June 2024
Kidney360
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June 2024
Kidney360
June 2024
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3 Reads
Kidney International
May 2024
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9 Reads
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1 Citation
JAMA The Journal of the American Medical Association
Importance Recipient outcomes after kidney transplant from deceased donors who received dialysis prior to kidney donation are not well described. Objective To compare outcomes of transplant recipients who received kidneys from deceased donors who underwent dialysis prior to kidney donation vs recipients of kidneys from deceased donors who did not undergo dialysis. Design, Setting, and Participants A retrospective cohort study was conducted including data from 58 US organ procurement organizations on deceased kidney donors and kidney transplant recipients. From 2010 to 2018, 805 donors who underwent dialysis prior to kidney donation were identified. The donors who underwent dialysis prior to kidney donation were matched 1:1 with donors who did not undergo dialysis using a rank-based distance matrix algorithm; 1944 kidney transplant recipients were evaluated. Exposure Kidney transplants from deceased donors who underwent dialysis prior to kidney donation compared with kidney transplants from deceased donors who did not undergo dialysis. Main Outcomes and Measures The 4 study outcomes were delayed graft function (defined as receipt of dialysis by the kidney recipient ≤1 week after transplant), all-cause graft failure, death-censored graft failure, and death. Results From 2010 to 2018, 1.4% of deceased kidney donors (805 of 58 155) underwent dialysis prior to kidney donation. Of these 805 individuals, 523 (65%) donated at least 1 kidney. A total of 969 kidneys (60%) were transplanted and 641 kidneys (40%) were discarded. Among the donors with kidneys transplanted, 514 (mean age, 33 years [SD, 10.8 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) underwent dialysis prior to donation and were matched with 514 (mean age, 33 years [SD, 10.9 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) who did not undergo dialysis. Kidney transplants from donors who received dialysis prior to donation (n = 954 kidney recipients) were associated with a higher risk of delayed graft function compared with kidney transplants from donors who did not receive dialysis (n = 990 kidney recipients) (59.2% vs 24.6%, respectively; adjusted odds ratio, 4.17 [95% CI, 3.28-5.29]). The incidence rates did not significantly differ at a median follow-up of 34.1 months for all-cause graft failure (43.1 kidney transplants per 1000 person-years from donors who received dialysis prior to donation vs 46.9 kidney transplants per 1000 person-years from donors who did not receive dialysis; adjusted hazard ratio [HR], 0.90 [95% CI, 0.70-1.15]), for death-censored graft failure (22.5 vs 20.6 per 1000 person-years, respectively; adjusted HR, 1.18 [95% CI, 0.83-1.69]), or for death (24.6 vs 30.8 per 1000 person-years; adjusted HR, 0.76 [95% CI, 0.55-1.04]). Conclusions and Relevance Compared with receiving a kidney from a deceased donor who did not undergo dialysis, receiving a kidney from a deceased donor who underwent dialysis prior to kidney donation was associated with a significantly higher incidence of delayed graft function, but no significant difference in graft failure or death at follow-up.
May 2024
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22 Reads
Journal of Internal Medicine
Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.
May 2024
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18 Reads
Clinical Journal of the American Society of Nephrology
Background Cognitive dysfunction is a well-known complication of chronic kidney disease, but it is less known whether cognitive decline occurs in survivors after acute kidney injury (AKI). We hypothesized that an episode of AKI is associated with poorer cognitive function, mediated, at least in part, by persistent systemic inflammation. Methods ASSESS-AKI enrolled patients surviving three months after hospitalization with and without AKI matched based on demographics, comorbidities, and baseline kidney function. A subset underwent cognitive testing using the modified mini-mental status examination (3MS) at 3, 12, and 36 months. We examined the association of AKI with 3MS scores using mixed linear models and assessed the proportion of risk mediated by systemic inflammatory biomarkers. Results Among 1538 participants in ASSESS-AKI, 1420 (92%) completed the 3MS assessment at 3 months and had a corresponding matched participant. Participants with AKI had lower 3MS scores at three years (difference -1.1 (95% CI: -2.0, -0.3) P=0.009 ) compared to participants without AKI. A higher proportion of AKI participants had a clinically meaningful (≥ 5 point) reduction in 3MS scores at three years compared to participants without AKI (14% vs. 10%, P=0.04 ). In mediation analyses, plasma soluble tumor necrosis factor receptor-1 (sTNFR-1) at three months after AKI mediated 35% ( P=0.02 ) of the AKI related risk for 3MS scores at three years. Conclusions AKI was associated with lower 3MS scores and sTNFR-1 concentrations appeared to mediate a significant proportion of the risk of long-term cognitive impairment. Further work is needed to determine if AKI is causal or a marker for cognitive impairment.
May 2024
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10 Reads
Kidney International Reports
April 2024
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32 Reads
Scientific Reports
Serum creatinine levels are insensitive to real-time changes in kidney function or injury. There is a growing interest in assessing kidney injury by measuring biomarkers in body fluid. From our previous studies, we identified and reported three urinary biomarkers namely Uromodulin (UMOD), Osteopontin (OPN), and Interleukin-9 (IL-9) to be associated with kidney health. The availability of a rapid point-of-care test for these urinary biomarkers will potentially accelerate its applicability and accessibility. In this study, we aimed to develop novel lateral flow device (LFD) for UMOD, OPN and IL-9. We tested paired antibodies using Enzyme Linked Immunosorbent Assay wherein we observed functionality only for UMOD and OPN and not for IL-9. A conjugation buffer pH of 7.8 and 8.5 was found suitable at a detection antibody concentration of 15 µg/mL for LFD development. The developed LFDs were found to quantitatively measure UMOD standard (LLOD of 80,000 pg/mL) and OPN standard (LLOD of 8600 pg/mL) respectively. The LFD was also able to measure human urinary UMOD and OPN with a percent CV of 12.12 and 5.23 respectively.
