-
Something wrong with this record ?
An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes
M. Živná, K. Kidd, M. Zaidan, P. Vyleťal, V. Barešová, K. Hodaňová, J. Sovová, H. Hartmannová, M. Votruba, H. Trešlová, I. Jedličková, J. Sikora, H. Hůlková, V. Robins, A. Hnízda, J. Živný, G. Papagregoriou, L. Mesnard, BB. Beck, A. Wenzel, K....
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
Grant support
R01 DK119631
NIDDK NIH HHS - United States
R21 DK106584
NIDDK NIH HHS - United States
T32 DK007731
NIDDK NIH HHS - United States
NV17-29786A
MZ0
CEP Register
Digital library NLK
Full text - Article
NLK
Freely Accessible Science Journals
from 1972
Open Access Digital Library
from 1972-01-01
- MeSH
- Anemia * MeSH
- Child MeSH
- Adult MeSH
- Cohort Studies MeSH
- Humans MeSH
- Young Adult MeSH
- Mutation MeSH
- Polycystic Kidney Diseases * genetics MeSH
- Renin genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.
1st Department of Pediatrics Semmelweis University Budapest Hungary
AP HP CIC BT 504 Créteil France
AP HP Groupe Hospitalier Henri Mondor Albert Chenevier Créteil France
Centre Hospitalier Universitaire de Toulouse Toulouse France
Département Biologie cellulaire INSERM U1151 Institut Necker Enfants Malades Paris France
Department of Biochemistry University of Cambridge Cambridge UK
Department of Nephrology and Renal Transplantation University Hospitals Leuven Leuven Belgium
Department of Nephrology Evangelismos Private Hospital Pafos Cyprus
Department of Nephrology‒Transplantation Necker Hospital APHP Paris France
Department of Pediatric Nephrology Medical University Wrocław Poland
Division of Nephrology Department of Pediatrics University of Florida Gainesville Florida USA
Division of Nephrology Indiana University School of Medicine Indianapolis Indiana USA
Division of Nephrology Ospedale Sant'Orsola‒Malpighi Bologna Italy
Duke Clinical Research Institute Durham North Carolina USA
Exeter Kidney Unit Royal Devon and Exeter NHS Foundation Trust Exeter Devon UK
France Rare Renal Disease Reference Centre Toulouse France
Institute of Pathophysiology 1st Faculty of Medicine Charles University Prague Czech Republic
Laboratory of Human Molecular Genetics Faculty of Medicine University of Sfax Sfax Tunisia
Medical Genetics Department of Hedi Chaker Hospital Sfax Tunisia
Medical Genetics Unit Policlinico S Orsola Malpighi Bologna Italy
MTA SE Lendület Nephrogenetic Laboratory Semmelweis University Budapest Hungary
Nephrology Division University of Montreal Hospital Centre Hopital Saint Luc Montréal Québec Canada
NIHR Newcastle Biomedical Research Centre Newcastle University Newcastle upon Tyne UK
Paris Descartes University Sorbonne Paris Cité Paris France
Pediatric Nephrology Centre Hospitalier Universitaire de Toulouse Toulouse France
Pediatric Nephrology University of Texas Southwestern Medical Center Dallas Texas USA
Pediatrics Nephrology Marshfield Medical Center Marshfield Wisconsin USA
Renal Services The Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UK
Section on Nephrology Wake Forest School of Medicine Winston Salem North Carolina USA
Service de Néphrologie‒Transplantation Hôpital de Bicêtre Le Kremlin Bicêtre France
Université Paris Est Créteil Equipe 21 INSERM U 955 Créteil France
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc21019751
- 003
- CZ-PrNML
- 005
- 20221212090442.0
- 007
- ta
- 008
- 210728s2020 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.kint.2020.06.041 $2 doi
- 035 __
- $a (PubMed)32750457
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Živná, Martina $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 245 13
- $a An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes / $c M. Živná, K. Kidd, M. Zaidan, P. Vyleťal, V. Barešová, K. Hodaňová, J. Sovová, H. Hartmannová, M. Votruba, H. Trešlová, I. Jedličková, J. Sikora, H. Hůlková, V. Robins, A. Hnízda, J. Živný, G. Papagregoriou, L. Mesnard, BB. Beck, A. Wenzel, K. Tory, K. Häeffner, MTF. Wolf, ME. Bleyer, JA. Sayer, ACM. Ong, L. Balogh, A. Jakubowska, A. Łaszkiewicz, R. Clissold, C. Shaw-Smith, R. Munshi, RM. Haws, C. Izzi, I. Capelli, M. Santostefano, C. Graziano, F. Scolari, A. Sussman, H. Trachtman, S. Decramer, M. Matignon, P. Grimbert, LR. Shoemaker, C. Stavrou, M. Abdelwahed, N. Belghith, M. Sinclair, K. Claes, T. Kopel, S. Moe, C. Deltas, B. Knebelmann, L. Rampoldi, S. Kmoch, AJ. Bleyer
- 520 9_
- $a There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.
