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Since its first use several decades ago, scanning electron microscopy has been used in numerous investigations dedicated to biological systems. This contribution focuses on observations on pathological calcifications in order to review several major applications of primary importance to the clinician. Among these, we highlight such observations as medical diagnostic tools in pathologies arising from primary hyperoxaluria and urinary infections.

OBJECTIVE To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or RESULTS There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

Lithium treatment can induce nephrogenic diabetes insipidus (NDI), but no consensus intervention is offered to date. We evaluated in these patients patterns of urine concentration and the correlates of 24-hour urine output.Prospective, single-center, observational study of 217 consecutive lithium-treated individuals, with 24-hour urine collection, desmopressin (1-deamino-arginine vasopressin [DDAVP]) concentrating test, fasting plasma vasopressin measurement (copeptin measurement inOf the individuals, 21% displayed polyuria (3 l/d), but 55% displayed elevated fasting vasopressin level (5 pg/ml). Uosm was significantly lower and urinary output and free water clearance were significantly higher in individuals treated for10 years. MaxUosm was600 mOsm/KgHHigher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce polyuria in these patients.

Background A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. Methods Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. Results In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of –0.6 and –3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. Conclusion In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.

Background Inter-individual variations of non-glomerular filtration rate (GFR) determinants of serum creatinine, such as muscle mass, account for the imperfect performance of estimated GFR (eGFR) equations. We aimed to develop an equation based on creatinine and total lumbar muscle cross-sectional area measured by unenhanced computed tomography scan at the third lumbar vertebra. Methods The muscle mass–based eGFR (MMB-eGFR) equation was developed in 118 kidney donor candidates (iohexol clearance) using linear regression. Validation cohorts included 114 healthy subjects from another center (51Cr-EDTA clearance, validation population 1), 55 patients with chronic diseases (iohexol, validation population 2), and 60 patients with highly discordant creatinine and cystatin C–based eGFR, thus presumed to have atypical non-GFR determinants of creatinine (51Cr-EDTA, validation population 3). Mean bias was the mean difference between eGFR and measured GFR, precision the standard deviation (SD) of the bias, and accuracy the percentage of eGFR values falling within 20% and 30% of measured GFR. Results In validation population 1, performance of MMB-eGFR was not different from those of CKD-EPICr2009 and CKD-EPICr2021. In validation population 2, MMB-eGFR was unbiased and displayed better precision than CKD-EPICr2009, CKD-EPICr2021 and EKFC (SD of the biases: 13.1 vs 16.5, 16.8 and 15.9 mL/min/1.73 m2). In validation population 3, MMB-eGFR had better precision and accuracy {accuracy within 30%: 75.0% [95% confidence interval (CI) 64.0–86.0] vs 51.5% (95% CI 39.0–64.3) for CKD-EPICr2009, 43.3% (95% CI 31.0–55.9) for CKD-EPICr2021, and 53.3% (95% CI 40.7–66.0) for EKFC}. Difference in bias between Black and white subjects was −2.1 mL/min/1.73 m2 (95% CI −7.2 to 3.0), vs −8.4 mL/min/1.73 m2 (95% CI −13.2 to −3.6) for CKD-EPICr2021. Conclusion MMB-eGFR displayed better performances than equations based on demographics, and could be applied to subjects of various ethnic backgrounds.

