Assessment Of Kidney Function Research Articles

Alleviation of High-Fat Diet-Induced Hyperlipidemia in Mice by Stachys sieboldii Miq. Huangjiu via the Modulation of Gut Microbiota Composition and Metabolic Function.

Hyperlipidemia is a chronic disease that is difficult to cure, and long-term pharmacotherapy may have negative consequences. Dietary therapy is a very promising strategy, and Chinese rice wine (Huangjiu) will play an important role because of its many biologically active components. In this work, the alleviating effect of Stachys sieboldii Miq. Huangjiu (CSCHJ) on high-fat diet-induced hyperlipidemia in mice was investigated, which is brewed from the wheat Qu with the addition of Stachys sieboldii Miq. and contains 15.54 g/L of polysaccharides. The experimental results showed that CSCHJ inhibited appetite, reduced body weight and blood sugar levels, and downregulated the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) while concurrently upregulating high-density lipoprotein cholesterol (HDL-C) in the high-fat diet-induced hyperlipidemia mice. At the same time, it was discovered that alcohol worsens hyperlipidemia symptoms and related physiological markers, implying that CSCHJ polysaccharides may play a role in hyperlipidemia treatment. Through the assessment of organ indices, liver and kidney function, and tissue staining, CSCHJ demonstrated efficacy in repairing liver, kidney, and colon mucosal damage in hyperlipidemic mice. Furthermore, 16S rDNA sequencing and gas chromatography studies revealed that CSCHJ effectively restored the intestinal microbial structure and enhanced the quantity of fecal short-chain fatty acids (SCFAs) in hyperlipidemic mice. Therefore, the alleviating effect of CSCHJ on hyperlipidemia in mice may be attributed to its regulation of energy metabolism by repairing liver, kidney, and colon mucosal damage and restoring the gut microbiota structure, among other mechanisms. Overall, our findings provide evidence that CSCHJ contains active ingredients capable of alleviating hyperlipidemia, thereby laying a theoretical foundation for the extraction of bioactive substances from Huangjiu for future medical or dietary use.

Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy.

The aim of this study is to assess the impact of serum magnesium (Mg) levels on prognostic outcomes in patients with non-small cell lung cancer (NSCLC) undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). A cohort comprising 91 patients with NSCLC with epidermal growth factor receptor mutations received EGFR-TKI therapy. Assessments of liver and kidney function and electrolyte levels were conducted before treatment initiation and after completing two cycles of EGFR-TKI therapy. Data on variables such as age, gender, presence of distant metastasis, smoking history, other therapeutic interventions, and the specific TKI used were collected for analysis. Cox regression analysis revealed that patients with higher Mg levels prior to EGFR-TKI therapy had significantly longer progression-free survival (PFS) and overall survival (OS). Elevated Mg levels remained predictive of PFS and OS after two cycles of EGFR-TKI therapy. Multiple regression analysis confirmed these findings. Additionally, it was observed that smokers might represent a unique population, demonstrating a correlation between OS and Mg levels. Our findings indicate that serum Mg level is a prognostic factor in patients with NSCLC undergoing EGFR-TKI therapy. This may provide new insights into the underlying mechanisms of EGFR-TKI therapy related to electrolyte balance.

The impact of obesity on body surface area adjusted estimated glomerular filtration rate in patients with chronic kidney disease.

