Search

Background: Acute kidney injury (AKI) is a major complication following cardiac surgery with a high incidence in those with existing kidney dysfunction. Platelet distribution width (PDW) reflects variability in platelet size and serves as an indicator of platelet activation. Recent investigations linked PDW changes to kidney pathology, suggesting its utility in identifying individuals at risk for AKI, thus necessitating exploration of its predictive value., Methods: Patients with preoperative renal dysfunction [15 ≤ estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m 2 ] who underwent cardiac surgery from January 2018 to December 2021 were retrospectively enrolled. PDW values were measured preoperatively and again upon admission to the ICU immediately after cardiac surgery, with the change in PDW (dPDW) defined as the difference between these two measurements. The primary outcome was postoperative AKI, defined base on the Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging criteria. Multivariate regression models were performed to identify the association between dPDW and AKI and its potential trend. Restricted cubic spline analysis assessed non-linear associations between dPDW and AKI. The Youden index identified an optimal dPDW cut-off for AKI prediction. Subgroup analysis was performed to elucidate the consistency of these associations across the various subgroups., Results: AKI occurred in 53.10% (513/966) of patients, accompanied by significant PDW increases in cases of AKI (P < 0.001). After adjusting confounders, dPDW was identified as a significant risk factor for AKI [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.02 ~ 1.16), P = 0.012]. Patients in the highest dPDW quartile (Q4) had a 195% higher AKI risk compared to those in the lowest quartile (Q1) (OR = 2.95, 95% CI:1.78 ∼ 4.90, P < 0.001). Trend analysis indicates that the risk of AKI increased with higher dPDW quartiles (P for trend < 0.001). Youden index showed that dRDW = 1.1 was identified as the optimal diagnostic cut-off value for AKI. Subgroup analyses and interaction tests showed a robust association between dPDW and AKI in all subgroups (P for interaction > 0.05)., Conclusions: This study underscored perioperative PDW changes as a significant predictor of postoperative AKI in patients with renal insufficiency, highlighting its potential in refining risk stratification and management strategies., Clinical Trial Number: Not applicable for this observational retrospective study., (© 2024. The Author(s).)

Introduction: The direct factor Xa inhibitor apixaban is partially eliminated by the kidneys but is still prescribed at fixed doses without therapeutic drug monitoring across varying levels of renal function. If apixaban accumulates due to renal impairment, this may translate into safety concerns, e.g. the risk for bleeding. The purpose of this study was to measure apixaban trough concentrations in patients with different stages of renal function/renal impairment., Methods: Apixaban trough concentrations were measured using LC-MS/MS in patients with atrial fibrillation, having normal renal function (apixaban 5 mg BID, n=39), moderate renal impairment (apixaban 5 mg BID, n=40) and severe renal impairment (apixaban 2.5 mg BID, n=6). The median (min-max) relative eGFR values were 84.8 (71.7-111.4), 51.4 (31.3-67.2) and 23.0 (21.9-28.4) mL/min/1.73 m², in the three groups, respectively., Results: Patients with moderate renal impairment had significantly higher apixaban trough concentrations than patients with normal renal function. The median (min-max) trough concentrations were 59.8 ng/mL (15.5-170.9) for normal renal function, 128.9 ng/mL (41.4-295.4) for moderate renal impairment and 81.7 ng/mL (61.8-109.0) for severe renal impairment. The trough concentrations correlated significantly with renal function measured as relative/absolute eGFR creatinine/cystatin C., Conclusions: The standard dosing regimen of 5 mg apixaban BID renders exposure that is roughly twice as high in patients with moderately reduced renal function compared to patients with normal renal function. We suggest that patients with moderately reduced renal function ought to be monitored. Possibly, a dose reduction may be considered to achieve similar exposure as in patients with normal renal function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Multiple myeloma (MM) is a malignant incurable disease characterized by monoclonal plasma cell increase associated with renal impairment. Evaluation of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), hemoglobin/red cell distribution width (HB/RDW), interleukin-20 (IL-20), and vascular endothelial growth factor-A (VEGFA) in patients with MM (with or without renal impairment) as prognostic and severity indicators., Research Design and Methods: A cross-sectional study was conducted on sixty MM patients with renal impairment, sixty MM patients without renal impairment, and sixty subjects (control group). Complete blood count, IL-20 immunoassay, and gene expression of IL-20, and VEGFA were evaluated., Results: Higher levels of NLR, MLR, and IL-20, and moreover lower levels of PLR, HB/RDW, as well as upregulation of IL-20, and VEGFA gene expression were detected in MM patients, especially those with renal impairment. Receiver operating characteristic curves analysis of NLR, MLR, PLR, and IL-20 showed high sensitivity and specificity in the diagnosis of MM and disease stages., Conclusions: NLR, MLR, PLR, HB/RDW, IL-20, and VEGFA may be implicated in the inflammatory process of MM and renal impairment pathogenesis. NLR, MLR, and IL-20 can be used as prognostic markers in MM stages.

Background: Hypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies., Methods: We enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m 2 , SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed., Results: Among 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman's coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76-30.35])., Conclusion: In patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient., (© 2024. The Author(s).)

Objective: To evaluate the serum neutrophil gelatinase-associated lipocalin levels in multiple myeloma patients as an indicator of disease progression., Methods: The case-control study was conducted at the Clinical Biochemistry Department of the National Centre of Haematology, Mustansiriyah University, Baghdad, Iraq, from October 2020 to July 2021, amd comprised diagnosed multiple myeloma patients and healthy controls of either gender aged 40-60 years. Neutrophil gelatinaseassociated lipocalin and renal functions were measured for all patients in addition to obtaining a complete history and physical examination. Data was analysed using MedCalc., Results: Of the 60 sujects, 30(50) were cases with mean age 64±2.1 years and 30(50%) were controls with mean age 60 ±3.2 years. There were 18(68%) males among the cases and 17(55%) among the controls. In the cases group, mean levels of creatinine, urea and neutrophil gelatinase-associated lipocalin were 1.62±0.85mg/dl, 55.56±28.05mg/dl and 389.39±116.12pg/mL, respectively. The corresponding values for the controls were 0.9518±0.1623mg/dl, 30.17±8.47mg/dl and 120.82±68'52pg/ml. The neutrophil gelatinase-associated lipocalin cutoff level >190pg/ml in multiple myeloma patients was strongly associated with renal impairment (p<0.001)., Conclusions: Neutrophil gelatinase-associated lipocalin was found to be an accurate indicator of early kidney disease in patients with de novo multiple myeloma.

