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International audience; Background The pathophysiology of AKI during tumor lysis syndrome (TLS) is not well understood due to the paucity of data. We aimed to decipher crystal-dependent and crystal-independent mechanisms of TLS-induced AKI. Methods Crystalluria, plasma cytokine levels, and extracellular histones levels were measured in two cohorts of patients with TLS. We developed a model of TLS in syngeneic mice with acute myeloid leukemia, and analyzed ultrastructural changes in kidneys and endothelial permeability using intravital confocal microscopy. In parallel, we studied the endothelial toxicity of extracellular histones in vitro. Results The study provides the first evidence that previously described crystal-dependent mechanisms are insufficient to explain TLS-induced AKI. Extracellular histones that are released in huge amounts during TLS caused profound endothelial alterations in the mouse model. The mechanisms of histone-mediated damage implicates endothelial cell activation mediated by Toll-like receptor 4. Heparin inhibits extracellular histones and mitigates endothelial dysfunction during TLS. Conclusion This study sheds new light on the pathophysiology of TLS-induced AKI and suggests that extracellular histones may constitute a novel target for therapeutic intervention in TLS when endothelial dysfunction occurs.

Oxalate is a metabolite promoting the formation of calcium oxalate crystals in urine. Hyperoxaluria is a feature of genetic diseases, known as primary hyperoxaluria, leading to chronic kidney disease. Ethylene glycol poisoning induces the crystallization of calcium oxalate crystals in renal tubules, promoting acute renal failure. Urine oxalate results from glyoxylate transformation to oxalate in the liver, due to lactate dehydrogenase (LDH) activity, especially the LDH-5 isoenzyme. Genetic RNA interference therapy targeting lactate dehydrogenase lowers urine oxalate excretion in murine models. Stiripentol is a drug inhibiting neuronal LDH-5 isoenzyme activity. We hypothesized that stiripentol would also reduce hepatic oxalate production and urine oxalate excretion. In vitro Stiripentol decreases oxalate synthesis by hepatocytes. In vivo, stiripentol decreases urine oxalate excretion in rats and protects kidney tissue and function against ethylene glycol intoxication and hydroxyproline-induced calcium oxalate crystalline nephropathy. The use of stiripentol in clinical practice deserves further clinical studies.

Parathyroidectomy (PTX) is routinely performed in hypercalciuric renal stone patients with primary hyperparathyroidism (PHPT). However, some data indicate a persistent stone activity following PTX, raising the issue of the link between PHPT and stone disease. We performed an observational study on 30 renal stone patients diagnosed with PHPT. Patients were selected among 1448 hypercalciuric patients referred in our department for a diagnostic evaluation. Patients with no parathyroid surgery or any biological follow-up were excluded. Clinical and biological data (including 24-h urine collection and a calcium load test) were collected before and within 12 months following surgery. Stone recurrence was evaluated by direct phone contact (median 43 months). Comparison of biological data before and after surgery showed a significant decrease of ionized calcium and serum parathyroid hormone after PTX. All stones contained calcium-dependent species such as carbapatite, brushite or dihydrate calcium oxalate. Urine saturation indexes and calciuria significantly decreased after surgery (from 9.9 to 5.9 mmol/d, p

International audience; We have previously shown that ultrasonography can detect hyperechogenic crystal deposits in the kidney medulla of patients with gout. In this cross-sectional study we investigated the frequency and clinical correlates of hyperechogenic kidney medulla in 502 consecutive primary consultants for gout (ACR/EULAR criteria) at the Vien Gut medical center in Ho Chi Minh City, Vietnam. None of these patients received urate-lowering drugs. Kidney medulla echogenicity on B-mode ultrasonography was compared to that of the kidney cortex. Overall, 36% patients showed a hyperechoic pattern of Malpighi pyramids. On univariate analysis, the pattern was significantly associated with age, estimated gout duration, steroid-dependency, clinical tophi, urate arthropathy, double contour thickness at the scanned joints, coronary heart disease, arterial hypertension, hyperuricemia, proteinuria, leukocyturia, and decreased estimated glomerular filtration rate. On multivariable analysis, the hyperechoic pattern was associated with estimated disease duration, clinical tophi, urate arthropathy, double contour thickness and decreased estimated glomerular filtration rate. No hyperechoic pattern was observed in 515 consecutive consultants without gout. Thus, hyperechoic kidney medulla was frequently demonstrated in Vietnamese patients with tophaceous gout and associated with features of tubulointerstitial nephritis. This finding revives the hypothesis of microcrystalline nephropathy of gout, predominantly seen in untreated gouty patients, which could be an important target for urate-lowering therapy.

BACKGROUND AND AIMS Sickle cell disease (SCD) induces a decline in urine concentration and progressive deterioration of kidney (K) function. Hyperfiltration is often observed before this decline, and plasma urea is low. Oral urea or hydroxyurea improves the condition of these patients (pts). These observations draw the attention to renal urea handling in SCD. Studies suggest that addition of urea into the loop of Henle may indirectly modify NaCl concentration at the macula densa and induce a rise in glomerular filtration rate (GFR) by depressing the tubule-glomerular feedback (TGF) [1]. The urine-to-plasma urea concentration ratio (U/P urea) is a novel marker associated with GFR and the progression of disease in ADPKD [2]. The present study addresses the relationship of U/P urea with GFR in SCD pts. METHOD A total of 184 homozygous SCD pts referred to our department were included. They underwent extensive evaluation including measured GFR (mGFR) (51Cr EDTA clearance) and plasma and 24-h urine chemistries. The association between mGFR and U/P urea was tested using univariate, and multivariate stepwise regression analyses. RESULTS Mean age was 35.6 ± 2.8 years (mean ± SD) and body mass index (BMI) 22.2 ± 0.3 kg/m2. Mean mGFR was 107 ± 3 ml/min x 1.73m2. Hyperfiltration was observed in 37% of pts. Urine volume (UV) 1.71 ± 0.75 L/24h. Urea excretion 267 ± 151 mmol/24h. In 13% of pts fractional excretion of urea (FEurea) exceeded 50%. U/P urea (42 ± 20) varied from 6 to 112. It was not associated with 24-h urea excretion but showed a negative association with UV (P < 0.007). mGFR was strongly and positively associated with U/P urea (r = 0.58, P < 0.0001) but not with U/P osmolarity (see Figure and Table). mGFR was also associated with U/P creatinine although more weakly (r = 0.266, p < 0.0001) and with BMI and negatively associated with age, MAP and serum creatinine (creat). After adjustment for U/P creat, the association between mGFR and U/P urea remained highly significant, whereas, after adjustment for U/P urea, the association between mGFR and U/P creat disappeared. In multivariate regression, mGFR remained strongly associated with U/P urea. CONCLUSION Our data show a strong association between mGFR and U/P urea that remains highly significant after multivariate analysis. i) This suggests that a specific estimated GFR equation for SCD patients including the U/P urea ratio could be clinically more relevant than CKD-EPI equations. ii) A specific mechanism may link GFR and intrarenal urea handling, as U/P urea but not U/P osmolarity appears to be involved. Urea could play a role, indirectly, in the regulation of GFR [1]. In SCD, the longer transit time of the blood in vasa recta may favour countercurrent exchanges and lead to a greater addition of urea in loops of Henle (increasing the U/P urea ratio) and thus increasing GFR by reducing TGF. Sickled red cells and resulting in slower blood flow in the medulla may selectively influence urea handling, participating in high FEurea and GFR often observed in SCD pts. iii) As is the case in ADPKD, more attention should be given to longitudinal studies to the relationship between U/P urea and kidney disease progression in SCD pts.

