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Abstract Cotrimoxazole (Trimethoprim/Sulfamethoxazole-SMX) is frequently used in critically ill and immunocompromised patients. SMX is converted to N-acetyl-sulfamethoxazole (NASM) and excreted by the kidneys. NASM may form crystals in urine, especially in acid urine, that may induce a crystalline nephropathy. However, the imputability of crystals in acute kidney injury (AKI) has not been proven. We aimed to assess whether NASM crystals may promote AKI and to investigate risk factors associated with NASM crystalline nephropathy. Patients from Ile-de-France, France who developed AKI under SMX treatment introduced during hospitalization and had a crystalluria positive for NASM crystals were selected. Patients with excessive preanalytical delay for crystalluria or missing data regarding SMX treatment were excluded. We used the Naranjo score to assess the causal relationship between SMX and the development of AKI in patients with positive NASM crystalluria. Fourteen patients were included. SMX was the probable cause of AKI for 11 patients and a possible cause for 3 patients according to Naranjo score. Patients were exposed to high doses of SMX (but within recommended ranges), and most of them had a preexisting chronic kidney disease and were hypoalbuminemic. Urine pH was mildly acid (median 5.9). AKI occured more rapidly than expected after introduction of SMX (median 4 days) and recovered rapidly after drug discontinuation in most, but not all, cases. SMX is a probable cause of crystalline nephropathy. Monitoring of crystalluria in patients exposed to SMX may be of interest to prevent the development of crystalline nephropathy. Approval number of the study: BPD-2018-DIAG-008.

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.

Renal oxalosis is a rare cause of renal failure whose diagnosis can be challenging. Synchrotron deep ultraviolet (UV) fluorescence was assayed to improve oxalosis detection on kidney biopsies spatial resolution and sensitivity compared with the Fourier transform infrared microspectroscopy gold standard. The fluorescence spectrum of synthetic mono-, di- and tri-hydrated calcium oxalate was investigated using a microspectrometer coupled to the synchrotron UV beamline DISCO, Synchrotron SOLEIL, France. The obtained spectra were used to detect oxalocalcic crystals in a case control study of 42 human kidney biopsies including 19 renal oxalosis due to primary (PHO, n = 11) and secondary hyperoxaluria (SHO, n = 8), seven samples from PHO patients who received combined kidney and liver transplants, and 16 controls. For all oxalocalcic hydrates samples, a fluorescence signal is detected at 420 nm. These spectra were used to identify standard oxalocalcic crystals in patients with PHO or SHO. They also revealed micrometric crystallites as well as non-aggregated oxalate accumulation in tubular cells. A nine-points histological score was established for the diagnosis of renal oxalosis with 100% specificity (76–100) and a 73% sensitivity (43–90). Oxalate tubular accumulation and higher histological score were correlated to lower estimated glomerular filtration rate and higher urinary oxalate over creatinine ratio.

Introduction The therapy to reduce urinary oxalate excretion in primary hyperoxaluria type 1 is still required. Case presentation A 37‐year‐old hemodialyzed man suffered from systemic oxalosis secondary to primary hyperoxaluria type 1 exhibited a drastic plasma oxalate decrease from 110 to 22 µmol/L two months after adjunction of lanthanum carbonate to classical treatment (intensive hemodialysis with pyridoxine). A 34‐year‐old woman with normal kidney function presented 10 years of bilateral kidney stones due to primary hyperoxaluria type 1 [hyperoxaluria (109.2 mg/24 h), plasma oxalate (56.0 µmol/L)]. The oxalate level remained uncontrolled despite of low oxalate‐normal calcium diet, pyridoxine and increased water intake though the lanthanum carbonate adjunction resulted in significant decrease in plasma oxalate and oxaluria. Conclusion We report the lanthanum efficacy in reducing circulating and urinary oxalate levels in type 1 primary hyperoxaluria. Possible mechanism of observed falls in oxalate concentration would be a decrease in the intestinal absorption of oxalate.

