Hyperoxaluria Research Articles

N-acetylcysteine regulates oxalate induced injury of renal tubular epithelial cells through CDKN2B/TGF-β/SMAD axis.

This study was aimed to investigate the preventive effects of N-acetyl-L-cysteine (NAC) against renal tubular cell injury induced by oxalate and stone formation and further explore the related mechanism. Transcriptome sequencing combined with bioinformatics analysis were performed to identify differentially expressed gene (DEG) and related pathways. HK-2 cells were pretreated with or without antioxidant NAC/with or silencing DEG before exposed to sodium oxalate. Then, the cell viability, oxidative biomarkers of superoxidase dismutase (SOD) and malondialdehyde (MDA), apoptosis and cell cycle were measured through CCK8, ELISA and flow cytometry assay, respectively. Male SD rats were separated into control group, hyperoxaluria (HOx) group, NAC intervention group, and TGF-β/SMAD pathway inhibitor group. After treatment, the structure changes and oxidative stress and CaOx crystals deposition were evaluated in renal tissues by H&E staining, immunohistochemical and Pizzolato method. The expression of TGF-β/SMAD pathway related proteins (TGF-β1, SMAD3 and SMAD7) were determined by Western blot in vivo and in vitro. CDKN2B is a DEG screened by transcriptome sequencing combined with bioinformatics analysis, and verified by qRT-PCR. Sodium oxalate induced declined HK-2 cell viability, in parallel with inhibited cellular oxidative stress and apoptosis. The changes induced by oxalate in HK-2 cells were significantly reversed by NAC treatment or the silencing of CDKN2B. The cell structure damage and CaOx crystals deposition were observed in kidney tissues of HOx group. Meanwhile, the expression levels of SOD and 8-OHdG were detected in kidney tissues of HOx group. The changes induced by oxalate in kidney tissues were significantly reversed by NAC treatment. Besides, expression of SMAD7 was significantly down-regulated, while TGF-β1 and SMAD3 were accumulated induced by oxalate in vitro and in vivo. The expression levels of TGF-β/SMAD pathway related proteins induced by oxalate were reversed by NAC. In conclusion, we found that NAC could play an anti-calculus role by mediating CDKN2B/TGF-β/SMAD axis.

Potential Role of Lactobacillus and Bifidobacterium for Preventing Kidney Stones.

A probiotic is a living microorganism that promotes host health when grown under appropriate conditions. Kidney stones are one of the universal agonizing diseases that have increased dramatically in recent years. One of the causes of this disease is hyperoxaluria (HOU), which is known to be an important factor in the formation of oxalate stones and is manifested by high levels of oxalate in the urine. In addition, about 80% of kidney stones contain oxalate, and decomposition of this material by microbes is one way to dispose of it. Therefore, we examined a bacterial mixture containing Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Bifidobacterium longum to prevent of oxalate production in Wistar rats with kidney stones. We divided the rats into 6 groups defined in the method. The results of this study clearly show a decrease in urinary oxalate levels by exogenous means by L. plantarum, L. casei, L. acidophilus, and B. longum at the beginning of the experiment. Therefore, these bacteria can be used to control and prevent the formation of kidney stones. However, further studies should be conducted on the effects of these bacteria, and it is recommended to identify the gene responsible for the degradation of oxalate in order to develop a new probiotic.

Ефективність застосування препарату Канефрон® H у лікуванні дітей з вторинною гіпероксалурією

