Publications by authors named "Christian Combe"

180 Publications

Adherence to the Kidney Disease: Improving Global Outcomes CKD Guideline in Nephrology Practice Across Countries.

Kidney Int Rep 2021 Feb 17;6(2):437-448. Epub 2020 Dec 17.

Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.

Introduction: The uptake of the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 chronic kidney disease (CKD) Guideline is not fully described in real-world nephrology practice across the world.

Methods: We used baseline data from the CKD Outcomes and Practice Patterns Study (2013-2017), a 4-country cohort of patients with estimated glomerular filtration rate <60 ml/min per 1.73 m recruited from national samples of nephrology clinics, to describe adherence to measures for monitoring and delaying CKD progression. Data were collected as in clinical practice, except laboratory measures per protocol in France.

Results: The mean age ranged from 65 years in Brazil to 72 years in Germany. Albuminuria (mostly proteinuria) was measured routinely in 36% to 43% of patients in Brazil, Germany, and the United States. Blood pressure control (≤140/90 mm Hg) ranged from 49% in France to 76% in Brazil; <40% of patients had blood pressure ≤130/80 mm Hg everywhere but Brazil (52%). More than 40% of nephrologists in Brazil reported a systolic blood pressure target ≤130 mm Hg for nondiabetic patients without proteinuria, but only 19% to 24% elsewhere. Prescription of renin-angiotensin aldosterone system inhibitors ranged from 52% in the United States to 81% in Germany. Dietary advice was more frequent for salt than protein intake; dietitian visits were uncommon. In nondiabetic patients, achievement of all 3 targets including blood pressure ≤130/80 mm Hg, renin-angiotensin aldosterone system inhibition, and dietary advice, ranged from 10% in the United States to 32% in Brazil; in treated diabetic patients, this ranged from 6% to 11% after including hemoglobin A1c target.

Conclusion: Adherence to recommendations to slow CKD progression is low in typical practice settings, and substantial variation among countries for some indicates opportunities for improvement.
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http://dx.doi.org/10.1016/j.ekir.2020.11.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879121PMC
February 2021

Water intake and progression of chronic kidney disease: the CKD-REIN cohort study.

Nephrol Dial Transplant 2021 Feb 12. Epub 2021 Feb 12.

CESP (Centre de recherche en Epidémiologie et Santé des Populations), INSERM U1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif, France.

Background: Optimal daily water intake to prevent chronic kidney disease (CKD) progression is unknown. Taking kidney urine-concentrating ability into account, we studied the relation of kidney outcomes in patients with CKD to total and plain water intake and urine volume.

Methods: Including 1265 CKD patients (median age, 69 years; mean estimated glomerular filtration rate [eGFR], 32 ml/min per 1.73 m2) from the CKD-REIN cohort (2013-2019), we assessed fluid intake at baseline interviews, collected 24-h urine volumes, and estimated urine osmolarity (eUosm). Using Cox and then linear mixed models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney failure and eGFR decline associated with hydration markers, adjusting for CKD progression risk factors and eUosm.

Results: Patients' median daily intake was 2.0 (interquartile range: 1.6-2.6) L total water and 1.5 (1-1.7) L plain water; median urine volume was 1.9 (1.6-2.4) L/24 h, and mean eUosm, 374 ± 104 mosm/L. Neither total water intake nor urine volume was associated with either kidney outcome. Kidney failure risk increased significantly with decreasing eUosm below 292 mosm/L. Adjusted HRs for kidney failure associated with plain water intake were 1.88 (95%CI 1.02; 3.47), 1.59 (1.06; 2.38), 1.76 (0.95; 3.24), and 1.55 (1.03; 2.32) in patients drinking <0.5, 0.6-1.0, 1.6-2.0, and >2.0 L/day, compared with those drinking 1.0-1.5 L/day. High plain water intake was also significantly associated with faster eGFR decline.

Conclusion: In patients with CKD, the relation between plain water intake and progression to kidney failure appears to be U-shaped. Both low and high intake may not be beneficial in CKD.
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http://dx.doi.org/10.1093/ndt/gfab036DOI Listing
February 2021

A plea for renin-angiotensin system blockers as first-line treatment in cases of severe acute hypertension.

Nephrol Dial Transplant 2020 Dec 25. Epub 2020 Dec 25.

Néphrologie, Transplantation, Dialyse et Aphérèse, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.

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http://dx.doi.org/10.1093/ndt/gfaa313DOI Listing
December 2020

[Contributions of a geriatric outpatient consultation in a dialysis facility].

