Soil-mustard revitalization via rice husk ash, a promising soil amendment material for sustainable management of heavy metal contamination in tropical ecosystem.

Prolonged wastewater irrigation in agriculture has led to the accumulation of heavy metals in soil, endangering both the soil quality and food safety, thereby posing a potential threat to human health through the consumption of contaminated crops. The present study aimed to enhance the yield of mustard (Brassica juncea L. cv. Varuna and NRCHB 101) plants and stabilize heavy metals (Cd, Cr, Ni, Cu, and Zn) in wastewater-irrigated soil using rice husk ash (RHA), rice mill by-product, collected from Chandauli region of Eastern Uttar Pradesh, India. Results demonstrated significant improvements in growth, biomass, physiology, and yield of mustard plant with increasing RHA application in wastewater irrigated soil (p ≤ 0.05). Heavy metal accumulation in different parts of mustard plants decreased as RHA application rate increased. Applying RHA at 2% in soil proved to be most effective in reducing Cd, Cr, Ni, Cu, and Zn accumulation in seeds by 29%, 29.6%, 23.1%, 21.3% and 20.1%, respectively in Varuna and 30.1%, 21.4%, 11.1%, 12.1%, and 28.5%, respectively in NRCHB 101cultivars. The present findings showed that RHA amendment in wastewater irrigated soil had reduced bioaccumulation of Cd, Cr, Ni, Cu, and Zn and consequently their toxicity in cultivated mustard plants. A novel application of RHA is unveiled in this research, offering a promising solution to promote sustainable agriculture and to reduce heavy metal associated health risks within the soil-mustard system.

Screening of mustard cultivars for phytoremediation of heavy metals contamination in wastewater irrigated soil systems.

The mustard (Brassica juncea L.) plant is a well-known and widely accepted hyper-accumulator of heavy metals. The genetic makeup of mustard's cultivars may significantly impact their phytoremediation capabilities. The present study aimed to investigate the growth performance, yield attributes, and heavy metal accumulation potential of B. juncea cv. Varuna, NRCHB 101, RH 749, Giriraj, and Kranti, cultivated in soil irrigated with wastewater (EPS) and bore-well water (MPS). EPS contributed more Cr, Cd, Cu, Zn, and Ni to tested mustard cultivars than the MPS. EPS reduced morphological, biochemical, physiological, and yield attributes of tested mustard cultivars significantly (p < 0.05) than the MPS. Among the tested cultivars of mustard plants, Varuna had the highest heavy metal load with the lowest harvest index (35.8 and 0.21, respectively). Whereas NRCHB 101 showed the lowest heavy metal load with the highest harvest index (26.9 and 0.43, respectively). The present study suggests that B. juncea cv. Varuna and NRCHB 101 could be used for the phytoextraction of heavy metals and reducing their contamination in food chain, respectively in wastewater irrigated areas of peri-urban India. The outcomes of the present study can also be utilized to develop a management strategy for sustainable agriculture in heavy metal polluted areas resulting from long-term wastewater irrigation.

Nrf2 is expressed more extensively in neurons than in astrocytes following an acute epileptic seizure in rats.

The modulation of the nuclear factor erythroid 2-like 2 (Nrf2) activity has been reported to be implicated in the pathology of various neurological disorders, including epilepsy. Previous studies have demonstrated that Nrf2 is activated in the post-status epilepticus rat model; however, the spatiotemporal as well as cell type-specific expression of Nrf2 following brief epileptic seizures remains unclear. Here, we evaluated how an acute epileptic seizure affected the expression of Nrf2 and its downstream genes in the rats' cortex and the hippocampus up to 1 week following the induced seizure. We found that after a pentylenetetrazol-induced seizure, Nrf2 significantly increased at 24 h at the mRNA level and 3 h at the protein level in the cortex. In the hippocampus, the Nrf2 mRNA level peaked at 3 h after the seizure, and no significant changes were observed in the protein level. Interestingly, the mRNA level of Nrf2 downstream genes peaked at 3-6 h after seizure in both the cortex and the hippocampus. A significant increase in the expression of Nrf2 was observed in the neuronal population of CA1 and CA3 regions of the hippocampus, as well as in the cortex. Moreover, we observed no change in the co-localization of Nrf2 with astrocytes neither in the cortex nor in CA1 and CA3. Our results revealed that following a brief acute epileptic seizure, the expression of Nrf2 and its downstream genes is transiently increased and peaked at early timepoints after the seizure predominantly in the hippocampus, and this expression is restricted to the neuronal population.

Repurposing dimethyl fumarate as an antiepileptogenic and disease-modifying treatment for drug-resistant epilepsy.

