Metformin, widely used for type 2 diabetes, raises concerns about its use in chronic kidney disease (CKD) due to risks like lactic acidosis and renal function impact. This study uses Mendelian randomization (MR) and summary data-based MR (SMR) to explore metformin's potential causal relationship with CKD and associated genes.

We employed MR methods (MR-Egger, weighted median, IVW) and sensitivity analyses to explore the causal relationship between metformin and CKD. SMR was used to analyze eQTL and CKD data from the UK Biobank and FinnGen, intersecting these with metformin drug targets to identify genes associated with CKD.

MR analysis indicated that metformin may increase CKD risk (IVW model: OR = 144.67, p < 0.01). However, given the high OR value, additional studies are warranted to validate this finding. SMR identified genes ANPEP, STK11, ACACB, and RPS6KB as significantly associated with CKD risk.

The study suggests metformin could elevate CKD risk and identifies relevant genes. Clinicians should exercise caution when prescribing metformin, particularly for patients with renal issues. Further research is needed to confirm these findings and guide clinical practices.

There is a lack of evidence to suggest that outcomes of adolescent and adult-onset glomerular disease differ. Still, most glomerular disease trials include adults but exclude adolescents.

We designed a retrospective study using the CureGN database to compare individuals with adolescent-onset glomerular disease relative to individuals with older and younger age at onset. The two main outcomes were sustained proteinuria remission off immunosuppression treatment and composite eGFR decline.

Our data did not show a significant difference in sustained proteinuria remission off treatment or composite eGFR decline between adolescent onset glomerular disease and either childhood (age 5-12), young adult (age 20-29), or adult (age 30-39) onset glomerular disease. Having high-risk APOL1 alleles and hypertension at the time of study enrollment decreased the likelihood of achieving sustained proteinuria remission off treatment. While participants with minimal change disease and IgA nephropathy were similarly likely to achieve sustained proteinuria remission off treatment, participants with focal segmental glomerulosclerosis and membranous nephropathy were less likely to achieve sustained proteinuria remission off treatment compared to participants with minimal change disease. CKD stage, high-risk APOL1 alleles, hypertension stage, and education all significantly impacted the likelihood of progression to the composite eGFR decline outcome.

Approximately 25% of each age cohort reached the composite eGFR decline outcome within 5 years. As more glomerular disease clinical trials become available, we must consider opening these trials to people with childhood and adolescent onset disease since like adults they are at high risk of progressive kidney function decline.

Application of machine learning-based methods to identify novel bacterial enzymes capable of degrading a wide range of xenobiotics offers enormous potential for bioremediation of toxic and carcinogenic recalcitrant xenobiotics such as pesticides, plastics, petroleum, and pharmacological products that adversely impact ecology and health. Using 6814 diverse substrates involved in ∼141 200 biochemical reactions, we have developed 'XenoBug', a machine learning-based tool that predicts bacterial enzymes, enzymatic reaction, the species capable of biodegrading xenobiotics, and the metagenomic source of the predicted enzymes. For training, a hybrid feature set was used that comprises 1603 molecular descriptors and linear and circular fingerprints. It also includes enzyme datasets consisting of ∼3.3 million enzyme sequences derived from an environmental metagenome database and ∼16 million enzymes from ∼38 000 bacterial genomes. For different reaction classes, XenoBug shows very high binary accuracies (>0.75) and F1 scores (>0.62). XenoBug is also validated on a set of diverse classes of xenobiotics such as pesticides, environmental pollutants, pharmacological products, and hydrocarbons known to be degraded by the bacterial enzymes. XenoBug predicted known as well as previously unreported metabolic enzymes for the degradation of molecules in the validation set, thus showing its broad utility to predict the metabolism of any input xenobiotic molecules. XenoBug is available on: https://metabiosys.iiserb.ac.in/xenobug.

To assess the association between Body Roundness Index (BRI) and chronic kidney disease (CKD) risk in individuals with diabetes.

A cross-sectional analysis of 6,971 individuals with diabetes from NHANES 1999-2018 was conducted. BRI was calculated using waist circumference and height. CKD was defined as eGFR < 60 mL/min/1.73 m2 or ACR ≥ 30 mg/g. Weighted multivariable logistic regression assessed the BRI-CKD association. Subgroup and mediation analyses assessed heterogeneity and potential pathways.

Higher BRI was independently associated with increased CKD risk. In fully adjusted models, each unit increase in BRI corresponded to 10.5 % higher odds of CKD (OR: 1.109; 95 % CI: 1.040-1.183; p = 0.002). Stronger associations were found in males, younger individuals, and those with elevated blood pressure or uric acid. An inverse association was observed in participants with severe proteinuria. Mediation analysis showed partial effects through HbA1c (3.9 %), serum creatinine (27.7 %), and albumin (-26.2 %).

BRI is an independent marker of CKD risk in individuals with diabetes and may reflect contributions from glycaemic control, kidney function, and nutritional status. It may serve as a practical tool for CKD risk stratification.

Chronic kidney disease (CKD) associates with high morbidity and mortality due to CKD progression and cardiovascular disease (CVD). Blood pressure (BP) lowering reduces the risk of CVD and CKD progression. Despite the large number of BP medications available, a significant proportion of patients with CKD have BP above the goal. The current practice involves licensed providers performing medication titrations to achieve BP goals and is associated with limited patient engagement. Here, we evaluate the effectiveness of pharmacist-guided patient-driven titration of BP medications in CKD.

Randomized clinical trial.

One hundred and sixty Veterans with uncontrolled hypertension and either stage 2 CKD with albuminuria or stage 3 or 4 CKD are recruited from the Iowa City VA Healthcare system.

Subjects are randomized to the pharmacist self-guided management arm or the self-monitoring arm for 12 months.

This is a mixed methods study. The primary outcome is change in standardized office systolic BP at 12 months. Secondary outcomes include change in standardized office diastolic BP, change in home systolic and diastolic BPs, change in conventional office systolic and diastolic BPs, and emergency room visits for uncontrolled hypertension or hypertensive emergency. The study team will conduct semi-structured interviews to evaluate the acceptability and the adherence to the self-management approach to Veterans and to assess potential barriers and facilitators to implementation of the self-management approach.

