Clinical characteristics and outcomes of kidney transplantation in autosomal dominant polycystic kidney disease patients.

BACKGROUND: Kidney transplantation (KT) is the best kidney replacement treatment for autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate the clinical characteristics and outcomes of KT in ADPKD patients compared to those in non-ADPKD patients. METHODS: We retrospectively analyzed KT recipients in two Korean transplantation centers from 2005 to 2020. Propensity score-matching and Cox regression analysis were used to assess the clinical outcomes of ADPKD compared to non-ADPKD and identify prognostic factors influencing outcomes in ADPKD. RESULTS: Among a total of 4452 KT patients, 189 (4.2%) were ADPKD patients. Median age at transplantation was 53.0 and 47.0 in ADPKD and non-ADPKD patients, respectively. In both groups, living-donor KT was more common than deceased-donor KT. The ADPKD group had a 4.09-fold higher risk of post-transplant diabetes mellitus and a 1.65-fold higher risk of post-transplant infection compared to the non-ADPKD group; however, subjects with ADPKD had similar risk of rejection, graft failure, and mortality. In the ADPKD group, kidney volume decreased after KT, irrespective of kidney volume status (Mayo classification), while the size of hepatic cysts increased. Neither kidney volume nor nephrectomy of native kidneys were associated with risk of infection, graft failure, or mortality in the ADPKD group. CONCLUSIONS: ADPKD patients have a higher risk of post-transplant diabetes mellitus and infection than non-ADPKD patients, with no significant impact of kidney volume or nephrectomy on post-transplant outcomes.

Spontaneous Bacterial Peritonitis Due to Bacillus licheniformis in an Autosomal Dominant Polycystic Kidney Disease Patient on Peritoneal Dialysis: A Rare Presentation Linked to Avian Exposure.

This case report details a rare instance of Bacillus licheniformis-induced peritonitis in a 43-year-old male diagnosed with autosomal dominant polycystic kidney disease (ADPKD) undergoing peritoneal dialysis (PD). The patient presented with acute onset of severe abdominal pain and fever, prompting a microbiological investigation that revealed Gram-positive bacilli. Initial empirical treatment with ceftazidime and vancomycin was followed by targeted vancomycin therapy upon identification of B. licheniformis. The patient's clinical course showed steady improvement, corroborated by a recent history of avian contact. This case underscores the critical consideration of uncommon pathogens and environmental exposures in managing peritonitis among peritoneal dialysis patients.

Reactive Oxygen Species in Cystic Kidney Disease.

Polycystic kidney disease (PKD) is a rare but significant renal condition with major implications for global acute and chronic patient care. Oxidative stress and reactive oxygen species (ROS) can significantly alter its pathophysiology, clinical outcomes, and treatment, contributing to negative outcomes, including hypertension, chronic kidney disease, and kidney failure. Inflammation from ROS and existing cysts propagate the generation and accumulation of ROS, exacerbating kidney injury, pro-fibrotic signaling cascades, and interstitial fibrosis. Early identification and prevention of oxidative stress and ROS can contribute to reduced cystic kidney disease progression and improved longitudinal patient outcomes. Increased research regarding biomarkers, the pathophysiology of oxidative stress, and novel therapeutic interventions alongside the creation of comprehensive guidelines establishing methods of assessment, monitoring, and intervention for oxidative stress in cystic kidney disease patients is imperative to standardize clinical practice and improve patient outcomes. The integration of artificial intelligence (AI), genetic editing, and genome sequencing could further improve the early detection and management of cystic kidney disease and mitigate adverse patient outcomes. In this review, we aim to comprehensively assess the multifactorial role of ROS in cystic kidney disease, analyzing its pathophysiology, clinical outcomes, treatment interventions, clinical trials, animal models, and future directions for patient care.

Renal Pelvic Cancer with Multiple Lung Metastases in a Patient with Polycystic Kidney Disease, Initially Diagnosed as Non-small Cell Lung Cancer: An Autopsy Case Report.

A 64-year-old man with autosomal dominant polycystic kidney disease (ADPKD) on hemodialysis presented with multiple lung masses. A computed tomography (CT)-guided biopsy revealed non-small-cell lung cancer (NSCLC). A cavitary mass in the right lung indicated primary NSCLC (cT2N1M1a, stage IVA). Pembrolizumab was initiated because of a high programmed death-ligand 1 (PD-L1) expression (90%). On day 10 post-treatment, he developed acute respiratory failure with diffuse ground-glass opacities on chest CT, indicative of pembrolizumab-induced lung injury. Despite steroid pulse therapy, the patient died on day 13. An autopsy revealed left renal pelvic cancer with lung metastases, highlighting the diagnostic challenges in ADPKD.

