Unveiling primary Hyperoxaluria type 1: a fortuitous discovery through bone marrow biopsy.

This paper details a rare case of primary hyperoxaluria type 1 (PH1) identified through a bone marrow biopsy in a 46-year-old female patient with a history of nephrolithiasis and chronic renal failure. Genetic analysis identified the p.Ile244Thr mutation in the AGXT gene, confirming the diagnosis of PH1. The paper aims to highlight this case, focusing on the genetic basis of the disorder, including the identified mutation. It underscores the importance of early diagnosis of infantile and childhood nephrolithiasis, particularly in cases with familial history, to prevent renal loss and systemic oxalosis.

The Elephant in the Room: Clinical Progression and Management of Elephant Ear Plant Toxicity in an Adult.

Elephant ear plants are popular ornamental plants renowned for their large foliage. These plants have been implicated in various inadvertent and deliberate ingestions. The leaves and roots of these plants contain raphides, which are needle-shaped calcium oxalate crystals. Ingestion of these crystals results in a localized inflammatory response, typically manifesting as irritation, edema, hypersalivation, and dysphagia. Herein, we describe a case of an older gentleman who presented to our institution following intentional ingestion of the leaves and roots of an elephant ear plant. This report describes the clinical manifestations secondary to the toxicities related to the ingestion of this plant and displays the successful conservative management approach employed following multiple diagnostic studies.

From Smoothies to Dialysis: The Impact of Oxalate Nephropathy.

Oxalate nephropathy is a rare cause of acute kidney injury that can lead to end-stage renal disease. This case report describes a 54-year-old male with type 2 diabetes mellitus and chronic kidney disease who presented for a routine clinic follow-up. Laboratory tests revealed significant deterioration in renal function with an unrevealing history and symptoms suggestive of the process. Initial investigations for worsening renal function were inconclusive, prompting a renal biopsy that confirmed acute tubular injury with abundant calcium oxalate deposits. Further investigation into dietary history revealed that the patient regularly consumed high-oxalate foods, such as spinach and kale smoothies, under the impression they were beneficial for his diabetes. Despite the initiation of hemodialysis, the patient did not recover renal function and remains dialysis-dependent. This case underscores the need for a high index of suspicion for oxalate nephropathy in chronic kidney disease patients presenting with unexplained acute kidney injury. Diagnosis is confirmed through renal biopsy and should be considered in patients with relevant dietary histories.

Clinical manifestations and renal pathology of ethylene glycol.

Ethylene glycol (EG) poisoning is a critical medical emergency often associated with suicide attempts in adults. EG is metabolized by alcohol dehydrogenase, leading to the formation of toxic metabolites that cause metabolic acidosis, renal failure, hypocalcemia, aciduria, and disorders of the central nervous and cardiovascular systems. Calcium oxalate, a metabolite of EG, contributes to acute tubular necrosis. Despite limited reports on human renal pathology, we present a case detailing renal pathology following EG ingestion. A 44-year-old male, admitted due to loss of consciousness, had ingested a lethal dose of EG. Blood tests indicated metabolic acidosis, while urinary examination revealed calcium oxalate crystals. Continuous renal replacement therapy corrected the acidosis; however, nephrogenic diabetes insipidus subsequently developed. A renal biopsy on day 31 revealed calcium oxalate crystal deposition and tubulointerstitial damage. Notably, various stages of crystal deposition, adherence, and degradation were observed. This case underscores the importance of considering EG poisoning in cases of unexplained metabolic acidosis and renal dysfunction, with renal biopsy serving as a valuable diagnostic tool. Understanding the renal effects of EG is essential for timely intervention and effective management of poisoning cases.

Syrupy herbal formulation of green bean pod extract of Phaseolus vulgaris L.: Formulation optimization by central composite design, and evaluation for anti-urolithiatic activity.

