The nephron index provides a non-invasive and theoretical estimate of the functional nephrons based on the assumption that serum fibroblast growth factor 23 (FGF23) concentrations correlate with phosphate excretion per functional nephron. This study aimed to investigate the effects of exercise on the nephron index under different conditions. Nine middle-aged adults performed exercise under three experimental conditions: moderate-intensity continuous exercise (MICE), high-intensity intermittent exercise (HIIE), and moderate-intensity intermittent exercise (MIIE). Blood and urine samples were collected before exercise, immediately after exercise and 60 minutes post-exercise. The nephron index was assessed using blood and urine phosphate and creatinine concentrations, serum FGF23 levels, and the estimated glomerular filtration rate. A significant time effect was observed for the log-transformed nephron index (p = 0.012, ηp² = 0.42). The log-transformed nephron index increased immediately after exercise (p = 0.059) and 60 minutes post-exercise (p = 0.008) across MICE, HIIE, and MIIE conditions. Additionally, urinary fractional excretion of phosphate (defined as the ratio of phosphate to creatinine clearance) significantly increased at 60 minutes post-exercise across all conditions (p = 0.038). These findings suggest that a single bout of exercise may result in acute beneficial effects on renal microcirculation. These results suggest that a single bout of exercise may influence nephron responsiveness in middle-aged individuals. However, as this is a preliminary study, further investigations are warranted to confirm the physiological relevance of the nephron index under dynamic conditions.
The distal nephron segments play a critical role in maintaining electrolyte balance, yet the mechanisms that preserve epithelial identity and segmental organization within this region remain poorly defined. Yes-associated protein (YAP), a key effector of Hippo signaling, is essential for kidney development, but its function in distal nephron epithelia is unknown. Using a genetic gain-of-function approach to activate YAP selectively in distal nephron segments, we found that sustained YAP activity profoundly disrupts epithelial organization and nephron patterning. Lineage tracing revealed that both distal convoluted tubule and connecting tubule cells originate from Slc12a3-expressing cells, and YAP activation in these segments led to increased proliferation, displacement of lineage-labeled cells beyond expected segment boundaries, and loss of segment-specific gene expression. These changes were accompanied by defects in apicobasal polarity and junctional integrity, consistent with epithelial plasticity. Unexpectedly, YAP activation in distal nephron segments also suppressed proximal tubule gene expression, indicating non-cell-autonomous effects on nephron differentiation. Together, these findings identify YAP as a critical regulator of epithelial identity in the distal nephron segments and reveal a previously unrecognized role for Hippo signaling in coordinating intersegmental organization during kidney development.
Bioengineered, transplantable kidney tissue using decellularized scaffolds offers a promising strategy to overcome the shortage of donor kidneys that limits organ transplantation for patients with end stage renal disease. These kidney scaffolds retain essential extracellular matrix architecture, providing a biologically active niche for recellularization. Successful generation of bioengineered kidney tissues includes enhanced patent vasculature and mature, functional nephrons with collecting ducts. Here, we report the development of engineered kidney tissue consisting of reconstituted kidney scaffolds and human pluripotent stem cell-derived nephron and ureteric bud progenitors. Structural analysis of recellularized kidney scaffolds showed advanced nephron structures that became more mature and exhibited interconnected nephron and collecting ducts. In vivo engraftment of reconstituted kidney scaffolds in mice led to vascularization, maturation, and secretory function. Notably, mouse-graft vascular anastomosis was evident with erythrocytes present in vasculature and nephron-secreted proteins detected in mouse urine, indicating functional integration. This approach demonstrates the feasibility to generate advanced bioengineered kidney tissues that offer a versatile platform for disease modeling, drug screening, and regenerative medicine.