Nephrol Ther 2020 Nov 1;16(6):364-371. Epub 2020 Nov 1.

Pôle de gérontologie clinique, hôpital Xavier-Arnozan, CHU de Bordeaux, avenue du Haut-Lévêque, 33000 Bordeaux, France; Association pour l'utilisation du rein artificiel à domicile (AURAD) d'Aquitaine, 2, allée des Demoiselles, 33170 Gradignan, France. Electronic address:

Context: The role of comprehensive geriatric assessment for older patients with advanced chronic kidney disease still needs to be defined. In this population, data is lacking on the care proposals made by geriatricians during comprehensive geriatric assessment and on the follow-up of these proposals.

Objectives: To describe a population of older outpatients with advanced renal disease seen at a geriatric consultation, and geriatric syndromes identified. To study care suggestions made by the geriatrician, and the follow-up of these suggestions.

Methods: Retrospective monocentric study, including all outpatients treated with hemodialysis and seen at the geriatric consultation implemented in a dialysis facilities network in Aquitaine region, France, from 2014 to 2017. Six domains were analysed: functional independence, cognition, gait/balance, mood, nutrition and drug prescription.

Results: Among 49 patients, mean age 79 years, 50% had a loss of independence, 32% cognitive impairment, 24% mood disturbance, 55% gait or balance disturbance, and 65% potentially inappropriate medications. The most frequent care suggestions of the geriatrician were drugs optimisation, intervention of a psychologist, a dietetician or a speech and language therapist, home support service implementation, and the exploration of cognitive impairment. Suggestions of intervention of other healthcare professionals, drug optimisation and biological/imaging tests were followed in respectively 46, 33 and 18% of cases.

Conclusion: A geriatric outpatient consultation in a nephrology facility allows identification of frequent and multiples geriatric syndromes, requiring coordinated interventions. Collaboration between healthcare professionals, including a geriatrician, should be reinforced to improve design and follow-up of the individualised care plan for older patients with advanced chronic kidney disease.
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http://dx.doi.org/10.1016/j.nephro.2020.07.210DOI Listing
November 2020

Chronic kidney disease of unknown origin in agricultural communities: beyond tropical mist?

Nephrol Dial Transplant 2020 Oct 27. Epub 2020 Oct 27.

Service de Néphrologie, Transplantation, Dialyse et Aphérèses, CHU de Bordeaux, Bordeaux, France.

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http://dx.doi.org/10.1093/ndt/gfaa265DOI Listing
October 2020

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients.

Clin Rheumatol 2020 Oct 24. Epub 2020 Oct 24.

Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France.

Objective: IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer.

Methods: We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study.

Results: Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p < 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p < 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p < 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p < 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV.

Conclusion: Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.
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http://dx.doi.org/10.1007/s10067-020-05455-zDOI Listing
October 2020

[Impaired hypertension control in France: What the nephrologist needs to know].

Nephrol Ther 2020 Nov 14;16(6):347-352. Epub 2020 Oct 14.

Fondation de recherche sur l'hypertension artérielle, 12, rue des Colonnes-du-Trône, 75012 Paris, France.

In France, 1 adult out of 3 is affected by hypertension and only 1 hypertensive out of 4 achieves blood pressure targets (<140/90mmHg). This proportion is significantly better in similar countries (e.g. England, Germany, the USA). Nephrologists are particularly concerned since although more than 90 % of Chronic Kidney Disease (CKD) stages 3 and 4 patients are hypertensive, the CKD-REIN cohort shows that in France more than 1 out of 2 patients with CKD remains with a blood pressure above 140/90mmHg. This report, based on the latest French studies and surveys, raises an important warning about the situation in France, discusses the main reasons for these results and offers some suggestions for improvement. Otherwise we risk a dramatic increase in the incidence of myocardial infarction, stroke, dependency and dementia in the coming years.
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http://dx.doi.org/10.1016/j.nephro.2020.10.001DOI Listing
November 2020

Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD.

Kidney Int Rep 2020 Aug 2;5(8):1240-1250. Epub 2020 Jun 2.

University Paris-Saclay, UVSQ, University Paris-Sud, Inserm, Clinical Epidemiology team, CESP, Villejuif, France.

Introduction: In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown.

Methods: We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort.

Results: Patients' median age was 68 (interquartile range [IQR], 59-76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs Q1) was 4.24 (95% confidence interval [CI], 1.53-6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18-7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19-1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14-1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings.

