Search

Prunus cerasoides D. Don is a plant of great venerative value in the Himalayan region. The fruits and seed kernels of this plant are traditionally used for the treatment of urinary stones. Present study was aimed to demonstrate the in vitro and preclinical antilithic potential of the hydroethanolic extract of Prunus cerasoides fruits against calcium oxalate urolithiasis. In vitro antiurolithiatic screening was done by nucleation, and aggregation assay, while preclinical evaluation was carried out on ethylene glycol (0.75% v/v) and ammonium chloride (1% w/v) rendered urolithiasic male Wistar rats. P. cerasoides fruit extract induced nucleation of multiple small sized calcium oxalate crystals and inhibited their aggregation in the metastable solutions. P. cerasoides fruit extract to a large extent prevented lithogenic treatment induced anorexia, weight loss, polydipsia, polyuria, crystalluria, hypercalciuria, hyperoxaluria, hyperuricosuria, hyperphosphaturia, hypocitraturia and hypomagnesuria. It also showed preventive effect on the deposition of calcium, oxalate and phosphate in kidney tissues and exhibited ameliorative effect on serum urea, creatinine and uric acid. Moreover, inhibitory effect on oxidative stress induced degeneration of renal tissue was also recorded from histopathological analysis of the kidneys. PCFE showed promising outcomes as an antiurolithiatic both prophylactically and curatively. The effects can be attributed to its ability to restore the equilibrium between the urinary promoters and inhibitors of CaOx crystallization, its anticrystallization activity and its ameliorating effects on renal cellularity, urine and serum chemistry.

1. Amanda J. Clark, MD* 2. Lauren Matevish, MD† 3. Marta Hernanz-Schulman, MD‡ 4. Emily F. Mason, MD, PhD§ 5. Tracy E. Hunley, MD¶ 1. *Division of Pediatric Nephrology, Boston Children’s Hospital, Boston, MA 2. †Vanderbilt University School of Medicine, Nashville, TN 3. ‡Division of Diagnostic Imaging, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN 4. §Division of Hematopathology, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 5. ¶Division of Pediatric Nephrology, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN A 13-year-old girl presents to the pediatric clinic with complaints of malaise, progressive nausea, emesis, and poor oral intake since removal of her wisdom teeth 1 month earlier. In that month she completed a course of clindamycin to treat a suspected postoperative oral infection. Review of systems revealed a 10-lb unintentional weight loss, intermittent joint pain, and decreased urine output. She denies any fevers. Vital signs are normal other than blood pressure of 130/72 mm Hg and pulse of 121 beats/min. Physical examination shows a tired-appearing but polite young lady with a slightly enlarged, asymmetrical thyroid and otherwise normal examination findings. A complete blood cell count shows a hemoglobin level of 11.6 g/dL (116 g/L), a platelet count of 0.153 × 103/mcL (0.153 × 109/L), and a white blood cell count of 5.3/µL (0.01 × 109/L) with a normal differential cell count. Thyrotropin and free T4 levels are normal. Her sedimentation rate is 43 mm/hr. A complete metabolic panel reveals normal sodium, potassium, chloride, carbon dioxide, albumin, total protein, and calcium levels. Her creatinine level is elevated to 2.29 mg/dL (202.44 µmol/L), blood urea nitrogen level is 36 mg/dL (12.9 mmol/L), total bilirubin level is 1.1 mg/dL (18.8 µmol/L), aspartate aminotransferase level is 53 U/L (0.89 µkat/L), and alanine aminotransferase level is 37 U/L (0.62 µkat/L). The urine pregnancy test result is negative. Dipstick urinalysis reveals yellow urine, specific gravity of 1.010, pH 5.5, moderate blood, trace protein, positive nitrites, negative leukocyte esterase, and small bilirubin. Urine microscopy is striking for numerous uric acid crystals (Figs 1 and 2). Additional serum testing and imaging lead to the diagnosis. Figure 1. Urine microscopy at 10× magnification showing the striking presence of crystalluria. Figure 2. Urine microscopy at 40× magnification again showing striking crystalluria with several morphologies of uric acid crystal, including diamonds (thin arrow), rhomboid …

A large population is suffering from multifactorial urolithiasis worldwide with a reoccurrence rate of almost 70%–80% in males and 47%–60% in females. In the present study, the nephroprotective effect of silver nanoparticles (AgNPs) synthesised by Bryophyllum pinnatum was evaluated in ethylene glycol‐induced urolithiasis in rat. B. pinnatum‐mediated AgNPs which were found to be spherical and polydispersed particles with an average size of 32.65 nm determined by transmission electron microscopy analysis, and showing an absorption peak at 432 nm by the UV‐Vis spectrophotometric analysis, revealing the role of hydroxyl group in the synthesis by Fourier Transformed Infrared Spectroscopy analysis, with a zeta potential value of −15.7 mV. The crystalline nature and fcc structure was demonstrated based on X‐ray diffraction analysis. Animal study was performed on 36 male Wistar rats divided into six equal groups, which demonstrated significant increase in serum total protein, albumin and globulin and significant decrease in AST, ALT, creatinine, BUN, calcium and phosphorus in group V and VI when compared with group II and IV. No crystalluria was observed in rats given B. pinnatum AgNPs. Histopathological observations in group V and VI showed mild degenerative changes and restoration or maintenance of kidney parenchyma when compared with group II and IV rats. Thus, the authors conclude with the beneficial preventive and therapeutic nephroprotective effect of B. pinnatum‐mediated AgNPs against ethylene glycol‐induced urolithiasis in rats.

Cystinuria, a rare inherited aminoaciduria condition, is characterized by the hyperexcretion of cystine, ornithine, lysine, and arginine. Its main clinical manifestation is cystine stone formation in the urinary tract, being responsible for 1–2% total and 6–8% pediatric lithiasis. Cystinuria patients suffer from recurrent lithiasic episodes that might end in surgical interventions, progressive renal functional deterioration, and kidney loss. Cystinuria is monitored for the presence of urinary cystine stones by crystalluria, imaging techniques or urinary cystine capacity; all with limited predicting capabilities. We analyzed blood and urine levels of the natural antioxidant L-ergothioneine in a Type B cystinuria mouse model, and urine levels of its metabolic product S-methyl-L-ergothioneine, in both male and female mice at two different ages and with different lithiasic phenotype. Urinary levels of S-methyl-L-ergothioneine showed differences related to age, gender and lithiasic phenotype. Once normalized by L-ergothioneine to account for interindividual differences, the S-methyl-L-ergothioneine to L-ergothioneine urinary ratio discriminated between cystine lithiasic phenotypes. Urine S-methyl-L-ergothioneine to L-ergothioneine ratio could be easily determined in urine and, as being capable of discriminating between cystine lithiasis phenotypes, it could be used as a lithiasis biomarker in cystinuria patient management., This work has been supported by the Spanish Health Institute Carlos III Grants FIS PI13/00121-R-FEDER, PI16/00267-R-FEDER and PI20/00200-R_FEDER (to VN), Generalitat de Catalunya Grant SGR2017-191 (to VN). VN acknowledge the support of the CERCA Program/Generalitat de Catalunya.

Simple Summary Cystinuria, as an inborn error of metabolism, is a problem with worldwide distribution and has been reported in various canine and feline breeds. Transepithelial transport of cystine is mediated by COLA transporter and the mutation in genes coding this transporter may cause cystinuria. Urolithiasis associated with typical clinical signs may be the clinical consequence of cystinuria. The mutation causing cystinuria and the mode of inheritance have been determined only in several canine breeds. This makes cystinuria difficult to control and gradually decreases its prevalence. In cats, cystinuria occurs only rarely. Abstract The purpose of this review is to summarize current knowledge on canine and feline cystinuria from available scientific reports. Cystinuria is an inherited metabolic defect characterized by abnormal intestinal and renal amino acid transport in which cystine and the dibasic amino acids ornithine, lysine, and arginine are involved (COLA). At a normal urine pH, ornithine, lysine, and arginine are soluble, but cysteine forms a dimer, cystine, which is relatively insoluble, resulting in crystal precipitation. Mutations in genes coding COLA transporter and the mode of inheritance were identified only in some canine breeds. Cystinuric dogs may form uroliths (mostly in lower urinary tract) which are associated with typical clinical symptoms. The prevalence of cystine urolithiasis is much higher in European countries (up to 14% according to the recent reports) when compared to North America (United States and Canada) where it is approximately 1–3%. Cystinuria may be diagnosed by the detection of cystine urolithiasis, cystine crystalluria, assessment of amino aciduria, or using genetic tests. The management of cystinuria is aimed at urolith removal or dissolution which may be reached by dietary changes or medical treatment. In dogs with androgen-dependent cystinuria, castration will help. In cats, cystinuria occurs less frequently in comparison with dogs.

