Extracorporeal Shockwave Lithotripsy for Cystine Stones in Children: An Observational, Retrospective, Single-Center Analysis

Purpose: Cystinuria is a genetic disorder characterized by a defective reabsorption of cystine and dibasic amino acids leading to development of urinary tract calculi from childhood onward. Cystine lithiasis is known to be resistant to fragmentation. The aim was to evaluate our long-term experience with extracorporeal shockwave lithotripsy (ESWL) used as first-line urological treatment to treat cystine stones in children.Methods: We retrospectively reviewed the charts of all children who underwent ESWL for cystine stone. We assessed the 3-month stone-free rate, according to age, younger (group 1) or older (group 2) than 2 years old.Results: Between 2003 and 2016, 15 patients with a median (IQR) age at first treatment of 48 (15–108) months underwent ESWL in monotherapy. Median age was, respectively, 15 and 108 months in each group. The median (IQR) stone burden was 2,620 (1,202–8,265) mm3 in group I and 4,588 (2,039–5,427) mm3 in group II (p = 0.96). Eleven patients had bilateral calculi. ESWL was repeated on average 2.4 times, with a maximum of 4 for patients of group I, and 4.8 times, with a maximum of 9 for group II (p > 0.05). ESWL in monotherapy was significantly more efficient to reach stone-free status for children under 2 years of age: 83% vs. 6.2% (p = 0.040). The median (IQR) follow-up of the study was 69 (42–111) months.Conclusion: ESWL appears as a valid urological option for the treatment of cystine stones, in young children. Even if cystine stones are known to be resistant to fragmentation, we report 83% of stone-free status at 3 months with ESWL used in monotherapy in children under 2 years old with cystinuria. In older children, the success rate is too low to recommend ESWL as a first line approach.

Stone composition of renal stone formers from different global regions

Objective: To study urinary stone composition patterns in different populations around the world. Materials and methods: Data were collected by reviewing charts of 1204 adult patients of 10 countries with renal or ureteral stones (> 18 years) in whom a stone analysis was done and available. Any method of stone analysis was accepted, but the methodology had to be registered. Results: In total, we observed 710 (59%) patients with calcium oxalate, 31 (1%) with calcium phosphate, 161 (13%) with mixed calcium oxalate/calcium phosphate, 15 (1%) with carbapatite, 110 (9%) with uric acid, 7 (< 1%) with urate (ammonium or sodium), 100 (9%) with mixed with uric acid/ calcium oxalate, 56 (5%) with struvite and 14 (1%) with cystine stones. Calciumcontaining stones were the most common in all countries ranging from 43 to 91%. Oxalate stones were more common than phosphate or mixed phosphate/oxalate stones in most countries except Egypt and India. The rate of uric acid containing stones ranged from 4 to 34%, being higher in Egypt, India, Pakistan, Iraq, Poland and Bulgaria. Struvite stones occurred in less than 5% in all countries except India (23%) and Pakistan (16%). Cystine stones occurred in 1% of cases. Conclusions: The frequency of different types of urinary stones varies from country to country. Calcium-containing stones are prevalent in all countries. The frequency of uric acid containing stones seems to depend mainly on climatic factors, being higher in countries with desert or tropical climates. Dietary patterns can also lead to an increase in the frequency of uric acid containing stones in association with high obesity rates. Struvite stones are decreasing in most countries due to improved health conditions.

S-Methyl-L-Ergothioneine to L-Ergothioneine Ratio in Urine Is a Marker of Cystine Lithiasis in a Cystinuria Mouse Model

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.