Background: Individuals with kidney failure have a compromised haemostatic system making them susceptible to both thrombosis and bleeding., Objectives: Assessment of primary haemostasis in patients treated with either haemodialysis (HD) or haemodiafiltration (HDF) was performed through the measurement of several coagulation-based tests, both pre- and post-dialysis., Patients/methods: 41 renal failure patients and 40 controls were recruited. Platelet aggregometry, Factor XIII (FXIII), Fibrinogen, Von Willebrand Factor (VWF) and Soluble P-Selectin (sP-Sel) levels were measured., Results: Maximum platelet aggregation was diminished in renal patients irrespective of aspirin intake. Post-dialysis, platelet function was exacerbated. Pre-dialysis FXIII levels were similar to the healthy cohort and became elevated post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis. Fibrinogen levels were already elevated pre-dialysis and further increased post-dialysis. This elevation was associated with the relative decrease of water by dialysis. VWF levels in males were similar to the healthy cohort and became elevated post-dialysis. This elevation was associated with dialysis-related water loss. VWF antigen and activity in female patients were already elevated pre-dialysis and further increased post-dialysis with the exception of VWF activity in HDF treated female patients. sP-Sel levels were lower than those of the healthy cohort and became similar to the healthy cohort post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis., Conclusions: Whilst platelet aggregometry was diminished, we noted elevated clotting factors such as fibrinogen, FXIII and VWF with no significant differences between HD and HDF-treated patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale & Objective: Biomarkers that enable better identification of persons with chronic kidney disease (CKD) who are at higher risk for disease progression and adverse events are needed. This study sought to identify urine and plasma metabolites associated with progression of kidney disease., Study Design: Prospective metabolome-wide association study., Setting & Participants: Persons with CKD enrolled in the GCKD (German CKD) study with metabolite measurements, with external validation within the ARIC (Atherosclerosis Risk in Communities) Study., Exposures: 1,513 urine and 1,416 plasma metabolites (Metabolon Inc) measured at study entry using untargeted mass spectrometry., Outcomes: Main end points were kidney failure (KF) and a composite kidney end point (CKE) of KF, estimated glomerular filtration rate<15mL/min/1.73m 2 , or a 40% decrease in estimated glomerular filtration rate. Death from any cause was a secondary end point. After a median of 6.5 years of follow-up, 500 persons had experienced KF, 1,083 had experienced the CKE, and 680 had died., Analytical Approach: Time-to-event analyses using multivariable proportional hazard regression models in a discovery-replication design with external validation., Results: 5,088 GCKD study participants were included in analyses of urine metabolites, and 5,144 were included in analyses of plasma metabolites. Among 182 unique metabolites, 30 were significantly associated with KF, 49 with the CKE, and 163 with death. The strongest association with KF was observed for plasma hydroxyasparagine (HR, 1.95; 95% CI, 1.68-2.25). An unnamed metabolite measured in plasma and urine was significantly associated with KF, the CKE, and death. External validation of the identified associations of metabolites with KF or the CKE revealed directional consistency for 88% of observed associations. Selected associations of 18 metabolites with study outcomes have not been previously reported., Limitations: Use of observational data and semiquantitative metabolite measurements at a single time point., Conclusions: The observed associations between metabolites and KF, the CKE, or death in persons with CKD confirmed previously reported findings and also revealed several associations not previously described. These findings warrant confirmatory research in other study cohorts., Plain-Language Summary: Incomplete understanding of the variability of chronic kidney disease (CKD) progression motivated the search for new biomarkers that would help identify people at increased risk. We explored metabolites in plasma and urine for their association with unfavorable kidney outcomes or death in persons with CKD. Metabolomic analyses revealed 182 metabolites significantly associated with CKD progression or death. Many of these associations confirmed previously reported findings or were validated by analysis in an external study population. Our comprehensive screen of the metabolome serves as a valuable foundation for future investigations into biomarkers associated with CKD progression., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Data about the impacts of hemodialysis on antioxidant status and markers of oxidative stress are controversial, probably due to the use of different methodological approaches. The aim of this study was to assess the changes in the oxidative damage markers and antioxidant enzymes, and the serum antioxidant capacity by using in vitro model systems of free radical generation before and after one hemodialysis session. Blood samples were collected from 40 patients with kidney failure before and after hemodialysis. In pre- and post-hemodialysis serum samples, concentrations of biomarkers of oxidative damage and the activities of antioxidant enzymes were measured, as well as the in vitro antioxidant potential. The high concentrations of oxidative stress markers in serum of kidney failure patients were decreased after one hemodialysis session. In pre-hemodialysis, low activities of antioxidant enzymes were observed, including paraoxonase-1, however paraoxonase-1 activity was partially recovered after hemodialysis. Crocin bleaching and radical scavenging assays showed that serum antioxidant potential was decreased after hemodialysis. Although one hemodialysis session increased paraoxonase-1 activity and decreased oxidative stress markers, it caused a decrease in the serum antioxidant potential. Future research is needed to prospect strategies to mitigate the impacts of oxidative stress in the scenario of hemodialysis repetitions.

Purpose: This study aimed to investigate the correlation between serum creatinine levels and the presence and severity of radiographic knee osteoarthritis (OA) in individuals aged ≥50 years while adjusting for potential confounders., Materials and Methods: Cross-sectional data from the 2009-2011 Korea National Health and Nutrition Examination Survey comprising 3428 individuals aged ≥50 years were utilized. The Kellgren-Lawrence (K-L) grading scale was used to assess the radiographic presence and severity of knee OA. Logistic regression and receiver operating characteristic analyses were used to investigate the association between serum creatinine levels and the presence of knee OA, whereas ordinal regression was used to assess the impact of creatinine levels on knee OA severity., Results: The presence of radiographic knee OA conferred by low serum creatinine levels was found to be significant in both sexes [odds ratio (OR), 0.118; 95% confidence interval (CI), 0.045-0.314, p <0.001 for men; OR, 0.148; 95% CI, 0.040-0.549, p =0.004 for women]. Low serum creatinine was significantly associated with knee OA-graded K-L severity in each sex-based group [β, -1.923; standard error, 0.478; p <0.001 for men and β, -1.532; SE, 0.575; p =0.008 for women]., Conclusion: Low serum creatinine level was associated with a higher presence of knee OA in both men and women, and was also linked to the severity of the disease. These findings suggest that the serum creatinine level may be a potential biomarker for assessing the presence and severity of knee OA., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.

Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5'-cytosine-phosphate-guanine-3' loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10 -14 . In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.

Introduction: We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN., Methods: We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states., Results: There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity., Conclusion: Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Guo, Wei, Zhu, Luo and Luo.)

Introduction: The main objective of this study was to evaluate the impact of hemoadsorption on the elimination of inflammatory mediators., Methods: A prospective, bicenter, observational cohort study was conducted between March 2020 and February 2022 to explore the immunomodulatory response, demographic and clinical characteristics of individuals with COVID-19 admitted to the ICU with severe acute respiratory failure and in need of CRRT with Oxiris® with or without AKI., Results: Sixty-four patients were analyzed. Statistically significant differences were observed between exposed and unexposed groups, in relation to the reduction in D-dimer levels -15,614 (24,848.9) versus -4,136.5 (9,913.47) (p 0.031, d: 1.59, 95% CI: -21,830, -1,126). An increase in PCT was observed 0.47 (2.08) versus -0.75 (2.3) (p 0.044 95% CI: 0.03, 2.44). No differences were found in a decrease in CRP -4.21 (7.29) versus -1.6 (9.02) (p 0.22) nor in the rest of inflammatory parameters fibrinogen, IL-6, ferritin, lymphocytes, and neutrophils. Subgroup analysis in patients exposed to therapy also showed a significant decrease in D-dimer of 55% from baseline: 6,000 (1,984.5-27,750) pre-therapy versus 2,700 (2,119.5-6,145) (95% CI: -23,000, -2,489) post-therapy with a strong effect size (p 0.001, d: 0.65)., Conclusion: The hemoadsorptive therapy in COVID-19 was associated with a significant decrease in D-dimer parameters without showing decreases in the rest of the clinical, inflammatory parameters and severity scales analyzed., (© 2024 S. Karger AG, Basel.)