Abstract Background The Democratic Republic of Congo has been a country of intensive mining activities for centuries, but the data on the presence of heavy metals in stones are lacking. This study aimed to identify different heavy metals in urinary tract stones and to investigate their association with the main components of urinary stones. Methods Thirty-six stones from urolithiasis patients (n = 36) followed in 10 hospitals in the Democratic Republic of Congo between January 2016 and September 2019 were analyzed by Fourier transform infrared spectrophotometry. Further analysis using X-ray fluorescence was conducted at the Laboratory of Solids Physics. Results Eight heavy metals were detected in all the stones analyzed. The average (SD) number of heavy metals detected by stone was 5 (1.2). Iron and strontium were detected in all the stones analyzed. Other heavy metals detected included zinc, copper, bromine, rubidium, lead and nickel. Rubidium had the highest concentration in the stones regardless of the sampling site. There was no statistically significant association between the content of heavy metals at the center level and at the crown level of the stones. Rubidium had more affinity with phosphates and purines (p ˂ 0.001). Iron and strontium exhibited a high affinity with weddellite than with whewellite. Conclusion Iron and Strontium were present in all stones analyzed. The presence of heavy metals in stones analyzed might suggest environmental pollution rather than crystalline induction factors.

Abstract Background Urolithiasis is increasingly diagnosed worldwide. Stone analysis is an important part in the assessment of patients with urolithiasis. However, in sub-Saharan Africa, data on the composition of urinary stones are limited. This study aimed to describe the composition and sites of urinary stones and to investigate relationship between socio-demographic characteristics, clinical profile of patients, and the composition of urinary stones. Methods A retrospective analysis of 132 patients with urolithiasis who visited one of the seven hospitals in the Democratic Republic of Congo during eight years of study period (January 2010 to January 2018) was conducted. Stones were analyzed by infrared spectrophotometry. Results Most of stones analyzed (n = 82, 62.1%) originated from the upper urinary tract with a difference across gender (58.5% males vs. 41.5% females, p = 0.001). Only three stones (two from whewellite and one from anhydrous uric acid) were considered pure (2.3%), excluding the protein frame (less than 5%). Whewellite, proteins, and carbapatite were identified in 97.7%, 96.2%, and 80.3% of the stones analyzed, respectively; and in 91.7%, 89.4%, and 67.7% of the nuclei of the stones analyzed, respectively. Taking into account the proportion of each constituent in the stones analyzed, whewellite (68.9%), anhydrous uric acid (10.6%), and carbapatite (8.3%) were the main constituents in respectively 68, 9%, 10.6%, and 8.3% of the stones analyzed. Conclusion Whewellite, anhydrous uric acid, and carbapatite represented the most frequent main components of stones identified, suggesting that dietary hyperoxaluria could be an important factor in lithogenesis in the Democratic Republic of Congo.

Maintenance of hydration status requires a tight balance between fluid input and output. An increase in water loss or a decrease in fluid intake is responsible for dehydration status, leading to kidney water reabsorption. Thus, urine volume decreases and concentration of the different solutes increases. Urine dilution is the main recommendation to prevent kidney stone recurrence. Monitoring hydration status and urine dilution is key to preventing stone recurrence. This monitoring could either be performed via spot urine or 24 h urine collection with corresponding interpretation criteria. In laboratory conditions, urine osmolality measurement is the best tool to evaluate urine dilution, with less interference than urine-specific gravity measurement. However, this evaluation is only available during time lab examination. To improve urine dilution in nephrolithiasis patients in daily life, such monitoring should also be available at home. Urine color is of poor interest, but reagent strips with urine-specific gravity estimation are currently the only available tool, even with well-known interferences. Finally, at home, fluid intake monitoring could be an alternative to urine dilution monitoring. Eventually, the use of a connected device seems to be the most promising solution.

Stone analysis by physical methods is critical to determine their chemical nature and to diagnose the underlying conditions affecting kidney stone formers. This analysis should be completed by a morphologic examination of stone surface and section, leading to the diagnosis of anatomical or metabolic disorders and of specific diseases. Crystalluria study, the analysis of urine crystals, provides complementary information and is extremely useful for both diagnosis and patient follow-up. This review describes briefly how these techniques may be used and in which conditions stone morphology and urine crystal description are particularly relevant for patients medical care.