A 10-year-old golden retriever bitch was treated for diarrhea and vomiting that lasted about 1 month without a specific diagnosis until a hepatic biopsy provided a histopathologic diagnosis of lymphoma. The dog was referred to the Swedish University of Agricultural Science and treated with one dose of l-asparaginase. The day after chemotherapy, the urine was dark yellow, very turbid, and had large amounts of small amorphous crystals and many casts made of similar appearing material identified by infrared spectroscopy to be 100% uric acid dihydrate. Serum uric acid was elevated at 224 μmol/L (RI 0-59). The dog's illness became worse after chemotherapy. Lymphoma treatment was not continued, and the dog was euthanized 9 days after the l-asparaginase treatment. Among other problems were persistent proteinuria with a urine protein-to-creatinine ratio of 2.3 and severe hypoalbuminemia. Serum protein electrophoresis performed 3 weeks prior to chemotherapy indicated hyperproteinemia (total protein 78 g/L) having a biclonal gammopathy with 35 g/L β-2 globulins and 11 g/L γ globulins. Despite prominent cylinduria and crystalluria, the patient did not develop azotemia or isosthenuria.

Background Primary hyperoxaluria type 1 (PH1) is an inherited disease caused by mutations in alanine-glyoxylate aminotransferase (AGXT). It is characterized by abnormal metabolism of glyoxylic acid in the liver leading to endogenous oxalate overproduction and deposition of oxalate in multiple organs, mainly the kidney. Patients of PH1 often suffer from recurrent urinary tract stones, and finally renal failure. There is no effective treatment other than combined liver-kidney transplantation. Methods Microinjection was administered to PH1 rats. Urine samples were collected for urine analysis. Kidney tissues were for Western blotting, quantitative PCR, AGT assays and histological evaluation. Results In this study, we generated a novel PH1 disease model through CRISPR/Cas9 mediated disruption of mitochondrial localized Agxt gene isoform in rats. Agxt-deficient rats excreted more oxalate in the urine than WT animals. Meanwhile, mutant rats exhibited crystalluria and showed a slight dilatation of renal tubules with mild fibrosis in the kidney. When supplied with 0.4% ethylene glycol (EG) in drinking water, mutant rats excreted greater abundance of oxalate and developed severe nephrocalcinosis in contrast to WT animals. Significantly elevated expression of inflammation- and fibrosisrelated genes was also detected in mutants. Conclusion These data suggest that Agxt-deficiency in mitochondria impairs glyoxylic acid metabolism and leads to PH1 in rats. This rat strain would not only be a useful model for the study of the pathogenesis and pathology of PH1 but also a valuable tool for the development and evaluation of innovative drugs and therapeutics.

Graphical abstract, Background To investigate the antilithiatic effect of hydroalcoholic extract of Kabab Chini (Piper cubeba L.) fruit in male Sprague Dawley rats. Methods Rats were divided into six groups of six each. Group I received regular rat food and drinking water ad libitum. Groups II to VI were administered with ethylene glycol (EG) 0.75% (V/V) and ammonium chloride (AC) 1% (W/V) in drinking water for 7 days to induce urolithiasis. From 8th day Group I received 1 mL of 5% gum acacia. Group IV was treated with Cystone; V and VI groups with the hydro-alcoholic extract of Piper cubeba L. Treatment was continued for further 14 days, thereafter animals sacrificed. While Group II animals were sacrificed just after 7 days treatment with EG and AC. Group III was left untreated until 14 days and sacrificed on 22nd day. Crystalluria was analyzed on 8th and 22nd day while, urinary calcium, phosphorus, creatinine, sodium and magnesium on 22nd day. Biochemistry and histopathological studies of kidney were also carried out. Results Test groups showed significant reduction (p

A 2-year-old male castrated domestic shorthair cat was presented for recommendations for dietary management of chronic FLUTD using a strictly plant-based diet as per the stipulations of the cat's owner. The cat had a history of urethral obstruction of unknown etiology, persistent marked struvite crystalluria, and persistent inappropriate elimination. Commercial plant-based products meeting the nutritional recommendations for maintenance of adult cats with the lowest concentration of struvite precursors were identified, but the cat would not eat them. At the request of the client, a homemade plant-based diet was formulated with the intention of increasing water intake and promoting acidic, dilute urine. Urine concentration was able to be decreased somewhat and struvite crystalluria resolved, but the urine remained more alkaline than intended. The cat clinically improved and no further FLUTD episodes were reported by the client.

Kidney stones are becoming more prevalent worldwide in adults and children. The most common type of kidney stone is comprised of calcium oxalate (CaOx) crystals. Crystalluria occurs when urine becomes supersaturated with minerals (e.g., calcium, oxalate, phosphate) and precedes kidney stone formation. Standard methods to assess crystalluria in stone formers include microscopy, filtration, and centrifugation. However, these methods primarily detect microcrystals and not nanocrystals. Nanocrystals have been suggested to be more harmful to kidney epithelial cells than microcrystals in vitro. Here, we describe the ability of Nanoparticle Tracking analysis (NTA) to detect human urinary nanocrystals. Healthy adults were fed a controlled oxalate diet prior to drinking an oxalate load to stimulate urinary nanocrystals. Urine was collected for 24 hours before and after the oxalate load. Samples were processed and washed with ethanol to purify samples. Urinary nanocrystals were stained with the calcium binding fluorophore, Fluo-4 AM. After staining, the size and count of nanocrystals were determined using NTA. The findings from this study show NTA can efficiently detect nanocrystalluria in healthy adults. These findings suggest NTA could be a valuable early detection method of nanocrystalluria in patients with kidney stone disease.

The major etiologies of gout and kidney stone formation are similar－hyperuremia , which is caused by unbalanced uric acid production/exertion. And gout is one of the important risk factor that promotes kidney stone formation. It’s worth noting that crystals retension/aggregation is the early stage of stone formation. However, the mechanism between gout and crystalluria remains unclear. Our previous studies found good correlation between auto-fluorescent crystals and urolithiasis. Higher proportion of auto-fluorescent crystalluria in gout patients were also noted. It this paper, we demonstrated characterization of auto-fluorescent urinary crystals in gout patients by micro-Raman system and laser confocal microscopy. Our purpose is to figure out the mechanism among gout flare, urolithiasis and auto-fluorescent crystal retention. And the results supported that fluorophore inside the crystals may be a powerful indicator for crystals retention. Further studies are required to validate our hypothesis.

Introduction Crystalluria is thought to be associated with kidney stone formation and can occur when urine becomes supersaturated with calcium, oxalate, and phosphate. The principal method used to identify urinary crystals is microscopy, with or without a polarized light source. This method can detect crystals above 1 μm in diameter (microcrystals). However, analyses of calcium oxalate kidney stones have indicated that crystallite components in these calculi are 50–100 nm in diameter. Recent studies have suggested that nanocrystals (, Graphical abstract

Lesch–Nyhan disease results from mutations in the gene for hypoxanthine quinine phosphoribosyltransferase hypoxanthine guanine phosphoribosyltransferase. Patients have varying degrees of diminished activity of the enzyme, but a majority with the complete syndrome have essentially zero activity. Patients have crystalluria, hematuria, and renal stone disease. Neurologic development is severe; patients do not walk or sit alone. Involuntary movements are characteristic. Self-injurious behavior includes characteristic biting injury, which may lead to loss of tissue about the mouth or fingers. Treatment with allopurinol prevents hyperuricemia and its consequences, but it has no effect on the neurology or the behavior. Phosphoribosylpyrophosphate syntheses deficiency leads also to clinical gout and urolithiasis. The disease is transmitted as an X-linked dominant; so females are clinically affected.

