Journal of the American Society of Nephrology : JASN
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Parathyroid Hormone Receptor 1 Facilitates Cyst Growth in Genetic Models of Autosomal Dominant Polycystic Kidney Disease

Jun 23, 2026

The authors investigate the role of parathyroid hormone receptor 1 (Pth1r) in promoting cyst growth in autosomal dominant polycystic kidney disease (ADPKD) models, aiming to identify specific ciliary receptors that mediate extracellular signals contributing to cyst progression. Their findings reveal that Pth1r is upregulated in early cystic kidneys, localizes to primary cilia, and its genetic inactivation significantly reduces cyst growth, suggesting it acts as a ciliary GPCR that links parathyroid hormone signaling to cyst-promoting pathways in ADPKD. Additionally, treatment with the calcimimetic cinacalcet was shown to alleviate cystic burden and normalize PTH levels, highlighting its potential therapeutic relevance.

Alanyl-tRNA Synthetase 1 and Cyst Growth in Autosomal Dominant Polycystic Kidney Disease

Jun 22, 2026

The authors investigate the role of alanyl-tRNA synthetase 1 (AARS1) in the progression of autosomal dominant polycystic kidney disease (ADPKD), particularly its involvement in lactate-driven metabolic reprogramming and cyst growth. They demonstrate that genetic deletion of AARS1 in mouse models significantly delays cyst growth and preserves kidney function by modulating lactylation-dependent activation of key signaling pathways. The study identifies AARS1 as a crucial metabolic sensor that links lactate to transcriptional and epigenetic changes driving ADPKD progression.

Evaluating Barriers to Kidney Transplantation in the United States

Jun 20, 2026

The authors aimed to evaluate the barriers to kidney transplantation in the United States by analyzing the progression from referral to evaluation, waitlisting, and transplantation among 720,348 adults from 2014 to 2025. They found that only 48% of referred patients were evaluated and 19% were waitlisted, with significant attrition influenced by individual, center-level, and geographic factors. The study highlights the disparities in access to transplantation, particularly in low-volume centers and among certain demographic groups.

Comparing Catheters to Fistulas in Older Patients Starting Hemodialysis (ACCESS HD)

Jun 19, 2026

The authors aimed to determine the feasibility of conducting a randomized controlled trial comparing the use of catheters versus fistulas for vascular access in older patients starting hemodialysis. Despite screening 1287 patients, only 67 were randomized, revealing that patient preference heavily favored continued catheter use, which resulted in more favorable outcomes for the catheter group. The findings suggest that a definitive trial comparing these two access methods may not be feasible in the current healthcare environment.

Smooth Muscle Cell-Specific Expression of Cyclic Nucleotide Phosphodiesterase 10a Promotes the Development of Medial Artery Calcification

Jun 17, 2026

The authors aimed to investigate the role of phosphodiesterase 10A (PDE10A) in the development of medial artery calcification, particularly in the context of chronic kidney disease (CKD) and peripheral artery disease. They found that PDE10A expression was elevated in calcifying vascular smooth muscle cells and that its inhibition reduced calcification both in vitro and in vivo, suggesting that PDE10A is a critical mediator of this process and a potential therapeutic target.

Sex Dimorphism of NAD+De Novo Biosynthesis Mediates Sex-Biased Susceptibility to Ischemia-Reperfusion-Induced Acute Kidney Injury

Jun 17, 2026

The authors investigate how sex differences influence susceptibility to ischemia-reperfusion-induced acute kidney injury (AKI) through the modulation of NAD+ de novo biosynthesis. They find that male mice are more vulnerable to AKI due to lower levels of NAD+ and impaired biosynthesis linked to downregulation of the enzyme kynureninase (KYNU), which is influenced by androgen levels. Their results suggest that targeting NAD+ metabolism could be a potential therapeutic strategy for mitigating sex-biased AKI.

Elevations in Donor-Derived Cell-Free DNA and Allograft Outcomes in Kidney Transplantation

Jun 16, 2026

The authors aimed to determine whether initial elevations in donor-derived cell-free DNA (dd-cfDNA) during routine surveillance could predict allograft dysfunction and loss in kidney transplant recipients. Their findings revealed that intermediate and high dd-cfDNA levels were associated with significantly increased risks of allograft loss, while persistently low levels correlated with favorable outcomes, indicating the potential of dd-cfDNA as a biomarker for monitoring transplant health.

Genetic Landscape of Kidney Failure in a Korean Transplant Cohort: Genome-Wide Association and Multi-Polygenic Risk Score Analyses

Jun 16, 2026

The authors aimed to identify genetic loci associated with kidney failure and its subtypes, as well as evaluate the effectiveness of multi-polygenic risk scores (PRSs) in predicting kidney failure risk. Their genome-wide association study revealed distinct genetic factors linked to different subtypes of kidney failure, highlighting the disease's genetic heterogeneity. Additionally, the study demonstrated that multi-PRS models significantly enhance risk prediction compared to traditional clinical factors.

Expression of Apolipoprotein L1 Risk Variants at the Plasma Membrane and Haplotype-Dependent Cytotoxicity

Jun 15, 2026

The authors aimed to elucidate the mechanisms by which apolipoprotein L1 (APOL1) risk variants G1 and G2 contribute to kidney disease in individuals of African ancestry. Their findings reveal that these variants facilitate increased calcium influx through the plasma membrane, leading to cytotoxicity, while the protective effects of the M1 variant and the APOL1 inhibitor VX-147 suggest potential therapeutic strategies to mitigate this risk.

Optimizing Sample Size Calculation for Early-Stage CKD Trials Using eGFR Slope

Jun 9, 2026

The authors aimed to derive a sample size formula for early-stage chronic kidney disease (CKD) trials that accounts for various design parameters, including slope difference, trial duration, measurement frequency, and dropout patterns. Their findings indicate that frequent measurements significantly reduce sample size requirements in short-term trials, while long-term trials are more suitable for detecting small slope differences. Additionally, incorporating dropout patterns into sample size calculations leads to more accurate estimations compared to traditional methods.