Oligomeganephronia (OMN) is a rare congenital renal hypoplasia characterized by markedly reduced nephron number with compensatory glomerular hypertrophy. Although typically diagnosed in childhood, adult-onset OMN is uncommon and often under-recognized. A 29-year-old man born at 28 weeks of gestation as one of triplets, with a birth weight of 740 g, was referred for evaluation of persistent proteinuria. Proteinuria had been intermittently detected for 10 years but remained uninvestigated. Three months before admission, the urinary protein-to-creatinine ratio increased to 1.20 g/gCr with serum creatinine 1.54 mg/dL. He had engaged in regular resistance exercise and consumed protein supplements. On admission, urinary β2-microglobulin was mild elevated, and a discrepancy between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR) was observed, whereas inulin clearance was preserved. Kidney biopsy revealed markedly enlarged glomeruli, reduced glomerular density, and perihilar variant focal segmental glomerulosclerosis, consistent with OMN with secondary hyperfiltration injury. Treatment with losartan resulted in a rapid reduction in proteinuria and stable renal function over 9 months. This case illustrates that latent OMN in individuals born extremely preterm may remain subclinical until additional hyperfiltration stressors precipitate overt renal injury. Early recognition and renin-angiotensin system inhibition can ameliorate proteinuria and stabilize renal function.
Nephronophthisis (NPH), a rare but serious ciliopathy, is the predominant genetic cause of end-stage kidney disease (ESKD) in children and adolescents. Renal tubular dilatation and cyst formation are key pathological features of NPH. The mechanisms underlying renal cystogenesis remain poorly understood. This study employed sex-balanced Nphp1 deletion gene knockout (Nphp1KO) mice at 8, 12, and 24 weeks of age to investigate the spatiotemporal dynamics of renal tubules and cyst development, aiming to identify the origins of renal cysts. Quantitative evaluation of cyst progression revealed a significant increase in cyst number from 8 to 12 weeks of age, but no substantial change from 12 to 24 weeks. Additionally, cyst size remained stable throughout the study period. Serial section tracing and segment-specific tubular marker analysis confirmed that these cysts originated from the distal convoluted tubule (DCT), which displayed segmental dilation while preserving anatomical connections with adjacent, morphologically normal DCT. 3D reconstruction revealed that renal cysts appeared either as a single or in a bead-like arrangement. We demonstrated that human renal cyst epithelial cells from patients with NPH1 also originate primarily from the DCT. This study provides critical experimental evidence of the histopathological features of renal cysts in NPH1, advancing our understanding of the pathogenesis of NPHP-associated tubular dilation and cystogenesis.
Type 4 renal tubular acidosis (RTA) is a common disorder characterized by hyperkalemic non-anion gap metabolic acidosis. Although type 4 RTA is generally attributed to impaired renal ammoniagenesis induced by hyperkalemia, whether defects in distal nephron acidification contribute to its pathophysiology remains unclear. Here, we investigated alterations in distal nephron acidification machinery in Kelch-like 3 knock-in (KLHL3-KI) mice, a genetically engineered model of pseudohypoaldosteronism type II. KLHL3-KI mice exhibited hyperkalemia, hyperchloremia, and reduced serum bicarbonate levels, consistent with type 4 RTA. Phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme involved in proximal tubular ammoniagenesis, was significantly reduced in KLHL3-KI mice as compared with wild-type mice. In addition, ATP6V1B1, a subunit of the vacuolar H+-ATPase selectively expressed in intercalated cells, was significantly decreased in membrane fraction. Renal medullary expression of Rh C glycoprotein (RHCG), a major ammonia transporter in the distal nephron, was also reduced. To determine whether these changes were secondary to hyperkalemia, KLHL3-KI mice were fed a low-K+ diet. Correction of hyperkalemia with a low-K+ diet significantly increased RHCG abundance, whereas ATP6V1B1 levels remained unchanged. By immunostaining, we found that WNK1 bodies were detected in a subset of ATP6V1B1-positive cells. In sum, these findings demonstrate that distal nephron acidification pathways are dysregulated in KLHL3-KI mice. Whereas RHCG downregulation appears to be potassium-dependent, ATP6V1B1 reduction persists despite correction of hyperkalemia, suggesting the involvement of potassium-independent mechanisms. Our findings raise the possibility that dysregulated KLHL3 signaling contributes to impaired distal nephron acidification in type 4 RTA, which merits further investigation.