New Mutation Associated with Polycystic Kidney Disease Type I: A Case Report.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent heritable disorders, characterized by the progressive development of kidney cysts leading to renal failure. It is primarily caused by mutations in the PKD1 and PKD2 genes, which account for approximately 85% and 15% of cases, respectively. This case report describes a previously unreported mutation in the PKD1 gene, identified in a family involving an aunt and her niece with ADPKD. CASE PRESENTATION: The index case, a 56-year-old female with chronic kidney disease stage 3b secondary to ADPKD and hypertension, exhibited a strong family history of polycystic kidney disease (PKD). Initial genetic evaluations did not identify any recognized pathogenic mutations, leading to a more detailed investigation which revealed a novel mutation in the PKD1 gene. This mutation was also found in her niece, who presented with early-onset disease. CONCLUSIONS: The identification of a heterozygous six-nucleotide deletion, c.2084_2089del, resulting in the in-frame deletion of two amino acids, p.Pro695_Ala696del, in the PKD1 gene, has been linked with ADPKD in these patients. This report emphasizes the need for continuous updates to genetic data for a deeper understanding of the diagnosis and prognosis of ADPKD that could potentially aid in targeted therapy.

Effectiveness of tolvaptan on renal replacement therapy in patients with autosomal dominant polycystic kidney disease: a retrospective cohort study from the TriNetX global collaborative network.

BACKGROUND AND HYPOTHESIS: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major genetic contributor to end-stage kidney disease (ESKD). Current evidence on tolvaptan primarily focuses on slowing estimated glomerular filtration rate (eGFR) decline and kidney volume growth. However, direct confirmation of its effectiveness in reducing the need for hemodialysis in ESKD remains limited. METHODS: We included ADPKD patients aged ≥18 years using TriNetx data from Sep 2, 2018, to Sep 3, 2023. Propensity score matching (PSM) ensured baseline comparability (standardized mean difference (SMD) <0.1). Hazard ratios (HRs) with 95% confidence intervals (CIs) evaluated outcomes, and subgroup analyses were performed. RESULTS: After 1:1 PSM, both groups comprised 673 patients. The average age was 45, with generally good health (3-5% diabetes, 2-3% ischemic heart disease). Baseline eGFR averaged ∼55 ml/min/1.732m2. Post-matching, all SMDs were <0.1, indicating successful matching. Tolvaptan users exhibited lower eGFR (51.45 ± 30.09 vs. 57.37 ± 33.65, p < 0.001) and higher risk of stage 4-CKD (HR: 2.436, 95% CI:1.649, 3.599) compared to non-users. However, tolvaptan users showed significantly reduced chances of initiating hemodialysis (HR:0.362, 95%CI:0.176, 0.745), experiencing urinary tract infections (HR:0.581, 95%CI:0.354, 0.956), and all-cause mortality (HR:0.355, 95% CI:0.180, 0.700). Kaplan-Meier curves for hemodialysis initiation indicated higher survival rates among tolvaptan users across age and number of medication refill subgroups. CONCLUSIONS: This real-world study, employing precise matching, reveals tolvaptan's role in reducing hemodialysis initiation risk in ADPKD, despite initial hemodynamic-induced lower eGFR.

Trigger Warning: How Modern Diet, Lifestyle, and Environment Pull the Trigger on Autosomal Dominant Polycystic Kidney Disease Progression.

