2022 Recommendations of the AFU Lithiasis Committee: Epidemiology, stone analysis and composition.

The incidence of urinary lithiasis is rising steadily in industrialized countries, and its prevalence in the general population of France is estimated at 10%. Renal colic accounts for 1-2% of emergency department consultations. At a time when the new LASER stone fragmentation techniques available to urologists will lead to ever finer in situ pulverization of stones, the exact identification of the compounds that form the stone is essential for etiological diagnosis. Constitutional analysis by infrared spectrophotometry or X-ray diffraction is therefore recommended, to be complemented by morphological typing of the calculi. METHODOLOGY: These recommendations have been drawn up using two methods: the Recommendation for Clinical Practice (RPC) method and the ADAPTE method, depending on whether or not the issue was considered in the EAU recommendations (https://uroweb.org/guidelines/urolithiasis) [EAU 2022] and their adaptability to the French context.

Morbidity and long-term results of subcutaneous pyelovesical bypass in chronic ureteral obstruction.

BACKGROUND: We present the long-term results and complications of the DETOUR® prosthesis, a permanent subcutaneous pyelovesical bypass for the treatment of ureteral obstruction. PATIENTS AND METHODS: Between 2006 et 2018, 34 prosthesis were implanted in 28 patients (mean age 65,8 years) with ureteral obstruction of malignant or benign etiologies. The prosthesis, composed to an inner tube of silicone and an outer tube of expanded polytetrafluoroethylene, is placed subcutaneously between the kidney and the bladder. We are performed infrared spectrophotometry and scanning electron microscopy on two removed prostheses to explore the prosthetic encrustation. RESULTS: The average follow-up was 25,8 months (Maximum: 64 months). Stent revision was required for early bladder fistula in three patients. The major long-term complications were infection (46%), obstruction (3 patients) and bladder fistula (7 patients). The most frequently infection are non-severe, but two patients died from septic shock after fungic colonization of the prosthesis. The infrared spectrophotometry and scanning electron microscopy analysis showed that the obstruction was favored by urinary infection and an alkaline medium. The functional prosthesis rate at 1,2 and 3 years was 94%, 71% and 62%, respectively. CONCLUSION: The DETOUR® subcutaneous extra-anatomical urinary bypass is an effective and minimally invasive alternative to permanent percutaneous nephrostomy, for both malignant and benign ureteral obstructions in selected patients. LEVEL OF EVIDENCE: 3.

Pediatric urolithiasis in Morocco: Composition of 432 urinary calculi analyzed by infrared spectroscopy.

PURPOSE: Incidence of pediatric urolithiasis is decreasing in most developing countries where endemic bladder stones are less prevalent than in the past years. In parallel, stone composition has changed. Only few data are available in North Africa, except for Tunisia. We report stone composition in the Moroccan pediatric population. MATERIAL AND METHODS: Composition of 432 stones from children (302 boys, 130 girls) was determined by infrared spectroscopy. The samples were collected during the period 1999-2016. Stone morphology, which is an important aspect for etiology was determined by examination of each stone under a stereomicroscope. Stone composition was compared to patients' age and gender. RESULTS: The global male-to-female ratio was 2.32. Regarding stone composition, calcium oxalate was the main component in 51.6% of the stones, followed by struvite (18.1%), ammonium urate (9.5%) and carbapatite (9%). Significant differences were found between males and females: calcium oxalate accounted for 72.3% of stones in girls and 42.7% in boys (P<10-6); conversely, struvite was more frequent in boys than in girls (22.2 vs 8.5%, P<10-4). The same was found for calcium phosphate stones (11.9% in boys; 4.6% in girls, P<0.05). Stone morphology helped us for detecting several pathological conditions: type Ic whewellite stones, as a marker for primary hyperoxaluria, was found in 17.6% of stones and type IIId ammonium urate stones, suggestive for infectious diarrhea, was identified in 20.1% of all stones. CONCLUSION: This is the largest series of pediatric stones in Morocco studied by infrared analysis and morphological examination. LEVEL OF EVIDENCE: 3.

A virtuous diagnostic and therapeutic roadmap triggered by a motivated and skilful urinary sediment examination.

In this paper we describe how an accurate urinary sediment examination, which revealed the presence of a severe 2,8-dihydroxyadenine crystalluria, opened the way to an articulate and successful diagnostic and therapeutic roadmap for a rare and potentially severe renal disease.