Purpose: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis., Methods: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK + ] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK + of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy., Findings: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK + concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK + of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively., Implications: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis., Clinicaltrials: gov identifier: NCT04217590., Competing Interests: Declaration of Competing Interest Xiangwen Meng, Zhiren Chang, June Zhao, Peter Wessman, and Peng Xiang are employees of, and hold or may hold stock in, AstraZeneca. Zhaohui Ni, Chaosheng Chen, and Xinzhou Zhang declare grant support from AstraZeneca, and Yi Li declares grant and educational event support from AstraZeneca. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Two dimensional GC (GC × GC)-time-of-flight mass spectrometry (TOFMS) has been used to improve accurate metabolite identification in the chemical industry, but this method has not been applied as readily in biomedical research. Here, we evaluated and validated the performance of high resolution GC × GC-TOFMS against that of GC-TOFMS for metabolomics analysis of two different plasma matrices, from healthy controls (CON) and diabetes mellitus (DM) patients with kidney failure (DM with KF). We found GC × GC-TOFMS outperformed traditional GC-TOFMS in terms of separation performance and metabolite coverage. Several metabolites from both the CON and DM with KF matrices, such as carbohydrates and carbohydrate-conjugate metabolites, were exclusively detected using GC × GC-TOFMS. Additionally, we applied this method to characterize significant metabolites in the DM with KF group, with focused analysis of four metabolite groups: sugars, sugar alcohols, amino acids, and free fatty acids. Our plasma metabolomics results revealed 35 significant metabolites (12 unique and 23 concentration-dependent metabolites) in the DM with KF group, as compared with those in the CON and DM groups (N = 20 for each group). Interestingly, we determined 17 of the 35 (14/17 verified with reference standards) significant metabolites identified from both the analyses were metabolites from the sugar and sugar alcohol groups, with significantly higher concentrations in the DM with KF group than in the CON and DM groups. Enrichment analysis of these 14 metabolites also revealed that alterations in galactose metabolism and the polyol pathway are related to DM with KF. Overall, our application of GC × GC-TOFMS identified key metabolites in complex plasma matrices., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis of myocardial infarction in patients with kidney impairment is unclear. Here, we describe implementation of hs-cTnI testing on the diagnosis, management, and outcomes of myocardial infarction in patients with and without kidney impairment. Consecutive patients with suspected acute coronary syndrome enrolled in a stepped-wedge, cluster-randomized controlled trial were included in this pre-specified secondary analysis. Kidney impairment was defined as an eGFR under 60mL/min/1.73m 2 . The index diagnosis and primary outcome of type 1 and type 4b myocardial infarction or cardiovascular death at one year were compared in patients with and without kidney impairment following implementation of hs-cTnI assay with 99th centile sex-specific diagnostic thresholds. Serum creatinine concentrations were available in 46,927 patients (mean age 61 years; 47% women), of whom 9,080 (19%) had kidney impairment. hs-cTnIs were over 99th centile in 46% and 16% of patients with and without kidney impairment. Implementation increased the diagnosis of type 1 infarction from 12.4% to 17.8%, and from 7.5% to 9.4% in patients with and without kidney impairment (both significant). Patients with kidney impairment and type 1 myocardial infarction were less likely to undergo coronary revascularization (26% versus 53%) or receive dual anti-platelets (40% versus 68%) than those without kidney impairment, and this did not change post-implementation. In patients with hs-cTnI above the 99th centile, the primary outcome occurred twice as often in those with kidney impairment compared to those without (24% versus 12%, hazard ratio 1.53, 95% confidence interval 1.31 to 1.78). Thus, hs-cTnI testing increased the identification of myocardial injury and infarction but failed to address disparities in management and outcomes between those with and without kidney impairment., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The concentration of Cys C in the patient's serum can reflect the level of glomerular filtration rate and indicate the occurrence of renal failure. The establishment of a simple and rapid analytical method to quantitatively monitor the concentration of Cys C in serum could help timely detection of renal failure. In this study, we have developed an Eu (III) chelate nanoparticles based lateral flow immunoassay to fulfill real-time monitoring of Cys C concentration in serum within 15 min. This method was performed as a sandwich immunoassay with a wide detection range (0.05-10 μg/mL) and a low limit of detection (24.54 ng/mL). The intra and inter-assay coefficients of variation were 8.31-8.61% and 8.92-9.95%, respectively. Furthermore, the application of this method was evaluated by comparing the determined results with those obtained by chemiluminescence immunoassay, exhibiting a satisfactory correlation (R 2  = 0.9830). The developed LFIA method with satisfactory analytical performance has great potential for real-time monitoring of renal failure and self-detection for the high-risk population., (Copyright © 2022. Published by Elsevier B.V.)

Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; P =0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; P <0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each P <0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12616000535471.

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m 2 ), moderately impaired (M) (≥30 to <60 ml/min/1.73 m 2 ), and severely impaired (S) (<30 ml/min/1.73 m 2 ) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end-stage renal disease at 2 years after LDL-A treatment. These results suggest that LDL-A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m 2 ., (© 2021 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 μg/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 μg/day) or vehicle via s.c. osmotic pumps. At the end of the HS challenge, both groups exhibited similar outcomes for GFR, heart weight, plasma electrolytes, BUN, and creatinine. Sacubitril exacerbated kidney hypertrophy, but did not affect levels of renal fibrosis. We also observed aggravated glomerular lesions and increased formation of protein casts in the sacubitril-treated animals compared to controls. Thus, in Dahl SS rats, administration of sacubitril without renin-angiotensin-system blockage had adverse effects on renal disease progression, particularly in regards to glomerular damage and protein cast formation. We can speculate that while ANP levels are increased because of neprilysin inhibition, there are off-target effects of sacubitril, which are detrimental to renal function in the SS hypertensive state.