Мета: вивчення клінічної ефективності застосування фітопрепарату Канефрон® Н при вторинній гипер­оксалурії в дітей у комплексі з дієтою порівняно з одним дієтичним лікуванням. Матеріали та методи. Обстежено 46 дітей у віці 6–18 років з вторинною гіпероксалурією. Залежно від схеми лікування пацієнти розділені на групи: основна група (23 дитини) і група порівняння (23 дитини). Всі діти отримували дієтичне лікування з виключенням високооксалогенних продуктів і достатній питний режим. Пацієнтам основної групи крім дієтолікування застосовували препарат Канефрон® Н протягом 3 місяців. Вивчено добову екскрецію оксалатів, кальцію, сечової кислоти, фосфатів із сечею, відношення кальцій/креатинін у ранковій сечі до лікування і через 3 місяці терапії. Результати. Через 3 місяці терапії відзначено зниження добової екскреції оксалатів із сечею в обох групах спостереження. Коефіцієнт зниження екскреції оксалатів із сечею на тлі терапії був більш істотним у дітей основної групи у зіставленні групою порівняння (3,05 ± 0,32 проти 1,600 ± 0,102, р < 0,001). Частота гіпероксалурії на тлі терапії в основній групі зменшилася зі 100 до 56,5 % (p < 0,01), в групі порівняння практично не змінилася (зі 100 до 82,6 %, р > 0,05). Частота гіперкальциурії в обох групах спостереження не змінилася. При цьому в основній групі істотно зменшилася добова екскреція кальцію, фосфору, сечової кислоти з сечею. У хворих основної групи відзначено зменшення частоти еритроцитурії з 52,2 до 17,4 % (р < 0,01). У пацієнтів групи порівняння цей показник істотно не змінився. Рівень добової протеїнурії до і після лікування знизився лише в дітей основної групи з 0,117 до 0,052 г/добу (p < 0,02). Висновки. При вторинній гіпероксалурії в дітей призначення фітопрепарату Канефрон® Н протягом трьох місяців у поєднанні з дієтичним лікуванням є більш ефективним порівняно з монотерапією дієтою і призводить до зниження рівня оксалатів у сечі в 3 рази, тоді як лікування дієтою з обмеженням високооксалогенних продуктів — лише в 1,6 рази. Включення фітопрепарату Канефрон® Н супроводжується зниженням частоти еритроцитурії в 3 рази і зменшенням добової протеїнурії.

MP43-07 RESULTS OF A PHASE 2 STUDY OF RELOXALIASE IN SUBJECTS WITH ADVANCED OXALATE DISORDERS

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy (MP43)1 Apr 2020MP43-07 RESULTS OF A PHASE 2 STUDY OF RELOXALIASE IN SUBJECTS WITH ADVANCED OXALATE DISORDERS Felix Knauf, John Lieske, Mira Keddis, Annamaria Kausz, and Charles Scales* Felix KnaufFelix Knauf More articles by this author , John LieskeJohn Lieske More articles by this author , Mira KeddisMira Keddis More articles by this author , Annamaria KauszAnnamaria Kausz More articles by this author , and Charles Scales*Charles Scales* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000898.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hyperoxaluria (HOx) is a major risk factor for kidney stones, and can also lead to chronic kidney disease (CKD). With decreasing kidney function, plasma oxalate (POx) levels rise, resulting in oxalate deposition in the kidneys and other organs. There is an unmet need in patients with Enteric Hyperoxaluira (EH) and Primary Hyperoxaluira (PH), in whom the systemic and renal oxalate burden can contribute to worsening CKD, potentially leading to end-stage renal disease (ESRD). Reloxaliase is an oral, oxalate-specific enzyme therapy that is designed to degrade oxalate in the gastrointestinal (GI) tract, thereby reducing urinary oxalate (UOx). This study was conducted to evaluate whether reloxaliase can reduce UOx and POx in subjects with PH or severe EH and CKD. METHODS: This 12-week, open-label study of reloxaliase enrolled subjects with EH with CKD and hyperoxalemia (UOx ≥40 mg/24h, eGFR <45 mL/min/1.73m2 and POx >5 μmol/L, n=9 [6 with ESRD]), and PH (UOx ≥40 mg/24h, n=5) who received reloxaliase 7,500 u 5x/day with meals and snacks. POx and 24h UOx were obtained at baseline, Weeks 4, 8 and 12; UOx was not collected in ESRD subjects (eGFR <15 ml/min or dialysis). RESULTS: At the time of this report, 14 subjects were enrolled. In the EH subjects, there was a robust reduction in both UOx and POx as shown in the table below. No consistent effect was observed in PH subjects with normal kidney function. Reloxaliase was well tolerated, there were no study drug related serious adverse events. CONCLUSIONS: A substantial reduction in both POx and UOx was demonstrated in EH subjects with CKD. The mechanism of action of reloxaliase, to degrade oxalate in the GI tract, aligns with the pathophysiology of EH which involves excess oxalate absorption. To our knowledge, this is the first demonstration of a pharmacological therapy for POx reduction in subjects with EH and advanced CKD. This study suggests potential for reloxaliase to address an unmet need in subjects with EH and CKD, as this therapy could reduce systemic oxalate burden. Further clinical studies are warranted. Source of Funding: Allena Pharmaceuticals © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e649-e649 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Felix Knauf More articles by this author John Lieske More articles by this author Mira Keddis More articles by this author Annamaria Kausz More articles by this author Charles Scales* More articles by this author Expand All Advertisement PDF downloadLoading ...