BACKGROUND AND AIMS Vancomycin stands out both as being a potent cause of AKI (V-AKI) and as one of the most universally prescribed antimicrobial drugs. From a pathophysiological standpoint, it was hitherto believed that V-AKI stemmed from the intracellular accumulation of vancomycin in the proximal tubule, which elicits oxidative stress and ultimately translates in cell apoptosis. Recently, a study has shown that vancomycin in the setting of overt drug overdose, can co-precipitate with uromodulin causing microspheric obstructive aggregates in the tubular lumen both in experimental models and in patients [1]. Further documentation of this novel mechanism has been hindered by the need to procure kidney tissue so as to perform ad hoc immunostaining. Furthermore, it remains to be proven that the presence of vancomycin microspheres represents a reliable marker for V-AKI. Urine based vancomycin-immunostaining may represent a valuable non-invasive approach. METHOD The urine of patients presenting with vancomycin overdose determined by plasma trough levels >15 mg/L along with acute kidney injury (according to KDIGO guidelines) were subjected to light microscopic urinalysis. Whenever microscopic urinalysis yielded the presence of casts, immunostaining was performed. Briefly, a pellet of urine was spread on a slide and immunostaining performed with a specific anti-vancomycin antibody (Abbot 6E-4421, 1/1000) prior to repeat microscopic examination. Infrared spectrophotometry was performed to ascertain the nature of the casts by comparing the spectrum to a reference vancomycin spectrum. Patients were deemed to have V-AKI whenever at least one vancomycin positive cast was observed following immunostaining. The urine of control patients was subjected to the same procedure: they were defined as patients exposed to vancomycin with or without vancomycin overdose but with no AKI. RESULTS A total of 5 patients with vancomycin overdose KDIGO stage 3 AKI were found to exhibit casts with positive vancomycin immunostaining (Fig. 1). On light microscopic urinalysis, vitreous casts devoid of refringence after polarization could be observed in each case. Upon infrared spectrophotometry, the casts displayed a Fourier transform spectrum consistent with vancomycin. In three of the cases, V-AKI was considered the sole or primary cause of AKI. The patient displayed abundant and markedly stained casts upon anti-vancomycin immunostaining (Fig. 1A). Overt and massive vancomycin overdosing was evidenced in all cases. In one case, the patient concurrently received piperacillin-tazobactam and in another case the patient was exposed to iodinated contrast media. The renal function course was favourable with full recovery in all three instances. In two cases, competing causes of AKI were either evidenced or not. In one case, the patient displayed septic shock which indicated vancomycin therapy. In another case, the patient was suspected to have immunoallergic intersititial nephritis. The patients exhibited rare casts with only faint staining (Fig. 1B). In both cases, vancomycin overdose could not be documented. V-AKI was deemed a possible concurrent cause of AKI. None of the 5 control patients yielded casts after light microscopic urinalysis. CONCLUSION Vancomycin cast detection on urine microscopy is feasible and can be enhanced by a straightforward immunostaining technique and represents a unique opportunity for a non-invasive diagnosis of V-AKI. Further studies are required to refine diagnostic criteria-based urine immunostaining detection. They also needed to determine whether detection of V-AKI merely reflects impaired vancomycin urinary excretion in the setting of AKI or can be regarded as a sensitive and specific marker of vancomycin-induced tubular obstruction and injury.

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The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places. Electronic supplementary material The online version of this article (10.1007/s00240-020-01217-3) contains supplementary material, which is available to authorized users.

Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (−5) in 38% of cases. mGFR association with CI and SVR were significant at baseline (respectively ρ: 0.44, p = 0.008 and ρ: − 0.37, p = 0.02) and under ACEI (p = 0.007 and 0.01 respectively), in accordance with previous data showing that hyperfiltration was linked to an increased glomerular perfusion and a glomerulomegaly rather than increased capillary hydrostatic pressure. Of notice, after adjustment on CI, mGFR remained associated with reticulocyte count and albuminuria under ACEI (p = 0.006 and 0.02 respectively). Our results suggest that hyperfiltration is tightly linked to an increased cardiac output which may account for an increased renal blood flow. Chronic hemolysis could be a relevant factor accounting for hyperfiltration potentially acting on glomerular enlargement which appears as a key factor. Our data suggest that cardiac output assessment is a relevant tool in the routine management and monitoring of SCA nephropathy.

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Encrusted uropathy is a rare subacute to chronic inflammatory disorder caused by infection with urease-producing bacteria, mainlyCorynebacterium urealyticum. The disorder is characterized by urothelial deposition of struvite and carbonated apatite, resulting in encrustations and ulceronecrotic inflammation of the urothelium and surrounding tissues. Most commonly, encrusted uropathy is encountered in patients with predisposing conditions. The disease remains underdiagnosed. High urinary pH and negative conventional urine cultures should raise suspicion of the diagnosis. Prognosis is dependent on timely diagnosis and treatment installment, which consists of urological removal of encrustations in combination with urinary acidification and long-term antibiotic therapy.