Conclusion: In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment.
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http://dx.doi.org/10.1016/j.ekir.2020.05.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403539PMC
August 2020

Reliability and validity of the French adaptation of the Family Relationship Index-short form in patients' with chronic kidney disease.

J Health Psychol 2020 Aug 10:1359105320949921. Epub 2020 Aug 10.

Université de Paris, LPPS, Boulogne-Billancourt, France.

The Family Relationship Index (FRI) measures family cohesion, expressiveness and conflict. This study aimed to investigate its reliability and validity in patients with chronic kidney disease (CKD). Confirmatory factor analysis was performed on 1657 patients and on subgroups according to socio-demographics and medical variables. Two items with poor saturation were excluded. The indexes indicated an acceptable fit. Reliability was especially weak for expressiveness. Our results provide partial support for the use of the French-version of the FRI in patients with advanced CKD. The family relationship index should be used with caution, especially in certain subgroups and for the expressiveness subscale.
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http://dx.doi.org/10.1177/1359105320949921DOI Listing
August 2020

Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019.

Clin Kidney J 2020 Jun 6;13(3):354-361. Epub 2020 Jun 6.

Service de Médecine Intensive Réanimation, Hôpital Pellegrin et Hôpital Saint André, CHU de Bordeaux, Bordeaux, France.

Background: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported.

Methods: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated.

Results: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively.

Conclusion: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.
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http://dx.doi.org/10.1093/ckj/sfaa099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314187PMC
June 2020

Poor kidney graft survival in anorexia nervosa patients.

Eat Weight Disord 2020 Jul 15. Epub 2020 Jul 15.

Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Background: Anorexia nervosa is a condition associated with poor outcomes in a variety of circumstances such as recurrence of eating disorders, psychiatric disorders, and organ damage.

Objective: In the present study, we first sought to determine the 5-year kidney graft survival in patients with anorexia nervosa and then to evaluate the BMI course and medical complications.

Methods: In this multicenter, retrospective, case-control study, we analyzed the impact of anorexia nervosa on graft outcomes compared to transplant recipients with low or normal BMI.

Results: We enrolled 137 women in this study: 19 with anorexia nervosa, 59 with low BMI (BMI < 18.5 kg/m), and 59 with normal BMI (18.5-24.9 kg/m). Anorexia nervosa was significantly associated with lower graft survival compared to either of the other groups (hazard ratio 5.5 [95% CI 3.4-8.9], p = 0.005); there was no difference in graft survival between patients with low or normal BMI. Cardiovascular complications were more frequent in the anorexia nervosa group (37%) than in patients with low (6%) or normal BMI (7%) (p = 0.001).

Conclusion: We conclude that patients with anorexia nervosa should be considered a high-risk group.

Level Of Evidence: Level III, evidence obtained from well-designed cohort or case-control analytic studies.
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http://dx.doi.org/10.1007/s40519-020-00959-8DOI Listing
July 2020

Adverse Drug Reactions in Patients with CKD.

Clin J Am Soc Nephrol 2020 Aug 1;15(8):1090-1102. Epub 2020 Jul 1.

Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.

Background And Objectives: Little is known about the burden of adverse drug reactions in CKD. We estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors associated with adverse drug reactions in patients seen by nephrologists.

Design, Setting, Participants, & Measurements: The Chronic Kidney Disease-Renal Epidemiology and Information Network cohort included 3033 outpatients (65% men) with CKD and eGFR<60 ml/min per 1.73 m, with follow-up for 2 years. Adverse drug reactions were identified from hospitalization reports, medical records, and participant interviews and finally assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology.

Results: Median (interquartile range) age was 69 (60-76) years old; 55% had eGFR≥30 ml/min per 1.73 m, and 45% had eGFR<30 ml/min per 1.73 m. Participants were prescribed a median (range) of eight (five to ten) drugs. Over 2 years, 536 patients had 751 adverse drug reactions, 150 (in 125 participants) classified as serious, for rates of 14.4 (95% confidence interval, 12.6 to 16.5) and 2.7 (95% confidence interval, 1.7 to 4.3) per 100 person-years, respectively. Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable; 16 caused death, directly or indirectly. Renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%) were the drugs to which the most adverse drug reactions were imputed, but antithrombotic agents caused 34% of serious adverse drug reactions. The drug was discontinued in 71% of cases, at least temporarily. Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR<30 versus ≥30 ml/min per 1.73 m (1.8; 95% confidence interval, 1.3 to 2.6), in those prescribed more than ten versus less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4).