Nephrocalcinosis in childhood

Nephrocalcinosis (NC) describes the deposition of calcium-oxalate or calcium-phosphate crystals in the tubuli or interstitial kidney parenchyma. Whereas kidney stones are formed in every age NC is most frequently seen during the first years of life. Because of multiple causative factors NC is a diagnostic challenge. A mostly metabolic reason for the development of nephrocalcinosis can be identified in up to 75% of patients and hence adequately be treated. An imbalance of lithogenic and inhibitory substances is the pathophysiologic basis for the development of nephrocalcinosis. This imbalance is either transient, for example in patients with alimentary hyperoxaluria or short term immobilization induced hypercalciuria, or ongoing, e.g., in tubulopathies or inborn errors of metabolism. Hypercalciuria is the most prominent promotor for the development of nephro- calcinosis, either accompanied by hypercalcemia or not. Both hyperoxaluria, in its primary or secondary forms, as well as hypocitraturia, e.g., in renal tubular acidosis, or in the premature infant, are further specific risk factors. Of course, although mostly clinically silent, early diagnosis is mandatory to start treatment, which may help not only to prevent progression of NC but end stage renal failure relying on the underlying diseases.

Primary hyperoxaluria - An update

The primary hyperoxalurias (PH) types I, II and III are autosomal recessive inherited defects of the glyoxylate metabolism leading to endogenous oxalate overproduction and hence strongly elevated urinary oxalate excretion (> 1 mmol/1.73 m 2 body surface area per day; normal

Metabolic stone disease

Nevertheless, urolithiasis is much less common in children when compared to adults. In western countries, only about 2–5% of urinary stone patients are children [4–8]. This may be the reason that many recommendations for diagnosing and treating urolithiasis are derived from adults. In some parts of the world, however, e.g., South Asia, Pakistan and Turkey the numbers are considerably higher [9]. Not only in these regions, but also in countries with a low prevalence of stone disease in children, pediatric urolithiasis is of special interest. There are several features being different from adult stone disease. Concerning pathophysiology, genetic disorders like cystinuria and primary hyperoxaluria and anomalies of the urinary tract play an important role. Although urinary tract infections as a cause of pediatric stones were much more common in former times [8], infected stones are still more common in children when compared with adults. The presentation of stones is also somewhat different in children. Due to the pathophysiology of the ureter, in children small calculi may pass unnoticed – a condition being rare in adults. ___________________________________________

