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Abstract Background Our aim was to train and test a deep learning-based algorithm for automatically segmenting kidneys and renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods We retrospectively selected all ADPKD patients who underwent renal MRI with coronal T2-weighted imaging at our institution from 2008 to 2022. The 20 most recent examinations constituted the test dataset, to mimic pseudoprospective enrolment. The remaining ones constituted the training dataset to which eight normal renal MRIs were added. Kidneys and cysts ground truth segmentations were performed on coronal T2-weighted images by a junior radiologist supervised by an experienced radiologist. Kidneys and cysts of the 20 test MRIs were segmented by the algorithm and three independent human raters. Segmentations were compared using overlap metrics. The total kidney volume (TKV), total cystic volume (TCV), and cystic index (TCV divided by TKV) were compared using Bland–Altman analysis. Results We included 164 ADPKD patients. Dice similarity coefficients ranged from 85.9% to 87.4% between the algorithms and the raters’ segmentations and from 84.2% to 86.2% across raters’ segmentations. For TCV assessment, the biases ± standard deviations (SD) were 3–19 ± 137–151 mL between the algorithm and the raters, and 22–45 ± 49–57 mL across raters. The algorithm underestimated TKV and TCV in two outliers with TCV > 2800 mL. For cystic index assessment, the biases ± SD were 2.5–6.9% ± 6.7–8.3% between the algorithm and the raters, and 2.1–9.4 ± 7.4–11.6% across raters. Conclusion The algorithm’s performance fell within the range of inter-rater variability, but large TKV and TCV were underestimated. Relevance statement Accurate automated segmentation of the renal cysts will enable the large-scale evaluation of the prognostic value of TCV and cystic index in ADPKD patients. If these biomarkers are prognostic, then automated segmentation will facilitate their use in daily routine. Key Points Cystic volume is an emerging biomarker in ADPKD. The algorithm’s performance in segmenting kidneys and cysts fell within interrater variability. The segmentation of very large cysts, under-represented in the training dataset, needs improvement. Graphical Abstract

Numerous prevalence studies on Fabry disease (FD, OMIM #301500) have been conducted in dialysis populations across the world with variable and controversial results. The FABRYDIAL study aimed to estimate the prevalence of FD in patients aged 18 to 74 years on chronic dialysis in France. This cross-sectional study was conducted in patients undergoing dialysis. One hundred and twenty-four dialysis centers participated. Patients with proven causes of nephropathy unrelated to FD were excluded. Alpha-galactosidase A activity was assayed in men, and both α-galactosidase A and lyso-Gb3 were assayed in women from dried blood spots. GLA gene sequencing was performed in case of abnormal values. If a variant was identified, a diagnosis validation committee was consulted for adjudication. Among the 6032 targeted patients, 3088 were included (73.6% of the eligible patients). Biochemical results were available for 2815 (1721 men and 1094 women). A genetic variant of GLA was identified in five patients: a benign c.937G>T/p.(Asp313Tyr) variant in two individuals, a likely benign c.427G>A/(p.Ala143Thr) variant, a likely benign c.416A>G/(p.Asn139Ser) variant, and a pathogenic c.1185dupG/p.Phe396Glyfs variant. Among the screened patients, the prevalence was 0.058% [0.010;0.328] in males, 0% [0.000;0.350] in females, and 0.035% [0.006;0.201] when both genders were pooled. Among all patients aged 18–74 years undergoing dialysis without a previously known cause of nephropathy unlinked to FD, the prevalence was 0.028% [0.006;0.121]. The prevalence of FD in a cohort of French dialysis patients was low. However, considering the prognostic impact of earlier diagnosis, signs of FD should be sought in patients with nephropathies of uncertain etiology.

Background and objectivesActivation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease.MethodsWe conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3

Highlights • Cryoglobulinemia is frequent in SLE, but mostly asymptomatic. • Sixty-six percent of SLE patients tested positive for cryoglobulins, and 15% of the SLE patients with cryoglobulinemia developed a cryoglobulinemic vasculitis. • Features of the cryoglobulinemic vasculitis mainly involved skin, joints, and general signs. Severe manifestations of vasculitis were rare.

