Intraflagellar transport (IFT) is a fundamental process driving ciliogenesis in most eukaryotic organisms. IFT172, the largest protein of the IFT complex, plays a crucial role in cilium formation, and several disease-causing IFT172 variants have been identified in ciliopathy patients. While IFT172 is tethered to the IFT-B complex via its N-terminal domains, the function of its C-terminal domains has remained elusive. Here, using both human and Chlamydomonas reinhardtii IFT172, we reveal that the C-terminal part of IFT172 interacts with IFT-A complex subunits, providing a molecular basis for the role of IFT172 in bridging IFT-A and IFT-B complexes. We determine the crystal structure of the C-terminal part of IFT172, uncovering a conserved U-box-like domain often found in E3 ubiquitin ligases. This domain exhibits ubiquitin-binding properties, and IFT172 undergoes ubiquitin conjugation in vitro, an activity that is reduced in the C1727R patient ciliopathy variant. We use CRISPR-engineered RPE-1 cells to demonstrate that the U-box-like domain is essential for IFT172 protein stability and proper cilium formation. Notably, RPE-1 cells with heterozygous deletion of the U-box domain show altered TGF-β signaling responses, particularly in SMAD2 phosphorylation levels and AKT activation. Our findings suggest that IFT172, beyond its structural role in bridging IFT-A and IFT-B complexes within IFT trains, harbors a conserved U-box-like domain with potential involvement in ciliary ubiquitination processes and signaling, providing new insights into the molecular mechanisms underlying IFT172-related ciliopathies.

ABSTRACT The primary cilium is a microtubule-based sensory organelle projecting from the plasma membrane of most mammalian cells. Genetic defects in ciliary components cause chronic kidney disease (CKD) characterized by heightened production of inflammatory and fibrogenic mediators by tubular epithelial cells. Yet, whether this reflects a physiological role of the primary cilium remains unknown. Here, we show that primary cilia on kidney tubular cells bind uropathogenic Escherichia coli and, in response to bacterial components, initiate a fibro-inflammatory program reminiscent of CKD. Integrating single-cell transcriptomics with conditional mouse models, we observed that epithelial cilia orchestrate a similar fibro-inflammatory response in the absence of infection during CKD. This convergence reveals a shared cilia-dependent signalling axis governing both host–pathogen responses and CKD progression. Mechanistically, cilia ablation selectively impairs tubular responses to ADP-heptose, a pathogen-associated molecular pattern that activates NF-κB via the cytosolic innate immune receptor ALPK1. In human kidney organoids, ADP-heptose induces robust fibro-inflammation, and genetic or pharmacological inhibition of ALPK1 attenuates this response in a rodent CKD model. Together, these findings identify primary cilia as central orchestrators of a fibro-inflammatory program linking pathogen detection to kidney disease progression.

Background While pancreatic cysts have been described in syndromic ciliopathies, the pancreas is not commonly recognised as a target organ. However, several ciliary gene knockout mouse models develop a pancreatic phenotype combining acinar atrophy and adipocyte accumulation, here called adipopancreatosis, suggesting a link between ciliary dysfunction and pancreatic disease. Objective We investigated whether mutations in ciliopathy-associated genes are linked to pancreatic dysfunction in humans. Design We analysed a cohort of 341 patients with paediatric-onset pancreatic anomalies and characterised the pancreatic phenotype of new mouse models with conditional Nphp3 inactivation or bearing Nphp3 mutations recapitulating human mutations. In patients, pancreatic fat content was quantified using Dixon-MRI. Results Mutations in the cilium-related HNF1B and NPHP3 were identified in patients presenting with both renal and pancreatic dysfunction. Nphp3 mutant mice developed acinar atrophy, adipopancreatosis and moderate inflammation. Adipocytes in the pancreas exhibited a white adipocyte-like profile and may originate from mesothelial-derived fibroblasts. Reduced numbers and altered length of ductal cilia were monitored. Interestingly, secretory canaliculi, typically unnoticed structures found within and between acinar cells and connected to the acinar lumen, exhibited a microcystic morphology. Consistent with the mouse phenotype, Dixon-MRI revealed significantly increased pancreatic fat content in patients with HNF1B and NPHP3 mutations. Conclusion We describe a previously unrecognised pancreatic manifestation of ciliopathies, which we name ciliogenic pancreatopathy. Patients with known ciliopathy-causing mutations should be evaluated for this pancreatic condition, particularly those with kidney disease, as concomitant exocrine pancreatic insufficiency may further compromise renal function or the outcome of kidney graft.

