Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

Myeloid-derived Wnts play an indispensible role in macrophage and fibroblast activation and kidney fibrosis.

Wnt/ß-catenin signaling plays a pivotal role in the pathogenesis of chronic kidney diseases (CKD), which is associated with macrophage activation and polarization. However, the relative contribution of macrophage-derived Wnts in the evolution of CKD is poorly understood. Here we demonstrate a critical role of Wnts secreted by macrophages in regulating renal inflammation and fibrosis after various injuries. In mouse model of kidney fibrosis induced by unilateral ureteral obstruction (UUO), macrophages were activated and polarized to M1 and M2 subtypes, which coincided with the activation of Wnt/ß-catenin signaling. In vitro, multiple Wnts were induced in primary cultured bone marrow-derived macrophages (BMDMs) after polarization. Conversely, Wnt proteins also stimulated the activation and polarization of BMDMs to M1 and M2 subtype. Blockade of Wnt secretion from macrophages in mice with myeloid-specific ablation of Wntless (Wls), a cargo receptor that is obligatory for Wnt trafficking and secretion, blunted macrophage infiltration and activation and inhibited the expression of inflammatory cytokines. Inhibition of Wnt secretion by macrophages also abolished ß-catenin activation in tubular epithelium, repressed myofibroblast activation and reduced kidney fibrosis after either obstructive or ischemic injury. Furthermore, conditioned medium from Wls-deficient BMDMs exhibited less potency to stimulate fibroblast proliferation and activation, compared to the controls. These results underscore an indispensable role of macrophage-derived Wnts in promoting renal inflammation, fibroblasts activation and kidney fibrosis.

Exploration of Diagnostic Markers Associated with Inflammation in Chronic Kidney Disease Based on WGCNA and Machine Learning.

Chronic kidney disease (CKD) is a common disorder related to inflammatory pathways; its effective management remains limited. This study aimed to use bioinformatics analysis to find diagnostic markers that might be therapeutic targets for CKD. CKD microarray datasets were screened from the GEO database and the differentially expressed genes (DEGs) in CKD dataset GSE98603 were analyzed. Gene set variation analysis (GSVA) was used to explore the activity scores of the inflammatory pathways and samples. Algorithms such as weighted gene co-expression network analysis (WGCNA) and Lasso were used to screen CKD diagnostic markers related to inflammation. Then functional enrichment analysis of inflammation-related DEGs was performed. ROC curves were conducted to examine the diagnostic value of inflammation-related hub-genes. Lastly, quantitative real-time PCR further verified the prediction of bioinformatics. A total of 71 inflammation-related DEGs were obtained, of which 5 were hub genes. Enrichment analysis showed that these genes were significantly enriched in inflammation-related pathways (NF-κB, JAK-STAT, and MAPK signaling pathways). ROC curves showed that the 5 CKD diagnostic markers (TIGD7, ACTA2, ACTG2, MAP4K4, and HOXA11) also exhibited good diagnostic value. In addition, TIGD7, ACTA2, ACTG2, and HOXA11 expression was downregulated while MAP4K4 expression was upregulated in LPS-induced HK-2 cells. The present study identified TIGD7, ACTA2, ACTG2, MAP4K4, and HOXA11 as reliable CKD diagnostic markers, thereby providing a basis for further understanding of CKD in clinical treatments.

UroAngel: a single-kidney function prediction system based on computed tomography urography using deep learning.

BACKGROUND: Accurate estimation of the glomerular filtration rate (GFR) is clinically crucial for determining the status of obstruction, developing treatment strategies, and predicting prognosis in obstructive nephropathy (ON). We aimed to develop a deep learning-based system, named UroAngel, for non-invasive and convenient prediction of single-kidney function level. METHODS: We retrospectively collected computed tomography urography (CTU) images and emission computed tomography diagnostic reports of 520 ON patients. A 3D U-Net model was used to segment the renal parenchyma, and a logistic regression multi-classification model was used to predict renal function level. We compared the predictive performance of UroAngel with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and two expert radiologists in an additional 40 ON patients to validate clinical effectiveness. RESULTS: UroAngel based on 3D U-Net convolutional neural network could segment the renal cortex accurately, with a Dice similarity coefficient of 0.861. Using the segmented renal cortex to predict renal function stage had high performance with an accuracy of 0.918, outperforming MDRD and CKD-EPI and two radiologists. CONCLUSIONS: We proposed an automated 3D U-Net-based analysis system for direct prediction of single-kidney function stage from CTU images. UroAngel could accurately predict single-kidney function in ON patients, providing a novel, reliable, convenient, and non-invasive method.

Assessment and Risk Prediction of Chronic Kidney Disease and Kidney Fibrosis Using Non-Invasive Biomarkers.

