Kashani, Kianoush

Background Public awareness and regional engagement with cardiorenal syndrome (CRS) remain poorly understood. We examined temporal trends and geographic patterns of U.S. public interest in CRS and their relationship with disease burden. Methods Google Trends™ data (2004–2025) annual relative search interest (RSI) for CRS. CRS-related mortality was derived from CDC WONDER (2007–2020) using hypertensive heart and chronic kidney disease deaths. Temporal trends were assessed via augmented Dickey-Fuller tests and linear regression. Associations between RSI and mortality were evaluated using Pearson correlation, AR(1) modeling, first-difference, and cumulative change analysis. State-level correlations were examined with and without adjustment for income, education, and insurance coverage. Results Both RSI and mortality exhibited strong non-stationary upward trend ( p = 0.98 and 0.42). Raw data showed a strong correlation analysis (r = 0.79, p = 0.001); but first-differenced year-over-year changes were not significant (r = −0.36, p = 0.23), consistent with AR(1) modeling ( β =1.58, p = 0.11). Cumulative changes remained strongly correlated (r = 0.80, p = 0.001), indicating parallel long-term trajectories. Findings were consistent with varying ICD-10 code definitions for CRS-related mortality. Geographically, RSI was highest in West Virginia and lowest in Texas and Georgia. State-level RSI showed no correlation with age-adjusted mortality, both unadjusted (r = −0.09, p = 0.52) and after adjustment for median income, educational, and insurance coverage ( β =0.03, p = 0.75). Conclusion Public interest in CRS has grown in parallel with mortality, reflecting its increasing epidemiological relevance. However, the lack of geographic correlation between search interest and mortality—even after socioeconomic adjustment—suggests awareness gaps and highlights opportunities for targeted education and resource allocation.

Scientific evidence regarding AKI and acute kidney care has advanced in recent years. However, a knowledge gap remains on the implementation of these evidence-based practices (EBPs) into clinical care. Implementation science (IS) is focused on ensuring that this knowledge is translated in an effective, efficient and sustainable fashion. Objectives: 1) Define the current status of IS; 2) Define a roadmap for accelerating IS with a focus on patient/care partner advocacy, digital tool application, social determinants of health, and resource-limited settings; and 3) Develop a robust and broad research agenda incorporating IS methodology into the programs. Evidence Review: ADQI XXXV was conducted through a modified Delphi process with virtual meetings preceding an in-person meeting. Five workgroups were determined a priori to focus on 1) IS definitions and methods applicable to AKI and acute kidney care; 2) IS literature in AKI and acute kidney care; 3) Innovations in IS to accelerate the adoption, adherence to, and sustainment of EBPs in AKI and acute kidney care; 4) IS methods in resource-limited settings; and 5) Recommendations to identify and evaluate EBPs that are ready for implementation or de-implementation. Prior to the in-person meeting, each workgroup met virtually to review the literature and develop framework questions to address their objectives. During the two-day in person meeting, through iterative discussions, questions and supporting statements were finalized. These questions and statements were agreed upon through voting to achieve consensus, defined as agreement of ≥80%. Conclusions and Relevance: We report a structured multidisciplinary consensus for defining the role of IS in AKI and acute kidney care. Future programs should address these consensus questions and apply these statements along with IS methodology in the translation of science into clinical practice and the implementation/de-implementation of EBPs in clinical care.

ABSTRACT Pregnancy-associated acute kidney injury (PrAKI) remains a major contributor to maternal and foetal 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 acute kidney injury episodes unrelated to pregnancy, PrAKI arises in a unique physiological context characterized by haemodynamic adaptation, immune tolerance, hormonal modulation, and the presence of the foetal–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 ischaemia 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 foetal 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.