Rare disease gene discovery is limited by small cohorts and the frequent absence of matched controls. We present the Case-Only Burden Test (COBT), a gene-based burden test for case-only designs accounting for multiple variants per individual and additive effects. COBT uses a Poisson model to test for excess variants in a gene relative to expectations from population mutation rates. Simulations show high power and competitive performance versus case-control burden tests. Validation on 1000 Genomes data demonstrated good model fit and low false-positive rates. Applied to 478 ciliopathy patients, COBT re-identified known causal genes and highlighted candidate variants in unsolved cases.

Primary cilia are tiny cellular protrusions of nearly every vertebrate cell controlling multiple cellular processes, such as proliferation, differentiation, migration etc. Their dysfunction results in severe human diseases collectively referred to as ciliopathies. Remarkably, many ciliopathies are associated with increased programmed cell death (PCD). However, it is largely unknown how primary cilia regulate PCD. In in vitro (murine and human cells) and in vivo ( Xenopus laevis and mouse) models, we observed elevated PCD in the absence of the ciliopathy protein RPGRIP1L. Mechanistically, our data elucidated that RPGRIP1L controls PCD by governing the activity of the ciliary proteasome. By using super-resolution microscopy, we first showed that the apoptosis inducer MOAP1 localises to primary cilia. Furthermore, our investigations revealed that RPGRIP1L controls PCD via the degradation of MOAP1 by the ciliary proteasome. Based on our finding that two more ciliopathy proteins, TCTN1 and CEP290, modulate PCD via regulating the activity of the ciliary proteasome, we suggest that the proteasomal degradation of MOAP1 represents a general mechanism by which primary cilia control PCD. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64

ABSTRACT Nephronophthisis (NPH) is n rare recessive kidney disease caused by biallelic variants in more than 25 NPHP genes encoding proteins that localize to primary cilia. It is characterized by three different forms depending on the age of onset and kidney lesions: infantile (cystic), juvenile/late onset (fibrotic). To date, the pathways linking altered primary cilia function to progressive kidney scarring in NPH remain poorly defined and therapeutic options are lacking. To address these questions, we generated two new mouse NPH models by inactivating Nphp3 specifically in kidney tubules either during embryogenesis or in adult, recapitulating the infantile and juvenile forms of the disease, respectively. Embryonic inactivation produced a rapid and severe cystic phenotype with tubular dedifferentiation, progressive interstitial fibrosis, inflammation and kidney failure, while postnatal inactivation led to a slowly progressive tubulointerstitial nephropathy characterized by tubular atrophy, fibrosis and immune cell infiltration without cyst formation. Strikingly, cilia were preserved in the early stages of both models, indicating that ciliogenesis impairment is not a primary driver of NPH3 pathogenesis. Transcriptomic profiling of the juvenile model revealed that disease initiation is driven by mitochondrial dysfunction, innate immune activation and aberrant cell cycle progression, while epithelial-to-mesenchymal transition and Wnt/β-catenin remodelling emerges only at later stages of disease progression. Therapeutic intervention with the PGE1 (alprostadil) failed to rescue the cystic/infantile model but significantly attenuated fibrosis, inflammation and interstitial fibrosis in the fibrotic/juvenile model. The ability to recapitulate both disease forms through temporal modulation of gene inactivation suggests that primary cilia serve distinct, stage-specific functions in kidney tubular homeostasis, with different cellular processes being selectively vulnerable depending on the causative gene or variant. Collectively, these findings uncover early pathogenic mechanisms that may constitute tractable therapeutic targets for the treatment of nephronophthisis.

