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Article ; Online: Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence.

Knebelmann, Bertrand / Haydock, Ludwig

2023 Volume 388, Issue 21, Page(s) 2013–2014

MeSH term(s)	Humans ; Hydrochlorothiazide/therapeutic use ; Kidney Calculi ; Kidney
Chemical Substances	Hydrochlorothiazide (0J48LPH2TH)
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2304100
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Article ; Online: Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans.

Halbritter, Jan / Bizet, Albane A / Schmidts, Miriam / Porath, Jonathan D / Braun, Daniela A / Gee, Heon Yung / McInerney-Leo, Aideen M / Krug, Pauline / Filhol, Emilie / Davis, Erica E / Airik, Rannar / Czarnecki, Peter G / Lehman, Anna M / Trnka, Peter / Nitschké, Patrick / Bole-Feysot, Christine / Schueler, Markus / Knebelmann, Bertrand / Burtey, Stéphane /

Szabó, Attila J / Tory, Kálmán / Leo, Paul J / Gardiner, Brooke / McKenzie, Fiona A / Zankl, Andreas / Brown, Matthew A / Hartley, Jane L / Maher, Eamonn R / Li, Chunmei / Leroux, Michel R / Scambler, Peter J / Zhan, Shing H / Jones, Steven J / Kayserili, Hülya / Tuysuz, Beyhan / Moorani, Khemchand N / Constantinescu, Alexandru / Krantz, Ian D / Kaplan, Bernard S / Shah, Jagesh V / Hurd, Toby W / Doherty, Dan / Katsanis, Nicholas / Duncan, Emma L / Otto, Edgar A / Beales, Philip L / Mitchison, Hannah M / Saunier, Sophie / Hildebrandt, Friedhelm

American journal of human genetics

2013 Volume 93, Issue 5, Page(s) 915–925

Abstract: ... A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor ... Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles ... in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed ...

Abstract	Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.
MeSH term(s)	Alleles ; Amino Acid Sequence ; Animals ; Asian Continental Ancestry Group/genetics ; Bone and Bones/abnormalities ; Bone and Bones/metabolism ; Bone and Bones/pathology ; Cerebellar Ataxia/genetics ; Cerebellar Ataxia/pathology ; Craniosynostoses/genetics ; Craniosynostoses/pathology ; Cytoplasmic Dyneins/genetics ; Cytoplasmic Dyneins/metabolism ; Dyneins/genetics ; Dyneins/metabolism ; Ectodermal Dysplasia/genetics ; Ectodermal Dysplasia/pathology ; Ellis-Van Creveld Syndrome/genetics ; Ellis-Van Creveld Syndrome/pathology ; Epistasis, Genetic ; European Continental Ancestry Group/genetics ; Female ; Fibroblasts/pathology ; Gene Knockdown Techniques ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Kidney Diseases, Cystic/genetics ; Kidney Diseases, Cystic/pathology ; Male ; Molecular Sequence Data ; Mutation ; Phenotype ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/pathology ; Zebrafish/genetics
Chemical Substances	DYNC2H1 protein, human ; Intracellular Signaling Peptides and Proteins ; Cytoplasmic Dyneins (EC 3.6.4.2) ; Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2013-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2013.09.012
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Article ; Online: Rituximab in severe lupus nephritis: early B-cell depletion affects long-term renal outcome.

Melander, Catherine / Sallée, Marion / Trolliet, Pierre / Candon, Sophie / Belenfant, Xavier / Daugas, Eric / Rémy, Phillipe / Zarrouk, Virginie / Pillebout, Evangéline / Jacquot, Christian / Boffa, Jean-Jacques / Karras, Alexandre / Masse, Virginie / Lesavre, Philippe / Elie, Caroline / Brocheriou, Isabelle / Knebelmann, Bertrand / Noël, Laure-Hélène / Fakhouri, Fadi

Clinical journal of the American Society of Nephrology : CJASN

2009 Volume 4, Issue 3, Page(s) 579–587

Abstract: ... effects. Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients ... of rituximab. The achievement of B cell depletion 1 mo after rituximab, which negatively correlated with black ... in relapsing or refractory lupus nephritis when early B cell depletion is obtained. ...

