Kashani, Kianoush

Abstract Acute kidney injury (AKI) is a syndrome that entails a rapid decline in kidney function with or without injury. The consequences of AKI among acutely ill patients are dire and lead to higher mortality, morbidity, and healthcare cost. To prevent AKI and its short and long‐term repercussions, understanding its pathophysiology is essential. Depending on the baseline kidney histology and function reserves, the number of kidney insults, and the intensity of each insult, the clinical presentation of AKI may differ. While many factors are capable of inducing renal injury, they can be categorized into a few processes. The three primary processes reported in the literature are hemodynamic changes, inflammatory reactions, and nephrotoxicity. The majority of patients with AKI will suffer from more than one during their development and/or progression of AKI. Moreover, the development of one usually leads to the instigation of another. Thus, the interactions and progression between these mechanisms may determine the severity and duration of the AKI. Other factors such as organ crosstalk and how our concurrent therapies interact with these mechanisms complicate the pathophysiology of the progression of the AKI even further. In this narrative review article, we describe these three main pathophysiological processes that lead to the development and progression of AKI. © 2022 American Physiological Society. Compr Physiol 12: 3767–3780, 2022.

Background The digital transformation in medical education is reshaping how clinical skills, such as point-of-care ultrasound (POCUS), are taught. In nephrology fellowship programs, POCUS is essential for enhancing diagnostic accuracy, guiding procedures, and optimizing patient management. To address these evolving demands, we developed an artificial intelligence (AI)-driven POCUS curriculum using a multiagent approach that integrates human expertise with advanced AI models, thereby elevating educational standards and better preparing fellows for contemporary clinical practice. Methods In April 2024, the Mayo Clinic Minnesota Nephrology Fellowship Program initiated a novel AI-assisted process to design a comprehensive POCUS curriculum. This process integrated multiple advanced AI models—including GPT-4.0, Claude 3.0 Opus, Gemini Advanced, and Meta AI with Llama 3—to generate initial drafts and iteratively refine content. A panel of blinded nephrology POCUS experts subsequently reviewed and modified the AI-generated material to ensure both clinical relevance and educational rigor. Results The curriculum underwent 12 iterative revisions, incorporating feedback from 29 communications across AI models. Key features of the final curriculum included expanded core topics, diversified teaching methods, enhanced assessment tools, and integration into inpatient and outpatient nephrology rotations. The curriculum emphasized quality assurance, POCUS limitations, and essential clinical applications, such as fistula/graft evaluation and software integration. Alignment with certification standards further strengthened its utility. AI models contributed significantly to the curriculum's foundational structure, while human experts provided critical clinical insights. Conclusion This curriculum, enhanced through a multiagent approach that combines AI and human collaboration, exemplifies the transformative potential of digital tools in nephrology education. The innovative framework seamlessly integrates advanced AI models with expert clinical insights, providing a scalable model for medical curriculum development that is responsive to evolving educational demands. The synergy between technological innovation and human expertise holds promising implications for advancing fellowship training. Future studies should evaluate its impact on clinical competencies and patient outcomes across diverse practice environments.

