from each group were euthanized after one week of follow-up (M1 Moment) and the remaining, after four weeks (M2 Moment). All animals underwent 24h urine dosages of calcium, oxalate, uric acid, citrate and serum creatinine. Histology and histomorphometric analyses were performed using Image J program in the hematoxylin-eosin stains. Calcium deposits in the renal parenchyma were quantified by PIXE technique (Proton Induced X-Ray Emission). RESULTS: 24h urinary parameters did not show any significant variations after 28 days of experiment except by hyperoxaluria that was significantly higher in Group 3. Histomorphometric analyses showed a significantly higher nephrocalcinosis in Group 2 (p<0.01). The calcium deposits in the renal parenchyma were 10 and 100 times higher in Group 2 in comparison to other groups in the M1 and M2 moments, respectively. CONCLUSION: The Group 2 (vitamin D3+Ethylene Glycol 0.5%) was the best model to induce nephrocalcinosis in rats after 28 days.

La dieta en el tratamiento de la litiasis renal. Bases fisiopatológicas / [Diet in the treatment of renal lithiasis. Pathophysiological basis].

The composition of urine is influenced by diet and changes in dietary factors have been proposed to modify the risk of recurrent nephrolithiasis. Nutrients that have been implicated include calcium, oxalate, sodium, animal protein, magnesium and potassium. There is significant evidence showing that a high calcium diet is associated with a reduction of lithogenic risk. One of the possible mechanisms to explain this apparent paradox is that the higher intake of calcium in the intestine binds with dietary oxalate, reducing its absorption and urinary excretion. Oxalate from the diet seems to provide only a small contribution to excretion and dietary restriction is appropriate only in those with hyperoxaluria and hyperabsorption. Observational studies have shown a positive and independent association between sodium intake and the formation of new kidney stones. Consumption of animal protein creates an acid load that increases urinary excretion of calcium and uric acid and reduced citrate, all factors that could participate in the genesis of stones. Potassium-rich foods increase urinary citrate because of its alkali content. In prospective observational studies, diets rich in magnesium were associated with a lower risk of kidney stone formation in men. In conclusion, diet is a key element in the management of the patient with kidney stones but always subordinated to present metabolic risk factors.

A polyherbal formulation attenuates hyperoxaluria-induced oxidative stress and prevents subsequent deposition of calcium oxalate crystals and renal cell injury in rat kidneys / 中国天然药物

INTRODUCTION@#Cystone is an approved Ayurvedic polyherbal proprietary medicine used in India for various urinary disorders, including urolithiasis.@*AIM@#To evaluate the protective effect of Cystone against hyperoxaluria-induced oxidative stress and calcium oxalate crystal deposition in urolithiasis.@*METHODS@#Ethylene glycol (EG) (0.75%, V/V) in drinking water was given to rats for 28 days to induce urolithiasis with simultaneous treatment of Cystone (500 and 750 mg/kg body weight), and various urinary risk factors of urolithiasis and antioxidant markers were assessed.@*RESULTS@#EG treatment lead to increased urine volume and lowered urinary pH, along with increased urinary excretion of oxalate, calcium and phosphate in untreated animals. These changes caused extensive calcium oxalate crystal deposition, increased lipid peroxidation and decreased activity of antioxidant enzymes (SOD, catalase and GPx) in the kidney of untreated rats. Cystone prevented these hyperoxaluric manifestations and inhibited calcium oxalate crystal deposition in treated rats at both doses.@*CONCLUSIONS@#Cystone therapy provides protection against hyperoxaluria-induced oxidative stress and calcium oxalate crystal deposition by improving renal tissue antioxidant status and diuresis.

Screening of differentially expressed genes in the jejunum of rats with idiopathic hyperoxaluria / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Idiopathic hyperoxaluria (IH) may be caused by increased endogenous formation or exogenous absorption of oxalic acid. Characterization of the molecular pathogenesis of IH has been hampered by the lack of an ideal animal model. We therefore established a stabile rat IH model in order to analyze variation in gene expression profile in the jejunum and to investigate the association between IH pathogenesis and exogenous absorption of oxalic acid.</p><p><b>METHODS</b>A rat model of IH was established and three female rats with IH were assigned to the study group, while three normal rats served as controls. Total RNA was isolated from the jejunum of rats in the two groups and mRNA was purified, reversely transcribed, labeled with Cy5 or Cy3 and hybridized to 27K Rat Genome Array. Differences in gene expression profile between the 2 groups were analyzed by bioinformatics methods.</p><p><b>RESULTS</b>Comparative analysis revealed that the expression of 517 genes was up-regulated and that of 203 genes was down-regulated by at least two-fold in the jejunum of rats with idiopathic hyperoxaluria. These genes are related to many functions including cell signal transduction, DNA binding and transcription, ATP binding, ion binding and transport, cell receptors, immunity, cyclins, cytoskeleton structure, and metabolic proteins. Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis revealed that the variations of 239 pathway functional changes are statistically significant (P < 0.05).</p><p><b>CONCLUSIONS</b>cDNA microarray can be used effectively to screen differentially expressed genes in the jejunum of rats with idiopathic hyperoxaluria. These differentially expressed genes may underlie idiopathic hyperoxaluria pathophysiology and provide a platform for further studying molecular pathogenetic mechanisms.</p>