The proper management of cetacean populations requires life history and demographic parameters to be estimated at population level. In this study we focus on a reproductive pathology that has the potential to alter reproductive rate: the vaginal calculi or stones. The present work documents vaginal calculi prevalence and structure in the eastern North Atlantic common dolphin Delphinus delphis in order to infer their likely mechanisms of induction and possible effects on fecundity. The work is based on routine examinations and necropsies of stranded marine mammals reported by the French stranding scheme from 1972 to 2012. Vaginal calculi were described and measured, and their composition was analyzed by Fourrier-Transformed Infra-Red (FTIR) spectroscopy. Necropsies and reproductive tract examinations were performed on 435 female common dolphins since 1972 along the French coasts, of which 14 showed vaginal calculi, representing 3.2% of the examined females. All females with calculi were older than 7, and there was no relationship of calculus size with age. Histopathology revealed lesions due to an inflammatory response to the presence of the calculi: chronicle vaginitis, variable endometritis and cystitis. Calculus size varied from 1 to 21 cm in maximum dimension and 4–1,460 g in mass. Their internal structure was homogeneous, particularly due to the absence of core material, hence corresponding to the definition of primary calculi. All calculus spectra showed almost identical compositions, with struvite (magnesium ammonium phosphate hexahydrate) representing on average 87% of calculus mass. Dysfunction of the uro-genital tract, such as vesico-vaginal fistulae, would be the likely initial pathological condition that led to the formation of these stones. Both the initial chemical condition in the vagina and the resulting formation of a calculi are obstacles to successful reproduction.

Arterial calcification is a common feature of pseudoxanthoma elasticum (PXE), a disease characterized by ABCC6 mutations, inducing a deficiency in pyrophosphate, a key inhibitor of calcium phosphate crystallization in arteries. Methods: we analyzed whether long-term exposure of Abcc6−/− mice (a murine model of PXE) to a mild vitamin D supplementation, with or without calcium, would impact the development of vascular calcification. Eight groups of mice (including Abcc6−/− and wild-type) received vitamin D supplementation every 2 weeks, a calcium-enriched diet alone (calcium in drinking water), both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Aorta and kidney artery calcification was assessed by 3D-micro-computed tomography, Optical PhotoThermal IR (OPTIR) spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) and Yasue staining. Results: at 6 months, although vitamin D and/or calcium did not significantly increase serum calcium levels, vitamin D and calcium supplementation significantly worsened aorta and renal artery calcification in Abcc6−/− mice. Conclusions: vitamin D and/or calcium supplementation accelerate vascular calcification in a murine model of PXE. These results sound a warning regarding the use of these supplementations in PXE patients and, to a larger extent, patients with low systemic pyrophosphate levels.

Abstract Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation.

Limiting gastrointestinal oxalate absorption is a promising approach to reduce urinary oxalate excretion in patients with idiopathic and enteric hyperoxaluria. Phosphate binders, that inhibit gastrointestinal absorption of dietary phosphate by the formation of easily excretable insoluble complexes, are commonly used as a treatment for hyperphosphatemia in patients with end-stage renal disease. Several of these commercially available phosphate binders also have affinity for oxalate. In this work, a series of metallic cations (Li+, Na+, Mg2+, Ca2+, Fe2+, Cu2+, Zn2+, Al3+, Fe3+ and La3+) is investigated on their binding affinity to phosphate and oxalate on one side and anionic species that could be used to administer the cationic species to the body on the other, e.g., acetate, carbonate, chloride, citrate, formate, hydroxide and sulphate. Through quantum chemical calculations, the aim is to understand the competition between the different complexes and propose possible new and more efficient phosphate and oxalate binders.