NCT05546099.

Chronic kidney disease (CKD) is a global health epidemic that greatly increases mortality due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiac injury in CKD. High serum levels of fibroblast growth factor (FGF) 23 in patients with CKD may contribute mechanistically to the pathogenesis of LVH by activating FGF receptor (FGFR) 4 signaling in cardiac myocytes. Mitochondrial dysfunction and cardiac metabolic remodeling are early features of cardiac injury that predate development of hypertrophy, but these mechanisms have been insufficiently studied in models of CKD. We found in wild-type mice with CKD induced by adenine diet, that morphological changes occurred in mitochondrial structure and cardiac mitochondrial and that metabolic dysfunction preceded the development of LVH. In bioengineered cardio-bundles and neonatal rat ventricular myocytes grown in vitro, FGF23-mediated activation of FGFR4 caused mitochondrial pathology, characterized by increased bioenergetic stress and increased glycolysis that preceded the development of cellular hypertrophy. The cardiac metabolic changes and associated mitochondrial alterations in mice with CKD were prevented by global and cardiac-specific deletion of FGFR4. Our findings indicate that metabolic remodeling and mitochondrial dysfunction are early cardiac complications of CKD that precede structural remodeling of the heart. Mechanistically, FGF23-mediated activation of FGFR4 causes mitochondrial dysfunction, suggesting that early pharmacologic inhibition of FGFR4 might serve as novel therapeutic intervention to prevent development of LVH and heart failure in patients with CKD.

Accurate cardiovascular (CV) risk prediction tools may heighten awareness and monitoring, improve the use of evidence-based therapies and help inform shared decision making for patients with chronic kidney disease (CKD). The purpose of this study was to develop and externally validate a risk prediction model for incident and recurrent CV events across all stages of CKD using commonly available demographics and laboratory data.

A series of models were developed using administrative and laboratory data (n=36,317) from Manitoba, Canada, between April 1, 2006, and December 31, 2018, with external validation in health system's data from Alberta, Canada (n=95,191), and Stockholm, Sweden (n=83,000). Adults with incident CKD stages G1-G4 were followed for the occurrence of major adverse cardiovascular events (MACE) (myocardial infraction, stroke, and CV death), and MACE including hospitalization for heart failure (MACE+). Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUC), Brier scores, and plots of observed vs predicted risk, and the models were compared to an existing model from the Chronic Renal Insufficiency Cohort (CRIC).

In the Alberta cohort, the AUCs for predicting MACE and MACE+ were 0.77 (0.77-0.77) and 0.80 (0.79-0.80), respectively. In the Stockholm cohort, the model achieved an AUC of 0.87 (0.86-0.87) for predicting MACE and 0.88 (0.88-0.88) for MACE+. Overall performance was improved relative to CRIC.

A model including commonly available administrative data and laboratory results can predict the risk of MACE and MACE+ outcomes among individuals with CKD.

Renal protection is a frequent indication for urological surgery in pediatric patients; however, preoperative assessment is not routinely performed. We assessed the rates of preoperative renal function testing and stratified outcomes after major pediatric urological surgery. Pediatric urology patients, specifically high-risk patients undergoing genitourinary surgeries, are likely to have an underdiagnosis of renal dysfunction after surgery.

Cases were identified from the 2012 to 2019 National Surgical Quality Improvement Program-Pediatric database. Patients who underwent major urological surgery on an inpatient basis were included in this study. Abnormal renal function was defined as a creatinine (Cr) level of ≥0.5 mg/dL (younger than 2 years) and a glomerular filtration rate of <90 mL/min (2 years or older). Glomerular filtration rate was calculated using the bedside Schwartz equation (2 years or older): estimated glomerular filtration rate = 0.413 × (height/Cr).

A total of 17,315 patients were included, of whom 3792 (21.9%) had documented Cr values. Based on the defined criteria, abnormal renal function was found in 7.3% of infants (younger than 2 years), 6.3% of children (2-9 years), and 15.0% of adolescents (10-18 years). Patients with abnormal preoperative renal function values were significantly (p < 0.001) more likely to experience readmission (10.2% vs. 5.8%), reoperation (3.7% vs. 1.6%), surgical organ/space infection (0.9% vs. 0.4%), transfusion (1.5% vs. 0.6%), renal insufficiency (1.6% vs. 0.4%), or urinary tract infection (5.1% vs. 3.6%).

In this pediatric population, 21.9% of the patients had documented preoperative Cr values before major urological surgery. Patients with documented abnormal preoperative renal function tests experienced higher complication rates. These patients have higher rates of progressive renal insufficiency and acute renal failure than those with normal renal function. The introduction of a standardized and unbiased risk assessment tool has the potential to offer patients benefits by pinpointing individuals with a heightened risk of complications. Further investigation is necessary to enhance the precise categorization of at-risk patients.

The accuracy of the latest generation Dexcom G7 sensors in individuals with diabetes undergoing hemodialysis has not previously been investigated. Participants with diabetes undergoing hemodialysis were recruited, with paired sensor glucose from Dexcom G7 recorded with plasma glucose analyzed in the laboratory, as well as the Freestyle Precision Pro glucometer and EKF Biosen C-Line analyzer. Ten adults (median age 64.0 [58.0-74.5] years) were recruited. Overall percentage (%) mean and median absolute relative differences were 10.4% and 8.5% for matched laboratory pairs, respectively (n = 720). Diabetes Technology Society error grid analysis showed 99.7%, 100%, and 99.9% of pairs within zones A and B for lab, glucometer, and EKF methods, respectively. This, the first Dexcom G7 accuracy study conducted in people on hemodialysis, demonstrates accuracy and safety when compared with lab reference readings. These data support the accessibility of continuous glucose monitoring (CGM) and hybrid closed-loop systems for people with diabetes on hemodialysis.