Urolithiasis in Asian children: Evaluation of metabolic factors

This study was conducted to review urolithiasis in Asian children with a focus on urinary metabolic factors. A liter- ature search of Pub Med and Google identified pertinent articles from 20 different Asian countries which were subsequently reviewed. A totally of 12.913 children (M/F ratio of 2.37/1) were enrolled in the studies. Hypercalciuria, hyperuricosuria, hy- peroxaluria, hypocitraturia and decreased urinary magnesium excretion were reported in 652 of 4509 (14.45%), 276 of 3137 (8.8%), 1053 of 3973 (26.5%), 1940 of 2846 (68.2%), 32 of 240 (13.3%) of subjects, respectively. Cystinuria was noted in 112 of 4106 (2.7%) and mixed metabolic abnormalities were found in 175 of 724 (24.2%) patients. Association of urinary tract infection with stone disease was common in our series (2454 of 6430; (38.16) cases). Urologic abnormalities were uncommon and rec- orded in only 447 of 9788 patients (4.5%). The etiology of stone formation was idiopathic in 731 of 2731 (26.8%) patients. Analysis of 3977 stones indicated that 983 (24.9%) were pure Ca stones, whereas 1579 (40%), 411 (10.4%), 38 (0.95%) and 288 (7.35%) were mixed Ca, uric acid or urate, cystine and struvite stones respectively. The study showed that hypocitraturia and hyperoxaluria are the most common metabolic abnormalities. Overall, calcium was the main component of stones with the except that bladder stones were composed of urate or uric acid alone or in combination with calcium. In addition, uric acid stones which are uncommon among American children were frequently reported in Asian children.

Effects of oxalate-degrading enzyme on the calcium oxalate kidney stones formation in intestinal hy-peroxaluria rats

Objective To observe the effects of oxalate-degrading enzyme on the formation of calcium oxalate kidney stones in intestinal hyperoxaluria rats. Methods From May to June, 2014, 8 healthy rats were selected as the negative control group named Group A. Intestinal hyperoxaluria rats were randomly divided into three groups (n=8): positive control group (Group B), low-dose enzyme gavage group (Group C) and high-dose enzyme gavage group (Group D). Group A were treated with normal saline by gavage (3 ml/d). Group B were treated with 4% ammonium oxalate solution by gavage (3 ml/d). Group C and Group D were treated with 20 U/d or 40 U/d enzyme on the basis of Group B. The intervention lasted for 4 weeks. The oxalate concentrations of 24 hours urine in each group were detected in 0, 7th, 14th, 21th, 28th day. The renal function, the serum and urine Ca2+ in each group were measured in 0 and 28th day. In 28th day, the kidneys of rats in Group A, B, D were examined by spectral CT. The kidneys of 4 groups were examined microscopically for possible calcium oxalate crystals. Results In 0 day, the urinary oxalate concentrations of Group A, B, C and D were (0.61±0.06), (1.58±0.15), (1.59±0.10) and (1.64±0.20) mmol/L. There were no significant differences among B, C and D(P>0.05). Compared with A, the urinary oxalate concentrations of B, C and D were significantly higher (P<0.001). After the enzyme gavage, the urinary oxalate concentrations of Group C and D were significantly decreased, and Group D decreased more significantly. In 28th day, the urinary oxalate concentrations of Group A, B, C and D were (0.61±0.11), (1.64±0.12), (1.17±0.12) and (0.87±0.11) mmol/L. After statistical analysis, the urinary oxalate concentration of Group C and D were significantly lower than Group B (P<0.01), and Group D decreased more significantly than that in Group C (P<0.01). The CT post-processing workstation data analysis suggested that the average CT value of Group B were significantly higher than D (P<0.01), and both of the two groups were higher than Group A (P<0.01); The differences were more obvious in conditions of low-kilovolt. Renal tubular calcium oxalate crystal deposition were seen the most in Group B, less in Group C and lowest in Group D. Whereas, there was no crystallization in Group A. Conclusion Oxalate-degrading enzymes could inhibit the formation of calcium oxalate kidney stones in intestinal hyperoxaluria rats. Key words: Kidney calculi; Oxalate-degrading enzymes; Hyperoxaluria; Calcium oxalate stones; Rats

Hematuria and Dysuria with Hyperoxaluria Linked to Almond Milk Products

Almond milk products are a popular low-calorie nutrient for children avoiding lactose, gluten, or both. In the current report, investigators described

AB152. Analysis of altered microRNA expression profile in calcium oxalate stone formation