Conclusions: Adverse drug reactions are common and sometimes serious in patients with CKD. Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions.

Clinical Trial Registry Name And Registration Number: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), NCT03381950.
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http://dx.doi.org/10.2215/CJN.01030120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409761PMC
August 2020

Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex.

J Med Genet 2021 Jan 14;58(1):25-31. Epub 2020 May 14.

Service de Néphrologie, Transplantation, Dialyse et Aphérèses, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines.

Objectives: Our study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model.

Methods: Data on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually.

Results: 90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27-47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC.

Conclusion: We obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction.
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http://dx.doi.org/10.1136/jmedgenet-2019-106607DOI Listing
January 2021

Impact of age on cardiovascular drug use in patients with chronic kidney disease.

Clin Kidney J 2020 Apr 10;13(2):199-207. Epub 2019 Jun 10.

Service de Néphrologie-Dialyse, CHU Ambroise Paré, APHP, Boulogne-Billancourt, France.

Background: Elderly patients with chronic kidney disease (CKD) are often excluded from clinical trials; this may affect their use of essential drugs for cardiovascular complications. We sought to assess the impact of age on cardiovascular drug use in elderly patients with CKD.

Methods: We used baseline data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort including 3033 adult patients with CKD Stages 3 and 4. We studied the use of recommended drugs for coronary artery disease (CAD), stroke and atrial fibrillation by age, after adjusting for socio-demographic and clinical conditions.

Results: The patients' mean age was 66.8 years (mean estimated glomerular filtration rate 32.9 mL/min/1.73 m). The prevalence of CAD was 24.5% [81.3% receiving antiplatelet agents, 75.6% renin-angiotensin system (RAS) blockers, 65.4% β-blockers and 81.3% lipid-lowering therapy], that of stroke 10.0% (88.8% receiving antithrombotic drugs) and that of atrial fibrillation 11.1% (69.5% receiving oral anticoagulants). Compared with patients aged <65 years, older age (≥65 years) was associated with greater use of antithrombotic drugs in stroke [adjusted odds ratio (aOR) (95% confidence interval) = 2.83 (1.04-7.73) for patients aged (75-84 years)] and less use of RAS blockers [aOR = 0.39 (0.16-0.89) for patients aged ≥85 years], β-blockers [aOR = 0.31 (0.19-0.53) for patients aged 75-84 years] and lipid-lowering therapy [aOR = 0.39 (0.15-1.02) for patients aged ≥85 years, P for trend = 0.01] in CAD. Older age was not associated with less use of antiplatelet agents in CAD or oral anticoagulants in atrial fibrillation.

Conclusions: In patients with CKD, older age was not associated with the underuse of antithrombotic drugs but was for other major drugs, with a potential impact on cardiovascular outcomes.
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http://dx.doi.org/10.1093/ckj/sfz063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147308PMC
April 2020

Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres.

Nephrol Dial Transplant 2020 05;35(5):737-741

Manchester Academy of Health Sciences Centre, Manchester University Hospitals Foundation Trust and University of Manchester, Manchester, UK.

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease.
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http://dx.doi.org/10.1093/ndt/gfaa069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184437PMC
May 2020

CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine.

Mediators Inflamm 2020 31;2020:6357046. Epub 2020 Jan 31.

INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, France.

Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury.
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http://dx.doi.org/10.1155/2020/6357046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013356PMC
November 2020

Acute Severe Hypertension.

N Engl J Med 2020 02;382(7):e11

Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

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http://dx.doi.org/10.1056/NEJMc1916851DOI Listing
February 2020

Perceived Health and Quality of Life in Patients With CKD, Including Those With Kidney Failure: Findings From National Surveys in France.

Am J Kidney Dis 2020 06 23;75(6):868-878. Epub 2019 Dec 23.

CHRU-Nancy, INSERM, CIC, Epidémiologie Clinique, Nancy, France.

Rationale & Objective: Health-related quality of life (HRQoL) is a major outcome measure increasingly used in patients with chronic kidney disease (CKD). We evaluated the association between different stages of CKD and the physical and mental health domains of HRQoL.

Study Design: Cross-sectional study.

