After being metabolized in the liver, theobromine and its metabolites are excreted in urine, mainly as 7-methylxanthine (36%), theobromine (21%), 3-methylxanthine (21%), and 3,7-dimethyluric acid (1.3%). Gout’s principal feature is monosodium urate crystalline formation within the joints. The authors aimed to evaluate the effect of methylxanthines and uric acid derivatives in the monosodium urate crystallization in a research laboratory setting. As 7-methylxanthine decreased or completely avoided monosodium crystal formation, they concluded that theobromine intake to prevent uric acid stone formation could also inhibit or decrease monosodium urate crystallization in patients with gout by means of its metabolite 7-methylxanthine.

Both spontaneous (homogeneous) and heterogeneous nucleation of cystine crystals is difficult and high supersaturations are needed for its crystallization in urine. Cystine in vitro crystallization by turbidimetry and the effect of several substances including captopril, N-acetyl-cysteine, D-penicillamine, and thiosulfate were evaluated studying micro and macro-structure of 30 cystine kidney stones from 6 different patients. To avoid cystine formation it is necessary to combine it with substances as the aforementioned to decrease cystine supersaturation. D-penicillamine, captopril, and N-acetyl-cysteine complexed with cystine preventing from cystine crystallization. Thiosulfate transformed cystine into cysteine by disulfide bond oxidation. It is inferred that the use of N-acetyl-cysteine, a cheap drug, and free from significant side effects, could be used as a potential treatment for inhibiting cystine supersaturation.

Dr. Bahilo skillfully moderated this round table composed by experts in different specialties related to kidney stones. Scheduled committee meetings including committed endocrinologists, laboratory experts, nephrologists, microbiologists, case management nurses, and urologists would be advisable at urolithiasis units, at least in those reference centers. Proper stratification of stone patients depending on the severity of the disease is mandatory. For those recurrent or highly recurrent patients a primary or secondary hyperparathyroidism should be ruled out, as should be cases of RTA and other diseases with possible genetic origin in which genetic counseling could be advised. Of note is the importance of the so-called pre-analytical phase whenever a metabolic evaluation is performed for comprehensive medical management of the stone patients. Proper collection of blood and urine samples are key.

The microbiologic study both in urine and stones can be determinant in certain patients and gene sequencing techniques are now allowing to detect urine microbiota otherwise not suspected. Tele-mentoring and follow-up is also important especially either for those recurrent patients not needing frequent in person visits to the hospital and to remind medication and diet measures.

There’s no doubt that AI is going to star the following years in many fields with technologies such as myLit-Control App, including stone disease. It’s range of applications is huge, and of course affects both diagnostic and management of urolithiasis. Regarding to endourology and radio-diagnostic or radiomics, studies have already been conducted to predict spontaneous passage of ureteral stones, where artificial neural networks showed high performance in the estimation of stone passage rate (99.16%), to differentiate stones from phleboliths (accuracy rate 85% in renal and 97% in ureteral stones using non-contrast computed tomography scans), and to identify different types of stones (85% to 91%). When it comes to evaluating stone disease it can predict the stone free rate depending on the stone load and the endoscopic surgical technique employed for treatment (92 – 94%), the optimal fragmentation, retreatment rate (82-97%), renal damage, stone re-growth, JJ stent need (85%), and transfusion rate (95%).

Telemedicine, and interdisciplinary synergia, as well as formation with the endpoint of improving in certain aspects of different technologies or techniques (i.e. kidney puncture) are other applications of IA. It’s near future will probably include 3-dimensional models and virtual reality.

Devicare organized the 4th Edition of the Clinical Case Competition related to the non-surgical clinical management of Renal Lithiasis. Dra. Carmina Muñoz from the Clínica Universidad de Navarra was the winner of the competition whose prize is the registration to the EAU Congress 2024 with flight and accommodation included. The winner case titled “Recurrent prostatic cell encrusting lithiasis after Holmium laser enucleation of the prostate (HoLEP). Gradual resolution with urinary pH acidification” highlighted for its complexity and innovation using both Lit-Control® pH Down, Lit-Control® pH Meter and myLit-Control App, in an edition that broke a new record of participation with 17 cases presented. During the event, it was also announced that the next edition of the competition, which will be international for the first time, opened its convocation on 1 February of 2024.

Innovations in pharmacotherapy for stone disease are not comparable to those of technology or techniques for surgical treatment despite recurrent symptomatic kidney stone formers are at increased risk for chronic kidney disease. In the last years, three “new” medical treatments are impacting in stone disease.

First, Lumasiran, for Type 1 primary hyperoxaluria (PHO) due to AGT (alanine glyoxylate-aminotransferase enzime) deficiency. Lumasiran is a mRNA interference treatment that blocks the glycolate oxidase preventing the glyoxylate formation from glycolate, and consequently oxalate does not form from glyoxylate. Recently, a phase III trial (Illuminate-A) showed a reduction of oxalate both in 24-hours urine excretion of oxalate and plasma concentrations of oxalate after injection of Lumasiran, with similar side effects when compared to placebo, with only related to injection-site reactions in the intervention group.

Second, the phytate, phytic acid or Inositol hexaphosphate (IP6) is a well known inhibitor of stone disease, as diet rich in phytate is associated with a reduction in the risk of kidney stones. It has a triple anti-lithogenic effect in vitro: on the supersaturation, crystal formation and growth of calcium oxalate.

Third, theobromine, present in cocoa and chocolate acts as a uric acid crystallization inhibitor, with high clinical potential in the treatment and prevention of uric acid nephrolithiasis. It’s combination in one same formulation with urine citrate achieves a synergistic effect superior to the sum of the effects of each component separately (x12) and has also been used for uric acid stones dissolution.

Urinary pH in humans shows a circadian rhythm and can be affected by different situations including diet, drugs, stress, gender, and genetic and metabolic diseases. Apart from the balance between urinary stone promoters and inhibitors, both the time that the urine is within the urinary tract, and the urine pH are needed for a stone to form.

A high urine pH (>6.2), independent of diet, and hypocitraturia are the most important risk factors for calcium phosphate stones, especially in women. Fasting urine pH >5.8 non-responding to acidification, associated to hypercalciuria, and hypocitraturia, as well as the presence of apatite or brushite stones should direct suspicion to incomplete distal RTA. Low urine pH (<5.5) together with low urine volume and high uric acid (UA) osmolality will lead to UA stone formation. Cystine is highly soluble at urine pH higher than 7.5. The only stones that seem independent of urine pH are papillary calcium oxalate monohydrate (COM) and 2.8 dihydroxyadenine. Urine pH should be properly measured with laboratory pH meters, preferably within two hours of collection and after 12 hours fasting, or else with a digital pH meter (Lit-Control® pH Meter) several times a day (fasting, and after meals).

A correct pH measurement will allow to treat and monitor the patient with prophylactic alkalizing drugs (potassium citrate, sodium bicarbonate) and/or preventing UA stone formation or increasing its dissolution with theobromine, and/or decreasing UA in urine with allopurinol/febuxostat. Urine acidification can be achieved by using L-methionine and or ammonium chloride. Phytate is the correct choice for kidney stones prevention whenever pH is neutral.

The ESD Congress concluded with a symposium on the results of the Lit-Study: a cross-sectional online survey on the management of kidney stones in Spain and Jordan.

During this event, the results of the study were presented and compared in both countries, and it was offered the possibility of replicating the study in other interested countries by contacting medicalaffairs@devicare.com.

This study makes it possible to know the reality of the clinical practice of urologists in the medical management of kidney stones, to understand the problems involved and to find and offer a better solution to patients.