Adverse Kidney Outcomes Research Articles

Association of variabilities in body mass index and metabolic parameters with post-kidney transplantation renal outcomes

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients.

Association between different proportions of crescents and the progression of IgA nephropathy (IgAN): a systematic review and meta-analysis.

Immunoglobulin A nephropathy (IgAN) is a complex renal disease with a highly variable clinical course. Identifying reliable prognostic markers is crucial for risk stratification and treatment decisions. This study aimed to understand the influence of different proportions of crescents (Cs) on the progression of IgAN. Four databases (PubMed, Web of Science, Embase, and Cochrane Library) were searched until September 25, 2023. The study encompassed IgAN patients, focusing on kidney outcomes and end-stage kidney disease (ESKD). Statistical analysis included calculating hazard ratios (HR) for binary outcomes and examining publication bias. The meta-analysis involved thirteen studies comprising 11,849 patients. For kidney outcomes, crescent formation may be linked to an elevated risk (HR = 2.01, 95%CI 1.40-2.87, P < 0.001). Furthermore, significantly increased risks of kidney outcomes were observed with a crescent proportion > 10 (HR = 1.8, 95%CI 1.32-2.45, P < 0.001) and > 25%(HR = 2.11, 95% CI 1.47-3.02, P < 0.001). Regarding ESKD, a proportion > 25% also displayed an elevated risk (HR = 1.70, 95% CI 1.18-2.44, P = 0.004). However, a proportion > 10% (including > 25%) did not show a significant association with ESKD (HR = 1.12, 95% CI 0.36-3.47, P = 0.842) versus less. This systematic review and meta-analysis established a strong association between crescent proportions and the progression of IgAN. Higher proportions, notably exceeding 25%, were reliable prognostic markers, indicating a greater risk of adverse kidney outcomes and ESKD. These findings have significant clinical implications, offering the potential for more precise risk stratification in IgAN patients.

Dapagliflozin versus empagliflozin and major adverse cardiovascular events in type 2 diabetes: a nationwide cohort study

Abstract Background Large randomized clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus (T2DM) at high risk of atherosclerotic cardiovascular disease. Whether these effects might differ between individual SGLT2-inhbitors remain unclear given the lack of head-to-head comparisons. Purpose To examine the association between treatment with dapagliflozin versus empagliflozin and the long-term rate of major adverse cardiovascular events (MACE) in patients with T2DM. Methods Using nationwide registries, all Danish residents with T2DM, who initiated treatment with dapagliflozin or empagliflozin from 2015 to 2020, were identified. Only treatment with dapagliflozin or empagliflozin was considered in the present analysis, since approximately 3% initiated treatment with other SGLT2-inhibitors (i.e., canagliflozin and ertugliflozin). Patients were followed from date of the first claimed prescription of dapagliflozin or empagliflozin until the outcome of interest, emigration, death, or end of study (December 31, 2021). The primary outcome was a composite endpoint of major adverse cardiovascular events (i.e., time to first heart failure hospitalisation, acute myocardial infarction (AMI), stroke, or all-cause mortality). The primary outcome was compared between the dapagliflozin and empagliflozin group, overall and in prespecified subgroups of interest, with multivariable Cox proportional hazards regression models. Results In total, 61,031 patients with T2DM initiated treatment with dapagliflozin (N=21,028; 34.5%) or empagliflozin (N=40,003; 65.5%). The median age of study population was 62.6 years (25th-75th percentile, 54.2-70.8 years), and 62.6% were men. There were no clinically significant differences between the dapagliflozin and empagliflozin group with respect to age, sex, and clinical characteristics. The median follow-up was 3.1 years (25th-75th percentile, 1.9-4.5 years). The adjusted long-term hazard ratios of the primary outcome, overall and in prespecified subgroups of interest, are displayed in the Figure. Compared with empagliflozin, treatment with dapagliflozin was not associated with a significantly different rate of the primary outcome (HR 1.02 [95% CI, 0.97-1.07]). The observed association was consistent across clinically relevant subgroups, including in patients with and without heart failure, chronic kidney disease, and atherosclerotic cardiovascular disease. Conclusion In a large, nationwide cohort of patients with T2DM, treatment with dapagliflozin was associated with a similar rate of major adverse cardiovascular outcomes compared with empagliflozin, and this association was consistent across clinically relevant subgroups. These findings suggest that the benefits of SGLT2-inhibitors can be characterized as a class-effect.