BACKGROUND: Epilepsy affects over 65 million people worldwide and significantly burdens patients, caregivers, and society. Drug-resistant epilepsy occurs in approximately 30% of patients and growing evidence indicates that oxidative stress contributes to the development of such epilepsies. Activation of the Nrf2 pathway, which is involved in cellular defense, offers a potential strategy for reducing oxidative stress and epilepsy treatment. Dimethyl fumarate (DMF), an Nrf2 activator, exhibits antioxidant and anti-inflammatory effects and is used to treat multiple sclerosis. METHODS: The expression of Nrf2 and its related genes in vehicle or DMF treated rats were determined via RT-PCR and Western blot analysis. Neuronal cell death was evaluated by immunohistochemical staining. The effects of DMF in preventing the onset of epilepsy and modifying the disease were investigated in the kainic acid-induced status epilepticus model of temporal lobe epilepsy in rats. The open field, elevated plus maze and T-Maze spontaneous alteration tests were used for behavioral assessments. RESULTS: We demonstrate that administration of DMF following status epilepticus increased Nrf2 activity, attenuated status epilepticus-induced neuronal cell death, and decreased seizure frequency and the total number of seizures compared to vehicle-treated animals. Moreover, DMF treatment reversed epilepsy-induced behavioral deficits in the treated rats. Moreover, DMF treatment even when initiated well after the diagnosis of epilepsy, reduced symptomatic seizures long after the drug was eliminated from the body. CONCLUSIONS: Taken together, these findings suggest that DMF, through the activation of Nrf2, has the potential to serve as a therapeutic target for preventing epileptogenesis and modifying epilepsy.

Hydrogen adsorption and diffusion through a two dimensional sheet of lithium: a first principles study.

Two-dimensional (2D) materials have shown promise as highly selective, ultrathin membranes to transport ions, and atomic and subatomic particles. They have also been regarded as potential hydrogen storage candidates due to their chemical stability and high specific surface area. However, most of these studies have been carried out with semiconducting 2D materials. With recent explorations towards the existence and stability of 2D metals, we explore the hydrogen adsorption and diffusion through a 2D metallic sheet of lithium. We report that in the lowest energy metallic configuration, the sheet is predicted to crystallize in a highly buckled honeycomb structure. We calculate the adsorption energy for the diffusion of hydrogen on various high symmetry sites in the lattice, and find that adsorption is energetically favoured. We study the minimum energy pathways for diffusion through the sheet and find that the lowest energy barriers exist for tunneling through the honeycomb ring. Our results would be of direct technological relevance to the applications of 2D metallic nanostructures as membranes for selective transport or towards storage.

Estimated GFR Slope Across CKD Stages in Primary Hyperoxaluria Type 1.

RATIONALE & OBJECTIVE: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism that results in early-onset kidney stone disease, nephrocalcinosis, and kidney failure. There is an unmet need for reliable markers of disease progression to test effectiveness of new treatments for patients with PH. In this study, we assessed the rate of estimated glomerular filtration rate (eGFR) decline across chronic kidney disease (CKD) glomerular filtration rate (GFR) categories (CKD G2-G5) in a cohort of patients with PH1. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Patients with PH1 enrolled in the Rare Kidney Stone Consortium (RKSC) registry who did not have kidney failure at diagnosis and who had at least 2 eGFR values recorded from within 1 month of diagnosis until their last contact date or incident kidney failure event. PREDICTORS: CKD GFR category, baseline patient and laboratory characteristics. OUTCOME: Annualized rate of eGFR decline. ANALYTICAL APPROACH: Generalized estimating equations and linear regression were used to evaluate the associations between CKD GFR category, baseline patient and laboratory characteristics, and annual change in eGFR during follow-up. RESULTS: Compared with the slope in CKD G2 (-2.3 mL/min/1.73 m2 per year), the mean annual eGFR decline was nominally steeper in CKD G3a (-5.3 mL/min/1.73 m2 per year) and statistically significantly more rapid in CKD G3b and G4 (-14.7 and -16.6 mL/min/1.73 m2 per year, respectively). In CKD G2, older age was associated with a more rapid rate of eGFR decline (P = 0.01). A common PH1-causing variant of alanine glyoxylate aminotransferase, a glycine to arginine substitution at amino acid 170 (G170R), appeared to be associated with less severe annual decline in eGFR. LIMITATIONS: Data at regular time points were not available for all patients due to reliance on voluntary reporting in a retrospective rare disease registry. CONCLUSIONS: The eGFR decline was not uniform across CKD GFR categories in this PH1 population, with a higher rate of eGFR decline in CKD G3b and G4. Thus, CKD GFR category needs to be accounted for when analyzing eGFR change in the setting of PH1.

