Zivna, Martina, Kidd, Kendrah, Zaidan, Mohamad, Vyletal, Petr ORCID: 0000-0002-9357-1237, Baresova, Veronika, Hodanova, Katerina, Sovova, Jana, Hartmannova, Hana, Votruba, Miroslav, Treslova, Helena, Jedlickova, Ivana, Sikora, Jakub, Hulkova, Helena, Robins, Victoria, Hnizda, Ales, Zivny, Jan, Papagregoriou, Gregory, Mesnard, Laurent, Beck, Bodo B., Wenzel, Andrea, Tory, Kalman, Haeeffner, Karsten, Wolf, Matthias T. F., Bleyer, Michael E., Sayer, John A., Ong, Albert C. M., Balogh, Lidia, Jakubowska, Anna, Laszkiewicz, Agnieszka ORCID: 0000-0002-0317-4255, Clissold, Rhian, Shaw-Smith, Charles, Munshi, Raj, Haws, Robert M., Izzi, Claudia, Capelli, Irene, Santostefano, Marisa, Graziano, Claudio ORCID: 0000-0003-3875-6869, Scolari, Francesco, Sussman, Amy, Trachtman, Howard ORCID: 0000-0001-7447-9489, Decramer, Stephane, Matignon, Marie, Grimbert, Philippe, Shoemaker, Lawrence R., Stavrou, Christoforos, Abdelwahed, Mayssa, Belghith, Neila, Sinclair, Matthew, Claes, Kathleen, Kopel, Tal, Moe, Sharon, Deltas, Constantinos, Knebelmann, Bertrand, Rampoldi, Luca, Kmoch, Stanislav and Bleyer, Anthony J. (2020). An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes. Kidney Int., 98 (6). S. 1589 - 1605. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zivna, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kidd, KendrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zaidan, MohamadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vyletal, PetrUNSPECIFIEDorcid.org/0000-0002-9357-1237UNSPECIFIED
Baresova, VeronikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hodanova, KaterinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sovova, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmannova, HanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Votruba, MiroslavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Treslova, HelenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jedlickova, IvanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sikora, JakubUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hulkova, HelenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robins, VictoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hnizda, AlesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zivny, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papagregoriou, GregoryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mesnard, LaurentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, Bodo B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenzel, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tory, KalmanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haeeffner, KarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, Matthias T. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bleyer, Michael E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sayer, John A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ong, Albert C. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balogh, LidiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakubowska, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laszkiewicz, AgnieszkaUNSPECIFIEDorcid.org/0000-0002-0317-4255UNSPECIFIED
Clissold, RhianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shaw-Smith, CharlesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munshi, RajUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haws, Robert M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izzi, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Capelli, IreneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Santostefano, MarisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graziano, ClaudioUNSPECIFIEDorcid.org/0000-0003-3875-6869UNSPECIFIED
Scolari, FrancescoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sussman, AmyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trachtman, HowardUNSPECIFIEDorcid.org/0000-0001-7447-9489UNSPECIFIED
Decramer, StephaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matignon, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grimbert, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shoemaker, Lawrence R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stavrou, ChristoforosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abdelwahed, MayssaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belghith, NeilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sinclair, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claes, KathleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kopel, TalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moe, SharonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deltas, ConstantinosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knebelmann, BertrandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rampoldi, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kmoch, StanislavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bleyer, Anthony J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-309454
DOI: 10.1016/j.kint.2020.06.041
Journal or Publication Title: Kidney Int.
Volume: 98
Number: 6
Page Range: S. 1589 - 1605
Date: 2020
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1523-1755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SIGNAL PEPTIDE; ANGIOTENSIN SYSTEM; HUMAN PRORENIN; GENE; INSULIN; MUTANT; HYPERURICEMIA; PROSEGMENT; VARIANTS; ANEMIAMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/30945

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