Relationship of body mass index and kidney outcomes in patients with primary glomerulonephritis: A systematic review and meta-analysis.

Primary glomerulonephritis, is a major contributor to the development of chronic kidney disease and end-stage renal disease. Previous studies on the relationship between overweight/obesity with primary glomerulonephritis in the chronic kidney disease was inconsistent. This study aimed to systematically review and meta-analyze the relationship between body mass index and adverse kidney outcomes in patients with primary glomerulonephritis. PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure were searched. Patients were divided into an overweight/obesity group (group O) and a non-overweight/obesity group (group N) according to their body mass index values. Twenty-six studies with 11,038 patients were selected. Patients in group O had deteriorated baseline characteristics, including worse baseline estimated glomerular filtration rate (weighted mean differences [WMD] = -5.99), higher Scr (WMD = 7.34), uric acid (WMD = 47.53), 24-hour proteinuria (WMD = 0.40), and a higher prevalence rate of hypertension (odds ratio, OR = 2.70) and diabetes mellitus (OR = 2.644). On the histopathologic level, patients in group O had a significantly lower total glomerular number (WMD = -2.30); however, no difference was observed in mesangial cell proliferation, endocapillary hypercellularity, crescents, sclerosis, and tubular atrophy/interstitial fibrosis between the 2 groups. The incidence of adverse renal outcomes in the 2 groups was similar (OR = 0.96). The meta-analysis of hazard ratios from Cox regressions indicated a strong association between overweight/obesity and poor renal outcomes in glomerulonephritis (HR = 1.17). Overweight/obesity glomerulonephritis patients had remarkably poor baseline clinicopathological characteristics. Being overweight or obesity would likely impact the progression of primary glomerulonephritis but not serious enough to contribute to significant poor renal outcomes, which could be prevented by aggressive therapy.

The Association Between Vasopressin and Adverse Kidney Outcomes in Children and Young Adults Requiring Vasopressors on Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults. Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study. Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021. Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1-2), and late (days 3-7). None. Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20-2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17-6.11; p = 0.02) compared with early initiation. Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin.

Association of Pancreas Fat Fraction with Adverse Kidney and Cardiovascular Outcomes

Association of Pancreas Fat Fraction with Adverse Kidney and Cardiovascular Outcomes

Trace Element Intake and Major Adverse Kidney Outcomes in Critically Ill Patients with Severe Sepsis

Trace Element Intake and Major Adverse Kidney Outcomes in Critically Ill Patients with Severe Sepsis

Finerenone and Kidney Outcomes in Patients with Heart Failure: The FINEARTS-HF Trial.

Finerenone has kidney protective effects in patients with chronic kidney disease (CKD) with type 2 diabetes, but effects on kidney outcomes in patients with heart failure (HF) with and without diabetes and/or CKD are not known. Examine the effects of finerenone on kidney outcomes in FINEARTS-HF, a randomized trial of finerenone vs. placebo among patients with HF with mildly reduced or preserved ejection fraction. We explored the effects of finerenone on the secondary outcome of a sustained ≥50% eGFR decline or kidney failure (sustained eGFR decline <15 mL/min/1.73 m2; initiation of maintenance dialysis; renal transplant). In this prespecified analysis, we also report effects of finerenone on: 1) sustained ≥57% eGFR decline or kidney failure; 2) eGFR slope; 3) changes in urine albumin/creatinine ratio (UACR). Among 6,001 participants, mean baseline eGFR was 62 ±20mL/min/1.73m2; 48% had eGFR <60mL/min/1.73m2. Overall, 5,797 had baseline UACR data (median 18 [7,67]mg/g). Over 2.6 years median follow-up, the incidence of the composite kidney outcome (≥50% eGFR decline or kidney failure) was numerically, but non-significantly, higher for finerenone vs. placebo (75 vs. 55 events; HR 1.33; 95%CI 0.94, 1.89). Similar results were observed for the composite of ≥57% eGFR decline or kidney failure (41 vs. 31 events; HR 1.28; 95%CI 0.80, 2.05), though the overall event frequency was relatively low. During the first 3 months, finerenone led to an acute decline in eGFR of -2.9 mL/min/1.73m2 (95%CI -3.4, -2.4) but did not alter chronic (from 3 months) eGFR slope (+0.2 mL/min/1.73m2/year; 95%CI -0.1, +0.4), vs. placebo. The difference in total slope was -0.7 (95%CI -0.9 to -0.4) mL/min/1.73 m2/year. Finerenone reduced UACR by 30% (95%CI 25%, 34%) over 6 months vs. placebo, an effect that persisted throughout follow-up. Finerenone reduced the risk of new-onset of micro- and macroalbuminuria by 24% (HR 0.76; 95%CI 0.68, 0.83) and 38% (HR 0.62; 95%CI 0.53, 0.73), respectively. In FINEARTS-HF, a population at low risk of adverse kidney outcomes, finerenone did not significantly modify the kidney composite outcomes. Finerenone led to a greater reduction in initial eGFR, but did not result in a significant difference in chronic eGFR slope, vs. placebo. Finerenone led to early and sustained reductions in albuminuria and reduced the risk of new-onset micro- and macroalbuminuria.