Setting & Participants: 2,693 outpatients with moderate (stage 3, estimated glomerular filtration rate [eGFR], 30-60mL/min/1.73m) or advanced (stages 4-5, estimated glomerular filtration rate<30mL/min/1.73m, not on kidney replacement therapy [KRT]) CKD under the care of a nephrologist at 1 of 40 nationally representative facilities, 1,658 patients with a functioning kidney transplant, 1,251 patients on maintenance dialysis randomly selected from the national Renal Epidemiology and Information Network registry, and 20,574 participants in the French Decennial Health Survey, representative of the general population.

Predictor: Severity of kidney disease (moderate CKD, advanced CKD, maintenance dialysis as KRT, and functioning kidney transplant as KRT), compared with a sample of the general population.

Outcomes: HRQoL scores assessed using the Medical Outcomes Study 36-Item Short Form Health Survey or the Kidney Disease Quality of Life 36 scale.

Analytical Approach: Age- and sex-standardized (to the general population) prevalence of poor or fair health status was estimated for each study kidney disease group. Analysis of variance was used to estimate adjusted differences in mean physical and mental health scores between the kidney disease subgroups and the general population.

Results: Mean age was 67.2±12.6 (SD) years for patients with non-KRT-requiring CKD, 69.3±17.7 years for dialysis patients, and 55.3±14.2 years for those with functioning kidney transplants; 60% were men. Age- and sex-standardized health status was perceived as fair or poor in 27% of those with moderate CKD,>40% of those with advanced CKD or receiving dialysis, 12% with a functioning transplant, and 3% of the general population sample. HRQoL physical scores (adjusted for age, sex, education, obesity, and diabetes) were significantly lower in patients in all CKD subgroups than in the general population. For patients receiving dialysis, the magnitude of the difference in physical score versus the general population exceeded 4.5 points, the minimal clinically important difference for this score in this study; for both kidney transplant recipients and patients with advanced CKD, the magnitude of the difference was close to this threshold. For mental score, only dialysis patients had a score that differed from that of the general population by more than the minimal clinically important difference.

Limitations: Cross-sectional study design for each subpopulation.

Conclusions: This study highlights the degree to which perceived physical health is lower in the setting of CKD than in the general population, even in the absence of kidney failure, and calls for greater attention to CKD-related quality of life.
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http://dx.doi.org/10.1053/j.ajkd.2019.08.026DOI Listing
June 2020

The Incidence of Chronic Kidney Disease Three Years after Non-Severe Acute Kidney Injury in Critically Ill Patients: A Single-Center Cohort Study.

J Clin Med 2019 Dec 14;8(12). Epub 2019 Dec 14.

Service de Médecine Intensive Réanimation, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux Cedex, France.

The risk of chronic kidney disease (CKD) following severe acute kidney injury (AKI) in critically ill patients is well documented, but not after less severe AKI. The main objective of this study was to evaluate the long-term incidence of CKD after non-severe AKI in critically ill patients. This prospective single-center observational three-years follow-up study was conducted in the medical intensive care unit in Bordeaux's hospital (France). From 2013 to 2015, all patients with severe (kidney disease improving global outcomes (KDIGO) stage 3) and non-severe AKI (KDIGO stages 1, 2) were enrolled. Patients with prior eGFR < 90 mL/min/1.73 m were excluded. Primary outcome was the three-year incidence of CKD stages 3 to 5 in the non-severe AKI group. We enrolled 232 patients. Non-severe AKI was observed in 112 and severe AKI in 120. In the non-severe AKI group, 71 (63%) were male, age was 62 ± 16 years. The reason for admission was sepsis for 56/112 (50%). Sixty-two (55%) patients died and nine (8%) were lost to follow-up. At the end of the follow-up the incidence of CKD was 22% (9/41); Confidence Interval (CI) (9.3-33.60)% in the non-severe AKI group, tending to be significantly lower than in the severe AKI group (44% (14/30); CI (28.8-64.5)%; = 0.052). The development of CKD three years after non-severe AKI, despite it being lower than after severe AKI, appears to be a frequent event highlighting the need for prolonged follow-up.
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http://dx.doi.org/10.3390/jcm8122215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947258PMC
December 2019

Incidence, prognostic impact and clinical outcomes of renal impairment in patients with multiple myeloma: a population-based registry.

Nephrol Dial Transplant 2021 Feb;36(3):482-490

CHU de Bordeaux, Service de Néphrologie-Transplantation-Dialyse-Aphérèses, Hôpital Pellegrin, Bordeaux, France.

