Acute kidney injury and chronic kidney disease in individuals with Down syndrome: A nationwide cohort study

Exercise reduces the risk of chronic kidney disease in individuals with nonalcoholic fatty liver disease: A nationwide cohort study

Perioperative Acute Kidney Injury

The aim of this study was to investigate the potential association between retinol intake and the risk of chronic kidney disease (CKD) in individuals with type 2 diabetes mellitus (T2DM). The study included individuals diagnosed with T2DM between 2009 and 2018 from the NHANES database. Demographic and laboratory test data were collected for these individuals, as well as information on CKD diagnosis. Logistic regression models were utilized to estimate the relationship between different retinol intakes and the risk of CKD in patients with T2DM. A total of 3988 patients were included in the study. The mean prevalence of CKD in the T2DM population in the United States from 2009 to 2018 was 36.98 (0.02)%. Multivariate logistic regression analysis revealed a 26% decrease in the incidence of CKD in individuals with higher retinol intake compared to those with lower retinol intake in T2DM (OR = 0.74; 95% CI 0.56–0.98). Furthermore, an increase in retinol intake per 1-standard deviation (SD) was associated with a 16% decreased risk of the incidence of CKD (OR = 0.84; 95% CI 0.72–0.97). Lower retinol intake is an independent risk factor for the onset of CKD in patients with T2DM, and augmenting moderate quantities of retinol confers potential nephroprotective advantages.

The progression trajectory of renal filtration function has not been well characterized in patients with early-onset type 2 diabetes mellitus (T2DM) although albuminuria is often reported in this population. We aim to study the risk of progressive chronic kidney disease (CKD) in individuals with early-onset T2DM. In total, 1189 T2DM participants were followed for 3.9 (interquartile range 3.2-4.7) years. Progressive CKD was defined as estimated glomerular filtration rate (eGFR) decline of ≥5 mL/min/1.73 m2 per year. Early-onset T2DM was defined as age at T2DM diagnosis between 18 and 30 years. Compared with later-onset counterparts (N = 1032), participants with early-onset T2DM (N = 157) were more obese and had poorer glycaemic control at baseline. In the follow-up, 24.2% and 15.6% experienced progressive CKD in early-onset and later-onset participants, respectively (P = 0.007). Logistic regression suggested that participants with early-onset T2DM had 2.63-fold [95% confidence interval (CI) 1.46-4.75] higher risk of progressive CKD after accounting for multiple traditional risk factors. Furthermore, the excess risk of progressive CKD associated with early-onset T2DM mainly occurred in participants with preserved renal function [eGFR ≥60 mL/min/1.73 m2, odds ratio (OR) 2.85, 95% CI 1.50-5.42] and was more pronounced in those with diabetes duration <10 years (OR 3.67, 95% CI 1.51-8.90). Individuals with early-onset T2DM have a higher risk of progressive CKD. The excess risk mainly exhibits in early stage of CKD and cannot be solely attributed to traditional risk factors and a longer diabetes duration.

&lt;p dir="ltr"&gt;There is an increasing need for new biomarkers improving prediction of chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D). We aimed to identify blood-based epigenetic biomarkers associated with incident CKD and develop a methylation risk score (MRS) predicting CKD in newly-diagnosed individuals with T2D. DNA methylation was analysed epigenome-wide in blood from 487 newly-diagnosed individuals with T2D, of whom 88 developed CKD during 11.5-year follow-up. Weighted Cox regression was used to associate methylation with incident CKD. Weighted logistic models and cross-validation (k=5) were performed to test if the MRS could predict CKD. Methylation at 37 sites was associated with CKD development, based on FDR&lt;5% and absolute methylation differences ≥5% between individuals with incident CKD and those free of CKD during follow-up. Notably, 15 genes annotated to these sites, e.g., TGFBI, SHISA3, and SLC43A2 (encoding LAT4), have been linked to CKD or related risk factors including blood pressure, BMI, or eGFR. Using a MRS including 37 sites and cross-validation for prediction of CKD, we generated ROC curves with AUC=0.82 for the MRS and AUC=0.87 for the combination of MRS and clinical factors. Importantly, ROC curves including the MRS had significantly better AUCs versus the one only including clinical factors (AUC=0.72). The combined epigenetic biomarker had high accuracy in identifying individuals free of future CKD (negative predictive value=94.6%). We discovered a high-performance epigenetic biomarker for predicting CKD, encouraging its potential role in precision medicine, risk stratification, and targeted prevention in T2D.&lt;/p&gt;