Background & Objectives: Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). Materials and Methods: This prospective study included Caucasian IgAN patients diagnosed within the last 5 years, who had started a 10-month TRB treatment and were followed in the outpatient clinic. All participants had been on the maximal supportive care dose for at least the previous 6 months. Kidney function and proteinuria levels were recorded at the start of TRB treatment (T0) and at 3, 6, and 10 months (T3, T6, and T10, respectively), while urinary monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and clusterin (CLU) levels were measured at T0 and T3. Results: In the cohort of all patients (mean age 53.24 ± 12.76 years, estimated glomerular filtration rate (eGFR 52.84 ± 25.93 mL/min/1.73 m2, proteinuria 2.84 ± 1.26 g/24 h), significant correlations were observed at T0 between MMP-9 and MCP-1 (r = 0.74, p = 0.004), MMP-9 and uCLU (r = 0.77, p = 0.002), and MCP-1 and uCLU (r = 0.65, p = 0.01). At T3, a significant correlation between MMP-9 and urinary CLU (uCLU) persisted (r = 0.71, p = 0.03). Higher MCP-1 (r = -0.560, p = 0.046) and MMP-9 (r = -0.330, p = 0.012) levels at T0 were associated with reduced proteinuria. Conversely, increased clusterin at T3 (r = 0.599, p = 0.031) was associated with worsening proteinuria. Conclusions: The treatment response to TRB was heterogeneous, with recent diagnosis (RD) patients showing improved kidney function and proteinuria, while older diagnosis (OD) patients exhibited worsening biomarkers and declining kidney function. Therefore, early interventions are crucial in IgAN patients. Finally, the biomarkers studied can be used prognostically to monitor disease progression.

This study investigated how changes in metabolic phenotype, defined by obesity and metabolic health, impact chronic kidney disease (CKD) development in a large cohort.

A retrospective cohort study analyzed health data collected between 2011 and 2021 from 84,729 Panasonic Holdings Corporation (formerly Panasonic Corporation) employees aged ≥40 years. Metabolic phenotypes were classified as metabolically healthy with no obesity (MHNO), metabolically healthy with obesity (MHO), metabolic abnormalities with no obesity (MANO), and metabolic abnormalities with obesity (MAO). Changes in metabolic phenotype over 3 years and their association with CKD development were assessed using Cox proportional hazards models adjusted for confounding variables.

During a mean follow-up of 5.1 years, a total of 12,172 of participants (14.4%) developed CKD. Transitioning from MHO to MHNO and from MAO to MANO did not reduce CKD risk compared to each stable group. In contrast, participants in the MANO-to-MHNO and MAO-to-MHO groups significantly lowered CKD risk relative to each stable group, with hazard ratios of 0.86 (95% CI: 0.77-0.96) and 0.83 (95% CI: 0.67-1.02), respectively. The same results were observed when a rapid decline in renal function was used as the outcome.

The improvement of metabolic profile might outweigh weight reduction in CKD risk.

Predicting the progression of chronic kidney disease (CKD) to end-stage kidney disease (ESKD) is crucial for improving patient outcomes.

To reveal the highly predictive activity of serum bilirubin levels for the progression of CKD to ESKD, and to develop and validate a novel ESKD prediction model incorporating serum bilirubin levels.

We assessed the relative importance of 20 candidate predictors for ESKD, including serum bilirubin levels, in a CKD cohort (15 ≤ estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2), and subsequently developed a prediction model using the selected variables. The development cohort comprised 4103 individuals with CKD who underwent follow-up at Kyushu University Hospital, Japan, from 2008 to 2018. The primary outcome was incident ESKD, defined as an eGFR < 15 mL/min/1.73 m2, chronic dialysis, or renal transplantation.

The mean follow-up time was 7.0 ± 4.2 years, during which 489 individuals (11.9%) progressed to ESKD. The Cox proportional hazard model selected eGFR, serum bilirubin, proteinuria, age, diabetes, gender, hypertension, serum albumin, and hemoglobin in order of their importance. The predictive performance of the model was optimized by incorporating these 9 variables in discrimination evaluated by time-dependent area under the curve (AUC). This model also demonstrated excellent calibration. Additionally, this model exhibited excellent predictive performance in both discrimination (2-year AUC: 0.943, 5-year AUC: 0.935) and calibration in a validation cohort (n = 2799).

Serum bilirubin levels were strong predictors for the progression of CKD to ESKD. Our novel model that incorporates serum bilirubin levels could accurately predict ESKD in individuals with CKD.

Aortic valve calcium (AVC) is associated with increased risk of mortality, cardiovascular disease (CVD), non-CVD such as dementia. Traditional atherosclerotic CVD risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown.

To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of CVD.

We examined 6346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m2. AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m2 accompanied with an at least 40 % decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable adjusted Cox proportional hazard regression models to examine the association between AVC (categorical and log-transformed) and incident CKD.

Participants had a mean age 62.2 ± 10.1 years, 53 % were women, and AVC >0 was present in 795 (12 %) participants. During a median follow-up time of 16.9 years, 982 (15 %) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95 % CI: 1.02-1.10]; p = 0.005). Kaplan-Meier models showed a higher cumulative incidence for CKD with higher AVC levels. In the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95 % CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score (p = 0.024), Lp(a) (p = 0.004), and the APOE-ε4 genotype (p = 0.004).

In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD. Further work is needed to understand the multidirectional relationship between AVC, CKD, and atherosclerosis.