Primary Hyperoxaluria Type 3 Can Also Result in Kidney Failure: A Case Report.

Primary hyperoxaluria (PH) is a group of genetic disorders that result in an increased hepatic production of oxalate. PH type 3 (PH3) is the most recently identified subtype and results from mutations in the mitochondrial 4-hydroxy-2-oxoglutarate aldolase gene (HOGA1). To date, there have been 2 cases of kidney failure reported in PH3 patients. We present a case of a young man with a history of recurrent urinary tract infections and voiding dysfunction who developed kidney failure at 33 years of age. He developed a bladder stone and bilateral staghorn calculi at 12 years of age. Initial metabolic evaluation revealed hyperoxaluria with very low urinary citrate excretion on multiple measurements for which he was placed on oral citrate supplements. Further investigation of the hyperoxaluria was not completed as the patient was lost to follow-up observation until he presented at 29 years of age with chronic kidney disease stage 4 (estimated glomerular filtration rate 24mL/min/1.73m2). Hemodialysis 3 times a week was started at 33 years of age, and subsequent genetic testing revealed a homozygous HOGA1 mutation (C.973G>A p.Gly325Ser) diagnostic of PH3. The patient is currently being evaluated for all treatment options including possible liver/kidney transplantation. All cases of a childhood history of recurrent urinary stone disease with marked hyperoxaluria should prompt genetic testing for the 3 known PH types. Hyperhydration and crystallization inhibitors (citrate) are standard of care, but the role of RNA interference agents for all 3 forms of PH is also under active study.

Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2.

BACKGROUND: Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2. METHODS: Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62). RESULTS: PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P < 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P < 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients. CONCLUSIONS: Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.

Chronic graft-versus-host disease in pancreas after kidney transplant recipients - An unrecognized entity.

Graft-versus-host disease (GVHD), a common complication after peripheral blood stem cell or bone marrow transplantation, rarely occurs in kidney and pancreas transplant recipients. The true incidence may be confounded by the rarity of the disorder, with a resultant lack of appreciation of the diagnosis as a potential cause of common clinical manifestations such as cytopenias and immune dysfunction. Reports of GVHD in kidney and pancreas transplant recipients almost uniformly describe patients in the early posttransplant period (days to months) with the typical manifestations of acute GVHD involving the skin, liver, and intestines. In contrast, reports of solid organ transplant recipients with clinical features more consistent with chronic GVHD (cGVHD) are lacking, raising concern of underrecognition of this severe complication. Occurrence later after transplant may be even more likely to result in lack of recognition. We report 2 cases of possible cGVHD occurring in recipients of pancreas after kidney transplantation, which were diagnosed at 5.5 and 42 months after pancreas transplant. Both patients presented with severe pancytopenia, multiple opportunistic infections, and features suggestive of cGVHD. Transplant professionals should be aware of the possibility of acute and cGVHD in pancreas after kidney transplant recipients and be able to recognize the clinical manifestations.

Direct physical interaction of active Ras with mSIN1 regulates mTORC2 signaling.

BACKGROUND: The mechanistic (or mammalian) target of rapamycin (mTOR), a Ser/Thr kinase, associates with different subunits forming two functionally distinct complexes, mTORC1 and mTORC2, regulating a diverse set of cellular functions in response to growth factors, cellular energy levels, and nutrients. The mechanisms regulating mTORC1 activity are well characterized; regulation of mTORC2 activity, however, remains obscure. While studies conducted in Dictyostelium suggest a possible role of Ras protein as a potential upstream regulator of mTORC2, definitive studies delineating the underlying molecular mechanisms, particularly in mammalian cells, are still lacking. METHODS: Protein levels were measured by Western blotting and kinase activity of mTORC2 was analyzed by in vitro kinase assay. In situ Proximity ligation assay (PLA) and co-immunoprecipitation assay was performed to detect protein-protein interaction. Protein localization was investigated by immunofluorescence and subcellular fractionation while cellular function of mTORC2 was assessed by assaying extent of cell migration and invasion. RESULTS: Here, we present experimental evidence in support of the role of Ras activation as an upstream regulatory switch governing mTORC2 signaling in mammalian cancer cells. We report that active Ras through its interaction with mSIN1 accounts for mTORC2 activation, while disruption of this interaction by genetic means or via peptide-based competitive hindrance, impedes mTORC2 signaling. CONCLUSIONS: Our study defines the regulatory role played by Ras during mTORC2 signaling in mammalian cells and highlights the importance of Ras-mSIN1 interaction in the assembly of functionally intact mTORC2.

The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging.

Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18-29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70-75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.

Thiazide diuretic prophylaxis for kidney stones and the risk of diabetes mellitus.

PURPOSE: Thiazide diuretics used to treat hypertension are associated with a modest risk of diabetes mellitus. It is unknown if there is a similar risk with kidney stone prevention. MATERIALS AND METHODS: We identified and validated incident stone formers in Olmsted County, Minnesota from 1984 to 2011 with manual review of medical records using the Rochester Epidemiology Project. The risk of diabetes mellitus after thiazide therapy was evaluated with and without multivariate adjustment for hypertension, age, gender, race, family history of stones, body mass index and number of stone events. RESULTS: Among 2,350 incident stone formers with a median followup of 10 years, 332 (14%) were treated with thiazide diuretics at some point after the first stone event and 84 (3.6%) received the thiazide diuretic only for kidney stone prevention. Stone formers who received thiazide diuretics were more likely to be older, have hypertension, have higher body mass index and have more stone events. The incidence of diabetes mellitus at 10 years after the first stone event was 9.2% in the group that received thiazide diuretics vs 4.2% in those who did not (HR 2.91; 95% CI 2.02, 4.20). After multivariate adjustment the risk of diabetes mellitus was attenuated (HR 1.20; 95% CI 0.78, 1.83). The risk of diabetes mellitus among those receiving thiazide diuretics solely for kidney stones was further attenuated (multivariate adjusted HR 0.80; 95% CI 0.28, 2.23). CONCLUSIONS: Thiazide diuretic use for kidney stone prophylaxis was not associated with a high risk of diabetes mellitus. Larger studies are needed to determine if there is a modest risk of diabetes mellitus with thiazide diuretics.

Randomised controlled trial of tourniquet associated pain generated in lower limb after exsanguination by Esmarch bandage versus limb elevation.

BACKGROUND: Tourniquets are common adjuncts in the operating theatre but can be associated with post-operative pain. This study was designed to compare what effect pre-tourniquet Esmarch bandage exsanguination has on pain, compared to pre-tourniquet exsanguination by elevation alone. METHODS: 52 volunteers (104 lower limbs) were included in this study with each volunteer acting as their own matched control. The primary outcome was patient reported pain, measured in both legs simultaneously using area under curve. Secondary outcomes were pain score during inflation and deflation, cumulative pain score, duration of recovery and blood pressure during testing. RESULTS: Pain after Esmarch was superior to elevation as measured by area under pain curve (68.9 SD 26.1 vs 77.2 SD 27.3, p = 0.0010), independent of leg dominance. Cumulative pain scores demonstrated the same superiority after inflation (50.7 SD 17.1 vs 52.9 SD 17.0, p = 0.026) but not after deflation (p = 0.59). Blood pressure was not significantly different. Time to full recovery of the lower limb was the same for both groups-7.6 min (SD 2.1 min, p = 0.80). CONCLUSION: Previous studies describe a positive effect on pain when Esmarch bandage was used prior to tourniquet inflation for upper limb. Our findings suggest the same benefit from Esmarch when it was used on lower limbs-particularly during inflation of tourniquet. In addition to pain profiles, surgeon preference and patient factors need to be considered when deciding between elevation and Esmarch bandage.

Nrf2 is predominantly expressed in hippocampal neurons in a rat model of temporal lobe epilepsy.

BACKGROUND: Drug resistance is a particular problem in patients with temporal lobe epilepsy, where seizures originate mainly from the hippocampus. Many of these epilepsies are acquired conditions following an insult to the brain such as a prolonged seizure. Such conditions are characterized by pathophysiological mechanisms including massive oxidative stress that synergistically mediate the secondary brain damage, contributing to the development of epilepsy. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged in recent years as an attractive therapeutic approach targeting to upregulate the antioxidative defenses in the cell, to ameliorate the oxidative stress-induced damage. Thus, it is important to understand the characteristics of Nrf2 activation during epileptogenesis and epilepsy. Here, we studied the temporal, regional, and cell-type specific expression of Nrf2 in the brain, in a rat model of temporal lobe epilepsy. RESULTS: Early after status-epilepticus, Nrf2 is mainly activated in the hippocampus and maintained during the whole period of epileptogenesis. Only transient expression of Nrf2 was observed in the cortex. Nevertheless, the expression of several Nrf2 antioxidant target genes was increased within 24 h after status-epilepticus in both the cortex and the hippocampus. We demonstrated that after status-epilepticus in rats, Nrf2 is predominantly expressed in neurons in the CA1 and CA3 regions of the hippocampus, and only astrocytes in the CA1 increase their Nrf2 expression. CONCLUSIONS: In conclusion, our data identify previously unrecognized spatial and cell-type dependent activation of Nrf2 during epilepsy development, highlighting the need for a time-controlled, and cell-type specific activation of the Nrf2 pathway for mediating anti-oxidant response after brain insult, to modify the development of epilepsy.