Horseshoe kidney is an uncommon congenital fusion anomaly that can make renal tumor surgery especially challenging because of altered rotation, limited mobility, variable vascular supply, and an unpredictable collecting system (1-7). This video presents a robot-assisted partial nephrectomy for a high-complexity renal tumor in this setting. A 33-year-old man, with ECOG 0 and no relevant comorbidities, was diagnosed with a 7.5-cm solid renal mass in the central posterior portion of the left moiety of a horseshoe kidney. The lesion had a RENAL score of 10p. Contrast-enhanced computed tomography and three-dimensional reconstruction were used to understand the relationship between the tumor, aberrant vessels, renal hilum, and collecting system, supporting the decision to attempt nephron-sparing surgery (5, 8). Surgical technique and results: The procedure was performed through a transperitoneal robotic approach with the patient in right lateral decubitus using the Da Vinci Si platform. Port placement followed a standard renal robotic configuration, with a paramedian supraumbilical camera port, three robotic working ports along a craniocaudal lateral axis, a caudal fourth-arm port, and two medial assistant ports for suction, exposure, and support during renorrhaphy. After exposure of the horseshoe kidney and left hilar dissection, two arterial branches and one renal vein were identified. Tumor excision was performed under vascular control, with 20 minutes of warm ischemia and no collecting system opening, followed by two-layer absorbable renorrhaphy with adjunctive hemostatic agents. The operative time was 150 minutes. No transfusion, conversion, drain placement, or relevant immediate complication occurred. The urinary catheter was removed after 24 hours, and the patient was discharged 72 hours after surgery. Pathology showed clear cell renal cell carcinoma, Fuhrman grade 3, pT2N0M0, with negative surgical margins. During 12 months of oncologic follow-up, renal function remained stable and semiannual imaging showed no evidence of recurrence. Contemporary video reports have also emphasized the feasibility of advanced robotic renal surgery and complex partial nephrectomy strategies in selected patients (9, 10). In a carefully selected patient, robot-assisted partial nephrectomy supported by three-dimensional planning was feasible for a complex renal tumor in a horseshoe kidney, with negative surgical margins, preserved renal function, and no recurrence during 12 months of follow-up.
Human stem cell-derived miniature organs, including kidney organoids, reproduce aspects of tissue development but lack reliable spatial patterning. In embryos, spatial organization is often established by developmental organizers that generate morphogenetic fields. However, how such organizing geometry operates in kidney nephrogenesis-and whether it can be reconstructed in vitro-has remained unclear. Using spatial transcriptomics of human kidney development, we found that nascent nephrons establish a collecting duct adjacent-to-distant polarity bordering a WNT11-WNT9B signaling boundary. Engineered WNT-secreting cellular organizers introduced into kidney organoids restored this organizing geometry, biasing distal nephron differentiation and orienting nephron morphogenesis toward the signal source, which demonstrates that developmental signaling geometry can be reconstructed synthetically to control tissue patterning.