This study aims to investigate the association and causality between osteoarthritis (OA) and chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian Randomization (MR) analysis. Participants with OA, urinary albumin, urinary creatinine, urinary albumin-to-creatinine ratio (UACR), blood creatinine, and estimated glomerular filtration rate (eGFR) were selected from NHANES. CKD was calculated using the CKD-EPI equation, and logistic regression assessed by the OA-CKD association. A two-sample MR analysis was conducted using Genome-wide association studies (GWAS) data for OA, hip OA (HOA), knee OA (KOA), acute renal failure (ARF), chronic renal failure (CRF), cystatin C, serum creatinine (eGFRcrea), and microalbuminuria. The inverse variance weighted (IVW) method was used, with heterogeneity, sensitivity, and pleiotropy assessments. The cross-sectional analysis showed a significant positive association between OA and CKD [unadjusted OR: 2.398 (95% CI: 2.176-2.643), p < 0.001], which persisted after adjustment for demographic factors, socioeconomic status, lifestyle factors, and medical history [adjusted OR: 1.161 (95% CI: 1.029-1.310), p = 0.015]. The MR analysis revealed no significant causal relationship between overall OA and renal function markers but found a significant genetic association between HOA and cystatin C [IVW p = 0.0014, OR = 1.02, 95% CI: 1.01-1.03], and between KOA and cystatin C [IVW p < 0.0001, OR = 1.06, 95% CI: 1.04-1.08]. Our study indicates that HOA and KOA are risk factors for renal function injury, providing new insights for clinical OA management.

Individuals with chronic kidney disease (CKD) exhibit an increased risk for the development of cardiovascular disease (CVD) with its manifestations coronary artery disease, stroke, heart failure, arrhythmias, and sudden cardiac death. The presence of both, CVD and CKD has a major impact on the prognosis of patients. This association likely reflects the involvement of several pathophysiological mechanisms, including shared risk factors (e.g. diabetes and hypertension), as well as other factors such as inflammation, anaemia, volume overload, and the presence of uraemic toxins. Identifying and characterizing CKD is crucial for appropriate CVD risk prediction. Mitigating CVD risk in patients with CKD mandates a multidisciplinary approach involving cardiologists, nephrologists, and other health care professionals. The present State-of-the-Art Review addresses the current understanding on the pathophysiological link between CVD and CKD, clinical implications and challenges in the treatment of these patients.

Estimated glomerular filtration rate (eGFR) is commonly used to evaluate kidney function before surgery, but research on its impact on outcomes after ankle fracture open reduction and internal fixation (ORIF) is limited. This study aims to analyze how eGFR affects short-term complications and mortality following ankle fracture ORIF.

The American College of Surgeons (ACS) NSQIP database was queried from 2005 to 2019 to identify 44,755 patients who underwent ankle fracture ORIF using specific CPT codes. Patients were excluded for missing demographic data or preoperative eGFR exceeding 3 standard deviations above the mean (91.1 mL/min/1.73 m²). Patients were categorized by eGFR: end stage renal disease (ESRD) (<15 mL/min/1.73 m2 [1.39 %]), severe loss of kidney function (15-30 mL/min/1.73 m2 [2.32 %]), moderate loss of kidney function (30-60 mL/min/1.73 m2 [15.45 %]), mild loss of kidney function (60-90 mL/min/1.73 m2 [33.78 %]), normal kidney function (90-120 mL/min/1.73 m2 [29.47 %]), and hyperfiltration (>120 mL/min/1.73 m2 [17.57 %]). Demographics, hospital length of stay, 30-day complications, surgical site infections (SSI), Clavien-Dindo grade IV complications, readmissions, reoperations, and mortality rates were compared. The cohort was primarily female (64.5 %), with a mean age of 55.41 years (range, 16-89).

A total of 21,815 patients were included, with about 30 % having an eGFR of 90-120 mL/min/1.73 m², indicating "normal" kidney function. As eGFR decreased, patient age (p < .001), BMI (p < .001), female sex rate (p < .001), and comorbidities significantly increased. Multivariate regression analysis showed that compared to normal eGFR (>90), patients with ESRD or moderate to severe kidney loss had a significantly higher risk of complications (ESRD: OR=1.576; p = .028)(15-30: 1.978; p < .001), reoperation (ESRD: OR=1.872; p = .039)(30-60: 1.523; p = .012), and readmission (ESRD: OR=1.784; p = .013)(30-60: 1.389; p = .012).

In patients undergoing ankle fracture ORIF, worse kidney function, as indicated by eGFR, was significantly linked to higher rates of postoperative complications, reoperation, and readmission. Surgeons and patients should take these findings into account for those with reduced kidney function.

Level III, Retrospective Cohort Study.

To assess the association between objectively measured cardiorespiratory fitness (CRF) and mortality in patients with chronic kidney disease (CKD).

From a large cohort of US veterans (n=750,302) based on the ETHOS (Exercise Testing and Health Outcomes) study, we identified 45,674 men and women aged 30 to 95 years (mean, 65.1 ± 8.8 years) who completed an exercise treadmill test (ETT) within the Veterans Affairs hospitals across the United States. All were diagnosed with CKD before the ETT by International Classification of Diseases 9th and 10th revision codes. Age- and-sex-specific CRF categories (quintiles) were established based on peak metabolic equivalents (METs) achieved during the ETT. We computed HRs and 95% CIs with Cox regression analyses adjusted for comorbidities and medications.

During 15.9 years of follow-up, 24,310 individuals (53.2%) died. The adjusted association between CRF and mortality risk was inverse and graded. For each 1-MET increase in CRF, the adjusted HR for mortality was 12% lower (HR, 0.88; 95% CI, 0.875 to 0.885; P<.001). When risk was assessed across CRF categories using the least-fit CRF category as the referent, the adjusted HRs and CIs were 0.76 (95% CI, 0.73 to 0.78), 0.63 (95% CI, 0.61 to 0.66), 0.49 (95% CI, 0.47 to 0.51), and 0.33 (95% CI, 0.30 to 0.35), for low-fit, moderate-fit, fit, and high-fit individuals, respectively. The pattern of the CRF mortality risk association was similar regardless of age, race, or sex.

In this large multiethnic study, we found an independent, inverse, and graded association between CRF and mortality in CKD patients. These findings underscore the importance of increasing CRF in CKD patients to lower the risk of mortality.