The green bean pods of Phaseolus vulgaris L. are traditionally used as a folk remedy for treating calcium oxalate kidney stones. The current research aimed to develop a syrup formulation containing green bean pod extract for anti-urolithiatic activity. The syrup was prepared using a simple blending method and optimized through a central composite design (CCD) with two independent variables: the ratio of pod juice (PJ) to sugar solution (SS) ranging from 1:0.5 to 1:1.5, and the percentage of CMC from 0.2% to 0.4% w/v. These variables were analyzed for their impact on viscosity (CP) and sedimentation percentage, helping to identify the best formulation out of 13 variants. The finalized formulation (F-opt) underwent assessment for physicochemical characteristics such as organoleptic properties, viscosity, density, sedimentation rate, and stability. Additionally, a microbiological assessment was performed utilizing the spread plate method. Further, it was evaluated for in vitro, ex vivo, and in vivo anti-urolithiatic activity in rat models for 28 days and compared with that of the reference standard (Cystone syrup). Additionally, acute toxicity was assessed in albino Swiss mice. Histopathological evaluations were then conducted on the kidneys of the Wistar rats that had been used for the in vivo studies, providing insight into the treatment effects on kidney tissue structure. The optimized formulation (F-opt) was a green, viscous, clear syrup with a pH of 5.8, a viscosity of 256.38 CP, a density of 1.31 g/ml, and a sedimentation rate of 0.69%. The optimized formulation was found to be stable, showing no significant changes in physicochemical and microbiological properties. The results of the in vitro, ex vivo, and in vivo anti-urolithiatic studies indicated that the optimized formulation effectively inhibited the aggregation of calcium oxalate. The acute toxicity studies revealed no mortality or adverse effects for both the optimized formulation and pure bean pod juice at a dose of 2000 mg/kg body weight. Histopathological examination revealed that rats treated with the optimized formulation exhibited a significant reduction in both the number and size of calcium oxalate deposits within various parts of the renal tubules. It can be concluded that the syrupy formulation of Phaseolus vulgaris L. green bean pod extract demonstrated significant anti-urolithiatic activity. This activity could be due to its diuretic properties and its ability to inhibit the formation of calcium oxalate crystals. However, limitations of the study included a lack of elucidation of the mechanism and limited generalizability of the findings.

Localized calcium oxalate crystals in primary cutaneous aspergillosis.

Select Aspergillus species can produce oxalate as a fermentation byproduct, which may react with calcium ions to produce insoluble calcium oxalate crystals in tissues. These crystals are frequently associated with pulmonary Aspergillus infections, yet are rarely described in primary cutaneous aspergillosis. Herein, we report the presence of calcium oxalate crystals detected on cutaneous specimens from primary cutaneous Aspergillus niger and Aspergillus fumigatus infections in an immunocompromised, premature infant. No metabolic sources of oxalosis were found.

Oxalate Nephropathy and the Mechanism of Oxalate-Induced Kidney Injury.

Background: Hyperoxaluria is a major cause of oxalate nephropathy, which can lead to impaired renal function presenting as acute kidney injury, acute on chronic kidney disease, or chronic kidney disease. The Chronic Renal Insufficiency Cohort study showed that higher urinary oxalate is associated with renal outcome in patients with chronic kidney disease, supporting the nephrotoxicity of oxalate. Therefore, a better understanding of the role of oxalate in kidney injury is needed. This review describes the metabolism of oxalate and the clinical and pathology presentation of oxalate nephropathy. It also summarizes the available evidence for the underlying pathogenic mechanism and the development of treatments for oxalate-induced kidney injury. Summary: Disruption to any key step in the oxalate pathway including abnormal endogenous generation, ingestion of abnormally high dose of oxalate, increased absorption or attenuation of oxalate degradation in the gut, and reduced excretion through the kidney may lead to disrupted oxalate homeostasis. Oxalate nephropathy is mainly caused by hyperoxaluria. Oxalate crystal deposition in the kidney is usually accompanied with tubular toxicity, obstruction, interstitial fibrosis, and tubular atrophy. The mechanism of oxalate-induced renal injury has not been fully clarified. Evidence from both in vivo and in vitro studies shows that NLRP3 inflammasome activation and macrophage infiltration are involved in the processes of crystal adhesion, aggregation, and elimination and promote intrarenal inflammation and renal fibrosis. Novel treatment strategies have been developed and targeted therapies tested for oxalate nephropathy. Key Messages: Prompt diagnosis and management may help to reduce the deposition of calcium oxalate crystals in the kidney. Further studies are needed to clarify the underlying mechanisms to help develop more targeted therapies for oxalate nephropathy.

A Rare Sparkle: A Case of Calcified Kidneys in a Young Infant With Renal Failure.

Primary hyperoxaluria-1 (PH1) is an autosomal recessively inherited rare genetic condition due to the deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase which leads to high systemic levels of oxalate and subsequently, early end-stage renal disease and death. Here, we present a case of a three-month-old male infant who presented with loose stools, reduced oral intake, and decreased activity for 12-13 days along with edema and a peeling rash on cheeks, lips, and genitalia. During the entire duration of the inpatient stay, the child was oligoanuric. Kidney ultrasound (USG) was suggestive of bilateral hyperechoic kidneys with increased cortical echogenicity and a computed tomography scan showed bilateral diffusely calcified renal cortices with well-preserved renal architecture. A diagnosis of "oxalate nephropathy" was made from renal biopsy and genetic testing confirmed it to be "primary hyperoxaluria-1". The child was initially managed conservatively, and then peritoneal dialysis was done, following which the child was shifted to intermittent hemodialysis.