&lt;p dir="ltr"&gt;There is an increasing need for new biomarkers improving prediction of chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D). We aimed to identify blood-based epigenetic biomarkers associated with incident CKD and develop a methylation risk score (MRS) predicting CKD in newly-diagnosed individuals with T2D. DNA methylation was analysed epigenome-wide in blood from 487 newly-diagnosed individuals with T2D, of whom 88 developed CKD during 11.5-year follow-up. Weighted Cox regression was used to associate methylation with incident CKD. Weighted logistic models and cross-validation (k=5) were performed to test if the MRS could predict CKD. Methylation at 37 sites was associated with CKD development, based on FDR&lt;5% and absolute methylation differences ≥5% between individuals with incident CKD and those free of CKD during follow-up. Notably, 15 genes annotated to these sites, e.g., TGFBI, SHISA3, and SLC43A2 (encoding LAT4), have been linked to CKD or related risk factors including blood pressure, BMI, or eGFR. Using a MRS including 37 sites and cross-validation for prediction of CKD, we generated ROC curves with AUC=0.82 for the MRS and AUC=0.87 for the combination of MRS and clinical factors. Importantly, ROC curves including the MRS had significantly better AUCs versus the one only including clinical factors (AUC=0.72). The combined epigenetic biomarker had high accuracy in identifying individuals free of future CKD (negative predictive value=94.6%). We discovered a high-performance epigenetic biomarker for predicting CKD, encouraging its potential role in precision medicine, risk stratification, and targeted prevention in T2D.&lt;/p&gt;

Inflammatory Bowel Disease With Chronic Kidney Disease and Acute Kidney Injury

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Do Children With Acute Kidney Injury Require Long-term Evaluation for CKD?

Proton pump inhibitors (PPIs) have been linked to acute kidney injury (AKI) and chronic kidney disease (CKD); however, current evidence has only been evaluated in a small number of studies with short follow-up periods. This study examined the association between PPI use and risk of incident AKI and CKD in a large population-based health maintenance organization (HMO) cohort. Patients aged 18years or older, without evidence of preexisting renal disease, started on PPI therapy, and those continuously enrolled for at least 12months between July 1993 and September 2008 were identified in an HMO database. Incidences of AKI and CKD were defined using documented International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes or a glomerular filtration rate less than 60ml/min/1.73m2 after initiation of PPI therapy. Patients with AKI were followed for up to 90days (cohort 1), and patients with CKD required at least 1year of follow-up (cohort 2). Multivariable logistic regression analyses were used to adjust for differences in demographics (excluding race), comorbidities, and medication use between groups. In 93,335 patients in the AKI cohort, 16,593 of whom were exposed to PPIs, the incidence rate of AKI was higher in the PPI group than nonusers (36.4 vs 3.54 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPI exposure was associated with an increased risk of AKI (adjusted odds ratio [aOR] 4.35, 95% confidence interval [CI] 3.14-6.04, p<0.0001). In 84,600 patients in the CKD cohort, 14,514 of whom were exposed to PPIs, the incidence rate of CKD was higher in the PPI group than nonusers (34.3 vs 8.75 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPIs were associated with a higher risk of CKD compared with controls (aOR 1.20, 95% CI 1.12-1.28, p<0.0001). Associations between PPI use and AKI and CKD persisted in propensity score-matched analyses. The use of PPIs is associated with an increased risk of incident AKI and CKD. This relationship could have a considerable public health impact; therefore, health care provider education and deprescribing initiatives will be necessary to raise awareness and reduce health care burden.