Kidney Stone Composition in Various Country Around the World

To compare urinary stone composition patterns in different populations around the world in relation to the structure of their population, dietary habits, and climate. 1204 adult patients with urolithiasis and stone analysis was included . International websites were searched to obtain data. We observed 710(59%) patients with calcium oxalate, 31(1%) calcium phosphate, 161(13%) mixed calcium oxalate/calcium phosphate, 15(1%) carbapatite, 110(9%) uric acid, 7(<1%) urate, 100(9%) mixed uric acid/ calcium oxalate, 56(5%) struvite and 14(1%) cystine stones. Calcium stones were the most common in all countries (up to 91%) with the highest rates in Canada and China. Oxalate stones were more common than phosphate or mixed phosphate/oxalate stones except Egypt and India. The rate of uric acid stones, being higher in Egypt, India, Pakistan, Iraq, Poland, and Bulgaria. Struvite stones occurred in less than 5% except India (23%) and Pakistan (16%). Cystine stones occurred in 1%. The frequency of different types of urinary stones varies from country to country. Calcium stones are prevalent in all countries. Uric acid stones seems to depend mainly on climatic factors, being higher in countries with desert or tropical climates. Dietary patterns can also lead to an increase it. Struvite stones are decreasing in most countries.

The Long-Term Follow-Up of Patients with Cystine Stones: A Single-Center Experience for 13 Years

Introduction: Cystine stone development is relatively uncommon among patients with urolithiasis, and most studies have reported only on small sample sizes and short follow-up periods. We evaluated clinical courses and treatment outcomes of patients with cystine stones with long-term follow-up at our center. Methods: We retrospectively analyzed 22 patients diagnosed with cystine stones between January 1989 and May 2019. Results: The median follow-up was 160 (range 6–340) months, and the median patient age at diagnosis was 46 (range 12–82) years. All patients underwent surgical interventions at the first visit (4 extracorporeal shockwave lithotripsy, 5 ureteroscopy, and 13 percutaneous nephrolithotripsy). The median number of stone events and surgical interventions per year was 0.45 (range 0–2.6) and 0.19 (range 0–1.3) after initial surgical intervention. The median time to stone events and surgical intervention was 2 years and 3.25 years, respectively. There was a significant difference in time to stone events and second surgical intervention when patients were divided at 50 years of age at diagnosis (p = 0.02, 0.04, respectively). Conclusions: Only age at a diagnosis under 50 was significantly associated with recurrent stone events and intervention. Adequate follow-up and treatment are needed to manage patients with cystine stones safely.

Types of Renal Stones and its Variation with Age and Gender in a University Hospital of Nepal

Background Types of renal stones have profoundly changed in the last half-century, parallel to the change in lifestyle and dietary habit, with an increase of calcium stones. Among many lithogenic factors age and gender are considered to be associated with the types of renal stones. Studies evaluating the influence of age and gender on the distribution of the types of urinary calculi are scarce in Nepal. Objective To explore the influence of age and gender on different types of urolithiasis. Method This is a single center prospective study encompassing urolithiasis during a study period of 18 months. All the stone retrieved from the patients after surgery were sent for biochemical analysis of the stone. The result was then compared with the age and gender of the study population. Result Calculi from a total of 107 patients were analyzed (62 from males and 45 from females). Mixed stones consisting of calcium oxalate and calcium phosphate were the predominant constituent in 74.16% of stones, followed by uric acid, struvite and cystine stones. We found predominance of Calcium stones in males (47.66%) vs 36.44% in females and predominance of struvite stones in females (7.47%) vs 3.73% in males. Age group of 21-40 years has the main burden of stone. Conclusion Being aware and having better knowledge of risk factors, composition and correlation with age and gender can provide personalized guidance to prevention and avoid recurrence of urolithiasis.

Non-contrast computed tomography characteristics in a large cohort of cystinuria patients