The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places., This article is based on the results of a Consensus Conference held during the 4th INTERNATIONAL MEETING OF THE MENARINI FOUNDATION ON NEPHROLITHIASIS, Verona, June 20-22, 2019 generously supported by the International Foundation Menarini, Milan, Italy with an unrestricted educational Grant.

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.

International audience; Rationale & objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).Study design: Prospective longitudinal cohort study.Setting & participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.Predictor: Fasting urinary osmolality measured using delta cryoscopy.Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance.Analytical approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.Limitations: Fasting was self-reported.Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.

Objective To develop French Society of Rheumatology-endorsed recommendations for the management of gout flares. Methods These evidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and 2 Delphi rounds to finalize them. Results A set of 4 overarching principles and 4 recommendations was elaborated. The overarching principles emphasize the importance of patient education, including the need to auto-medicate for gout flares as early as possible, if possible within the first 12 h after the onset, according to a pre-defined treatment. Patients must know that gout is a chronic disease, often requiring urate-lowering therapy in addition to flare treatment. Comorbidities and the risk of drug interaction should be screened carefully in every patient as they may contraindicate some anti-inflammatory treatments. Colchicine must be early prescribed at the following dosage: 1 mg then 0.5 mg one hour later, followed by 0.5 mg , 2 to 3 times/day over the next days. In case of diarrhea, which is the first symptom of colchicine poisoning, dosage must be reduced. Colchicine dosage must also be reduced in patients with chronic kidney disease or taking drugs, which interfere with its metabolism. Other first-line treatment options are systemic/intra-articular corticosteroids, or non-steroidal anti-inflammatory agents (NSAIDs). IL-1 inhibitors can be considered as a second-line option in case of failure, intolerance or contraindication to colchicine, corticosteroids and NSAIDs. They are contraindicated in cases of infection and neutrophil blood count should be monitored. Conclusion These recommendations aim to provide strategies for the safe use of anti-inflammatory agents, in order to improve the management of gout flares.

Objective To develop French Society of Rheumatology-endorsed recommendations for the management of urate-lowering therapy (ULT). Methods Evidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and two Delphi rounds to finalize them. Results A set of 3 overarching principles and 5 recommendations was elaborated. The overarching principles emphasize the importance of patient education, especially the need for explaining the objective of lowering serum urate (SU) level to obtain crystal dissolution, clinical symptoms disappearance and avoidance of complications. ULT is indicated as soon as the diagnosis of gout is established. SU level must be decreased below 300 μmol/l (50 mg/l) in all gout patients or at least below 360 μmol/l (60 ml/l) when the 300 μmol/l target cannot be reached, and must be maintained at these targets and monitored life-long. The choice of the ULT primarily relies on renal function: in patients whose estimated glomerular filtration rate (eGFR) is above 60 ml/min/1.73 m2, first-line ULT is allopurinol; in those with eGFR between 30 and 60 ml/min/1.73 m2, allopurinol use must be cautious and febuxostat can be considered as an alternative; and in those whose eGFR is below 30 ml/min/1.73 m2, allopurinol must be avoided and febuxostat should be preferred. Prophylaxis of ULT-induced gout flares involves progressive increase of ULT dosage and low-dose colchicine for at least 6 months. Cardiovascular risk factors and diseases, the metabolic syndrome and chronic kidney disease must be screened and managed. Conclusion These recommendations aim to provide simple and clear guidance for the management of ULT in France.

Background Chronic kidney disease is associated with a high cardiovascular risk. Compared with glomerular filtration rate–matched CKD patients (CKDps), we previously reported a 2.7-fold greater risk of global mortality among kidney transplant recipients (KTRs). We then examined aortic stiffness [evaluated by carotid–femoral pulse wave velocity (CF-PWV)] and cardiovascular risk in KTRs compared with CKDps with comparable measured glomerular filtration rate (mGFR). Methods We analysed CF-PWV in two cohorts: TransplanTest (KTRs) and NephroTest (CKDps). Propensity scores were calculated including six variables: mGFR, age, sex, mean blood pressure (MBP), body mass index (BMI) and heart rate. After propensity score matching, we included 137 KTRs and 226 CKDps. Descriptive data were completed by logistic regression for CF-PWV values higher than the median (>10.6 m/s). Results At 12 months post-transplant, KTRs had significantly lower CF-PWV than CKDps (10.1 versus 11.0 m/s, P = 0.008) despite no difference at 3 months post-transplant (10.5 versus 11.0 m/s, P = 0.242). A lower occurrence of high arterial stiffness was noted among KTRs compared with CKDps (38.0% versus 57.1%, P Conclusions Aortic stiffness was significantly less marked in KTRs 1 year post-transplant than in CKDps matched for GFR and other variables. This observation is compatible with the view that the pathogenesis of post-transplant cardiovascular disease differs, at least in part, from that of CKD per se.

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Purpose of review Oxalate is a metabolic end-product promoting the formation of calcium oxalate crystals in urine. Massive urine oxalate excretion occurs in genetic diseases, mainly primary hyperoxaluria type I and II, threatening renal function. Ethylene glycol poisoning may induce the precipitation of calcium oxalate crystals in renal tubules, leading to acute renal failure. In both cases, oxalate results from glyoxylate transformation to oxalate in the liver, by lactate dehydrogenase (LDH) enzymes, especially the LDH-5 isoenzyme. The purpose of the review is to highlight LDH as a potential therapeutic target according to recent publications. Recent findings Genetic therapy targeting LDH metabolism decreases urine oxalate excretion in rodents. Stiripentol is an antiepileptic drug that has been shown recently to inhibit neuronal LDH-5 isoenzyme. Stiripentol was hypothesized to reduce hepatic oxalate production and urine oxalate excretion. In vitro, stiripentol decreases oxalate synthesis by hepatocytes. In vivo, stiripentol oral administration decreases urine oxalate excretion in rats and protects renal function and renal tissue against ethylene glycol intoxication and chronic calcium oxalate crystalline nephropathy. Summary The use of stiripentol in-vitro and in-vivo highlights that targeting hepatic LDH by pharmacological or genetic tools may decrease oxalate synthesis, deserving clinical studies.