Abstract Rationale Septic shock patients require vasopressors to maintain adequate mean arterial pressure (MAP). The 2021 Surviving Sepsis Campaign Guideline recommends norepinephrine (NE) as first line, followed by vasopressin (VP). Early NE initiation is associated with faster achievement of MAP goals, lower fluid requirements, increased PaO2/FiO2 ratio, more mechanical-free ventilation days, and lower mortality. However, higher NE dosages can cause excessive vasoconstriction, impaired perfusion, lower Pa/Fi ratios, and increase in-hospital mortality. We tested the association between timing and cumulative dose of the NE with PaO2/FiO2 ratio, duration of invasive mechanical ventilation (IMV) and hospital length of stay (LOS). Methods We conducted a retrospective cohort analysis of adult septic shock patients treated with NE at Mayo Clinic Rochester Medical ICU between January 3, 2006, and April 17, 2018. Patients receiving other initial vasopressors were excluded. We developed linear regression models to assess how NE initiation time, defined as hours from sepsis identification, and cumulative dose, defined as total NE administered during ICU stay, affected median PaO2/FiO2 ratio, duration of IMV, and hospital LOS. We assessed for associations using: 1) an unadjusted model; 2) an adjusted model for baseline demographics and comorbidities (age, sex, weight, and Charlson Comorbidity Index); 3) an adjusted model for illness severity on day 1, using APACHE III and SOFA scores. Results Of 1,082 patients, 70% (n = 759) started NE as initial vasopressor. Timing of NE initiation was independently linked to shorter IMV and hospital LOS, but not to PaO2/FiO2 ratio. Across all models, earlier NE use significantly reduced IMV duration (β over 1.3992 ± 0.11 and p < 0.0001) and hospital LOS (average β 0.067 ± 0.01 and p < 0.0001). In contrast, a higher cumulative NE dose during the ICU stay was associated with a lower median PaO2/FiO2 ratio (β: -0.0053 ± 0.002, p = 0.0061), and remained significant in the adjusted models (β -0.0065 ± 0.002, p = 0.0013; and β -0.005 ± 0.002, p = 0.0132). Additionally, higher NE doses were significantly associated with longer IMV duration and hospital LOS in all models with p < 0.0001. Conclusion Although earlier initiation of vasopressor support with NE is associated with shorter durations of IMV and hospital LOS, higher cumulative doses are linked to the opposite effect. Increased NE doses were associated with lower PaO2/FiO2 ratios, delayed extubation and prolonged hospitalization. These findings highlight the importance of early NE administration and careful dose titration to optimize patient recovery. This abstract is funded by: None

Abstract Rationale Hypophosphatemia affects about one-third of intensive care unit (ICU) patients and is linked to longer hospital stays, illness severity and poor outcomes, yet guidelines for monitoring and correction remain unclear. Studies show a strong association between hypophosphatemia and both prolonged invasive mechanical ventilation (IMV) and weaning failure in patients with respiratory failure, due to reduced adenosine triphosphate generation and weakened respiratory muscle performance. Although phosphate abnormalities correlate with higher mortality in sepsis and septic shock, their impact on IMV duration in this population remains unclear. Therefore, we aimed to evaluate the independent association between hypophosphatemia during ICU stay and the duration of IMV in patients with septic shock. Methods We studied adult patients with septic shock admitted to the medical ICU at Mayo Clinic, Rochester, between March 1, 2006, and April 17, 2018. A retrospective analysis was conducted to examine the association between hypophosphatemia—defined as any serum phosphate level < 2.5 mg/dL during the ICU stay—and the duration of IMV in hours. The following linear regression models were used: 1, unadjusted; 2, adjusted for baseline demographics (age, sex, weight); 3, adjusted for baseline respiratory comorbidities and Charlson Comorbidity Index (CCI); and 4, adjusted for illness severity (using APACHE III and SOFA scores) and oxygenation (minimum PaO2/FiO2 score during ICU stay). For each model, the β-coefficient was reported, which represents additional hours of IMV associated with hypophosphatemia, along with 95% confidence intervals and p-values. Results The study included 1082 patients, among them 653 (60.4%) required IMV. 53.6% (n = 350) developed hypophosphatemia during their ICU stay. The mean duration of IMV was significantly longer in patients with hypophosphatemia compared with those without (184 ± 218 h vs 100 ± 126 h; p < 0.001; 95% CI 56-112). This association persisted across all multivariable linear regression models. After adjustment for baseline demographics, hypophosphatemia remained significantly associated with longer IMV duration (β = 79.8 h; 95% CI 51.8-107.8; p < 0.001). Further adjustment for respiratory comorbidities and CCI yielded similar results (β = 81.8 h; 95% CI 54.2-109.4; p < 0.001). After controlling for illness severity and oxygenation status, hypophosphatemia remained independently associated with prolonged IMV duration (β = 69.2 h; 95% CI 39.9-98.4; p < 0.001). Conclusion Hypophosphatemia was independently associated with longer duration of IMV in patients with septic shock, which prolongs ICU level care and delays rehabilitation. This highlights the need for updates on guidelines for maintaining optimal serum phosphate levels in patients who are mechanically ventilated. This abstract is funded by: None