Cyclosporine A (CsA) preconditioning is known to target mitochondrial permeability transition pore and protect renal function after ischemia reperfusion (IR). The upregulation of heat-shock protein 70 (Hsp70) expression after CsA injection is thought to be associated with renal protection. The aim of this study was to test the effect of Hsp70 expression on kidney and mitochondria functions after IR. Mice underwent a right unilateral nephrectomy and 30 min of left renal artery clamping, performed after CsA injection and/or administration of the Hsp70 inhibitor. Histological score, plasma creatinine, mitochondrial calcium retention capacity, and oxidative phosphorylation were assessed after 24 h of reperfusion. In parallel, we used a model of hypoxia reoxygenation on HK2 cells to modulate Hsp70 expression using an SiRNA or a plasmid. We assessed cell death after 18 h of hypoxia and 4 h of reoxygenation. CsA significantly improved renal function, histological score, and mitochondrial functions compared to the ischemic group but the inhibition of Hsp70 repealed the protection afforded by CsA injection. In vitro, Hsp70 inhibition by SiRNA increased cell death. Conversely, Hsp70 overexpression protected cells from the hypoxic condition, as well as the CsA injection. We did not find a synergic association between Hsp70 expression and CsA use. We demonstrated Hsp70 could modulate mitochondrial functions to protect kidneys from IR. This pathway may be targeted by drugs to provide new therapeutics to improve renal function after IR.

(1) Background: The Vaccine Coverage Rate of influenza remains low and omnichannel efforts are required to improve it. The objective was to evaluate the feasibility and outcomes of a QR Code nudging system in outpatient departments. (2) Methods: The study was performed in 6 departments ensuring ambulatory activities in a French university Hospital between November and December 2021. By scanning QR codes, users accessed anonymously to the ELEFIGHT® web app, which provides medical information on influenza and invites them to initiate a discussion about influenza prevention with their physicians during the consultation. (3) Results: 351 people made 529 scans with an average reading time of 1 min and 4 s and a conversion rate of 32%, i.e., people willing to engage in a discussion. (4) Conclusions: The study suggests that direct access to medical information through QR codes in hospitals might help nudge people to raise their awareness and trigger their action on influenza prevention.

Introduction: We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients. Methods: CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013−2016) who had not been on chronic dialysis or undergone kidney transplantation. Data were collected from patients’ interviews and medical records. Patients were followed up at 1 year. Results: Among 2542 patients (mean [SD] age 67 [13] years, 34% women) with LDL-C measurements at baseline (mean [SD] LDL-C 2.7 [1.1] mmol/l; cholesterol 4.8 [1.3] mmol/l), 63% were on LLT; 24% were at high (CKD stage G3, no cardiovascular disease [CVD] or diabetes) and 74% at very high (CKD stage G3 with diabetes or CVD, or CKD stage G4/5) cardiovascular risk. Among high-risk patients, 45% of those on statin and/or ezetimibe achieved the LDL-C treatment target (

Renal ischemia-reperfusion (IR) injury can lead to acute kidney injury, increasing the risk of developing chronic kidney disease. We hypothesized that mild therapeutic hypothermia (mTH), 34 °C, applied during ischemia could protect the function and structure of kidneys against IR injuries in mice. In vivo bilateral renal IR led to an increase in plasma urea and acute tubular necrosis at 24 h prevented by mTH. One month after unilateral IR, kidney atrophy and fibrosis were reduced by mTH. Evaluation of mitochondrial function showed that mTH protected against IR-mediated mitochondrial dysfunction at 24 h, by preserving CRC and OX-PHOS. mTH completely abrogated the IR increase of plasmatic IL-6 and IL-10 at 24 h. Acute tissue inflammation was decreased by mTH (IL-6 and IL1-β) in as little as 2 h. Concomitantly, mTH increased TNF-α expression at 24 h. One month after IR, mTH increased TNF-α mRNA expression, and it decreased TGF-β mRNA expression. We showed that mTH alleviates renal dysfunction and damage through a preservation of mitochondrial function and a modulated systemic and local inflammatory response at the acute phase (2–24 h). The protective effect of mTH is maintained in the long term (1 month), as it diminished renal atrophy and fibrosis, and mitigated chronic renal inflammation.