The number of patients requiring dialysis therapy continues to increase worldwide because of the lack of effective treatments for chronic kidney disease (CKD). Furthermore, no curative treatments for acute kidney injury (AKI) have been established. The therapeutic effects of human induced pluripotent stem cell-derived nephron progenitor cells (hiPSC-NPCs) on AKI have been reported in mice but not clinically confirmed. There are also no reports examining the therapeutic potential of hiPSC-NPCs on CKD. Although large numbers of uniform hiPSC-NPCs are required for cell therapies for AKI and CKD, effective expansion cultures remain to be developed. Here, we established a culture medium for cells that enabled more than 100-fold proliferation of hiPSC-NPCs from multiple hiPSC lines in two passages. We demonstrated that hiPSC-NPCs expanded by our medium named CFY or by their conditioned medium alone attenuated kidney injury and improved survival in cisplatin-induced AKI mice. We also observed that hiPSC-NPCs prevented kidney functional decline, interstitial fibrosis, and senescence in aristolochic acid-induced CKD mice. In addition, we found c-MET to be a specific cell surface marker for hiPSC-NPCs and confirmed that purified c-MET+ hiPSC-NPCs had therapeutic effects on AKI and CKD mice. Furthermore, we found that hiPSC-NPCs exerted their therapeutic effects in AKI and CKD mice by secreting vascular endothelial growth factor A. Expanded hiPSC-NPCs may be useful cell therapies for AKI and CKD and may open avenues for treating kidney diseases.

We sought to construct a simple clinical mortality prediction model in trauma patients that required pre-injury hemodialysis: Hemodialysis Outcomes Score in Trauma (HOST).

Trauma patients on pre-injury hemodialysis admitted between July 2013 to December 2021 were reviewed. Univariate and multivariable analysis was used to determine independent predictors of mortality and construct the HOST score.

There were 663 patients identified as receiving pre-injury hemodialysis. Most patients were male (54.6 ​%), suffered a blunt mechanism (97.4 ​%), and were severely injured (median ISS 21). Mortality at 28-days for patients receiving pre-injury hemodialysis was 6.8 ​% compared to 4.8 ​% in injured patients that did not require pre-injury hemodialysis (p ​= ​0.03). Multivariate logistic regression identified GCS, HR, and hematocrit to be associated with 28-day mortality.

HOST may serve as a tool with readily accessible input variables that is able to predict 28-day mortality.

Chronic kidney disease affects around 10% of the global population and is associated with significant risk of progression to end-stage renal disease and vascular events. Aldosterone receptor antagonists such as spironolactone have shown prognostic benefits in patients with heart failure, but effects on patients with chronic kidney disease are uncertain.

To determine the effect of low-dose spironolactone on mortality and cardiovascular outcomes in people with chronic kidney disease stage 3b.

Prospective randomised open blinded end-point trial.

Three hundred and twenty-nine general practitioner practices throughout the United Kingdom.

Patients meeting the criteria for chronic kidney disease stage 3b (estimated glomerular filtration rate 30-44 ml/minute/1.73 m2) according to National Institute for Health and Care Excellence guidelines were recruited. Due to the higher than anticipated measurement error/fluctuations, the eligible range was extended to 30-50 ml/minute/1.73 m2 following the initial recruitment period.

Participants were randomised 1 : 1 to receive either spironolactone 25 mg once daily in addition to standard care, or standard care only.

Primary outcome was the first occurring of all-cause mortality, first hospitalisation for heart disease (coronary heart disease, arrhythmia, atrial fibrillation, sudden death, failed sudden death), stroke, heart failure, transient ischaemic attack or peripheral arterial disease, or first occurrence of any condition not listed at baseline. Secondary outcome measures included changes in blood pressure, renal function, B-type natriuretic peptide, incidence of hyperkalaemia and treatment costs and benefits.

One thousand four hundred and thirty-four participants were randomised of the 3022 planned. We found no evidence of differences between the intervention and control groups in terms of effectiveness with the primary combined vascular end points, nor with the secondary clinical outcomes, including progression in renal decline. These results were similar for the total treatment periods or a 3-year follow-up period as originally planned. More adverse events were experienced and more participants discontinued treatment in the intervention group. Two-thirds of participants randomised to spironolactone stopped treatment within six months because they met pre-specified safety stop criteria. The addition of low-dose spironolactone was estimated to have a cost per quality-adjusted life-year gained value above the National Institute for Health and Care Excellence's threshold of £30,000.

Main limitations were difficulties in recruiting eligible participants resulting in an underpowered trial with poor ethnic diversity taking twice as long as planned to complete. We have explored the data in secondary analyses that indicate that, despite these difficulties, the findings were reliable.

The benefits of aldosterone receptor antagonism in chronic kidney disease trial found no evidence to support adding low-dose spironolactone (25 mg daily) in patients with chronic kidney disease stage 3b: there were no changes to cardiovascular events during the trial follow-up, either for the combined primary or individual components. There was also no evidence of benefit observed in rates of renal function decline over the trial, but much higher initial creatinine rise and estimated glomerular filtration rate decline, and to a higher percentage rate, in the intervention arm in the first few weeks of spironolactone treatment, which resulted in a high proportion of participants discontinuing spironolactone treatment at an early stage. These higher rates of negative renal change reduced in scale over the study but did not equalise between arms. The addition of 25 mg of spironolactone therefore provided no reno- or cardio-protection and was associated with an increase in adverse events.

These findings might not be applicable to different mineralocorticoid receptor antagonists.

Current Controlled Trials ISRCTN44522369.

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/01/52) and is published in full in Health Technology Assessment; Vol. 29, No. 5. See the NIHR Funding and Awards website for further award information.

Family with sequence similarity 20 C (FAM20C) is a Golgi protein kinase that phosphorylates the serine residue in the S-x-E/pS motif of target proteins. FAM20C phosphorylates most secreted proteins, which play important roles in multiple biological processes, including cancer progression, biomineralization, and lipid homeostasis. Numerous studies have documented the potential contribution of FAM20C to the growth, invasion, and metastasis of glioma, breast cancer, and other cancers, as well as to the mineralization process of teeth and bone. In addition, FAM20C has been found to be associated with the occurrence and development of certain cardiovascular diseases and endocrine metabolism disorders. It raises hopes that understanding the disease-specific mechanisms of FAM20C may hold the key to developing new strategies for these diseases. This review comprehensively covers the existing literature to provide a summary of the structure and biological functions of FAM20C, with a particular focus on its roles in the disease context.