Resume Cette etude a compare les composants chimiques des calculs du haut et du bas appareil urinaire chez des patients congolais, et identifie les facteurs associes aux differents types de calculs. Les calculs extraits du haut appareil urinaire de 119 patients et les calculs extraits du bas appareil urinaire de 75 autres patients ont ete analyses par spectrophotometrie infrarouge. Parmi 119 patients presentant des calculs du haut appareil, l’âge variait de 10 a 81 ans, avec une moyenne (ecart-type) de 45,8 (13,6) ans. Les hommes etaient plus nombreux (55,5 %) que les femmes. La whewellite etait le corps majoritaire preponderant. Parmi les 75 patients presentant des calculs du bas appareil urinaire, l’âge variait de 4 a 87 ans, avec une moyenne (ecart-type) de 51,6 (21,6) ans. Les hommes etaient preponderants (89,3 %). La whewellite (44 %) et l’acide urique anhydre (22,7 %) etaient les corps majoritaires les plus importants. Dans l’ensemble, les facteurs associes a l’oxalate de calcium etaient le siege au niveau du haut appareil urinaire (4,95 ; IC 95 % 2,35–10,44) et le petit diametre des calculs (3,03 ; IC 95 % 1,45–6,25) ; la residence a Kinshasa (0,05 ; IC 95 % 0,01–0,29) etait associee au phosphate de calcium. Au niveau du haut appareil urinaire, le siege (0,19 ; IC 95 % 0,06–0,63) et le petit diametre des calculs (0,10 ; IC 95 % 0,03–0,38) etaient associes aux calculs d’infection. Le jeune âge des patients (0,26 ; IC 95 % 0,09–0,71) et le siege au niveau du haut appareil urinaire (0,23 ; IC 95 % 0,07–0,68) etaient associes aux calculs uriques. Le profil epidemiologique et chimique des calculs du haut appareil differe de celui des calculs du bas appareil urinaire. Plusieurs facteurs sont associes a la composition chimique et cristalline des calculs en Republique Democratique du Congo.

Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients responsible for a high morbidity and mortality. However, sickle cell nephropathy natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using Cox model. 535 SCA patients were included with a median follow-up of 5.33 (IQR:2.10-8.13) years. Median age was 22 (IQR:19-30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 [95% CI: 1.61;9.43], diastolic blood pressure (DBP) above 70 mmHg HR: 2.02 [1.02-3.971], LDH (for 100 UI/L increase) HR: 1.28 [1.12;1.48] and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 [1.20- 6.99]. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 [1.09;1.16] and a 13.3 fold increase above 30 years (p

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.

The production of 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for glomerular filtration rate (GFR) measurement in Europe, was recently halted by the manufacturer. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance has so far mostly been restricted to assessment of separate renal function by scintigraphy, but scarcely used and validated for GFR measurement. We compared the performances of 51Cr-EDTA and 99mTc-DTPA for GFR and extracellular fluid measurement. In a multi-centre prospective study, 51Cr-EDTA and 99mTc-DTPA were simultaneously injected into 88 patients, and their urinary and plasma clearances, as well as their volumes of distribution, were measured during seven 30-min periods after a 90-min equilibrium time. Mean age was 52.2 ± 14.5 years, 59% were men. Urinary clearances of 51Cr-EDTA and 99mTc-DTPA were 64.1 ± 27.6 and 66.1 ± 28.0 mL/min, respectively, with a mean bias of 2.00 ± 2.25 mL/min, an accuracy within 10% of 95% [95% CI 91–99], and a coefficient of determination (R2) of 0.994. Plasma clearances of 51Cr-EDTA and 99mTc-DTPA were 66.1 ± 25.8 and 68.1 ± 26.6 mL/min, respectively, with a mean bias of 1.96 ± 3.32 mL/min, an accuracy within 10% of 91% [95% CI 85–97] and a R2 of 0.985. Distribution volumes were 17.3 ± 4.6 L for 51Cr-EDTA and 16.6 ± 4.6 L for 99mTc-DTPA (R2 0.930). The accuracy and precision of 99mTc-DTPA clearance, compared to 51Cr-EDTA clearance, was excellent for both urinary and plasma clearance methods, despite an approximate 2 mL/min overestimation, showing that the tracer is a reliable alternative to 51Cr-EDTA for GFR measurement.

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

Most human urinary stones are calcium-based and are often associated with hypercalciuria. A simple test described in 1975 by Pak et al allows for pathogenic classification of hypercalciuria: the calcium load test (CLT). The CLT explores calcium homeostasis after a low-calcium diet and then a calcium load (typically oral administration of 1 g of elemental calcium). Only simple laboratory equipment is required. Inadequate calcium excretion after a calcium-free diet or a calcium load is suggestive of resorptive or absorptive hypercalciuria, respectively. The CLT is particularly valuable in diagnosing primary hyperparathyroidism, even in most early stages of this disease. PATIENT SUMMARY: Kidney stone formation can be linked to calcium metabolism. When high calcium levels are found in urine despite adequate diet changes, a calcium load test may help to understand the underlying mechanisms. Urine and blood levels are explored during a low-calcium diet phase, and after a calcium load phase in the test. The calcium load test is particularly advantageous for revealing abnormally high function of the parathyroid gland, which is called hyperparathyroidism.

