Cystinuria Complicated by Anuria From Bilateral Obstructing Stones Requiring Bilateral Mini Percutaneous Nephrolithotomy in a 22-Month-Old.

Pediatric nephrolithiasis is increasing in incidence and presents differently compared to adults. We report a case of nephrolithiasis in a pediatric patient, presenting with complaints of emesis, anuria, hematuria, and abdominal distension, leading to a diagnosis of bilateral obstructing cystine stones requiring bilateral percutaneous nephrolithotomy. Pediatric patients with anuria should be evaluated for bilateral nephrolithiasis as an etiology. Calculous anuria requires prompt recognition of the pathologic process and relief of the obstruction with close follow-up and supportive care until definitive stone management. Bilateral percutaneous nephrolithotomy can provide definitive surgical intervention without significant morbidity.

The genetics of cystinuria - an update and critical reevaluation.

PURPOSE OF REVIEW: We aimed to critically evaluate how the establishment of genotype-based treatment for cystinuria has been hampered due to the large number of variants of unknown significance (VUS) within the disease causing genes as well as challenges in accessing a large enough sample size for systematic analysis of endpoint parameters that truly reflect disease severity. This review further discusses how to overcome these hurdles with the establishment of a cystinuria-specific refinement of the current American College of Medical Genetics and Genomics (ACMG)-criteria of variant interpretation. RECENT FINDINGS: Novel tools such as AlphaMissense combined with the establishment of a refined ACMG criterion will play a significant role in classifying VUS within the responsible disease genes SLC3A1 (rBAT) and SLC7A9 (BAT1). This will also be essential in elucidating the role of promising candidate genes, such as SLC7A13 (AGT1), which have been derived from murine model systems and still need further research to determine if they are involved in human cystinuria. SUMMARY: Cystinuria was one of the first disorders to receive a gene-based classification, nonetheless, the clinically actionable implications of genetic diagnostics is still minor. This is due to poorly characterized genotype-phenotype correlations which results in a lack of individualized (genotype-) based management and metaphylaxis.

Postnatal outcome of children with antenatal colonic hyperechogenicity.

OBJECTIVE: To evaluate the postnatal outcome of children with antenatal colonic hyperechogenicity, currently considered as a sign of lysinuria-cystinuria, but which may also be a sign of other disorders with a more severe prognosis. METHOD: We carried out a French multi-centric retrospective study via 15 Multidisciplinary Center for Prenatal Diagnosis from January 2011 to January 2021. We included pregnancies for which fetal colonic hyperechogenicity had been demonstrated. We collected the investigations performed during pregnancy and at birth as well as the main clinical features of the mother and the child. We then established the prevalence of pathologies such as lysinuria-cystinuria (LC), hypotonia-cystinuria syndrome (HC), or lysinuric protein intolerance (LPI). RESULTS: Among the 33 cases of colonic hyperechogenicity collected, and after exclusion of those lost to follow-up, we identified 63% of children with lysinuria-cystinuria, 8% with lysinuric rotein intolerance, and 4% with hypotonia-cystinuria syndrome. CONCLUSION: Management of prenatal hyperechoic colon should include a specialized consultation with a clinical geneticist to discuss further investigations, which could include invasive amniotic fluid sampling for molecular diagnosis. A better understanding of diagnoses and prognosis should improve medical counseling and guide parental decision making.

Hydration for Adult Patients with Nephrolithiasis: Specificities and Current Recommendations.