Understanding chronic kidney disease (CKD) through the lens of evolutionary biology highlights the mismatch between our Paleolithic-optimized genes and modern diets, which led to the dramatically increased prevalence of CKD in modern societies. In particular, the Standard American Diet (SAD), high in carbohydrates and ultra-processed foods, causes conditions like type 2 diabetes (T2D), chronic inflammation, and hypertension, leading to CKD. Autosomal dominant polycystic kidney disease (ADPKD), a genetic form of CKD, is characterized by progressive renal cystogenesis that leads to renal failure. This review challenges the fatalistic view of ADPKD as solely a genetic disease. We argue that, just like non-genetic CKD, modern dietary practices, lifestyle, and environmental exposures initiate and accelerate ADPKD progression. Evidence shows that carbohydrate overconsumption, hyperglycemia, and insulin resistance significantly impact renal health. Additionally, factors like dehydration, electrolyte imbalances, nephrotoxin exposure, gastrointestinal dysbiosis, and renal microcrystal formation exacerbate ADPKD. Conversely, carbohydrate restriction, ketogenic metabolic therapy (KMT), and antagonizing the lithogenic risk show promise in slowing ADPKD progression. Addressing disease triggers through dietary modifications and lifestyle changes offers a conservative, non-pharmacological strategy for disease modification in ADPKD. This comprehensive review underscores the urgency of integrating diet and lifestyle factors into the clinical management of ADPKD to mitigate disease progression, improve patient outcomes, and offer therapeutic choices that can be implemented worldwide at low or no cost to healthcare payers and patients.

Native nephrectomy in patients with autosomal dominant polycystic kidney disease in kidney transplant program: long-term single-center experience.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently leads to end-stage renal disease. In this study, we examine the indications, procedures, and outcomes of native nephrectomy (NN) in ADPKD patients at our transplant center. Drawing on 25 years of clinical practice, we aim to provide insights into the surgical management of ADPKD, focusing on the specific factors influencing NN. MATERIALS AND METHODS: A retrospective study was conducted involving ADPKD patients who underwent KT and NN between 1999 and 2023. Collected data encompassed demographics and surgery parameters, such as duration, hospital stay length, blood loss, and complications. Patients were classified based on the urgency (acute/planned) of the NN and its type (unilateral/bilateral), followed by an analysis of the outcomes per group. RESULTS: Out of 152 patients post-KT for ADPKD, 89 (58.6%) underwent NN. The procedures were predominantly unilateral (71; 64%), with bilateral NN accounting for 40 (36%) cases. NN timing relative to KT was 31 (27.9%) pretransplant, 9 (8.1%) concomitant, 51 (45.9%) posttransplant, and 10 (9%) patients undergoing the sandwich technique. Acute NN were performed in 42 cases, while 69 were planned. Acute NNs were associated with longer surgeries, greater blood loss, and a higher incidence of perioperative complications compared to planned NNs. Specifically, unilateral acute NN had a 23.8% complication rate compared to 2.9% in planned cases; bilateral acute NN showed a 28.6% complication rate versus 4.3% in planned cases. CONCLUSION: This investigation accentuates the significance of planning and selection in NN for ADPKD, factoring in the heightened risk of complications. Acute NN are linked to worse outcomes, including higher rates of complications. The data emphasize the necessity of tailored surgical approaches based on individual patient circumstances.

Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease.

BACKGROUND: Renal cell carcinoma (RCC) is more common in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts, often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage. AIM: To analyze the prevalence and characterize the clinical features of RCC in patients with ADPKD undergoing simultaneous bilateral native nephrectomy. METHODS: Between May 2017 and April 2024, 19 ADPKD patients undergoing hemodialysis and awaiting kidney transplantation due to end-stage renal disease (ESRD) underwent bilateral nephrectomies in a single center. Parameters such as patient characteristics, intraoperative blood loss, blood transfusion volume, length of hospital stay, and postoperative complications were documented. Pathological findings for RCC were reviewed. RESULTS: A total of 38 kidneys were excised from 19 patients, with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months. Eight patients underwent open nephrectomies, and 11 underwent hand-assisted laparoscopic nephrectomies. RCC was detected in 15.8% of kidneys, affecting 21.1% of patients. Two patients had multifocal RCC in both kidneys. All RCC cases were pT1 stage, with the largest lesion averaging 16.5 mm in diameter. The average operative duration was 120 minutes, with intraoperative blood loss averaging 184.2 mL. Five patients required blood transfusions. Postoperative complications occurred in five patients, with a mean hospital stay of 17.1 days. The mean follow-up period was 28.1 months. CONCLUSION: The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone. Thus, clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD, particularly those on dialysis.

Sarcomatoid Urothelial Carcinoma Arising in Autosomal Dominant Polycystic Kidney Disease: A Case Report and Literature Review.