Introduction A genetic diagnosis can transform care for patients with monogenic kidney disease—guiding treatment, prognosis, family-planning and care for relatives. Despite technological advancements, nephrologists still experience barriers to implementing diagnostic genetic testing in daily practice. Methods We surveyed 240 pediatric nephrologists, adult nephrologists and clinical geneticists across 39 European countries on the accessibility of and barriers to genetic testing for suspected genetic kidney disease. Using the Consolidated Framework for Implementation Research (CFIR) model, we assessed barriers at national, hospital, individual and implementation-process levels. Results were stratified by region (North, East, South, West-Europe and non-Organisation for Economic Co-operation and Development (OECD) countries). Binary logistic regression identified factors associated with barrier experience. Results 97% regarded genetic testing an important tool to improve care – yet 50% experienced barriers in daily practice. Median barrier severity score was 4.0 (IQR 4, scale 1-10). Non-OECD countries showed higher scores (6.8 (IQR 3.6), p<0.001). Most reported national-level barriers were lacking clear professional guidelines and concerns about post-test insurability. Hospital-level barriers included: insufficient clinic’s resources (costs, time, technical facilities, staffing), missing protocols for eligible patients/workflow and turnaround time (non-urgent: 12 weeks (IQR 12), urgent: 3 weeks (IQR 2)). Ranking barriers by region revealed a gradient from fewest barriers in Northern-Europe, followed by West, South, East and most in non-OECD countries. Lack of external funding and non-OECD origin were associated with barriers. Conclusion We identified barriers that must be addressed at a European level and within regions. We provide recommendations to promote equitable care for patients with suspected hereditary kidney disease in Europe.

Abstract Objectives Rare diseases often require longitudinal monitoring to characterise progression, yet much clinical information remains locked in unstructured electronic health records (EHRs). Efficient recovery of such data is critical for accurate prognostic modelling and clinical trial preparation. We aimed to develop and evaluate a small language model (SLM)-based pipeline for extracting longitudinal information from French clinical notes of patients with rare kidney diseases. Methods As a use case, we focused on serum creatinine, a key biomarker of kidney function. We analyzed 81 clinical notes comprising 200 measurements (triplet of date, value and unit). Four open-source SLMs (Mistral-7B, Llama-3.2-3B, Qwen3-4B, Qwen3-8B) were systematically tested with different prompting strategies in French and English. Outputs were post-processed to standardize formats and resolve inconsistencies, and performance was assessed across model size, prompting, language, and robustness to text duplication. Results All SLMs extracted structured triplets, with F1-scores ranging from 0.519 to 0.928 (Qwen3-8B), outperforming the rule-based baseline. Larger models generally performed better, while prompting strategy and language had modest effects across models. SLMs also showed variable robustness to duplicated content common in real-world EHR notes. Discussion Lightweight, locally deployable language models can accurately extract longitudinal biomarkers from unstructured clinical notes. Our findings highlight their practicality for rare diseases where data scarcity often limits task-specific model training. Conclusion SLMs provide a privacy-preserving and resource-efficient solution for recovering longitudinal biomarker trajectories from unstructured notes, offering potential to advance real-world research and patient care in rare kidney diseases. 1) What is already known? Longitudinal monitoring is essential in rare kidney diseases, yet key biomarker data are often locked in unstructured clinical notes. Large language models (LLMs) have shown strong performance in clinical text processing tasks but face major challenges related to privacy, computational cost, and implementation feasibility in healthcare settings. Small language models (SLMs) are emerging as lightweight, locally deployable alternatives whose potential for clinical applications is increasingly recognized. 2) What does this paper add? This study provides the first real-world evaluation of SLMs for extracting longitudinal biomarker measurements in rare kidney disease cohorts. It introduces and validates an efficient extraction pipeline that combines document preselection, SLM prompting, and post-processing to accurately retrieve biomarker measurements from French clinical notes. The findings show that SLM-based extraction can help mitigate data scarcity in rare diseases, thereby improving prognosis modeling and supporting clinical research.