Research on pathological calcifications constitutes an exciting topic at the interface between physics, chemistry and medicine. The relationship between their physicochemical characteristics and the pathology responsible for their formation offers a unique opportunity to perform a significant medical diagnosis, to assess the interaction between drugs and these biological entities as well as to develop new drugs. Regarding synchrotron radiation, the emergence of microbeam allows the clinician to perform an early diagnosis. Indeed, we will start this review with a clinical case where Fourier transform infrared spectroscopy using synchrotron radiation as a probe allowed the clinician to save the kidney function of a patient. Following this example, we will see that investigations on pathological calcifications constitute an elegant way to gather major information on different public health problems such type 2 diabetes as well as on rare diseases. To attain this goal, this mini-review dedicated to structural and chemical investigations and based on selected and recent data collected through techniques using third generation synchrotron radiation as a probe is proposed to the reader.

Thyroid calcification is frequent in thyroid nodules. The aim of our study was to evaluate the prevalence of calcifications in thyroid tissue samples of patients with various thyroid diseases, and to identify their composition according to their localization. Among 50 thyroid samples included, 56% were malignant (papillary carcinoma) and 44% were benign (adenoma, multinodular goiter, Graves' disease, sarcoidosis). Calcifications were found in 95% of samples using polarised light microscopy, whereas only 12% were described in initial pathological reports. Three types were individualised and analyzed by infrared spectrometry (μFTIR): colloid calcifications composed of calcium oxalate, capsular calcifications and psammoma bodies, both composed of calcium phosphate. Of notice, psammoma bodies characterized by FE-SEM were composed of concentric structure suggesting a slow process for crystal deposition. Calcium phosphates were found only in malignant samples whereas calcium oxalate was not associated with a define pathology. Proliferation assessed by KI67 staining was high (33% of positive follicles), and RUNX2, OPN, and CD44 positive staining were detected in thyrocytes with a broad variation between samples. However, thyrocyte proliferation and differentiation markers were not associated with the number of crystals. TRPV5 and CaSR expression was also detected in thyrocytes. mRNA transcripts expression was confirmed in a subgroup of 10 patients, altogether with other calcium transporters such as PMCA1 or Cav1.3. Interestingly, TRPV5 mRNA expression was significantly associated with number of colloid calcifications (rho = -0.72; p = 0.02). The high prevalence of calcium oxalate crystals within colloid gel raises intriguing issues upon follicle physiology for calcium and oxalate transport.

Dietary management is a cornerstone of Chronic Kidney Disease (CKD) monitoring, and dietary surveys often difficult to perform. We studied in a CKD patient cohort with two years follow-up, whether validated 24-h urine ionogram would be a relevant tool for diet evaluation and compliance. We included 404 non-dialysis CKD patients, with three evaluations, including repeated measurements of fractional renal creatinine clearance and 24-h urine collection. Completeness of the 24-h urine collection, assessed by daily urine creatinine excretion extrapolated from fractional creatinine clearance, was 64.6%, 75.5%, and 78.2% at the first, second, and third visits, respectively. One hundred sixty-eight patients (41.6%) had three complete collections, with a measured glomerular filtration of 42.3 mL/min/1.73 m2 at baseline and prevalence of anemia and secondary hyperparathyroidism of 13.9% and 26.2%, respectively, increasing during follow-up to 15% and 31.5% (p < 0.001 and p < 0.001). The urine analysis showed at baseline a urine volume of above 2 L/day, and estimated sodium and protein intake within targets in 51.6% and 40.3% of cases, which improved during follow-up only for protein (to 45.9%, p < 0.0001). Our data suggest that a 24-h urine ionogram is an interesting, reliable tool in CKD patients for dietary monitoring to achieve target recommendation noteworthy salt and protein intake.

Green tea is widely used as a ‘’healthy’’ beverage due to its high level of antioxidant polyphenol compounds. However tea is also known to contain significant amount of oxalate. The objective was to determine, in a cross-sectional observational study among a population of 273 hypercalciuric stone-formers referred to our center for metabolic evaluation, whether daily green tea drinkers (n = 41) experienced increased stone risk factors (especially for oxalate) compared to non-drinkers. Stone risk factors and stone composition were analyzed according to green tea status and sex. In 24-h urine collection, the comparison between green tea drinkers and non-drinkers showed no difference for stone risk factors such as urine oxalate, calcium, urate, citrate, and pH. In females, the prevalence of calcium oxalate dihydrate (COD) and calcium phosphate stones, assessed by infrared analysis (IRS) was similar between green tea drinkers and non-drinkers, whereas prevalence of calcium oxalate monohydrate (COM) stones was strikingly decreased in green tea drinkers (0% vs. 42%, p = 0.04), with data in accordance with a decreased oxalate supersaturation index. In males, stone composition and supersaturation indexes were similar between the two groups. Our data show no evidence for increased stone risk factors or oxalate-dependent stones in daily green tea drinkers.