Background: Patients receiving maintenance dialysis represent a high-risk, immune-compromised population with 15%-25% COVID-19 mortality rate who were unrepresented in clinical trials of mRNA vaccines., Methods: All patients receiving maintenance dialysis who received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021, were included. Response was on the basis of levels of Ig-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike-antigen (seropositive ≥2 U/L) using an FDA-approved semiquantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G)., Results: Among 186 patients on dialysis from 30 clinics in eight states tested 23±8 days after receiving two vaccine doses, there were 165 (88.7%) responders with 70% at maximum titer. There was no significant difference between BNT162b2/Pfizer (148 out of 168, 88.1%) and mRNA-1273/Moderna (17 out of 18, 94.4%), P =0.42. All 38 patients with COVID-19 history were responders, with 97% at maximum titer. Among patients without COVID-19, 127 out of 148 (85.8%) were responders, comparable between BNT162b2/Pfizer (113 out of 133) and mRNA-1273/Moderna (14 out of 15) vaccines (85.0% versus 93.3%, P =0.38)., Conclusions: Most patients receiving maintenance dialysis responded after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine, suggesting the short-term development of antispike antibody is good, giving hope that most of these patients who are vulnerable, once immunized, will be protected from COVID-19. Longer-term evaluation is needed to determine antibody titer durability and if booster dose(s) are warranted. Further research to evaluate the approach to patients without a serologic response is needed, including benefits of additional dose(s) or administration of alternate options., (Copyright © 2021 by the American Society of Nephrology.)

With increased life expectancy among patients with beta-thalassemia major (β-TM) renal insufficiency has been frequently noted because of the persistence of anemia, iron overload and some drug side effects. Serum creatinine becomes elevated in late stage of kidney affection. Cystatin-C is more sensitive biomarker for kidney dysfunction. Our aim was to measure Cystatin-C serum level among patients with β-TM as a marker of early nephropathy. Serum Cystatin-C was measured in 94 patients with β-TM using Enzyme-Linked Immunosorbent Assay (ELISA) and correlated to other clinical, laboratory and radiologic data. Glomerular hyperfiltration was observed in 30.8% while Cystatin-C was elevated in 56.3% of β-TM. Patients having high serum Cystatin-C were older in age and having higher serum levels of aspartate aminotransferases and urea. Cystatin-C level was positively correlated with serum creatinine and urea and negatively correlated with glomerular filtration rate. Periodic assessment of Cystatin-C in patients with β-TM is recommended for early diagnosis of renal dysfunction especially during drug dosing prescription aiming to obtain the maximum effectiveness and safety. Controlling anemia by maintaining appropriate hemoglobin level with close monitoring of iron overload are also recommended to preserve renal function among β-TM patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We aimed to investigate the prevalence of thyroid hormone abnormalities and the relationship between free triiodothyronine (fT3), thyroid stimulating hormone (TSH) and free thyroxine (fT4) serum levels with kidney function and proteinuria in 4108 subsequent patients admitted to a Nephrology Clinic at a tertiary Medical Centre., Methods: All patients were categorized based on their estimated glomerular filtration rate (eGFR) as follows: normal-eGFR ≥ 60 ml/min, mild kidney impairment-30 ≤ eGFR < 60 ml/min, and severe kidney impairment-eGFR < 30 ml/min., Results: Subjects with normal eGFR presented a laboratory constellation of hypothyroidism in 3.38% and "low-T3 syndrome" in 8.28%, while subjects with severe kidney impairment were diagnosed with hypothyroidism in 2.82% and "low-T3 syndrome" in 22.9%. Multivariate regression analysis showed that eGFR was a strong independent predictor of serum fT3 levels in patients with eGFR < 60 ml/min. Impaired kidney function was associated with low fT4 and fT3 but not TSH. Our findings showed an inverse correlation of fT3 and fT4 levels and proteinuria range. FT4 inversely correlated with the extent of proteinuria in all subgroups of patients. In contrast, the inverse correlation of fT3 serum levels and proteinuria disappeared in patients with eGFR < 60 ml/min., Conclusion: In a large cohort of inpatients, the prevalence of low-T3 syndrome was 2.5 times higher in patients with advanced kidney disease, compared to those with normal kidney function. In advanced CKD, both eGFR and proteinuria were strongly correlated with thyroid hormones. Therefore, close screening of the "thyroid profile" in patients with any stage of CKD, especially to those with proteinuria, might be warranted., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Introduction: Imperfect hemostasis after arteriovenous fistula (AVF) and arteriovenous graft (AVG) cannulation can cause a hematoma or pseudoaneurysm and leads to poor satisfaction. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation in a rat AVF and AVG model., Method: A hydrogel comprised of sodium alginate (SA), hyaluronic acid (HA), and calcium carbonate was coated onto the surface of suture needles using a rotating system. The needles were observed using scanning electron microscopy (SEM) and immunofluorescence. Rat AVF with or without renal failure and AVG were punctured using bare and hydrogel-coated needles. The tissues were examined by histology., Result: The hydrogel was successfully coated onto the surface of 30 G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after AVF and AVG cannulation in rat., Conclusion: In this preliminary animal research, hydrogel-coated needles can stop AVF and AVG puncture-site bleeding; but additional clinical studies are needed to justify whether it is still effective in clinical., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: This study was designed to probe into the changes and clinical significance of GRP78 and miR-495-3p in renal failure (RF) patients during high-flux dialysis (HFD) combined with hemoperfusion (HP)., Methods: Sixty-five RF patients and 74 health check-ups who were admitted in our hospital from March 2015 to February 2017 were prospectively selected, and the related characteristics were retrospectively collected for analysis. GRP78 and miR-495-3p were detected in RF patients at admission (before treatment), 12 weeks after treatment (during treatment), 24 weeks after treatment (after treatment), and the control group at admission, and the relationship between the two and the occurrence, efficacy, and recurrence of RF was analyzed., Results: Before treatment, the GRP78 mRNA level in RF patients was higher than that in health check-ups, while the miR-495-3p level was lower ( P < 0.05). GRP78 mRNA in RF patients was lower than that before treatment and was the lowest after treatment. On the contrary, miR-495-3p was higher than that before treatment and was the highest after treatment ( P < 0.05). The two had a significant effect on predicting RF before treatment, efficacy of patients, and their recurrence after treatment (all P < 0.001)., Conclusion: GRP78 decreased during the treatment of high-flux hemodialysis (HF-HD) combined with systemic HP in RF patients, while miR-495-3p increased. Both of them have a good reference value for RF occurrence, treatment results, and recurrence., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wei Fan et al.)

Objective: To aid the clinician in correctly interpreting serum tryptase levels., Data Sources: Primary peer-reviewed literature., Study Selections: Clinical and basic science peer-reviewed studies characterizing the genetic and physiological bases for tryptase generation, secretion, and elevation, including those describing serum tryptase levels in population-based cohort studies., Results: Clinically measured basal serum tryptase (BST) consists of ostensibly inactive alpha- and beta-tryptase precursors. The autosomal dominant genetic trait hereditary alpha-tryptasemia is the most often cause for elevated BST levels, with other acquired causes, such as renal failure and clonal myeloid diseases being far less common. Acute increases in serum tryptase levels resulting from release of mature tryptase from secretory granules is specific to mast cell degranulation but is not detected in all cases of systemic anaphylaxis., Conclusion: Understanding the differences and distinguishing between acute increases in serum tryptase and chronic elevations in BST owing to inherited or acquired conditions is critical in the correct interpretation of this useful clinical biomarker., (Published by Elsevier Inc.)