Autosomal dominant polycystic kidney disease (ADPKD) may be associated with various epithelial malignancies. The most reported ones are papillary renal cell carcinoma (RCC) and clear cell RCC. Only one noninvasive urothelial carcinoma arising in the renal pelvis has been previously reported in the setting of ADPKD in the English literature. A 52-year-old patient with ADPKD and a history of renal transplant presented with a poorly differentiated sarcomatoid neoplasm in his native left polycystic kidney. A recognizable urothelial or renal cell carcinoma differentiation was not identified in the resected neoplasm microscopically. The initial diagnosis for this specimen was challenging on morphology and immunohistochemistry, but targeted next-generation sequencing provided molecular evidence in support of urothelial origin, indicating a hotspot mutation -124 C > T in the TERT promoter (C228 T) and loss of heterozygosity on chromosomes 9p and 8p. This tumor is unique because, to our knowledge, this is the first report of upper tract sarcomatoid urothelial carcinoma in a patient with ADPKD.

Kidney growth progression patterns in autosomal dominant polycystic kidney disease.

BACKGROUND: Prognosis for autosomal dominant polycystic kidney disease (ADPKD), the main inherited cause of kidney failure, relies on estimating cystic growth using linear formulas derived from height-adjusted total kidney volume (Ht-TKV). However, nonlinear renal growth patterns may occur in typical ADPKD. AIMS: To determine kidney outcomes of subjects diagnosed with typical ADPKD exhibiting nonlinear, and unpredictable cystic growth during follow-up. METHODS: Retrospective cohort study. We categorized TKV changes in individuals with typical ADPKD according to observed kidney growth trajectories. Ht-TKV was calculated from consecutive CT or MRI using the ellipsoid method. We compared estimated glomerular filtration rate (eGFR) trajectories with linear mixed models. RESULTS: We included 83 individuals with ADPKD (67% women; age 47 ± 12 years; follow-up 5.2 years [IQR 2.8-9.0]). Three kidney growth patterns were observed: slow progression (24%, <3%/year linear increase), fast progression (39%, ≥3%/year linear increase), and atypical progression (37%, nonlinear growth). Adjusted ht-TKV change in mL/m/year was +1.4 (IQR -4.5 to +10.0), +40.3 (+16.9 to +89.3), and +32.8 (+15.9 to +85.9) for slow, fast, and atypical progressors, respectively (p < 0.001). Atypical progressors exhibited a significantly greater decline in eGFR in mL/min/m²/year (-7.9, 95% CI -6.5, -3.9) compared to slow (-0.5, 95% CI -3.1 to +0.5) and fast progressors (-3.4, 95% CI -7.9, -2.0; between-group p < 0.001). Atypical progressors had a higher proportion of acute complications, including hemorrhages, infections, and urolithiasis (84%), compared to slow (20%) and fast progressors (31%) (p < 0.001). CONCLUSION: In typical ADPKD, nonlinear, abrupt, and unpredictable cyst growth occurs frequently, leading to a higher risk of acute complications and kidney function decline.

A rare cause of echogenic kidneys with oligohydramnios in the fetus: report of two different cases.

BACKGROUND: Prenatal ultrasound findings of fetal bilateral echogenic kidneys accompanied by oligohydramnios can be highly stressful for both pregnant women and physicians. The diversity of underlying causes makes it challenging to confirm a prenatal diagnosis, predict postnatal outcomes, and counsel regarding recurrence risks in future pregnancies. CASE PRESENTATION: We report two cases of abnormal fetal echogenic kidneys with oligohydramnios detected in the early third trimester. Autosomal recessive polycystic kidney disease (ARPKD), a rare genetic syndrome, was initially suspected in both cases. However, postnatal diagnoses differed: the first case was confirmed as glomerulocystic kidney disease (GCKD) through renal pathology, while the second case was diagnosed as ARPKD with a compound heterozygous likely pathogenic PKHD1 mutation. CONCLUSION: Prenatal diagnosis of fetal echogenic kidneys with oligohydramnios should prioritize accurate diagnosis. Given the differences in the clinical spectrum, GCKD should be considered a differential diagnosis for this condition, particularly ARPKD. This study highlights the importance and benefits of molecular diagnosis and postnatal renal pathology for precise diagnosis and effective counseling.

Distribution and classifications of PKHD1 gene variants in a Turkish population using the next generation sequencing method.