Association of accelerometer-derived “weekend warrior” moderate to vigorous physical activity, chronic kidney disease and acute kidney injury

Objective: We aimed to investigate the association of BMI in late adolescence and BMI trajectories in adulthood with chronic kidney disease (CKD), end-stage kidney disease (ESKD) and acute kidney injury (AKI) later in life. Design and method: Two cohort analyses were performed, firstly evaluating the link between adolescent BMI and CKD, ESKD and AKI throughout life, secondly assessing the link between BMI change from adolescence to midlife, and the risk of CKD, ESKD and AKI thereafter. Data from the Swedish Conscription Register, the Northern Sweden Health and Disease Study, the Swedish National Patient Register and the Cause of Death Register were included. Patients were stratified into quintiles of BMI in adolescence and BMI change until midlife. Data were analysed using Cox proportional hazards model. Results: 1 324 831 subjects met the inclusion criteria for BMI evaluation in late adolescence. The mean age at conscription was 18.3±0.8 years and the average BMI was 21.6±2.6 kg/m2. 5593 subjects developed CKD, 2358 developed ESKD and 8029 developed AKI. In the adjusted analyses, an increased risk of developing CKD and ESKD was seen from the fourth BMI quintile (HR 1.25, 95% CI 1.15-1.36 for BMI 21.9-23.6 kg/m2; HR 2.13, 95% CI 1.97-2.31 for BMI &gt;23.6 kg/m2, for CKD), whereas the risk of AKI was increased already from the third BMI quintile (HR 1.15, 95%CI 1.15-1.24 for BMI 20.7-21.9 kg/m2). 32 221 subjects in a regional cohort had an additional BMI evaluation at mean age 42.1±8.6 years. The mean change in BMI between assessments was 4.8±3.2 kg/m2. We found that BMI increase of &gt;7 kg/m2 from late adolescence to mid-life was associated with higher risk of CKD (HR 2.78, 95%CI 1.45-5.30) and AKI (3.49, 2.23-5.47) in non-adjusted analyses; only AKI persisted after adjustment (HR 2.60, 95%CI 1.58-4.28). Conclusions: To conclude, BMI in late adolescence is associated with CKD and ESKD, with increased risk from BMI levels &gt;21.9 kg/m2. BMI increase during adulthood was only associated with an increased risk of AKI after covariate-adjustment, suggesting that adolescence is a critical period for the association between BMI and future kidney disease.

Does Inflammation Fuel the Fire in CKD?

Risk of chronic kidney disease in individuals on lithium therapy in Iceland: a nationwide retrospective cohort study