Nephrolithiasis affects around 10% of the population and is frequently associated with impaired dietary factors. The first one is insufficient fluid intake inducing reduced urine volume, urine supersaturation, and subsequently urinary lithiasis. Kidneys regulate 24 h urine volume, which, under physiological conditions, approximately reflects daily fluid intake. The aim of this study is to synthesize and highlight the role of hydration in the treatment of nephrolithiasis. Increasing fluid intake has a preventive effect on the risk of developing a first kidney stone (primary prevention) and also decreases the risk of stone recurrence (secondary prevention). Current guidelines recommend increasing fluid intake to at least at 2.5 L/day to prevent stone formation, and even to 3.5-4 L in some severe forms of nephrolithiasis (primary or enteric hyperoxaluria or cystinuria). Fluid intake must also be balanced between day and night, to avoid urinary supersaturation during the night. Patients should be informed and supported in this difficult process of increasing urine dilution, with practical ways and daily routines to increase their fluid intake. The liquid of choice is water, which should be chosen depending on its composition (such as calcium, bicarbonate, or magnesium content). Finally, some additional advice has to be given to avoid certain beverages such as those containing fructose or phosphoric acid, which are susceptible to increase the risk of nephrolithiasis.

Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study.

More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded.

Novel compound heterozygous pathogenic variants in the SLC3A1 gene in a Chinese family with cystinuria.

BACKGROUND: Cystinuria is an autosomal recessive disorder characterized by a cystine transport deficiency in the renal tubules due to mutations in two genes: SLC3A1 and SLC7A9. Cystinuria can be classified into three forms based on the genotype: type A, due to mutations in the SLC3A1 gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to mutations in both genes. METHODS: We report a 12-year-old boy from central China with cystine stones. He was from a non-consanguineous family that had no known history of genetic disease. A physical examination showed normal development and neurological behaviors. Whole-exome and Sanger sequencing were used to identify and verify the suspected pathogenic variants. RESULTS: The compound heterozygous variants c.898_905del (p.Arg301AlafsTer6) is located in exon5 and c.1898_1899insAT (p.Asp634LeufsTer46) is located in exon10 of SLC3A1 (NM_000341.4) were deemed responsible for type A cystinuria family. The variant c.898_905del was reported in a Japanese patient in 2000, and the variant c.1898_1899insAT is novel. CONCLUSION: A novel pathogenic heterozygous variant pair of the SLC3A1 gene was identified in a Chinese boy with type A cystinuria, enriching the mutational spectrum of the SLC3A1 gene. We attempted to find a pattern for the association between the genotype of SLC3A1 variants and the manifestations of cystinuria in patients with different onset ages. Our findings have important implications for genetic counseling and the early clinical diagnosis of cystinuria.

Entrando en el manejo 2.0 de la cistinuria con una herramienta médica digital para monitorizar el pH de la orina: un estudio prospectivo y aleatorizado / Entering into 2.0 cystinuria management with a medical digital tool to monitor urine pH: A prospective, randomized study

Introducción y objetivos Las personas con cistinuria pueden experimentar eventos recurrentes de litiasis debido a la relativa insolubilidad de la cistina en el pH fisiológico de la orina, lo que resulta en deterioro de la función renal. El pHmetro Lit-Control® es un dispositivo médico que permite la automedición precisa del pH de la orina. El objetivo principal de este estudio fue comparar la usabilidad del pHmetro Lit-Control® con las tiras reactivas para la automonitorización domiciliaria del pH urinario por parte de pacientes con cistinuria, y su satisfacción general con cada herramienta.Pacientes y métodosSe incluyeron 28 pacientes (9 mujeres y 19 varones, de 19 a 76 años), que fueron asignados aleatoriamente a monitorizar su pH urinario con tiras reactivas (n=17) o el pHmetro Lit-Control® (n=11).ResultadosDespués de 6 meses de uso, la satisfacción con los 2 métodos fue similarmente alta, pero los pacientes calificaron (en una escala de 0 a 10) mejor el pHmetro en términos de facilidad de aprendizaje (media± DE, 8,11±0,60 vs. 7,06±1,18; p=0,038), facilidad de preparación (8,22±0,67 vs. 7,25±1,18; p=0,034) y facilidad de uso (8,22±0,67 vs. 7,25±1,39; p=0,062). En general, los pacientes no alcanzaron los objetivos de alcalinización (pH entre 7,0 y 8,0).ConclusionesEl pHmetro Lit-Control® demostró ser un dispositivo fácil de usar que puede facilitar el control del pH urinario en los pacientes con cistinuria. Queda justificado un estudio prospectivo para evaluar la correlación entre la monitorización del pH de la orina, una estrategia de tratamiento por objetivo y la recurrencia de los cálculos de cistina. (AU)