April 2024
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4 Reads
American Journal of Kidney Diseases
April 2024
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4 Reads
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2 Citations
Kidney International
April 2024
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10 Reads
Kidney Medicine
Rationale & Objective Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD. Study Design Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]). Setting & Participants Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m² and without diabetes in the ARIC, REGARDS, and MESA studies. Exposures Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1. Outcome Incident CKD or end-stage kidney disease. Analytical Approach Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts. Results 872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m². In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31). Limitations Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts. Conclusions In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.
... The gut microbiome, proteomic and metabolomic landscape of renal diseases offers insights into pathogenesis, treatment, and prevention, yet transcriptomic studies remain scarce (50,(72)(73)(74)(75). Scientists are also promoting the discovery of new treatments and targets for various types of nephritis (76)(77)(78)(79). Indeed, integrating transcriptomics with other omics can further advance the discovery of novel mechanisms and biomarkers for renal diseases (80). Therefore, we leveraged transcriptomic data from IgA nephropathy and lupus nephritis to elucidate their lipid metabolism and immune features, as dysregulation of immune regulatory molecules or immune function is also considered a contributing factor to nephritis onset and progression (38). ...
December 2023
Science Translational Medicine
... [45][46][47] Because of the simplicity of the KFRE and accessibility of the variables included in the KFRE, it has previously been implemented into EMR systems to support both clinical practice and research on CDS tool integration. 38,45,46,[48][49][50][51][52][53][54][55][56][57][58][59][60] Via its integration with EMR systems, KFRE can be automatically calculated, improving the identification of patients at risk of developing kidney failure and improving provider workflow. [45][46][47]49,52,53,55,57,60,61 Others 45,47 have suggested that incorporating automatic prompts into a KFRE CDS tool to encourage providers to order urinary albumin-to-creatinine ratio testing, which is not routinely collected, would improve the accuracy of KFRE and downstream patient outcomes. ...
September 2023
Kidney International Reports
... Köttgen et al. reported higher UMOD level was associated with an increased CKD risk (OR 1.72; 95% CI 1.07-2.77) [65], but Chen et al. reported that a lower UMOD level at baseline was associated with a greater risk of subsequent kidney failure with replacement therapy [66]. ...
September 2023
American Journal of Kidney Diseases
... Assessing EGF levels in bodily fluids, like blood, saliva, and urine can offer insights into the degree of tissue damage and the ongoing healing process. Steven Menez and colleagues showed elevated levels of urinary EGF to creatinine ratio (uEGF/Cr) during the postdischarge period following an acute kidney injury (AKI) event, suggesting a sign of adaptive repair [42]. Yet, HGF decreased in the conditioned media of HC and HKD MSCs once exposed to HPC, with no effect on HTN MSCs. ...
August 2023
Kidney International
... In the inpatient clinical setting, acute kidney injury (AKI) is encountered frequently in elderly patients and recent studies have demonstrated that patients aged 65 and older are at higher risk of developing AKI and that subsequently some will progress to chronic kidney disease (CKD) (6)(7)(8). The cellular and molecular features of the AKI to CKD transition are beginning to be characterized, and an important aspect of this transition is that some epithelial cells undergo "failed" or "maladaptive" repair, adopting a proinflammatory and profibrotic phenotype that is hypothesized to drive the AKI to CKD transition (9)(10)(11)(12)(13). Whether or not defects in the early epithelial proliferative response my promote the AKI to CKD transition remains undefined. ...
July 2023
Nature
... Over the more than seven decades since the initial use of CPB by Dr. John Gibbon, Jr., there continue to be significant opportunities to advance the care and outcomes of patients undergoing cardiac surgery. Several initiatives have been undertaken by professional societies to address gaps in observed versus idealized outcomes, including but not limited to the creation and dissemination of evidence-based guidelines [20,[24][25][26][27] and professional consensus-based standards and guidelines [28]. Nonetheless, prior studies have identified significant gaps in translating evidence-based guidelines into practice [29]. ...
December 2022
The Journal of extra-corporeal technology
... Thus, urinary IL-9 levels could be measured to predict the corticosteroid treatment response. Recently, a diagnostic biomarker for AIN, urinary C-X-C motif chemokine ligand 9 (CXCL9), was identified and validated [29]. They adopted urinary CXCL9-to-creatinine ratios, in which values above 58.9 ...
July 2023
The Journal of clinical investigation
... Patients may not present alterations in serum creatinine levels due to compensatory hypertrophy of residual nephrons. They frequently do not present with hematuria, and creatinine and proteinuria increase relatively late during kidney damage [66,67]. Childhood CKD can progress to kidney failure, from the early postnatal period to late adulthood [68]. ...
June 2023
Kidney360
... Three articles employed rehospitalization as a MAKE component: two articles with AKI-related rehospitalization and one with rehospitalization (with cause unspecified) [22,27,43,46,48,92,94,97,103,108,109,112,117,129,133,135,138,140] evaluated MAKE at multiple time points. Overall, thirteen different observation periods were employed across articles, with 30 days (27.9% in single period articles, 55.6% in multiple period articles) and 90 days (22.1% in single period articles, 77.8% in multiple period articles) as the most frequently used periods for evaluation. ...
May 2023
American Journal of Kidney Diseases
... the multiple lists which are used in inpatient and critical care medicine [32,33]. Considering this, healthcare providers and their patients frequently lack awareness of the potential nephrotoxic effects, which may lead to inadequate monitoring and delayed care. ...
May 2023
Drug Safety