The Acute Kidney Intervention and Pharmacotherapy (AKIP) List: Standardized List of Medications That Are Renally Eliminated and Nephrotoxic in the Acutely Ill.

The objective of this project was to develop a standardized list of renally eliminated and potentially nephrotoxic drugs that will help inform initiatives to improve medication safety. Several available lists of medications from the published literature including original research articles and reviews, and from regulatory agencies, tertiary references, and clinical decision support systems were compiled, consolidated, and compared. Only systemically administered medications were included. Medication combinations were included if at least 1 active ingredient was considered renally dosed or potentially nephrotoxic. The medication list was reviewed for completeness and clinical appropriateness by a multidisciplinary team of individuals with expertise in critical care, nephrology, and pharmacy. An initial list of renally dosed and nephrotoxic drugs was created. After reconciliation and consensus from clinical experts, a standardized list of 681 drugs is proposed. The proposed evidence-based standardized list of renally dosed and potentially nephrotoxic drugs will be useful to harmonize epidemiologic and medication quality improvement studies. In addition, the list can be used for clinical purposes with surveillance in nephrotoxin stewardship programs. We suggest an iterative re-evaluation of the list with emerging literature and new medications on an approximately annual basis.

Iohexol plasma clearance measurement protocol standardization for adults: a consensus paper of the European Kidney Function Consortium.

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation.

Prospective Cohort Study Examining the Ability of Performance-Based and Self-Reported Frailty Measures to Predict 30-Day Rehospitalizations After Kidney Transplantation.

Performance-based measures of frailty are associated with healthcare utilization after kidney transplantation (KT) but require in-person assessment. A promising alternative is self-reported frailty. The goal of this study was to examine the ability of performance-based and self-reported frailty measures to predict 30-day rehospitalizations after KT. We conducted a prospective, observational cohort study involving 272 adults undergoing KT at Mayo Clinic in Minnesota, Florida, or Arizona. We simultaneously measured frailty before KT using the physical frailty phenotype (PFP), the short physical performance battery (SPPB), and self-report (the Patient-Reported Outcomes Measurement Information System [PROMIS] 4-item physical function short form v2.0). Both the PFP and self-reported frailty were independently associated with more than a 2-fold greater odds of 30-day rehospitalizations, while the SPPB was not. To our knowledge, this is the first study to assess the prognostic value of all three of the above frailty measures in patients undergoing KT. The PFP is more prognostic than the SPPB when assessing the risk of 30-day rehospitalizations; self-reported frailty can complement the PFP but not replace it. However, the 4-item survey assessing self-reported frailty represents a simple way to identify patients undergoing KT surgery who would benefit from interventions to lower the risk of rehospitalizations.

IFTA Foci Density: An Unrecognized Highly Prognostic Measurement of Fibrosis in Kidney Transplant Biopsies.

BACKGROUND: Contraction of interstitial fibrosis/tubular atrophy (IFTA) may cause %IFTA to under-represent the severity of nephron loss. Higher density of IFTA foci is an important predictor of progressive chronic kidney disease in native kidneys independent of %IFTA. METHODS: We studied kidney transplant recipients transplanted between 2000-2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff ci score (interstitial fibrosis) was obtained from the pathology reports. After digitizing the biopsies, we traced cortex area and each distinct IFTA focus on a single trichrome-stained section. Percent IFTA area and IFTA foci density (count of IFTA foci/cortex area) were calculated. Cox models assessed the risk of death-censored graft failure after the 5-year biopsy with Banff ci score, morphometric %IFTA, and IFTA foci density. RESULTS: There were 58 death-censored allograft failures among 835 kidney recipients during the 5 years of follow-up. Biopsies from grafts that failed had higher mean Banff ci score (1.5 vs 0.7, p<0.0001), %IFTA (22.2% vs 7.0%, p<0.0001), and IFTA foci density (1.3 vs. 0.4 per mm2, p<0.001). After adjusting for other Banff scores or clinical variables, Banff ci did not correlate with allograft failure, but both higher %IFTA (HR=1.56, p<0.0001) and higher IFTA foci density (HR=2.34, p<0.001) did. All but 4 allograft failures by 10 years had biopsies in the top quartile of either %IFTA or IFTA foci density at 5 years. A model using just these two morphometric measures without clinical characteristics resulted in a c-statistic of 0.891 with respect to allograft failure. CONCLUSIONS: Morphometric characterization of IFTA foci density is a strong predictor of death censored allograft failure not captured in current Banff classification for grading of kidney fibrosis.