Background: Primary cilia are sensory antennas that are present on the majority of quiescent vertebrate cells where they mediate key signaling during development and in response to environmental stimuli. Defects in primary cilia result in a group of heterogeneous inherited disorders with overlapping phenotypes, called ciliopathies. Nephronophthisis is an autosomal recessive tubulo-interstitial kidney ciliopathy with more than 25 identified genes called NPHP. Presently, no treatment exists beyond supportive care and kidney transplant, underscoring the need for novel therapies. Methods: Using a phenotypic screening approach in cultured cell lines, we previously identified prostaglandin analogues as candidate therapeutic molecules based on their ability to rescue ciliogenesis defects in kidney tubular cells from NPHP1 patients. Here, we have investigated the potential beneficial effects of ROCK inhibitors and Eupatilin, similarly identified by other groups in different NPHP contexts, in kidney cells from NPHP1 and IQCB1/NPHP5 patients as well as in a zebrafish NPHP mutant line (traf3ip1/ift54). Results: Eupatilin partially rescued NPHP1-associated ciliogenesis defects. Transcriptomic analyses pointed out that cell cycle progression was inhibited by Eupatilin, likely explaining its broad effects on cilia assembly. Interestingly, while ciliary defects also observed in NPHP5 patient cells were rescued by both prostaglandins and Eupatilin, only prostaglandin analogues were able to reduce pronephric cysts size in the used nphp zebrafish model. Conclusion: Our study indicates that these molecules can show beneficial effects across genetic contexts and shed light on their potential as therapeutic interventions for nephronophthisis. ### Competing Interest Statement JPA and LBR are shareholders at Medetia Pharmaceuticals; SS, LBR, JPA are authors in the patent application WO2109/075369A1, currently on PCT National examination phase. There are no other conflicts of interest.

KEY POINTS:Exome sequencing solved 26% of nephronophthisis cases, identifying nephropathy and extrarenal disease genes beyond classic ciliopathy panels. Exome sequencing uncovered GN and tubular nephropathy genes misdiagnosed as ciliopathy-associated nephropathy, underscoring diagnostic overlap in kidney diseases. Patients with nonciliary genetic variants may present with ciliopathy-like extrarenal symptoms, showing phenocopies in kidney ciliopathy diagnostics. BACKGROUND:Nephronophthisis (NPH) is an autosomal recessive tubulointerstitial kidney disease and a leading genetic cause of chronic kidney failure in children and young adults. As a ciliopathy, NPH is caused by biallelic variants in genes encoding proteins involved in the structure and function of primary cilia. The broad clinical spectrum of NPH results in a clinically and genetically heterogeneous disease, posing diagnostic challenges and leaving approximately 30% of cases unresolved with current gene panels. METHODS:After targeted gene panel for ciliopathy-associated genes failed to identify diagnostic variants, exome sequencing (ES) was conducted on 42 unrelated index patients with a clinical diagnosis of NPH, defined as cystic nephropathy progressing to kidney failure within the first two decades of life, or by unspecific CKD accompanied by extrarenal features indicative of a ciliopathy. RESULTS:Pathogenic or likely pathogenic variants were identified in 11 of the 42 patients (26%). Variants were detected in known nephropathy genes ( LAMB2 , COQ8B , COL4A3 , MUC1 ) and a multisystem disease gene with secondary kidney involvement ( AGXT ). In addition, ES elucidated deleterious variants explaining extrarenal phenotypes without corresponding kidney disease in six patients ( APTX , TUBB3 , DHX38 , IQCE, CRX , RPGR ). Variants of unknown significance were identified in three patients, while heterozygous variants in genes associated with recessive disease were observed in three others. A potential candidate gene for syndromic tubulointerstitial nephropathy, SSBP1 , was also identified, suggesting a novel pathway involving mitochondrial dysfunction. CONCLUSIONS:ES enabled the identification of pathogenic variants in known genes associated with kidney diseases, nonkidney conditions, and multisystem disorders with secondary kidney involvement, thereby improving diagnosis accuracy, even in incomplete or atypical cases, and guiding specific diagnostic and therapeutic approaches. The identification of SSBP1 in association with tubulointerstitial nephropathy may provide new insights into the pathogenesis of ciliopathies.