Background and objectives Individuals with cystinuria can experiment recurrent lithiasis events due to the relative insolubility of cystine at physiological urine pH, resulting in renal function decline. The Lit-Control® pH Meter is a medical device that accurately allows urine pH self-monitoring. The main objective of this study was to compare the usability of the Lit-Control® pH Meter with the reactive strips for self-monitoring of urinary pH at home by patients with cystinuria, and their overall satisfaction with each tool.Patients and methodsWe included 28 patients (9 females and 19 males, age 19-6 years), who were randomly assigned to monitor their urine pH with reactive strips (n=17) or the Lit-Control® pH Meter (n=11).ResultsAfter six months of use, the satisfaction with the two methods was similarly high, but the patients rated (0-10 scale) the pH meter better in terms of ease of learning (mean±SD, 8.11±0.60 vs. 7.06±1.18; P=.038), ease to prepare (8.22±0.67 vs. 7.25±1.18; P=0.034), and ease of use (8.22±0.67 vs. 7.25±1.39; P=.062). Overall, patients did not reach the alkalinization goals (pH between 7.0 and 8.0).ConclusionsThe Lit-Control® pH Meter demonstrated to be an easy-to-use device that can facilitate urinary pH control by cystinuric patients. A prospective study is warranted to assess the correlation between urine pH monitoring, a treat to target approach, and the recurrence of cystine stones. (AU)

Chemical Modification of Tiopronin for Dual Management of Cystinuria and Associated Bacterial Infections.

Cystinuria is an inherited autosomal recessive disease of the kidneys of recurring nature that contributes to frequent urinary tract infections due to bacterial growth and biofilm formation surrounding the stone microenvironment. In the past, commonly used strategies for managing cystinuria involved the use of (a) cystine crystal growth inhibitors such as l-cystine dimethyl ester and lipoic acid, and (b) thiol-based small molecules such as N-(2-mercaptopropionyl) glycine, commonly known as tiopronin, that reduce the formation of cystine crystals by reacting with excess cystine and generating more soluble disulfide compounds. However, there is a dearth of simplistic chemical approaches that have focused on the dual treatment of cystinuria and the associated microbial infections. This work strategically exploited a single chemical approach to develop a nitric oxide (NO)-releasing therapeutic compound, S-nitroso-2-mercaptopropionyl glycine (tiopronin-NO), for the dual management of cystine stone formation and the related bacterial infections. The results successfully demonstrated that (a) the antibacterial activity of NO rendered tiopronin-NO effective against the stone microenvironment inhabitants, Escherichia coli and Pseudomonas aeruginosa, and (b) tiopronin-NO retained the ability to undergo disulfide exchange with cystine while being reported to be safe against canine kidney and mouse fibroblast cells. Thus, the synthesis of such a facile molecule aimed at the dual management of cystinuria and related infections is unprecedented in the literature.

Population genetics analysis of SLC3A1 and SLC7A9 revealed the etiology of cystine stone may be more than what our current genetic knowledge can explain.