After stone removal, accurate analysis of urinary stone composition is the most crucial laboratory diagnostic procedure for the treatment and recurrence prevention in the stone-forming patient. The most common techniques for routine analysis of stones are infrared spectroscopy, X-ray diffraction and chemical analysis. The aim of the present study was to assess the quality of urinary stone analysis of laboratories in Europe. Nine laboratories from eight European countries participated in six quality control surveys for urinary calculi analyses of the Reference Institute for Bioanalytics, Bonn, Germany, between 2010 and 2014. Each participant received the same blinded test samples for stone analysis. A total of 24 samples, comprising pure substances and mixtures of two or three components, were analysed. The evaluation of the quality of the laboratory in the present study was based on the attainment of 75% of the maximum total points, i.e. 99 points. The methods of stone analysis used were infrared spectroscopy (n = 7), chemical analysis (n = 1) and X-ray diffraction (n = 1). In the present study only 56% of the laboratories, four using infrared spectroscopy and one using X-ray diffraction, fulfilled the quality requirements. According to the current standard, chemical analysis is considered to be insufficient for stone analysis, whereas infrared spectroscopy or X-ray diffraction is mandatory. However, the poor results of infrared spectroscopy highlight the importance of equipment, reference spectra and qualification of the staff for an accurate analysis of stone composition. Regular quality control is essential in carrying out routine stone analysis.

The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption—as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements.

Purpose of review: To provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients. Source of information: Pubmed literature search. Setting: Primary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria) that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD) and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation. Key messages: Patients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis). We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR) and a history of kidney stones. In APRT deficiency, stones may be confused with uric acid stones, unless specialized techniques are used (infrared spectroscopy or X-ray crystallography for urinary crystals or stone analysis; Fourier transform infrared microscopy for crystals in kidney biopsy). Where these are unavailable, and for confirmation, the diagnosis can be made by measurement of enzyme activity in red blood cell lysates or by genetic testing. In patients with primary hyperoxaluria, levels of urinary and plasma oxalate; and the presence of nearly pure calcium oxalate monohydrate in stones, which often also have an unusually pale colour and unorganized structure, increase diagnostic suspicion. Molecular genetic testing is the criterion measure. Lifelong allopurinol therapy, with high fluid intake if appropriate, may stabilize kidney function in APRT deficiency; if ESRD has occurred or is near, results with kidney transplantation after initiation of allopurinol are excellent. In primary hyperoxaluria recognized before ESRD, pyridoxine treatment and high fluid intake may lead to a substantial decrease in urinary calcium oxalate supersaturation and prevent renal failure. In non-responsive patients or those recognized later in their disease, liver transplantation cures the underlying defect and should be considered when the GFR falls below 30 ml/min/1.73 m 2 ; in those which or near ESRD, liver transplantation and intensive dialysis before kidney transplantation may be considered to reduce the total body oxalate burden before kidney transplantation. Limitations: The availability of diagnostic tests varies between countries and centres. Data on long term outcomes after kidney transplantation are limited, especially for APRT deficiency patients. Implications: Increasing transplant physicians knowledge of APRT deficiency and primary hyperoxaluria should enable them to implement adequate diagnostic and therapeutic interventions, thereby achieving good outcomes after kidney transplantation.

