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Includes "Ultimate Default Management System" (Coppock); "Effective Job Placement for the 90s" (Yena); "Planning the Future of Your School" (Herzing); "Budgeting: Your Financial Road Map" (Sears); "Making the Americans with Disabilities Act Work for You" (Leonard); "Helping Students to Succeed" (Bainter); and "Effective Small School Management" (Meanor). (JOW)

Discusses various types of job skills: necessary (writing, speaking, listening), traditional (interpersonal, phone usage, records management, keyboard, office management), and new skills (computer literacy, ability to conceptualize mentally), and the corresponding curricular needs. The college's role in this process is presented also. (CT)

BACKGROUND An unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin-angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer- term treatment with sparsentan for FSGS are unknown. METHODS In this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of El.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated. RESULTS A total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P= 0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, there were no significant between-group differences in the eGFR slope; the between-group difference in total slope (day 1 to week 108) was 0.3 ml per minute per 1.73 mz of body-surface area per year (95% confidence interval ICI], -1.7 to 2.4), and the between-group difference in the slope from week 6 to week 108 (i.e., chronic slope) was 0.9 ml per minute per 1.73 mz per year (95% CI, -1.3 to 3.0). The mean change in eGFR from baseline to week 112 was -10.4 ml per minute per 1.73 mz with sparsentan and -12.1 ml per minute per 1.73 mz with irbesartan (difference, 1.8 ml per minute per 1.73 mz; 95% CI, -1.4 to 4.9). Sparsentan and irbesartan had similar safety profiles, and the frequency of adverse events was similar in the two groups. CONCLUSIONS Among patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan. (Funded by Travere Therapeutics; DUPLEX ClinicalTrials.gov number, NCT03493685.) [ABSTRACT FROM AUTHOR]

Glomerular diseases (GDs) represent the third leading cause of end-stage kidney disease (ESKD) in the US Diabetes was excluded from the CureGN Study, an NIH/NIDDK-sponsored observational cohort study of four leading primary GDs: IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). CureGN-Diabetes, an ancillary study to CureGN, seeks to understand how diabetes influences the diagnosis, treatment, and outcomes of GD. It is a multicenter, prospective cohort study, targeting an enrollment of 300 adults with prevalent type 1 or type 2 diabetes and MCD, FSGS, MN, or IgAN, with first kidney biopsy obtained within 5 years of enrollment in 80% (20% allowed if biopsy after 2010). CureGN and Transformative Research in DiabEtic NephropaThy (TRIDENT) provide comparator cohorts. Retrospective and prospective clinical data and patient-reported outcomes are obtained. Blood and urine specimens are collected at study visits annually. Kidney biopsy reports and digital images are obtained, and standardized pathologic evaluations performed. Light microscopy images are uploaded to the NIH pathology repository. Outcomes include relapse and remission rates, changes in proteinuria and estimated glomerular filtration rate, infections, cardiovascular events, malignancy, ESKD, and death. Multiple analytical approaches will be used leveraging the baseline and longitudinal data to compare disease presentation and progression across subgroups of interest. With 300 patients and an average of 3 years of follow-up, the study has 80% power to detect a HR of 1.4-1.8 for time to complete remission of proteinuria, a rate ratio for hospitalizations of 1.18-1.56 and difference in eGFR slope of 6.0-8.6 mL/min/year between two groups of 300 participants each. CureGN-Diabetes will enhance our understanding of diabetes as a modifying factor of the pathology and outcomes of GDs and support studies to identify disease mechanisms and improve patient outcomes in this understudied patient population., Competing Interests: None of the authors have a COI related to this study. A.K.M. has received research support from Alexion, Bayer, Boehringer-Ingelheim, Calliditas, Duke Clinical Research Institute, and Pfizer; consulting fees from Bayer; and royalties from UpToDate. L.H.M. receives research support from Boehringer-Ingelheim and Travere Therapeutics; consulting fees from Reata Pharmaceuticals, Chinook Therapeutics, Travere Therapeutics, and Calliditas Therapeutics., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration., Methods: We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29-84 days)., Results: Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively)., Conclusion: A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed., Competing Interests: Competing interests: SG receives research funding from GE Healthcare and BTG International and is President and Founder of the American Society of Onconephrology. CGC has received travel and congress fees support from AstraZeneca, Esteve, NovoNordisk, Boehringer Ingelheim Lilly, Astellas, Otsuka, Novartis, Astellas, and Baxter and has given scientific lectures and participated in advisory boards organized by AstraZeneca, Boehringer Ingelheim Lilly, Mundipharma, and NovoNordisk. DSS participates in the speakers’ bureau at Genentech. FBC is a consultant for ChemoCentryx and Retrophin. AA is supported by the Division of Internal Medicine Immuno-Oncology Toxicity Award Program of the University of Texas MD Anderson Cancer Center. BS is a senior clinical investigator at the Research Foundation Flanders (F.W.O.) (1842919N) and is supported by Stichting tegen Kanker (grant C/2020/1380). AR is a consultant for Otsuka Pharmaceutical, and treasurer of the American Society of Onconephrology. SMH is supported by the Mayo Clinic K2R award. KB receives grant support from Olympia Morata Programme, Foundations Commission of University of Heidelberg, Rheumaliga Baden-Württemberg e.V., AbbVie, and Novartis. KB also serves as a consultant/receives speaker fee/travel reimbursements from AbbVie, BMS, Janssen, MSD, Viatris, Gilead/Galapagos, Lilly, Medac, Mundipharma, Novartis, Pfizer, Roche, and UCB. MES has served on a scientific advisory board for Mallinckrodt. LC serves as a consultant/receives honorarium/travel reimbursements from Pfizer, Bristol Myers Squibb, MSD. The remaining authors have no conflicts of interest or disclosures. MJS reports personal fees from NovoNordisk, Janssen, Mundipharma, AstraZeneca, Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU, Pfizer, Bayer, Travere Therapeutics, GE Healthcare and Boehringer Ingelheim. MJS is a consultant for NovoNordisk, Travere Therapeutics, GE Healthcare, AstraZeneca, and Boehringer. MJS receives grant support form Boehringer Ingelheim, ISCIIII-FEDER and ISCIII-RETICS REDinREN, grant number PI17/00257, PI21/01292, RD16/0009/0030, RICORS RD21/0005/0016, Marató TV3 2020 421/C/2020, Marató TV3 2021 215/C/2021, and EIN2020-112338. MJS is elected Editor-in-Chief of Clinical Kidney Journal., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Inflammation is an important component of fibrosis but immune processes that orchestrate kidney fibrosis are not well understood. Here we apply single-cell sequencing to a mouse model of kidney fibrosis. We identify a subset of kidney tubule cells with a profibrotic-inflammatory phenotype characterized by the expression of cytokines and chemokines associated with immune cell recruitment. Receptor-ligand interaction analysis and experimental validation indicate that CXCL1 secreted by profibrotic tubules recruits CXCR2 + basophils. In mice, these basophils are an important source of interleukin-6 and recruitment of the T H 17 subset of helper T cells. Genetic deletion or antibody-based depletion of basophils results in reduced renal fibrosis. Human kidney single-cell, bulk gene expression and immunostaining validate a function for basophils in patients with kidney fibrosis. Collectively, these studies identify basophils as contributors to the development of renal fibrosis and suggest that targeting these cells might be a useful clinical strategy to manage chronic kidney disease., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer., Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI., Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI., Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)