Effective management of chronic kidney disease (CKD), a major health problem worldwide, requires accurate and timely diagnosis, prognosis of progression, assessment of therapeutic efficacy, and, ideally, prediction of drug response. Multiple biomarkers and algorithms for evaluating specific aspects of CKD have been proposed in the literature, many of which are based on a small number of samples. Based on the evidence presented in relevant studies, a comprehensive overview of the different biomarkers applicable for clinical implementation is lacking. This review aims to compile information on the non-invasive diagnostic, prognostic, and predictive biomarkers currently available for the management of CKD and provide guidance on the application of these biomarkers. We specifically focus on biomarkers that have demonstrated added value in prospective studies or those based on prospectively collected samples including at least 100 subjects. Published data demonstrate that several valid non-invasive biomarkers of potential value in the management of CKD are currently available.

Iron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction.

Chronic kidney disease (CKD) affects around 850 million people worldwide, posing significant challenges in healthcare due to complications like renal anemia, end-stage kidney disease, and cardiovascular diseases. This review focuses on the intricate interplay between iron metabolism, inflammation, and renal dysfunction in CKD. Renal anemia, prevalent in CKD, arises primarily from diminished erythropoietin (EPO) production and iron dysregulation, which worsens with disease progression. Functional and absolute iron deficiencies due to impaired absorption and chronic inflammation are key factors exacerbating erythropoiesis. A notable aspect of CKD is the accumulation of uremic toxins, such as indoxyl sulfate (IS), which hinder iron metabolism and worsen anemia. These toxins directly affect renal EPO synthesis and contribute to renal hypoxia, thus playing a critical role in the pathophysiology of renal anemia. Inflammatory cytokines, especially TNF-α and IL-6, further exacerbate CKD progression and disrupt iron homeostasis, thereby influencing anemia severity. Treatment approaches have evolved to address both iron and EPO deficiencies, with emerging therapies targeting hepcidin and employing hypoxia-inducible factor (HIF) stabilizers showing potential. This review underscores the importance of integrated treatment strategies in CKD, focusing on the complex relationship between iron metabolism, inflammation, and renal dysfunction to improve patient outcomes.

Incidence, risk factors, and outcomes of the transition of HIPEC-induced acute kidney injury to acute kidney disease: a retrospective study.

BACKGROUND: Acute kidney injury (AKI) is recognized as a common complication following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Characterized by prolonged renal function impairment, acute kidney disease (AKD) is associated with a higher risk of chronic kidney disease (CKD) and mortality. METHODS: From January 2018 to December 2021, 158 patients undergoing CRS-HIPEC were retrospectively reviewed. Patients were separated into non-AKI, AKI, and AKD cohorts. Laboratory parameters and perioperative features were gathered to evaluate risk factors for both HIPEC-induced AKI and AKD, with the 90-day prognosis of AKD patients. RESULTS: AKI developed in 21.5% of patients undergoing CRS-HIPEC, while 13.3% progressed to AKD. The multivariate analysis identified that ascites, GRAN%, estimated glomerular filtration rate (eGFR), and intraoperative (IO) hypotension duration were associated with the development of HIPEC-induced AKI. Higher uric acid, lessened eGFR, and prolonged IO hypotension duration were more predominant in patients proceeding with AKD. The AKD cohort presented a higher risk of 30 days of in-hospital mortality (14.3%) and CKD progression (42.8%). CONCLUSIONS: Our study reveals a high incidence of AKI and AKI-to-AKD transition. Early identification of risk factors for HIPEC-induced AKD would assist clinicians in taking measures to mitigate the incidence.

Trying to understand the illness: A qualitative investigation of health literacy of patients undergoing maintenance hemodialysis.

Limited health literacy is high among patients with chronic kidney disease, which can pose challenges in health care. Evidence of health literacy in Indonesia, particularly regarding patients undergoing hemodialysis, is lacking. In this study, we aimed to explore health literacy in adult patients undergoing maintenance hemodialysis. An inductive qualitative study was conducted. Individual semi-structured interviews were conducted with 10 adult patients undergoing hemodialysis, four family caregivers, and four healthcare professionals. Interviews were transcribed verbatim and analyzed thematically. Three themes emerged from the data: "Trying to understand the illness," "searching and obtaining health information," and "applying health information." Understanding and accepting the illness included raising awareness of the changes in their lives and accepting these changes. Participants actively sought information from healthcare professionals and other sources and used it carefully. Behavioral changes included patients' adherence to therapy, although participants often felt bored during the illness trajectory. Understanding the illness and being willing to seek and critically evaluate health information before implementing it are important. These aspects may affect patient outcomes and require further intervention and research.

Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults.

BACKGROUND: Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults. METHODS: In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD. RESULTS: In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20-3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01-3.12). CONCLUSIONS: This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.

Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

BACKGROUND: Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. OBJECTIVE: To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). DESIGN: Multicenter prospective cohort study. SETTING: 7 U.S. clinical centers. PARTICIPANTS: 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. MEASUREMENTS: Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. RESULTS: Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. LIMITATION: UACR was measured once. CONCLUSION: Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. PRIMARY FUNDING SOURCE: None.