Abstract Background Diuretic resistance (DR) is the failure to achieve adequate natriuresis despite high diuretic doses, reflecting a state of low diuretic efficiency (DE). In heart failure (HF) and general intensive care cohorts, low DE and the presence of DR have been associated with adverse outcomes, including increased risk of rehospitalization and mortality (1-3). Quantitative data, however, remains limited in patients admitted to the cardiac intensive care unit (CICU) – a population characterized by cardiac critical illnesses and substantial cardiorenal interactions. Purpose The aim of this study is to investigate and characterize the association between DR and associated mortality outcomes in CICU patients. Methods This retrospective cohort study included adult CICU patients (2007-2018) who received loop diuretics on day 1 of admission. Patients with a stay <1 day or oliguria [<400mL urine output (UOP) total] were excluded. DR was defined as <500mL of UOP per 40mg oral furosemide equivalent (FSE). Acute kidney injury (AKI) was defined per KDIGO guidelines. Primary outcome was all-cause in-hospital mortality (including CICU deaths), and secondary outcome was all-cause 1-year mortality. In-hospital mortality predictors were evaluated using logistic regression and 1-year mortality predictors by Cox proportional-hazards models. 1-year survival was assessed using Kaplan-Meier curves. Multivariable models were adjusted for known confounders. Results 3,229 total patients were included. Median age was 71.2 (61.2, 80.7) years and 41.3% were female. Admission diagnoses included HF exacerbation (79.9%), acute coronary syndrome (34.5%), and respiratory failure (38.9%), among others. 1,098 (34.0%) patients met DR criterion; they had higher severity of illness scores, more comorbidities (including HF, diabetes mellitus, lung disease, and chronic kidney disease, p<0.001), and greater laboratory derangements. On admission, 23.6% patients had AKI, of which 54.3% patients met DR criterion. During hospitalization, 56.0% patients had AKI; those with DR had higher prevalence and severity of AKI (unadjusted OR 3.55 [3.02-4.17], p<0.001). Overall in-hospital mortality was 9.8% (including 5.2% in the CICU). In patients with DR, in-hospital mortality was 17.0% (9.7% in the CICU). Notably, 59.4% of all in-hospital deaths occurred in patients with DR. DR was independently associated with higher in-hospital (adjusted OR 2.00 [1.51-2.64], p<0.001) and 1-year (adjusted HR 1.64 [1.44-1.88], p<0.001) mortality. Patients with DR had higher mortality in each AKI stage (Figure 1), and patients with concomitant DR and AKI had the highest risk of 1-year mortality (Figure 2). Conclusion DR, defined by our easily applicable threshold, emerged as a powerful, independent predictor of adverse outcomes and was associated with substantially higher mortality, demonstrating potential as a valuable risk stratifying tool.