Establishment of a rat model of low calcium diet related hyperoxaluria / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish a rat model of low calcium diet related hyperoxaluria and explore its features.</p><p><b>METHODS</b>By means of randomized blocks design, totally 24 SD male rats were divided into low calcium diet group, medium calcium diet group, and high calcium diet group. Each group was sequentially fed on different calcium diets for 3 days. The urinary volume within 24 hours was recorded, the consistency of urinary oxalate by high-efficiency liquid chromatography, and the consistency of urine creatinine by automatic biochemical analyzer. The consistency was corrected to the output of urinary oxalate of rats in 24 hours, and the results were evaluated by repeated measurement of variance analysis and multivariate analysis of variance.</p><p><b>RESULTS</b>The output of urinary oxalate of rats in 24 hours varied with time (F=7.893, P0.05). The output of urinary oxalate of rats in 24 hours varied with group division (F=3.565, P<0.05). The output of urinary oxalate in 24 hours in three groups on the third day was significantly higher than that on the first day (P<0.05).</p><p><b>CONCLUSION</b>By controlling the calcium intake, we successfully established the model of low calcium diet related hyperoxaluria in rat.</p>

Nefrolitiasis: fisiopatología, evaluación metabólica y manejo terapéutico / Nephrolithiasis: pathofisiology, metabolic evaluation, and therapy

La nefrolitiasis es un trastorno frecuente en países desarrollados y en desarrollo. Su prevalencia varía entre el 4 y 20% según diferentes series y depende de la edad de la población analizada, las condiciones geográficas y socioeconómicas del grupo en estudio. La prevalencia de litiasis renal aumenta con la edad tanto en varones como en mujeres; es más común en varones jóvenes. Una de las características de la litiasis renal es la alta recurrencia y muchas veces la solución de los cólicos requiere de intervenciones endoscópicas u otro tratamiento urológico y esto hace a la morbilidad de la enfermedad. El promedio de diferentes trabajos que estudiaron la evolución natural de la enfermedad muestra que la posibilidad de recurrencia al año del primer episodio es del 15%, a los 5 años 40% y a los 10 años del 60%. Tanto los factores genéticos como los medioambientales contribuyen a la formación de cálculos. Los factores genéticos explican la tendencia a la agregación familiar de la enfermedad. El rol de la herencia es claro en algunas enfermedades como cistinuria o hiperoxalurias primarias, pero la litiasis idiopática también tiene una tendencia familiar, si bien los genes involucrados aún no se conocen. Dentro de los factores medioambientales se destaca la dieta, o sea determinados hábitos de ingesta que expresan la propensión a la litogénesis que tienen algunos sujetos. En aproximadamente 90% de los afectados es posible identificar alteraciones metabólicas que ayudan no sólo al diagnóstico etiológico sino que permiten también un manejo adecuado, con modificaciones dietéticas e intervenciones farmacológicas específicas. El tratamiento es eficaz en disminuir significativamente la tasa de recurrencias. En esta revisión analizamos la fisiopatología de la hipercalciuria, la hiperoxaluria, la hipocitraturia, y las litiasis úrica y cistínica. Se detallan el manejo del cólico renal y el tratamiento dietético y farmacológico apropiado para cada tipo de litiasis.