ObjectiveCalcium oxalate stones account for over 80% of urinary stones, while the molecular mechanism of its formation has been unclear. Hyperoxaluria plays an important role in the pathophysiological process of stone formation. The difference of miRNA expression profiles between experimental hyperoxaluric rats and normal rats is analyzed in our study, in order to find out the target genes and signaling pathways in the pathogenesis procedure of hyperoxaluria.MethodsFeeding ethylene glycol and ammonium chloride to culture male experimental hyperoxaluric rats as the experimental group, and age-matched male rats were selected as the control group. The oxalate concentration of 24 hour urine of each experimental rat was measured, of which the three highest were selected for microarray test. MicroRNA microarray was applied to evaluate the expression difference between the two groups and screen miRNA whose fold change were above 2.0 or below 0.5. Quantitative real-time PCR (qRT-PCR) technology was used to validate the microarray results. Target prediction, Gene Ontology (GO) analysis and pathway analysis were applied to predict the potential roles of microRNAs in biological processes.ResultsThere are 28 miRNAs differentially expressed with a more than 2.0-fold change. Among these miRNAs, 20 were up-regulated while 8 were down-regulated. After GO analysis and pathway analysis, the insulin resistance pathway and PI3K-Akt signaling pathway were associated with miRNA regulation.ConclusionsThis study identified differentially expressed miRNAs in hyperoxaluric rats, providing new insights into the role of miRNA in the formation of calcium oxalate stones.

Kidney stone risk following Roux-en-Y gastric bypass surgery.

Since the first report in 2005, Roux-en-Y gastric bypass (RYGB) surgery has been linked to a variety of metabolic changes that alter kidney stone risk. The studies with the highest level of evidence, performed in non-stone forming patients before and after RYGB, cite a number of kidney stone risk factors, including a 25% increase in urinary oxalate, a 30% decrease in urinary citrate, and reduction in urine volume by half a liter. In addition to these, recent clinical and experimental studies have contributed to our understanding of the pathophysiology of stone disease in this unique population. This review summarizes the current RYGB urinary chemistry profiles and epidemiological studies, outlines known and theoretical mechanisms of hyperoxaluria and hypocitrituria, and provides some standard recommendations for reducing stone risk in RYGB stone formers as well as some novel ones, including correction of metabolic acidosis and use of probiotics.

Primary hyperoxaluria.

Primary hyperoxaluria (PH) occurs due to an autosomal recessive hereditary disorder of the metabolism of glyoxylate, which causes excessive oxalate production. The most frequent and serious disorder is due to enzyme deficit of alanine-glyoxylate aminotransferase (PH type I) specific to hepatic peroxisome. As oxalate is not metabolised in humans and is excreted through the kidneys, the kidney is the first organ affected, causing recurrent lithiasis, nephrocalcinosis and early renal failure. With advance of renal failure, particularly in patients on haemodialysis (HD), calcium oxalate is massively deposited in tissues, which is known as oxalosis. Diagnosis is based on family history, the presence of urolithiasis and/or nephrocalcinosis, hyperoxaluria, oxalate deposits in tissue forming granulomas, molecular analysis of DNA and enzyme analysis if applicable. High diagnostic suspicion is required; therefore, unfortunately, in many cases it is diagnosed after its recurrence following kidney transplantation. Conservative management of this disease (high liquid intake, pyridoxine and crystallisation inhibitors) needs to be adopted early in order to delay kidney damage. Treatment by dialysis is ineffective in treating excess oxalate. After the kidney transplant, we normally observe a rapid appearance of oxalate deposits in the graft and the results of this technique are discouraging, with very few exceptions. Pre-emptive liver transplantation, or simultaneous liver and kidney transplants when there is already irreversible damage to the kidney, is the treatment of choice to treat the underlying disease and suppress oxalate overproduction. Given its condition as a rare disease and its genetic and clinical heterogeneity, it is not possible to gain evidence through randomised clinical trials. As a result, the recommendations are established by groups of experts based on publications of renowned scientific rigour. In this regard, a group of European experts (OxalEurope) has drawn up recommendations for diagnosis and treatment, which were published in 2012.

