Physical activity patterns and chronic kidney disease risk: a 5-year study in stage 1 cardiovascular-kidney-metabolic syndrome.

SGLT2 inhibitors and the risk of incident chronic kidney disease in type 2 diabetes: a nationwide emulated target trial in Taiwan.

Although the American Diabetes Association (ADA) recently established a diagnostic algorithm for the early detection of liver fibrosis among high-risk individuals, its implications for chronic kidney disease (CKD) risk stratification remain unclear. We investigated whether the ADA diagnostic algorithm can effectively stratify CKD risk in individuals at risk of cirrhosis. This retrospective cohort study included 9264 adults without pre-existing CKD who underwent vibration-controlled transient elastography from April 2006 to October 2018. Participants were categorized into three groups: (1) no metabolic criteria; (2) low-risk (FIB-4 < 1.3 or 1.3-2.67 with liver stiffness [LS] < 8 kPa) and (3) high risk (FIB-4 > 2.67, or 1.3-2.67 with LS ≥ 8 kPa). The primary outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or proteinuria (≥ 1+) on two consecutive tests. Secondary outcomes included ≥ 25% eGFR decline on two visits and 3- and 5-year risk of CKD. During a mean follow-up of 3.7 years, 440 (4.7%) participants developed incident CKD. When stratified by the ADA algorithm, multivariable Cox models revealed a 1.52-fold (95% confidence interval [CI], 1.09-2.13) higher risk of incident CKD in the high-risk group than those with no metabolic abnormalities. The high-risk group also had a 2.30-fold higher risk (95% CI, 1.83-2.90) of a 25% eGFR decline (mean follow-up 3.5 years) than those with no metabolic abnormalities. The two-step ADA algorithm can effectively stratify CKD risk in individuals at high risk of future cirrhosis.

Diabetes-dependent association between metabolic score for visceral fat and chronic kidney disease: findings from a longitudinal cohort study.

The relationship between APOL1 risk variants and with preeclampsia and fetal outcomes.

Metabolic dysfunction-associated fatty liver disease and the risk of incident chronic kidney disease: A 10-year prospective cohort study.

Platelet indices, including platelet distribution width (PDW) and mean platelet volume (MPV), reflect platelet activation and have been associated with kidney disease progression in various populations. However, whether these indices are associated with incident chronic kidney disease (CKD) in high-risk individuals remains unclear. We retrospectively examined the associations of PDW and MPV with incident CKD using longitudinal data from 1,281 individuals without CKD but with one or more established CKD risk factors (hypertension, diabetes mellitus, dyslipidemia, or a history of cardiovascular disease) in the Fukushima Cohort Study. Participants were categorized into quartiles according to baseline PDW or MPV. The primary outcome was incident CKD. During a median follow-up of 5.2 years, 384 participants developed incident CKD. Higher quartiles of PDW and MPV were associated with increased cumulative incidence of CKD in Kaplan-Meier analyses. Compared with the second PDW quartile, the highest quartile was associated with a significantly higher risk of incident CKD (adjusted hazard ratio 1.51, 95% confidence interval 1.11-2.06). A similar association was observed for MPV. However, when PDW and MPV were simultaneously included in the multivariable model, only PDW remained significantly associated with incident CKD, whereas the association of MPV was no longer statistically significant. In addition, analyses treating these indices as continuous variables did not show statistically significant associations. PDW and MPV showed associations with incident CKD in high-risk individuals; however, these findings were not consistent across all analyses. Therefore, the results should be interpreted as hypothesis-generating and require further confirmation.