Purpose Cystine stones are widely considered hard and difficult to treat. Hounsfield Units (HU) are used in other stone types to estimate ‘hardness’ and treatments based on that finding. Our objective was to report mean HU of cystine stones in vivo in a large case series of cystinuria patients and assess for differences in genotype. Methods A prospective case series of cystinuria patients referred to a specialist centre was analysed. CT imaging was assessed by two independent radiologists to determine in vivo attenuation of cystine calculi. Mean HU was compared for both cystinuria genes (SLC3A1 and SLC7A9) using an independent t-test. Results 164 adult cystinuric patients were identified (55% male), median age 43 years (range 18–80). Median follow up was 31 months (IQR 10–62). Genetic data available for 153/164 (93%) demonstrated 97 SLC3A1 (63%) and 55 (36%) SLC7A9 mutations (39 homozygous, 16 heterozygous) and one heterozygous for both SLC3A1/SLC7A9. 107 patients had CT images available demonstrating calculi. Median HU across the cohort was 633 (5th to 95th centile 328–780). There was no difference in mean HU between SLC3A1 and SLC7A9 genotypes (p = 0.68) or homo and heterozygous SLC7A9 (p = 0.70). Mean HU correlated with stone size (Pearson correlation coefficient = 0.51, p < 0.001). Conclusion In this large single centre cystinuria cohort, mean HU was low for stones that are difficult to treat. Calculi of < 800 HU should prompt consideration of a cystinuria diagnosis. Attenuation was not associated with genotype, and distinct ‘smooth’ and ‘rough’ stones were not observed. Calculi with HU > 1000 are unlikely pure cystine, and in a known cystinuric would suggest conversion to another stone type.

Intervention strategies for cystinuria: A systematic review

Purpose: This systematic review evaluates the current intervention strategies for cystinuria and assesses their quality and efficacy in order to determine the need to identify new and improved strategies for treatment. Materials and Methods: A literature search for interventions in cystinuria was conducted on key electronic databases for studies published between 1996 and 2019. Quality was assessed using Methodological Index for Non-Randomized Studies (MINORS). Studies meeting the inclusion criteria were assessed for study design, patient characteristics and outcomes of interventions, including urinary cystine levels, stone-free rate and stone recurrence rate. A qualitative and critical analysis was performed. Results: Common treatment strategies for cystinuria include hydration and diuresis, alkali therapy and thiol-based therapeutics. Conservative therapies such as adequate hydration and urinary alkalization effectively increased urinary pH, decreased urinary cystine levels and the formation of cystine stones. Second line agents reported included thiols such as Tiopronin, D-penicillamine and captopril. Non-invasive surgical procedures were found to reduce operative trauma and preserved renal function. Combined treatment approaches with hydration and thiols after surgical procedures were associated with less stones and reduced stone recurrence rates. Patient compliance to interventions was often poor and contributed to recurrent cystine stones. Conclusions: Despite existing pharmacological intervention strategies, cystinuria patients frequently require surgical procedures. A more detailed understanding of the mechanisms of pathogenesis of cystinuria as well as an evaluation of patients on an individual basis may be beneficial in reducing the severity of cystinuria, by reducing stone recurrence and associated renal complications.

Phytochemical screening, antioxidant and antilithiasis activities of Juncus acutus

The objective of this work was to perform a phytochemical screening of Juncus acutus and to evaluate its antioxidant activity and antilithiasis activity. Phytochemical screening has demonstrated the presence of catechin, tannins and alkaloids in the various extracts studied. The antioxidant activity of the methanolic and ethyl acetate extracts by ultrasound and maceration was evaluated by the method of DPPH, FRAP and phosphomolybdate. The ethyl acetate extract by ultrasound, the methanolic extract by maceration and ultrasound respectively showed IC 50 with DPPH of 1,449mg / ml, 1,535mg / ml and 4,771mg / ml and a reducing power was observed at concentrations of 419,561mgBHA /100g, 207,143mgBHA /100g and 142,20mgBHA /100g by FRAP and at concentrations of 839,470mgAAE/100g, 283,260mgAAE/100g and 141,018mgAAE/100g by the phosphomolybdate test. The determination of the total polyphenols of the ethyl acetate extract by ultrasound, the methanolic extract by maceration and by ultrasound presented respectively contents of 2,428 mg GAE / g, 1,960mg GAE / g and 1,172mg GAE / g, likewise, the flavonoid assay showed respectively concentrations of 14,469mg EQ/g, 6,466 mg EQ/g and 3,143 mg EQ/g. Antilithiasis activity was evaluated on carbapatite, cystine and uric acid stones. The mass loss of uric acid, carbapatite and cystine stones was respectively 42%, 7% and 16%.