Increased Pretransplant Inflammatory Biomarkers Predict Death With Function After Kidney Transplantation.

BACKGROUND: Chronic systemic inflammation is associated with mortality in patients with chronic kidney disease, cardiovascular disease, and diabetes. The goal of this study was to examine the relationship between pretransplant inflammatory biomarkers (growth differentiation factor-15 [GDF-15], interleukin-6 [IL-6], soluble tumor necrosis factor receptor-1, monokine induced by gamma interferon/chemokine [C-X-C motif] ligand 9 [MIG/CXCL9], monocyte chemoattractant protein-1, soluble FAS, tumor necrosis factor-α, interleukin-15, and interleukin-1ß) and death with function (DWF) after kidney transplantation (KT). METHODS: We retrospectively measured inflammatory biomarker levels in serum collected up to 1 y before KT (time from blood draw to KT was 130 ±â€…110 d) in recipients transplanted between January 2006 and December 2018. Kaplan-Meier estimation, Cox regression, and Gradient Boosting Machine modeling were used to examine the relationship between inflammatory biomarkers and DWF. RESULTS: Our cohort consisted of 1595 KT recipients, of whom 62.9% were male and 83.2% were non-Hispanic White. Over a mean follow-up of 7.4 ±â€…3.9 y, 21.2% of patients (n = 338) experienced DWF. Patients with the highest quartile levels of GDF-15 (>4766 pg/mL), IL-6 (>6.11 pg/mL), and MIG/CXCL9 (> 5835 pg/mL) had increased rates of DWF, and each predicted mortality independently of the others. When adjusted for clinical factors (age, diabetes, etc), the highest quartile levels of GDF-15 and IL-6 remained independently associated with DWF. Adding inflammatory markers to a clinical Cox model improved the C-statistic for DWF from 0.727 to 0.762 using a Gradient Boosting Machine modeling approach. CONCLUSIONS: These findings suggest that pre-KT serum concentrations of GDF-15, IL-6, and MIG/CXCL9 may help to risk stratify and manage patients undergoing KT and suggests that chronic inflammation may play a role in mortality in KT recipients.

End-Stage Kidney Disease After Partial and Radical Nephrectomy Among Patients with Severe Chronic Kidney Disease.

PURPOSE: AUA guidelines prioritize nephron sparing in patients with preexisting chronic kidney disease (CKD). However, few studies analyze long-term renal function in patients with preoperative severe CKD who undergo extirpative renal surgery. Herein, we compare the hazard of progression to end-stage kidney disease (ESKD) following partial nephrectomy (PN) and radical nephrectomy (RN) among patients with preoperative severe CKD. MATERIALS AND METHODS: Patients with stage 4 CKD who underwent PN or RN from 1970 to 2018 were identified. A multivariable Fine-Gray subdistribution hazard model was employed to assess associations with progression to ESKD accounting for the competing risk of death. RESULTS: A total of 186 patients with stage 4 CKD underwent PN (n = 71; 38%) or RN (n = 115; 62%) for renal neoplasms with median follow-up of 6.9 years (interquartile range 3.8-14.1). On multivariable analyses adjusting for competing risk of death, the subdistribution hazard ratio (SHR) for older age at surgery (SHR for 5-year increase 0.81; 95% CI 0.73-0.91; P < .001) and higher preoperative estimated glomerular filtration rate (SHR for 5-unit increase 0.63; 95% CI 0.47-0.84; P = .002) was associated with lower hazard of progression to ESKD. There was no significant difference in hazard of ESKD between PN and RN (SHR 0.82; 95% CI 0.50-1.33; P = .4). CONCLUSIONS: Among patients with preoperative severe CKD, higher preoperative estimated glomerular filtration rate was associated with lower hazard of progression to ESKD after extirpative surgery for renal neoplasms. We did not observe a significant difference in overall hazard for developing ESKD between PN and RN.

Consequences of low estimated glomerular filtration rate either before or early after kidney donation.