Albuminuria is an early marker of kidney damage and an essential component of chronic kidney disease (CKD) risk stratification. Quantitative measurement of the urine albumin to creatinine ratio (ACR) in a spot, preferably morning, urine sample is the recommended standard. In low throughput laboratories and point of care settings, semiquantitative strip tests are sometimes used for screening, although their diagnostic performance is limited. To evaluate the clinical utility of a commercial semiquantitative urine strip test for albumin and creatinine by comparison with quantitative ACR measurement. Eighty-four spot urine samples were analysed. Semiquantitative ACR categories were obtained using an ACON Mission strip test, according to the manufacturer's instructions. Quantitative ACR was measured on a Beckman Coulter AU480 analyser (immunochemical albumin, enzymatic creatinine). Diagnostic performance was assessed using sensitivity, specificity, positive and negative predictive values, Matthew's correlation coefficient (MCC) and Cohen's κ. A decision threshold of 3 mg/mmol (30 mg/g) was applied. Sensitivity for detecting albuminuria (≥3mg/mmol, ≥30 mg/g) was 80.6% (95% CI 62.5 - 92.5) and specificity was 60.4% (95% CI 46.0 - 73.5). The negative and positive predictive values were 84.2% and 54.3%, respectively. Overall categorical agreement across A1 - A3 was 63.1% (κ = 0.334; MCC = 0.398). Most discrepancies reflected overclassification of low-grade albuminuria by the strip test in samples classified as normoalbuminuric by quantitative ACR. The semiquantitative strip test shows high sensitivity with moderate specificity and is suitable for screening for albuminuria. Positive results should be confirmed by quantitative ACR measurement in accordance with current guidelines.

Chronic kidney disease (CKD) incidence, rate of progression toward end-stage kidney disease, and its adverse outcomes are greater in under-resourced, minoritized United States (US) communities where health-related social determinants contribute to their risk for incidence of and adverse outcomes from CKD and other chronic diseases. Research needed in these communities at high risk for CKD and other chronic diseases to develop better community-based management strategies is hindered by the justified historic mistrust these communities have for the US clinical and research enterprise. Insights and conclusions derived from initial community-based studies designed to examine the benefits to kidney health of healthy eating including added dietary fruits and vegetables, adjunctive to standard pharmacologic kidney-protective care. These studies required first to establish and then leverage collaboration with leadership of community institutions with already established community trust. The studies described herein successfully established and then leveraged trust of the leadership of local churches and other community-based institutions in under-resourced, minoritized communities. This then enabled recruitment and retention of study participants from these communities at high risk for CKD and other chronic diseases, with recruitment and follow up occurring at these institutions rather than in traditional academic settings. The studies showed enhanced kidney health with healthy eating adjunctive to standard pharmacologic kidney-protective care. These studies show the necessity of gaining community trust to facilitate studies done in under-resourced, minoritized communities at high risk for CKD and other chronic diseases. This trust was gained through collaborating with institutional community leadership that already had community trust. Future research to develop needed evidenced based strategies for CKD and other chronic diseases will require proactive outreach to establish trust that will enable collaborative and effective working relationships with community-based institutions.

To examine the association between urinary protein excretion (UPE) level in preeclampsia and long-term risk of maternal hypertension, chronic kidney disease (CKD), and cardiovascular disease (CVD). Nationwide, population-based cohort study utilising routinely collected individual-level data from medical databases. Denmark, 1998-2018, with follow-up through 2021. All pregnancies ≥ 20 weeks among women aged ≥ 15 years. We calculated cumulative incidences (risks) of hypertension, CKD, and CVD by preeclampsia status, including UPE level (no/mild versus moderate/severe, based on established urine protein/albumin cutoffs). Adjusted risk differences and risk ratios were computed for women with preeclampsia compared with those without, adjusting for age, smoking, obesity, residential region, and year. 10-year risk, adjusted risk difference, and risk ratio of hypertension, CKD and CVD by preeclampsia status and UPE level. Among 286 078 pregnant women, 9538 (3.3%) developed preeclampsia, which was associated with higher risks of later hypertension, CKD or CVD. Among women with preeclampsia with no/mild UPE, 10-year risks were 11.9% (95% CI: 10.9-13.0) for hypertension, 1.2% (95% CI: 0.9-1.6) for CKD and 1.1% (95% CI: 0.8-1.5) for CVD. With moderate/severe UPE, 10-year risks were 16.0% (95% CI: 14.6-17.5) for hypertension, 5.1% (95% CI: 4.3-5.9) for CKD and 1.2% (95% CI: 0.8-1.7) for CVD. For hypertension and CVD, adjusted risk differences and risk ratios were similar across UPE levels, whereas CKD risk increased with higher UPE. Preeclampsia is associated with increased long-term maternal risk of hypertension, CKD, and CVD. Higher UPE levels correlate with higher risk of later hypertension and CKD.