Physicochemical characterization of inorganic deposits associated with granulomas in cutaneous sarcoidosis.

BACKGROUND: Sarcoidosis, characterized by epithelioid granulomas, is considered to be caused by a complex interplay between genetics and environmental agents. It has been hypothesized that exogenous inorganic particles as crystalline silica could be a causal or adjuvant agent in sarcoidosis onset. OBJECTIVES: To investigate the location, frequency and physicochemical characteristics of foreign materials and mineral tissue deposits in the granulomatous area of cutaneous sarcoidosis. METHODS: Skin biopsies (n = 14) from patients diagnosed with cutaneous sarcoidosis (mean age 43 years; 11 patients with extracutaneous involvement) were investigated using polarized light examination (PLE), µFourier Transform Infra-Red (µFT-IR) spectroscopy and Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (FE-SEM/EDX). RESULTS: Combined PLE, µFT-IR, FE-SEM/EDX analysis allowed to characterize mineral deposits in 7/14 biopsies (50%). It identified crystalline silica (SiO2 ) inside granulomas in three biopsies and calcite (CaCO3 ) at their periphery in 4. CONCLUSION: This study emphasizes the need of using combined methods for assessment of mineral deposits in granulomatous diseases. According to the location and characteristics of deposits, we can hypothesize that SiO2 particles contribute to the granuloma formation, whereas CaCO3 deposits are related to the granuloma biology. However, the significance of the association between SiO2 deposits and sarcoidosis is still disputed.

Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: Two cases.

INTRODUCTION: Tumoral calcinosis (TC) is a difficult-to-treat complication that can occur during several diseases such as dermatomyositis or genetic hyperphosphatemia. It is a painful and disabling condition that can lead to local complications including joint mobility reduction, cutaneous ulceration and superinfection. For the largest lesions, the treatment relies essentially on surgery. Intravenous sodium thiosulfate (STS) is efficient to treat calciphylaxis in patients undergoing hemodialysis. Local injections of STS seem efficient in superficial calcifications. OBJECTIVE: To report the efficacy and safety of intra-lesional injections of STS in tumoral calcinosis. RESULTS: We report two cases of successful intra-lesional injections of STS. A 44-year-old woman, with a history of dermatomyositis, presenting large subcutaneous calcifications in the right elbow, and a 42-year-old man, with a history of familial tumoral calcinosis, presenting large intramuscular calcifications in the right buttock, received weekly intra-lesional of 1-3g STS injections for 12 and 21 months, respectively. In both cases, the treatment relieved pain and greatly reduced the tumoral calcinosis with a very significant functional improvement without specific adverse effects. In case 1, TC size decreased from 28.7*56.0mm at baseline to 21.5*30.6mm at M12 treatment (59% reduction). In case 2, TC reduced from 167.5*204.3mm at baseline to 86.2*85.2mm at M21 treatment (79% reduction). CONCLUSION: Local injection of STS could be a promising therapeutic strategy for large and deep TC lesions and could therefore be an alternative to surgery.

"Daisy-like" crystals: A rare and unknown type of urinary crystal.

BACKGROUND: Crystals are well known structures of urinary sediment, most of which are identified by the combined knowledge of crystal morphology, birefringence features at polarized light, and urine pH. In this paper, we report on a cohort of subjects whose urine contained a very rare type of crystal, which we first described in 2004 and which, based on its peculiar morphology, we define as "daisy-like crystal" (DLcr). METHODS: Reports on DLcr were spontaneously sent to our laboratory over a 10.5-year period by different laboratory professionals and by one veterinary clinician who, in their everyday work, had come across DLcr. After the examination of DLcr images submitted, a number of other information were requested and partly obtained. RESULTS: DLcr were found in 9 human beings in 7 different laboratories, located in 4 countries (Italy, Belgium, Croatia, France). DLcr were found mostly in female (8/9), at all ages (3.5 to 93years), mostly in alkaline urine (pH6.0 to 7.5), at variable specific gravity values (1.010 to 1.030), either as isolated particles (2/8) or in association with other crystals (5/8) and/or leucocytes or bacteria (3/8). In addition, DLcr were found in the urine of a 1-year-old dog, examined in a veterinary clinic of Czech Republic. In 3 cases, DLcr were identified by manual microscopy, while in 7 cases by automated urine sediment analyzers. CONCLUSIONS: This paper confirms the possible presence in the urine of DLcr. However, further cases are needed to clarify their frequency, clinical meaning, and composition.