Background: Renal impairment (RI), a severe complication in multiple myeloma (MM), is considered as a poor prognostic factor. Patient survival has increased with the use of novel drugs and autologous stem-cell transplantation (ASCT). However, specific evolution of the incidence of RI in MM and its impact on prognosis remain unclear.

Methods: Using a population-based registry of 1038 newly diagnosed MM in Gironde, France, we evaluated the incidence trends of RI in MM patients and assessed net survival according to factors of interest using Pohar-Perme indicator and excess mortality rate regression. We also reviewed 114 cases of MM with RI to describe their clinical outcomes.

Results: In our population-based study, 24.6% of MM patients presented with RI (12.9% required haemodialysis). Median survival time was 21 months in patients with RI versus not reached at 3 years for other patients (P < 0.01). Age >73 years, RI, comorbidities and non-use of drugs or ASCT were associated with excess mortality risk. The effect of RI on excess mortality rates was maximum in the first 6 months after diagnosis. In the observational study, median follow-up time was 22.5 months; factors associated with renal response were haematologic response [odds ratio (OR) 6.81; P < 0.01] and previous chronic kidney disease (OR 0.26; P = 0.04). Factors associated with 1-year overall survival were haematological [hazard ratio (HR) 0.13; P < 0.01] and renal response (HR 0.27; P = 0.03).

Conclusions: RI represents an independent negative prognostic factor in MM in the first 6 months after diagnosis. Renal recovery and haematologic response are the strongest markers associated with patient survival.
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http://dx.doi.org/10.1093/ndt/gfz211DOI Listing
February 2021

No Improvement of Hepatitis B Vaccination Response in Patients Dialysed with a Polymethylmethacrylate Membrane Compared to High-Flux Polysulfone: Results of the HEPADIAL Study.

Blood Purif 2020 13;49(3):265-271. Epub 2019 Nov 13.

Department of Immunology and Immunogenetics, Bordeaux University Hospital, Bordeaux, France.

Background: An altered immune response and decreased vaccine response are observed in patients with chronic renal failure. A preliminary study of 15 non-immunised patients, despite appropriate previous hepatitis B vaccination, showed a 60% seroconversion rate after 3 months of dialysis with a polymethylmethacrylate (PMMA) membrane. This response was associated with circulating soluble CD40 (CD40s) decrease, a natural inhibitor of the humoral immune response. The aim of the study is to confirm these results in a randomised study.

Methods: We conducted a multicentre randomised intention-to-treat superiority clinical trial comparing polysulfone and a PMMA membrane in 2 parallel patient groups. The primary end point was the vaccine response rate, as defined by an anti-HBs antibodies titre of >10 IU/L, 1 month after the last vaccination with a double dose of Engerix B20®, performed at weeks 12, 16, 20, and 36.

Results: Twenty-five patients were randomised and included in an intention-to-treat analysis. They were dialysed on polysulfone (n = 11) or PMMA (n = 14) for 40 weeks. Fifty percent of the PMMA patients versus 54.5% of the polysulfone patients achieved seroconversion (p = 1.00). The median anti-HBs antibody titre in responders at week 40 was 496 (92-750) versus 395 (43-572) UI/mL for PMMA and polysulfone, respectively (p = 0.46). The median CD40s titre at week 12 was 306 (193-448) versus 491 (281-515) pg/mL (p = 0.21). The CD40s median variation between week 0 and week 12 was 5 (-105 to 90) versus 64 (-63 to 123) pg/mL (p = 0.55). The CD40s level at week 12 in non-responders was slightly inferior to that of the responders: median 193 (168-331) versus 413 (281-512) pg/mL (p = 0.08).

Conclusion: We did not observe a better vaccine response with the PMMA membrane compared to high-flux polysulfone. The PMMA membrane did not decrease the CD40s more than the polysulfone membrane probably because the titre was previously low in the 2 groups.
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http://dx.doi.org/10.1159/000504035DOI Listing
November 2019

Adult onset tubulo-interstitial nephropathy in MT-ND5-related phenotypes.

Clin Genet 2020 04 9;97(4):628-633. Epub 2020 Jan 9.