Preterm birth disrupts kidney development, resulting in reduced nephron number and structural immaturity of glomeruli and podocytes that increases the risk of hypertension, proteinuria, and subsequently chronic kidney disease (CKD) later in life. Since nephrogenesis ceases around 36 weeks of gestation, preterm infants cannot generate new nephrons after birth, making them vulnerable to long-term renal dysfunction. Unravelling the mechanisms behind this impaired development has been limited by the complexity of human nephrogenesis and the lack of physiologically relevant experimental models. Recent advances in human induced pluripotent stem cell-derived kidney organoids have made it possible to model nephrogenesis in vitro. These organoids replicate key processes such as nephron differentiation, ureteric bud branching, and kidney vascularization, allowing detailed study of kidney development and injury. Moreover, molecular interventions-including retinoic acid (RA), glial-cell-line-derived neurotrophic factor (GDNF), and insulin-like growth factor 1 (IGF1)-show the potential to enhance nephron formation and protect against kidney injury. Key Messages • Kidney organoids provide a powerful, human-relevant system to study nephrogenesis and CKD mechanisms. • Integration of the ureteric bud and enhanced vascularization significantly improves organoid maturity towards a more in vivo-like state. • Targeted molecular interventions such as RA, GDNF, and IGF1 offer potential strategies to enhance nephron endowment and mitigate CKD risk in preterm-born individuals, and may be studied using kidney organoids.

Study of the association between metabolic liver disease and renal function impairment: an updated systematic review and meta-analysis of prospective studies (2020-2025)

Background: the dietary index for gut microbiota (DI-GM) is a recently proposed index that reflects the diversity of the gut microbiota from the perspective of dietary intake. However, its association with chronic kidney disease (CKD) has not been widely studied. Methods: this prospective cohort study included 166 865 participants free of CKD at baseline. The DI-GM was assessed through a 24 h dietary recall questionnaire. Incident CKD was ascertained using hospital inpatient records, death registry data, and primary care data. A genetic risk score for gut microbial abundance was constructed based on 19 variants. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for CKD incidence. Results: during a median follow-up of 9.44 years, 3977 participants developed CKD. In the fully adjusted model, compared with the lowest group for the DI-GM (0-3 points), participants in higher DI-GM groups (4, 5, and ≥6 points) had a significantly lower risk of CKD. The adjusted HRs (95% CIs) for these groups were 0.81 (0.74, 0.88), 0.79 (0.72, 0.86), and 0.73 (0.67, 0.80), respectively (P for trend <0.0001). Significant multiplicative interactions were observed between genetically predicted gut microbial abundance and adherence to the DI-GM (P for interaction = 0.004). Conclusion: adherence to the DI-GM was strongly linked to a reduced risk of incident CKD, particularly in individuals with high gut microbial abundance.