Introduction: Worldwide, the incidence of kidney stones has been progressively increasing. Various factors can influence the risk of stone formation, including lifestyle and eating habits. The dietary investigation is a standard of care in patients with urolithiasis. The objectives of this study were to determine the dietary habits of lithiasis patients in the city of Kinshasa and to investigate the association between dietary habits and the composition of the stones. Material and Methods: From January 2017 to September 2019, 85 patients attending 8 hospitals participated in the nutrition survey. Various foods commonly consumed in the Democratic Republic of Congo were categorized based on their composition: foods rich in animal proteins, foods rich in calcium, foods high in sugar, foods high in oxalate, and various vegetables and fruits. We also investigated daily water intake. The composition of the collected stones was analyzed by infrared spectrophotometry. Results: The mean (SD) age of patients was 47.1 (14.0) years, 63.5% of patients were males, 75.3% of the patients had stones located in the upper urinary tract, and 7.1% were undernourished. Most of patients consumed vegetables (77.6%), animal proteins (62.4%), and foods rich in oxalate (58.8%). The daily water intake was less than 1500 mL in more than half of the patients (68.2%). Major anhydrous uric acid stones were associated with a high body mass index (p = 0.025). Male patients with a high oxalate diet had more calcium oxalate stones (64.3%) compared to other types of stones (p = 0.041). Conclusion: High consumptions of vegetables and low water intake were linked to the formation of calcium oxalate monohydrate stones. More data are needed to confirm these findings.

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 Current Glomerular filtration rate (GFR) estimating equations based on serum creatinine are facing increased criticism due to the inclusion of a race correction in black Americans with the CKD-EPI equation (CKD-EPIASR, A = Age, S = Sex, R = Race). A new equation without race (CKD-EPIAS) has been proposed. However, this equation was developed mainly from US cohorts. The performance of this new equation has been poorly compared with current European-developed creatinine-based equations, i.e. the Lund-Malmö Revised (LMR), and the new European Kidney Function Consortium (EKFC) METHOD Data from subjects over 18 years, representing 11 cohorts from Europe (previously described as the EKFC dataset, n = 13 856), and enhanced with data from Brazil (n = 100), France (n = 4429) and Africa [Democratic Republic of Congo (DRC) and Côte d'Ivoire, n = 508] were considered (n = 18 893 for the whole cohort). The EKFC cohort was considered as non-black population. All data from Africa derived from black individuals. From France, 964 subjects were self-reported as black (=Blacks from Paris). Measured GFR as a reference method and IDMS creatinine results were available. Median bias (eGFR—mGFR) with 95% confidence intervals (CI), imprecision (interquartile range: IQR), and P30 accuracy (percentage of eGFR-values within ± 30% of mGFR) with 95% CI were calculated. RESULTS Results are summarized in Table. CONCLUSION The new CKD-EPIAS has been launched in the USA for societal reasons and is now recommended by US guidelines. However, in Europe and Africa, its performance was suboptimal. The EKFC equation, using the usual Q values, or population-specific Q values (when available), displays the best performance over the whole age range for populations in Europe and Africa.

International audience; ObjectiveFamilial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss‐of‐function mutations of the calcium‐sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1.Design and patientsThis observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.ResultsHypercalcaemia was diagnosed at a median age of 53 years [IQR: 38‐61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63‐2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1‐7.1], and the median 24‐hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9‐4.0]. Osteoporosis (dual X‐ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established.ConclusionThis large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.

