Refining Kidney Survival in 383 Genetically Characterized Patients With Nephronophthisis
Jens König, Rebeka Karsay, Joachim Gerß, Karl‐Peter Schlingmann, Mareike Dahmer‐Heath, Anna-Katharina Telgmann, Sabine Kollmann, Gema Ariceta, Valentine Gillion, Detlef Böckenhauer, Aurélia Bertholet‐Thomas, Antonio Mastrangelo, Olivia Boyer, Marc R. Liliën, Stéphane Decramer, Joost P. Schanstra, Martin Pöhl, Raphael Schild, Stefanie Weber, Julia Hoefele, Jens Drube, Metin Cetiner, Matthias Hansen, Julia Thumfart, Burkhard Tönshoff, Sandra Habbig, Max C. Liebau, Martin Bald, Carsten Bergmann, Petra Pennekamp, Martin Konrad, P. Antczak, Johannes Birtel, C. Bergmann, Metin Cetiner, Mareike Dahmer‐Heath, Jens Drube, Joachim Gerß, Dieter Haffner, Thomas Illig, I. Kamp-Becker, N. Klopp, Sabine Kollmann, Jens König, Moira Konrad, Max C. Liebau, C. Nittel, C. Okorn, Heymut Omran, Lars Pape, Petra Pennekamp, Franz Schäfer, Bernhard Schermer, H. Storf, J. Vasseur, Stefanie Weber, Kai Wohlgemuth, Wolfgang Ziegler, Charlotte Gimpel, J. Göbel, B. Schlevogt
Abstract
IntroductionNephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical characteristics with declining kidney function.MethodsData was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry (n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases (n = 60), and a literature search (n = 218).ResultsA total of 383 individuals were available for analysis: 116 NPHP1, 101 NPHP3, 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3–12.0); NPHP1, 13.5 years (interquartile range 10.5–16.5); NPHP4, 16.0 years (interquartile range 11.0–25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7–28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1, NPHP3, and NPHP4. Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline.ConclusionThe presented data will enable clinicians to better estimate kidney prognosis of distinct patients with NPH and thereby allow personalized counseling.