Gabapentinoids are widely prescribed in patients with chronic kidney disease (CKD), yet whether routine renal dose adjustment is sufficient to mitigate cognitive safety risk remains unresolved. Gabapentin and pregabalin differ markedly in pharmacokinetic behavior under impaired clearance: gabapentin half-life extends from 5–7 hours to 52–132 hours in advanced CKD (a 10-to 20-fold increase), versus an approximately 4-fold extension for pregabalin. We examined whether CKD amplifies gabapentin-associated dementia risk relative to pregabalin in a real-world active comparator cohort, with external replication.Among 33,791 adults aged ≥40 years with hypertension initiating gabapentinoids in the Rutgers Clinical Research Data Warehouse (2018–2024), gabapentin was associated with substantially elevated dementia risk in patients with CKD (hazard ratio [HR] 7.39; 95% CI, 3.43–15.92;P<0.001) versus a near-null association in patients without CKD (HR 1.09; 95% CI, 0.89–1.34;P=0.41). The elevated risk in CKD persisted within the low-dose stratum (≤300 mg: HR 5.06 in CKD vs. 1.27 in non-CKD), suggesting that dose adjustment alone may not fully offset cognitive safety risk. The signal concentrated in non-dialysis CKD (KDIGO G3b–G4: HR 4.54; 95% CI, 1.62–12.76) and attenuated in CKD stage 5 (HR 1.57;P=0.18), a pattern consistent with renal pharmacokinetic exposure as the dominant driver. External replication in the NIH All of Us Research Program (N=47,079) confirmed the gabapentin–pregabalin signal (HR 1.59; 95% CI, 1.35–1.88;P<0.001) with a directionally consistent eGFR gradient. FAERS pharmacovigilance analysis showed disproportionately higher renal adverse event reporting for gabapentin versus pregabalin (chronic kidney disease ROR 5.98; renal failure ROR 2.43).These findings are consistent with the interpretation that CKD may transform routine gabapentin prescribing into a renal pharmacokinetic cognitive safety problem, with risk concentrated in the non-dialysis CKD population and persisting even at low prescribed doses. Standard dose adjustment alone may be insufficient. Renal function stage warrants closer integration into gabapentinoid selection in patients with CKD, with pregabalin a candidate alternative where cardiovascular risk permits.Key PointsIn an active comparator new-user cohort of 33,791 gabapentinoid initiators, gabapentin was associated with substantially elevated dementia risk in patients with chronic kidney disease (CKD) compared with pregabalin, with the excess risk persisting even within the low-dose stratum (≤300 mg) — a pattern consistent with the interpretation that standard renal dose adjustment alone may not fully offset the cognitive safety risk of gabapentin in CKD.The signal concentrated in non-dialysis CKD (KDIGO stages G3b–G4) and attenuated in CKD stage 5, paralleling expected pharmacokinetic exposure: gabapentin half-life extends 10-to 20-fold in advanced CKD versus approximately 4-fold for pregabalin, while dialysis partially restores clearance.Convergent evidence from external replication in the NIH All of Us Research Program (N=47,079) and FDA FAERS pharmacovigilance data — including disproportionately higher renal adverse event reporting for gabapentin versus pregabalin (chronic kidney disease reporting odds ratio [ROR] 5.98; renal failure ROR 2.43) — supported the interpretation of a renal pharmacokinetic cognitive safety vulnerability.These findings suggest that renal function stage warrants closer integration into gabapentinoid selection in older adults with CKD, with pregabalin a candidate alternative where cardiovascular risk permits.

Coffee is one of the most widely consumed beverages globally. Caffeine has been linked to antioxidant, anti-inflammatory, antifibrotic, and anticancer effects. However, the relationship between caffeine consumption and the risk of chronic kidney disease (CKD) has yielded conflicting findings. Research on the health effects of caffeine relies mainly on exploratory observational studies, which may be affected by biases such as residual confounding. Variations in behaviour, health status, intake, and metabolism also influence outcomes. A comprehensive understanding of the mechanisms and population-specific factors mediating the impact of caffeine on kidney health is essential. In this article, we describe the metabolism and mechanism of action of caffeine, as well as its potential adverse effects. We synthesize current evidence and clarify the complex relationship between caffeine, CKD, and cardiovascular disease. Current evidence suggests that moderate caffeine intake is probably safe in CKD and may be potentially beneficial. Stronger evidence is needed before robust recommendations can be made for clinical practice.