BACKGROUND: Cystine stone is a Mendelian genetic disease caused by SLC3A1 or SLC7A9. In this study, we aimed to estimate the genetic prevalence of cystine stones and compare it with the clinical prevalence to better understand the disease etiology. METHODS: We analyzed genetic variants in the general population using the 1000 Genomes project and the Human Gene Mutation Database to extract all SLC3A1 and SLC7A9 pathogenic variants. All variants procured from both databases were intersected. Pathogenic allele frequency, carrier rate, and affected rate were calculated and estimated based on Hardy-Weinberg equilibrium. RESULTS: We found that 9 unique SLC3A1 pathogenic variants were carried by 26 people and 5 unique SLC7A9 pathogenic variants were carried by 12 people, all of whom were heterozygote carriers. No homozygote, compoun d heterozygote, or double heterozygote was identified in the 1000 Genome database. Based on the Hardy-Weinberg equilibrium, the calculated genetic prevalence of cystine stone disease is 1 in 30,585. CONCLUSION: The clinical prevalence of cystine stone has been previously reported as 1 in 7,000, a notably higher figure than the genetic prevalence of 1 in 30,585 calculated in this study. This suggests that the etiology of cystine stone is more complex than what our current genetic knowledge can explain. Possible factors that may contribute to this difference include novel causal genes, undiscovered pathogenic variants, alternative inheritance models, founder effects, epigenetic modifications, environmental factors, or other modifying factors. Further investigation is needed to fully understand the etiology of cystine stone.

Declaration: Novel SLC3A1 mutation in a cystinuria patient with xanthine stones: a case report.

BACKGROUND: Cystinuria and xanthinuria are both rare genetic diseases involving urinary calculi. However, cases combining these two disorders have not yet been reported. CASE PRESENTATION: In this study, we report a case of cystinuria with xanthine stones and hyperuricemia. The 23-year-old male patient was diagnosed with kidney and ureteral stones, solitary functioning kidney and hyperuricemia after admission to the hospital. The stones were removed by surgery and found to be composed of xanthine. CONCLUSION: Genetic testing by next-generation sequencing technology showed that the patient carried the homozygous nonsense mutation c.1113 C> A (p.Tyr371*) in the SLC3A1 gene, which was judged to be a functionally pathogenic variant. Sanger sequencing revealed that the patient's parents carried this heterozygous mutation, which is a pathogenic variant that can cause cystinuria. The 24-h urine metabolism analysis showed that the cystine content was 644 mg (<320 mg/24 h), indicating that the patient had cystinuria, consistent with the genetic test results. This case shows that cystinuria and xanthine stones can occur simultaneously, and provides evidence of a possible connection between the two conditions. Furthermore, our findings demonstrate the potential value of genetic testing using next-generation sequencing to effectively assist in the clinical diagnosis and treatment of patients with urinary calculi.

Interpretation of SLC3A1 and SLC7A9 variants in cystinuria patients: The significance of the PM3 criterion and protein stability.

Cystinuria is a genetic disorder caused by defects in the b0,+ transporter system, which is composed of rBAT and b0,+AT coded by SLC3A1 and SLC7A9, respectively. Variants in SLC3A1 and SLC7A9 follow autosomal recessive inheritance and autosomal dominant inheritance with reduced penetrance, respectively, which complicates the interpretation of cystinuria-related variants. Here, we report seven different SLC3A1 variants and six different SLC7A9 variants. Among these variants were two novel variants previously not reported: SLC3A1 c.223C > T and SLC7A9 c.404A > G. In silico analysis using REVEL correlated well with the functional loss upon SLC7A9 variants with scores of 0.8560-0.9200 and 0.4970-0.5239 for severe and mild decrease in transport activity, respectively. In addition, DynaMut2 was able to predict a decreased protein expression level resulting from the SLC7A9 variant c.313G > A with a ΔΔGStability -2.93 kcal/mol. Our study adds to the literature as additional cases of a variant allow applying the PM3 criterion with higher strength level. In addition, we suggest the clinical utility of REVEL and DynaMut2 in interpreting SLC3A1 and SLC7A9 variants. While a decreased protein expression level is not embraced in the current variant interpretation guidelines, we believe in silico protein stability predicting tools could serve as evidence of protein function loss.

The antioxidant l-Ergothioneine prevents cystine lithiasis in the Slc7a9-/- mouse model of cystinuria.