A Case of Oxalate Nephropathy Associated With Prolonged Cholecystostomy Tube Placement.

Oxalate nephropathy is a rare pathology that can be difficult to diagnose. It results from calcium oxalate crystals that are deposited in the renal interstitium or renal tubules. Once the deposition ensues, a multitude of complications can occur, including renal failure. One etiology for oxalate nephropathy is a lack of biliary acid. The diagnosis of oxalate nephropathy is typically based on visualization of oxalate crystals in the renal tubules on biopsy, and treatment based on the etiology can range from simple removal of the offending agent or a change in diet to liver/kidney transplant in the setting of primary hyperoxaluria. This report discusses a case of severe oxalate nephropathy related to long-term cholecystostomy tube placement resulting in a deficiency of biliary acid.

A case of acute kidney injury due to ethylene glycol intoxication.

In this article we describe a case of acute kidney injury caused by ethylene glycol intoxication which partially reversed after temporary hemodialysis treatment. The diagnosis was obtained after the patient's clinical history and the finding of ethylene glycol in the blood, numerous intratubular crystals at renal biopsy, and the presence of large amounts of atypical - spindle-like and needle-like - calcium oxalate crystals in the urinary sediment.

Dynamics of differentiated-renal epithelial cell monolayer after calcium oxalate injury: The role of cyclooxygenase-2.

AIMS: Calcium oxalate (Oxa), constituent of most common kidney stones, damages renal tubular epithelial cells leading to kidney disease. Most in vitro studies designed to evaluate how Oxa exerts its harmful effects were performed in proliferative or confluent non-differentiated renal epithelial cultures; none of them considered physiological hyperosmolarity of renal medullary interstitium. Cyclooxygenase 2 (COX2) has been associated to Oxa deleterious actions; however, up to now, it is not clear how COX2 acts. In this work, we proposed an in vitro experimental system resembling renal differentiated-epithelial cells that compose medullary tubular structures which were grown and maintained in a physiological hyperosmolar environment and evaluated whether COX2 â†’ PGE2 axis (COX2 considered a cytoprotective protein for renal cells) induces Oxa damage or epithelial restitution. MAIN METHODS: MDCK cells were differentiated with NaCl hyperosmolar medium for 72 h where cells acquired the typical apical and basolateral membrane domains and a primary cilium. Then, cultures were treated with 1.5 mM Oxa for 24, 48, and 72 h to evaluate epithelial monolayer restitution dynamics and COX2-PGE2 effect. KEY FINDINGS: Oxa completely turned the differentiated phenotype into mesenchymal one (epithelial-mesenchymal transition). Such effect was partially and totally reverted after 48 and 72 h, respectively. Oxa damage was even deeper when COX2 was blocked by NS398. PGE2 addition restituted the differentiated-epithelial phenotype in a time and concentration dependence. SIGNIFICANCE: This work presents an experimental system that approaches in vitro to in vivo renal epithelial studies and, more important, warns about NSAIDS use in patients suffering from kidney stones.

How Tree Decline Varies the Anatomical Features in Quercus brantii

Drought has serious effects on forests, especially semi-arid and arid forests, around the world. Zagros Forest in Iran has been severely affected by drought, which has led to the decline of the most common tree species, Persian oak (Quercus brantii). The objective of this study was to determine the effects of drought on the anatomical structure of Persian oak. Three healthy and three declined trees were sampled from each of two forest sites in Ilam Forest. Discs were cut at breast height, and three sapwood blocks were taken near the bark of each tree for sectioning. The anatomical characteristics measured included fiber length (FL), fiber wall thickness (FWT), number of axial parenchymal cells (NPC), ray number (RN), ray width (RW), and number of calcium oxalate crystals. Differences between healthy and declined trees were observed in the abundance of NPC and in RN, FL, and FWT, while no differences occurred in the number of oxalate crystals. The decline had uncertain effects on the FL of trees from sites A and B, which showed values of 700.5 and 837.3 µm compared with 592.7 and 919.6 µm in healthy trees. However, the decline resulted in an increase in the FWT of trees from sites A and B (9.33 and 11.53 µm) compared with healthy trees (5.23 and 9.56 µm). NPC, RN, and RW also increased in declined individuals from sites A and B (28.40 and 28.40 mm−1; 41.06 and 48.60 mm−1; 18.60 and 23.20 µm, respectively) compared with healthy trees (20.50 and 19.63 mm−2; 31.60 and 28.30 mm−2; 17.93 and 15.30 µm, respectively). Thus, drought caused measurable changes in the anatomical characteristics of declined trees compared with healthy trees.