Background: The association between N-terminal pro brain natriuretic peptide (NT-proBNP) level and long-term mortality in Japanese hemodialysis patients has not been fully assessed., Methods: This prospective, multicenter study included 1428 hemodialysis outpatients. Baseline NT-proBNP levels were measured at the first hemodialysis session of the week and participants were followed for 5 years. The areas under the curve were calculated from receiver operating characteristic curves. Groups determined by quartiles of baseline NT-proBNP level were assessed by the Kaplan-Meier method and log-rank test. The association between NT-proBNP level and mortality was assessed using multivariate Cox proportional hazards models., Results: During the 5-year follow-up, we observed 370 deaths and 256 censored cases. The areas under the curve of pre-hemodialysis NT-proBNP for all-cause mortality and cardiovascular disease mortality after 1 year were 0.75 and 0.78, respectively, and significantly greater than the areas under the curve at the 3- and 5-year follow-up. Cut-off values for all-cause mortality and cardiovascular disease mortality after 1 year were 4550 and 5467 ng/L, respectively (sensitivity: 82% and 81%; specificity: 59% and 64%). Kaplan-Meier survival analysis showed that the group with pre-hemodialysis NT-proBNP ≥ 8805 ng/L had increased all-cause mortality (P < 0.001) and cardiovascular disease mortality (P < 0.001). Finally, multivariate Cox analysis showed that NT-proBNP level was associated with all-cause mortality (P < 0.001) and cardiovascular disease mortality (P = 0.004) independently from other clinical parameters., Conclusion: NT-proBNP is a useful marker to predict both all-cause and cardiovascular disease mortality in hemodialysis patients., (© 2021. Japanese Society of Nephrology.)

The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction., Competing Interests: The author reports no conflicts of interest in this work., (© 2021 Chauin.)

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker and risk factor for kidney diseases, with a potential prognostic value in critically ill patients. In this monocentric prospective study, we measured plasma suPAR levels immediately after ICU admission in unselected 237 consecutive patients using a turbidimetric assay. Primary objective was the prognostic value for ICU- and 28-day mortality. Secondary objectives were association with sequential organ failure assessment (SOFA) score, coagulation and inflammation markers, AKI-3 and differences in prespecified subgroups. Median suPAR levels were 8.0 ng/mL [25th-75th percentile 4.3-14.4], with lower levels in ICU survivors than non-survivors (6.7 vs. 11.6 ng/mL, p < 0.001). SuPAR levels were higher in COVID-19, kidney disease, moderate-to-severe liver disease, and sepsis. ICU mortality increased by an odds ratio (OR) of 4.7 in patients with the highest compared to lowest quartile suPAR. Kaplan-Meier overall survival estimates at 3 months were 63% and 49%, in patients with suPAR below/above 12 ng/mL (log-rank p = 0.027). Due to an observed interaction between SOFA score and suPAR, we performed a random forest method identifying cutoffs. ICU mortality was 53%, 17% and 2% in patients with a SOFA score > 7, SOFA ≤ 7 & suPAR > 8 ng/mL, and SOFA score ≤ 7 & suPAR ≤ 8 ng/mL, respectively. suPAR was a significant predictor for AKI-3 occurrence (OR per doubling 1.89, 95% CI: 1.20-2.98; p = 0.006). suPAR levels at ICU admission may offer additional value for risk stratification especially in ICU patients with moderate organ dysfunction as reflected by a SOFA score ≤ 7., (© 2021. The Author(s).)

BACKGROUND The thyroid state significantly influences renal function. However, a direct link between thyroid and kidney dysfunction has not been identified. Thyroid hormones affect cardiac output and vascular resistance, and thus can modify kidney perfusion. This prospective study aimed to test the association between renal cortical perfusion (RCP) estimated in color Doppler sonographic dynamic tissue perfusion measurement (DTPM) with thyroid hormones in 36 patients treated with levothyroxine following total thyroidectomy for resectable thyroid cancer. MATERIAL AND METHODS Blood tests, blood pressure monitoring, and DTPM of the renal cortex were performed. To exclude possible reading errors, the intrarater reliability of the ultrasound perfusion measurement method was estimated. RESULTS The absolute difference between the 2 ultrasound RCP measurements was 5.2±4.4%. RCP correlated significantly with free thyroxine (FT₄) (r=0.46; p=0.006) but not with triiodothyronine and thyroid-stimulating hormone. In the adjusted to age backward stepwise multivariable regression analysis model, including estimated glomerular filtration rate, mean arterial pressure, and FT₄, only FT₄ was independently associated with RCP (R²=0.21; p=0.006). CONCLUSIONS Renal cortical perfusion is independently associated with free thyroxine, which can contribute to renal function abnormalities in the condition of impaired thyroid function. This small prospective study from a single center showed that the renal cortex's color Doppler sonographic dynamic tissue perfusion measurement had very good intraobserver reproducibility.

Objectives: Static glomerular filtration rate formulas are not suitable for critically ill patients because of nonsteady state glomerular filtration rate and variation in the volume of distribution. Kinetic glomerular filtration rate formulas remain to be evaluated against a gold standard. We assessed the most accurate kinetic glomerular filtration rate formula as compared to iohexol clearance among patients with shock., Design: Retrospective multicentric study., Setting: Three French ICUs in tertiary teaching hospitals., Patients: Fifty-seven patients within the first 12 hours of shock., Measurements and Main Results: On day 1, we compared kinetic glomerular filtration rate formulas with iohexol clearance, with or without creatinine concentration correction according to changes in volume of distribution and ideal body weight. We analyzed three static glomerular filtration rate formulas (Cockcroft and Gault, modification of diet in renal disease, and Chronic Kidney Disease-Epidemiology Collaboration), urinary creatinine clearance, and seven kinetic glomerular filtration rate formulas (Jelliffe, Chen, Chiou and Hsu, Moran and Myers, Yashiro, Seelhammer, and Brater). We evaluated 33 variants of these formulas after applying corrective factors. The bias ranged from 12 to 47 mL/min/1.73 m2. Only the Yashiro equation had a lower bias than urinary creatinine clearance before applying corrective factors (15 vs 20 mL/min/1.73 m2). The corrected Moran and Myers formula had the best mean bias, 12 mL/min/1.73 m2, but wide limits of agreement (-50 to 73). The corrected Moran and Myers value was within 30% of iohexol-clearance-measured glomerular filtration rate for 27 patients (47.4%) and was within 10% for nine patients (15.8%); other formulas showed even worse accuracy., Conclusions: Kinetic glomerular filtration rate equations are not accurate enough for glomerular filtration rate estimation in the first hours of shock, when glomerular filtration rate is greatly decreased. They can both under- or overestimate glomerular filtration rate, with a trend to overestimation. Applying corrective factors to creatinine concentration or volume of distribution did not improve accuracy sufficiently to make these formulas reliable. Clinicians should not use kinetic glomerular filtration rate equations to estimate glomerular filtration rate in patients with shock., Competing Interests: Dr. Desgrouas’ institution received funding from Firalis SA; he received funding from French Intensive Care Society (FICS). Dr. Ehrmann declares receiving consulting fees, unrestricted research grants and equipment research support from Aerogen, unrestricted research grant from Fisher & Paykel, unrestricted research grant form Hamilton medical, and consulting fees from La Diffusion Technique Française. Dr. Gandonnière’s institution received funding from Firalis SA; she received funding from FICS. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Rationale & Objective: Immune activation is fundamental to the pathogenesis of many kidney diseases. Innate immune molecules such as soluble urokinase-type plasminogen activator receptor (suPAR) have been linked to the incidence and progression of chronic kidney disease (CKD). Whether other biomarkers of immune activation are associated with incident kidney failure with replacement therapy (KFRT) in African Americans with nondiabetic kidney disease is unclear., Study Design: Prospective cohort., Setting & Participants: African American Study of Kidney Disease and Hypertension (AASK) participants with available baseline serum samples for biomarker measurement., Predictors: Baseline serum levels of soluble tumor necrosis factor receptor 1 (sTNFR1), sTNFR2, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ)., Outcomes: Incident KFRT, all-cause mortality., Analytical Approach: Cox proportional hazards models., Results: Among 500 participants with available samples, mean glomerular filtration rate was 44.7mL/min/1.73m 2 , and median urinary protein-creatinine ratio was 0.09g/g at baseline. Over a median follow up of 9.6 years, there were 161 (32%) KFRT and 113 (23%) death events. In models adjusted for demographic and clinical factors and baseline kidney function, each 2-fold higher baseline level of sTNFR1, sTNFR2, and TNF-α was associated with 3.66-fold (95% CI, 2.31-5.80), 2.29-fold (95% CI, 1.60-3.29), and 1.35-fold (95% CI, 1.07-1.71) greater risks of KFRT, respectively; in comparison, each doubling of baseline suPAR concentration was associated with 1.39-fold (95% CI, 1.04-1.86) greater risk of KFRT. sTNFR1, sTNFR2, and TNF-α were also significantly associated with death (up to 2.2-fold higher risks per 2-fold higher baseline levels; P≤0.01). IFN-γ was not associated with either outcome. None of the biomarkers modified the association of APOL1 high-risk status (genetic risk factors for kidney disease among individuals of African ancestry) with KFRT (P>0.05 for interaction)., Limitations: Limited generalizability to other ethnic groups or causes of CKD., Conclusions: Among African Americans with CKD attributed to hypertension, baseline levels of sTNFR1, sTNFR2, and TNF-α but not IFN-γ were associated with KFRT and mortality., (Copyright © 2021 National Kidney Foundation, Inc. All rights reserved.)