Evaluation for the anti-urolithiatic activity of Launaea procumbens against ethylene glycol-induced renal calculi in rats

Launaea procumbens Linn. is a plant commonly found in the west India and has been reported to decrease the renal calculi. This study investigated the anti-urolithiatic activity of L. procumbens against ethylene glycol-induced urolithiasis and its possible underlying mechanisms. The crude methanolic extract of L. procumbens leaves was studied using ethylene glycol-induced renal calculi in rat model. Results indicate that ethylene glycol feeding to rats resulted in to hyper oxaluria, hypercalciuria, as well as increased renal excretion of phosphate. Supplementation with methanolic extract of L. procumbens leaves (MELP) significantly prevented changes in urinary calcium, oxalate and phosphate excretion dose-dependently. The increased calcium and oxalate level and number of calcium oxalate crystal in the kidney tissue of calculogenic rats were significantly reverted by supplementation with MELP. The MELP supplementation also prevents the impairment of renal functions. The mechanism underlying this effect is mediated possibly through antioxidant nephroprotection and its effect on urinary concentration of stone forming constituents and risk factor. ConclusionThese results indicate that methanolic extracts of L. procumbens leaves are effective against the urolithiasis.

Primary hyperoxaluria with development of renal failure during infancy: Report of two cases

Primer hiperokzaluri (PH), okzalatin asiri sistemik uretimine yol acan, nadir gorulen gliokzalat metabolizma bozuklugudur. Okzalatin asiri uretimi ve idrarla atiliminin artmasi, tekrarlayan uriner sistem taslari ve nefrokalsinozis ile sonuclanir. Vucutta okzalat birikimi sistemik okzalozise neden olur ve glomeruler filtrasyon hizi ilerleyici bobrek tutulumuna bagli olarak azalir. Infantil donemde PH tanisi alan ve bobrek yetmezligi gelisen iki vaka sunulmustur.

Construction and identification of recombinant lentiviral expressing vectors formyl-CoA transferase gene and Oxalyl-CoA decarboxylase gene of oxalobacter formigenes from Chinese feces

Objective To clone the formyl-CoA transferase gene (FRC),and Oxalyl-CoA decarboxylase gene ( OXC),in oxalobacter formigenes from Chinese feces (OxCF),and construct the recombinant lentiviral expressing vectors pLenti6.3-FRC-IRES-EGFP and pLenti6.3-OXC-IRES-DsRED,providing a basis for further study on gene therapy for hyperoxalurias.Methods Total RNA was isolated from OxCF,and the FRC and OXC cDNA was amplified by polymerase chain reaction (PCR) and then ligated with pMD18T simple vectors after retrieve and purification.The ligation products were transformed into competent DH5α.The positive recombinant clones were selected and identified by a complementation,restriction endonuclease digestion.The cloning vector and the lentiviral vectors pLenti6.3/v5 DEST-IRES-EGFP and pLenti6.3/v5 DEST-IRES-DsRED first digested with BamHⅠ were ligated and transformed respectivly.The enzyme and PCR analyses were performed to confirm the recombinant vector,and then DNA sequence were analysis.The titer of constucted lentivirus vectors were tested.Results Two fragments of 1287 bp and 1707 bp were obtained by PCR respectivly.The enzyme and PCR analyses revealed that the correct FRC and OXC cDNA was cloned.The sequence of pLenti6.3-FRC-IRES-EGFP and pLenti6.3-OXC-IRES-DsRED was identical to that of cloned cDNA respectivly.HEK293T cells had green and red fluorescence 24 h after transfection.The titers of two types of virus were 1.15 × 108 TU/ml and 9.75 × 107 TU/ml respectively.Conclusion FRC and OXC are cloned correctly and the recombinant lentiviral vectors pLenti6.3-FRC-IRES-EGFP and pLenti6.3-OXC-IRES-DsRED are constructed successfully. Key words: Oxalobacter formigenes; Lentiviral vector; Hyperoxalurias

Hyperoxaluric rats do not exhibit alterations in renal expression patterns of Slc26a1 (SAT1) mRNA or protein