Introduction La nephropathie oxalique est une pathologie rare mais possiblement sous-estimee, avec un pronostic reserve. Elle est caracterisee par la precipitation intra parenchymateuse de cristaux d’oxalate de calcium. L’hyperoxalurie est le facteur de pathogenicite principal, avec de multiples etiologies. Methodes Nous avons repris les biopsies renales realisees dans deux centres de l’APHP entre 2006 et 2021. Nous rapportons les caracteristiques clinico-biologiques, l’etiologie, la prise en charge et l’evolution. Le diagnostic etait retenu s’il existait une alteration de la fonction renale (DFGe Resultats Le diagnostic de nephropathie oxalique a ete retenu chez 40 patients, 18 etaient insuffisants renaux chroniques (IRC) (45 %). Le tableau initial etait celui d’une insuffisance renale aigue (IRA) dans 2 cas (55 %), d’une IRA sur IRC dans 13 cas (32,5 %), ou d’une IRC dans 5 cas (12,5 %). Une proteinurie tubulaire et de debit moyen etait presente (1,8 ± 3,6 g/g), avec une hematurie dans 35 % et une leucocyturie dans 45 % des patients. La cristallurie a permis d’identifier des cristaux de whewellite chez 7 patients sur 24 (29 %). L’enquete etiologique a retrouve une malabsorption digestive dans 23 cas (57,5 %), un exces d’apport alimentaire dans 3 cas (7,5 %). Dans 14 cas, le diagnostic etiologique n’a pas pu etre etabli (35 %). Une hemodialyse lors de la prise en charge initiale a ete necessaire dans 17 cas (42,5 %), avec sevrage chez 9 patients (53 %). Au dernier suivi (23 mois en moyenne), une IRC terminale ou pre-terminale etait presente dans 66 % des cas. Conclusion La nephropathie oxalique est une pathologie rare, de cause indeterminee chez encore un tiers des patients. La gravite de ces maladies et la faible efficacite des traitements actuels appellent a intensifier la recherche clinique et physiopathologique.

Introduction Une etude recente a mis en lumiere l’obstruction intra-tubulaire par nanopheres de vancomycine comme un mecanisme possible d’insuffisance renale aigue dans un contexte de surdosage de vancomcycine. Neanmoins cette hypothese est difficile a verifier en routine clinique car elle requiert une biopsie renale et ce d’autant plus que la resolution de l’IRA est la regle. Description Un patient de 62 ans sans antecedent pesant 82 kg de fonction renale normale (creatinine plasmatique : 70 μmol/L ; eGFR : 94 mL/min selon CKD-EPI) a ete admis dans les suites d’une pneumonie a Enterococcus faecium et Pseudomonas aeruginosa ayant motive une antibiotherapie combinant tazocilline (4 g × 3 par jour) et vancomycine (2500 mg, deux administrations intraveineuse discontinues quotidiennes). Trente-six heures apres le debut de l’antibiotherapie, la patiente developpe une IRA KDIGO3 avec un pic de creatinine plasmatique a 570 μmol/L. Le patient etait moderement hypertendu avec un examen clinique normal et une evaluation echographique renale normale. Les explorations urinaires sont compatibles avec une agression tubulaire avec une proteinurie moderee (ratio proteinurie/creatininurie : 0,1 g/mmol) composee d’albuminurie de bas poids (urine albuminurie/creatininurie : 34 mg/mmol) et des niveaux eleves de retinol-binding protein : 3,29 mg/L (valeur Methodes La microscopie optique urinaire a montre des cylindres vitreux non refringents. Un echantillon d’urine est etale sur une lame et incube avec une anticorps specifique anti-vancomycine (Abbot 6E-4421, 1/1000) completee par la spectrophotometrie infra-rouge (SPIR). Resultats L’immunomarguage confirme la presence de cylindres de vancomycine ( Fig. 1 ) corroboree par la SPIR. L’immunomarquage etait negatif sur plusieurs echantillons d’urines temoin composees de cristaux et proteines variees. Conclusion L’immunomarquage urinaire couplee a l’analyse microscopique constitue donc une alternative potentielle non invasive a visee diagnostique.

Volume overload has been shown to be an independent risk factor for mortality in patients receiving chronic dialysis, but data in non-dialysis patients are scarce. Therefore we evaluated the prognostic value of extracellular fluid (ECF) volume for chronic kidney disease (CKD) progression and mortality in a prospective hospital-based cohort with CKD stage 1-4 (NephroTest Study). ECF (scaled to body surface area) and the measured glomerular filtration rate (mGFR) were determined using the distribution volume and clearance of 51Cr-EDTA, respectively. Cause-specific Cox and linear mixed-effect regression models were used to analyze the association of ECF with end-stage kidney disease (ESKD) and mortality, and with mGFR decline, respectively. The 1593 patients were mean age 58.8 years, 67% were men, mean mGFR of 43.6 mL/min/1.73m2 and mean ECF 15.1 L/1.73m2. After a median follow-up of 5.3 years, ESKD occurred in 324 patients and 185 patients died before ESKD. In multivariable analysis, ECF was significantly associated with the risk of ESKD (hazard ratio per 1L/1.73m2 increase: 1.14; 95% confidence interval [1.07; 1.21]) and with a faster GFR decline (adjusted mean difference in mGFR slope per 1L/1.73m2 increase -0.14 [-0.23; -0.05] mL/min/year). The relationship of ECF with mortality was non-linear and not significant (per 1L/1.73m2 increase 0.92, [0.73; 1.16]), below 15L/1.73m2, but significant (1.28; [1.14-1.45]) above 15L/1.73m2. Thus, in this large cohort of carefully phenotyped patients with CKD, ECF was an independent risk factor of CKD progression and mortality. Hence, close monitoring and treatment of fluid overload are important for the clinical management of patients with non-dialysis CKD.