AimTo assess the effect of periodontal treatment (PT) on glomerular filtration rate (GFR), systemic inflammation, or mortality in patients with chronic kidney disease (CKD).MethodsA literature search was performed on PubMed and Web of Science databases on articles published until December 2019. The PRISMA guidelines were used throughout the manuscript.ResultsOf the total studies found, only 18 met the inclusion criteria; four retrospective and 14 prospective studies (including 3 randomized controlled trials-RCT). After PT, 3 studies investigated GFR, 2 found significant improvement; 11 (including 2 RCTs) investigated C-reactive protein levels, 9 found a significant improvement (including the 2 RCTs); 5 (including 3 RCTs) investigated Interleukine-6 level, 4 found a significant improvement (including 2 RCTs) and 2 studies evaluated mortality, one (retrospective study) found a significant difference.ConclusionsWithin the limitations of the present study, PT seems to improve CKD status, especially by reducing the systemic inflammation. Further RCTs are needed to confirm the results and specifically assess the influence of different types of PT in CKD patients. Taking into consideration the ability of PT to prevent further tooth loss and denutrition, early management of periodontitis is extremely important in patients with impaired renal function.

BackgroundIn atherosclerotic renal artery disease, the benefit of revascularization is controversial. A clinical decision-making process based on a multidisciplinary meeting was formalized in the Lyon university hospital.ObjectivesTo investigate whether this decisional process ensured a clinical benefit to patients assigned to renal revascularization.MethodsSingle-centre retrospective cohort study, including patients diagnosed from April 2013 to February 2015 with an atherosclerotic renal artery disease with a peak systolic velocity >180cm/s. For each patient, the decision taken in multidisciplinary meeting (medical treatment or revacularization) was compared to the one guided by international guidelines. Blood pressure values, number of antihypertensive medications, presence of an uncontrolled or resistant hypertension, and glomerular filtration rate at one-year follow-up were compared to baseline values. Safety data were collected.ResultsForty-nine patients were included: 26 (53%) were assigned to a medical treatment and 23 (47%) to a renal revascularization. Therapeutic decision was in accordance with the 2013 American Health Association guidelines and with the 2017 European Society of Cardiology guidelines for 78% and 22% of patients who underwent revascularization, respectively. Patients assigned to revascularization presented a significant decrease in systolic blood pressure (-23±34mmHg, p = 0.007), diastolic blood pressure (-12±18mmHg, p = 0.007), number of antihypertensive medications (-1.00±1.03, p = 0.001), and number of uncontrolled or resistant hypertension (p = 0.022 and 0.031) at one-year follow-up. Those parameters were not modified among patients assigned to medical treatment alone. There was no grade 3 adverse event.ConclusionBased on a multidisciplinary selection of revascularization indications, patients on whom a renal revascularization was performed exhibited a significant improvement of blood pressure control parameters with no severe adverse events.

Lipid aldehydes originating from the peroxidation of n-3 and n-6 polyunsaturated fatty acids are increased in hemodialysis (HD) patients, a process already known to promote oxidative stress. However, data are lacking for patients with chronic kidney disease (CKD) before the initiation of HD. We prospectively evaluated the changes of plasma concentrations of two major lipid aldehydes, 4-HHE and 4-HNE, according to the decrease of glomerular filtration rate (GFR) in 40 CKD and 13 non-CKD participants. GFR was measured by inulin or iohexol clearance. Thus, 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE) were quantitated in plasma by gas chromatography coupled with mass spectrometry and their covalent adducts on proteins were quantified by immunoblotting. On the one hand, 4-HHE plasma concentration increased from CKD stage I–II to CKD stage IV–V compared to non-CKD patients (4.5-fold higher in CKD IV–V, p < 0.005). On the other hand, 4-HNE concentration only increased in CKD stage IV–V patients (6.2-fold, p < 0.005). The amount of covalent adducts of 4-HHE on plasma protein was 9.5-fold higher in CKD patients than in controls (p < 0.005), while no difference was observed for 4-HNE protein adducts. Plasma concentrations of 4-HNE and 4-HHE are increased in CKD IV–V patients before the initiation of hemodialysis.