Improving diagnostic methods for the appointment of effective treatment of animals with urocystitis is an extremely important problem in veterinary medicine. Microscopy of urine sediment is a necessary and important part of general clinical research. With this research method, it is possible to clarify the localization of the inflammatory process in the urinary tract, establish the degree of mucosal damage, differentiate urinary tract diseases from kidney diseases, and conduct differential diagnosis of neoplasms. Urine sediment in dogs suffering from urocystitis revealed postrenal microhematuria (in the field of view of the microscope 5-20 red blood cells), pyuria due to neutrophils (in the field of view 20-100), bacteriuria and the appearance of a significant number of transitional and superficial epithelial cells (in the field of view 3-5 cells), which were placed, both singly and in the form of layers. The admission of a large amount of transitional epithelial cells epithelium into the urine of the male dogs indicated the development of an inflammatory process of bacterial origin in the bladder and distal urethra, sometimes with prostate damage. In 50% of the dogs with urocystitis, crystalluria and spermatorea were noted. Of the unorganized sediments in the urine of experimental animals, crystals of ammonium biurate (acidic uric acid ammonium) were most often found, less often crystals of phosphoric acid calx, and even less often struvite crystals.

To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria.Data from 442 patients with cystinuria were recorded retrospectively. Crystalluria was studied in 89 patients. A mixed-effects logistic regression model was used to estimate how urine pH, specific gravity and cysteine-binding thiols (CBT) correlate with risk of cystine crystalluria.Alkalizing agents and CBT agents were given to 88.8% (n = 381) and 55.3% (n = 238) of patients, respectively. Gastrointestinal AEs were reported in 12.3%, 10.4% and 2.6% of patients treated with potassium bicarbonate, potassium citrate and sodium bicarbonate, respectively (P = 0.008). The percentages of patients who experienced at least one AE with tiopronin (24.6%) and with D-penicillamine (29.5%) were similar (P = 0.45). Increasing urine pH and decreasing urine specific gravity significantly reduced the risk of cystine crystalluria, whereas D-penicillamine and tiopronin treatments did not reduce this risk (odds ratio [OR] 1 for pH ≤6.5; OR 0.52 [95% confidence interval {95% CI} 0.28-0.95] for 7.0pH ≤7.5, P = 0.03; OR 0.26 [95% CI 0.13-0.53] for 7.5pH ≤8.0, P0.001; OR 1 for specific gravity ≤1.005 OR 5.76 [95% CI 1.45-22.85] for 1.006 ≤ specific gravity ≤1.010, P = 0.01; and OR 11.06 [95% CI 2.76-44.26] for 1.011 ≤ specific gravity ≤ 1.014, P0.001). Increased urine pH significantly increased the risk of calcium phosphate crystalluria (OR 1 for pH≤ 6.5; OR 6.09 [95% CI 2.15-17.25] for pH8.0, P0.001).Adverse events were frequent with D-penicillamine and tiopronin. Alkaline hyperdiuresis was well tolerated and reduced cystine crystalluria. Urine specific gravity ≤1.005 and urine pH7.5, while warning about calcium-phosphate crystallization, should be the goals of medical therapy.

Imipenem/cilastatin is a broad-spectrum β-lactam antibiotic used to treat several bacterial infections. The present study was designed to validate the nephrotoxic effect of this drug in rats and to explore its potentional urolithiatic effect. Thirty two Wistar rats were randomly divided into four groups: three experimental groups treated with different imipenem/cilastatin dosages (30, 50 and 80 mg/kg/day) and a control group.The experimental groups were given intraperitoneal imipenem/cilastatin injections twice daily for 7 days, and the control group was given intraperitoneal vehicle NaCl 0.9% solution. Nephrotoxic effect of this antibiotic was assessed based on urine and plasma biochemistry, oxidative stress parameters, histopathological examination and infrared spectroscopy characterization. Imipenem/cilastatin administration resulted in alkaline urine, polyuria, crystalluria, raised plasma levels of urea, creatinine and uric acid, decreased contents of plasma gamma glutamyltranspeptidase and alkaline phosphatase, oxidative stress status, malpighian metaplasia as well as crystal deposition in kidneys and urinary tracts of Wistar rats. In addition, the precise nature of the calculi was identified, being formed by imipenem/cilastatin, thus confirming their iatrogenic origin. In conclusion, this study demonstrated through rat model that subacute exposure to imipenem/cilastatin may induce nephrotoxicity and increase the risk for developing kidney stones even at therapeutic dose levels in a dose-dependent manner.

Urolithiasis is a common urological disease the prevalence of which tends to increase. The main targets of therapy for patients with uric acid nephrolithiasis include normalization of purine metabolism, dissolution of stones, and prevention of stone formation. Oral administration of a citrate mixture or sodium bicarbonate results in urine alkalinization and dissolution of the uric acid stone. The article demonstrates the results of the recent Russian studies of the efficacy and safety of litholytic therapy for uric acid nephrolithiasis both as monotherapy and in combination with remote lithotripsy. The studies show that citrate therapy is a highly effective, non-invasive method for the treatment and metaphylaxis of uric acid nephrolithiasis.

Desmosium styracifolium (D. styracifolium), which is considered as a Chinese herbal medicine, has been reported to treat the kidney stone diseases. However, the potential phytochemically active components and the underlying mechanisms associated with its efficacy in targeting urolithiasis remain to be elucidated. This study aims to investigate the anti-urolithiatic effect of total flavonoids of D. styracifolium (TFDS) on calcium oxalate (CaOx) renal stones in Sprague-Dawley rats. Animal models of CaOx urolithiasis were established in male Sprague-Dawley rats by adding 5% w/w hydroxy-L-proline (HLP) in regular rat chow. The TFDS orally at 100, 400 mg/kg, respectively, were administered along with HLP for 28 days. At the end of 28 days of treatment, urine and serum samples were collected for crystalluria determination and various biochemical analysis. Kidney tissues were isolated and processed for antioxidant parameters measurement and histopathological examinations. HLP-induced hyperoxaluria alone reliably caused CaOx nephrolithiasis in rats. We showed that TFDS significantly reduced crystalluria and CaOx crystal deposits in the kidney sections as compared to untreated HLP group. Also, TFDS was observed to decrease urinary oxalate excretion, alleviate the pro-acidosis condition, improve the impaired renal functions and renal epithelial cell injury. Moreover, TFDS protected against the oxidative stress changes via reducing MDA content, increasing CAT and GSH-Px activities in renal homogenate, as well as attenuating the expression of MCP-1, OPN and TGF-β proteins. These results indicated that TFDS had beneficial effect on inhibition of CaOx formation in the rat kidney probably through a combination of antioxidant, anti-inflammatory, urine alkalinizing activities, and lowering the concentration of urinary stone-forming constituents. Thus, TFDS might have clinical implications in preventing oxidative renal cell injury and, ultimately, kidney stone formation. The data provide a rationale for the medicinal use of TFDS in nephrolithiasis and identify this agent as a potential source of new antiurolithic drugs.

Purpose. Definition of types of crystalluria in various forms of urolithiasis and biochemical signs of phosphate crystals in the urine, while phosphate urolithiasis (infectious origin). Patients and methods. The study involved 144 patients with recurrent urolithiasis — 75 women and 69 men. Of these, 46 — diagnosed calculi with uric acid, 44 — calcium oxalate or mixed with a prevalence of calcium oxalate, in 54 — phosphate rocks (carbonate-apatite and/or struvite). The age of patients ranged from 21 to 74 years. 93 people have been under long-term, within 2–15 years, outpatient observation. The examination included the collection of anamnesis, general and microbiological analysis of urine, biochemical blood serum and urine on 10 indicators, reflecting renal function, state of the protein, water and electrolyte metabolism, uric acid metabolism, the chemical composition of the stone analysis. Results. It was found that in patients with calcium oxalate stones phosphaturia has been diagnosed in 2% of cases. And, along with calcium phosphate crystals they had oxalate crystals. In patients with phosphate urolithiasis phosphaturia observed in 96% of patients, in two patients (4%) they determined except phosphates also oxalate salt in urine sediment. Patients with phosphate urolithiasis at occurrence of phosphate crystalluria have metabolic state changes: increased serum uric acid concentration from 0.322 ± 0.009 to 0.367 ± 0.018 mmol/l daily renal excretion of inorganic phosphate 23.94 ± 2.93 mmol/day to 32.12 ± 4.39 mmol/day, and reduced total calcium content in urine 6.61 ± 0.94 mmol/day to 3.37 ± 0.89 mmol/day. The results led to the following conclusion. Conclusion. Biochemical signs of occurrence of phosphate crystalluria in patients with stones of infectious origin can be: the approaching level of excretion in the urine of inorganic phosphates to 32,12 ± 4,39 mmol/day, serum uric acid concentration to 0,367 ± 0,018 mmol/l, and the total content of calcium in the urine to 3.37 ± 0.89 mmol/day