Abstract	Background and objectives: Standard treatment for lupus nephritis, including corticosteroids and cyclophosphamide, is efficient but is still associated with refractory or relapsing disease, or severe deleterious effects. Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients with lupus nephritis, but reported series were small and had a short follow-up. Design, setting, participants, & measurements: The authors analyzed clinical and histologic data of 20 patients who were treated with rituximab for lupus nephritis and followed up for at least 12 mo. Results: Nineteen women and one man received rituximab as induction treatment for an active class IV (15 cases) or class V (5 cases) lupus nephritis. Rituximab was given for lupus nephritis refractory to standard treatment (12 cases), for relapsing disease (6 cases), or as first-line treatment (2 cases). Three patients received cyclophosphamide concomitantly with rituximab. Ten received new injections of rituximab as maintenance therapy. Side effects included mainly five infections and four moderate neutropenias. After a median follow-up of 22 mo, complete or partial renal remission was obtained in 12 patients (60%). Lupus nephritis relapsed in one patient, who responded to a new course of rituximab. The achievement of B cell depletion 1 mo after rituximab, which negatively correlated with black ethnicity and hypoalbuminemia, was strongly associated with renal response. Rapidly progressive glomerulonephritis did not respond to rituximab. Conclusion: Rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis when early B cell depletion is obtained.
MeSH term(s)	African Continental Ancestry Group ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Murine-Derived ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; Cyclophosphamide/therapeutic use ; Disease Progression ; Drug Therapy, Combination ; Female ; France ; Glomerulonephritis, Membranous/drug therapy ; Glomerulonephritis, Membranous/ethnology ; Glomerulonephritis, Membranous/immunology ; Glomerulonephritis, Membranous/physiopathology ; Humans ; Hypoalbuminemia/drug therapy ; Hypoalbuminemia/immunology ; Immunologic Factors/adverse effects ; Immunologic Factors/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Kidney/drug effects ; Kidney/physiopathology ; Kidney Function Tests ; Lupus Nephritis/drug therapy ; Lupus Nephritis/ethnology ; Lupus Nephritis/immunology ; Lupus Nephritis/physiopathology ; Lymphocyte Depletion/methods ; Male ; Patient Selection ; Recurrence ; Retrospective Studies ; Rituximab ; Severity of Illness Index ; Time Factors ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Murine-Derived ; Immunologic Factors ; Immunosuppressive Agents ; Rituximab (4F4X42SYQ6) ; Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2009-03-04
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.04030808
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Article ; Online: Performance and clinical utility of a new supervised machine-learning pipeline in detecting rare ciliopathy patients based on deep phenotyping from electronic health records and semantic similarity.

Faviez, Carole / Vincent, Marc / Garcelon, Nicolas / Boyer, Olivia / Knebelmann, Bertrand / Heidet, Laurence / Saunier, Sophie / Chen, Xiaoyi / Burgun, Anita

Orphanet journal of rare diseases

2024 Volume 19, Issue 1, Page(s) 55

Abstract: Background: Rare diseases affect approximately 400 million people worldwide. Many of them suffer from delayed diagnosis. Among them, NPHP1-related renal ciliopathies need to be diagnosed as early as possible as potential treatments have been recently ... ...

Abstract	Background: Rare diseases affect approximately 400 million people worldwide. Many of them suffer from delayed diagnosis. Among them, NPHP1-related renal ciliopathies need to be diagnosed as early as possible as potential treatments have been recently investigated with promising results. Our objective was to develop a supervised machine learning pipeline for the detection of NPHP1 ciliopathy patients from a large number of nephrology patients using electronic health records (EHRs). Methods and results: We designed a pipeline combining a phenotyping module re-using unstructured EHR data, a semantic similarity module to address the phenotype dependence, a feature selection step to deal with high dimensionality, an undersampling step to address the class imbalance, and a classification step with multiple train-test split for the small number of rare cases. The pipeline was applied to thirty NPHP1 patients and 7231 controls and achieved good performances (sensitivity 86% with specificity 90%). A qualitative review of the EHRs of 40 misclassified controls showed that 25% had phenotypes belonging to the ciliopathy spectrum, which demonstrates the ability of our system to detect patients with similar conditions. Conclusions: Our pipeline reached very encouraging performance scores for pre-diagnosing ciliopathy patients. The identified patients could then undergo genetic testing. The same data-driven approach can be adapted to other rare diseases facing underdiagnosis challenges.
MeSH term(s)	Humans ; Rare Diseases ; Electronic Health Records ; Semantics ; Supervised Machine Learning ; Ciliopathies/diagnosis ; Ciliopathies/genetics ; Algorithms
Language	English
Publishing date	2024-02-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2225857-7
ISSN	1750-1172 ; 1750-1172
ISSN (online)	1750-1172
ISSN	1750-1172
DOI	10.1186/s13023-024-03063-7
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Article ; Online: Neuro-image: Emesis-induced Orbital Subperiosteal Hematoma.