To evaluate associations between brain structure/function with physical function and functional capacity in older adults with CKD and cognitive complaints.

We evaluated associations between neuroimaging and cognitive function with functional capacity and physical function in older adults (60-80years) with CKD and cognitive complaints (n = 39; age 67.6 years).

In multivariable analysis, each standard deviation (SD) increase in 6-minute walk test (6MWT) distance (functional capacity) was associated with better attention/information processing (Trails Making Test-A (TMT-A) (ß -10.86, 95% Confidence Interval (CI) -16.67, -5.06); digit symbol test (ß 5.24, 95% CI 1.02, 9.46)), and each SD increase in short physical performance battery (SPPB)(physical function) was associated with better attention/information processing (TMT-A) (ß -10.99, 95% CI -16.59, -5.39). 6MWT distance and SPPB were associated with some indicators of brain structure/diffusivity.

In older adults with CKD and cognitive complaints, functional capacity and physical function may be associated with cognition and brain structure/function.

The impact of baseline estimated glomerular filtration rate (eGFR) on the risk of adverse outcomes according to metabolic parameter variabilities in chronic kidney disease has rarely been investigated.

We conducted a retrospective nationwide cohort study using the National Health Insurance System data in Korea from 2007 to 2013 to identify individuals with three or more health screenings. The metabolic components variability was defined as intraindividual variability between measurements using the variability independent of the mean. The metabolic variability score was defined as the total number of high-variability metabolic components. Multivariable-adjusted Cox regression analysis was conducted to evaluate the risks of all-cause mortality, myocardial infarction, and ischemic stroke.

During a mean follow-up of 6.0 ± 0.7 years, 223,531 deaths, 107,140 myocardial infarctions, and 116,182 ischemic strokes were identified in 9,971,562 patients. Low eGFR categories and higher metabolic variability scores were associated with a higher risk of adverse outcomes. The degree of association between metabolic variability and adverse outcomes was significantly larger in those with low eGFR categories than in those with preserved eGFR (p for interaction < 0.001). Representatively, those with high metabolic variability in the eGFR of <15 mL/min/1.73 m2 group showed a prominently higher risk for all-cause mortality (adjusted hazard ratio [aHR], 5.28; 95% confidence interval [CI], 4.02-6.94) when the degree was compared to the findings in those with preserved (eGFR of ≥60 mL/min/1.73 m2) kidney function (aHR, 2.55; 95% CI, 2.41-2.69).

The degree of adverse association between metabolic variability and poor prognosis is accentuated in patients with impaired kidney function.

The circulating renin-angiotensin system (RAS) is an endocrine system with key functions in maintaining blood pressure, fluid volume, and electrolytes. The RAS in the kidney (intrarenal RAS) plays a critical role in the onset and progression of kidney diseases. However, the mechanism underlying the onset and progression of diabetic nephropathy in relation to the expression and secretion of angiotensinogen (AGT) in the kidneys remains unclear. In this review, we present an overview of the intrarenal RAS and its role in diabetic nephropathy, as well as reviewing the evidence for the use of urinary AGT as a biomarker of this system in diabetic nephropathy. We also describe the roles of isoflavones in the context of diabetic nephropathy. The considered studies show that the intrarenal RAS-especially AGT-plays a diversified role in diabetic nephropathy; for instance, the increase in AGT due to oxidative stress is suppressed by polyphenols with antioxidant capacity, which is thought to affect the progression of diabetic nephropathy. Therefore, clarification of how polyphenols affect the onset and progression of diabetic nephropathy may provide insights into new treatments for this illness.

The stress hyperglycemia ratio (SHR) is an emerging biomarker used to assess blood glucose levels under acute stress conditions and has been linked to the incidence of adverse clinical outcomes. However, the precise role of SHR in patients with diabetic kidney disease (DKD) and chronic kidney disease (CKD), particularly in relation to mortality, remains poorly understood. This study seeks to investigate the clinical value of SHR as a predictive tool for all-cause and cardiovascular mortality in these patient groups. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018, encompassing 3,507 individuals diagnosed with diabetic kidney disease (DKD) or chronic kidney disease (CKD). The primary endpoints included all-cause mortality and cardiovascular mortality, with mortality data obtained from the National Death Index (NDI) through December 31, 2019. Participants were categorized into quartiles based on the stress hyperglycemia ratio (SHR), and Cox proportional hazards regression models were employed to examine the association between SHR and mortality. Model 1 did not account for any covariates, Model 2 adjusted for age, sex, and race, while Model 3 additionally incorporated adjustments for educational attainment, marital status, body mass index, smoking behavior, hypertension, hyperlipidemia, and cardiovascular disease. The study comprised 3,507 patients with a mean age of 60.7 years, of whom 56% were female. The overall incidence of all-cause mortality was 38,000 per 100,000 person-years, while cardiovascular mortality was 11,405 per 100,000 person-years. Kaplan-Meier survival analysis revealed that the second quartile of the stress hyperglycemia ratio (SHR) (Q2) exhibited the lowest all-cause mortality (log-rank P = 0.003). Cox regression analysis indicated that the hazard ratio (HR) for all-cause mortality in Q2 was 0.76 (95% CI: 0.63, 0.92), whereas the HR for Q4 was 1.26 (95% CI: 1.04, 1.52). Restricted cubic spline (RCS) analysis revealed a J-shaped association between SHR and all-cause mortality, as well as a U-shaped association with cardiovascular mortality. The minimum risk values for SHR were 0.923 for all-cause mortality and 1.026 for cardiovascular mortality. In patients with diabetic kidney disease (DKD) and chronic kidney disease (CKD), SHR demonstrated a J-shaped relationship with all-cause mortality and a U-shaped relationship with cardiovascular mortality. Subgroup analyses indicated that the effect of spontaneous hypertension on mortality was consistent across all subgroups. This study highlights a significant association between the stress hyperglycemia ratio (SHR) and both all-cause and cardiovascular mortality in patients with diabetic kidney disease (DKD) or chronic kidney disease (CKD). SHR may serve as a critical biomarker for prognostic assessment in these populations, enabling clinicians to identify high-risk patients and tailor personalized treatment strategies that enhance patient quality of life and mitigate mortality risk.