Introduction:Nephronophthisis (NPH) is a renal ciliopathy characterized by chronic tubulointerstitial fibrosis. Despite discovery of multiple disease genes, mechanisms of NPH-associated kidney degeneration remain poorly understood. In this study, we present details of clinical and molecular mechanisms of MAPKBP1 (NPHP20) loss-of-function. Methods:This study was a systematic clinical and in vitro analysis of all published and newly identified cases using overexpression systems, patient fibroblasts, and mitogen-activated protein kinase binding protein 1 (MAPKBP1) knock down cells. Results:We demonstrated that MAPKBP1-NPH follows a distinct natural history, characterized by predominantly nonsyndromic kidney disease and exceptionally slow progression. Furthermore, we showed that endogenous MAPKBP1 is lost from ciliary basal bodies in patients with NPHP20 and in MAPKBP1 knock down, accompanied by shortened primary cilia. Overexpression of MAPKBP1 patient variants revealed impaired microtubule, centrosomal, and basal body localization. We propose that the activation status of Jun N-terminal kinase (JNK) determines the switch between centriolar association or dissociation of MAPKBP1 via distinct protein domains. Importantly, we found that JNK activation leads to the disassembly of cilia concomitantly with MAPKBP1 dissociation from the basal body. Downstream, we observed that impaired trafficking of phosphorylated JNK upon loss of MAPKBP1 and pharmacological disassembly of the JNK-target, actin, restores ciliary length in patients with NPHP20. Overall, MAPKBP1-associated molecular alterations appeared to be relatively modest, in line with late onset kidney function decline in patients with NPHP20. Conclusion:In summary, we propose alterations in cilia-related JNK pathways as a novel mechanism in the development of NPH. Thus, a more detailed investigation of JNK signaling and involved protein interactions are promising for the discovery of novel targets for urgently needed treatment strategies in NPH.

Introduction:Primary cilia (PCs) are sensory antennae that are present on the majority of quiescent vertebrate cells where they mediate key signaling during development and in response to environmental stimuli. Defects in PCs result in a group of heterogeneous inherited disorders with overlapping phenotypes, called ciliopathies. Nephronophthisis is an autosomal recessive tubulointerstitial kidney ciliopathy with > 25 identified genes called NPHP. Presently, no treatment exists beyond supportive care and kidney transplant, underscoring the need for novel therapies. Methods:Using a phenotypic screening approach in cultured cell lines, we previously identified prostaglandin analogues as candidate therapeutic molecules based on their ability to rescue ciliogenesis defects in kidney tubular cells from patients with NPHP1 . Here, we investigated the potential beneficial effects of ROCK inhibitor and Eupatilin, similarly identified by other groups in different NPHP contexts, in kidney cells from patients with NPHP1 and those with IQCB1/NPHP5 as well as in a zebrafish nphp mutant line (traf3ip1/ift54). Results:Eupatilin partially rescued NPHP1-associated ciliogenesis defects. Transcriptomic analyses pointed out that cell cycle progression was inhibited by Eupatilin, likely explaining its broad effects on cilia assembly. Interestingly, though ciliary defects also observed in NPHP5 patient cells were rescued by both prostaglandins and Eupatilin, only prostaglandin analogues were able to reduce pronephric cysts size in the used nphp zebrafish model. Conclusion:Our study indicates that these molecules can show beneficial effects across genetic contexts and shed light on their potential as therapeutic interventions for nephronophthisis.

Background: Defects in photoreceptor ciliary function cause retinal ciliopathies, a major group of inherited blinding disorders. Current therapies are limited by extensive genetic heterogeneity, small patient populations, and high development costs, underscoring the need for mutation-agnostic strategies. This study investigates cAMP signaling modulation as a means to enhance ciliogenesis and preserve retinal structure and function in models of retinal ciliopathies. Methods: Taprenepag, a selective prostaglandin E₂ EP2 receptor agonist, was characterized for receptor specificity and downstream signaling. Its ability to enhance ciliogenesis was assessed by immunofluorescence microscopy in patient-derived urine-derived renal epithelial cells (URECs) carrying NPHP1 or CEP290 mutations and in dermal fibroblasts from CEP290 , BBS1 , and BBS10 patients. In CEP290-deficient cells, which exhibited a spectrum of baseline ciliary defects, taprenepag’s effect on ciliogenesis was compared with forskolin and cAMP analogs. Intracellular cAMP levels were measured by ELISA to confirm EP2-mediated signaling. In vivo efficacy was evaluated in Cep290 -deficient mice following systemic taprenepag administration, with retinal morphology assessed by histology and function by electroretinography. Statistical significance was determined using one- or two-way ANOVA with appropriate post hoc tests. Results: Taprenepag significantly enhanced ciliogenesis across all mutant cell types through EP2-mediated cAMP elevation, effectively bypassing the need for gene-specific correction. In severely cilia-depleted cells, elevated cAMP alleviated early ciliogenesis defects, acting upstream of axoneme assembly and intraflagellar transport, suggesting that spatially restricted EP2 signaling initiates cilium formation. In Cep290 -deficient mice, taprenepag promoted photoreceptor outer segment development, increased outer nuclear layer thickness, and partially restored retinal responses, indicating both structural preservation and functional rescue. Conclusions: EP2 receptor activation and subsequent cAMP signaling constitute a mutation-independent mechanism to promote ciliogenesis and neuroprotection in retinal ciliopathies. Taprenepag demonstrates broad therapeutic potential across diverse genetic backgrounds, supporting cAMP modulation as a promising avenue for treating inherited retinal degeneration. These findings provide a foundation for the preclinical advancement of EP2 agonists as mutation-agnostic therapies for retinal ciliopathies.