Knebelmann, Paul / Kerleroux, Basile / Manchon, Aurelie / Reyre, Anthony / Delmas, Florent / Hak, Jean François

Neurology India

2023 Volume 71, Issue 5, Page(s) 1102–1103

MeSH term(s)	Humans ; Orbital Diseases ; Tomography, X-Ray Computed ; Hematoma/diagnostic imaging ; Hematoma/etiology ; Vomiting/etiology ; Exophthalmos
Language	English
Publishing date	2023-11-06
Publishing country	India
Document type	Journal Article
ZDB-ID	415522-1
ISSN	1998-4022 ; 0028-3886
ISSN (online)	1998-4022
ISSN	0028-3886
DOI	10.4103/0028-3886.388067
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Article ; Online: Stabilité de l'hémoglobine: résultats d'essais cliniques.

Knebelmann, B

Nephrologie & therapeutique

2009 Volume 5, Issue 5 Suppl, Page(s) 15–20

Title translation	Hemoglobin stability: results of clinical trials.
MeSH term(s)	Clinical Trials as Topic ; Hemoglobins/analysis ; Humans ; Randomized Controlled Trials as Topic ; Renal Insufficiency/blood
Chemical Substances	Hemoglobins
Language	French
Publishing date	2009-09
Publishing country	France
Document type	Journal Article
ZDB-ID	2229575-6
ISSN	1872-9177 ; 1769-7255
ISSN (online)	1872-9177
ISSN	1769-7255
DOI	10.1016/S1769-7255(09)75176-4
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Article: Effect of urine alkalization on urinary inflammatory markers in cystinuric patients.

Prot-Bertoye, Caroline / Jung, Vincent / Tostivint, Isabelle / Roger, Kevin / Benoist, Jean-François / Jannot, Anne-Sophie / Van Straaten, Alexis / Knebelmann, Bertrand / Guerrera, Ida Chiara / Courbebaisse, Marie

Clinical kidney journal

2024 Volume 17, Issue 3, Page(s) sfae040

Abstract: Background: Cystinuria is associated with a high prevalence of chronic kidney disease (CKD). We previously described a urinary inflammatory-protein signature (UIS), including 38 upregulated proteins, in cystinuric patients (Cys-patients), compared with ... ...

Abstract	Background: Cystinuria is associated with a high prevalence of chronic kidney disease (CKD). We previously described a urinary inflammatory-protein signature (UIS), including 38 upregulated proteins, in cystinuric patients (Cys-patients), compared with healthy controls (HC). This UIS was higher in Cys-patients with CKD. In the present observational study, we aimed to investigate the UIS in Cys-patients without CKD and patients with calcium nephrolithiasis (Lith-patients), versus HC and the effect of urine alkalization on the UIS of Cys-patients. Methods: UIS was evaluated by nano-liquid chromatography coupled to high-resolution mass spectrometry in adult HC, Lith-patients and non-treated Cys-patients with an estimated glomerular filtration rate >60 mL/min/1.73 m Results: Twenty-one Cys-patients [12 men, median age (interquartile range) 30.0 (25.0-44.0) years], 12 Lith-patients [8 men, 46.2 (39.5-54.2) years] and 7 HC [2 men, 43.1 (31.0-53.9) years] were included. Among the 38 proteins upregulated in our previous work, 11 proteins were also upregulated in Cys-patients compared with HC in this study (5 circulating inflammatory proteins and 6 neutrophil-derived proteins). This UIS was also found in some Lith-patients. Using this UIS, we identified two subclusters of Cys-patients (5 with a very high/high UIS and 16 with a moderate/low UIS). In the Cys-patients with very high/high UIS, urine alkalization induced a significant decrease in urinary neutrophil-derived proteins. Conclusion: A high UIS is present in some Cys-patients without CKD and decreases under alkalizing treatment. This UIS could be a prognostic marker to predict the evolution towards CKD in cystinuria.
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfae040
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Article ; Online: Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease.

Dang, Julien / Scemla, Anne / Loheac, Charlotte / Chaba, Anis / Bienaimé, Frank / Joly, Dominique / Legendre, Christophe / Knebelmann, Bertrand / Charlier, Caroline

Mayo Clinic proceedings

2022 Volume 97, Issue 7, Page(s) 1305–1317

Abstract: Objective: To determine the impact of antibiotic therapy (ATBT) on outcomes of renal cyst infection (CyI) in patients with polycystic kidney disease.: Patients and methods: We undertook a single-center retrospective study of CyI in autosomal dominant ...