A symposium on kidney stones and mineral metabolism held on December 2017 in Brussels, Belgium was the first international multidisciplinary conference of the International Collaborative Network on Kidney Stones and Mineral Metabolism. This meeting addressed epidemiology, underlying pathophysiological mechanisms, genetics, pathological, as well as clinical and research topics. The participants included clinicians and recognized experts in the field from Europe and the United States interacted closely during the symposium which promoted a chance to explore new frontiers in the field of kidney stone disease. This manuscript summarizes some of the major highlights of the meeting., info:eu-repo/semantics/published

Background Pseudoxanthoma elasticum (PXE) is a genetic disease caused by mutations in the ABCC6 gene that result in low pyrophosphate levels and subsequent progressive soft tissue calcifications. PXE mainly affects the skin, retina, and arteries. However, many patients with PXE experience kidney stones. We determined the prevalence of this pathology in patients with PXE and examined the possible underlying mechanisms in murine models. Methods We conducted a retrospective study in a large cohort of patients with PXE and analyzed urine samples and kidneys from Abcc6 −/− mice at various ages. We used Yasue staining, scanning electron microscopy, electron microscopy coupled to electron energy loss spectroscopy, and Fourier transform infrared microspectroscopy to characterize kidney calcifications. Results Among 113 patients with PXE, 45 (40%) had a past medical history of kidney stones. Five of six computed tomography scans performed showed evidence of massive papillary calcifications (Randall plaques). Abcc6 −/− mice spontaneously developed kidney interstitial apatite calcifications with aging. These calcifications appeared specifically at the tip of the papilla and formed Randall plaques similar to those observed in human kidneys. Compared with controls, Abcc6 −/− mice had low urinary excretion of pyrophosphate. Conclusions The frequency of kidney stones and probably, Randall plaque is extremely high in patients with PXE, and Abcc6 −/− mice provide a new and useful model in which to study Randall plaque formation. Our findings also suggest that pyrophosphate administration should be evaluated for the prevention of Randall plaque and kidney stones.

Background Aortic stiffness assessed by carotid-femoral pulse wave velocity (CF-PWV) is a predictor of mortality in several populations. However, little is known in kidney transplant recipients. Our objectives were to evaluate the ability of CF-PWV measured 3 months following transplantation to predict mortality, graft loss and its potential links to measured Glomerular Filtration Rate (mGFR) or kidney graft microvasculature parameters. Methods The study is based on a monocentric retrospective cohort including 220 adult kidney graft recipients evaluated three months after transplantation. CF-PWV measures, clinical, laboratory and histological data performed at 3 (M3) and 12 months (M12) following transplantation were retrospectively collected. The two primary endpoints were all-cause mortality and occurrence of end stage renal disease (ESRD) defined by initiation of dialysis. Results After a median follow up of 5.5 years [1.9; 8.8], death and graft loss occurred in 10 and 12 patients respectively. M3 CF-PWV was an independent mortality risk factor (HR = 1.29 [1.03; 1.61]; p = 0.03), despite no aortic stiffness variation during the first year of transplantation. Of notice, M3 CF-PWV was not associated with M12 mGFR or ESRD outcome. Graft microcirculation assessed by Banff vascular fibrous intimal thickening score (cv) worsened between M3 and M12 (p = 0.01), but no link was found with CF-PWV, mGFR or ESRD outcome. Surprisingly, acute rejections at M3 were associated after adjustment with mortality (p = 0.03) but not ESRD. Conclusion Aortic stiffness measured 3 months after kidney transplantation is a strong predictor of mortality with no obvious influence on kidney graft microvasculature or graft loss.

Introduction L’endocardite infectieuse (EI) est une pathologie rare mais frequemment compliquee d’insuffisance renale (IR). Parmi les mecanismes physiopathologiques decrits, la nephropathie microcristalline aux cristaux d’antibiotiques semble etre sous evaluee. L’objectif de notre etude est de decrire la prevalence et l’impact sur le pronostic renal des cristaux urinaires d’antibiotique ainsi que d’identifier les facteurs associes a leur survenue. Methodes Tous les patients admis pour suspicion d’EI sur une periode de 12 mois et traites par antibiotherapie ont beneficie d’une ou plusieurs cristalluries. Cette analyse etait realisee par microscopie en lumiere polarise et spectroscopie infrarouge sur urines fraiches. Le critere de jugement principal etait la presence de cristaux d’antibiotique. Les criteres de jugement secondaires etaient la survenue d’une IRAigue durant l’hospitalisation et le DFG a j14. Un modele de regression mixte a ete applique afin de prendre en compte le caractere longitudinal des cristalluries realisees. Resultats obtenus ou attendus 65 cristalluries issues de 34 patients ont ete realisees. Le delai median de realisation de la 1e cristallurie etait de 5[3–6]jours. 18/65 prelevements issus de 14/34 patients sont revenus positifs. La creatininemie concomitante de l’analyse urinaire etait de 99[65–206]μmol/L. La presence de cristaux etait associee a une concentration serique d’amoxicilline elevee (OR = 1,02[1,01–1,05]) et un pH urinaire bas (OR = 0,79[0,62–0,94]). Une IRAigue etait observee chez 18/34 des patients. Aucune association entre une cristallurie positive et la survenue d’une IRA n’etait retrouve (p = 0,9). A j14, 11/34 patients avaient un DFG Conclusion Chez les patients traites par antibiotherapie pour EI, la survenue de cristaux urinaire d’antibiotiques est frequemment observee et associe au pH urinaire et a la concentration serique d’antibiotique. Il n’a pas ete observe d’association avec le pronostic renal. Des etudes supplementaires sont necessaires pour confirmer ces resultats.

International audience; Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.