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies., Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β =  - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E-06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria., Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.

Renal (RIP) and hepatic (HIP) impairments are prevalent conditions in cancer patients. They can cause changes in gastric emptying time, albumin levels, hematocrit, glomerular filtration rate, hepatic functional volume, blood flow rates, and metabolic activity that can modify drug pharmacokinetics. Performing clinical studies in such populations has ethical and practical issues. Using predictive physiologically-based pharmacokinetic (PBPK) models in the evaluation of the PK of alectinib, ruxolitinib, and panobinostat exposures in the presence of cancer, RIP, and HIP can help in using optimal doses with lower toxicity in these populations. Verified PBPK models were customized under scrutiny to account for the pathophysiological changes induced in these diseases. The PBPK model-predicted plasma exposures in patients with different health conditions within average 2-fold error. The PBPK model predicted an area under the curve ratio (AUCR) of 1, and 1.8, for ruxolitinib and panobinostat, respectively, in the presence of severe RIP. On the other hand, the severe HIP was associated with AUCR of 1.4, 2.9, and 1.8 for alectinib, ruxolitinib, and panobinostat, respectively, in agreement with the observed AUCR. Moreover, the PBPK model predicted that alectinib therapeutic cerebrospinal fluid levels are achieved in patients with non-small cell lung cancer, moderate HIP, and severe HIP at 1-, 1.5-, and 1.8-fold that of healthy subjects. The customized PBPK models showed promising ethical alternatives for simulating clinical studies in patients with cancer, RIP, and HIP. More work is needed to quantify other pathophysiological changes induced by simultaneous affliction by cancer and RIP or HIP., (© 2021 John Wiley & Sons Ltd.)

Background: The role of serum uric acid (SUA) after stroke is controversial and can be influenced by renal disease., Aim: to analyse the role of SUA in the acute phase of stroke based on the presence/absence of kidney disease and cardiovascular outcome., Methods: Retrospective cohort of a stroke registry followed-up for one year. The sample was divided according to the presence of renal disease defined by haematocrit, urea and gender (HUGE) formula, along with a SUA cut-off point obtained by receiver operating characteristic curves based on SUA levels and on the primary end-point occurrence., Results: 500 patients (268, 53.6% males) were analysed. Renal disease was present in 14.8% patients. The SUA cut-off for patients with renal disease was 404.46 μmol/L and 344.98 μmol/L for the remainder. Patients with higher SUA levels had decreased neurological disabilities (p = 0.04) and higher comorbidity (p = 0.00). Over a period of 42.3 (19) weeks, a primary end-point occurred in 17.4% patients. In the adjusted Cox model, SUA was associated with the primary end-point (HR 1.45, 95%CI 1.17-1.81, p = 0.01). Separated by the presence/absence of renal disease, SUA levels were associated with the primary endpoint for patients with renal disease (HR 1.29, 95%CI 1.06-1.58, p = 0.01) and for all other patients (HR 1.42, 95%CI 1.2-1.7, p = 0.00)., Conclusions: We observed a relationship between SUA levels and a negative cardiovascular outcome after ischaemic stroke both in patients with and without renal disease, with the worst outcomes occurring in patients with renal insufficiency.