In the general population, decreases in glomerular filtration rate (GFR) are associated with subsequent development of chronic kidney disease (CKD), cardiovascular disease (CVD), and death. It is unknown if low estimated GFR (eGFR) before or early after kidney donation was also associated with these risks. One thousand six hundred ninety-nine living donors who had both predonation and early (4-10 weeks) postdonation eGFR were included. We studied the relationships between eGFR, age at donation, and the time to sustained eGFR<45 (CKD stage 3b) and <30 mL/min/1.73m2 (CKD stage 4), hypertension, diabetes mellitus (DM), CVD, and death. Median follow-up was 12 (interquartile range, 6-21) years. Twenty-year event rates were 5.8% eGFR<45 mL/min/1.73m2; 1.2% eGFR<30 mL/min/1.73m2; 29.0% hypertension; 7.8% DM; 8.0% CVD; and 5.2% death. The median time to eGFR<45 mL/min/1.73m2 (N = 79) was 17 years, and eGFR<30 mL/min/1.73m2 (N = 22) was 25 years. Both low predonation and early postdonation eGFR were associated with eGFR<45 mL/min/1.73m2 (P < .0001) and eGFR<30 mL/min/1.73m2 (P < .006); however, the primary driver of risk for all ages was low postdonation (rather than predonation) eGFR. Predonation and postdonation eGFR were not associated with hypertension, DM, CVD, or death. Low predonation and early postdonation eGFR are risk factors for developing eGFR<45 mL/min/1.73m2 (CKD stage 3b) and <30 mL/min/1.73m2 (CKD stage 4), but not CVD, hypertension, DM, or death.

Living Kidney Donation: A Narrative Review of Mid- and Long-term Psychosocial Outcomes.

Living kidney donors make a significant contribution to alleviating the organ shortage. The aim of this article is to provide an overview of mid- and long-term (≥12 mo) living donor psychosocial outcomes and highlight areas that have been understudied and should be immediately addressed in both research and clinical practice. We conducted a narrative review by searching 3 databases. A total of 206 articles were included. Living donors can be divided into those who donate to an emotionally or genetically related person, the so-called directed donors, or to an emotionally or genetically unrelated recipient, the so-called nondirected donors. The most commonly investigated (bio)psychosocial outcome after living donation was health-related quality of life. Other generic (bio)psychological outcomes include specific aspects of mental health such as depression, and fatigue and pain. Social outcomes include financial and employment burdens and problems with insurance. Donation-specific psychosocial outcomes include regret, satisfaction, feelings of abandonment and unmet needs, and benefits of living kidney donation. The experience of living donation is complex and multifaceted, reflected in the co-occurrence of both benefits and burden after donation. Noticeably, no interventions have been developed to improve mid- or long-term psychosocial outcomes among living donors. We highlight areas for methodological improvement and identified 3 areas requiring immediate attention from the transplant community in both research and clinical care: (1) recognizing and providing care for the minority of donors who have poorer long-term psychosocial outcomes after donation, (2) minimizing donation-related financial burden, and (3) studying interventions to minimize long-term psychosocial problems.

Association between anxiety, depression symptoms, and academic burnout among Chinese students: the mediating role of resilience and self-efficacy.

BACKGROUND: To explore the associations between anxiety and depression symptoms and academic burnout among children and adolescents in China, and to examine the role of resilience and self-efficacy in addressing academic burnout. METHODS: A total of 2,070 students in grades 4-8 were recruited from two primary and three middle schools in Shanghai, completed the Elementary School Student Burnout Scale (ESSBS), the Multidimensional Anxiety Scale for Children-Chinese (MASC-C), the Center for Epidemiological Studies Depression Scale (CES-D), the Connor-Davidson Resilience Scale (CD-RISC), and the General Self-Efficacy Scale (GSES), with 95.04% effective response rate. Multivariable regression analyses examining the associations between anxiety / depression symptoms and academic burnout (as well as the associations between resilience / self-efficacy and academic burnout) were performed using STATA 16.0 and SmartPLS 3.0. RESULTS: Anxiety symptoms (ß = 0.124, p < 0.01) and depression symptoms (ß = 0.477, p < 0.01) were positively correlated with academic burnout. Resilience partially mediated the association between depression symptoms and academic burnout (ß = 0.059, p < 0.01), with a mediation rate of 12.37%. Self-efficacy partially mediated the associations between anxiety symptoms and academic burnout (ß = 0.022, p < 0.01) and between depression symptoms and academic burnout (ß = 0.017, p < 0.01), with mediation rates of 17.74% and 3.56%, respectively. Resilience and self-efficacy together (ß = 0.041, p < 0.01) formed a mediating chain between depression symptoms and academic burnout, with a mediation rate of 8.6%. CONCLUSIONS: Anxiety and depression symptoms were positively associated with academic burnout. Resilience and self-efficacy were found to mediate the associations partially.