Introduction Le Pseudoxanthome elastique (PXE) est une maladie genetique recessive liee a une mutation du gene ABCC6, exprime dans le foie et le rein. Cette mutation est a l’origine d’un defaut systemique de production de pyrophosphate, un inhibiteur de la mineralisation. Les patients atteints de PXE developpent des calcifications de la peau, de la retine et des arteres mais la presence de calcifications renales chez ces patients a ete tres peu documentee. Patients/Materiels et methodes Une etude retrospective sous forme de questionnaire a ete conduite parmi 113 patients atteints de PXE afin d’evaluer la prevalence de la maladie lithiasique et de ses complications. Les scanners renaux et analyses biologiques de 6 patients atteints de PXE et de lithiase ont egalement ete analyses. Enfin, une etude a ete menee in vivo a l’aide d’un modele murin de PXE (souris Abcc6−/−), dont la biologie urinaire et les calcifications renales ont ete analysees entre l’âge de 2 mois et 2 ans. Chez certains animaux la fonction hepatique d’ABCC6 a ete restauree par transfection d’un gene fonctionnel humain, avec des animaux controles transfectes par un gene mute non fonctionnel. Les calcifications ont ete etudiees par la coloration de Yasue, par microscopie electronique a balayage et a transmission et par micro-spectrometrie infrarouge. Observation/Resultats Parmi les 113 patients ayant repondu au questionnaire, 45 (40 %) ont ete atteints de colique nephretique liee a des calculs renaux. Les scanners ont mis en evidence des calcifications papillaires massives chez 5 patients sur 6. Les souris Abcc6−/− ont developpe spontanement des calcifications avec l’âge, manifestes apres 12 mois et massives a 24 mois, localisees electivement a la pointe des papilles renales, interstitielles, faites de phosphate de calcium amorphe et d’apatite, soit toutes les caracteristiques de la plaque de Randall humaine. L’expression de la proteine ABCC6 fonctionnelle dans le foie de ces animaux a permis de restaurer la production de pyrophosphate et de prevenir le developpement de la plaque de Randall dans le rein. Discussion Le deficit en pyrophosphate circulant lie a une mutation ou une deletion d’ABCC6 est suffisant pour induire des calcifications papillaires massives, des plaques de Randall qui sont la premiere etape de la formation ulterieure des calculs urinaires chez l’homme. Conclusion Il s’agit du premier modele murin mimant reellement les caracteristiques de la plaque de Randall humaine. Le traitement par pyrophosphates exogenes, potentiellement realisable chez l’homme, pourrait ainsi prevenir le developpement de ces calcifications pathologiques.

Introduction La nephropathie a 2,8 di-hydroxyadenine (2,8 DHA) est une maladie severe, secondaire a une mutation autosomique recessive du gene qui code pour l’adenine phosphoribosyl transferase (APRT). Elle se manifeste par la survenue de lithiase renale et/ou par la precipitation intratubulaire de 2,8 DHA et conduit a la maladie renale chronique, recidivant sur le greffon renal. Le traitement preventif repose sur l’administration d’inhibiteurs de la xanthine oxydase. L’objectif de cette etude etait d’evaluer l’impact de ces depots cristallins sur l’inflammation tissulaire renale. Patients/materiels et methodes Nous avons analyse 17 biopsies renales realisees chez 12 patients atteints de mutations de l’APRT (10 femmes, 2 hommes ; 12 greffons et 5 reins natifs). Nous avons realise des immunomarquages des cellules inflammatoires. En parallele, nous avons etudie in vitro la reponse inflammatoire induite par des cristaux de DHA (et des cristaux d’urate de sodium comme controles positifs) sur une lignee de macrophages murins RAW 264.7, notamment la secretion de cytokines (Elisa et qPCR). Resultats Les cristaux de DHA avaient un aspect tres variable selon les prelevements : irreguliers (n = 17), spheriques (n = 16), ou en anneau (n = 10). Leur aspect en lumiere polarisee etait radial dans 100 % des biopsies (n = 17), en aiguilles (n = 7) ou en croix de malte (n = 6). Leur localisation etait intratubulaire (n = 16), intra-epitheliale (n = 17) ou interstitielle (n = 12). L’ensemble des prelevements comportait des lesions de necrose tubulaire (n = 17), souvent une atrophie tubulaire et une fibrose interstitielle (n = 14), et une inflammation interstitielle diffuse (n = 9). Des lesions granulomateuses ont ete observees dans 88 % des biopsies (n = 15), avec presence de cellules geantes multinucleees englobant les cristaux et entoures de fibrose interstitielle. Les macrophages etaient repartis de facon stereotypee autour des cristallites (M1 au centre, M2 a l’exterieur). In vitro, les cristaux de DHA ont induit la formation de granulomes (macrophages « geants », avec aspect dendritique, cellules multinuclees), a partir de la 72e heure. L’exposition des macrophages aux cristaux de 2,8 DHA a induit une augmentation de secretion de cytokines, notamment de TNF-alpha. Conclusion La nephropathie a 2,8 DHA est une maladie granulomateuse, ou l’inflammation tissulaire joue probablement un role majeur dans la degradation de la fonction renale, qui n’est donc probablement pas liee qu’a l’obstruction tubulaire. Des modeles in vivo vont permettre de determiner si l’ajout de traitements anti-inflammatoires (ciblant le TNF-alpha) peut ameliorer la fonction renale en synergie avec les inhibiteurs de la xanthine oxydase.

Introduction Le Hungry Bone Syndrome (HBS) est defini par une hypocalcemie persistante pendant plusieurs jours apres l’effondrement des taux de PTH, par un processus actif de remineralisation osseuse. C’est une complication de la parathyroidectomie realisee dans le cadre des hyperparathyroidies primaires, ou autonomisees chez l’insuffisant renal. Un HBS peut etre observe a minima apres transplantation renale. Nous decrivons ici un cas extremement severe de HBS dans les suites d’une transplantation renale. Patients/Materiels et methodes/Observation Une patiente de 36 ans, Malienne, hemodialysee depuis 5 ans, beneficie d’une transplantation renale d’un donneur decede quatre semaines apres une parathyroidectomie subtotale (hyperplasie diffuse). Le jour de la greffe la calcemie corrigee est a 2,18 mmol/L et la PTH a 51 ng/L (n = 17–65 pg/mL) avec des dosages de 25-OH D3 et de calcitriol normaux. Les suites sont marquees par une reprise immediate de fonction avec un nadir de creatininemie a 124 μmol/L a j10. Elle consulte a j21 de la greffe pour crampes, spasmes de la face et du cou. On note une calcemie corrigee a 1,21 mmol/L, ionisee a 0,58 mmol/L (n = 1,14–1,31 mmol/L), un taux de parathormone inapproprie a 35 pg/mL, une hyperphosphoremie transitoire a 2 mmol/L, et une hypomagnesemie a 0,66 mmol/L. La calciurie, la magnesurie et la phosphaturie sont effondrees, le calcitriol est augmente, sous alfacalcidol (172 pg/mL, 17 En depit d’apports calciques per os de plusieurs grammes par jour et d’un traitement par alfacalcidol a pres de 2 μg/jour, la calcemie ne peut etre maintenue a un taux suffisant pour eviter les symptomes qu’au prix d’une perfusion de calcium, avec des apports IV allant jusqu’a 12 grammes/jour sur voie centrale. Durant plus de 3 semaines, la calciurie reste effondree et la calcemie reste basse en depit des apports massifs de calcium, traduisant un flux osseux entrant de calcium extremement eleve. Le TEP-scanner au fluorure de sodium objective une intense captation intense et diffuse du traceur par le squelette axial et peripherique proximal. Resultats/Discussion/Conclusion La conjonction dans le temps de deux etiologies de HBS, la parathyroidectomie et la transplantation renale, ont abouti a une hypocalcemie profonde et symptomatique necessitant des doses massives de calcium IV en plus des apports per os de calcium et de vitamine D active de facon prolongee. Une surveillance rapprochee de la calcemie et de la calciurie doit etre realisee dans les suites d’une transplantation renale suivant une parathyroidectomie recente.