THE AIM: to study clinical and laboratory manifestations of hypercalciuria in children of Barnaul, living in the zone of sharply continental climate of the South of Western Siberia. PATIENTS AND METHODS. The study included 239 children aged from 1 month to 16 years (mean age of 6.6±2,72 years) with idiopathic hypercalciuria (IH), diagnosed according to the level of calcium/creatininemia coefficient (CCC), more than 0.6 mmol/mmol and normal plasma calcium and parathyroid hormone. Conducted physical examination and biochemical blood and urine determination of calcium, phosphorus, creatinine, urea and uric acid, ultrasound of the kidneys and bladder, radiopaque research methods indicated. RESULTS. Family history of urolithiasis have been reported in 56.1% children with hypercalciuria. Analysis of comorbidity showed a combination of IH with urolithiasis in 15.1% patients with urinary system infections(USI) – in 38.5%, with anomalies of the urinary system – 27,2% children with neurogenic disorders of urination – at 9.2 percent. The clinical picture of the disease prevailed dysuric disorders (48,5%) and moderately pronounced edema syndrome (45,6%). In the urinary sediment of children with hypercalciuria, the most frequently recorded crystalluria (31,8%), microhematuria (19,2%) and leukocyturia (13.8%). CONCLUSION. Idiopathic hypercalciuria in children is often combined with such pathological conditions as USI, neurogenic disorders of urination, abnormalities of the urinary system and it is the cause of the development of the urolithiasis already in childhood.

Crystalluria is a marker of urine supersaturation with substances deriving from metabolic disorders, inherited diseases or drugs. The investigation of crystalluria must be done according to a protocol which includes the delivery to the laboratory of a proper urine sample, the use of a microscope equipped with polarized light, the accurate knowledge of urine pH, and a comprehensive examination of the crystals, which is based on their identification, quantification and size measurement. For unusual crystals, infrared spectroscopy may also be needed. If the formation of stones is always preceded by crystalluria, the reverse is not true. In addition to the crystalline composition, stone morphology provides valuable information on stone activity and, for some crystalline species, major information regarding the underlying pathology. Fourier transform infrared spectroscopy (FTIR) reliably identify specific forms of nephrolithiasis, as common-type stones made of calcium oxalate (CaOx) and/or calcium phosphate that is combined with morphology classification; using this method, stones may be classified into 6 types subdivided in 22 subtypes. The investigation of crystalluria is an inexpensive and valuable tool for the detection and the monitoring of inherited and acquired diseases associated with urinary stone formation or acute or chronic renal function impairment from intrarenal crystal precipitation. Selective FTIR identification of the composition of core (or the umbilication), middle part, and surface of every stone allows identification of the initiating lithogenic process (in the nucleus or in the Randall's plaque) and the factors which subsequently contributed to stone growth. In conclusion, the proposed morpho-constitutional method of urinary stone analysis, which moreover is rapid and low cost, provides clinically relevant orientations for targeted etiologic evaluation.

A critical examination of data in the literature and in as yet unpublished laboratory records on the possible role of so-called inhibitors of crystallisation in preventing the formation of calcium-containing kidney stones leads to the following conclusions. So-called inhibitors of spontaneous "self-nucleation" are unlikely to play any role in the initiation of the crystallisation of CaOx or CaP in urine because excessive urinary supersaturation of urine with respect to these salts dominates the onset of "self-nucleation" within the normal time frame of the transit of tubular fluid through the nephron (3-4 min). Inhibitors of the crystal growth of CaOx crystals may or may not play a significant role in the prevention of CaOx stone-formation since once again excessive supersaturation of urine can overwhelm any potential effect of the inhibitors on the growth process. However, they may play a role as inhibitors of crystal growth at lower levels of metastable supersaturation when the balance between supersaturation and inhibitors is more equal. Inhibitors of CaOx crystal aggregation may play a significant role in the prevention of stones, since they do not appear to be strongly affected by excessive supersaturation, either in vitro or in vivo. Inhibitors of CaOx crystal binding to renal tubular epithelium may exist but further studies are necessary to elucidate their importance in reducing the risk of initiating stones in the renal tubules. Inhibitors of CaOx crystal binding to Randall's Plaques and Randall's Plugs may exist but further studies are necessary to elucidate their importance in reducing the risk of initiating stones on renal papillae. There may be an alternative explanation other than a deficiency in the excretion of inhibitors for the observations that there is a difference between CaOx crystal size and degree of aggregation in the fresh, warm urines of normal subjects compared those in urine from patients with recurrent CaOx stones. This difference may depend more on the site of "self-nucleation" of CaOx crystals in the renal tubule rather than on a deficiency in the excretion of so-called inhibitors of crystallisation by patients with CaOx stones. The claim that administration of potassium citrate, potassium magnesium citrate or magnesium hydroxide reduces the rate of stone recurrence may be due to the effect of these forms of medication on the supersaturation of urine with respect to CaOx and CaP rather than to any increase in "inhibitory activity" attributed to these forms of treatment. In summary, there is a competition between supersaturation and so-called inhibitors of crystallisation which ultimately determines the pattern of crystalluria in stone-formers and normals. If the supersaturation of urine with respect to CaOx reaches or exceeds the 3-4 min formation product of that salt, then it dominates the crystallisation process both in terms of "self-nucleation" and crystal growth but appears to have little or no effect on the degree of aggregation of the crystals produced. At supersaturation levels of urine with respect to CaOx well below the 3-4 min formation product of that salt, the influence of inhibitors increases and some may affect not only the degree of aggregation but also the crystal growth of any pre-formed crystals of CaOx at these lower levels of metastability.

Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA. The UPLC-MS/MS assay was optimized by a chemometric approach for absolute quantification of DHA, utilizing isotopically labeled DHA as an internal standard. Experimental screening was conducted with D-optimal design and optimization of the DHA response was performed with central composite face design and related to the peak area of DHA using partial least square regression. Acceptable precision and accuracy of the DHA concentration were obtained over a calibration range of 100 to 5000ng/mL on three different days. The intra- and inter-day accuracy and precision coefficients of variation were well within ±15% for quality control samples analyzed in replicates of six at three concentration levels. Absolute quantification of DHA in urine samples from patients with APRT deficiency was achieved wihtin 6.5min. Measurement of DHA in 24h urine samples from three patients with APRT deficiency, diluted 1:15 (v/v) with 10mM ammonium hydroxide (NH4OH), yielded a concentration of 3021, 5860 and 10563ng/mL and 24h excretion of 816, 1327 and 1649mg, respectively. A rapid and robust UPLC-MS/MS assay for absolute quantification of DHA in urine was successfully developed. We believe this method will greatly facilitate diagnosis and management of patients with APRT deficiency.