Sacubitril/Valsartan is a combination of neprilysin inhibitor and angiotensin II receptor blocker that proved its own efficacy and safety in heart failure patients to ameliorate cardiovascular morbidity and mortality compared to angiotensin II-converting enzyme inhibitors alone. However, end-stage renal disease patients have not been included in the randomized controlled trials, so the beneficial effects as well as the risk profile of this association remain still undefined in these patients. Only observational studies on this drug association have been carried out in end-stage renal disease patients investigating mostly biohumoral or echocardiographic markers. Therefore, its application is still controversial and not free of complications due to the potential risk of hypotension and hyperkaliemia. The efficacy to improve biohumoral markers and cardiac function in dialysis patients and the potential application especially in those patients with severe and resistant hypertension and/or left ventricular dysfunction could be crucial in end-stage renal disease patients. Ongoing long-term randomized controlled trials should thoroughly define the effective benefits and/or adverse effects in patients on substitutive treatment.

Chronic kidney disease is a significant cause of adverse obstetric outcomes. However, there are few studies assessing the risk of severe maternal morbidity and mortality among patients with chronic kidney disease and no studies assessing the association between individual indicators of severe maternal morbidity and chronic kidney disease.

To evaluate the risk of severe maternal morbidity and mortality among pregnant patients with chronic kidney disease.

This was a population-based, retrospective cohort study including U.S. delivery hospitalizations from 2010-2020 utilizing the Healthcare Cost & Utilization Project National Inpatient Sample database. Patients were identified as having a delivery hospitalization, chronic kidney disease, and severe maternal morbidity using International Classification Diagnoses codes (9th and 10th edition). The primary outcomes were severe maternal morbidity and mortality, as defined according to the Centers for Disease Control and Prevention criteria. Multivariate logistic regression analyses were performed to estimate adjusted relative risk and 95% confidence intervals of severe maternal morbidity and mortality among patients with chronic kidney disease. Subgroup analyses were performed by chronic kidney disease etiology, stage, race and ethnicity, and individual indicators of severe maternal morbidity.

Among the 38,374,326 parturients in this study, 95,272 (0.2%) had chronic kidney disease. The risk of severe maternal morbidity was higher for those with chronic kidney disease (12.2% vs 0.7%, aRR 6.4, 95% CI 6.0-6.8) compared to those without. Among severe maternal morbidity indicators, those with chronic kidney disease were at highest risk for acute renal failure (aRR 21.7, 95% CI 19.8-23.7) and sepsis (aRR 9.0, 95% CI 7.6-10.5). Chronic kidney disease was also associated with an increased risk of maternal death (aRR 4.1, 95% CI 2.9-5.8). Black individuals had higher adjusted population attributable fraction (aPAF) between severe maternal morbidity and chronic kidney disease (aPAF 4.0%, 95% CI 3.6-4.3). Increased risk of severe maternal morbidity was associated with all chronic kidney disease subtypes, stages, and a history of renal transplant. Maternal death was significantly associated with diabetic nephropathy, renovascular, and obstructive or unspecified renal disease (aRR 7.3-14.1), as well as stages 3-5 of chronic kidney disease and a history of renal transplant (aRR 15.5-32.6). Risk of severe maternal morbidity and mortality were similar in those with a history of renal transplant and those with stage 1 chronic kidney disease. The number needed to treat with renal transplant to prevent 1 severe maternal morbidity event or maternal death in those with stages 3-5 chronic kidney disease was 2.6 (95% CI 2.4-2.9) and 45.0 (95% CI 31.0-82.0), respectively.

Chronic kidney disease in pregnancy was significantly associated with severe maternal morbidity, mortality, and other adverse perinatal outcomes, warranting close surveillance and multidisciplinary management throughout pregnancy.

Sedentary behavior is highly prevalent and associated with morbidity and mortality in chronic kidney disease (CKD). A Sit Less, Interact and Move More (SLIMM) sedentary activity coaching intervention can reduce sedentary duration among persons with CKD, but preliminary data suggest that effects may not persist. Prior studies have suggested that moderate/vigorous intensity physical activities are not sustainable in persons with CKD. Therefore, we aimed to determine whether guided resistance training ± oral semaglutide co-intervention improves adherence and/or persistence of the SLIMM intervention.

The SLIMM-2 is a two-center study designed with a 3-month sedentary activity coaching (SLIMM) followed by a 9-month randomized controlled trial with three arms: SLIMM + standard of care resistance training + oral placebo, SLIMM + guided resistance training + oral placebo, or SLIMM + guided resistance training + oral semaglutide. The study is recruiting persons with CKD (eGFR 20 to ≤60 ml/min/1.73 m2). ActivPAL, a wearable tri-axial accelerometer, is used to assess outcomes including sedentary duration (primary outcome), stepping duration and the average number of steps per day. Additional outcomes include 6-min walk distance and body fat percentage. Persons randomized to standard of care resistance training will be encouraged to maintain individualized physical activity goals; those randomized to guided resistance training will attend guided sessions per month and be prescribed daily independent exercises.

Enrollment, interventions, and follow-up are ongoing.

Results from the SLIMM-2 study are expected to inform clinical practice, with the potential to enhance physical health and functioning among persons with CKD.