International audience

International audience; Background: Lithium therapy during bipolar disorder is associated with an increased risk of chronic kidney disease (CKD) that is slowly progressive and undetectable at early stages. We aimed at identifying kidney image texture features as possible imaging biomarkers of decreased measured glomerular filtration rate (mGFR) using radiomics of T2-weighted magnetic resonance imaging (MRI).Methods: One hundred and eight patients treated with lithium were evaluated including mGFR and kidney MRI, with T2-weighted sequence single-shot fast spin-echo. Computed radiomic analysis was performed after kidney segmentation. Significant features were selected to build a radiomic signature using multivariable Cox analysis to detect an mGFR

Understanding the physico-chemistry related to cristalline pathologies constitutes a challenge in several medical specialities such as nephrology, dermatology or oncology. Regarding nephrology, the chemical diversity of concretions such as kidney stones calls for characterization techniques to determine the chemical composition of concretions. The starting point of this contribution is given by Fourier Transform InfraRed (FTIR) spectroscopy which is routinely used at the hospital to deter-mine the chemical composition of kidney stones as well as ectopic calcifications present in kidney biopsy. For kidney stones, the quantity of sample is sufficient to perform a significant analysis through classical FTIR. For ectopic calcifications, mu FTIR can be inefficient in the case of mu calcification in the tissue when their size is less than 10 mu m. For such samples, Optical PhotoThermal IR (OPT-IR) spectroscopy may constitute a way to overcome this experimental difficulty through the acquisition of IR spectrum with a spatial resolution close to 500 nm.To illustrate such opportunity, we first compare the IR spectrum acquired with a classical experimental set-up related to classical IR spectroscopy to IR spectrum collected with a OPT-IR one for different compounds namely calcium oxalate monohydrate, calcium oxalate dehydrate, calcium phosphate apatite and magnesium ammonium phosphate hexahydrate. Such comparison helps us to assess specificity of OPT-IR. Then, we consider several pathological calcifications associated to hyperoxaluria, adenine phosphoribosyltransferase (APRT) deficiency or the presence of Randall's plaque. We will see that the nanometer spatial resolution constitutes a major advantage versus a micrometre one. Also, in the case of Randall's plaque, we show that OPT-IR can determine the chemical composition of microscopic concretion without any kind of preparation. Such experimental fact is clearly a major advantage. Finally, we also extended this first investigation in nephrology by considering breast calcifications. In that case, if the number of chemical phases is quite low compared to the number of chemical phases identified in ectopic calcifications present in kidney (four instead of 24), the challenge is related to the possibility to distinguish between the different calcium phosphate namely amorphous carbonated calcium phosphate, CA and whitlockite.The complete set of data indicates the limitations and the advantages of OPT-IR spectroscopy.

Synchrotron deep ultraviolet imaging highlighting pathological calcium oxalate detection in kidney is presented., 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.

Most papers on kidney stones arising from infection concentrate on the mineral struvite. In this contribution, we would like to call attention to other mineral phases such as highly carbonated calcium phosphate apatite, ammonium urate, and whitlockite, by presenting clinical and chemical data. We start with epidemiological data which emphasize the increase in the prevalence of kidney stones related to infection. Then we present a statistical analysis of more than 85,000 stones which have been analysed at the Laboratoire des Lithiases of Assistance Publique-Hôpitaux de Paris which gives insights regarding the link between urinary tract infection and struvite, carbonated calcium phosphate apatite (carbapatite), and also surprisingly whitlockite. Some information regarding the pathogenesis of kidney stones linked to infection, the nature of the bacteria which have been identified, and the approach to precisely analyse infrared spectra to identify struvite, carbapatite, and whitlockite, conclude this first part. To complete this clinical description, we describe the crystallographic structure and the chemistry of three relevant compounds namely carbonated calcium phosphate, struvite, and whitlockite. To conclude this second part, the dependence of crystallite morphology of struvite on pH and on the presence, or absence, of bacteria, is described. Based on clinical and chemical data, it is becoming clear that struvite is not the only mineral intimately related to renal infectious processes, but that whitlockite and carbapatite with a high carbonation rate are strongly associated with urinary tract infection as well.