Systemic oxalosis in a free-ranging green turtle (Chelonia mydas).

A female juvenile green turtle (Chelonia mydas), found alive in Guanabara Bay, Rio de Janeiro, Brazil, was weak, dehydrated and cachectic, with a healed fracture in the caudal portion of the carapace. Despite supportive treatment, the animal died after 9 days. At necropsy the main lesions were pallor of visceral organs, arthritis and deposits of whitish granular material in the wall of large arteries and the trachea. Histopathological analysis revealed mild to severe deposition of crystals, consistent with calcium oxalate, in both kidneys and the spleen, heart, small intestine, pancreas, thymus and salt gland, as well as bacterial meningitis, septic arthritis, spirorchidiasis and a fibropapilloma on the nictitating membrane. The main pathological findings were suggestive of septic shock, mainly due to the bacterial meningitis and septic arthritis, with systemic oxalosis and spirorchidiasis as contributing lesions. Although renal oxalosis has been described in green turtles as an incidental finding, presumably due to ingestion of oxalate-containing plants, this turtle had an unusual systemic deposition of oxalate crystals.

Pulmonary aspergilloma with prominent oxalate deposition.

Some Aspergillus species produce oxalic acid, which reacts with tissue calcium or blood to precipitate calcium oxalate. Oxalate crystals can induce lung and kidney damage. The presence of oxalate crystals can suggest the diagnosis of aspergillosis, even when Aspergillus hyphae are absent on microscopic slides.

Formation of Unique Placental Seed Capsules in the Maturation Process of the Tomato Fruit.

The morphological and anatomical study of the seed formation features in a juicy tomato fruit was carried out. The ovules, which form on the placenta, have been shown to be gradually enveloped by the protrusions of placental tissue that arises simultaneously with them. As a result of this process, each seed is enclosed in an individual capsule. These seed capsules have been shown in vivo to be airtight and air-filled. Tomato seeds, as has been shown in this study, develop inside these capsules until the full maturity of the fruit and do not come into contact with the detached and moldered cells of the placenta protrusions, which convert into a gel (pulp). Using scanning electron microscopy, it was possible to reveal the details of a ribbon-like "pubescence" formation of the tomato seed, as well as to understand the mechanism of cracking of the outer layer cells in the seed coat, associated with the detection of calcium oxalate crystals in these cells. The unique outer layer of the tomato seed coat seems to play the role of a scaffold that maintains a constant volume of the protective capsule.

Amaranth calcium oxalate crystals are associated with chloroplast structures and proteins.

Calcium oxalate (CaOx) crystals in plants are formed in crystal idioblasts cells and have specific geometric shapes. Their proposed functions include calcium homeostasis and carbon source, among others. Amaranth is a plant that presents high tolerance to abiotic stresses and accumulates considerable amounts of CaOx crystals; however, few studies have focused on characterizing the crystals ultrastructure and none is related to identifying proteins bound to them. This information is of great interest to understand the mechanisms related to CaOx crystal formation and to support their proposed functions. Thus, this work aimed to characterize CaOx crystals in amaranth leaves. Crystals were purified and the proteins bound to them were isolated and identified by nLC-MS/MS. Leaf sections were analyzed by light and electron microscopy. The identified proteins were related to the chloroplast such as ATPb synthase, RuBisCO large subunit, and cell wall-related proteins, which were validated by immunohistochemistry and immunogold labeling. In addition, it was observed that CaOx crystal idioblasts were formed from parenchyma cells associated with mesophyll and veins, in which the thylakoid membranes of degraded chloroplasts turned into crystal chambers. These results significantly advance our understanding of the mechanisms of CaOx crystal formation and the potential function as an alternative carbon source in leaves.

Puerarin prevents calcium oxalate crystal-induced renal epithelial cell autophagy by activating the SIRT1-mediated signaling pathway.