A model-informed drug development approach was used to select ceftaroline fosamil high-dose regimens for pediatric patients with complicated skin and soft-tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory concentration (MIC) of 2 or 4 mg/L. Steady-state ceftaroline concentrations were simulated using a population pharmacokinetics (PK) model for ceftaroline fosamil and ceftaroline including data from 304 pediatric subjects and 944 adults. Probability of target attainment (PTA) for various simulated pediatric high-dose regimens and renal function categories were calculated based on patients achieving 35% fT>MIC (S. aureus PK/pharmacodynamic target for 2-log 10 bacterial killing). For extrapolation of efficacy, simulated exposures and PTA were compared to adults with normal renal function receiving high-dose ceftaroline fosamil (600 mg 2-h infusions every 8 h). For safety, predicted ceftaroline exposures were compared with observed pediatric and adult data. Predicted ceftaroline exposures for the approved pediatric high-dose regimens (12, 10, or 8 mg/kg by 2-h infusions every 8 h for patients aged >2 to <18 years with normal/mild, moderate, or severe renal impairment, respectively; 10 mg/kg by 2-h infusions every 8 h for patients aged ≥2 months to <2 years with normal renal function/mild impairment) were well matched to adults with normal renal function. Median predicted maximum concentration at steady state (C max,ss ) and area under the plasma concentration-time curve over 24 h at steady state pediatric to adult ratios were 0.907-1.33 and 0.940-1.41, respectively. PTAs (>99% and ≥81% for MICs of 2 and 4 mg/L, respectively) matched or exceeded the adult predictions. Simulated C max,ss values were below the maximum observed data in other indications, including a high-dose pediatric pneumonia trial, which reported no adverse events related to high exposure., (© 2021 Pfizer R&D UK Limited. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Abstract: Bilateral kidney damage in hypertensive patients is not parallel. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), as a commonly used antihypertensive drug, could protect kidney function and delay its deterioration. Most studies focused on overall renal function, but the researches on split renal function (SRF) are rare. We investigated the effects of ACEI/ARB on the SRF in patients with primary hypertension.Patients with primary hypertension (n = 429; male: 213; female: 216) admitted to our department between January 2014 and December 2016 were included in this study. The glomerular filtration rate (GFR) of split and total renal function were determined using diethylenetriaminepentaacetic acid tagged with 99mTc renal dynamic imaging method. For the same patient, the side with high GFR was considered as higher GFR kidney, whereas that with a low GFR was considered as lower GFR kidney. The split function score (Q value) was utilized to evaluate the differences of bilateral renal function. The patients were divided into 3 groups based on the Q values (Group 1, Q value <5%; Group 2, Q value of 5%-10%; Group 3, Q value ≥10%). All the patients received antihypertensive therapy based on ACEI/ARB. The renal dynamic imaging was performed in the 1-year follow-up to investigate the changes of the SRF.Compared with the baseline level, significant decline was noticed in the serum creatinine (Scr) in Group 2 and Group 3 (P < .05). The cystatin C in Group 3 showed significant decline (P < .05). Compared with the baseline, there was significant decline in the Q value in Group 2, whereas the GFR of lower GFR kidney showed significant increase (P < .05). No statistical differences were noticed in the Q value and split GFR in Group 1 and Group 3 (P > .05).In primary hypertension patients, ACEI/ARB therapy could improve the SRF of lower GFR kidney in the presence of certain differences between the SRF. As a result, the SRF difference was reduced. In case of Q value in a range of 5% to 10%, ACEI/ARB could improve the renal function effectively. It may be significant for the design of antihypertensive drugs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

We aimed to compare the demographic, clinical and laboratory characteristics between IgG4-related kidney disease (IgG4-RKD+) and extrarenal IgG4-related disease (IgG4-RKD-) in a large Chinese cohort, as well as describing the radiological and pathological features of IgG4-RKD+. We retrospectively analyzed the medical records of 470 IgG4-related disease (IgG4-RD) patients at Peking University People's Hospital from January 2004 to January 2020. The demographic, clinical, laboratory, radiological and pathological characteristics between IgG4-RKD+ and IgG4-RKD- were compared. Twenty IgG4-RD patients who had definite etiology of renal impairment including diabetes, hypertension and etc. were excluded. Among the remained 450 IgG4-RD patients, 53 were diagnosed with IgG4-RKD+ . IgG4-RKD+ patients had older age at onset and at diagnosis. Male to female ratio of IgG4-RKD+ patients is significantly higher. In the IgG4-RKD+ group, the most commonly involved organs were salivary gland, lymph nodes and pancreas. It was found that renal function was impaired in approximately 40% of IgG4-RKD+ patients. The most common imaging finding is multiple, often bilateral, hypodense lesions. Male sex, more than three organs involved, and low serum C3 level were risk factors for IgG4-RKD+ in IgG4-RD patients. These findings indicate potential differences in pathogenesis of these two phenotypes.

Background: Any definition of preeclampsia should identify women and babies at greatest risk of adverse outcomes., Objective: This study aimed to investigate the ability of the American College of Obstetricians and Gynecologists and International Society for the Study of Hypertension in Pregnancy definitions of preeclampsia at term gestational age (≥37 0/7 weeks) to identify adverse maternal and perinatal outcomes., Study Design: In this prospective cohort study at 2 maternity hospitals in England, women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation underwent assessment that included history; ultrasonographic estimated fetal weight; Doppler measurements of the pulsatility index in the uterine, umbilical, and fetal middle cerebral arteries; and serum placental growth factor-to-soluble fms-like tyrosine kinase-1 ratio. Obstetrical records were examined for all women with chronic hypertension and those who developed new-onset hypertension, with preeclampsia (de novo or superimposed on chronic hypertension) defined in 5 ways: traditional, based on new-onset proteinuria; American College of Obstetricians and Gynecologists 2013 definition; International Society for the Study of Hypertension in Pregnancy maternal factors definition; International Society for the Study of Hypertension in Pregnancy maternal factors plus fetal death or fetal growth restriction definition, defined according to the 35 0/7 to 36 6/7 weeks' gestation scan as either estimated fetal weight <3rd percentile or estimated fetal weight at the 3rd to 10th percentile with any of uterine artery pulsatility index >95th percentile, umbilical artery pulsatility index >95th percentile, or middle cerebral artery pulsatility index <5th percentile; and International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance definition, defined as placental growth factor <5th percentile or soluble fms-like tyrosine kinase-1-to-serum placental growth factor >95th percentile. Detection rates for outcomes of interest (ie, severe maternal hypertension, major maternal morbidity, perinatal mortality or major neonatal morbidity, neonatal unit admission ≥48 hours, and birthweight <10th percentile) were compared using the chi-square test, and P<.05 was considered significant., Results: Among 15,248 singleton pregnancies, the identification of women with preeclampsia varied by definition: traditional, 15 of 281 (1.8%; 248); American College of Obstetricians and Gynecologists, 15 of 326 (2.1%; 248); International Society for the Study of Hypertension in Pregnancy maternal factors, 15 of 400 (2.6%; 248); International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, 15 of 434 (2.8%; 248); and International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, 15 of 500 (3.3%; 248). Compared with the traditional definition of preeclampsia, the International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance best identified the adverse outcomes: severe hypertension (40.6% [traditional] vs 66.9% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P<.0001], 59.2% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, P=.004], 56.2% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.013], 46.1% [American College of Obstetricians and Gynecologists, P=.449]); P<.0001); composite maternal severe adverse event (72.2% [traditional] vs 100% for all others; P=.046); composite of perinatal mortality and morbidity (46.9% [traditional] vs 71.1% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P=.002], 62.2% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, P=.06], 59.8% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.117], 49.4% [American College of Obstetricians and Gynecologists, P=.875]); neonatal unit admission for ≥48 hours (51.4% [traditional] vs 73.4% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P=.001], 64.5% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, P=.070], 60.7% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.213], 53.3% [American College of Obstetricians and Gynecologists, P=.890]); birthweight <10th percentile (40.5% [traditional] vs 78.7% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P<.0001], 70.1% [International Society for the Study of Hypertension in Pregnancy maternal-fetal, P<.0001], 51.3% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.064], 46.3% [American College of Obstetricians and Gynecologists, P=.349])., Conclusion: Our findings present an evidence base for the broad definition of preeclampsia. Our data suggest that compared with a traditional definition, a broad definition of preeclampsia can better identify women and babies at risk of adverse outcomes. Compared with the American College of Obstetricians and Gynecologists definition, the more inclusive International Society for the Study of Hypertension in Pregnancy definition of maternal end-organ dysfunction seems to be more sensitive. The addition of uteroplacental dysfunction to the broad definition optimizes the identification of women and babies at risk, particularly when angiogenic factors are included., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Extracorporeal cardiopulmonary resuscitation (eCPR) is a rapidly growing treatment strategy due to significant improvement in selected patients' survival rates. Gender-related differences might impact the outcome of therapeutic measures. Therefore, we sought to investigate patients with eCPR at our interdisciplinary extracorporeal membrane oxygenation center regarding sex-related differences with the view to potentially adjusting current selection criteria. From January 2016 to December 2019, 71 patients underwent eCPR at our institution. Data before eCPR and early outcome parameters were analyzed comparing male and female patients. The cohort analyzed consisted of 60 male (84%) and 11 female (15%) patients. Comparing both groups, male patients significantly more frequently suffered out-of-hospital cardiac arrest (68% male vs. 36% female, P = .04), whereas female patients were associated with more in-hospital cardiac arrest (32% male vs. 64% female, P = .04). Creatinine levels differed significantly (1.5 (1.1;2.1) mg/dL in male vs. 1.0 (0.7;1.5) mg/dL in female patients, P = .03). Also, several hepatic parameters showed a significant difference between the groups: aspartate aminotransferase 423 (249;804) U/L in male vs. 115 (61;408) U/L in female patients, P = .01; alanine aminotransferase 174 (102;446) U/L in male vs. 86 (36;118) U/L in female patients, P = .01). Renal failure requiring hemodialysis occurred more frequently in men than in women (P < .01). There is a significant effect of male sex regarding renal failure with subsequent continuous venovenous hemodialysis (CVVH) (R 2  = 0.11, ANOVA P = .01, 95% CI = -0.79--0.079). However, in-hospital mortality was comparable between the groups (78% in male vs. 72% in female patients, P = .68). Our retrospective study showed several gender-related differences associated with different cardiac arrest scenarios. Male sex was associated with a significantly higher risk for renal failure requiring CVVH. Survival rates were comparable between the groups. Further investigations should include gender in the evaluation of risk stratification for eCPR-related complications to further improve selection criteria for this demanding therapy., (© 2020 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation and Wiley Periodicals LLC.)