Background/aim: Autosomal recessive polycystic kidney disease is an inherited kidney disease. This study aims to detect rare and common DNA variants of the PKHD1 gene using next-generation sequencing (NGS) and to classify them in terms of being pathogenic according to The American College of Medical Genetics and Genomics. Materials and methods: NGS analysis was performed on the DNA of 304 patients who were referred to Ege University Molecular Medicine Laboratory with suspected polycystic kidney disease. Results: As a result, a total of 82 different DNA variants, 16 of which were novel, were detected. The breakdown of the variants found is as follows: 73 (89.02%) were missense variants, six (7.32%) nonsense variants, two (2.44%) frameshift deletions, and one (1.22%) nonframeshift deletion. According to The American College of Medical Genetics and Genomics classification of these variants, 26 were benign (Class 5), two were likely benign (Class 4), 36 were of uncertain significance (Class 3), and nine were likely pathogenic (Class 2), nine of which are pathogenic variants (Class 1). Heterozygosity was found in 39 (63.9%) patients, homozygosity in six (9.8%) patients, compound heterozygosity in 12 (19.7%) patients, and complex genotype in four (6.6%) patients in which variants in Class 1, Class 2 and Class 3 were determined according to ACMG classification. When the exon distributions of the DNA variants detected in the PKHD1 gene were analyzed, the most common exons of the DNA variant are exon 32 (n = 9), exon 58 (n = 8), exon 67 (n = 6), exon 61 (n = 5), 30 exons (n = 4). Conclusion: This fast and economical molecular diagnostic approach will provide a reliable prenatal diagnostic option, enabling definitive disease diagnosis and the identification of carriers.

Integrated mRNA-seq and miRNA-seq analysis reveals key transcription factors of HNF4α and KLF4 in ADPKD.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent genetic disorder affecting the kidneys. Understanding epigenetic regulatory mechanisms and the role of microRNAs (miRNAs) is crucial for developing therapeutic interventions. Two mRNA datasets (GSE7869 and GSE35831) and miRNA expression data (GSE133530) from ADPKD patients were used to find differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), with a focus on genes regulated by hub transcription factors (TFs) and their target genes. The expression of hub TFs was validated in human kidneys and animal models through Western Blot (WB) and RT-PCR analysis. The location of the hub TF proteins in kidney cells was observed by a laser confocal microscope. A total of 2037 DEGs were identified. DEM analysis resulted in 59 up-regulated and 107 down-regulated miRNAs. Predicted target DEGs of DEMs indicated two top dysregulated TFs: hepatocyte nuclear factor 4 alpha (HNF4α) and Kruppel-like factor 4 (KLF4). RT-PCR, WB, and immunochemistry results showed that mRNA and protein levels of HNF4α were significantly decreased while KLF4 levels were significantly up-regulated in human ADPKD kidneys and Pkd1 conditional knockout mice compared with normal controls. Laser confocal microscopy revealed that KLF4 was mainly located in the cytoplasm while HNF4α was in the nucleus. Functional enrichment analysis indicated that genes regulated by HNF4α were mainly associated with metabolic pathways, while KLF4-regulated genes were linked to kidney development. Drug response prediction analysis revealed potential drug candidates for ADPKD treatment, including BI-2536, Sepantronium, and AZD5582. This integrated analysis provides new epigenetic insights into the complex miRNA-TF-mRNA network in ADPKD and identifies HNF4α and KLF4 as key TFs. These findings offer valuable resources for further research and potential drug development for ADPKD.

EZH2 inhibition or genetic ablation suppresses cyst growth in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent genetic disorder characterized by the formation of renal cysts leading to kidney failure. Despite known genetic underpinnings, the variability in disease progression suggests additional regulatory layers, including epigenetic modifications. METHODS: We utilized various ADPKD models, including Pkd1 and Ezh2 conditional knockout (Pkd1delta/delta:Ezh2delta/delta) mice, to explore the role of Enhancer of Zeste Homolog 2 (EZH2) in cystogenesis. Pharmacological inhibition of EZH2 was performed using GSK126 or EPZ-6438 across multiple models. RESULTS: EZH2 expression was significantly upregulated in Pkd1-/- cells, Pkd1delta/delta mice, and human ADPKD kidneys. EZH2 inhibition attenuates cyst development in MDCK cells and a mouse embryonic kidney cyst model. Both Ezh2 conditional knockout and GSK126 treatment suppressed renal cyst growth and protected renal function in Pkd1delta/delta mice. Mechanistically, cAMP/PKA/CREB pathway increased EZH2 expression. EZH2 mediated cystogenesis by enhancing methylation and activation of STAT3, promoting cell cycle through p21 suppression, and stimulating non-phosphorylated ß-catenin in Wnt signaling pathway. Additionally, EZH2 enhanced ferroptosis by inhibiting SLC7A11 and GPX4 in ADPKD. CONCLUSION: Our findings elucidate the pivotal role of EZH2 in promoting renal cyst growth through epigenetic mechanisms and suggest that EZH2 inhibition or ablation may serve as a novel therapeutic approach for managing ADPKD.