Nephrocalcinosis in neonates: report of 5 cases

The nephrocalcinosis is a pathologic entity rarely revealed to the neonatal period. The etiologies are dominated by hypercalciuria of prematurity whose origin is mostly iatrogenic. In full-term newborn, it refers primarily to the early revelation tubulopathy [distal tubular acidosis, Bartter syndrome] and primary hyperoxaluria, pathology common in the North African population. The prognosis depends on the extension of calcium deposits, the etiology and therapeutic options. In the pediatric nephrology department of the Charles Nicolle hopital, and during a period of 7 years from 2002 to 2008, we supported for nephrocalcinosis, 5 full-term newborns who fall into 3 boys and 2 girls. The average age of discovery is 19 days with extremes of 15 to 25 days. Consanguinity was present in 4 cases. The circumstances of discovery are: Acute dehydration with underweight in 2 patients. A urinary tract infection in one patient. NeonataI convulsions secondary to hypomagnesaemia. A chance discovery in the exploration of a symptomatology evocative of a gastrosophageal ref lux disease in a patient. Explorations turned up the diagnosis of distal tubular acidosis in 2 patients, a primary hyperoxaluria in 1 patient, idiopathic hypercalciuria in a patient and a family hypomagnesaemia with hypercalciuria and nephrocalcinosis in another patient

Antilithiatic effect of grains of Eleusine coracana

The effect of aqueous and alcohol extracts of Eleusine coracana Linn. [Poaceae] on calcium oxalate nephrolithiasis has been studied in male albino rats. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. Supplementation with aqueous and alcohol extracts of E. coracona grains [300 mg/kg b.w., p.o.] significantly reduced the elevated urinary oxalate, showing a regulatory action on endogenous oxalate synthesis. The increased deposition of stone forming constituents in the kidneys of calculogenic rats was significantly lowered by curative and preventive treatment using aqueous and alcohol extracts. From this study, we conclude that both the prophylactic and therapeutic treatment with aqueous and alcohol extracts of grains of E. coracana had an inhibitory effect on crystal growth, with improvement of kidney function as well as cytoprotective effect

Development of Yvrk Gene-Recombinant E. coli Degrading Oxalate

PURPOSE: Recently, the whole DNA sequence of Bacillus subtilis (B. subtilis) was identified, revealing the existence of the YvrK gene encoding a 43 kD oxalate decarboxylase (OXDC), which degrades oxalate by a simple pathway. The objective of this study was to develop recombinant Escherichia coli (E. coli) expressing the Yvrk gene from B. subtilis. MATERIALS AND METHODS: After the extraction of total DNA from B. subtilis, the YvrK gene was cloned by polymerase chain reaction. The cloned DNA encoding OXDC was inserted into the pBAD/gIII-A vector, downstream of the L-arabinose promotor. The plasmid vector was transformed into TOP 10 E. coli, and the transformants were selected with ampicillin. The recombinant E. coli, named pBy, was then analyzed by DNA sequencing and Western blot. To evaluate the oxalate-degrading function of pBy, pBy was cultured in LB broth containing oxalate, and then the amount of oxalate in the medium was assessed. The oxalate-degrading activity of homogenates of pBy was evaluated. RESULTS: DNA sequencing showed the successful transformation of the YvrK gene into TOP 10 E. coli. Western blot analyses showed that pBy expressed OXDC. pBy removed oxalate during the overnight culture in oxalate-containing LB broth, and the homogenate of pBy degraded 90% of oxalate under acidic conditions. CONCLUSIONS: A recombinant E. coli expressing the YvrK gene was successfully produced. The bacteria showed potent oxalate-degrading activity. The results of this study will provide a solution to the treatment of calcium oxalate stones and hyperoxaluria, for which there are few medical treatment modalities.

Estudio metabólico en pacientes con urolitiasis de alto riesgo de recurrencia / Metabolic study in patients with urinary lithiasis at high risk of recurrence

Introducción: La urolitiasis es considerada actualmente una enfermedad metabólica con tendencia ala recurrencia. El objetivo de este trabajo es evaluar la prevalencia de alteraciones metabólicas en pacientes de alto riesgo y su impacto según sexo y edad. Materiales y métodos: Es un estudio descriptivo de 36 pacientes (25 hombres y 11 mujeres), portadores de patología litiásica con alto riesgo de recurrencia. El estudio metabólico consistió en: calcemia, uricemia, fosfemia, PTH sérica, calciuria/24 hrs, uricosuria/24 hrs, fosfaturia/24 hrs, oxalaturia/24 hrs,citraturia/24 hrs y creatininuria/24 hrs. Los valores obtenidos fueron ajustados de acuerdo a la creatininuria y peso. Para el análisis estadístico se utilizó t-student (STATA 7.0). Se consideró significativo p<0,05.Resultados: En el 69 por ciento (25/36) se observó alguna alteración metabólica; el 36 por ciento (13/36) presentó 2 omás alteraciones metabólicas. Las alteraciones más frecuentes fueron la hipercalciuria (30,6 por ciento; 11/36), la hipocitraturia (30,6 por ciento; 11/36), la hiperuricemia (19,4 por ciento; 7/36) y la hiperoxalaturia (13, por ciento; 5/36).No se observó diferencias significativas de edad o sexo entre los grupos con y sin alteración metabólica. Conclusiones: La mayoría de los pacientes con patología litiásica recurrente o de alto riesgo presentan una o más alteraciones metabólicas, predominando la hipercalciuria y la hipocitraturia. En este estudio no hubo diferencias entre ambos sexos en la mayoría de las alteraciones metabólicas, ni tampoco en su distribución etaria. Estos resultados demuestran la necesidad de realizar estudios metabólicos en pacientes de alto riesgo, dado que existen herramientas terapéuticas que permiten un manejo médico de las alteraciones metabólicas y de esta forma reducir la recurrencia de litiasis.