The search for crystalluria and morphologic analysis of urinary crystals is of interest in the diagnostic evaluation and assessment of efficacy of therapeutic strategies in stone formers. In common calcium oxalate (CaOx) nephrolithiasis, identification of the monohydrate or dihydrate form of CaOx orients toward hyperoxaluria or hypercalciuria as the main lithogenic mechanism, respectively. An unusual high abundance of crystals exclusively made of CaOx monohydrate is highly suggestive of primary hyperoxaluria, the most severe of all types of renal stone diseases. The identification of crystal species such as struvite, cystine, 2,8-dihydroxyadenine, which are not found in normal urine, is indicative of specific pathological conditions, namely, infection stones and hereditary diseases such as cystinuria and dihydroxyadeninuria. Such diseases expose to progressive loss of renal function unless they are prevented by specific therapeutic measures. The presence of crystals made of drugs may entail the risk of kidney dysfunction because of crystallization of the drug or its metabolites.Serial determination of crystalluria, which reflects the activity of stone disease and its response to therapeutic measures, is of major interest in the follow-up of patients suffering from nephrolithiasis. It should be more largely used in clinical practice in most stone formers, still more for the surveillance of patients affected by severe, hereditary renal stone diseases such as primary hyperoxaluria, cystinuria, and dihydroxyadeninuria, where determination of the global crystal volume allows assessing the efficacy of therapeutic measures and optimizing the medical management of the patients., L’étude de la cristallurie et de ses caractéristiques qualitatives et quantitatives est d'un intérêt clinique majeur pour le diagnostic de la maladie lithiasique et l’évaluation de l'efficacité des mesures thérapeutiques proposées aux patients. Dans la lithiase oxalocalcique commune, la forme cristalline, whewellite ou weddellite, oriente respectivement vers une hyperoxalurie ou une hypercalciurie. Une quantité élevée de cristaux de whewellite traduit une forte hyperoxalurie et doit faire rechercher une hyperoxalurie primaire. L'identification de cristaux particuliers tels que la struvite, la cystine, la dihydroxy-2,8-adénine permet le diagnostic de pathologies spécifiques qui exposent à une altération progressive de la fonction rénale lorsqu'elles ne sont pas traitées précocement par des mesures adaptées. La présence de cristaux médicamenteux peut expliquer l'origine d'une insuffisance rénale aiguë développée sous traitement.Au cours du suivi des patients souffrant de lithiase, la détermination de la cristallurie sur des prélèvements sériés est d'un grand intérêt pour la prévention du risque de récidive de calculscar elle reflète l'activité de la maladie lithiasique et sa réponse aux mesures diététiques et thérapeutiques. Elle peut donc bénéficier à la plupart des patients lithiasiques. Elle se doit d’être réalisée chez tout patient souffrant d'une forme héréditaire sévère de lithiase telle que cystinurie, hyperoxalurie primaire ou dihydroxyadéninurie pour en optimiser la prise en charge thérapeutique, la détermination du volume cristallin global dans ces pathologies cristallines sévères permettant d'adapter le traitement médical, d’évaluer l'efficacité des mesures thérapeutiques proposées et de modifier celles-ci en fonction des résultats obtenus.

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay. METHODS: Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (RKSC; http://www.rarekidneystones.org/) who had provided 24-hour and first-morning void urine samples for DHA measurements, were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-hr urinary DHA excretion between groups. Associations were examined using Spearman’s correlation coefficient. RESULTS: The median 24-hr urinary DHA excretion was 138 (64–292) mg/24 hr and the DHA/Cr ratio in the first-morning void samples was 13 (4–37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-hr DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (r(s) = 0.84, p

Dietary oxalate is plant-derived and may be a component of vegetables, nuts, fruits, and grains. In normal individuals, approximately half of urinary oxalate is derived from the diet and half from endogenous synthesis. The amount of oxalate excreted in urine plays an important role in calcium oxalate stone formation. Large epidemiological cohort studies have demonstrated that urinary oxalate excretion is a continuous variable when indexed to stone risk. Thus, individuals with oxalate excretions >25 mg/day may benefit from a reduction of urinary oxalate output. The 24-h urine assessment may miss periods of transient surges in urinary oxalate excretion, which may promote stone growth and is a limitation of this analysis. In this review we describe the impact of dietary oxalate and its contribution to stone growth. To limit calcium oxalate stone growth, we advocate that patients maintain appropriate hydration, avoid oxalate-rich foods, and consume an adequate amount of calcium.

Objectives The aim of the study was to identify any dietary, signalment, geographic and clinical factors associated with hematuric struvite crystalluria (HSC) in a population of cats that visit general care veterinary hospitals in the USA. Methods In total, 4032 cats that had a first-time diagnosis of HSC and 8064 control cats with no history of hematuria or crystalluria were identified from medical records of all cats examined between 2007 and 2011 at 790 US veterinary hospitals. Extracted variables included age, sex, neuter status, breed, diet, urinalysis results and history of cystitis. Potential associations between these variables and HSC were estimated. Results Controlling for other factors, young cats fed a dry diet had an increased likelihood of HSC relative to young cats fed a non-dry diet. However, as age increased, the likelihood of HSC declined for cats fed a dry diet and increased for cats fed a non-dry diet. Moreover, the odds of HSC were significantly greater when cats were unneutered (vs neutered; odds ratio [OR] 45.52) or had a thin (vs heavy) body condition (OR 23.81), diagnosis of cystitis (OR 2.84), urine protein concentration >30 mg/dl (OR 4.72), alkaline (vs neutral) urine pH (OR 3.34), pyuria (OR 23.67) or bacteriuria (OR 2.24). Conclusions and relevance The present study provides estimates of the strengths of association between HSC and certain signalment and clinical characteristics of cats. This information could help clinicians to perform a more directed screening for struvite crystalluria in certain cat populations. Follow-up studies that build on the findings of this study could explore the clinical importance of HSC in cats.

Resumo: A acidificação urinária com cloreto de amônio (CA) é um método preventivo eficiente em urolitíase obstrutiva em ovinos. Os objetivos deste estudo com ovinos confinados, que receberam dieta concentrada com elevado teor proteico, foram: verificar o efeito da dieta sobre a formação de urólitos e o desenvolvimento da doença; analisar as características macroscópicas e histopatológicas do sistema urinário; relacionar os achados clínicos, laboratoriais e necroscópicos com a presença de urólitos. Utilizaram-se 60 ovinos machos: grupo CA (n=40), 400 mg/kg CA/dia, tratados via oral, por 42 dias consecutivos; grupo-controle (n=20), não tratado. Determinaram-se sete momentos de colheita de amostras com intervalos de sete dias, no total de 56 dias de confinamento. Encontraram-se microcálculos na pelve renal em cinco animais de ambos os grupos. As lesões renais microscópicas mais relevantes foram congestão vascular e necrose tubular. Concluiu-se que a dieta rica em concentrado provocou lesão renal em ambos os grupos, embora sem alterar a função renal, o que foi comprovado em testes pela ureia e creatinina séricas. O cloreto de amônio fornecido ao grupo CA não impediu a calculogênese, mas reduziu sua prevalência em relação ao grupo-controle. Os ovinos do grupo-controle tiveram maior comprometimento renal, pela alta incidência de cristalúria e pela necrose tubular, induzidas pelo consumo da dieta rica em grãos. Abstract: The urinary acidification with ammonium chloride (AC) is an efficient preventive method for urolithiasis in sheep. The objectives of this study with feedlot sheep receiving concentrated diet with high protein content were (1) to verify the effect of diet on urolith formation and development of the disease, (2) to analyze the macroscopic and histopathological characteristics of the urinary system, and (3) to relate the clinical, laboratory and necropsy findings with the presence of uroliths. Sixty male sheep were used: AC group (n=40), 400mg/kg AC/day, orally treated for 42 consecutive days, and control group (n=20), untreated. Seven times were determined for sampling with a seven-day interval, totaling 56 days of feedlot. Small uroliths were found in the renal pelvis of five sheep in both groups. The most relevant microscopic renal lesions were vascular congestion and tubular necrosis. It was concluded that the highly concentrated diet caused renal injury in both groups, without changing the renal function, what was proven by laboratory tests of urea and creatinine. Ammonium chloride provided to the CA group did not prevent urolith formation, but reduced its prevalence in comparison with the control group. Sheep of the control group had increased kidney damage, which resulted in higher incidence of crystalluria and tubular necrosis induced by the consumption of a diet rich in grains.

Objective To provide correlations between crystalluria and chemical structure of calculi in situ to help making decision in the use of the extracorporeal shock wave lithotripsy (ESWL). Methods A crystalluria study was carried out on 644 morning urines of 172 nephrolithiasis patients (111 males and 61 females), and 235 of them were in situ stone carriers. After treating by ESWL, the recovered calculi have been analyzed by Fourier transform infrared spectroscopy and their compositions were correlated to the nature of urinary crystals. Results We obtained successful treatment for 109 patients out of 157 and 63 patients out of 78 with stones had a treatment failure (33.2%). The correlations showed that for the overwhelming crystalluria containing calcium oxalate dihydrate (COD) with mixed crystals without calcium oxalate monohydrate, we should have 68% to 88 % success rate. However, the obtained result was 79%. Similarly, for crystalluria with COD + calcium oxalate monohydrate ± carbapatite, the prediction was 11% to 45% and the result was approximately 39%. When the majority of crystalluria was calcium phosphate, the prediction of 50% to 80% was confirmed by 71% success rate. For those majority containing magnesium ammonium phosphate hexahydrate (struvite) ± diammonium urate ± COD, we predicted between 80% to 100%, and the result gave a success rate of 84%. Conclusions The analysis of crystalluria of morning urine can help to know the composition of calculi in situ and can predict the success rate of ESWL for maximum efficiency.