Measurement of flourishing: a scoping review.

Introduction: Flourishing is an evolving wellbeing construct and outcome of interest across the social and biological sciences. Despite some conceptual advancements, there remains limited consensus on how to measure flourishing, as well as how to distinguish it from closely related wellbeing constructs, such as thriving and life satisfaction. This paper aims to provide an overview and comparison of the diverse scales that have been developed to measure flourishing among adolescent and adult populations to provide recommendations for future studies seeking to use flourishing as an outcome in social and biological research. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we conducted a scoping review across PubMed and EMBASE of studies introducing original flourishing scales (defined as a previously unpublished measure of mental health or wellbeing that used "flourishing" in its definition). Studies focusing on adult populations that were published before April 28, 2023 were considered eligible for inclusion. Results: Out of 781 studies retrieved, we identified seven eligible studies covering seven unique flourishing scales. We find that all seven scales are multidimensional and assess features over monthly or yearly intervals. While most of the scales (six out of seven) include indicators of both hedonic and eudaimonic wellbeing, the operationalization of these dimensions of wellbeing varies considerably between scales. Several of the scales have been translated and validated across multiple geographical contexts, including higher- and lower-income countries. Discussion: Complementing self-report measures with other social, economic, regional, and biological indicators of flourishing may be useful to provide holistic and widely applicable measures of wellbeing. This review contributes to concept validation efforts that can guide strategies to sustain flourishing societies.

Morphometric analysis of chronicity on kidney biopsy: a useful prognostic exercise.

Chronic changes on kidney biopsy specimens include increasing amounts of arteriosclerosis, glomerulosclerosis, interstitial fibrosis and tubular atrophy, enlarged nephron size, and reduced nephron number. These chronic changes are difficult to accurately assess by visual inspection but are reasonably quantified using morphometry. This review describes the various patient populations that have undergone morphometric analysis of kidney biopsies. The common approaches to morphometric analysis are described. The chronic kidney disease outcomes associated with various chronic changes by morphometry are also summarized. Morphometry enriches the characterization of chronicity on a kidney biopsy and this can supplement the pathologist's diagnosis. Artificial intelligence image processing tools are needed to automate the annotations needed for practical morphometric analysis of kidney biopsy specimens in routine clinical care.

Abdominal Body Composition Reference Ranges and Association With Chronic Conditions in an Age- and Sex-Stratified Representative Sample of a Geographically Defined American Population.

BACKGROUND: Body composition can be accurately quantified from abdominal computed tomography (CT) exams and is a predictor for the development of aging-related conditions and for mortality. However, reference ranges for CT-derived body composition measures of obesity, sarcopenia, and bone loss have yet to be defined in the general population. METHODS: We identified a population-representative sample of 4 900 persons aged 20 to 89 years who underwent an abdominal CT exam from 2010 to 2020. The sample was constructed using propensity score matching an age and sex stratified sample of persons residing in the 27-county region of Southern Minnesota and Western Wisconsin. The matching included race, ethnicity, education level, region of residence, and the presence of 20 chronic conditions. We used a validated deep learning based algorithm to calculate subcutaneous adipose tissue area, visceral adipose tissue area, skeletal muscle area, skeletal muscle density, vertebral bone area, and vertebral bone density from a CT abdominal section. RESULTS: We report CT-based body composition reference ranges on 4 649 persons representative of our geographic region. Older age was associated with a decrease in skeletal muscle area and density, and an increase in visceral adiposity. All chronic conditions were associated with a statistically significant difference in at least one body composition biomarker. The presence of a chronic condition was generally associated with greater subcutaneous and visceral adiposity, and lower muscle density and vertebrae bone density. CONCLUSIONS: We report reference ranges for CT-based body composition biomarkers in a population-representative cohort of 4 649 persons by age, sex, body mass index, and chronic conditions.