ABSTRACT Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are nephroprotective and their use is recommended for adults with chronic kidney disease (CKD). The role of SGLT2i and GLP‐1 RAs in patients with acute kidney injury (AKI) is unknown. This systematic review aimed to estimate the effect of SGLT2i or GLP‐1 RAs on clinical outcomes in AKI. We systematically searched Embase, MEDLINE, Scopus, Web of Science Core Collection, and clinical trials registries for observational studies and clinical trials from database inception to July 3, 2025. Included studies evaluated adults (≥ 18 years) with AKI during a hospitalization and compared patients subsequently exposed to either SGLT2i or GLP‐1 RAs to a non‐exposed control group. Random effects meta‐analyses were performed. Six studies related to SGLT2i (five observational, one randomized trial) and one related to GLP‐1 RAs (one observational) met eligibility criteria ( N = 432,048 patients). SGLT2i/GLP‐1 RA exposure was associated with lower odds of major adverse kidney events (MAKE) (OR 0.63, 95% CI 0.46–0.86) and all‐cause mortality [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.21–0.62] compared to controls. The odds for kidney replacement therapy were lower with SGLT2i therapy in the three studies where it was evaluated (OR 0.61, 95% CI 0.40–0.93). Sensitivity analyses restricted to SGLT2i data were consistent with the overall findings [MAKE OR 0.63 (95% CI 0.42–0.95); Mortality OR 0.34 (95% CI 0.18, 0.65)]. Exposure to SGLT2i or GLP‐1 RAs after AKI, examined primarily in observational studies, was associated with improved clinical outcomes. These findings are promising and warrant evaluation in randomized clinical trials.

Background The prognostic significance of an adverse acid–base milieu despite venoarterial extracorporeal membrane oxygenation support in patients with cardiogenic shock remains poorly defined. We examined metabolic and respiratory disturbances in the ELSO (Extracorporeal Life Support Organization) Registry among patients who received venoarterial extracorporeal membrane oxygenation support for refractory cardiogenic shock. Methods Arterial blood gas acid–base values at 24 hours following venoarterial extracorporeal membrane oxygenation initiation were analyzed, with patients classified by pH, arterial partial pressure of carbon dioxide, and bicarbonate. Multivariable logistic regression and exploratory machine learning analyses were used to assess predictors of in‐hospital mortality. Results Among 15 144 adult patients, 74.6% (10 860) had neither respiratory nor metabolic acidosis, 13.1% (1909) had isolated respiratory acidosis, 11.6% (1684) had isolated metabolic acidosis, and 0.7% (100) had combined acidosis. In‐hospital mortality occurred in 7719 (51.0%) patients and increased incrementally across patients with lower pH (adjusted odds ratio [OR], 2.03 with each 0.1‐unit decrease in pH, using 7.4 as a reference point [95% CI, 1.82–2.26]), bicarbonate (adjusted OR, 1.93 per each 5‐mEq/L <24 mEq/L [95% CI, 1.76–2.12]) or base excess (adjusted OR, 1.90 per each 5‐mEq/L <0 mEq/L [95% CI, 1.75–2.07]) (all P <0.01). Mortality varied significantly, being highest for the low‐pH metabolic acidosis cluster (adjusted OR, 1.90 [95% CI, 1.70–2.12], P <0.01). Conclusions Survival decreased progressively with worse acidemia or metabolic acidosis despite 24 hours of hemodynamic support with venoarterial extracorporeal membrane oxygenation among patients with cardiogenic shock. Our findings emphasize the prognostic significance of metabolic parameters as potentially modifiable risk factors and underscore the need for early recognition and interventions to mitigate severe metabolic derangements.

The glomerular filtration rate (GFR) is a key indicator of kidney function, yet no ideal method exists for its direct measurement. This two-part review examines the development of GFR measurement techniques, focusing on their physiologic basis, performance characteristics, and clinical applications. Part 1 reviews endogenous markers used to estimate GFR (eGFR), including creatinine- and cystatin C-based equations, with emphasis on their derivation, limitations, and clinical use. Part 2 addresses exogenous filtration markers and measured GFR (mGFR) methodologies, highlighting comparative performance and specific uses. Emphasis is placed on innovation in marker development, highlighting the need for continued development and standardization to enhance accuracy and clinical utility.