The high recurrence rate of cystine lithiasis observed in cystinuria patients highlights the need for new therapeutic options to address this chronic disease. There is growing evidence of an antioxidant defect in cystinuria, which has led to test antioxidant molecules as new therapeutic approaches. In this study, the antioxidant l-Ergothioneine was evaluated, at two different doses, as a preventive and long-term treatment for cystinuria in the Slc7a9-/- mouse model. l-Ergothioneine treatments decreased the rate of stone formation by more than 60% and delayed its onset in those mice that still developed calculi. Although there were no differences in metabolic parameters or urinary cystine concentration between control and treated mice, cystine solubility was increased by 50% in the urines of treated mice. We also demonstrate that l-Ergothioneine needs to be internalized by its transporter OCTN1 (Slc22a4) to be effective, as when administrated to the double mutant Slc7a9-/-Slc22a4-/- mouse model, no effect on the lithiasis phenotype was observed. In kidneys, we detected a decrease in GSH levels and an impairment of maximal mitochondrial respiratory capacity in cystinuric mice that l-Ergothioneine treatment was able to restore. Thus, l-Ergothioneine administration prevented cystine lithiasis in the Slc7a9-/- mouse model by increasing urinary cystine solubility and recovered renal GSH metabolism and mitochondrial function. These results support the need for clinical trials to test l-Ergothioneine as a new treatment for cystinuria.

Thulium fiber laser in cystine calculi.

INTRODUCTION: Thulium Fiber Laser (TFL) is the most modern technology to treat nephrolithiasis and ureterolithiasis in endourology. Although there are a lot of new studies coming up, we still don't have data on how this laser works in some rare diseases.Cystinuria is the most common genetic nephrolithiasis disorder (1), known for its recurrent lithiasis (2). Our main goal in this video is to show a successful case of cystine calculi treated with Thulium Fiber Laser (Laser Fiber Dust/Quanta System™). Cystinuria is the most common genetic nephrolithiasis disorder (1), known for its recurrent lithiasis (2). MATERIALS AND METHODS: A 25 years-old male, cystinuric, presented with a CT scan, showing a 10mm stone on the right side and two calculi 6 and 7 mm on the left side, all located in the lower calyx. Bilateral flexible ureteroscopy was done using a reusable digital flexible ureteroscope. Starting on the left side, we repositioned the stone from the lower to the upper calyx, using a tipless front opening basket. Lithotripsy was performed using TFL. Settings were 100 Hz (frequency) and 100 mJ (energy) for dusting.  Popcorn technique was also used, setting the laser at 100Hz and 200 mJ, obtaining good dusting. On the right side, lithotripsy was performed in the inferior calyx, also resulting in "snowstorm". Procedure time was 120 minutes. RESULTS: The postoperative was uneventful. Follow up CT showed a 3 mm residual fragment in the right kidney. CONCLUSION: This video demonstrates the treatment of bilateral cystine calculi with Thulium Fiber Laser. Reasonable procedure time and excellent dusting results are encouraging, pointing towards great improvements in endourology.

Self-Assembly of Cysteine into Nanofibrils Precedes Cystine Crystal Formation: Implications for Aggregation Inhibition.

The self-association of metabolites into well-ordered assemblies at the nanoscale has significant biological and medical implications. The thiol-containing amino acid cysteine (CYS) can assemble into amyloid-like nanofibrils, and its oxidized form, the disulfide-bonded cystine (CTE), forms hexagonal crystals as those found in cystinuria due to metabolic disorder. Yet, there have been no attempts to connect these two phenomena, especially the fibril-to-crystal transition. Here, we reveal that these are not separated events, and the CYS-forming amyloid fibrils are mechanistically linked to hexagonal CTE crystals. For the first time, we demonstrated that cysteine fibrils are a prerequisite for forming cystine crystals, as observed experimentally. To further understand this mechanism, we studied the effects of thiol-containing cystinuria drugs (tiopronin, TIO; and d-penicillamine, PEN) and the canonical epigallocatechin gallate (EGCG) amyloid inhibitor on fibril formation by CYS. The thiol-containing drugs do not solely interact with monomeric CYS via disulfide bond formation but can disrupt amyloid formation by targeting CYS oligomers. On the other hand, EGCG forms inhibitor-dominant complexes (more than one EGCG molecule per cysteine unit) to prevent CYS fibril formation. Interestingly, while CYS can be oxidized into CTE, the thiol drugs can reduce CTE back to CYS. We thus suggest that the formation of crystals in cystinuria could be halted at the initial stage by targeting CYS fibril formation as an alternative to solubilizing the water-insoluble hexagonal CTE crystals at a later stage. Taken together, we depicted a complex hierarchical organization in a simple amino acid assembly with implications for therapeutic intervention.