Introduction L’amoxicilline (AMX) est un des antibiotiques les plus prescrits et sa toxicite renale est peu decrite. La presence de cristaux d’AMX dans les urines au cours de cas d’insuffisance renale aigue (IRA) associees a l’AMX a fait evoquer un mecanisme de precipitation intra-tubulaire. Cependant, il n’existe pas de description de cristaux d’AMX dans le parenchyme renal. Methodes Nous decrivons deux patients presentant une IRA secondaire a l’AMX et ayant beneficie d’une biopsie renale. Nous avons ensuite elabore un modele de toxicite chez le rongeur. Nous decrivons ces deux cas de nephropathie associee a l’AMX et l’analyse de leurs biopsies renales avec spectrophotometrie infra-rouge (SPIR) et microscopie electronique a balayage (MEB). Dans un deuxieme temps, differentes doses d’AMX (de 200 a 3000 mg/kg/jour) ont ete injectees par voie intra-peritoneale pendant 48 heures aux rats, et jusqu’a 9 jours aux souris. Nous avons analyse au sacrifice la cristallurie, la fonction renale et l’histologie des rongeurs. Resultats obtenus ou attendus Deux patients de 58 et 68 ans hospitalises pour une meningite bacterienne ont presente une IRA a l’AMX. Ils recevaient 12 g/jour et 25 g/jour respectivement en intraveineux. L’analyse en microscopie optique des biopsies revele dans les deux cas une tubulopathie severe avec des lesions de nephrose osmotique. Dans un des cas, l’analyse SPIR combinee a la MEB confirme la presence d’un depot intra-tubulaire d’AMX. La cristallurie n’etait pas disponible pour ces deux cas. In vivo, l’injection aux rongeurs d’AMX a posologie croissante aboutit a une IRA avec necrose tubulaire aigue et nephrose osmotique. On ne retrouve pas de cristaux d’AMX intraparenchymateux chez le rongeur ni de cristallurie. Conclusion Ces deux cas suggerent qu’il peut exister une toxicite tubulaire directe de l’AMX avec des lesions de nephrose osmotique reproduites dans le modele animal. On decrit, pour la premiere fois, un depot intratubulaire d’AMX chez l’Homme suggerant une precipitation intratubulaire associee.

Introduction Grâce a une prise en charge precoce, l’esperance de vie des patients drepanocytaires homozygotes augmente expliquant l’incidence des complications chroniques liees a cette maladie. La prevalence de la maladie renale chronique (MRC) serait de 85 % chez les patients de plus de 65 ans drepanocytaires. L’objectif de notre etude est de determiner les facteurs de risque d’apparition d’une MRC stade 2. Methodes Etude prospective observationnelle monocentrique d’une cohorte de 688 patients suivis entre 2007 et 2018 dans un centre de drepanocytose. Un total de 660 patients ayant un eDFG > 90 ml/min/1.73 m2 (CKD EPI) ont ete inclus. L’evenement etudie etait l’apparition d’une MRC stade 2 (DFG Resultats obtenus ou attendus Le delai median de suivi etait de 3,7 ans (IQR 0,76–7,36). L’âge median a l’inclusion etait de 22 ans (IQR 19–29), avec 377 (57,12 %) femmes. Une hyperfiltration glomerulaire (DFG > 130 ml/min/1,73m2) etait presente chez 380 patients (57,58 %), une microalbuminurie et une macroalbuminurie chez 218 (33,70 %) et 83 (12,83 %) patients respectivement. Les pressions arterielles systoliques et diastoliques moyennes (± deviation standard) etaient basses ; respectivement 114,8 mmHg (± 13,6) et 66,0 (± 9,7) mmHg. Les facteurs associes a l’apparition d’une MRC stade 2 etaient (analyse multivariee) : la proteinurie (pour 100 mg/mmol creatinine) HR : 1,24 [1,07–1,45] p = 0,005, la pression arterielle diastolique (PAD) (pour 10 mmHg) HR : 1,35 [1,03–1,76] p = 0,029 et les LDH HR : 1,22 [1,04–1,43] p = 0,015, le DFG initial HR : 0,92 [0,90–0,95] p Conclusion Notre etude montre une augmentation significative du risque de degradation de la fonction renale dans les cas de macroalbuminurie, d’augmentation de la PAD et d’hemolyse chronique intense. Ces resultats suggerent l’importance d’un controle tensionnel dans cette population avec des valeurs cibles particulierement basses.

International audience; 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.; Introduction: Les calcifications pathologiques rénales qu’elles s’apparentent à des concrétions ou à des calcifications tissulaires impliquent de savoir déterminer correctement les composés chimiques qui les composent afin de porter un diagnostic menant à une prise en charge adéquate. Le but de cet article de revue est de dépeindre les techniques physicochimiques aptes à réaliser cette caractérisation structurale et chimique à l’échelle du micromètre et de montrer leur insertion au sein même de l’hôpital.Méthode: Les résultats acquis ces dix dernières années utilisant des techniques de caractérisation de laboratoire ou spécifiques aux grands instruments comme le synchrotron Soleil ou le laboratoire Léon-Brillouin sont présentés. Leur pertinence dans l’activité du clinicien a été examinée.Résultats: Le rôle des éléments traces dans la pathogenèse des calculs rénaux au travers de données acquises par fluorescence X est discuté. Si leurs propriétés catalytiques ne sont pas confirmées par les données expérimentales, l’analyse fine a dévoilé certaines particularités intéressantes concernant les teneurs en Zn des deux composés d’oxalate de calcium, i.e. whewellite et weddellite. En effet, les calculs de weddellite présentent des bipyramides aux angles et arêtes vifs susceptibles d’induire une inflammation tissulaire. L’analyse morphoconstitutionnelle des biopsies rénales dévoile une grande diversité chimique puisque 22 corps différents ont été identifiés. Cette diversité indique que les méthodes de coloration dont l’anatomopathologiste dispose sont insuffisantes pour caractériser ces corps. Enfin, nous énumérons différentes problématiques abordées par les grands instruments et définies par le clinicien.Conclusion: La complexité structurale et la diversité chimique des calcifications pathologiques invitent à la mise en œuvre de techniques de caractérisation physicochimiques. Seule cette approche permet au clinicien la pose d’un diagnostic fiable et donc une prise en charge adéquate du patient.