Introduction: Urolithiasis is a metabolic disorder with a tendency to relapse. The aim of this study was to assess the prevalence of metabolic abnormalities in patients at high risk and the impact of sex and age. Materials and methods: Descriptive study of 36 patients (25 men and 11 women),with lithiasic pathology at high risk of recurrence. The metabolic study included the measurement of calcemia, uricemia, fosfemia, parathormone, calciuria/24hrs, uricosuria/24hrs, fosfaturia/24hrs, oxalaturia/24hrs, citraturia/ 24hrs and creatinine/24hrs. The values obtained were corrected according to weight and creatinine. The test used for statistical analysis was t-student (STATA 7.0). It was considered significant p <0.05.Results: In 69 percent (25/36) of the cases a metabolic abnormality was observed and in 36 percent (13/36) there was 2 or more alterations present. The metabolic disorders most frequently observed were hypercalciuria (30.6 percent; 11/36), hypocitraturia (30.6 percent; 11/36), hyperuricemia (19.4 percent; 7/36) and hyperoxaluria (13.9 percent; 5/36). There was no significant difference in age or sex between the groups with and without metabolic abnormality. Conclusions: Most patients with recurrent lithiasic pathology or at high-risk display one or more metabolic disorders, being hypercalciuria and hypocitraturia the most frecuently encountered. In this study, there was no difference between sexes in most of the metabolic disorders, nor in its age distribution. These results demonstrate the need for metabolic studies in high-risk patients, since there are tools that allow therapeutic medical management of metabolic disorders and thus reduce the recurrence of lithiasis.

Epidemiology and etiopathogenesis of urinary calculi in western Nepal (Pokhara).

Urinary stone disease is recorded in the literature from the dawn of the history and has spared no segment of society irrespective of age, gender, occupation and socio-economic status. It is still termed as "Refractory Disease" as complete medical management to prevent occurrence or recurrence is not so far available. We conducted a preliminary survey from the Manipal Teaching Hospital and carried out urinalyses to ascertain risk factors in the local population. This preliminary survey indicates the prevalence of stone disease is in moderate zone. Hyperoxaluria is an important risk factor in more than one fourth of the stone formers; and hypernatriuria is distinctly most common potentiating risk factor.

Treatment of pediatric urolithiasis in Iraq: five-year study

To report our experience with the management of childhood urolithiasis during a 5 year period. Between April 1999 and April 2004, 204 children with urolithiasis were prospectively evaluated, treated, and followed up in a university hospital in Baghdad. There were 150 males [73.5%] and 54 females [26.5%]. There was a history of previous stones in 73 [35.8%]. Stones were located in multiple sites in 80 children. Metabolic disorders were present in 58 [72.5%] of those with multiple sites. Etiology for stone formation was established in 89.7% of cases; 10.3% were idiopathic. Metabolic disorders were detected in 147 patients [72.1%]. Recurrent urinary tract infection was present in 87 patients [42.6%]. Anatomical defects of the renal system were present in 25 patients [12.3%]. The follow up of 156 patients [76.5%] ranged from one month to 5 years [mean= 36 months]. of those 156 patients, surgery was performed on 51. Extracorporeal shock wave lithotripsy [ESWL] was performed in 26, medical therapy was used in 111, and 19 patients were kept on observation. The ultimate stone free rates were 78.7%, 38.5% and 24.3% following surgery, ESWL and medical therapy respectively. Recurrence of stone disease was 19.7% following surgery. Respectively, 46.9% and 11.5% of patients receiving medical therapy, ESWL had no change in stone size. A combined approach with one or more techniques was applied to our patients. Our results indicate that a comprehensive approach to the care of pediatric urolithiasis requires attention to metabolic disorders