Assessment of kidney function is necessary for prescribing renally excreted drugs. The estimated glomerular filtration rate (eGFR) routinely reported by laboratories is indexed to a body surface area (BSA) of 1.73 m2. In obese patients, the indexed eGFR may underestimate directly measured GFR. To determine the prevalence of obesity in patients with chronic kidney disease (CKD) and examine the effect of adjusting the indexed eGFR for patient BSA (deindexing) across CKD Stages 2-5. We conducted a cross-sectional study of 575 adults with stable CKD from two general nephrology clinics over 6 months. Dialysis and kidney transplant patients were excluded. We used four equations (Mosteller, Dubois, Haycock and Schlich) to determine BSA based on actual body weight and applied Bland-Altman plots and piecewise linear regression to examine the relationship between deindexed and indexed eGFR. The median age was 68 years (58% male). The prevalence of overweight and obesity was 31% and 47% respectively. Mean body mass index was 29.7 kg/m2. The Schlich equation for BSA produced the smallest adjustment in eGFR, while the Haycock equation produced the largest adjustment. Males experienced the largest change in eGFR from deindexing because of larger BSAs. Although bias became increasingly positive with higher eGFR, the linear regression stratified by CKD stage indicated that deindexing had little impact with eGFR <45 mL/min/1.73 m2. In CKD, deindexing the Chronic Kidney Disease Epidemiology Collaboration eGFR may not be necessary when the eGFR is <45 mL/min/1.73 m2, particularly if the patient is female.

Underrepresentation of black individuals in pivotal trials for novel anticancer drugs: Potential consequence of using estimated creatinine clearance to assess kidney function?

BackgroundBlack individuals are historically underrepresented in oncology clinical trials. One potential reason for this is the prevalence of kidney disease in Black individuals, utilization of estimated creatinine clearance as a surrogate for glomerular filtration rate (GFR) in oncology, and GFR-based trial eligibility criteria. We characterized the representation of racial minorities in anticancer agent pivotal trials and examined if GFR-based trial eligibility criteria impact the proportion of Black individuals in trial populations. MethodsWe constructed a data repository for anticancer drugs FDA-approved from 2015 to 2019 and associated pivotal trials, from which we extracted trial population racial compositions and GFR-based trial eligibility criteria. We calculated the participation-to-incidence ratio (PIR) and participation-to-mortality ratio (PMR) for a variety of cancer sites, where PIR or PMR >1.2 and <0.8 indicate overrepresentation and underrepresentation, respectively. We evaluated the relationship between GFR eligibility cutoffs and the proportion of Black enrollees with Spearman rank correlation coefficient. ResultsWe assessed 24,698 patients in 74 trials. Black individuals were underrepresented in all trials (PIR ≤0.48, PMR ≤0.50). For trials with GFR-based eligibility criteria (n = 49), a lower GFR cutoff was modestly associated with a higher proportion of Black enrollees (r = −0.29, p = 0.039). This relationship was strengthened for trials that only used estimated creatinine clearance to estimate GFR (r = −0.43, p = 0.004). ConclusionsGFR-related eligibility, and specifically the use of estimated creatinine clearance, may contribute to Black individuals being disproportionately excluded from cancer clinical trials. This highlights the need for implementation of contemporary GFR equations and other interventions to boost racial minority trial enrollment.

Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155

BackgroundChronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence.MethodsAmong the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization.ResultsCompared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs.ConclusionsOur work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.

Kidney function assessment using cystatin C and serum creatinine in heart transplantation recipients: Implications for valganciclovir dosing

BackgroundAmong heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in extrarenal variables (e.g., muscle mass). Cystatin C (cysC) is less influenced by muscle mass; however, obesity and steroid use may increase cysC levels. Herein, we: i) longitudinally compared changes in eGFRcysC and eGFRsCr among HT recipients; ii) investigated the association of body mass index (BMI), steroid use and muscle mass with discrepancies between eGFRs; and iii) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing. MethodscysC and sCr were measured in 294 blood samples obtained from 80 HT recipients. Intra-individual differences between eGFRs (eGFRdiffcysC-sCr) were calculated. Negative eGFRdiffcysC-sCr values correspond to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n=21), pectoralis muscle measures were derived from computed tomography scans. ResultsMarked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiffcysC-sCr -28 ml/min/1.73 m2). eGFRcysC demonstrated stability following a transient post-operative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiffcysC-sCr values. Conversely, pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiffcysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction. ConclusionsAmong HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.

