1. J Cell Sci. 2025 Oct 15;138(20):jcs264141. doi: 10.1242/jcs.264141. Epub 2025 
Sep 8.

Urinary renal epithelial cells can be used for NPHP1 phenotyping and a 
personalized therapeutic strategy.

Sudhindar PD(1), Olinger E(1)(2), Sentell ZT(3), Mabillard H(1), Dicka B(1), 
Wood K(4), Rutland D(1), Collins C(2), Trevisan-Herraz M(1), Sayer JA(3)(5)(6), 
Arcila-Galvis JE(3).

Author information:
(1)Translational and Clinical Research Institute, Faculty of Medical Sciences, 
Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
(2)Center for Human Genetics, Cliniques Universitaires Saint-Luc, Brussels, 
Belgium.
(3)Biosciences Institute, Faculty of Medical Sciences, Newcastle University, 
Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
(4)Royal Victoria Infirmary, Newcastle upon Tyne, NE2 4LP, UK.
(5)Renal Services, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle 
upon Tyne, NE7 7DN, UK.
(6)NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, NE4 5PL, UK.

Nephronophthisis (NPHP) is a recessive tubulointerstitial nephropathy and a 
leading genetic cause of kidney failure in children and young adults. The most 
common genetic cause is a homozygous deletion of NPHP1, which encodes 
nephrocystin-1, a protein essential for primary cilium structure and cell 
junctions. Using personalized medicine and deep phenotyping, we investigated a 
family with three siblings carrying a homozygous NPHP1 deletion. We compared 
kidney biopsy tissue and human urine-derived renal epithelial cells (hURECs) 
from these individuals. Bulk RNA-seq on patient hURECs revealed altered 
expression in EGFR signalling, extracellular components and adherens junctions, 
which is consistent with the known roles for nephrocystin-1. Treatment with 
alprostadil, a proposed NPHP therapy, increased ciliation but worsened ciliary 
elongation. By contrast, the EGFR kinase inhibitor AG556 rescued of ciliary 
length and morphology. Transcriptional profiling post-treatment showed AG556 
reversed the disease signature more effectively that alprostadil. These findings 
suggest that EGFR inhibition might offer a more promising therapeutic strategy 
for NPHP1-associated renal ciliopathy, warranting further testing in in vivo 
models before clinical application.

© 2025. Published by The Company of Biologists.

DOI: 10.1242/jcs.264141
PMCID: PMC12450468
PMID: 40776899 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests The authors declare no 
competing or financial interests.