[Nephrolithiasis of adult: From mechanisms to preventive medical treatment]. / Lithiase rénale de l'adulte : des mécanismes au traitement médical préventif.

Nephrolithiasis is a very common (prevalence around 10 to 12% in France) and recurrent disorder. Nephrolithiasis is associated to chronic kidney disease and is responsible for 2 to 3% of cases of end-stage renal disease, mainly if it is associated to nephrocalcinosis or to a monogenic disorder (1.6% of nephrolithiasis in adults, among them 1% of cystinuria). To understand the underlying pathophysiological processes, stone analysis (morphology and using infrared spectrophotometry) as well as minimal biological assessment including urine crystal research are required. The calcic nephrolithiasis is the more frequent subtype (>80%). Its medical treatment relies on simple dietary rules: non-alkaline hyperdiuresis>2 liters/day, calcium intake normalization (1 gram per day divided between the three principal meals), normalization of sodium (6 to 7 grams per day) and protein intake (1g/kg of theoretical body weight/day), and eviction of foods rich in oxalate. In case of persistent hypercalciuria (>0.1mmol/kg of theoretical body weight/day on free diet), a thiazide diuretic can be started while being aware to correct iatrogenic decrease in plasma potassium and urine citrate excretion. Measurement of bone mineral density must systematically be performed in patients with high 24 h-urinary calcium excretion. The medical treatment of uric acid nephrolithiasis relies on alkaline hyperdiuresis (goal of urine pH: 6.2 to 6.8). The use of allopurinol is justified only if urine uric acid is over 4mmol/day. Thanks to a well-managed preventive medical treatment, one can expect to stop the activity of nephrolithiasis in more than 80% of cases, making it one of the most accessible renal pathologies to preventive medical treatment.

[The role of physicochemistry in urology and nephrology, selected results obtained during the last ten years]. / La place de la physicochimie en urologie et en néphrologie : le bilan de 10ans de collaboration entre physiciens, chimistes et praticiens hospitaliers.

INTRODUCTION: The presence of pathological calcifications, which can be either concretions or ectopic call for physicochemical characterisation techniques in order to define a significant diagnosis. The aim of this review is to present a set of characterisation techniques able to describe at the micrometer scale their structural and chemical characteristics and show their place at the hospital. METHOD: Results already published in the last ten years based on characterisation techniques present in laboratories or specific to large-scale instruments are presented. Their usefulness for the clinician is discussed. RESULTS: The presence and role of heavy metals in urinary stones through data collected through µX-ray fluorescence is debated. If these data suggest a simple substitution process of calcium, recent data suggest that weddellite is associated to a Zn-rich environment, partly favoured by an inflammation process. Investigation on the chemistry and the structure of unusual deposits in kidney biopsies show a great chemical diversity of ectopic calcifications. Such diversity shows that staining procedures to characterize such deposits are obsolete. Finally, several diseases which can be assessed through techniques specific to large-scale instruments and defined by the clinician are presented. CONCLUSION: The chemical and structural complexity of pathological calcifications call for a characterization through physicochemical techniques. Only such approach allows the clinician to define a significant diagnosis and to care the patient.

Calcium oxalate precipitation by diffusion using laminar microfluidics: toward a biomimetic model of pathological microcalcifications.

The effect of mixing calcium and oxalate precursors by diffusion at miscible liquid interfaces on calcium oxalate crystalline phases, and in physiological conditions (concentrations and flow rates), is studied using a microfluidic channel. This channel has similar dimensions as the collection duct in human kidneys and serves as a biomimetic model in order to understand the formation of pathological microcalcifications.

[Composition of 359 kidney stones from the East region of Algeria]. / Détermination de la composition de 359 calculs du haut appareil urinaire collectés dans la région Est-algérien.