Chinese expert consensus on the guidance of anti-tumor drugs for patients with tumor combined chronic kidney disease (2024 edition)

The incidence of malignant tumors has steadily increased year by year in China in recent decades. The emergence of innovative anti-cancer drugs has bolstered the prognosis of cancer patients, making it a chronic disease. Kidney injuries are frequent complications of cancer treatment clinically manifested as acute kidney injury (AKI), chronic kidney disease (CKD), proteinuria, and electrolyte disorders, etc. Although kidney injuries affect up to 50% of the patients, there is a lack of professional management guidance for anti-cancer drug dosage adjustment. The clinical pharmacology branch of the Chinese Medical Association has initiated the "Chinese expert consensus on the guidance of anti-tumor drugs for patients with tumor combined chronic kidney disease (2024 edition)". We unified national multidisciplinary experts to analyze clinical evidence with the Delphi method, and conducted expert interviews and seminars focusing on kidney function assessment, anti-tumor drug dosage adjustment for kidney disease patients. We make recommendations on selection and dose adjustment of anti-tumor drugs (chemotherapy, small molecules and antibodies) according to chemotherapeutic drug classifications, providing practical and feasible scientific guidance for clinicians.

Role of OPG/RANKL/RANK/TLR4 signaling pathway in sepsis-associated acute kidney injury

BackgroundSepsis-associated acute kidney injury (SA-AKI) has high mortality rates. The osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK)/Toll-like receptor 4 (TLR4) pathway and its potential role in SA-AKI pathogenesis remain to be fully understood. Herein, we addressed this issue using mouse models.MethodsAn SA-AKI mouse model was established using the cecal ligation and puncture method (CLP). Mice were grouped into sham, CLP model, CLP + recombinant RANKL, and CLP + anti-RANKL groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured to assess kidney function. ELISA was used to detect serum IL-1β, TNF-α, and IL-6 levels. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of OPG, RANKL, RANK, and TLR4 in kidney tissues. HE staining was performed to evaluate the pathological changes.ResultsThe CLP model group showed higher levels of Scr and BUN, indicating impaired kidney function in SA-AKI, compared to the sham group. Treatment with recombinant RANKL in the CLP + recombinant RANKL group reduced Scr and BUN levels, while anti-RANKL treatment in the CLP + anti-RANKL group elevated their levels. Moreover, the CLP model group had significantly increased IL-1β, TNF-α, and IL-6 than the sham group, indicating elevated inflammation in SA-AKI. The CLP + recombinant RANKL group demonstrated decreased cytokine levels, whereas the CLP + anti-RANKL group showed an increase. Additionally, the histopathological evaluation revealed distinct kidney tissue damage in the CLP model group. Recombinant RANKL treatment reduced this damage, while anti-RANKL treatment exacerbated it. Mechanically, the mRNA and protein expression of RANKL were significantly decreased, while those of OPG, RANK, and TLR4 were significantly increased in the CLP model group and the CLP + anti-RANKL group. Interestingly, treatment with recombinant RANKL reversed these changes, as evidenced by significantly increased RANKL but decreased OPG, RANK, and TLR4.ConclusionThe OPG/RANKL/RANK/TLR4 pathway is involved in SA-AKI pathogenesis. Recombinant RANKL treatment attenuates the inflammatory response and kidney tissue damage in SA-AKI, possibly via regulating this pathway. This pathway shows promise as a therapeutic target for SA-AKI.