Proteinuria predicts chronic kidney disease progression and cardiometabolic mortality, yet how sustained urinary protein loss reshapes interorgan metabolism remains unclear. Here, we tested whether proteinuric kidney disease alters whole-body amino-acid and nitrogen handling by applying long-term dietary arginine isotope tracing in a proteinuric podocin-mutant mouse model, complemented by ex vivo nephron-segment metabolism and human cohort analyses. Because arginine connects amino acid use in protein synthesis, amino acid catabolism, and the urea cycle, the dietary isotope label allowed us to follow both metabolite flux and protein incorporation across organs over time. Proteinuria did not trigger a broad compensatory increase in protein synthesis. Instead, it caused a kidney-centered rerouting of arginine metabolism. Arginine use shifted away from hepatic ureagenesis and toward renal glutamate-, proline-, and aspartate-linked fate. Across organs, most proteins incorporated recycled arginine, whereas albumin preferentially incorporated diet-derived arginine, identifying albumin as a major non-recycled arginine sink during proteinuric disease. In the kidney, proximal nephron segments showed coordinated remodeling of arginine and proline metabolism in association with tubular albumin handling. This rerouting favored proline synthesis and early collagen incorporation before overt fibrosis was established. Isotope-resolved nitrogen tracing indicated that this renal diversion of arginine occurs at the expense of coordinated nitrogen and acid handling, as reflected by reduced urinary ammonium excretion, tissue accumulation of arginine-derived ammonia, and altered abundance of enzymes involved in ammonium detoxification. In humans, circulating aspartate was elevated during active proteinuric disease and decreased in remission, independently of glomerular filtration rate, and both aspartate and proline associated with histological markers of fibrotic remodeling in biopsies from glomerular disease patients. Consequently, in proteinuric mice, a high dietary content of aspartate/asparagine further aggravated collagen accumulation and fibrosis-related remodeling of high-proline-content proteins, while impairing acid excretion. Together, these findings define proteinuric kidney disease as a chronic interorgan nitrogen-redistribution state that links selective protein turnover, impaired ammonium disposal, acid retention, and a renal profibrotic metabolic environment.
Chronic kidney disease (CKD) affects millions globally and represents a major health burden. This narrative review adopts a life-course perspective to synthesize current evidence on CKD as a consequence of adverse early-life exposures that disrupt nephrogenesis, leading to kidney programming and reduced nephron endowment. The objective of this review is to integrate emerging mechanistic and translational evidence linking developmental programming, gut microbiota, and redox biology within a unified gut-redox axis framework, and to identify potential targets for early-life prevention of CKD. Central to this process is the gut-redox axis, a bidirectional network linking gut microbiota with host redox homeostasis. A balanced axis preserves epithelial integrity, metabolic stability, and immune regulation, whereas dysbiosis and oxidative stress form a self-perpetuating cycle that promotes CKD and related comorbidities. Maternal oxidative stress and impaired microbial transmission exacerbate early-life dysbiosis, persistent epigenetic alterations, and nephron deficits. In adulthood, protein-bound uremic toxins amplify oxidative injury and inflammation, further perturbing microbial composition. Experimental and clinical studies show that early-life interventions-including probiotics, prebiotics, postbiotics, antioxidants, and toxin-lowering strategies-can restore gut-redox balance and improve renal outcomes. These insights highlight opportunities for precision prevention and mechanism-based therapies targeting CKD across the life course.
Percutaneous cryoablation (CA) is increasingly used to manage small renal masses (SRMs) in selected patients, offering a nephron-sparing, minimally invasive alternative to surgical resection. We evaluated the safety, renal functional preservation, and short-term oncologic outcomes of CA in a high-complexity cohort at a tertiary referral center. We conducted a retrospective single-center analysis of consecutive patients treated with CA between 2020 and 2025. SRMs were defined as renal tumors ≤4 cm (cT1a). Procedures were performed under local anesthesia, primarily using combined Ultrasound and Cone-Beam Computed Tomography guidance. Primary outcomes included perioperative morbidity (Clavien-Dindo) and oncologic results (local failure, metastasis, and cancer-specific survival). Secondary outcomes focused on renal function preservation (eGFR). Seventy-one patients were included in the analysis. The cohort had a median age of 70 years and a high comorbidity burden, with a median Charlson Comorbidity Index of 5, prior renal surgery was present in 45% of patients and 13% a solitary kidney. All procedures achieved technical success. The overall complication rate was 20%, with no Clavien-Dindo grade ≥II complications. At a median follow-up of 10 months, early oncologic outcomes showed 11 patients with local failure (9 petients with residual disease, 2 patients with recurrence), reflecting the high proportion of "salvage" cases. Most failures (55%) were successfully managed with repeated CA. Metastatic progression occurred in 3% of cases, and cancer-specific mortality was 1.4%.. Median eGFR decline was 2.5 mL/min/1.73 m². CA represent a safe and effective nephron-sparing strategy for selected patients with SRMs. particularly in high-complexity cases. Despite a non-negligible local failure rate in salvage cases, cryoablation allows effective disease control while preserving renal function. These findings support CA as a valuable treatment option, although longer follow-up is needed to confirm long-term oncologic durability.