INTRODUCTION:Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a common monogenic kidney disease leading to kidney failure usually during mid adulthood. It is due to pathogenic variants in at least five genes. However, despite thorough screening of UMOD, MUC1, REN, HNF1B and SEC61A1, 25 to 50% of families remain without molecular diagnosis. METHODS:Here, we investigated a cohort of 203 families with ADTK, as well as sporadic cases of kidney disease of unknown etiology and cases of chronic kidney disease stage 5 from the Genomics England 100,000 Genomes Project. Expression of JAG1 in kidney and/or urinary epithelial cell (UREC) lines from patients carrying a pathogenic JAG1 variant associated with isolated ADTKD was studied using immunolabelling, Western blotting, targeted RNA-seq and quantitative RT-PCR. Endoplasmic reticulum (ER) stress was tested by analyzing ER protein BiP expression levels in URECs. RESULTS:A pathogenic or likely pathogenic variant in JAG1, the gene associated with Alagille syndrome, was identified in three large families with unsolved ADTKD, and additional rare variants were identified in sporadic cases. In two of the families, the diagnosis of Alagille syndrome was further established in one infant in the fourth or fifth generation; however, none of the 23 adult patients affected with isolated kidney failure (and tubulointerstitial nephritis in individuals with available kidney biopsy) had overt sign of liver, bile duct, heart, eye, or skeletal defect. JAG1 expression studies as well as ER stress analysis suggests that, despite a noteworthy expression of the JAG1-mutated RNAs, the tubulointerstitial renal disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function. CONCLUSIONS:JAG1 pathogenic variants can be associated with isolated tubulointerstitial nephropathy which, according to the KDIGO guidelines, should be classified as ADTKD-JAG1 when JAG1 variants lead to isolated chronic kidney disease that fulfills the criteria for ADTKD.

BACKGROUND:Patients with rare diseases frequently experience misdiagnoses and long diagnostic delays. Accelerating their diagnosis is essential to ensure timely access to appropriate care. Given the increasing availability of EHRs, combining artificial intelligence and deep phenotyping from large-scale clinical databases offers a promising approach to identify undiagnosed patients. This study assesses the impact of improved phenotype extraction on a screening algorithm for Jeune syndrome, a rare ciliopathy characterized by skeletal abnormalities. METHODS:Phenotypes from Jeune syndrome patients and controls were automatically extracted from patient unstructured EHRs relying on two thesauri separately: the standard UMLS Metathesaurus and the UMLS+, an enhanced version incorporating additional terms identified through deep learning. The machine learning pipeline that we designed for classifying patients with renal ciliopathy was adapted for Jeune syndrome detection. The model was trained and tested on both the datasets created using the two phenotyping strategies. RESULTS:Using UMLS+ strongly improved the classification of patients with Jeune syndrome, increasing the sensitivity from 49 % to 95 % while maintaining a 90 % specificity. The review of a subset of misclassified controls showed that most of them (69 %) had other genetic skeletal disorders, indicating that the model also captured patients who would benefit from referral to a bone disease geneticist. CONCLUSION:AI-based screening combined with high-quality deep phenotyping can help reduce diagnostic delay in rare diseases. The completeness and accuracy of phenotyping from EHRs have a strong impact on screening performances.

We develop a method for multi-structure segmentation of the mice kidney, which enables segmenting the renal cortex, the renal tubules, and tubular lumens. This facilitates quantitative exploration of kidney anatomy and the definition of image-based biomarkers. We apply this method to nephronophthisis (NPHP), a rare genetic renal disease from the family of ciliopathies, characterized by the appearance of large, dilated tubules within the cortex. We combine tubule detection with geometric criteria to select dilated structures. This enables the automatic computation of quantitative NPHP biomarkers with high correlation with manually collected measures, proving the reliability of the proposed method.