Macrotyloma uniflorum Linn. (Fabaceae) seeds are widely used for their diuretic and urolithiatic effects in India. The present study investigated the effect of aqueous extract of Macrotyloma uniflorum seeds (AEMU) on ethylene glycol induced urolithiasis in rats. To induce urolithiasis, 0.75% v/v ethylene glycol was administered orally for 14 days. The curative doses of 400 and 800 mg/kg were administered from 15th to 28th day. On the 28th day, 24 h urine, serum was collected and various biochemical parameters were estimated in urine, serum and kidney homogenate along with histology of kidney. Co-administration of AEMU with ethylene glycol has significantly (p < 0.001) increased the urine volume and the level of calculus inhibitors like magnesium, citrate and decreased the level of calculus promoters like calcium, oxalate, uric acid and urea also decreased in crystalluria in urine. AEMU supplement also prevented the pathological changes in the kidney and increased the glomerulus activity of the kidney. These results indicate that AEMU showed significant activity in urolithiasis which might be due to its diuretic, calcium oxalate crystal formation inhibitory effects and its ability to increase the levels of inhibitors and decrease the level of promoters of urolithiasis.

Secondary hyperaldosteronism is respondent aldosterone secretion increase, occurring due to some diseases or drug use. It may be accompanied by normal arterial pressure with/without water retention or arterial hypertension without water retention. Secondary hyperaldosteronism without arterial hypertension and without water retention is usually caused by the use of laxative and diuretic drugs. This condition is characterized by the lack of salt wasting symptoms, presence of myalgia and muscle weakness resulting from hypokalemia, calcium oxalate crystalluria and sonographic signs of medullary nephrocalcinosis. Such characteristics of water-salt exchange and presence of nephrocalcinosis in combination with hypercalciuria are defined as Bartter-like syndrome. Peculiarity of the given clinical case is determined not by a diagnostic difficulty of secondary hyperaldosteronism but concealment of long term self-administered use of laxatives 2 years without medical indications in a female patient, resulting in medullary nephrocalcinosis. A well-informed patient may endanger medical practice, because it is impossible to foresee everything including the uncontrolled self-administered drug use leading to the undesirable consequences.Вторичный гиперальдостеронизм реактивное увеличение секреции альдостерона, возникающее вследствие ряда заболеваний или приема медикаментов. Он может протекать с нормальным артериальным давлением с задержкой или без задержки воды или с артериальной гипертензией без задержки воды. Причиной вторичного гиперальдостеронизма, протекающего без артериальной гипертензии и без задержки воды, обычно является прием медикаментов: слабительных или мочегонных. Для этого состояния характерны отсутствие признаков потери соли, наличие миалгий и мышечной слабости в результате гипокалиемии, мочевой синдром в виде оксалатно-кальциевой кристаллурии, сонографические признаки медуллярного нефрокальциноза. Подобные особенности водно-солевого обмена, наличие медуллярного нефрокальциноза в сочетании с гиперкальциурией обозначают еще как Барттер-подобный синдром. Особенность представленного клинического случая заключалась не в трудности диагностики вторичного гиперальдостеронизма, а в сокрытии пациенткой факта длительного, в течение двух лет, самостоятельного использования слабительных без особых показаний. Это привело к нежелательным последствиям в виде медуллярного нефрокальциноза. Излишне информированный пациент может представлять опасность для врача, так как предусмотреть все, включая самостоятельное, неконтролируемое использование пациентом лекарств, приводящее к нежелательным последствиям, невозможно.

Cystinuria, a genetic disorder of cystine transport, is characterized by excessive excretion of cystine in the urine and recurrent cystine stones in the kidneys and, to a lesser extent, in the bladder. Males generally are more severely affected than females. The disorder may lead to chronic kidney disease in many patients. The cystine transporter (b0,+) is a heterodimer consisting of the rBAT (encoded by SLC3A1) and b0,+AT (encoded by SLC7A9) subunits joined by a disulfide bridge. The molecular basis of cystinuria is known in great detail, and this information is now being used to define genotype-phenotype correlations. Current treatments for cystinuria include increased fluid intake to increase cystine solubility and the administration of thiol drugs for more severe cases. These drugs, however, have poor patient compliance due to adverse effects. Thus, there is a need to reduce or eliminate the risks associated with therapy for cystinuria. Four mouse models for cystinuria have been described and these models provide a resource for evaluating the safety and efficacy of new therapies for cystinuria. We are evaluating a new approach for the treatment of cystine stones based on the inhibition of cystine crystal growth by cystine analogs. Our ongoing studies indicate that cystine diamides are effective in preventing cystine stone formation in the Slc3a1 knockout mouse model for cystinuria. In addition to crystal growth, crystal aggregation is required for stone formation. Male and female mice with cystinuria have comparable levels of crystalluria, but very few female mice form stones. The identification of factors that inhibit cystine crystal aggregation in female mice may provide insight into the gender difference in disease severity in patients with cystinuria.

International audience; Drug-induced calculi represent 1–2% of all renal calculi. The drugs reported to produce calculi may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favour crystallisation in the urine. Among them, drugs used for the treatment of patients with human immunodeficiency, namely atazanavir and other protease inhibitors, and sulphadiazine used for the treatment of cerebral toxoplasmosis, are the most frequent causes. Besides these drugs, about 20 other molecules may induce nephrolithiasis, such as ceftriaxone or ephedrine-containing preparations in subjects receiving high doses or long-term treatment. Calculi analysis by physical methods including infrared spectroscopy or X-ray diffraction is needed to demonstrate the presence of the drug or its metabolites within the calculi. Some drugs may also provoke heavy intra-tubular crystal precipitation causing acute renal failure. Here, the identification of crystalluria or crystals within the kidney tissue in the case of renal biopsy is of major diagnostic value. The second group includes drugs that provoke the formation of urinary calculi as a consequence of their metabolic effects on urinary pH and/or the excretion of calcium, phosphate, oxalate, citrate, uric acid or other purines. Among such metabolically induced calculi are those formed in patients taking uncontrolled calcium/vitamin D supplements, or being treated with carbonic anhydrase inhibitors such as acetazolamide or topiramate. Here, diagnosis relies on a careful clinical inquiry to differentiate between common calculi and metabolically induced calculi, of which the incidence is probably underestimated. Specific patient-dependent risk factors also exist in relation to urine pH, volume of diuresis and other factors, thus providing a basis for preventive or curative measures against stone formation.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5-312) weeks following the transplant procedure. Patients had delayed graft function (n=2), acute-on-chronic (n=5) or acute (n=1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8-DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8-DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n=7), remained stable (n=1) or worsened (n=1). At last follow-up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8-DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.

Increased intestinal absorption of oxalate causes hyperoxaluria, a major risk factor for kidney stone disease. Intestinal colonization of recombinant probiotic bacteria expressing oxalate-degrading gene (OxdC) is an effective therapeutic option for recurrent calcium oxalate (CaOx) stone disease. Therefore, we aimed to develop food-grade probiotic L. plantarum secreting OxdC using lactococcal group II intron, Ll.LtrB and evaluate its oxalate degradation ability in vivo . Male Wistar albino rats were divided into four groups. The rats of group I received normal rat chow and drinking water. Groups II, III and IV rats received 5% potassium oxalate containing diet for 28 days. Groups III and IV rats received L. plantarum and food-grade recombinant L. plantarum respectively from 15 to 28 days. Biochemical parameters and crystalluria were analysed in 24 h urine samples. At the end of experimental period, rats were sacrificed; intestine and kidneys were dissected out for colonization studies and histopathological analysis. Herein, we found that the administration of recombinant probiotics significantly reduced the urinary oxalate, calcium, urea, and creatinine levels in rats of group IV compared to group II. Furthermore, colonization studies indicated that recombinant probiotics have gastrointestinal transit and intestinal colonization ability similar to that of wild-type bacteria. In addition, gene expression studies revealed down-regulation of OPN and KIM -1 among group IV rats. Histopathological analysis showed less evidence of nephrocalcinosis in group IV rats. In conclusion, the study demonstrates that food-grade L. plantarum secreting OxdC is capable of degrading intestinal oxalate and thereby prevent CaOx stone formation in experimental rats.