- 650 _2
- $a dospělí $7 D000328
- 650 12
- $a anemie $7 D000740
- 650 _2
- $a dítě $7 D002648
- 650 _2
- $a kohortové studie $7 D015331
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a mutace $7 D009154
- 650 12
- $a polycystická choroba ledvin $x genetika $7 D007690
- 650 _2
- $a renin $x genetika $7 D012083
- 650 _2
- $a mladý dospělý $7 D055815
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a Research Support, N.I.H., Extramural $7 D052061
- 655 _2
- $a práce podpořená grantem $7 D013485
- 655 _2
- $a Research Support, U.S. Gov't, Non-P.H.S. $7 D013486
- 700 1_
- $a Kidd, Kendrah $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic; Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- 700 1_
- $a Zaidan, Mohamad $u Service de Néphrologie‒Transplantation, Hôpital de Bicêtre, Le Kremlin Bicêtre, France
- 700 1_
- $a Vyleťal, Petr $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Barešová, Veronika $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Hodaňová, Kateřina $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Sovová, Jana $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Hartmannová, Hana $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Votruba, Miroslav $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Trešlová, Helena $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic $7 xx0279684
- 700 1_
- $a Jedličková, Ivana $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Sikora, Jakub $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Hůlková, Helena $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Robins, Victoria $u Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- 700 1_
- $a Hnízda, Aleš $u Department of Biochemistry, University of Cambridge, Cambridge, UK
- 700 1_
- $a Živný, Jan $u Institute of Pathophysiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Papagregoriou, Gregory $u Center of Excellence in Biobanking and Biomedical Research, Molecular Medicine Research Center, University of Cyprus, Nicosia, Cyprus
- 700 1_
- $a Mesnard, Laurent $u Sorbonne Université, Urgences Néphrologiques et Transplantation Rénale, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Tenon, Paris, France
- 700 1_
- $a Beck, Bodo B $u University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Human Genetics, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC) and Center for Rare Diseases Cologneies(ZSEK), Cologne, Germany
- 700 1_
- $a Wenzel, Andrea $u University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Human Genetics, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC) and Center for Rare Diseases Cologneies(ZSEK), Cologne, Germany
- 700 1_
- $a Tory, Kálmán $u MTA-SE Lendület Nephrogenetic Laboratory, Semmelweis University, Budapest, Hungary; First Department of Pediatrics, Semmelweis University, Budapest, Hungary
- 700 1_
- $a Häeffner, Karsten $u Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, Universitätsklinikum Freiburg, Freiburg, Germany
- 700 1_
- $a Wolf, Matthias T F $u Pediatric Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 700 1_
- $a Bleyer, Michael E $u Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- 700 1_
- $a Sayer, John A $u Renal Services, The Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK
- 700 1_
- $a Ong, Albert C M $u Kidney Genetics Group, Academic Nephrology Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
- 700 1_
- $a Balogh, Lídia $u First Department of Pediatrics, Semmelweis University, Budapest, Hungary
- 700 1_
- $a Jakubowska, Anna $u Department of Pediatric Nephrology Medical University Wrocław, Poland
- 700 1_
- $a Łaszkiewicz, Agnieszka $u Laboratory of Molecular and Cellular Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
- 700 1_
- $a Clissold, Rhian $u Exeter Kidney Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UK
- 700 1_
- $a Shaw-Smith, Charles $u Exeter Kidney Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UK
- 700 1_
- $a Munshi, Raj $u Division of Nephrology, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA
- 700 1_
- $a Haws, Robert M $u Pediatrics-Nephrology, Marshfield Medical Center, Marshfield, Wisconsin, USA
- 700 1_
- $a Izzi, Claudia $u Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy
