Background: Proximal tubular cells (PTCs) are the most abundant cell type in the kidney. PTCs are central to normal kidney function and to regeneration versus organ fibrosis following injury. This study used single-nucleus RNA sequencing (snRNA-seq) to describe the phenotype of PTCs in renal fibrosis. Methods: Kidneys were harvested from naïve mice and from mice with renal fibrosis induced by chronic aristolochic acid administration. Nuclei were isolated using Nuclei EZ Lysis buffer. Libraries were prepared on the 10X platform and snRNA-seq completed using the Illumina NextSeq 550 System. Genome mapping was carried out with high-performance computing. Results: A total of 23,885 nuclei were analysed. PTCs were found in five abundant clusters, mapping to S1, S1-2, S2, S2-cortical S3, and medullary S3 segments. Additional cell clusters ("new PTC clusters") were at low abundance in normal kidney and in increased number in kidneys undergoing regeneration/fibrosis following injury. These clusters exhibited clear molecular phenotypes, permitting labelling as proliferating, New-PT1, New-PT2, and (present only following injury) New-PT3. Each cluster exhibited a unique gene expression signature, including multiple genes previously associated with renal injury response and fibrosis progression. Comprehensive pathway analyses revealed metabolic reprogramming, enrichment of cellular communication and cell motility, and various immune activations in new PTC clusters. In ligand-receptor analysis, new PTC clusters promoted fibrotic signaling to fibroblasts and inflammatory activation to macrophages. Conclusion: These data identify unrecognized PTC phenotype heterogeneity and reveal novel PTCs associated with kidney fibrosis.

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BackgroundAcute kidney injury (AKI) is a common complication of extracorporeal membrane oxygenation (ECMO) treatment. The aim of this study was to elucidate the long-term outcomes of adult patients with AKI who receive ECMO.Materials and methodsThe study analyzed encrypted datasets from Taiwan’s National Health Insurance Research Database. The data of 3251 patients who received first-time ECMO treatment between January 1, 2003, and December 31, 2013, were analyzed. Characteristics and outcomes were compared between patients who required dialysis for AKI (D-AKI) and those who did not in order to evaluate the impact of D-AKI on long-term mortality and major adverse kidney events.ResultsOf the 3251 patients, 54.1% had D-AKI. Compared with the patients without D-AKI, those with D-AKI had higher rates of all-cause mortality (52.3% vs. 33.3%; adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 1.53–2.17), chronic kidney disease (13.7% vs. 8.1%; adjusted subdistribution HR [aSHR] 1.66, 95% CI 1.16–2.38), and end-stage renal disease (5.2% vs. 0.5%; aSHR 14.28, 95% CI 4.67–43.62). The long-term mortality of patients who survived more than 90 days after discharge was 22.0% (153/695), 32.3% (91/282), and 50.0% (10/20) in the patients without D-AKI, with recovery D-AKI, and with nonrecovery D-AKI who required long-term dialysis, respectively, demonstrating a significant trend (Pfor trend <0.001).ConclusionAKI is associated with an increased risk of long-term mortality and major adverse kidney events in adult patients who receive ECMO.

Infective spondylodiscitis is a rare disease. This case review describes the clinical course, risk factors, and outcomes of adult patients on maintenance hemodialysis who presented with infective spondylodiscitis at a single medical center in Taiwan. There were 18 cases (mean age: 64.9 ± 10.8 years) over more than 10 years. Analysis of underlying diseases indicated that 50% of patients had diabetes, 55.6% had hypertension, 55.6% had coronary artery disease, 22.2% had congestive heart failure, 22.2% had a cerebral vascular accident, 16.7% had liver cirrhosis, and 11.1% had malignancies. Sixty-one percent of patients had a degenerative spinal disease and the most common symptom was back pain (83.3%). A total of 38.9% of patients had leukocytosis, 99.4% had elevated levels of C-reactive protein, 78.6% had elevated erythrocyte sedimentation rates, and 55.6% had elevated levels of alkaline phosphatase. The average hemodialysis duration was 72.8 ± 87.5 months, and 8 patients (44.4%) started hemodialysis within 1 year prior to infective spondylodiscitis. Four patients (22.2%) had vascular access infection-associated spondylodiscitis. The lumbar region was the most common location of infection (77.8%), 44.4% of patients developed abscesses, and Staphylococci were the most common pathogen (38.9%). The mortality rate was 16.7%, all due to sepsis. Thirty-three percent of the survivors had recurrent infective spondylodiscitis within 1 year. Infective spondylodiscitis should be considered in hemodialysis patients who present with prolonged back pain with or without fever. Non-contrast MRI is an appropriate diagnostic tool for this condition. Vascular access infection increases the risk for infective spondylodiscitis in hemodialysis patients.