The rodent Cerradomys goytaca is endemic to the coastal sandplains (restingas) of Brazil. This study aimed to investigate the renal morphology and physiology of this species to elucidate the possible mechanisms involved in urinary concentrating capacity and renal solute handling. Ten female specimens of C. goytaca werecompared with twenty female Wistar Rattus norvegicus. Feed intake and urinary flow were determined. The following parameters indicative of renal function were evaluated: clearance, fractional excretion, and urinary excretion of creatinine, osmolality, urea, sodium, potassium, and glucose. Additionally, morphological analyses of the kidneys were performed to evaluate cortical and medullary structure. C. goytaca showed a significantly higher renal mass index despite a lower nephron count compared to R. norvegicus. The species demonstrated the ability to produce more concentrated urine, with lower urinary flow and greater water reabsorption. Higher urinary excretion of sodium, potassium, and glucose was also observed. Together, these results suggest adaptive mechanisms for electrolyte and glucose handling, as well as water conservation, that may support the survival of this species in its natural habitat. O roedor Cerradomys goytaca é endêmico das planícies arenosas costeiras (restingas) do Brasil. Este estudo teve como objetivo investigar a morfologia e a fisiologia renal dessa espécie, a fim de elucidar os possíveis mecanismos envolvidos na capacidade de concentração urinária e no manejo renal de solutos. Dez espécimes fêmeas de C. goytaca foram comparadas a vinte fêmeas de Rattus norvegicus da linhagem Wistar. Foram determinados a ingestão de ração e o fluxo urinário. Os seguintes parâmetros indicativos da função renal foram avaliados: clearance, fração de excreção e excreção urinária de creatinina, osmolalidade, ureia, sódio, potássio e glicose. Além disso, análises morfológicas dos rins foram realizadas para avaliar as estruturas cortical e medular. C. goytaca apresentou um índice de massa renal significativamente maior, apesar de um menor número de néfrons em comparação com R. norvegicus. A espécie demonstrou capacidade de produzir urina mais concentrada, com menor fluxo urinário e maior reabsorção de água. Também foi observada maior excreção urinária de sódio, potássio e glicose. Em conjunto, esses resultados sugerem mecanismos adaptativos para o manejo de eletrólitos, glicose e conservação de água que podem favorecer a sobrevivência desta espécie em seu habitat natural.