&lt;p dir="ltr"&gt;Inflammatory bowel disease (IBD) and chronic kidney disease (CKD) are chronic conditions with a bidirectional relationship influenced by immune dysregulation, chronic inflammation, and gut-kidney axis interactions. IBD, characterized by persistent gastrointestinal inflammation, is associated with kidney complications such as nephrolithiasis and interstitial nephritis, often stemming from systemic effects or adverse drug reactions. Colectomy, a surgical intervention frequently required in severe IBD cases, can lead to dehydration and electrolyte imbalances, increasing the risk of kidney damage. While biologic therapies have transformed IBD treatment by targeting specific immune pathways to reduce inflammation and induce remission, they carry potential risks, including rare kidney complications like drug-induced interstitial nephritis. The intricate interplay between IBD and CKD remains underexplored, underscoring the need for comprehensive research to improve patient care and outcomes.&lt;/p&gt;&lt;p dir="ltr"&gt;This thesis aims to advance our understanding of the bidirectional relationship between IBD and kidney diseases through large-scale epidemiological studies utilizing real-world data.&lt;/p&gt;&lt;p dir="ltr"&gt;Study I investigated the relationship between reduced kidney function, measured by estimated glomerular filtration rate (eGFR), and the risk of developing IBD in a large adult population. Over nearly a decade of follow-up, reduced eGFR was associated with a higher risk of IBD, particularly Crohn's disease, with stronger associations observed in women. These findings suggest that impaired kidney function may predispose individuals to IBD.&lt;/p&gt;&lt;p dir="ltr"&gt;Study II examined the association between IBD and kidney-related complications, including CKD and acute kidney injury (AKI). Over a median 9-year follow-up, IBD patients were found to have significantly increased risks of CKD and AKI compared to non-IBD individuals. More than 10% of IBD patients developed CKD within 10 years of diagnosis, emphasizing the importance of regular kidney function monitoring and timely nephrological care.&lt;/p&gt;&lt;p dir="ltr"&gt;Study III explored the relationship between colectomy and the risk of AKI and kidney failure in patients with biopsy-confirmed IBD within a large Swedish nationwide population. During a median follow-up of 14 years, colectomy was associated with increased risks of these kidney outcomes, particularly in patients with total colectomy, prolonged stoma periods, or ulcerative colitis. These findings highlight the need for targeted kidney function monitoring in high-risk IBD populations undergoing colectomy.&lt;/p&gt;&lt;p dir="ltr"&gt;Study IV assessed the risk of kidney complications in IBD patients treated with vedolizumab compared to infliximab or adalimumab. Adapting a target trial emulation framework, the study revealed that vedolizumab was associated with higher risks of AKI and CKD compared to infliximab, with elevated but less pronounced risks compared to adalimumab. Younger patients were particularly vulnerable to AKI. These findings underscore the importance of close kidney function monitoring in IBD patients initiating vedolizumab therapy.&lt;/p&gt;&lt;p dir="ltr"&gt;In conclusion, this thesis provides robust real-world evidence on the complex interplay between IBD and kidney diseases. The findings emphasize a critical need for vigilant kidney function monitoring in IBD patients, particularly those undergoing colectomy or initiating vedolizumab therapy, to improve clinical outcomes and patient care.&lt;/p&gt;&lt;h3&gt;List of scientific papers&lt;/h3&gt;&lt;p dir="ltr"&gt;I. &lt;b&gt;Yang Y,&lt;/b&gt; Ludvigsson JF, Olen O, Sjölander A, Carrero JJ. Estimated Glomerular Filtration Rate and the Risk of Inflammatory Bowel Disease in Adults: A Swedish Population-Based Study. Inflammatory Bowel Diseases. 2024;30(5):718-725. &lt;a href="https://doi.org/10.1093/ibd/izac267" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1093/ibd/izac267&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;II. &lt;b&gt;Yang Y,&lt;/b&gt; Ludvigsson JF, Olen O, Sjölander A, Carrero JJ. Absolute and Relative Risks of Kidney and Urological Complications in Patients With Inflammatory Bowel Disease. American Journal of Gastroenterology. 2024;119(1):138-146. &lt;a href="https://doi.org/10.14309/ajg.0000000000002473" rel="noreferrer" target="_blank"&gt;https://doi.org/10.14309/ajg.0000000000002473&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;III. &lt;b&gt;Yang Y,&lt;/b&gt; Ludvigsson JF, Forss A, Faucon AL, Faye AS, Olen O, Sjölander A, Carrero JJ. Risk of Kidney Failure in Patients With Inflammatory Bowel Disease Undergoing Colectomy: A Nationwide Cohort Study. Clinical Gastroenterology and Hepatology. 2024;22(11):2291-2298.e17. &lt;a href="https://doi.org/10.1016/j.cgh.2024.05.010" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1016/j.cgh.2024.05.010&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;IV. &lt;b&gt;Yang Y,&lt;/b&gt; Forss A, Voghera S, Ludvigsson JF, Faucon AL, Sjölander A, Olén O, Carrero JJ. Adverse kidney events in patients with inflammatory bowel disease initiating biologics with vedolizumab, infliximab or adalimumab. [Manuscript]&lt;/p&gt;