- 700 1_
- $a Capelli, Irene $u Department of Experimental Diagnostic and Specialty Medicine, Nephrology, Dialysis and Renal Transplant Unit, S. Orsola Hospital, University of Bologna, Bologna, Italy
- 700 1_
- $a Santostefano, Marisa $u Division of Nephrology, Ospedale Sant'Orsola‒Malpighi, Bologna, Italy
- 700 1_
- $a Graziano, Claudio $u Medical Genetics Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy
- 700 1_
- $a Scolari, Francesco $u Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy
- 700 1_
- $a Sussman, Amy $u Department of Medicine, Division of Nephrology, University of Arizona Health Sciences Center, Tucson, Arizona, USA
- 700 1_
- $a Trachtman, Howard $u Division of Nephrology, Department of Pediatrics, New York University School of Medicine, New York, New York, USA
- 700 1_
- $a Decramer, Stephane $u Pediatric Nephrology, Centre Hospitalier Universitaire de Toulouse (CHU de Toulouse), Toulouse, France; France Rare Renal Disease Reference Centre (SORARE), Toulouse, France; Centre Hospitalier Universitaire de Toulouse (CHU de Toulouse), Toulouse, France
- 700 1_
- $a Matignon, Marie $u AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Créteil, France; Université Paris-Est-Créteil, (UPEC), DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Créteil, France
- 700 1_
- $a Grimbert, Philippe $u AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Créteil, France; Université Paris-Est-Créteil, (UPEC), DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), CIC-BT 504, Créteil, France
- 700 1_
- $a Shoemaker, Lawrence R $u Division of Nephrology, Department of Pediatrics, University of Florida, Gainesville, Florida, USA
- 700 1_
- $a Stavrou, Christoforos $u Department of Nephrology, Evangelismos Private Hospital, Pafos, Cyprus
- 700 1_
- $a Abdelwahed, Mayssa $u Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- 700 1_
- $a Belghith, Neila $u Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia; Medical Genetics Department of Hedi Chaker Hospital, Sfax, Tunisia
- 700 1_
- $a Sinclair, Matthew $u Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; Duke Clinical Research Institute, Durham, North Carolina, USA
- 700 1_
- $a Claes, Kathleen $u Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium; Laboratory of Nephrology, Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium
- 700 1_
- $a Kopel, Tal $u Nephrology Division, University of Montreal Hospital Centre, Hopital Saint-Luc, Montréal, Québec, Canada
- 700 1_
- $a Moe, Sharon $u Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- 700 1_
- $a Deltas, Constantinos $u Center of Excellence in Biobanking and Biomedical Research, Molecular Medicine Research Center, University of Cyprus, Nicosia, Cyprus
- 700 1_
- $a Knebelmann, Bertrand $u Department of Nephrology‒Transplantation, Necker Hospital, APHP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France; Département Biologie cellulaire, INSERM U1151, Institut Necker Enfants Malades, Paris, France
- 700 1_
- $a Rampoldi, Luca $u Molecular Genetics of Renal Disorders, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
- 700 1_
- $a Kmoch, Stanislav $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic; Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- 700 1_
- $a Bleyer, Anthony J $u Research Unit of Rare Diseases, Department of Pediatric and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic; Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. Electronic address: ableyer@wakehealth.edu
- 773 0_
- $w MED00010141 $t Kidney international $x 1523-1755 $g Roč. 98, č. 6 (2020), s. 1589-1604
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/32750457 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20210728 $b ABA008
- 991 __
- $a 20221212090440 $b ABA008
- 999 __
- $a ok $b bmc $g 1690541 $s 1140197
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2020 $b 98 $c 6 $d 1589-1604 $e 20200801 $i 1523-1755 $m Kidney international $n Kidney Int $x MED00010141
- GRA __
- $a R01 DK119631 $p NIDDK NIH HHS $2 United States
- GRA __
- $a R21 DK106584 $p NIDDK NIH HHS $2 United States
- GRA __
- $a T32 DK007731 $p NIDDK NIH HHS $2 United States
- GRA __
- $a NV17-29786A $p MZ0
- LZP __
- $a Pubmed-20210728