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Several clinical settings require an accurate estimation of the physiologically expected extracellular fluid volume (ECFV). We aimed to analyze the performances of existing ECFV-estimating equations and to develop a new equation.The performances of 11 ECFV-estimating equations were analyzed in 228 healthy kidney donor candidates (Bichat Hospital, Paris, France) who underwent ECFV measurement using the distribution volume ofParticipants from Bichat (mean age 45.2 ± 12.0 years, 43.0% men) and Tenon (47.8 ± 10.3 years, 29.6% men) hospitals had a mean measured ECFV of 15.4 ± 2.8 l and 15.1 ± 2.1 l, respectively. Available ECFV-estimating formulae have highly variable precision and accuracy. The new equation incorporating body weight, height, sex, and age had better precision and accuracy than all other equations in the external validation cohort, with a median bias of -0.20 (95% CI: -0.35 to -0.05) l versus -2.63 (-2.87 to -2.42) l to -0.57 (- 0.83 to -0.40) l and 0.21 (0.12 to 0.43) l to 2.89 (2.65 to 3.11) l, for underestimating and overestimating equations, respectively, an interquartile range for the bias of 0.88 (0.70 to 1.08) l versus 0.91 (0.71 to 1.20) l to 1.93 (1.67 to 2.25) l, and an accuracy within 10% of 90.9% (83.8 to 94.4) versus 88.0% (81.0 to 92.3) to 8.5% (4.2 to 13.4). These results were consistent across subgroups defined by sex, body mass index (BMI), body surface area (BSA), age, and ethnicity.We developed and validated a new equation to estimate the individual reference value of ECFV, which is easily usable in clinical practice. Further validation in cohorts including individuals of extreme age and corpulence remains needed.

Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients, (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT, (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p &lt, 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.

Here, we draw attention to a description consistent with the refeeding syndrome by Rodulfus Glaber (ca. 980–1046), a French monk who witnessed the Burgundy famine in 1033 (Brozek et al., 1946). Severe lack of food consequent to repeatedly failed harvests over three subsequent years struck all classes of inhabitants. Hunger made them to consume flesh of deceased humans which was even sold ready cooked at the local market (Brozek et al., 1946 ; Gariballa, 2008). In the five books of the Histories (Historiarum Libri Quinque), Glaber writes about people suffering from the famine that “even when they received food, they became distended and died immediately” (fourth book, chapter 4, 13 [Gariballa, 2008]) (figure 1, showing text from a 12th century copy in Latin and English translation). The distension described in this text may be ascribed to (beriberi-induced) heart failure, although it may also be primarily be due to hunger edema. Heart failure and sudden death upon refeeding is an appreciated feature of the refeeding syndrome (Kraft et al., 2005) Therefore, we consider the description by Rodulfus Glaber to fulfil the clinical criteria of what we currently capture as the refeeding syndrome.

Living kidney donors (LKD) partially compensate the initial loss of glomerular filtration rate (GFR), a phenomenon known as renal functional reserve (RFR). RFR is reduced in the elderly, a population with increased prevalence of chronic kidney disease. We hypothesized that the selected, healthy population of LKD, would specifically inform about the physiological determinants of the RFR and studied it using measured GFR (mGFR).We retrospectively analyzed pre-donation and post-donation mGFR in 76 LKD from Tenon Hospital (Paris, France) between 2002 and 2018. In addition to GFR measurements, we collected pre-donation morphologic parameters, demographic data, and kidney volumes.Mean pre-donation mGFR was 90.11 ± 12.64 mL/min/1.73 mWe found that pre-donation mGFR decreases with age and identified low total kidney volume as a predictor of RFR in healthy individuals. This suggests an adaptative and reversible decrease in kidney function rather than age-related damage. Older subjects may have reduced metabolic requirements with subsequent reduction in glomerular filtration and kidney volume and preserved RFR. Therefore, low GFR in older subjects should not preclude kidney donation.

BACKGROUND The underlying mechanisms of exercise intolerance in sickle cell anaemia (SCA) patients are complex and not yet completely understood. While latent heart failure at rest could be unmasked upon exercise, most previous studies assessed cardiac function at rest. We aimed to investigate exercise cardiovascular reserve as a potential contributor to exercise intolerance in adult SCA patients. METHODS In this observational prospective study, we compared prospectively 60 SCA patients (median age 31 years, 60% women) to 20 matched controls. All subjects underwent symptom-limited combined exercise echocardiography and oxygen uptake (VO2 ) measurements. Differences between arterial and venous oxygen content (C(a-v)O2 ) were calculated. Cardiac reserve was defined as the absolute change in cardiac index (Ci) from baseline to peak exercise. RESULTS Compared to controls, SCA patients demonstrated severe exercise intolerance (median peakVO2 , 34.3 vs. 19.7 ml/min/kg, respectively, p

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.