Introduction: Evidence on vitamin D and parathyroid hormone (PTH) status in patients with early kidney impairment is limited. We aimed to determine the associations among kidney function, vitamin D, and PTH status in community-dwelling elderly patients with mild-to-moderate kidney impairment., Methods: Community-dwelling elderly patients were enrolled in this Institutional Review Board approved cross-sectional study. The eligibility criteria were as follows: age > 60 years, no recent hospitalization within the past 12 months, no conditions that affect vitamin D status including vitamin D supplementation, and eGFR > 30 mL/min/1.73 m 2 . Serum 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels were assessed., Results: A total of 226 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 26.61 ± 10.44 ng/mL and the mean serum PTH was 50.67 ± 22.67 pg/mL. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] and secondary hyperparathyroidism [PTH > 65 pg/mL] were 25.3% and 18.1%, respectively. Patients with eGFR 30- < 60 mL/min/1.73m 2 had significantly higher prevalence of 25(OH)D < 20 ng/mL (33.7% versus 19.4%, p < 0.05) than patients with eGFR ≥ 60 mL/min/1.73 m 2 . Multiple regression analysis showed independent negative association of serum PTH level with eGFR (mL/min/1.73 m 2 , β: - 0.261, 95% CI [- 0.408, - 0.114]) and serum 25(OH)D (ng/mL, β: - 0.499, 95% CI [- 0.775, - 0.223], adjusted for possible confounders)., Conclusions: The prevalence of vitamin D deficiency was higher in patients with eGFR 30 - < 60 mL/min/1.73 m 2 than those with eGFR ≥ 60 mL/min/1.73 m 2 . Both decreased serum 25(OH)D levels and decreased eGFR were independently associated with increased serum PTH levels among these patients.

In randomized clinical trials (RCTs) of nonvitamin K antagonist oral anticoagulants (NOACs) for acute venous thromboembolism (VTE), ~ 12-13% of patients were elderly and ~ 26% had mild-to-moderate renal impairment. Observational studies are not restricted by the selection and treatment criteria of RCTs. In this ancillary analysis of the RE-COVERY DVT/PE global observational study, we aimed to describe patient characteristics, comorbidities, and anticoagulant therapy for subgroups of age (< or ≥ 75 years) and renal impairment (creatinine clearance [CrCl; estimated with Cockcroft-Gault formula] < 30 [severe], 30 to < 50 [moderate], 50 to < 80 [mild], ≥ 80 [normal] mL/min). Of 6095 eligible patients, 25.3% were aged ≥ 75 years; 38.2% (1605/4203 with CrCl values) had mild-to-moderate renal impairment. Comorbidities were more common in older patients (73.9% aged ≥ 75 vs. 58.1% < 75 years) and in those with mild or moderate versus no renal impairment (75.9%, 80.9%, and 59.3%, respectively). At hospital discharge or 14 days after diagnosis (whichever was later), most patients (53.7% and 55.1%, respectively) in both age groups received NOACs; 20.8% and 23.4%, respectively, received vitamin K antagonists, 19.0% and 21.8% parenteral therapy, 2.3% and 3.8% other anticoagulant treatments. Use of NOACs decreased with worsening renal impairment (none 58.5%, moderate 49.6%, severe 25.7%) and, in younger versus older patients with moderate renal impairment (33.1% vs. 56.1%). In routine practice, there are more elderly and renally impaired patients with VTE than represented in RCTs. Decreasing renal function, but not older age, was associated with less NOAC use. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT02596230. Decreasing renal function, particularly in the subgroup with CrCl < 30 mL/min, but not older age, was associated with less use of nonvitamin K antagonist oral anticoagulants (NOACs). Nevertheless, more than half of the older patients with moderate renal impairment received a NOAC as their oral anticoagulant.

Objective: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC)., Patients and Methods: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m 2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes., Results: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m 2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m 2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m 2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m 2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m 2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001)., Conclusions: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

The prognostic significance of suPAR in various kidney diseases has recently been demonstrated. Its role in transplantation-specific outcomes is still largely unknown. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx). We included 100 patients who had received a kidney transplantation between 2013 and 2015. The plasma concentration of suPAR was measured by ELISA assay. In recipients of living donations (LD), pre-transplant suPAR levels were significantly lower than those of recipients of deceased donations (DD). After KTx, suPAR levels significantly declined in LD and DD recipients, without a detectable difference between both groups any more. Higher suPAR levels in recipients one year after KTx were associated with a more severe eGFR loss in the following three years in multivariable cox-regression (n = 82, p = 0.021). suPAR-levels above 6212 pg/ml one year after KTx are associated with eGFR loss > 30%, which occurred almost twice as fast as in patients with suPAR ≤ 6212 pg/ml (p < 0.001). Hence, suPAR level at one year mark might be a risk indicator of increased eGFR loss.

Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform's chemical library. A role for uremic solutes in pruritus remains to be established., Competing Interests: TWM has served as a consultant for Baxter. This does not alter our adherence to PLOS ONE policies on sharing data and materials.