OBJECTIVES: Clinical features and risk factors for atazanavir (ATV)-associated urolithiasis have not been fully investigated. METHODS: We reviewed all cases of ATV-containing urolithiasis identified by infrared spectrophotometry among HIV-infected patients over a 5-year period to describe their clinical features and outcome. A case-control study was performed to identify risk factors associated with ATV-associated urolithiasis using univariate and multivariate logistic regression analyses. RESULTS: 30 cases of ATV-associated urolithiasis were analyzed. Patients were mostly men (87%), median age: 45.5 years, median CD4 cell count: 443 cells/µL and 97% had plasma HIV RNA level

Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile similar to that of patients with cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice, 129S2/SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the tetrameric transporter of dibasic amino acids was absent in proximal tubules and we identified a single pathogenic mutation in a highly conserved region of the Slc3a1 gene. This novel mouse model mimicking human disease would allow us further pathophysiological studies and may be useful to analyse the crystal/tissue interactions in cystinuria.

Backgroundbasic calcium phosphate (BCP) crystals are commonly found in osteoarthritis (OA) and are associated with cartilage destruction. BCP crystals induce in vitro catabolic responses with the production of metalloproteases and inflammatory cytokines such as interleukin-1 (IL-1). In vivo, IL-1 production induced by BCP crystals is both dependant and independent of NLRP3 inflammasome. We aimed to clarify 1/ the role of BCP crystals in cartilage destruction and 2/ the role of IL-1 and NLRP3 inflammasome in cartilage degradation related to BCP crystals.Methodology principal findingssynovial membranes isolated from OA knees were analysed by alizarin Red and FTIR. Pyrogen free BCP crystals were injected into right knees of WT, NLRP3 -/-, ASC -/-, IL-1α -/- and IL-1β-/- mice and PBS was injected into left knees. To assess the role of IL-1, WT mice were treated by intra-peritoneal injections of anakinra, the IL-1Ra recombinant protein, or PBS. Articular destruction was studied at d4, d17 and d30 assessing synovial inflammation, proteoglycan loss and chondrocyte apoptosis. BCP crystals were frequently found in OA synovial membranes including low grade OA. BCP crystals injected into murine knee joints provoked synovial inflammation characterized by synovial macrophage infiltration that persisted at day 30, cartilage degradation as evidenced by loss of proteoglycan staining by Safranin-O and concomitant expression of VDIPEN epitopes, and increased chondrocyte apoptosis. BCP crystal-induced synovitis was totally independent of IL-1α and IL-1β signalling and no alterations of inflammation were observed in mice deficient for components of the NLRP3-inflammasome, IL-1α or IL-1β. Similarly, treatment with anakinra did not prevent BCP crystal effects. In vitro, BCP crystals elicited enhanced transcription of matrix degrading and pro-inflammatory genes in macrophages.Conclusions significanceintra-articular BCP crystals can elicit synovial inflammation and cartilage degradation suggesting that BCP crystals have a direct pathogenic role in OA. The effects are independent of IL-1 and NLRP3 inflammasome.

Prostatic stones are a common condition in older men in industrialized countries. However, aging appears not to be the unique pathogenesis of these calcifications. Our morpho-constitutional investigation of 23 stone samples suggested that infection has a significant role in the lithogenic process of prostate calcifications, even without detection of infection by clinical investigation. Most stones (83%) showed bacterial imprints and/or chemical composition, suggestive of a long-term infection process. Chronic infection may induce persistent inflammation of the tissue and secondarily, a cancerization process within a few years. Thus, the discovery of prostate calcifications by computerized tomodensitometry, for example, might warrant further investigation and management to search for chronic infection of the prostate gland.

In most industrialized countries, different epidemiologic studies show that chronic renal failure is dramatically increasing. Such major public health problem is a consequence of acquired systemic diseases such as type II diabetes, which is now the first cause for end stage renal failure. Furthermore, lithogenic diseases may also induce intratubular crystallization, which may finally result in end-stage renal failure (ESRF). Up to now, such rare diseases are often misdiagnosed. In this study, based on twenty four biopsies, we show that SR µFTIR (Synchrotron Radiation-µFourier transform infrared) spectroscopy constitutes a significant opportunity to characterize such pathological µcalcifications giving not only their chemical composition but also their spatial distribution in the tissues. This experimental approach offers new opportunities to the clinicians to describe at the cell level the physico-chemical processes leading to the formation of the pathological calcifications which lead to ESRF.