Association between serum chloride levels and estimated glomerular filtration rate among US adults: evidence from NHANES 1999–2018

PurposeChloride, the predominant anion in extracellular fluid from humans, is essential to maintaining homeostasis. One important metric for thoroughly assessing kidney function is the estimated glomerular filtration rate (eGFR). However, the relationship between variations in serum chloride concentration and eGFR in general populations has been poorly studied. Therefore, the purpose of this study is to elucidate the correlation between serum chloride levels and eGFR within the United States’ adult population.MethodsThis cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES), which covered the years 1999–2018. We employed multiple linear regression analysis and subgroup analysis to evaluate the correlation between serum chloride concentration and eGFR. To examine the nonlinear association between serum chloride levels and eGFR, restricted cubic spline analyses were employed.ResultsData from 49,008 participants in this cohort study were used for the chloride analysis. In the comprehensively adjusted model, a noteworthy inverse relationship was discovered between chloride plasma concentration and eGFR. Restricted cubic spline analyses revealed a significant nonlinear relationship between chloride levels and eGFR (P for overall < 0.001 and P for nonlinear < 0.001). A significant interaction was observed between eGFR and plasma chloride concentration (all P < 0.001 for interaction) among the subgroups characterized by sex, household income to poverty ratio, BMI, hypertension, and diabetes.ConclusionOur findings suggest that higher levels of chloride plasma concentration were linked to decreased eGFR. These findings underscore the significance of monitoring chloride plasma concentration as a potential indicator for identifying individuals at risk of developing chronic kidney disease (CKD).

Evaluation of Renal Function in Living Kidney Donors by Isotopic Measurement of Glomerular Filtration Rate with 99mTc-DTPA

Introduction. Accurate assessment of kidney function in living kidney donors is essential prior to surgery. The aim of this study is to demonstrate the value of 99mTc DTPA isotope Glomerular Filtration Rate measurements (GFRmDTPA) in kidney donors compared to the estimated technique (GFReMDRD). Methods. 203 kidney donor’s candidates (119 women and 84 men) had a GFRmDTPA after intravenous injection of 37 MBq 99mTc-DTPA, followed by two blood samples at 2h and 4h post-injection. DFGmDTPA was compared to GFReMDRD and patients were classified according to KDIGO 2012 stages. Patients selected for transplantation were those with a GFR ≥ 80ml/min/1.73m2. Results. Mean GFRmDTPA was 93 ml/min/1.73m2 versus 95 ml/min/1.73m2 for GFReMDRD. 124 patients (61.1%) were at stage 1 with GFRmDTPA vs 113 by GFReMDRD (55.7%). 73 patients (36%) at stage 2 by GFRmDTPA vs 87 by GFReMDRD (42.9%). 6 patients (3%) were at stage 3 by GFRmDTPA and 3 by GFReMDRD (1.5%). A total of 151 patients achieved a GFRmDTPA ≥ 80ml/min/1.73m2 and selected into the transplant protocol, compared to 146 by GFReMDRD. 52 patients with GFRmDTPA less than 80ml/min/1.73m2 compared to 57 by estimated technique were rejected from the transplant protocol based on GFRmDTPA results. Conclusion. GFRmDTPA is a referent method in the evaluation and selection of potential kidney donors’ candidates with an impact on the transplant decision, but requires indications adapted to this population.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study

BackgroundChronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries.MethodsA retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months.ResultsOut of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing.ConclusionOur findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Association between exposure to metalworking fluid aerosols, occupational noise and chronic kidney disease: a cross-sectional study in China