International audience; Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm3). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.

Introduction La presence de micro-calcification (MC) dans le parenchyme renal est polymorphe et inconstamment rapportee au sein des ponctions biopsies renales (PBR). Nous en donnons une description standardisee. Patients et methodes Etude retrospective multicentrique descriptive par analyse de registre suivie d’une relecture standardisee (optique, lumiere polarisee, colorations) des lames de PBR avec MC et recueils des donnees cliniques et biologiques. Resultats Des MC etaient decrites sur 214 (4,7 %) biopsies realisees entre janvier 2000 et 2016, chez 4512 adultes. Cent cinquante-cinq dossiers etaient analysables. L’iconographie revelait 3 nephrocalcinoses radiologiques. Les MC predominaient en intra-tubulaire (86,5 %), a la jonction cortico-medullaire (74,8 %) en presence d’une necrose tubulaire (NTA) dans 60 % des cas. Une reaction cellulaire y etait associee dans 47 % des cas. L’aspect des MC evoquait une nature phosphocalcique (P-Ca), violettes, arrondies, non refringentes ; oxalocalcique (Ox-Ca), incolores, refringentes et radiaires ; et mixte dans 44 %, 24,5 % et 29 % des cas respectivement. Le Von kossa colorait a la fois les MC P-Ca et Ox-Ca. Les MC Ox-Ca etaient plus nombreuses (moyenne de 1,87 vs 0,54 MC par champs X200), mais de meme taille (moyenne de 0,096 vs 0,90 mm) que les P-Ca. Elles etaient plus souvent associees a une NTA, dans un contexte d’IRA, avec une creatininemie plus eleve que les MC P-Ca. Une etiologie specifique aux MC etait retrouvee dans 26 % des cas (17 malabsorptions, 17 hypercalcemies, 7 medicaments). Discussion La frequence declaree des MC est de 4,7 % des biopsies avec 44 % de P-Ca, 24,5 % d’Ox-Ca et 29 % de mixte. La coloration de Von Kossa ne distingue pas le P-Ca de l’Ox-Ca. Les MC sont majoritairement intra-tubulaires, cortico-medullaire et associee a de la de NTA. Une etiologie est retrouvee dans 1/4 des cas. Une etude en imager est en cours, afin de caracteriser la nature de ces cristaux. Conclusion Cette etude permet d’obtenir une cartographie des nephropathies cristallines du Nord-Pas-de-Calais. Nos resultats suggerent l’importance du role joue par la NTA dans la retention cristalline. Groupe(s) de travail Reseau Nephronor.

Introduction Apres une transplantation renale, 4 a 78 % des patients presentent des calcifications du greffon. L’abondance de celles-ci est correlee au pronostic du greffon, avec une moins bonne survie renale en cas de nombreuses calcifications. Nous avons mis au point un modele murin de nephropathie cristalline ischemique afin d’etudier la cinetique d’apparition des cristaux, leurs compositions, localisations et le role d’une proliferation tubulaire precoce ou retardee apres insuffisance renale aigue ischemique. Materiels et methodes Souris femelles C57BL6 J ayant un regime comprenant glucose phosphate disodique et gavage par ergocalciferol soumises a une ischemie renale de 45 minutes avec nephrectomie controlaterale (IRA). En fonction des groupes, induction (ou non) d’une proliferation tubulaire a j2 par l’administration intraperitoneale de FGF7 en fin de chirurgie. Analyse histologique, infrarouge, en microscopie electronique a balayage et immunohistochimique des reins a differents temps pour les groupes IRA avec et sans FGF7, IRA avec et sans diete phosphatee et mesure des clairances de l’inuline a j30. Resultats On observe a j2 des depots de lipoproteines et de carbapatite a la jonction corticomedullaire (JCM) et une plus faible proportion de cristaux medullaires (CM). Leur nombre est majore dans le groupe IRA + FGF7. A j6, ces depots sont tres abondants. A j30, on observe une clairance presque complete des cristaux corticaux et de JCM. Les CM persistent, mais sont moins abondants dans le groupe FGF7. On n’observe pas de cristaux dans les groupes sans diete enrichie en phosphates (PO4). Nos resultats preliminaires suggerent une diminution de la clairance de l’inuline a j30 dans le groupe IRA + diete PO4 par rapport aux groupes IRA + diete PO4 + FGF7 et IRA sans diete PO4. Discussion La presence d’une diete PO4 lors d’une IRA est responsable a court terme de calcifications de JCM reversibles, mais de CM tubulaires persistantes a j30 qui semblent deleteres sur la fonction renale. L’administration de FGF7 au moment de l’IRA, responsable d’une proliferation tubulaire precoce, semble benefique sur les calcifications et la fonction renale a long terme en conditions de sursaturation urinaire. Conclusion Ce travail ouvre la perspective d’une utilisation de FGF7 au decours d’une greffe renale afin d’ameliorer le pronostic renal a long terme.

International audience; A 26-year-old woman was referred for recurrent urolithiasis. The first manifestation occurred 3 years before, followed by recurrent acute episodes. She underwent one ureteral stent placement, one shock wave lithotripsy, and at last a flexible ureteroscopy that allowed to retrieve all the remaining stones. She had no other medical history with the exception of paroxysmal tachycardia, poor dairy intake in her diet and did not take any medication interfering with calcium or phosphate homeostasis. Regarding her family history, her mother had also recurrent renal colic due to urolithiasis. Morphoconstitutional analysis revealed a stone made of calcium phosphate and to a lesser extent calcium oxalate, in concentric layers. According to infrared spectra analysis, the stone consisted mainly of calcium phosphate: 56% carbonated apatite, 20% octacalcium phosphate pentahydrate (OCP), 12% calcium oxalate monohydrate, 10% calcium oxalate dihydrate and 2% proteins.