Little is known about oxalate transport in renal epithelia under basal conditions, let alone in hyperoxaluria when the capacity for renal oxalate excretion is increased. Sulfate anion transporter 1 (SAT1, Slc26a1) is considered to be a major basolateral anion-oxalate exchanger in the proximal tubule and we hypothesized its expression may correlate with urinary oxalate excretion. We quantified changes in the renal expression of SAT1 mRNA and protein in two rat models, one with hyperoxaluria (HYP) and one with renal insufficiency (HRF) induced by hyperoxaluria. The hyperoxaluria observed in the HYP group could not simply be ascribed to changes in SAT1 mRNA or protein abundance. However, when hyperoxaluria was accompanied by renal insufficiency, significant reductions in SAT1 mRNA and protein were detected in medullary and papillary tissue. Together, the results indicate that transcriptional modulation of the SAT1 gene is not a significant component of the hyperoxaluria observed in these rat models.

The clinical spectrum of idiopathic hyperuricosuria in children: Isolated and associated with hypercalciuria/hyperoxaluria

The clinical manifestations of hyperuricosuria (HU) are usually underestimated by the clinician. The aim of this study was to review the clinical spectrum of symptomatology of HU and to evaluate the presence of associated hypercalciuria (HC) and hyperoxaluria (HX). A retrospective review was done on 64 children with HU seen between January 2004 and December 2008. The patients were divided into HU 19, HU + HC 4, HU + HX 21 and HU + HC + HX 20. The mean age at diagnosis was 80 months (range six to 156 months). Duration of follow-up ranged was from six to 66 months. There were 228 symptomatic episodes for 64 patients (males 31, females 33). The relationship of symptomatology to age and gender were not significant. The most common symptoms were abdominal pain 67.2% (in 7/44 it was localized to the right lower quadrant, mimicking appendicitis), flank pain 59.4%, increased urinary frequency 43.4%, urgency 39%, enuresis 31.25%, oliguria 29.7%, dysuria 25%, red urine 20.35%, vaginal itching 15.21%, dribbling 14.06%, orange urine 12.5%, hesitancy 12.5% and penile pain 7.81%. To our knowledge, the vaginal itching and penile pain were not previously described. Family history was positive for stones and/or gout in 62.5%. The presence of a positive family history and red urine were significant (P-value <0.05) for the presence of an underlying HU. In the presence of recurrent abdominal/flank pain, hematuria without proteinuria or edema and urological symptomatology, especially in the presence of red urine, and a positive family history of gout or stones, a search for HU is in order. This will avoid unnecessary and invasive investigations.

Acute renal failure due to oxalate crystal deposition and enteric hyperoxaluria.

Acute renal failure due to oxalate crystal deposition and enteric hyperoxaluria.

A primary study on the mechanisms of calculus crystal transport by macraphage in rat's kidney

Objective To investigate the mechanisms of calculus crystal transport by macro-phage in kidney. Methods Hyperoxaluria rat model was established by administration of 1% ethyl-ene glycol and 1% ammonium chloride in drinking water. 24 h rat urine was collected, urinary oxalate were analyzed by ion chromatography. The expression and location of osteopontin and macrophage in kidney were observed by immunohistochemistry. Macrophage and calculus crystal at the basement membrane of renal tubular epithelial cells and interstitium were observed. Results The urinary ox-slate concentration were (0.22±0.13), (0.29±0.08), (0. 50±0.26), (0. 41±0. 22), (0.25±0. 12) ng/ml among these 5 groups. The osteoponitin expression was 0.16±0.04, 0.25±0.09, 0.37±0.10, 0.23±0.08, 0.19±0.02 respectively. The expression of osteopontin was positively correlated with urinary oxlate concentration(r=0.887, P<0.05). The macrophage at the basement membrane of renal tubular epithelial cells was 0.12±0.08, 0.19±0.06, 0.27±0.04, 0.16±0.03, 0.18±0.03 respectively. The macrophage distribution was positively correlated with the expression of osteopontin (r= 0.596, P<0.05). The macrophage moved from vessel to the basement membrane of loops of Henle, then disrupted and released the calculus crystal. Conclusions The macrophage might take part in the calculus crystal transport in kidney at the basement membrane of loops of Henle, which may be the source of Randall plaque. This process may be mediated by osteopontin. Key words: Kidney calculi; Hyperotreti; Macrophage