Association Between Glycemic Variability and Persistent Acute Kidney Injury After Noncardiac Major Surgery: A Multicenter Retrospective Cohort Study.

While the relationship between glycemic variability (GV) and acute kidney injury (AKI) has been a subject of interest, the specific association of GV with persistent AKI beyond 48 hours postoperative after noncardiac surgery is not well-established. This retrospective cohort study aimed to describe the patterns of different GV metrics in the immediate 48 hours after noncardiac surgery, evaluate the association between GV indices and persistent AKI within the 7-day postoperative window, and compare the risk identification capabilities of various GV for persistent AKI. A total of 10,937 patients who underwent major noncardiac surgery across 3 medical centers in eastern China between January 2015 and September 2023 were enrolled. GV was characterized using the coefficient of variations (CV), mean amplitude of glycemic excursions (MAGE), and the blood glucose risk index (BGRI). Multivariable logistic regression was used to examine the relationship between GV and AKI. Optimal cutoff values for GV metrics were calculated through the risk identification models, and an independent cohort from the INformative Surgical Patient dataset for Innovative Research Environment (INSPIRE) database with 7714 eligible cases served to externally validate the risk identification capability. Overall, 274 (2.5%) of the 10,937 patients undergoing major noncardiac surgery met the criteria of persistent AKI. Higher GV was associated with an increased risk of persistent AKI (CV: odds ratio [OR] = 1.26, 95% confidence interval [CI], 1.08-1.46; MAGE: OR = 1.31, 95% CI, 1.15-1.49; BGRI: OR = 1.18, 95% CI, 1.08-1.29). Compared to models that did not consider glycemic factors, MAGE and BGRI independently contributed to predicting persistent AKI (MAGE: areas under the curve [AUC] = 0.768, P = .011; BGRI: AUC = 0.764, P = .014), with cutoff points of 3.78 for MAGE, and 3.02 for BGRI. The classification of both the internal and external validation cohorts using cutoffs demonstrated good performance, achieving the best AUC values of 0.768 for MAGE in the internal cohort and 0.777 for MAGE in the external cohort. GV measured within 48 hours postoperative period is an independent risk factor for persistent AKI in patients undergoing noncardiac surgery. Specific cutoff points can be used to stratify at-risk patients. These findings indicate that stabilizing GV may potentially mitigate adverse kidney outcomes after noncardiac surgery, highlighting the importance of glycemic control in the perioperative period.

Conventional machine learning-based prediction models did not outperform the International IgA Nephropathy Prediction Tool.

Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage kidney disease (ESKD). The International IgA Nephropathy Prediction Tool (IIgAN-PT) predicts IgAN prognosis, but improvement in the prediction performance using machine learning (ML)-based methods is needed. We analyzed 4,425 biopsy-confirmed patients with IgAN and ≥6 months of follow-up from nine tertiary university hospitals in Korea. The study population was divided into development and validation cohorts. Using the collected 87 clinicodemographic and pathological variables, ML-based prediction models for ESKD or estimated glomerular filtration rate were constructed: 1) the conventional CatBoost model, 2) the optimized CatBoost model with Cox proportional hazards, 3) the deep Cox proportional hazards model, and 4) the deep Cox mixture model. The area under the curve (AUC) and calibration plots were used to investigate the discriminative and calibration performance of the models, which were then compared with those of the IIgAN-PT full model. The full model showed excellent performance (AUC [95% confidence interval] for 5-year outcome, 0.896 [0.8530.940]), with acceptable calibration results. The ML-based models showed good performance in predicting adverse kidney outcomes and revealed acceptable discrimination performance in the external validation (AUC [95% confidence interval] for the 5-year outcome: 1) 0.829 [0.791-0.866]; 2) 0.847 [0.804-0.890]; 3) 0.823 [0.784-0.862]; and 4) 0.832 [0.794-0.870]), although they underestimated the external validation cohort risks. With the validation data, the overall performance of the IIgAN-PT was non-inferior to that of the ML-based model. Conclusions: Our ML-based models showed good performance in predicting adverse kidney outcomes in patients with IgAN but they did not outperform the IIgAN-PT.

