Type 2 diabetes and uric acid stones: A powder neutron diffraction investigation

International audienceBackground: Recent epidemiologic investigations have identified an association between type 2 diabetes and uric acid kidney stones. This association was more apparent in women than in men. However, male patients are more prone than women to form uric acid stones in upper and lower urinary tract. In addition, uric acid stone morphology may be different according to stone location. Finally, it was shown that uric acid stone prevalence is increasing with the patient’s age. Aim of the study: To compare uric acid crystal size as determined by powder neutron diffraction with clinical data and the gender of patients. Material and methods: Uric acid stones from 43 patients (24 males, 19 females) identified by Fourier transform infrared spectroscopy were investigated using Environmental Scanning Electron Microscopy and Powder neutron diffraction.Results: Uric acid anhydrous was the main crystalline form of the stones. The mean size of the crystals was 91.3 ± 28.5 nm. No significant differences were found regarding uric acid crystal size in the stones by comparison to the stone location or the patient’s age. However, particle sizes of uric acid kidney stones were significantly different between male and female patients (84.7 ± 5.3 vs. 140.2 ± 6.7 nm, p < 0.000003) in the absence of diabetes mellitus. Interestingly, when type 2 diabetes appeared, this structural difference between male and female vanished (76.1 ± 3.9 vs. 78.8 ± 4.2 nm, not significant). Thus, the complete set of structural data is in line with observations regarding epidemiological data. Some explanations based on supersaturation are discussed

A Physiological Approach to Recurrent Nephrolithiasis and its Genetic Determinants

We report a case of a 63-year-old patient with recurrent nephrolithiasis for over 40 years and a significant family history of nephrolithiasis. The patient underwent full investigation at our department. He presented hypercalcemia, hypophosphatemia and hypercalciuria, with parathyroid hormone level in the normal range. A calcium load test and a fluorocholine PET-CT excluded primary hyperparathyroidism. Abnormal secretion of parathyroid hormone-related protein and sarcoidosis were also excluded. Genetic analysis showed mutations encoding for 25(OH)-vitamin D3-24-hydroxylase (CYP24A1) and Na-dependent phosphate cotransporter 2c (SLC34A3). This case affords insights into the biological pathways that underlie the role of genetic inheritance and accrued risk of development of nephrolithiasis.info:eu-repo/semantics/publishedVersio

From urolithiasis to pathological calcifications: A journey at the interface between physics, chemistry, and medicine. A tribute to Michel Daudon

International audienceMichel Daudon is a worldwide recognized biologist who performed several major breakthroughs in the field of urolithiasis. It is indeed difficult to address his outstanding personality and his great contributions to urolithiasis. Michel Daudon studied many aspects of urolithiasis, from urine crystals to kidney stone morphoconstitutional analysis. He is the author of more than 500 scientific articles on urolithiasis, and more generally on pathological calcifications, including several books and nice articles in the New England Journal of Medicine, The Lancet, Kidney International, among many others. Michel Daudon is not only a prolific writer; his broad fields of interests range from chemistry to biology or renal pathology, but also clinical bedside subjects explain his success and his attractive way of explaining pathophysiological processes. He has already given more than 300 lectures, in France as abroad

Chronic urine acidification by fludrocortisone to treat infectious kidney stones

Chronic urinary tract infections by urease-producing bacteria may increase urine pH and promote thereby the formation of recurrent kidney stones made of highly carbonated calcium phosphate apatite and struvite, a magnesium ammonium phosphate. To date, there is no safe and effective treatment decreasing urine pH on a long term. We hypothesized that fludrocortisone, a mineralocorticoid, would decrease urine pH by increasing proton secretion in the kidney collecting tubule. We report three cases of patients with kidney stone suffering from chronic urinary infection by urease-producing germs, treated by fludrocortisone on a long term. Urine pH decreased sustainably over several months and tolerance was good

Chronic urine acidification by fludrocortisone to treat infectious kidney stones

Chronic urinary tract infections by urease-producing bacteria may increase urine pH and promote thereby the formation of recurrent kidney stones made of highly carbonated calcium phosphate apatite and struvite, a magnesium ammonium phosphate. To date, there is no safe and effective treatment decreasing urine pH on a long term. We hypothesized that fludrocortisone, a mineralocorticoid, would decrease urine pH by increasing proton secretion in the kidney collecting tubule. We report three cases of patients with kidney stone suffering from chronic urinary infection by urease-producing germs, treated by fludrocortisone on a long term. Urine pH decreased sustainably over several months and tolerance was good