In CKD, empagliflozin reduced kidney disease progression at a median 2 y, regardless of primary kidney disease type.

SOURCE CITATION: EMPA-KIDNEY Collaborative Group. Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol. 2024;12:51-60. 38061372.

Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION.

BACKGROUND: We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France. METHODS AND RESULTS: CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2 819 655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining International Classification of Diseases, Tenth Revision (ICD-10) coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes. CONCLUSIONS: Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.

Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

Relationship of plasma 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid concentration with OATP1B activity in patients with chronic kidney disease.

Organic anion-transporting polypeptides (OATP)1B are drug transporters mainly expressed in the sinusoidal membrane. Many studies have suggested that OATP1B activity is affected by genetic factor, the uremic toxin 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Coproporphyrin-I (CP-I) is spotlighted as a highly accurate endogenous substrate of OATP1B. We previously reported a positive correlation between plasma CMPF and CP-I concentrations in patients with chronic kidney disease (CKD). The present study evaluated the impact of genetic polymorphisms, CMPF, IL-6, TNF-α, and estimated glomerular filtration rate (eGFR) on individual differences in OATP1B activity in patients with CKD. Seventy-three patients with CKD who received kidney transplant at least 3 months earlier were analyzed. Plasma CP-I concentration was higher in OATP1B1*15 carriers than in non-carriers. In all patients, CP-I did not correlate significantly with CMPF, IL-6, TNF-α, or eGFR. However, when the dataset was cut off at CMPF concentration of 8 and 7 µg/mL, 4 µg/mL, 3 µg/mL or 2 µg/mL, CMPF correlated positively with CP-I, and correlation coefficient tended to be higher as plasma CMPF concentration was lower. In conclusion, OATP1B1*15 impacted OATP1B activity in patients with CKD, but IL-6 and TNF-α did not. However, the impact of CMPF on OATP1B activity was limited to low CMPF concentrations, and the effect could be saturated at high concentrations. When prescribing an OATP1B substrate drug for patients with CKD, the OATP1B1*15 carrier status and plasma CMPF concentration may need to be considered to decide the dose regimen.

Exploring the Preventive and Therapeutic Mechanisms of Probiotics in Chronic Kidney Disease through the Gut-Kidney Axis.

Gut dysbiosis contributes to deterioration of chronic kidney disease (CKD). Probiotics are a potential approach to modulate gut microbiota and gut-derived metabolites to alleviate CKD progression. We aim to provide a comprehensive view of CKD-related gut dysbiosis and a critical perspective on probiotic function in CKD. First, this review addresses gut microbial alterations during CKD progression and the adverse effects associated with the changes in gut-derived metabolites. Second, we conduct a thorough examination of the latest clinical trials involving probiotic intervention to unravel critical pathways via the gut-kidney axis. Finally, we propose our viewpoints on limitations, further considerations, and future research prospects of probiotic adjuvant therapy in alleviating CKD progression. Enhancing our understanding of host-microbe interactions is crucial for gaining precise insights into the mechanisms through which probiotics exert their effects and identifying factors that influence the effectiveness of probiotics in developing strategies to optimize their use and enhance clinical outcomes.

Myosteatosis and aortic calcium score on abdominal CT as prognostic markers in non-dialysis chronic kidney disease patients.

We aimed to examine the relationship between abdominal computed tomography (CT)-based body composition data and both renal function decline and all-cause mortality in patients with non-dialysis chronic kidney disease (CKD). This retrospective study comprised non-dialysis CKD patients who underwent consecutive unenhanced abdominal CT between January 2010 and December 2011. CT-based body composition was measured using semiautomated method that included visceral fat, subcutaneous fat, skeletal muscle area and density, and abdominal aortic calcium score (AAS). Sarcopenia and myosteatosis were defined by decreased skeletal muscle index (SMI) and decreased skeletal muscle density, respectively, each with specific cutoffs. Risk factors for CKD progression and survival were identified using logistic regression and Cox proportional hazard regression models. Survival between groups based on myosteatosis and AAS was compared using the Kaplan-Meier curve. 149 patients (median age: 70 years) were included; 79 (53.0%) patients had sarcopenia and 112 (75.2%) had myosteatosis. The median AAS was 560.9 (interquartile range: 55.7-1478.3)/m2. The prognostic factors for CKD progression were myosteatosis [odds ratio (OR) = 4.31, p = 0.013] and high AAS (OR = 1.03, p = 0.001). Skeletal muscle density [hazard ratio (HR) = 0.93, p = 0.004] or myosteatosis (HR = 4.87, p = 0.032) and high AAS (HR = 1.02, p = 0.001) were independent factors for poor survival outcomes. The presence of myosteatosis and the high burden of aortic calcium were significant factors for CKD progression and survival in patients with non-dialysis CKD.

Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.