BackgroundChronic kidney disease (CKD) carries a high public health burden yet little is known about the relationship between metalworking fluid (MWF) aerosols, occupational noise and CKD. We aimed to explore the relationship between occupational MWF aerosols, occupational noise and CKD.MethodsA total of 2,738 machinists were sampled from three machining companies in Wuxi, China, in 2022. We used the National Institute for Occupational Safety and Health (NIOSH) method 5524 to collect individual samples for MWF aerosols exposure, and the Chinese national standard (GBZ/T 189.8–2007) method to test individual occupational noise exposure. The diagnostic criteria for CKD were urinary albumin/creatinine ratio (UACR) of ≥ 30 mg/g and reduced renal function (eGFR < 60 mL.min− 1. 1.73 m− 2) lasting longer than 3 months. Smooth curve fitting was conducted to analyze the associations of MWF aerosols and occupational noise with CKD. A segmented regression model was used to analyze the threshold effects.ResultsWorkers exposed to MWF aerosols (odds ratio [OR] = 2.03, 95% confidence interval [CI]: 1.21–3.41) and occupational noise (OR = 1.77, 95%CI: 1.06–2.96) had higher prevalence of CKD than nonexposed workers. A nonlinear and positive association was found between increasing MWF aerosols and occupational noise dose and the risk of CKD. When daily cumulative exposure dose of MWF aerosols exceeded 8.03 mg/m3, the OR was 1.24 (95%CI: 1.03–1.58), and when occupational noise exceeded 87.22 dB(A), the OR was 1.16 (95%CI: 1.04–1.20). In the interactive analysis between MWF aerosols and occupational noise, the workers exposed to both MWF aerosols (cumulative exposure ≥ 8.03 mg/m3-day) and occupational noise (LEX,8 h ≥ 87.22 dB(A)) had an increased prevalence of CKD (OR = 2.71, 95%CI: 1.48–4.96). MWF aerosols and occupational noise had a positive interaction in prevalence of CKD.ConclusionsOccupational MWF aerosols and noise were positively and nonlinearly associated with CKD, and cumulative MWF aerosols and noise exposure showed a positive interaction with CKD. These findings emphasize the importance of assessing kidney function of workers exposed to MWF aerosols and occupational noise. Prospective and longitudinal cohort studies are necessary to elucidate the causality of these associations.

Assessment of Testosterone Levels, Kidney Function and Alkaline Phosphatase in Patients with Benign Prostatic Enlargement in Kirkuk City/Iraq

The present study is designed to evaluate the concentration of Testosterone, Creatinine, Urea urea, and alkaline phosphatase levels in patients with benign prostatic hyperplasia. This study was conducted for the period from the beginning of October 2023 to the end of February 2024 at Kirkuk Hospital. General and specialized medical clinics in the city of Kirkuk. The study included (70) males with benign prostatic hyperplasia, ages (45-75) years, and average weight (82) kg. In addition to 20 samples of healthy people with the same rate of ages and weights of patients, study samples were distributed as follows: The first group: the control group and included (20) healthy males, and the second group: the patient group and distributed to three groups according to the age groups first category ( 45-55) years and included 25 patients, the second age group (56-65) years and included 20 patients, the third age group (66-75) years and included 25 patients. The results of the current study showed a significant increase (p ≤ 0.05) in the concentration of urea, creatinine and alkaline phosphatase enzyme in patients with benign prostatic hyperplasia compared to healthy people, and the current study showed a significant decrease (P ≤ 0.05) in testosterone concentration in patients with benign prostatic hyperplasia compared to healthy people. According to age groups, the results showed no significant differences (p ≤ 0.05) in the concentrations of urea, creatinine and alkaline phosphatase enzyme in patients with prostatic hyperplasia, and the results showed a significant decrease (p≤ 0.05) in the concentration of testosterone according to the age groups of patients with benign prostatic hyperplasia.

A case of biopsy proven acute tubular injury from cyclin dependent kinase 4/6 inhibitor

Cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with endocrine therapy, stand as one of the preferred first-line treatment regimens for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. However, data regarding renal toxicities from CDK 4/6 inhibitors is conflicting. Some literature suggests a link to pseudo-acute kidney injury (AKI), while others indicate a potential intrinsic injury. These conflicting findings are compounded by the novelty of the treatment. We report a case of a 66-year-old woman with metastatic breast cancer who developed a true AKI on ribociclib, a CDK4/6 inhibitor. Upon evaluation, her urinalysis demonstrated proteinuria, and her serologic workup (including complements and free light chains) was within normal limits. Her Cystatin C-based eGFR was also found to be decreased. She ultimately underwent a kidney biopsy that demonstrated acute tubular injury (ATI). The etiology of her ATI was thought to be secondary to her CDK 4/6 inhibitor, as other factors causing ATI were ruled out. This case highlights that although much attention is put on CDK 4/6 inhibitors causing pseudo-AKI, it is imperative to ensure that patients are not experiencing true AKIs by assessing kidney function with alternative methods outside of creatinine, such as Cystatin C and exogenous filtration markers such as radionuclides, along with pursuing a renal biopsy when appropriate.