Quercetin has anti-inflammatory properties. This study aims to explore the association between dietary quercetin intake, stroke risk, and long-term survival in chronic kidney disease (CKD) patients. The analysis included 2001 CKD participants from National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018, with a weighted total population of 25,005,023. A weighted logistic regression model, restricted cubic splines (RCS) curve, weighted COX proportional hazards model, subgroup analysis, and Kaplan-Meier curve were constructed to comprehensively analyze the relationship between dietary quercetin intake and stroke prevalence as well as long-term survival. At the same time, propensity score matching (PSM) was used to reduce the influence of confounding factors. After adjusting for all covariates, for every 1 mg/day increase in dietary quercetin intake, the prevalence of stroke decreases by 4% (OR = 0.96, 95% CI: 0.92-1.00). The RCS curve indicates that the protective effect of dietary quercetin intake on the prevalence of stroke is a linear relationship. Moreover, subgroup analysis indicated that the protective effect of dietary quercetin intake on the prevalence of stroke might be achieved by reducing inflammation. Meanwhile, for every 1 mg/day increase in dietary quercetin intake, the mortality decreases by 2% (HR = 0.98, 95% CI: 0.96-1.00). This observational cohort study showed that increased dietary quercetin intake is associated with reduced stroke risk and increased long-term survival in CKD patients. It is necessary to recommend increasing dietary quercetin intake as a supplementary treatment for CKD patients.

BackgroundType 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) are significant global health challenges, particularly in older adults where their coexistence exacerbates disease burden and leads to adverse outcomes. Chronic kidney disease (CKD), a severe complication of T2DM, is increasing in prevalence and significantly contributes to morbidity and mortality. Early detection of CKD in older patients with T2DM and CVD is crucial for timely intervention.MethodsThis study developed a predictive model using electronic health record data from 28,443 older inpatients with T2DM and CVD at the Affiliated Banan Hospital of Chongqing Medical University (2018–2025). The study population was divided into training (n=21,234) and validation (n=7,209) sets. Predictive variables were selected through univariate logistic regression, LASSO regression, and multivariate logistic regression analyses. The model was visualized using a nomogram and validated using ROC curves, calibration curves, and decision curve analysis (DCA).ResultsThe model identified seven independent predictors of CKD: systolic blood pressure, uric acid (UA), hemoglobin, glycated hemoglobin, white blood cell count, triglyceride glucose, and UA/Cr ratio. The nomogram demonstrated good discriminative ability with AUCs of 0.845 (95% CI: 0.836–0.853) in the training set and 0.853 (95% CI: 0.838–0.867) in the validation set. Calibration curves showed good agreement between predicted and observed risks. DCA indicated that the model provided a net benefit across a range of threshold probabilities, highlighting its clinical utility.ConclusionThe developed nomogram provides a practical tool for clinicians to predict CKD risk in older patients with T2DM and CVD using readily available clinical data. This model can facilitate early identification and intervention for high-risk patients, potentially improving outcomes.