The use of next-generation sequencing technologies such as exome and genome sequencing in research and clinical care has transformed our understanding of the molecular architecture of genetic kidney diseases. Although the capability to identify and rigorously assess genetic variants and their relationship to disease has advanced considerably in the past decade, the curation of clinically relevant relationships between genes and specific phenotypes has received less attention, despite it underpinning accurate interpretation of genomic tests. Here, we discuss the need to accurately define gene-disease relationships in nephrology and provide a framework for appraising genetic and experimental evidence critically. We describe existing international programmes that provide expert curation of gene-disease relationships and discuss sources of discrepancy as well as efforts at harmonization. Further, we highlight the need for alignment of disease and phenotype terminology to ensure robust and reproducible curation of knowledge. These collective efforts to support evidence-based translation of genomic sequencing into practice across clinical, diagnostic and research settings are crucial for delivering the promise of precision medicine in nephrology, providing more patients with timely diagnoses, accurate prognostic information and access to targeted treatments.

Chronic kidney disease (CKD) is a prevalent global health issue affecting millions of patients worldwide, impacting quality of life, impeding physical and psychological well-being, causing financial stress, and increasing mortality rates. This study aimed to highlight the prevalence of CKD and its associated risk factors across Saudi Arabia.

This is a cross-sectional study conducted from 2015 to 2022, using data from 42 branches of a major network of diagnostic laboratories in Saudi Arabia, covering the country's 13 administrative areas.

The mean age was 40.35 ± 14.5 years. The highest proportion of participants resided in the Makkah region at 35.77%, followed by the Riyadh region at 25.75%. The overall prevalence of CKD was 4.76%, with most having CKD in stage 3 (3.5%). The prevalence of CKD was higher among males compared to females (5.83% vs. 3.88%) and increased significantly with age, being 0.45% among participants aged 18-29 years and reaching 50.94% among participants aged 90 years or older. Predictors of CKD included increasing age, male sex, administrative area (Makkah 1.40 [95% CI:1.26-1.55], Jazan 1.34 [95% CI:1.18-1.52], Najran 0.47 [95% CI, 0.39-0.57], Alqasim 0.73 [95% CI, 0.64-0.82]), and a high hemoglobin A1C. CKD in Saudi Arabia is influenced by various demographic and geographic determinants contributing to its prevalence and associated burden on the population.

These findings emphasize the need for targeted screening and prevention strategies, especially for at-risk populations. Continued surveillance, early detection, and effective management are crucial to reducing CKD's burden and improving kidney health outcomes in Saudi Arabia. Further research is essential to better understand the disease's regional and demographic drivers.

Anticoagulation therapy for atrial fibrillation (AF) has undergone major changes following the introduction of direct oral anticoagulants (DOAC) in 2011. However, the transition of anticoagulation therapy for AF patients with severe renal dysfunction remains to be elucidated.

Follow-up data, including creatinine clearance (CrCl), were available for 3,706 patients in the Fushimi AF Registry. We divided patients into 3 groups based on CrCl as follows: (1) CrCl ≥50 mL/min; (2) 50 mL/min>CrCl≥30 mL/min; and (3) CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50>CrCl≥30 mL/min, prescription of oral anticoagulants increased year-by-year from 2011 to 2021 with a growing proportion of DOAC; however, the prescription of oral anticoagulants remained almost unchanged in those with CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50 mL/min>CrCl≥30 mL/min, the incidence of adverse events, including stroke/systemic embolism and major bleeding, was lower among patients enrolled after 2014 than before 2013. However, these trends were not seen in patients with CrCl <30 mL/min.

Despite the increased use of DOAC in patients with AF since 2011, anticoagulation therapy for AF patients with severe renal dysfunction has largely remained unchanged, and a reduction in adverse events in those patients has not been observed.

Renal anemia stems mainly from chronic inflammation with elevated hepcidin levels, iron deficiency, and reduced red blood cell lifespan. Inadequate erythropoietin (EPO) production, worsened kidney function, leads to symptoms such as low energy, fatigue, and impaired physical function, significantly affecting patients' quality of life. We conducted a comprehensive search across electronic databases including PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Airiti library, and Wanfang, to compile recent clinical trials and pilot studies on conventional and complementary alternative medicine approaches for renal anemia. This discussion focuses on the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) axis theory, from lab research to clinical applications. It explores non-extracorporeal treatments for renal anemia, including pharmaceutical interventions, dietary strategies, and complementary and alternative medicine (CAM). The article details the effects of Roxadustat, Ferumoxytol, and Epodion. Clinical studies show that modulating the gut microbiome can reduce inflammation and improve renal anemia. Clinical trials suggest that CAM therapy can improve renal anemia through mechanisms such as enhanced iron metabolism, anti-inflammatory effects, reduced hepcidin levels, and increased EPO and HIF expressions. By synthesizing this information, the review aims to furnish valuable insights and treatment recommendations aimed at ameliorating renal anemia in individuals grappling with chronic kidney disease.

Apolipoprotein L1 gene (APOL1) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population.

We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex.

Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis.

In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.).

We aimed to assess the global impact of chronic kidney disease (CKD) attributable to dietary risk factors.

The research utilized data from the Global Burden of Disease Study 2021 to evaluate age-standardized mortality rates (ASMR), disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) linked to CKD resulting from dietary risk factors.

From 1990 to 2021, both the ASMR and age-standardized DALY rate (ASDR) for CKD attributable to dietary risk factors exhibited an overall increasing trend globally. The mortality EAPC was 0.65, while the EAPC for DALYs stood at 0.39. Among dietary risk factors examined, a diet high in sugar-sweetened beverages was associated with the most substantial increase in CKD burden. Notably, Central sub-Saharan Africa bore the highest burden of CKD due to dietary risk factors, with an ASMR of 10.24 and an ASDR of 229.23. The increases in ASMR and ASDR were more pronounced in high-income regions, particularly in Latin America and the Caribbean, where the EAPC values for ASMR were 1.45 and 1.05, respectively, and for ASDR were 1.08 and 0.96. Furthermore, the burden of CKD was notably higher among middle-aged and elderly individuals, especially men aged 65 and above.

The global disease burden attributed to dietary risk factors for CKD is increasing. A diet high in sugar-sweetened beverages exerted the most significant impact on CKD. There is a high incidence in Central sub-Saharan Africa, as well as in high-income regions and Latin America and the Caribbean.