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.

Spectrum of chemical analysis of 150 consecutive upper urinary tract stones with critical analysis in respect of demographic and geographical distribution

Background: The aim of the study was to evaluate the chemical composition of urinary stones and pattern of changes according to the patient's demographic and geographical distribution.Methods: 150 patients of upper tract urolithiasis were prospectively selected during the study period. Chemical composition was analyzed by FTIR spectroscopy. A subgroup study based on the patient's age, sex and geographical origin was done. For subgroup analysis patients were divided into two age groups; group A (5-18 years, 14 patients) and group B (>18 years, 136 patients). The geographical origin of the patients was recorded according to the administrative division.Results: Male were predominant in all age groups with ratio of 2.49:1. Most of the patients were from Rangpur (28.67%) and Mymensingh (20.67) division. Mixed composition stones were much more common than pure one (75.99% vs 24.01%). Overall, combination of calcium oxalate monohydrate with dehydrate was the most common composition (56.67%). Calcium oxalate was the predominant chemical composition in 82% of stones, followed by struvite in 9.33%, apatite in 4.67%, uric acid in 3.33% and cystine in 0.67%. The proportion of calcium oxalate stone was increasing while that of struvite, uric acid, and cystine stone was decreasing with age. But stone composition did not show any significant difference on geographical distribution.Conclusions: Calcium oxalate is the most common composition of urinary stones in all age groups. Mixed stones are more common than pure ones. The incidence of calcium oxalate stone increases while that of struvite, uric acid, and cystine stone decreases with age.

The Impact of Diet on Urinary Risk Factors for Cystine Stone Formation

Despite the importance of dietary management of cystinuria, data on the contribution of diet to urinary risk factors for cystine stone formation are limited. Studies on the physiological effects of diet on urinary cystine and cysteine excretion are lacking. Accordingly, 10 healthy men received three standardized diets for a period of five days each and collected daily 24 h urine. The Western-type diet (WD; 95 g/day protein) corresponded to usual dietary habits, whereas the mixed diet (MD; 65 g/day protein) and lacto-ovo-vegetarian diet (VD; 65 g/day protein) were calculated according to dietary reference intakes. With intake of the VD, urinary cystine and cysteine excretion decreased by 22 and 15%, respectively, compared to the WD, although the differences were not statistically significant. Urine pH was significantly highest on the VD. Regression analysis showed that urinary phosphate was significantly associated with cystine excretion, while urinary sulfate was a predictor of cysteine excretion. Neither urinary cystine nor cysteine excretion was affected by dietary sodium intake. A lacto-ovo-vegetarian diet is particularly suitable for the dietary treatment of cystinuria, since the additional alkali load may reduce the amount of required alkalizing agents.

Patient Experience: Living with Cystinuria During the COVID-19 Pandemic

Background and ObjectivesCystinuria is a rare genetic cause of recurrent urolithiasis and requires multimodal treatment, and stringent follow up. We wanted to evaluate the fears and concerns of patients with cystinuria during the COVID-19 pandemic. Materials and MethodsAn online survey using Google Forms was emailed to 165 patients with cystinuria who are maintained on a prospective database and had previously consented for email correspondence. ResultsFifty-five responses were received following a single invitation, 23 were men and 32 women with a median age of 43 (range: 18-72) years. Thirty-nine (70.9%) out of 55 were isolating during the COVID-19 pandemic although only 7(12.7%) were given specific advice to shield officially. Six (10.9%) reported having COVID or COVID like symptoms, but none reported having a positive test. Only 9 (16.4%) had been able to work as usual. In comparison, 20 (36.4%) were able to work from home. Ten out of 19 patients (52.6%) on chelating medication described difficulty in access to their medicine, either due to a shortage at the pharmacy or prescription access. Reassuringly 34 (61.8%) patients described no issues with access to any of their cystinuria medications.Twenty-two patients (40%) reported experiencing pain or passing a stone during the COVID-19 pandemic, while 30 (54.5%) reported no problems. Of patients who felt it applicable, 16/31 (51.6%) were worried about attending the Emergency Department during this time. Of patients who had scheduled hospital appointments during this time, 26/44 (59.1%) had experienced cancellations. The majority of the respondents (37 (67.3%)) did not state any difference in the ability to stay hydrated during the lockdown.Twenty-eight (50.9%) were more anxious about their overall health during the pandemic, and 20 (36.4%) had expressed more concern about their kidney stones. ConclusionThis personal fully patient-reported snapshot of the impact of the COVID-19 pandemic on a population of cystine stone formers in the United Kingdom has highlighted additional challenges for patients with a rare disease. The lockdown measures enforced have had a varying effect on patients’ ability to work as normal, access medications, health anxieties, in addition to cancellations of the planned hospital appointments and Emergency Department attendance, which will impact on their future health and pose evolving challenges in delivery of their future care.