Objective: To describe the prevalence of chronic kidney disease (CKD) in adults in Anhui Province and evaluate the dose-response relationship between blood pressure (BP) and CKD. Methods: Based on multistage stratified cluster random sampling, China Chronic Disease and Risk Factor Surveillance was conducted in 12 prefectures of Anhui in 2023. A total of 7 597 permanent residents aged ≥18 years were recruited for questionnaire interviews, physical measurements, and laboratory tests. Logistic regression combined with restricted cubic splines (RCS) was used to evaluate the association between BP and CKD. Results: After exclusion, 7 346 participants were included in the final analysis. The analysis indicated that the weighted prevalence of CKD was 11.7% (95%CI: 9.9%-13.6%) in adults, with 11.4% (95%CI: 9.2%-13.5%) in men and 12.1% (95%CI: 9.4%-14.9%) in women, in Anhui in 2023. After adjustment for relevant confounders, compared with individuals with SBP <130 mmHg, the odds ratios for CKD were 1.72 (95%CI: 1.45-2.05) time, 2.00 (95%CI: 1.62-2.49) time, and 3.24 (95%CI: 2.38-4.41) time in those with SBP 140-, 160-, and ≥180 mmHg, respectively. Compared with individuals with DBP <80 mmHg, the odds ratios for CKD were 1.20 (95%CI: 1.04-1.39) time, 1.39 (95%CI: 1.15-1.68) time, 1.72 (95%CI: 1.25-2.35) time, and 2.69 (95%CI: 1.46-4.96) time in those with DBP 80-, 90-, 100-, and ≥110 mmHg. RCS analyses revealed linear dose-response relationships of SBP and DBP with CKD. Below 130/80 mmHg, the risk for CKD remained relatively low, whereas once blood pressure reached or exceeded 130/80 mmHg, the risk for CKD increased obviously. Conclusion: Elevated blood pressure might be a key risk factor for the onset of CKD, and blood pressure level at 130/80 mmHg might indicate that it is necessary to conduct intervention for CKD prevention.

Associations of ozone exposure and residential greenness with early chronic kidney disease in young adults from the Tianshan cohort.

Air pollution exposure is increasingly recognized as a risk factor for chronic kidney disease (CKD), but the underlying mechanisms, especially the complex gene-environment interactions as reflected in genetic susceptibility, transcriptomic, and proteomic signatures, remain to be elucidated. We conducted a large-scale prospective cohort study including 330,002 UK Biobank participants with an average follow-up of 13.0 years. Annual average concentrations of PM2.5, PM2.5-10, PM10, NO2, and NOX were assessed. Cox proportional hazards models were applied to estimate CKD risk associated with long-term air pollution exposure. We further evaluated non-linear relationships using restricted cubic splines (RCS), potential mediators via mediation analyses, and CKD susceptibility through additive interaction analyses with baseline comorbidities and polygenic risk scores (PRS). Additionally, transcriptome-wide association study (TWAS) and proteome-wide two-step Mendelian randomization (MR) were integrated to explore potential molecular pathways. Higher exposures to PM2.5 (HR: 1.36, 95% CI: 1.22-1.51, per 5µg/m³), PM2.5-10 (HR: 1.25, 95% CI: 1.07-1.46, per 5µg/m³), PM10 (HR: 1.20, 95% CI: 1.06-1.36, per 10µg/m³), and NOX (HR: 1.04, 95% CI: 1.02-1.07, per 20µg/m³) were significantly associated with increased CKD risk, whereas NO2 showed no significant association(HR: 0.98, 95% CI: 0.95-1.00, per 10µg/m³). RCS revealed non-linear relationships for PM2.5-10 and PM10. Mediation analyses indicated that incident hypertension and type 2 diabetes mellitus (T2DM) acted as potential mediators in these associations. Crucially, additive interaction analyses revealed that participants with pre-existing hypertension or type 1 diabetes mellitus (T1DM) were significantly more vulnerable to specific pollution-driven CKD. Compared to individuals with low genetic risk and low air pollution exposure, those with both high genetic risk and high exposure exhibited the highest CKD risk, demonstrating a clear gradient effect across categories.TWAS identified shared genes potentially linking air pollutants with CKD, including upregulated transcripts (STX2, PHOSPHO2, NECAB3) and downregulated transcripts (CDK3, MEIOB, NDUFAF1, CRIPAK). Furthermore, proteome-wide MR analyses identified ALDH3A1, F12, and SNCG as potential risk proteins, and GNLY and MEGF10 as protective proteins. This study provides comprehensive evidence that long-term air pollution exposure is associated with increased CKD risk and offers exploratory insights into the potential molecular pathways underlying this association, advocating the incorporation of renal health considerations into air quality control policies.