Calcium oxalate crystalluria appears to be a common problem in most of small animal clinics. This current study aimed at inducing a condition of oxalate crystalluria in beagles and record the primary changes in canine blood and urine on response to oxalates injection. 15 dogs were divided into two groups; those in the treatment group were injected intravenously with 0.5 M potassium oxalate and the dogs of control group were injected with physiological saline for five successive days. Urine test revealed a significant decrease in urinary creatinine and urinary urea nitrogen levels. The ultrastructural examination of urine sediment showed typical and atypical phases of calcium oxalate crystals and the X-ray defractionation of these crystals showed high content of calcium in addition to other minerals. Therefore potassium oxalate injection may provide an example of calcium oxalate crystalluria which may answer some question around the pathogenesis of this problem in dogs.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine. The low solubility of DHA results in precipitation and formation of urinary crystals and kidney stones. The disease can be present as recurrent urolithiasis or nephropathy secondary to crystal precipitation into renal parenchyma (DHA nephropathy). The diagnostic tools available, including stone analysis, crystalluria, and APRT activity in red blood cells, make the diagnosis easy to confirm when APRT deficiency is suspected. However, the lack of recognition of this metabolic disorder frequently resulted in a delay in diagnosis and treatment with grave consequences. The early recognition and treatment of APRT deficiency are of crucial importance to prevent irreversible loss of renal function. This review summarizes the genetic and metabolic mechanisms underlying DHA stones formation and chronic kidney disease, along with the issues of diagnosis and management of APRT deficiency. Moreover, we report the mutations in the APRT gene responsible for APRT deficiency in 51 French patients (43 families) including 22 pediatric cases (18 families) among the 64 patients identified in the biochemistry laboratories of Necker Hospital, Paris (1978-2013).

Background: Cyperus rotundus L. is used in various dosage forms by Unani physicians in the treatment of urolithiasis. Aims and Objectives: The present study aims to evaluate the effect of hydroalcoholic extract of Cyperus rotundus in nephrolithiatic male Sprague Dawley rats. Materials and Methods: The animals were divided into 6 groups of 6 each. Group I received regular rat food and drinking water ad libitum. Group II to VI were treated with Ethylene glycol (0.75%, V/V) and Ammonium chloride (1%, W/V) in drinking water for 7 days to induce urolithiasis. Group II was sacrificed after 7 days administration of lithogenic agents however, from 8th day, group IV was treated with Cystone (750 mg/kg) and group V and VI with hydroalcoholic extract of Cyperus rotundus (100 mg/kg and 170 mg/kg, respectively) for further 14 days. Group III left untreated after 7 days administration of lithogenic agent till 14 days and sacrificed on 22nd day. Urine, biochemical parameters, kidney homogenate analysis and histopathology were carried out. Crystalluria analysed by light microscopy. Results: The test drug at both the doses showed significant reduction (P

When seen, some habits of calcium oxalate monohydrate crystals (whewellite) are so typical of ethylene glycol intoxication that they may be helpful for its diagnosis when circumstances are not clearly established.

Lesch-Nyhan syndrome is a rare inborn error of metabolism with very poor prognosis. Patients vary in many ways but all seem to have impairments to some degree in uric acid metabolism, motor development, and behavior. A careful evaluation is essential toward making the appropriate diagnosis. A case of infant with motor delay, spasticity, dystonia, and crystalluria is reported. Treatment based on allopurinal (12 mg/kg of body weight/24 h) reduced serum hyperuricemia to values

Calcium oxalate crystalluria is a problem of growing concern in dogs. A few reports have discussed acute kidney injury by oxalates in dogs, describing ultrastructural findings in particular. We evaluated the possibility of deposition of calcium oxalate crystals in renal tissue and its probable consequences. Six dogs were intravenously injected with 0.5 M potassium oxalate (KOx) for seven consecutive days. By the end of the experiment, ultrasonography revealed a significant increase in the renal mass and renal parenchymal echogenicity. Serum creatinine and blood urea nitrogen levels were gradually increased. The histopathological features of the kidneys were assessed by both light and electron microscopy, which showed CaOx crystal deposition accompanied by morphological changes in the renal tissue of KOx injected dogs. Canine renal oxalosis provides a good model to study the biological and pathological changes induced upon damage of renal tissue by KOx injection. This article has been retracted. Link to the retraction 10.2298/ABS150615077E

Clinical interest for the identification of the crystalline phase of CaOx, either monohydrate (COM) or dihydrate (COD), in crystalluria analysis is debated. In the present study, we simultaneously determined calcium and oxalate concentration and identified the two crystalline phases of CaOx crystals in 1288 first morning urine samples from 407 CaOx stone formers with crystalluria.The mean concentration of oxalate ions was higher in urine samples containing COM than in those containing COD crystals, and conversely the mean concentration of calcium ions was markedly higher in urine samples containing COD than in those containing COM crystals. COM crystals were predominant (93%) in urine samples with a Ca/Ox molar ratio 14 (i.e. markedly hypercalciuric). In the intermediate Ca/Ox values, mixed COD and COM crystals were present. Logistic regression analysis showed that increasing the concentration of calcium resulted in a higher risk of COD than of COM crystal formation, whereas increasing oxalate concentration was associated with a greater COM than COD crystal formation. In conclusion, this study demonstrates the calcium-dependence of COD and the oxalate-dependence of COM crystal formation. Thus, a crystalluria mainly composed of COD suggests a search for conditions associated with hypercalciuria whereas an abundant crystalluria made of COM crystals should prompt a search for heavy hyperoxaluria and noteworthy primary hyperoxaluria.

Xanthium strumarium has traditionally been used in the treatment of urolitiasis especially by the rural people in India, but its antiurolithiatic efficacy was not explored scientifically till now. Therefore, the present study was designed to validate the ethnic practice scientifically, and explore the possible antiurolithiatic effect to rationalize its medicinal use. Urolitiasis was induced in hyperoxaluric rat model by giving 0.75% ethylene glycol (EG) for 28days along with 1% ammonium chloride (AC) for first 14days. Antiurolithiatic effect of aqueous-ethanol extract of Xanthium strumarium bur (xanthium) was evaluated based on urine and serum biochemistry, oxidative/nitrosative stress indices, histopathology, kidney calcium and calcium oxalate content and immunohistochemical expression of matrix glycoprotein, osteopontin (OPN). Administration of EG and AC resulted in hyperoxaluria, crystalluria, hypocalciuria, polyurea, raised serum urea, creatinine, erythrocytic lipid peroxidise and nitric oxide, kidney calcium content as well as crystal deposition in kidney section in lithiatic group rats. However, xanthium treatment significantly restored the impairment in above kidney function test as that of standard treatment, cystone. The up-regulation of OPN was also significantly decreased after xanthium treatment. The present findings demonstrate the curative efficacy of xanthium in ethylene glycol induced urolithiasis, possibly mediated through inhibition of various pathways involved in renal calcium oxalate formation, antioxidant property and down regulation of matrix glycoprotein, OPN. Therefore, future studies may be established to evaluate its efficacy and safety for clinical use.

The aim of present investigation was to evaluate the effect of Pedalium murex fruit extract in ethylene glycol-induced urolithiasis in male rats. Nephrolithiasis was induced in male Wistar rats by adding ethylene glycol (0.75%) in drinking water for 28 days. Animals divided in six groups each containing six animals. Vehicle control, model control, P. murex methanol extract in different doses 100, 200 and 400 mg/kg p.o. cystone (750 mg/kg, p.o.) used as standard. Hyperoxaluria as well as the increase in the excretion of calcium, phosphate, uric acid and decrease in citrate and magnesium in urine, impairment of renal function and oxidative imbalance in kidney observed in calculi induce group. Treatment with P. murex decreases hyperoxaluria, calcium, uric acid, improves renal function and also produces antioxidant effect. Crystalluria was characterized by excretion of large calcium oxalate crystals in lithogenic group but smaller in drug treated group. The histology showed depositions of large number of calcium oxalate crystals in kidney in calculi induced group while in the treated group small and fewer deposits. The result indicates antiurolithiatic activity of P. murex mediated possibly by calcium oxalate crystal inhibition, diuretic, antioxidant and maintaining balance between stone promoters and inhibitors constituents and this study rationalized its medicinal use in urolithiasis.