Abstract	Objective: To determine the impact of antibiotic therapy (ATBT) on outcomes of renal cyst infection (CyI) in patients with polycystic kidney disease. Patients and methods: We undertook a single-center retrospective study of CyI in autosomal dominant polycystic kidney disease (January 1, 2000, through December 31, 2018). Cyst infections were classified as definite (microbiologically proven), probable (radiologic signs), or possible (clinical or biologic signs only). We studied the determinants of ATBT failure (persistence of infection beyond 72 hours of microbiologically adequate initial ATBT, with requirement for ATBT change, cyst drainage, or nephrectomy) and recurrences (>14 days after the end of ATBT). Results: Among 90 patients, 139 CyIs (11 definite, 74 probable, 54 possible) were compiled. Cultures were positive in 106 of 139 (76%) episodes, with Escherichia coli found in 89 of 106 (84%). Treatment failures and recurrences within 1 year of follow-up were more frequent in definite/probable CyI (20/85 [34%] and 16/85 [19%]) than in possible CyI (2/54 [4%] and 4/54 [7%]; P<.01 and P=.08, respectively). Male sex (odds ratio [OR], 7.79; 95% CI, 1.72 to 46.68; P<.01), peak C-reactive protein level above 250 mg/L (OR, 7.29; 95% CI, 1.78 to 35.74; P<.01; to convert C-reactive protein values to nmol/L, multiply by 9.524), and cyst wall thickening (OR, 7.70; 95% CI, 1.77 to 43.47; P=.01) but not the modalities of initial ATBT were independently associated with higher risk of failure. In a Cox proportional hazards model, kidney transplant recipients exhibited higher risk of recurrence (hazard ratio, 3.76; 95% CI, 1.06 to 13.37; P=.04), whereas a total duration of ATBT of 28 days or longer was protective (hazard ratio, 0.02; 95% CI, 0.00 to 0.16; P<.001), with an inverse correlation between duration and recurrence (81% for treatment <21 days, 47% for 21 to 27 days, 2% for ≥28 days; P<.0001). Conclusion: Initial first-line ATBT had no significant effect on renal CyI treatment failure. Treatment duration of 28 days and longer reduced recurrences.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; C-Reactive Protein ; Cysts/complications ; Cysts/drug therapy ; Humans ; Male ; Polycystic Kidney Diseases/complications ; Polycystic Kidney Diseases/drug therapy ; Retrospective Studies
Chemical Substances	Anti-Bacterial Agents ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2022-07-04
Publishing country	England
Document type	Journal Article
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2022.01.027
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Article ; Online: HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial.

Bais, Thomas / Meijer, Esther / Kramers, Bart J / Vart, Priya / Vervloet, Marc / Salih, Mahdi / Bammens, Bert / Demoulin, Nathalie / Todorova, Polina / Müller, Roman-Ulrich / Halbritter, Jan / Paliege, Alexander / Gall, Emilie Cornec-Le / Knebelmann, Bertrand / Torra, Roser / Ong, Albert C M / Karet Frankl, Fiona E / Gansevoort, Ron T

Trials

2024 Volume 25, Issue 1, Page(s) 120

Abstract: Background: Autosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available ... ...

Abstract	Background: Autosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD. Methods: The HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is powered to enroll 300 rapidly progressive patients with ADPKD aged ≥ 18 years, with an eGFR of > 25 mL/min/1.73 m Outcomes: The primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73 m Conclusion: The HYDRO-PROTECT study will demonstrate whether co-treatment with HCT can improve the renoprotective efficacy and tolerability of tolvaptan in patients with ADPKD.
MeSH term(s)	Humans ; Tolvaptan/adverse effects ; Polycystic Kidney, Autosomal Dominant/diagnosis ; Polycystic Kidney, Autosomal Dominant/drug therapy ; Hydrochlorothiazide/adverse effects ; Quality of Life ; Glomerular Filtration Rate ; Antidiuretic Hormone Receptor Antagonists/adverse effects ; Kidney ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic
Chemical Substances	Tolvaptan (21G72T1950) ; Hydrochlorothiazide (0J48LPH2TH) ; Antidiuretic Hormone Receptor Antagonists
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1745-6215
ISSN (online)	1745-6215
ISSN	1468-6694 ; 1745-6215
DOI	10.1186/s13063-024-07952-x
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Article ; Online: VNtyper enables accurate alignment-free genotyping of

Saei, Hassan / Morinière, Vincent / Heidet, Laurence / Gribouval, Olivier / Lebbah, Said / Tores, Frederic / Mautret-Godefroy, Manon / Knebelmann, Bertrand / Burtey, Stéphane / Vuiblet, Vincent / Antignac, Corinne / Nitschké, Patrick / Dorval, Guillaume

iScience

2023 Volume 26, Issue 7, Page(s) 107171

Abstract: The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease- ...

Abstract	The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease-
Language	English
Publishing date	2023-06-17
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107171
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