Key Points The Standard versus Accelerated Initiation of Renal Replacement Therapy in AKI trial found that starting dialysis earlier for AKI resulted in a 74% higher risk of still receiving dialysis at 90 days. Among patients who likely would have started dialysis under usual practice, the risks of dialysis dependence were similar. This suggests much of the risk observed may have been due to starting dialysis (versus never starting) rather than starting slightly earlier. Background The Standard versus Accelerated Initiation of Renal Replacement Therapy in AKI Trial showed that among critically ill patients with AKI, an accelerated KRT initiation strategy resulted in more KRT dependence at 90 days, as compared with a standard strategy. However, it is unclear whether this difference exists among participants who likely would have been treated with KRT in usual practice. Methods Secondary analysis of the Standard versus Accelerated Initiation of Renal Replacement Therapy in AKI randomized controlled trial, analyzing participants who received more than the median number of days of KRT, which served as a proxy for high probability of requiring KRT under usual practice. Two sensitivity analyses redefined the cohort as ( 1 ) those with ≥24 hours of oliguria who received KRT and ( 2 ) those who received any KRT. Using the same statistical approach as the original trial, we calculated unadjusted relative risks with 95% confidence intervals (CIs) for the exposure of randomized KRT initiation strategy (accelerated versus standard) on the outcome of KRT dependence at 90 days among survivors. Results Among the 1184 participants who received ≥6 days of KRT (670 and 514 in the accelerated and standard arms, respectively), baseline characteristics remained balanced between treatment arms. The relative risk of KRT dependence at 90 days was attenuated and nonsignificant: 1.21 (95% CI, 0.84 to 1.78), compared with 1.74 (95% CI, 1.24 to 2.43) in the overall trial. The results were similar in sensitivity analyses. Conclusions Among patients who likely would have been treated with KRT in usual practice, there was no significant difference in 90-day KRT dependence among survivors between those randomized to the accelerated and standard KRT initiation strategies. These results suggest that the harm of long-term KRT dependence may be largely due to KRT initiation (versus never initiation) rather than earlier initiation. Clinical Trial registry name and registration number: NCT02568722.

Purpose: This study evaluated the predictive value of SCAI shock staging for mortality in patients with sepsis and septic shock admitted to the medical ICU. Materials and Methods: This is a single-center historical cohort study. We analyzed data for adults (≥ 18-year-old) admitted to the medical ICU at Mayo Clinic St. Mary’s campus with sepsis between June 1, 2018, and December 31, 2021. Sepsis was identified using the Sepsis-III criteria. Patients were stratified based on SCAI shock staging. Our primary outcome was all-cause 30-day mortality. Results: We identified 3,079 eligible adult patients with sepsis or septic shock. The distribution of SCAI shock stages A through E was 9%, 12%, 25%, 49%, and 5%, respectively. The overall 30-day mortality was 24%. There was progression in all outcomes including ICU, hospital and 30-day mortality across SCAI shock stages. However, only SCAI shock stages D and E, had statistically significant adjusted HRs of 1.6 and 3, respectively. When compared to SOFA score, SCAI shock staging performed similarly in predicting ICU mortality with no statistically significant difference in AUCs, p-value of 0.07. Conclusions: Our results support the use of SCAI shock staging in critically ill medical patients with sepsis and septic shock for risk stratification. We propose that the SCAI shock staging may be used as a universal system for grading the severity of shock in critically ill patients regardless of etiology.

AbstractBackgroundAccurately estimating glomerular filtration rate (GFR) is crucial for dosing medications in hospitalized patients. Due to limitations of serum creatinine for GFR estimation, serum cystatin C (CysC) has been explored as an alternative functional kidney biomarker. This study assessed discordance between eGFRCr and eGFRCysC in a large sample of hospitalized patients and examined the frequency of renally eliminated medications affected by eGFR discordance.MethodsThis multisite historical study included adults hospitalized between 2011 and 2023 with CysC and serum creatinine reported within 24 h of each other. The first concurrent biomarker pair for each patient was analyzed. eGFR discordance and use of renally eliminated medications were described.Results17,718 hospitalized patients with concurrent creatinine and CysC assessments were included. The median eGFRCr was 65 mL/min, and the eGFRCysC was 46 mL/min. The median absolute difference of eGFRCr−eGFRCysC was 15 mL/min, and 7972 patients (45%) had a > 30% absolute difference. There was a significantly greater percentage of patients with an eGFR <30 mL/min based on eGFRCysC (26%) compared to eGFRCr (15%) (p < 0.001). Patients were prescribed an average of 20 medications in the 24 h surrounding the concurrent biomarker assessment. Renally eliminated medications accounted for 39% ± 13% of medication orders, and 80% of patients with eGFR discordance were prescribed five or more renally eliminated medications.ConclusionSubstantial eGFR discordance between eGFRCysC and eGFRCr was observed in hospitalized patients, which directly affects the dosing of renally eliminated medications. Further research is needed to optimize the pharmacotherapy of renally eliminated medications with discordant GFR assessments to improve medication safety and effectiveness.