Ethnopharmacological relevance A well-known traditional herb Solanum xanthocarpum is widely used in India for the management of different ailments including urolithiasis. This study was designed to rationalize the use of Solanum xanthocarpum in kidney stone and to investigate its mechanism of action. Materials and methods The saponin rich fraction prepared from fruits of Solanum xanthocarpum (SXS) was evaluated for antiurolithiatic activity by in vitro and in vivo studies. In ethylene glycol (EG, 0.75% in drinking water for 28 days) induced urolithiasis model, two different experimental doses (20 mg/kg and 40 mg/kg, p.o., for 28 days) of saponin rich fraction were selected by dose fixation study. After 28 days, various biochemical parameters were measured in urine, serum and kidney homogenate. Kidneys were also subjected to histopathological analysis. Results In vitro calcium oxalate crystal (CaOx) nucleation as well as aggregation was inhibited in artificial urine solution by SXS. The lithogenic treatment caused polyuria, damage renal function and oxidative stress, manifested as increased malondialdehyde, depleted reduced glutathione and decreased antioxidant enzyme catalase activities of the kidneys, which were prevented by simultaneous administration with SXS. Lithogenic treatment also caused crystalluria, hyperoxaluria, hypercalciuria, hypocitrauria, and hypomagnesaemia. Deposition of CaOx in renal tissue and cellular injury were seen in histopathology. Co-administration of SXS had potential to prevent these pathological changes due to lithogenic treatment. Moreover, SXS raised level of glycosaminoglycan, a stone inhibitor macromolecule found in urine which decreased. Conclusion The antiurolithiatic activity in Solanum xanthocarpum is mediated possibly through the inhibition of CaOx crystal formation and its effect on the urinary concentration of stone-forming constituents and nephrolithiasis inducing factors and this study rationalizes its medicinal use in urolithiasis.

This study was designed to evaluate the effects of Solanum xanthocarpum fruit extract in ethylene-glycol-induced urolithiasis in the male Wistar rats. Nephrolithiasis was induced in male Wistar rats by adding ethylene glycol (0.75%) in drinking water for 28 days. Animals were divided into six groups, each containing six viz. Vehicle control, model control, S. xanthocarpum methanol extract in different doses of 100, 200, and 400 mg/kg p.o., Cystone (750 mg/kg, p.o.) served as a standard. Hyperoxaluria as well as an increase in the excretion of calcium, phosphate, uric acid and decrease in citrate and magnesium in urine, impairment of renal function and oxidative imbalance in kidney were observed in the calculi-induced group. Treatment with S. xanthocarpum decreases hyperoxaluria, calcium, and uric acid, improves renal function, and also produces antioxidant effects. Crystalluria was characterized by excretion calcium oxalate (CaOX) crystals, which were enormous in the lithogenic group but smaller in the drug-treated group. The histology showed that the calculi-induced group had a large deposition of CaOX crystals in kidney while the treated group had trivial and fewer deposits. The result indicates the antiurolithiatic activity of S. xanthocarpum mediated possibly by CaOX crystal inhibition, diuretic, antioxidant and maintaining balance between stone promoter and inhibitor constituents, and this study rationalized its medicinal use in urolithiasis.

Aggregation (AGN) of freshly precipitated calcium oxalate crystals was photometrically studied in urine of 30 calcium stone patients and 30 controls, in solutions containing urinary macromolecules (UMS) and in an inhibitor free control solution (CS). Crystals were produced by oxalate titration and crystallization was monitored measuring optical density (OD). Tests were repeated adding hydroxyapatite (HAP) to urine and UMS and adding citrate and pyrophosphate (PPi) to UMS of the controls. AGN was recognized as a rapid OD decrease being at least three times faster than sedimentation of single crystals (p < 0.001) and used to calculate an extent of AGN (EA%). The time between the end of titration and the beginning of AGN was determined as suspension stability (SS). The main effect of urinary inhibitors was retardation of AGN without changing EA, SS being higher in urine than UMS (p < 0.001) and in UMS than CS (p < 0.001). In urine of 63% of controls but only in 33% of patients, no AGN was recorded (p < 0.05). The high inhibitory activity of urine could not be reproduced in UMS even in combination with 3.5 mM citrate or 0.05 mM PPi. 0.05 mg/mL HAP reduced SS in all urine samples to low values and increased the rate of rapid OD decrease, being a measure for the size of aggregates. Retarding AGN of crystals during their passage through the kidney seems to be an important mechanism to prevent stone formation during crystalluria. The promotion of AGN by HAP reveals a new role of Randall’s plaques in nephrolithiasis.

Experimental animal model studies suggest that calcium oxalate (CaOx) crystal deposition in the kidneys is associated with the development of oxidative stress, epithelial injury and inflammation. There is increased production of inflammatory molecules including osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1) and various subunits of inter-alpha-inhibitor such as bikunin. What does the increased production of such molecules suggest? Is it a cause or consequence of crystal deposition? We hypothesized that over-expression and increased production of MCP-1 is a result of the interaction between renal epithelial cells and CaOx crystals after their deposition in the renal tubules. We induced hyperoxaluria in MCP-1 null as well as wild type mice and examined pathological changes in their kidneys and urine. Both wild type and MCP-1 null male mice became hyperoxaluric and demonstrated CaOx crystalluria. Neither of them developed crystal deposits in their kidneys. Both showed some morphological changes in their renal proximal tubules. Significant pathological changes such as cell death and increased urinary excretion of LDH were not seen. Results suggest that at least in mice (1) Increase in oxalate and decrease in citrate excretion can lead to CaOx crystalluria but not CaOx nephrolithiasis; (2) MCP-1 does not play a role in crystal retention within the kidneys; (3) Expression of OPN and MCP-1 is not increased in the kidneys in the absence of crystal deposition; (4) Crystal deposition is necessary for significant pathological changes and movement of monocytes and macrophages into the interstitium.

Mechanisms of crystal collision being the first step of aggregation (AGN) were analyzed for calcium oxalate monohydrate (COM) directly produced in urine. COM was produced by oxalate titration in urine of seven healthy men, in solutions of urinary macromolecules and in buffered distilled water (control). Crystal formation and sedimentation were followed by a spectrophotometer and analyzed by scanning electron microscopy. Viscosity of urine was measured at 37 degrees C. From results, sedimentation rate (v (S)), particle diffusion (D) and incidences of collision of particles in suspension by sedimentation (I (S)) and by diffusion (I (D)) were calculated. Calculations were related to average volume and urinary transit time of renal collecting ducts (CD) and of renal pelvis. v (S) was in urine 0.026 +/- 0.012, in UMS 0.022 +/- 0.01 and in control 0.091 +/- 0.02 cm min(-1) (mean +/- SD). For urine, a D of 9.53 +/- 0.97 mum within 1 min can be calculated. At maximal crystal concentration, I (S) was only 0.12 and I (D) was 0.48 min(-1) cm(-3) which, even at an unrealistic permanent and maximal crystalluria, would only correspond to less than one crystal collision/week/CD, whereas to the same tubular wall being in horizontal position 1.3 crystals/min and to a renal stone 624 crystals/cm(2) min could drop by sedimentation. Sedimentation to renal tubular or pelvic wall, where crystals can accumulate and meet with a tissue calcification or a stone, is probably essential for stone formation. Since v (S) mainly depends on particle size, reducing urinary supersaturation and crystal growth by dietary oxalate restriction seems to be an important measure to prevent aggregation.

Although many information has been published regarding canine urolithiasis, sensitivity of radiography, ultrasound and urinary parameters have been poorly correlated with number, size, and composition of the stones. One hundred and thirteen clinical files of dogs with diagnosis of urolithiasis were retrospectively selected. Information regarding number, appearance, location, size, and composition of the stones were noted after surgical removed. Urolithiasis data was compared with radiographs and ultrasound images and urinalysis parameters. Pure struvite was found in 42.4% and calcium oxalate in 35.6%. Survey radiographs enabled the detection of radiopaque stones and when an ultrasound examination was also performed, the sensitivity was increased. Double contrast radiography enabled identification in 100% of radiolucent stones, and allowed for size measurement and number counts in 76.9% of radiolucent stones. Crystalluria had low sensitivity (31.5%) and specificity (58.8%). Hematuria (96.3%) and leukocyturia (61.1%) were the most common parameters found. We concluded that double contrast radiography can be considered the method of choice for detection of radiolucent stones. Crystalluria is not a good parameter to detect or predict type of stone. Hematuria and leukocyturia, although non-specific findings, can be used as triage for investigation of urolithiasis.