PKD2: An Important Membrane Protein in Organ Development.

PKD2 was first identified as the pathogenic protein for autosomal dominant polycystic kidney disease (ADPKD) and is widely recognized as an ion channel. Subsequent studies have shown that PKD2 is widely expressed in various animal tissues and plays a crucial role in tissue and organ development. Additionally, PKD2 is conserved from single-celled organisms to vertebrates. Here, we provide an overview of recent advances in the function of PKD2 in key model animals, focusing on the establishment of left-right organ asymmetry, renal homeostasis, cardiovascular development, and signal transduction in reproduction and mating. We specifically focus on the roles of PKD2 in development and highlight future prospects for PKD2 research.

Applying a Deep Learning Model for Total Kidney Volume Measurement in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease leading to end-stage renal disease. Total kidney volume (TKV) measurement has been considered as a surrogate in the evaluation of disease severity and prognostic predictor of ADPKD. However, the traditional manual measurement of TKV by medical professionals is labor-intensive, time-consuming, and human error prone. MATERIALS AND METHODS: In this investigation, we conducted TKV measurements utilizing magnetic resonance imaging (MRI) data. The dataset consisted of 30 patients with ADPKD and 10 healthy individuals. To calculate TKV, we trained models using both coronal- and axial-section MRI images. The process involved extracting images in Digital Imaging and Communications in Medicine (DICOM) format, followed by augmentation and labeling. We employed a U-net model for image segmentation, generating mask images of the target areas. Subsequent post-processing steps and TKV estimation were performed based on the outputs obtained from these mask images. RESULTS: The average TKV, as assessed by medical professionals from the testing dataset, was 1501.84 ± 965.85 mL with axial-section images and 1740.31 ± 1172.21 mL with coronal-section images, respectively (p = 0.73). Utilizing the deep learning model, the mean TKV derived from axial- and coronal-section images was 1536.33 ± 958.68 mL and 1636.25 ± 964.67 mL, respectively (p = 0.85). The discrepancy in mean TKV between medical professionals and the deep learning model was 44.23 ± 58.69 mL with axial-section images (p = 0.8) and 329.12 ± 352.56 mL with coronal-section images (p = 0.9), respectively. The average variability in TKV measurement was 21.6% with the coronal-section model and 3.95% with the axial-section model. The axial-section model demonstrated a mean Dice Similarity Coefficient (DSC) of 0.89 ± 0.27 and an average patient-wise Jaccard coefficient of 0.86 ± 0.27, while the mean DSC and Jaccard coefficient of the coronal-section model were 0.82 ± 0.29 and 0.77 ± 0.31, respectively. CONCLUSION: The integration of deep learning into image processing and interpretation is becoming increasingly prevalent in clinical practice. In our pilot study, we conducted a comparative analysis of the performance of a deep learning model alongside corresponding axial- and coronal-section models, a comparison that has been less explored in prior research. Our findings suggest that our deep learning model for TKV measurement performs comparably to medical professionals. However, we observed that varying image orientations could introduce measurement bias. Specifically, our AI model exhibited superior performance with axial-section images compared to coronal-section images.

Multiomics profiling of mouse polycystic kidney disease progression at a single-cell resolution.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to kidney failure. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single-nucleus multimodal atlas of an orthologous mouse PKD model at early, mid, and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes. We catalog differentially expressed genes and activated epigenetic regions in each cell type during PKD progression, characterizing cell-type-specific responses to Pkd1 deletion. We describe heterogeneous, atypical collecting duct cells as well as proximal tubular cells that constitute cyst epithelia in PKD. The transcriptional regulation of the cyst lining cell marker GPRC5A is conserved between mouse and human PKD cystic epithelia, suggesting shared gene regulatory pathways. Our single-nucleus multiomic analysis of mouse PKD provides a foundation to understand the earliest changes molecular deregulation in a mouse model of PKD at a single-cell resolution.