Pregnancy-associated acute kidney injury (PrAKI) remains a major contributor to maternal and fetal morbidity worldwide, with an estimated incidence of 40-100 per 10 000 pregnancies. PrAKI is substantially more prevalent in low- and middle-income countries. Unlike AKI episodes unrelated to pregnancy, PrAKI arises in a unique physiological context characterized by haemodynamic adaptation, immune tolerance, hormonal modulation, and the presence of the fetal-placental unit. These pregnancy-specific factors alter renal reserve, endothelial stability, and inflammatory responsiveness. The pathogenesis of PrAKI is multifactorial. Haemodynamic vasodilation and increased glomerular filtration rates during pregnancy reduce renal functional reserve, rendering the kidney vulnerable to hypovolemia and sepsis. Placental ischemia drives the release of antiangiogenic factors, particularly soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, causing systemic endothelial dysfunction and glomerular endotheliosis. Disruption of immune tolerance and complement regulation further contributes to microangiopathy and autoimmune-mediated renal injury. Structural urinary tract changes, metabolic stressors, and maternal comorbidities amplify susceptibility. Beyond the index event, PrAKI has lasting consequences. Maladaptive renal repair promotes chronic kidney disease and long-term cardiovascular risk, while fetal exposure to uremic toxins and placental dysfunction contribute to intrauterine growth restriction, prematurity, and reduced nephron mass with lifelong cardio-renal implications. Understanding the pathophysiology of PrAKI, particularly endothelial, immunologic, and placental interactions, has direct diagnostic and therapeutic implications, including the use of angiogenic biomarkers and targeted haemodynamic strategies. Future research must prioritize molecular predictors, global registries, and mechanistic studies to reduce intergenerational kidney and cardiovascular disease.
Image-guided percutaneous cryoablation (CA) has become an increasingly accepted nephron-sparing treatment for small renal masses, including complex endophytic tumors. This narrative review synthesizes current evidence on technical considerations, oncologic outcomes, and safety profiles of CA for endophytic renal cell carcinoma (RCC), with critical evaluation of factors influencing local tumor control and complications. Dedicated endophytic cohorts report primary 5-year local tumor progression-free survival of approximately 64%-75%, improving to 87%-89% after re-ablation, with excellent cancer-specific survival and minimal impact on renal function. However, high anatomical complexity, size, and proximity to vascular or collecting system structures that suggest more endophytic locations pose significant technical challenges; furthermore, they are associated with increased risk of incomplete ablation and major complications compared with exophytic or mixed tumors. Advances in procedural techniques-including hydrodissection, pyeloperfusion, transarterial embolization, and selective arterial balloon occlusion-have expanded the boundaries of safely treatable disease. CA demonstrates similar safety and renal function preservation vs. partial nephrectomy, without the increase in rates of major adverse events or longer hospitalization. For appropriately selected patients with clinical T1 endophytic RCC, image-guided CA provides a safe and effective therapeutic option with durable oncologic outcomes and substantial quality-of-life benefits. Ongoing multicenter registry data and prospective studies are needed to refine risk stratification and optimize procedural strategies for challenging tumor locations.
Renal tubular disorders are often overlooked causes of acquired or inherited bone hypomineralization and fragility fractures in adults. The proximal tubule reabsorbs glucose, phosphate, low-molecular-weight proteins, amino acids, bicarbonate, and much of the sodium, potassium, chloride, and calcium. The distal nephron-the thick ascending limb of the loop of Henle, the distal convoluted tubule, and the collecting duct-regulates urine concentration and dilution, maintains acid-base balance via urinary proton secretion, and controls electrolytes, including sodium, potassium, magnesium, and calcium. Tubular defects may cause hyperphosphaturia (high urinary phosphate), hypercalciuria (high urinary calcium), or chronic metabolic acidosis (renal tubular acidosis, RTA). These changes weaken bone mineralization, disrupt bone turnover, and raise the risk of muscle weakness and fractures. This review summarizes acquired and genetic tubulopathies linked to hyperphosphaturia, hypercalciuria, and RTA and outlines a practical diagnostic approach for outpatients with bone fragility and suspected renal tubulopathy.