Calcium oxalate (CaOx) crystals can activate autophagy, causing damage to renal tubular epithelial cells (TECs). Puerarin has been shown to have protective and therapeutic effects against a variety of diseases by inhibiting autophagy activation. However, the protective effect of puerarin against CaOx crystals and the underlying molecular mechanisms are unclear. Cell Counting Kit-8 (CCK-8) assays were used to evaluate the effects of puerarin on cell viability. Intracellular reactive oxygen species (ROS) levels were measured by the cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Immunofluorescence, immunohistochemistry, and western blotting were used to examine the expression of SIRT1, Beclin1, p62, and LC3, and explore the underlying molecular mechanisms in vivo and in vitro. Puerarin treatment significantly attenuated CaOx crystal-induced autophagy of TECs and CaOx cytotoxicity to TECs by altering SIRT1 expression in vitro and in vivo, whereas the SIRT1-specific inhibitor EX527 exerted contrasting effects. In addition, we found that the protective effect of puerarin was related to the SIRT1/AKT/p38 signaling pathway. The findings suggest that puerarin regulates CaOx crystal-induced autophagy by activating the SIRT1-mediated signaling pathway, and they suggest a series of potential therapeutic targets and strategies for treating nephrolithiasis.

Method for CaOx crystals isolation from plant leaves.

Although calcium oxalate (CaOx) crystals are present in many plants they are poorly studied. A possible limitation is the lack of methods for CaOx crystals isolation at high concentration and high purity, which is required for the analysis of their associated biomolecules such as proteins. To our knowledge, there are only four works that have isolated proteins from CaOx crystals. Those methods basically consist of grinding the plant material, filtration steps, enzymatic digestions, and density-based separation. However, they lack of steps to evaluate the quality and purity of the isolated crystals. Likewise, those works do not evaluate whether the crystals obtained carry contaminating proteins. In the present work a detailed method for CaOx crystals isolation from amaranth leaves is described, which can be used to isolate crystals from other plant leaves. The present method is based on previous works with the addition of cleaning steps to removal contaminating protein, separation of crystals by size, and microscopic monitoring to validate the purification efficiency. Main steps for CaOx crystals isolation:•Plant leaves are ground and several washing steps, including enzymatic digestions and centrifugation, are carried out to remove cellular debris and contaminating proteins.•CaOx crystals are enriched by centrifugation in sodium polytungstate.•The different forms of crystals are separated by filtration.

Morphological and anatomical traits during development: Highlighting extrafloral nectaries in Passiflora organensis.

Passiflora organensis is a small herbaceous vine with characteristic morphological variations throughout its development. The plant bears button-shaped extrafloral nectaries exclusively in adult leaves. Extrafloral nectaries are structures that secrete nectar and play an important role in plant-animal interactions as a strategy for protecting plants against herbivory. In this work, we performed anatomical and ultrastructural studies to characterize P. organensis extrafloral nectaries during their secretory phase. We showed extrafloral nectaries in Passiflora organensis are composed of three distinct regions: nectary epidermis, nectariferous parenchyma, and subnectariferous parenchyma. Our data suggests that all nectary regions constitute a functional unit involved in nectar production and release. The high metabolic activity in the nectary cells is characterized by the juxtaposition of organelles such as mitochondria and plastids together plasmalemma. In addition, calcium oxalate crystals are frequently associated to the nectaries. An increasing concentration of calcium during leaf development and nectary differentiation was observed, corresponding to the calcium deposition as calcium oxalate crystals. This is the first description of extrafloral nectaries in Passiflora organensis that is a promising tropical model species for several studies. RESEARCH HIGHLIGHTS: The anatomical and ultrastructural characteristics and the presence of calcium oxalate crystals in the nectary tissue suggest novel strategies against herbivory in the genus Passiflora.

Effect of calcium oxalate crystals on the micromechanical properties of sclerenchyma tissue from the pecan nutshell (Carya illinoinensis).

The objective of this study was to evaluate the effect of the presence of calcium oxalate (CaOx) crystals on the micromechanical properties of sclerenchyma tissue from the pecan nutshell (Carya illinoinensis). The microstructure of the cross-section nutshell was examined using light microscopy (LM) and atomic force microscopy (AFM). Using an instrumented indentation system, indentation tests with maximum loads of 500 mN were made on the biological material where the variables studied were the number of crystals present in the evaluated area and the size of individual crystals. Microscopic analysis revealed that the pecan nutshell consists of sclerenchyma tissue with multiple CaOx crystals randomly distributed throughout the material, exhibiting prismatic shapes and various sizes. The results of the indentation tests showed that the examined areas where there were crystals (1, 2 or up to 3) presented values of hardness and elastic modulus significantly higher (P < 0.05) compared to the sclerenchyma (without crystals). Likewise, there were no significant differences (P > 0.05) between the values of the micromechanical properties of the areas evaluated as a function of the number of crystals. On the other hand, it was observed that the size of the crystals did not show a direct correlation with the mechanical properties evaluated as expected. In conclusion, the biomineralization phenomenon is a successful strategy designed by nature to improve the rigidity of the pecan nutshell, where the CaOx crystals strengthen the structure by increasing the micromechanical properties.