Older Tissue Age Derived From Abdominal Computed Tomography Biomarkers of Muscle, Fat, and Bone Is Associated With Chronic Conditions and Higher Mortality.

OBJECTIVE: To determine whether body composition derived from medical imaging may be useful for assessing biologic age at the tissue level because people of the same chronologic age may vary with respect to their biologic age. METHODS: We identified an age- and sex-stratified cohort of 4900 persons with an abdominal computed tomography scan from January 1, 2010, to December 31, 2020, who were 20 to 89 years old and representative of the general population in Southeast Minnesota and West Central Wisconsin. We constructed a model for estimating tissue age that included 6 body composition biomarkers calculated from abdominal computed tomography using a previously validated deep learning model. RESULTS: Older tissue age associated with intermediate subcutaneous fat area, higher visceral fat area, lower muscle area, lower muscle density, higher bone area, and lower bone density. A tissue age older than chronologic age was associated with chronic conditions that result in reduced physical fitness (including chronic obstructive pulmonary disease, arthritis, cardiovascular disease, and behavioral disorders). Furthermore, a tissue age older than chronologic age was associated with an increased risk of death (hazard ratio, 1.56; 95% CI, 1.33 to 1.84) that was independent of demographic characteristics, county of residency, education, body mass index, and baseline chronic conditions. CONCLUSION: Imaging-based body composition measures may be useful in understanding the biologic processes underlying accelerated aging.

Kidney cortex shear wave motion simulations based on segmented biopsy histology.

BACKGROUND AND OBJECTIVE: Biopsy stands as the gold standard for kidney transplant assessment, yet its invasive nature restricts frequent use. Shear wave elastography (SWE) is emerging as a promising alternative for kidney transplant monitoring. A parametric study involving 12 biopsy data sets categorized by standard biopsy scores (3 with normal histology, 3 with interstitial inflammation (i), 3 with interstitial fibrosis (ci), and 3 with tubular atrophy (ct)), was conducted to evaluate the interdependence between microstructural variations triggered by chronic allograft rejection and corresponding alterations in SWE measurements. METHODS: Heterogeneous shear wave motion simulations from segmented kidney cortex sections were performed employing the staggered-grid finite difference (SGFD) method. The SGFD method allows the mechanical properties to be defined on a pixel-basis for shear wave motion simulation. Segmentation techniques enabled the isolation of four histological constituents: glomeruli, tubules, interstitium, and fluid. Baseline ex vivo Kelvin-Voigt mechanical properties for each constituent were drawn from established literature. The parametric evaluation was then performed by altering the baseline values individually. Shear wave velocity dispersion curves were measured with the generalized Stockwell transform in conjunction with slant frequency-wavenumber analysis (GST-SFK) algorithm. By fitting the curve within the 100-400 Hz range to the Kelvin-Voigt model, the rheological parameters, shear elasticity (µ1) and viscosity (µ2), were estimated. A time-to-peak algorithm was used to estimate the group velocity. The resultant in silico models emulated the heterogeneity of kidney cortex within the shear wave speed (SWS) reconstructions. RESULTS: The presence of inflammation showed considerable spatial composition disparities compared to normal cases, featuring a 23 % increase in interstitial area and a 19 % increase in glomerular area. Concomitantly, there was a reduction of 12 % and 47 % in tubular and fluid areas, respectively. Consequently, mechanical changes induced by inflammation predominate in terms of rheological differentiation, evidenced by increased elasticity and viscosity. Mild tubular atrophy showed significant elevation in group velocity and µ1. Conversely, mild and moderate fibrosis exhibited negligible alterations across all parameters, compatible with relatively limited morphological impact. CONCLUSIONS: This proposed model holds promise in enabling patient-specific simulations of the kidney cortex, thus facilitating exploration into how pathologies altering cortical morphology correlates to modifications in SWE-derived rheological measurements. We demonstrated that inflammation caused substantial changes in measured mechanical properties.