Clinical manifestations are scarce in AA amyloidosis and, contrary to other types of amyloidosis, involvement of the peripheral nervous system, including the autonomic nervous system, was rarely re...

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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Resume Objectifs Il n’y a actuellement pas de consensus sur la prise en charge chirurgicale de l’hyperparathyroidie secondaire dans l’insuffisance renale chronique terminale. Bien que les deux techniques de parathyroidectomie subtotale et totale permettent d’obtenir de faibles taux de recidives, ces procedures peuvent induire une hypoparathyroidie deletere pour les systemes osseux et cardiovasculaire. Le but de notre etude etait de comparer les parathyroidectomies conservatrices des trois quarts, des parathyroidectomies subtotales des 7/8 dans cette population, et de discuter des avantages d’un traitement plus conservateur. Type d’etude Etude prospective observationnelle dans un hopital universitaire entre 2010 et 2014. Materiel et methodes Cette etude a porte sur 34 patients ayant une insuffisance renale terminale avec hyperparathyroidie secondaire : 19 patients ont eu une parathyroidectomie des trois quarts (groupe A * 3/4) et 15 patients une parathyroidectomie des 7/8 (groupe B * 7/8). Le taux de 1–84 PTH intacte plasmatique (avant et 6 mois apres la chirurgie) et la duree d’hospitalisation ont ete compares entre les deux groupes. Resultats Les taux de iPTH preoperatoires etaient similaires entre les deux groupes. A 6 mois postoperatoires, les taux medians de iPTH etaient significativement plus eleves dans le groupe A*3/4 que dans le groupe B*7/8 (109 contre 24 pg/mL respectivement ; p Conclusions Dans cette etude preliminaire, la parathyroidectomie conservatrice des trois quarts apparait efficace, avec une moindre morbidite que la parathyroidectomie subtotale des 7/8, en limitant la frequence de survenue d’une hypoparathyroidie irreversible ; la duree d’hospitalisation est reduite. Niveau de preuve 3b.

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Resume La cystinurie est une maladie monogenique induisant une perte de fonction d’un transporteur d’acides amines dibasiques implique dans la reabsorption de cystine au niveau des tubules renaux proximaux. L’excretion urinaire de cystine chez ces patients est augmentee d’un rapport 10 a 60 par rapport au sujet sain, responsable d’une sursaturation avec precipitation de cristaux de cystine dans les reins et de calculs dans les cavites excretrices. La physiopathologie de la cystinurie est particuliere : la concentration plasmatique de cystine est souvent normale alors que l’absorption intestinale est diminuee. Ce paradoxe est explique par une absorption intestinale preservee de cysteine et de methionine qui sont deux acides amines soufres metabolises notamment en cystine. Le principe du traitement consiste a empecher la formation de cristaux de cystine dans les reins afin de prevenir la survenue d’une maladie lithiasique, mais aussi d’une authentique nephropathie cristalline responsable d’une insuffisance renale chez plus de la moitie des patients. Le traitement medical des patients cystinuriques repose (1) sur une diminution de l’excretion urinaire quotidienne de cystine qui est le reflet de l’absorption intestinale et donc des apports en methionine ; (2) sur une augmentation du seuil de solubilite urinaire de la cystine afin de prevenir une precipitation cristalline intratubulaire et intracavitaire par une dilution et une alcalinisation des urines avec des valeurs cibles de 3 L et un pH urinaire aux alentour de 7,5. Le traitement par sulfhydryle dont le but est de dissocier les ponts disulfures des molecules de cystine avec un effet modeste sur la dissolution des calculs de cystine constitues ne devrait en toute logique etre utilise en dernier recours une fois les mesures dietetiques et la cible de pH urinaire obtenue.