Why is childhood urolithiasis increasing? Etiology, diagnosis and management: a single-center experience.

BACKGROUND: Globally, urolithiasis is becoming more and more common among children. We aimed to determine the etiology, and the diagnostic and therapeutic approaches in patients with urolithiasis. METHODS: This was a retrospective study which included all patients (aged 1 month-18 years) admitted to the pediatric nephrology clinic in Elazig Fethi Sekin City Hospital with urolithiasis between November 2019 and 2021. Only patients whose diagnosis of urolithiasis was confirmed by urinary ultrasonography were included in the study, while patients with chronic diseases (neurological diseases such as epilepsy, cerebral palsy, chronic bowel diseases, etc.) predisposing to kidney stone formation were not. Demographic characteristics, serum and urine biochemical parameters, urine metabolic and kidney stone metabolic and chemical analyses, urinary tract ultrasonography findings and treatment modalities were collected. RESULTS: One hundred ninety-seven patients (91 female and 106 male) were included in the study. Hypervitaminosis D was detected in 4 (2%) patients, suppressed parathyroid hormone in 12 (6%) and hypercalcemia in 27 (14%) patients. Metabolic screening showed hypercalciuria in 69 (35%) patients, hypocitraturia in 39 (20%), hyperoxaluria in 15 (8%) and cystinuria in 6 (3%) patients. Eighty three (42%) patients had a positive family history for kidney stones. One hundred eighteen (60%) patients received potassium citrate treatment, 71 (36%) were given hydration and diet recommendations without medical treatment, 6 (3%) received tiopronin treatment, and 2 (1%) patients were treated surgically. CONCLUSIONS: Our study suggests that Vitamin D supplementation at doses higher than 400 IU/day may be a risk factor for kidney stones in children. We observed that mothers tend not to give water to infants who are breastfed or formula-fed in the first year of life. K-citrate treatment can be a good option for prevention and dissolution of stones by alkalinization.

Rapid detection of the biomarker for cystinuria by a metal-organic framework fluorescent sensor.

Arginine (Arg) is considered a valuable biomarker for various diseases, including cystinuria, and its concentration level holds significant implications for human health. To achieve the purposes of food evaluation and clinical diagnosis, it is imperative to develop a rapid and facile method for selective and sensitive determination of Arg. In this work, a novel fluorescent material (Ag/Eu/CDs@UiO-66) was synthesized by encapsulating carbon dots (CDs), Eu3+ and Ag + into UiO-66. This material can serve as a ratiometric fluorescent probe for detecting Arg. It exhibits a high sensitivity with a detection limit of 0.74 µM and a relatively broad linear range from 0-300 µM. After dispersing the composite Ag/Eu/CDs@UiO-66 in an Arg solution, the red emission of Eu3+ center at 613 nm was significantly enhanced, while the characteristic peak of CDs center at 440 nm remained unchanged. Therefore, a ratio fluorescence probe could be constructed based on the peak height ratio of the two emission peaks to achieve selective detection of Arg. In addition, the remarkable ratiometric luminescence response induced by Arg results in a significant color transition from blue to red under UV-lamp for Ag/Eu/CDs@UiO-66, which was convenient for visual analysis.

Unraveling the natural history of presymptomatic cystinuria.