Biomarkers in acute kidney injury and cirrhosis

The use of biomarkers for managing acute kidney injury (AKI) is still not routinely used in clinical practice due to the lack of robust evidence on their impact on patient outcomes. In cirrhotic patients’ serum creatinine (sCr) limitations are more pronounced, as malnutrition, altered volume status, and muscle mass loss are more frequently encountered. This can make the diagnosis of AKI challenging, and therefore, additional markers may be necessary for a more accurate evaluation. This review will discuss the renal biomarkers of filtration and injury in patients with cirrhosis, focusing on their possible clinical application. A combined evaluation of a panel of biomarkers could provide a comprehensive assessment of kidney function and help distinguish between hepatorenal syndrome and chronic kidney disease in situations involving liver or combined liver and kidney transplantation. We will demonstrate that some biomarkers have more evidence of their utility in cirrhotic patients, such as cystatin C for filtration. In contrast, others require further studies, such as proenkephalin, which is only used in liver transplantation and appears superior to cystatin C as the inflammatory state does not influence it in cirrhotic patients. Interleukin-18 (IL-18) as a biomarker of injury in renal dysfunction in cirrhotic patients is still unclear despite extensive analysis in various scenarios, including liver diseases. On the other hand, the utility of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) is well established in renal dysfunction and evaluating other outcomes.

Challenges in the development of novel methodologies for measuring glomerular filtration rate

Measurement of glomerular filtration rate (GFR) is crucial in assessing kidney function status. Estimating GFR using clearance methodologies is cumbersome, as plasma and urinary concentrations and timed urine collections are required. Recently, a transcutaneous sensor has been developed whereby the rate of renal washout of a fluorescent marker administered intravenously allows calculation of GFR. The challenge is to ensure that the values of GFR obtained using the washout approach are in accord with those obtained conventionally.

Rapid Conductometric Sensing of Chronic Kidney Disease Biomarkers: Specific and Precise Detection of Creatinine and Cystatin C in Artificial Saliva

AbstractChronic kidney disease (CKD) has asymptomatic early stages, whereby early detection is crucial to prevent its complications and progression. Creatinine and cystatin C (cysC) assays are known for assessing kidney function but there are limited point‐of‐care diagnostics which are rapid, precise, and easy to use. Here, high resistivity silicon conductometric sensors for detection of creatinine and cysC with a 10 min sample incubation is introduced. The sensors provide resistance‐based signals that can be quantified and measured wirelessly. The sensors successfully detect creatinine and cysC in both phosphate buffer saline (PBS) and artificial saliva in the nanomolar range, being able to distinguish their critical concentrations at 8.8 and 20 nm, respectively, for diagnosis of early stage of CKD. The detection limit for both creatinine and cysC is determined as 0.01 nm which is more than 500× and 1000× times lower than critical concentrations for the two biomarkers, respectively. Finally, these sensors are incorporated into a battery‐free, miniaturized electronic device for wireless biomarker detection as a proof‐of‐concept demonstration of a point‐of‐care tool for assessing kidney functionality.