Service de Néphrologie Transplantation Dialyse et Aphérèses, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Kidney is a highly adenosine triphosphate dependent organ in human body. Healthy and functional mitochondria are essential for normal kidney function. Clinical and genetic variability are the hallmarks of mitochondrial disorders. We report here the involvement of two MT-ND5 pathogenic variants encoding for ND5 subunit of respiratory chain complex I, the m.13513G>A and the m.13514A>G, in adult-onset kidney disease in three unrelated patients. The first patient had myopathy encephalopathy lactic acidosis and stroke syndrome, left ventricular hypertrophy with Wolff-Parkinson-White syndrome and tubulo-interstitial kidney disease. The second presented Leber hereditary optic neuropathy associated with tubulo-interstitial kidney disease. The third presented with an isolated chronic tubulo-interstitial kidney disease. These mutations have never been associated with adulthood mitochondrial nephropathy. These case reports highlight the importance to consider mitochondrial dysfunction in tubulo-interstitial kidney disease.
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http://dx.doi.org/10.1111/cge.13670DOI Listing
April 2020

[Hygieno-dietetic recommendations in the prevention of accumulation of advanced glycation products].

Nephrol Ther 2019 Dec 31;15(7):485-490. Epub 2019 Oct 31.

Service de néphrologie, hôpital Pellegrin, CHU de Bordeaux, 33000 Bordeaux, France.

Advanced glycation products are proteins whose structural and functional properties have been modified by a process of oxidative glycation. The accumulation of advanced glycation products in most tissues and the oxidative stress and inflammatory reactions that accompany it, account for the multi-systemic impairment observed particularly in the elderly, diabetics and in chronic renal failure. The advanced glycation products endogenous production is continuous, related to oxidative stress, but the most important source of advanced glycation products is exogenous, mainly of food origin. Exogenous advanced glycation products are developed during the preparation of food and beverages. The advanced glycation products content is higher for animal foods, but it is mainly the preparation and cooking methods that play a decisive role. Dietary advice is based on the selection of foods and the choice of methods of preparation. Several randomized controlled studies have confirmed the favorable effect of these recommendations on serum advanced glycation products concentrations. In humans, as in animals, regular physical activity also results in a reduction of serum and tissue concentrations of advanced glycation products. There is a need for prospective clinical study to confirm the effects of hygienic and dietary recommendations that have only been appreciated, so far, on biological markers.
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http://dx.doi.org/10.1016/j.nephro.2019.05.005DOI Listing
December 2019

Dietary protein restriction in chronic kidney disease: one size does not fit all.

Nephrol Dial Transplant 2020 05;35(5):731-732

Centre Hospitalier Universitaire de Bordeaux, Service de Néphrologie Transplantation Dialyse Aphérèse, Hôpital Pellegrin, Bordeaux, France.

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http://dx.doi.org/10.1093/ndt/gfz202DOI Listing
May 2020

Sudden cardiac death in dialysis patients: different causes and management strategies.

Nephrol Dial Transplant 2021 Feb;36(3):396-405

Division of Nephrology, Miulli General Hospital, Acquaviva delle Fonti, Italy.

Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.
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http://dx.doi.org/10.1093/ndt/gfz182DOI Listing
February 2021

Long term evolution of renal function in essential hypertensive patients with no baseline proteinuria.

J Hum Hypertens 2020 09 2;34(8):560-567. Epub 2019 Sep 2.

Hypertension excellence center, University hospital of Bordeaux, Hôpital Saint André, 1 avenue Jean Burguet, 33075, Bordeaux, France.

Data on the long term evolution of renal function in essential hypertensive patients are scarce, showing a low incidence of end stage renal diseases but without information on how the renal function evolves. Our aim is to describe the long term evolution of renal function and possible trajectories in hypertensive patients. We included patients from an ongoing cohort with essential hypertension, no proteinuria at baseline and no diabetes during follow-up and with at least two creatinine dosages 4 years apart. A long term (average 16 years) follow-up was available in 609 patients (baseline age 51.8 ± 11.1 years, 52 % male, mean office BP 156//95 mmHg). The trajectories of creatinine were modeled through a flexible latent class mixed model. The analysis identified three classes of significantly different trajectories. In the first (n = 560), there was no significant variation of creatinine over time. In the second (n = 40), there was a significant rise of creatinine (117 ± 20 vs 85 ± 17 µmol/l, p < 0.0001). The third class (n = 9) was very heterogeneous, mainly composed of outliers. Further analysis showed the nonlinearity of the evolution of creatinine in classes 2 and 3. So the model of progressive renal deterioration in essential hypertension does not fit with our results. A large majority (92%) of patients show no significant change in creatinine level with time. In the others 8%, the increase in creatinine is not progressive but conversely show one or more sudden bouts of elevation.
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http://dx.doi.org/10.1038/s41371-019-0245-4DOI Listing
September 2020

A prospective comparison of dynamic contrast-enhanced MRI and Cr-EDTA clearance for glomerular filtration rate measurement in 42 kidney transplant recipients.