PURPOSE OF REVIEW: Servais et al. recently published clinical practice recommendations for the care of cystinuria patients. However, these guidelines were largely based on retrospective data from adults and children presenting with stones. Significant questions remain about the natural history of cystinuria in presymptomatic children. RECENT FINDINGS: We review the natural history of cystinuria in presymptomatic children followed from birth. In total, 130 pediatric patients were assigned putative genotypes based on parental urinary phenotype: type A/A (N = 23), B/B (N = 6), and B/N (N = 101). Stones were identified in 12/130 (4% of A/A, 17% of B/B, and 1% of B/N patients). Type B/B patients had lower cystine excretion than type A/A patients. Although urine cystine/creatinine fell with age, urine cystine/l rose progressively in parallel with the risk of nephrolithiasis. Each new stone was preceded by 6-12 months of urine specific gravity of more than 1.020. However, average urine specific gravity and pH were not different in stone formers vs. nonstone formers, suggesting that intrinsic stone inhibitors or other unknown factors may be the strongest determinants of individual risk. SUMMARY: The current study reviews the clinical evolution of cystinuria in a cohort of children identified by newborn screening, who were categorized by urinary phenotype and followed from birth.

Entering into 2.0 cystinuric management with a medical digital tool to monitor urine pH: a prospective, randomized study.

BACKGROUND AND OBJECTIVES: Individuals with cystinuria can experiment recurrent lithiasis events due to the relative insolubility of cystine at physiological urine pH, resulting in renal function decline. The Lit-Control® pH Meter is a medical device that accurately allows urine pH self-monitoring. The main objective of this study was to compare the usability of the Lit-Control® pH Meter with the reactive strips for self-monitoring of urinary pH at home by patients with cystinuria, and their overall satisfaction with each tool. PATIENTS AND METHODS: We included 28 patients (9 females and 19 males, age 19-76 years), who were randomly assigned to monitor their urine pH with reactive strips (n = 17) or the Lit-Control® pH-meter (n = 11). RESULTS: After six months of use, the satisfaction with the two methods was similarly high, but the patients rated (0-10 scale) the pH meter better in terms of ease of learning (mean ±â€¯SD, 8.11 ±â€¯0.60 vs. 7.06 ±â€¯1.18; P = 0.038), ease to prepare (8.22 ±â€¯0.67 vs. 7.25 ±â€¯1.18; P = 0.034), and ease of use (8.22 ±â€¯0.67 vs. 7.25 ±â€¯1.39; P = 0.062). Overall, patients did not reach the alkalinization goals (pH between 7.0 and 8.0). CONCLUSIONS: The Lit-Control® pH Meter demonstrated to be an easy-to-use device that can facilitate urinary pH control by cystinuric patients. A prospective study is warranted to assess the correlation between urine pH monitoring, a treat to target approach, and the recurrence of cystine stones.

Evaluation of the value of genetic testing for cystinuria in the Danish population of English bulldogs.

Cystinuria is a genetic disease that can lead to cystine urolith formation. The English bulldog is the dog breed most frequently affected. In this breed, three missense mutations have been suggested to be associated with cystinuria: c.568A>G and c.2086A>G in SLC3A1 and c.649G>A in SLC7A9. In this study, the occurrence of these three mutations in the Danish population of English bulldogs was investigated. Seventy-one English bulldogs were genotyped using TaqMan assays. The dogs' owners were given questionnaires concerning the medical histories of their dogs. Allele frequencies of 0.40, 0.40, and 0.52 were found for the mutant alleles in the three loci: c.568A>G, c.2086A>G, and c.649G>A, respectively. For both mutations in SLC3A1, a statistically significant association was found between cystinuria and homozygosity for the G allele among male, English bulldogs. For the mutation in SLC7A9, there was no statistically significant association between homozygosity for the mutant allele and cystinuria. Due to high allele frequencies, limited genetic diversity, continued uncertainty about the genetic background of cystinuria, and more severe health problems in the breed, selection based on genetic testing for the mutations in SLC3A1 cannot be recommended in the Danish population of English bulldogs. However, results of the genetic test may be used as a guide to recommend prophylactic treatment.