PURPOSE: Determine stones composition of the upper urinary tract in the eastern region of Algeria. METHODS: Our study focuses on a set of 359 stones of the upper urinary tract collected between January 2007 and December 2012 at hospitals in the eastern region of Algeria and analyzed by Fourier transform infrared spectroscopy. RESULTS: The male/female ratio was only 1.32. Calcium oxalate prevailed in 68.5% of stones and 49.3% of nuclei, mainly as whewellite (51.8% of stones and 37.9% of nuclei vs 16.7% and 11.4% respectively for weddellite). Carbapatite prevailed in 15% of stones and 29.8% of nuclei. The struvite, identified in 11.1% of calculi, prevailed in 3.9% of stones and 3.1% of nuclei. Among purines, uric acid prevailed with frequencies quite close to 8.9% and 7% respectively in the stone and in the nucleus while the ammonium urate prevailed in only 0.3% of stones and 3.3% of nuclei. The cystine frequency was 3.6% in both stone and nucleus. The frequency of stone with umbilication was 26.2%. Whewellite was the main component of umbilicated stones with Randall's plaque. CONCLUSION: Our results suggest that stones of the urinary tract in the Algerian east region resemble those observed in industrialized countries. Some features such as stones location, the whewellite prevalence, the frequencies of main components in both the stone and the nucleus as well as the formation of stones on renal papilla confirm this trend. LEVEL OF EVIDENCE: 4.

[Urinary tract infections: Economical impact of water intake]. / Infections des voies urinaires : impact économique de la consommation d'eau.

BACKGROUNDS: This study aims to estimate the impact of preventing urinary tract infections (UTI), using a strategy of increased water intake, from the payer's perspective in the French health care system. METHODS: A Markov model enables a comparison of health care costs and outcomes for a virtual cohort of subjects with different levels of daily water intake. The analysis of the budgetary impact was based on a period of 5years. The analysis was based on a 25-year follow-up period to assess the effects of adequate water supply on long-term complications. RESULTS: The authors estimate annual primary incidence of UTI and annual risk of recurrence at 5.3% and 30%, respectively. Risk reduction associated with greater water intake reached 45% and 33% for the general and recurrent populations, respectively. The average total health care cost of a single UTI episode is €1074; for a population of 65 millions, UTI management represents a cost of €3.700 millions for payers. With adequate water intake, the model indicates a potential cost savings of €2.288 millions annually, by preventing 27 million UTI episodes. At the individual level, the potential cost savings is approximately €2915. CONCLUSIONS: Preventing urinary tract infections using a strategy of adequate water intake could lead to significant cost savings for a public health care system. Further studies are needed to assess the effectiveness of such an approach.

[Presence and role of trace elements in urinary calculi]. / Nature et rôle des éléments traces dans les calculs urinaires.

AIM: To assess the possible nature and role of trace elements in the pathogenesis of urinary stones. MATERIAL AND METHOD: A series of 76 calculi from the East-Algerian region has been investigated through Fourier transform infrared spectroscopy for chemical analysis and X-ray fluorescence for detecting trace elements. RESULTS: Among the detected trace elements, Zn, Sr, Pb, Cu, Rb and Se, only the first three had significant values. Overall, the calcium components, namely calcium oxalate and calcium phosphate, were the most loaded by these elements contrary to organic components such as uric acid and cystine, which had low contents. CONCLUSION: The correlation of contents of Zn and Sr with the stone components (carbapatite, weddellite and whewellite) suggests an adsorption of these trace elements in the case of calcium stones rather than a catalytic process. LEVEL OF EVIDENCE: 3.

Recurrent 2,8-dihydroxyadenine nephropathy: a rare but preventable cause of renal allograft failure.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5-312) weeks following the transplant procedure. Patients had delayed graft function (n=2), acute-on-chronic (n=5) or acute (n=1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8-DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8-DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n=7), remained stable (n=1) or worsened (n=1). At last follow-up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8-DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.

[First-line screening guidelines for renal stone disease patients: a CLAFU update]. / Bilan métabolique et prise en charge médicale de la lithiase: une mise au point du CLAFU.

This text summarizes the CLAFU first-line screening guidelines for renal stone disease patients. We have focused on the useful information provided by renal stone analysis and also the identification of relevant stone risk factors detected in a 24-hour urine collection. Indeed, evaluation of water, sodium and protein intake may be easily achieved in a current clinical setting and allows a useful pedagogic tool for patients' advices and follow-up: daily diuresis above 2000 mL, calcium intake between 800 mg and 1 g/day, a moderate daily sodium and proteins restricted diet (<9 g and <1.2 g/kg per day respectively). General therapeutical principles are reviewed, including circumstances requiring specialized management.