Eur J Radiol 2019 Aug 4;117:209-215. Epub 2019 Feb 4.

Centre Hospitalier Universitaire de Bordeaux, Service de Radiologie et d'Imagerie Diagnostique et Interventionnelle de l'Adulte, Groupe Hospitalier Pellegrin, France.

Objectives: To evaluate the performance of dynamic contrast-enhanced MRI measurement of glomerular filtration rate (GFR) compared with the reference standard technique of urinary clearance of Cr-EDTA.

Patients And Methods: All kidney transplant recipients (KTRs) with an indication for non-urgent contrast-enhanced MRI at our institution were prospectively included between 2008 and 2012. Renographies were acquired by low-dose dynamic contrast-enhanced MRI (DCE-MRI) then fitted with a two-compartment pharmacokinetic model. MR-GFR was compared with reference isotopic measurements using Bland-Altman diagrams, intraclass correlation coefficient (ICC) and concordance rates.

Results: Forty-two KTRs (mean age 51.5 years, 26-74) were analyzed. Mean estimated GFR was 48.5 ± 27 mL/min/1.73m (24-178 mL/min). The mean bias was +13.2 mL/min (6.4-20.0, +36.9%) ranging from -31.0 mL/min (-41.7%) to +101.4 mL/min (+89.2%) with a large variability (standard-deviation: 22.3 mL/min; limits of agreement: [-30.6 (-43.3--18.9); +57.0 (45.3-68.7)]). The ICC was 0.32 (0.02-0.56) and the concordance rate was 28.6% (14.9-42.2).

Conclusions: The large variability of MR-GFR compared with the reference technique precludes its use in KTRs, whose anatomical peculiarities make standardization of arterial input function (AIF) difficult.
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http://dx.doi.org/10.1016/j.ejrad.2019.02.002DOI Listing
August 2019

Prescription of renin-angiotensin-aldosterone system inhibitors (RAASi) and its determinants in patients with advanced CKD under nephrologist care.

J Clin Hypertens (Greenwich) 2019 07 6;21(7):991-1001. Epub 2019 Jun 6.

CESP, Center for Research in Epidemiology and Population Health, University Paris-Saclay, University Paris-Sud, UVSQ, Villejuif, France.

Renin-angiotensin-aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66-72 years; congestive heart failure [CHF] in 11%-19%; diabetes in 43%-54%; serum potassium ≥5 in 20%-35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong class-specific recommendations. Although the reasons for this variation could not be fully identified in this cross-sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.
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http://dx.doi.org/10.1111/jch.13563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771881PMC
July 2019

Towards an in vitro model of the glomerular barrier unit with an innovative bioassembly method.

Nephrol Dial Transplant 2020 02;35(2):240-250

Tissue Bioengineering, Université de Bordeaux, Bordeaux, France.

Background: The development of an artificial glomerular unit may be pivotal for renal pathophysiology studies at a multicellular scale. Using a tissue engineering approach, we aimed to reproduce in part the specific glomerular barrier architecture by manufacturing a glomerular microfibre (Mf).

Methods: Immortalized human glomerular cell lines of endothelial cells (GEnCs) and podocytes were used. Cells and a three-dimensional (3D) matrix were characterized by immunofluorescence with confocal analysis, Western blot and polymerase chain reaction. Optical and electron microscopy were used to study Mf and cell shapes. We also analysed cell viability and cell metabolism within the 3D construct at 14 days.

Results: Using the Mf manufacturing method, we repeatedly obtained a cellularized Mf sorting human glomerular cells in 3D. Around a central structure made of collagen I, we obtained an internal layer composed of GEnC, a newly formed glomerular basement membrane rich in α5 collagen IV and an external layer of podocytes. The cell concentration, optimal seeding time and role of physical stresses were modulated to obtain the Mf. Cell viability and expression of specific proteins (nephrin, synaptopodin, vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrandt factor (vWF)) were maintained for 19 days in the Mf system. Mf ultrastructure, observed with EM, had similarities with the human glomerular barrier.

Conclusion: In summary, with our 3D bio-engineered glomerular fibre, GEnC and podocytes produced a glomerular basement membrane. In the future, this glomerular Mf will allow us to study cell interactions in a 3D system and increase our knowledge of glomerular pathophysiology.
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http://dx.doi.org/10.1093/ndt/gfz094DOI Listing
February 2020