Asian Zika virus can acquire generic African-lineage mutations during in utero infection.

The Zika virus 2015 epidemic showed an unusual phenotype for human flaviviruses, specifically fetal infection. We previously showed that in utero inoculation with the Asian Zika virus isolated from the human sample causes persistent infection in porcine fetuses. Here, we characterized the evolution of the Asian Zika virus in the fetal brain and placenta. Interestingly, the Asian Zika virus acquired generic African lineage K101R (A408G) and R1609 K (G4932A) mutations during in utero infection. Both African mutations were nonsynonymous and had a high frequency of nearly 100% in the fetal brain. Then, we synthetically generated the wild-type Asian variant and fetal brain-specific variant with generic African-lineage K101R and R1609 K mutations. In mosquito C6/36 cells, but not in human and pig cells, the fetal brain-specific variant showed higher virus loads compared to the Asian wild-type prototype. While in utero infection with both variants caused comparable virus loads in the placenta and amniotic fluids, fetuses injected with the fetal brain-specific variant had the trend to higher virus loads in lymph nodes. Also, introduced K101R and R1609 K mutations were stable and had high nearly 100% frequency at 28 days after in utero inoculation in both directly injected and trans-infected fetuses. These findings evoke concerns because Zika persists in pig herds and mosquitoes on farms in Mexico. It will be essential to identify how persistent in utero infection affects virus evolution and whether in utero-emerged Zika variants have the potential for shedding into the environment, more efficient transmission, and more aggressive infection phenotypes.

Phytochemical Screening, Quantification, FT-IR Analysis, and In Silico Characterization of Potential Bio-active Compounds Identified in HR-LC/MS Analysis of the Polyherbal Formulation from Northeast India.

Diabetes is a group of metabolic disorders characterized by elevated blood sugar levels, leading to many undesirable health consequences. There are many herbal formulations, traditionally used by the Northeast Indian population for disease management. These formulations require scientific validations to optimize their efficacy and increase their popularity. In this study, we attempt to scientifically validate a polyherbal formulation traditionally used for the management of diabetes through preliminary phytochemicals investigation, characterization of potential phytochemicals using Fourier transform infrared (FT-IR) spectroscopy, high-resolution liquid chromatography mass spectrometry (HR-LC/MS) analysis, and in silico characterization of physiochemical, drug-likeness, and pharmacokinetic properties of identified phytochemical compounds. Qualitative phytochemical screening of various extracts of the formulation confirmed the presence of alkaloids, phenols and tannins, flavonoids, fats, and oils. Phytochemical quantification of the various extracts showed that the highest total phenolic content is present in the ethanolic extract (35.61 ± 0.15 mg GAE/g), while the highest total flavonoid content is present in the chloroform extract (76.33 ± 2.96 mg QE/g) of the formulation. FT-IR spectroscopic analysis revealed various characteristic band values with various functional groups in the formulation extract such as amines, alcohol, fluoro compounds, phenol, alkane, alkene, and conjugated acid groups. HR-LC/MS analyses identified nearly 51 compounds including 9 small peptides and 42 potential phytochemical compounds. In silico SwissADME analysis of identified compounds revealed 25 potential compounds following Lipinski's rule and showing drug-like characteristics, and out of them, 16 compounds exhibited good oral bioavailability, as revealed in the bioavailability radar. The overall study showed that the presented polyherbal formulation is enriched with bio-active phytochemical compounds with good pharmaceutical values.

The genetics of kidney stone disease and nephrocalcinosis.

Kidney stones (also known as urinary stones or nephrolithiasis) are highly prevalent, affecting approximately 10% of adults worldwide, and the incidence of stone disease is increasing. Kidney stone formation results from an imbalance of inhibitors and promoters of crystallization, and calcium-containing calculi account for over 80% of stones. In most patients, the underlying aetiology is thought to be multifactorial, with environmental, dietary, hormonal and genetic components. The advent of high-throughput sequencing techniques has enabled a monogenic cause of kidney stones to be identified in up to 30% of children and 10% of adults who form stones, with ~35 different genes implicated. In addition, genome-wide association studies have implicated a series of genes involved in renal tubular handling of lithogenic substrates and of inhibitors of crystallization in stone disease in the general population. Such findings will likely lead to the identification of additional treatment targets involving underlying enzymatic or protein defects, including but not limited to those that alter urinary biochemistry.