Increased water intake as a prevention strategy for recurrent urolithiasis: major impact of compliance on cost-effectiveness.

PURPOSE: We evaluated the economic impact of preventing recurrent stones using a strategy of increased water intake and determined the impact of compliance on cost-effectiveness for the French health care system. MATERIALS AND METHODS: A Markov model was constructed to compare costs and outcomes for recurrent kidney stone formers with less than 2 L vs 2 L or more daily fluid intake. Model assumptions included an annual prevalence of 120,000 stone episodes in France, 14.4% annual risk of stone recurrence and a 55% risk reduction in subjects with adequate water intake. Costs were based on resource use as estimated by a panel of experts and official national price lists. Outcomes were from the perspective of the public health payer, and encompassed direct and indirect costs. RESULTS: The total cost of an episode of urolithiasis was estimated at €4,267 including the cost of treatment and complications. This corresponds to an annual budget impact of €88 million for recurrent stones based on 21,000 stone events. Assuming 100% compliance with fluid intake recommendations of 2 L daily, 11,572 new stones might be prevented, resulting in a cost savings of €49 million. Compliance with water intake in only 25% of patients would still result in 2,893 fewer stones and a cost savings of €10 million. Varying the costs of managing stones had a smaller impact on outcomes since in many patients stones do not form. Varying the incidence of complications did not change the incidence of stones and had a negligible effect on overall cost. CONCLUSIONS: Preventing recurrent urolithiasis has a significant cost savings potential for a payer as a result of a reduced stone burden. However, compliance is an important factor in determining cost-effectiveness.

[Effect of plant extracts on the in vitro dissolution of cystine stones: a study at the mesoscopic scale]. / Effet des extraits de plantes médicinales sur la dissolution des calculs rénaux de cystine in vitro : étude à l'échelle mésoscopique.

AIM: Assessing the efficacy to dissolve cystine stones in vitro of plant extracts used in traditional medicine to treat or prevent urolithiasis. MATERIAL AND METHOD: Pure cystine stones were incubated during 8 weeks under magnetic stirring in the presence of four plant extracts or of NaCl 9 g/l solution used as control. Plants under examination were Arenaria ammophila (leaves and stems), Parietaria officinalis (leaves and flowers studied separately), Paronychia argentea (flowers). Each experiment was performed in triplicate. The mass loss of the stones and the pH of the solution were measured after each two weeks period. Possible changes in the cystine crystals at the stone surface were assessed at the mesoscopic scale using a scanning electron microscope. RESULTS: None of the plant extracts has revealed a significant effect to dissolve cystine stones by comparison to the control during the time of the experiment. The best result was a mass loss of 99 mg at the end of experiment in the presence of A. ammophila vs. 43.7 mg for the NaCl solution (P=0.051). Considering the slopes of the dissolution, only that extract could have an actual efficacy on a more prolonged period. CONCLUSION: Our study failed to demonstrate a significant effect of the tested plant extracts to dissolve cystine stones in vitro. However, the examination of the dissolution curves suggests that a more prolonged test period could allow an efficacy of some extracts, especially A. ammophila. Further studies are needed to verify such hypothesis. However, we cannot recommend the use of the tested plants to treat cystine stones in vivo.

Absence of bacterial imprints on struvite-containing kidney stones: a structural investigation at the mesoscopic and atomic scale.

OBJECTIVE: Bacterial imprints are always observed on highly carbonated apatite kidney stones but not struvite kidney stones. Struvite and carbonated apatite stones with a high CO(3)(2-)/PO(4)(3-) rate are believed to develop from infections, but their structural differences at the mesoscopic scale lack explanation. METHODS: We investigated 17 urinary calculi composed mainly of struvite or carbonated apatite by Fourier transform infrared, scanning electron microscopy, and powder neutron diffraction techniques. RESULTS: Carbonated apatite but not struvite stones showed bacterial imprints. If the same stone contained both carbonated apatite and struvite components, bacterial imprints were observed on the carbonated apatite but not the struvite part. Moreover, neutron powder diffraction experiments revealed the crystal size of struvite stones were larger than that of carbonated apatite stones (250 ± 50 vs 50 nm). CONCLUSION: Bacterial imprints may appear more easily on kidney stones with small nanocrystals, such as carbonated apatite than with large nanocrystals, such as struvite. This approach may help identify bacteria contributing to stone formation, perhaps with negative results of urine culture.