Foreword to microcrystalline pathologies: combining clinical activity and fundamental research at the nanoscale

This contribution underlines the key role of physicochemical characterisation techniques in the area of medical research. The starting point centres on the Mid-InfraRed platform located at the Tenon hospital and dedicated to multidisciplinary functional investigations. In the last two decades, we have enhanced this platform by creating a network combining researchers from varied disciplines such as physicists, chemists, and clinicians. The resultant research dynamism is underscored by metrics such as 71 references in Pubmed and 129 in Web of Science, and the high impact of the journals in which we have published (New England Journal of Medicine, Kidney International, Chemical Review...). It is of paramount importance to disseminate these physicochemical techniques among young doctors, and to establish collaborations with appropriate private companies

Foreword to microcrystalline pathologies: combining clinical activity and fundamental research at the nanoscale

This contribution underlines the key role of physicochemical characterisation techniques in the area of medical research. The starting point centres on the Mid-InfraRed platform located at the Tenon hospital and dedicated to multidisciplinary functional investigations. In the last two decades, we have enhanced this platform by creating a network combining researchers from varied disciplines such as physicists, chemists, and clinicians. The resultant research dynamism is underscored by metrics such as 71 references in Pubmed and 129 in Web of Science, and the high impact of the journals in which we have published (New England Journal of Medicine, Kidney International, Chemical Review...). It is of paramount importance to disseminate these physicochemical techniques among young doctors, and to establish collaborations with appropriate private companies

Crystal size in μ\mu crystalline pathologies and its clinical implication

International audienc

Vitamin D and Calcium Supplementation Accelerates Randall&#039;s Plaque Formation in a Murine Model

Most kidney stones are made of calcium oxalate crystals. Randall\u27s plaque, an apatite deposit at the tip of the renal papilla, is considered to at the origin of these stones. Hypercalciuria may promote Randall\u27s plaque formation and growth. We analyzed whether long-term exposure of Abcc6 mice (a murine model of Randall\u27s plaque) to vitamin D supplementation, with or without a calcium-rich diet, would accelerate the formation of Randall\u27s plaque. Eight groups of mice (including Abcc6 and wild type) received vitamin D alone (100,000 UI/kg every 2 weeks), a calcium-enriched diet alone (calcium gluconate 2 g/L in drinking water), both vitamin D supplementation and a calcium-rich diet, or a standard diet (controls) for 6 months. Kidney calcifications were assessed by 3-dimensional microcomputed tomography, μ-Fourier transform infrared spectroscopy, field emission-scanning electron microscopy, transmission electron microscopy, and Yasue staining. At 6 months, Abcc6 mice exposed to vitamin D and calcium supplementation developed massive Randall\u27s plaque when compared with control Abcc6 mice (P &lt; 0.01). Wild-type animals did not develop significant calcifications when exposed to vitamin D. Combined administration of vitamin D and calcium significantly accelerates Randall\u27s plaque formation in a murine model. This original model raises concerns about the cumulative risk of vitamin D supplementation and calcium intakes in Randall\u27s plaque formation

“Trust my morphology”, the key message from a kidney stone

International audienceThe Consensus Conference Group recently published an article in Urolithiasis highlighting the importance of urine and stone analysis in the metabolic evaluation of kidney stone formers (KSF) [1]. Indeed, each kidney stone contains the imprints of the conditions which created them during their 'lifetime in the kidney'. The morpho-constitutional classification method (MCC) established by Prof Michel Daudon correlates the morphological characteristics of stones with specific metabolic disorders [2]. Briefly, it distinguishes 7 types and 21 subtypes according to the crystalline composition and shape, color and structure of stones identified using an optical stereomicroscope (Table 1). This very specific method is easy to learn and provides the opportunity to quickly identify highly recurrent diseases, sometimes serious in their clinical consequences. Indeed, subtypes Ic, Ie, IIId, IVa2 and