Introduction: Cryoablation is an established nephron-sparing option for small renal masses, particularly in patients unsuitable for surgery. However, definitive histopathological assessment post-ablation is limited due to the in situ nature of treatment. This report details a case of delayed partial nephrectomy after cryoablation, enabling comprehensive histopathological evaluation of long-term treatment effects. Case presentation: A 50-year-old man with uncontrolled hypertension, diabetes, and triple-vessel coronary disease presented with a 2.5 cm right renal mass. Cardiovascular instability deferred initial surgery. Following coronary intervention requiring anticoagulation, percutaneous cryoablation was performed using CT-guided 3D reconstruction for precise probe placement and ice-ball confirmation. After 388 days, laparoscopic partial nephrectomy was performed. Histopathology revealed a 1.9 cm clear cell renal cell carcinoma. Approximately one-third of tissue showed post-cryoablation changes. Three distinct zones were identified: viable carcinoma, coagulative necrosis with preserved glomerular outlines, and viable parenchyma. Serial follow-up over 2 years showed transient creatinine elevation normalizing by 3 months, with no recurrence or metastasis. Conclusions: This case provides rare whole-lesion histopathological assessment after renal cryoablation, illustrating heterogeneous long-term tissue response and supporting cryoablation as a disease-control or bridging strategy in medically high-risk patients.
We report a 50-year-old female with bilateral duplex renal collecting systems and an ectopic ureterocele causing recurrent urinary tract infections and urgent incontinence. Transurethral incision using a thulium laser was performed. At 10-year follow-up, upper renal cortex thickness increased from 0.52 cm to 1.14 cm, hydronephrosis resolved, and symptoms did not recur. No secondary procedures were required. Thulium laser incision is a safe, durable nephron-sparing option for adult ectopic ureteroceles.
Emerging imaging strategies, such as tissue clearing and advanced light-sheet modalities, are transforming the visualization of cell differentiation, tissue reorganization, and morphogenesis in both model and non-model organisms, thereby driving future discoveries of conserved developmental programs and species-specific innovations. In this study, we present a versatile Bessel light sheet microscopy (BLX) system compatible with both immersion and capped air objectives, optimized for whole-mount three-dimensional imaging of cleared tissues. We demonstrate that autofluorescence-based light-sheet imaging enables reliable visualization of CUBIC-R-cleared mouse embryos, revealing microanatomical features such as nephrons during developmental stages. To support solvent-based clearing protocols, we designed a protective lens cap that shields objectives from solvent erosion and economically converts standard air objectives into high-performance immersion objectives. Using this capped BLX configuration, we achieved cellular-resolution imaging of whole PEGASOS-cleared mouse brains. The system's simplified design and open-source availability promote broader adoption for diverse applications in developmental biology.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2, which encode the ciliary proteins polycystin-1 and polycystin-2, respectively. Genetic ablation of primary cilia or disruption of ciliary membrane protein trafficking markedly suppresses cyst formation in adult-onset ADPKD models, indicating that cilia harbor membrane-associated signaling pathways that promote cyst progression. However, the specific ciliary receptors mediating these extracellular cyst promoting signals remain poorly defined. We performed RiboTag-based translational profiling of early cystic kidneys in genetic mouse models of ADPKD to identify differentially expressed genes, with a focus on transmembrane protein-coding candidates. The localization and function of parathyroid hormone receptor 1 (Pth1r) were examined using immunofluorescence, genetic inactivation in developmental and adult-onset ADPKD models, and in vitro studies of renal epithelial cells. Downstream signaling was assessed by cAMP measurements and CREB phosphorylation analysis. Therapeutic relevance was evaluated using the calcimimetic cinacalcet. RiboTag profiling identified upregulation of Pth1r in early cystic kidneys. Pth1r localized to primary cilia across nephron segments, and its genetic inactivation significantly attenuated cyst growth in both developmental and adult-onset ADPKD models. In vitro, parathyroid hormone (PTH) promoted Pth1r trafficking to cilia through a conserved VxP motif independently of polycystins. PTH stimulation increased intracellular cAMP levels in renal epithelial cells, with efficient downstream activation requiring intact primary cilia. In vivo, CREB phosphorylation was increased during cyst progression in Pkd1 mutant kidneys and was partially reduced by Pth1r inactivation. Cinacalcet treatment reduced cystic burden and normalized circulating PTH levels. These findings support a role for Pth1r as a ciliary GPCR linking systemic PTH signaling to cyst-promoting pathways in ADPKD.