Formulae for estimation of kidney function as an approach to calculating drug doses: A scoping review

Background: The kidneys are the main organ for drug excretion, and it is critical to assess kidney function when designing dosage regimens for drugs that undergo renal elimination. Various formulae have been used to estimate kidney function and safely adjust doses. Objective: This research reviewed studies that assessed patients' kidney function with various approaches to provide appropriate choices of kidney function estimation formulas based on patients' age and clinical conditions. Method: The search involved browsing scientific articles in PubMed and ScienceDirect with the keywords (("assessment") AND ("GFR") AND ("formula")) OR ("renal function") AND ("human")) AND (“Creatinine”). The articles included were those available in full text and English. Thirty articles addressing the formulae for kidney function assessment were reviewed. Result: The Schwartz formula is more appropriate for pediatric and adult patients, whereas the creatinine-based chronic kidney disease epidemiology (CKD-EPI) formula can be used in geriatrics, obese patients, and patients already known to have decreased kidney function. The cystatin C-based CKD-EPI formula is for patients with HIV and post-transplant patients. Conclusion: This study identified that physiological conditions, especially patients’ age and pathology, should be considered in devising formulae to estimate kidney function to accurately calculate safe drug doses.

#377 Assessment of kidney function by creatinine and cystatin C and cardiovascular outcomes in patients with atrial fibrillation

Abstract Background and Aims Atrial fibrillation (AF) in patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin C has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Our aim was to evaluate the associations between kidney function, assessed by creatinine and cystatin C, and cardiovascular events (CVE), its individual components, and major bleedings. Method We enrolled 326 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin C were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin C (GFRcy) or both (GFRc2). Primary outcome was major CVE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of major CVE and major bleeding. Multivariable adjusted Cox regression analyses were built to evaluate the associations between kidney function and outcome events. Results Mean age was 56 ± 9 years and 37% were female. Mean creatinine and cystatin С levels were 112 ± 21 μmol/l and 1.6 ± 0.3 mg/l, respectively, translating to a GFRc2 of 58.2 ± 16.8 ml/min/1.73 m2. Over a median follow-up of 2 years, the incidence rates for major CVE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 23.1, 20.3, 17.6 and 14.7, respectively. When using multivariable adjusted Cox regression analysis, major CVE was significantly associated with GFRcr (per 1 standard deviation: HR 0.89 (95% CI 0.79; 0.98) p = 0.01), GFRcy (HR 0.65 (CI 0.53; 0.72), p &amp;lt; 0.001) and GFRc2 (HR 0.74 (CI 0.63; 0.82), p &amp;lt; 0.001). This association was mainly driven by cardiovascular death. Major bleeding was associated with GFRcy (HR 0.78 (0.64-0.93) p = 0.001) and GFRc2 (HR 0.82 (0.69-0.97), p = 0.01), but not with GFRcr (HR 0.93 (95% CI 0.83-1.1) p = 0.33). Conclusion Among AF patients, GFR equations including cystatin C were associated both with major CVE and bleeding events, while creatinine based GFR equations were only associated with major CVE. Therefore, Cystatin C based GFR equations might offer more comprehensive risk stratification in patients with AF.

RFLSE: Joint radiomics feature‐enhanced level‐set segmentation for low‐contrast SPECT/CT tumour images

AbstractDoctors typically use non‐contrast‐enhanced computed tomography (NCECT) in the treatment of kidney cancer to map kidney and tumour structural information to functional imaging single‐photon emission computed tomography, which is then used to assess patient kidney function and predict postoperative recovery. However, the assessment of kidney function and formulation of surgical plans is constrained by the low contrast of tumours in NCECT, which hinders the acquisition of accurate tumour boundaries. Therefore, this study designed a radiomics feature‐enhanced level‐set evolution (RFLSE) to precisely segment small‐sample low‐contrast kidney tumours. Integration of high‐dimensional radiomics features into the level‐set energy function enhances the edge detection capability of low‐contrast kidney tumours. The use of sensitive radiomics features to control the regional term parameters achieves adaptive adjustment of the curve evolution amplitude, improving the level‐set segmentation process. The experimental data used low‐contrast, limited‐sample tumours provided by hospitals, as well as the public datasets BUSI18 and KiTS19. Comparative results with advanced energy functionals and deep learning models demonstrate the precision and robustness of RFLSE segmentation. Additionally, the application value of RFLSE in assisting doctors with accurately marking tumours and generating high‐quality pseudo‐labels for deep learning datasets is demonstrated.