There is experimental evidence that lethal ischemia-reperfusion injury (IRI) is largely due to mitochondrial permeability transition pore (mPTP) opening, which can be prevented by cyclosporine A (CsA). The aim of our study is to show that a higher dose of CsA (10 mg/kg) injected just before ischemia or a lower dose of CsA (3 mg/kg) injected further in advance of ischemia (1 h) protects the kidneys and improves mitochondrial function.All mice underwent a right unilateral nephrectomy followed by 30 min clamping of the left renal artery. Mice in the control group did not receive any pharmacological treatment. Mice in the three groups treated by CsA were injected at different times and with different doses, namely 3 mg/kg 1 h or 10 min before ischemia or 10 mg/kg 10 min before ischemia. After 24 h of reperfusion, the plasma creatinine level were measured, the histological score was assessed and mitochondria were isolated to calculate the calcium retention capacity (CRC) and level of oxidative phosphorylation.Mortality and renal function was significantly higher in the CsA 10 mg/kg-10 min and CsA 3mg/kg-1 h groups than in the CsA 3mg/kg-10 min group. Likewise, the CRC was significantly higher in the former two groups than in the latter, suggesting that the improved renal function was due to a longer delay in the opening of the mPTP. Oxidative phosphorylation levels were also higher 24 h after reperfusion in the protected groups.Our results suggest that the protection afforded by CsA is likely limited by its availability. The dose and timing of the injections are therefore crucial to ensure that the treatment is effective, but these findings may prove challenging to apply in practice.

Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted this study to explore renal excretion and mechanisms of accumulation of TMAO during CKD. We prospectively measured glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of trimethylamine (TMA), TMAO, choline, betaine, and carnitine by LC-MS/MS in 124 controls, CKD, and hemodialysis (HD) patients. Renal clearance of each metabolite was assessed in a sub-group of 32 patients. Plasma TMAO was inversely correlated with mGFR (r2 = 0.388, p < 0.001), confirming elevation of TMAO plasma levels in CKD. TMAO clearances were not significantly different from mGFR, with a mean ± SD TMAO fractional excretion of 105% ± 32%. This suggests a complete renal excretion of TMAO by glomerular filtration with a negligible participation of tubular secretion or reabsorption, during all stages of CKD. Moreover, TMAO was effectively removed within 4 h of hemodiafiltration, showing a higher fractional reduction value than that of urea (84.9% ± 6.5% vs. 79.2% ± 5.7%, p = 0.04). This study reports a strong correlation between plasma TMAO levels and mGFR, in CKD, that can be mainly related to a decrease in TMAO glomerular filtration. Clearance data did not support a significant role for tubular secretion in TMAO renal elimination.

Chronic kidney disease is associated with an increased cardiovascular risk, and altered biological properties of high-density lipoproteins (HDL) may play a role in these events. This study aimed to describe the HDL proteome from non-diabetic hemodialysis patients and identify potential pathways affected by the dysregulated expression of HDL proteins. HDL were sampled from nine non-diabetic hemodialysis (HD) and eight control patients. Samples were analyzed using a nano-RSLC coupled with a Q-Orbitrap. Data were processed by database searching using SequestHT against a human Swissprot database and quantified with a label-free quantification approach. Proteins that were in at least five of the eight control and six of the nine HD patients were analyzed. Analysis was based on pairwise ratios and the ANOVA hypothesis test. Among 522 potential proteins, 326 proteins were identified to be in the HDL proteome from HD and control patients, among which 10 were significantly upregulated and nine downregulated in HD patients compared to the control patients (p < 0.05). Up and downregulated proteins were involved in lipid metabolism, hemostasis, wound healing, oxidative stress, and apoptosis pathways. This difference in composition could partly explain HDL dysfunction in the chronic kidney disease (CKD) population and participate in the higher cardiovascular risk observed in this population.

Chronic kidney disease (CKD) is associated with an enhanced oxidative stress and deep modifications in lipid and lipoprotein metabolism. First, many oxidized lipids accumulate in CKD and were shown to exert toxic effects on cells and tissues. These lipids are known to interfere with many cell functions and to be pro-apoptotic and pro-inflammatory, especially in the cardiovascular system. Some, like F2-isoprostanes, are directly correlated with CKD progression. Their accumulation, added to their noxious effects, rendered their nomination as uremic toxins credible. Similarly, lipoproteins are deeply altered by CKD modifications, either in their metabolism or composition. These impairments lead to impaired effects of HDL on their normal effectors and may strongly participate in accelerated atherosclerosis and failure of statins in end-stage renal disease patients. This review describes the impact of oxidized lipids and other modifications in the natural history of CKD and its complications. Moreover, this review focuses on the modifications of lipoproteins and their impact on the emergence of cardiovascular diseases in CKD as well as the appropriateness of considering them as actual mediators of uremic toxicity.