Adverse cardiovascular and kidney outcomes in people with SARS-CoV-2 treated with SGLT2 inhibitors

BackgroundWhether use of SGLT2 inhibitors reduces the risk of cardiovascular and kidney events in people who contracted SARS-CoV-2 infection is not clear.MethodsWe used the healthcare databases of the United States Department of Veterans Affairs to build a cohort of 107,776 participants on antihyperglycemic therapy and had SARS-CoV-2 infection between March 01, 2020 and June 10, 2023. Within them, 11,588 used SGLT2 inhibitors and 96,188 used other antihyperglycemics. We examined the risks of major adverse cardiovascular events (MACE)—a composite of death, myocardial infarction and stroke, and major adverse kidney events (MAKE)—a composite of death, eGFR decline > 50%, and end stage kidney disease after balancing baseline characteristics between groups through inverse probability weighting. Survival analyses were conducted to generate hazard ratio (HR) and absolute risk reduction per 100 person-years (ARR).ResultsOver a median follow up of 1.57 (IQR: 1.05–2.49) years, compared to the control group, SGLT2 inhibitors use is associated with reduced risk of MACE (HR 0.82 (0.77, 0.88), ARR 1.73 (1.21, 2.25)) and reduced risk of MAKE (HR 0.75 (0.71, 0.80), ARR 2.62 (2.13, 3.11)). Compared to the control group, SGLT2 inhibitors use is associated with reduced risk of the secondary outcomes of hospitalization (HR 0.94 (0.90, 0.98), ARR 1.06 (1.36, 1.76)), anemia (HR 0.71 (0.65, 0.76), ARR 2.43 (1.95, 2.90)), and acute kidney injury (HR 0.84 (0.79, 0.89), ARR 1.86 (1.29, 2.42)).ConclusionsAmong people with SARS-CoV-2 infection on antihyperglycemic therapy, compared to those on other antihyperglycemics, those on SGLT2 inhibitors have less risk of adverse cardiovascular and kidney outcomes.

Abstract 07: Ambulatory Blood Pressure Variability, Progression of Kidney Disease, and Cardiovascular Outcomes in the Chronic Renal Insufficiency Cohort

Background: Visit-to-visit blood pressure variability is strongly associated with adverse kidney and cardiovascular outcomes in a wide range of patient populations. Patients with chronic kidney disease (CKD) have abnormal circadian blood pressure patterns which may affect 24-hour ambulatory blood pressure variability (ABPV). Methods: We used ambulatory blood pressure monitoring (ABPM) data from participants in the Chronic Renal Insufficiency Cohort (CRIC). Blood pressures were obtained every 30 minutes during day and night. We assessed 24-hour, daytime and nighttime systolic ABPV using average real time variability (ARV); the sum of the absolute differences between consecutive BP readings divided by the total number of readings minus one. Cox proportional hazards models were used to evaluate the association of ARV with the development of 50% reduction in eGFR or end stage kidney disease or adverse cardiovascular (CV) events (myocardial infarction, stroke, peripheral artery disease, new atrial fibrillation, and heart failure). Results: There were 1502 CRIC participants included in the analysis of whom 44% were female and mean age was 63 years (standard deviation 10). Anthropometric and clinical factors associated with higher tertile of ARV included older age, higher BMI, higher urine protein to creatinine ratio, lower estimated glomerular filtration rate, diabetes, hypertension, dyslipidemia and atherosclerotic heart disease. In unadjusted Cox proportional hazard models, 24-hour systolic ARV was associated with both adverse kidney (Hazard Ratio [HR] 1.16 95% confidence interval [CI] 1.06-1.27) and CV events (HR 1.35 95%CI 1.22-1.50). However, in adjusted models that included clinical and sociodemographic factors, there were no statistically significant associations of 24-hour systolic ARV with either adverse kidney (HR 1.02, 95%CI 0.91-1.14) or CV events (HR 0.93, 95%CI 0.84 -1.04). Similarly, daytime and nighttime ARV were not statistically significantly associated with kidney and CV events in adjusted analyses. Conclusions: In a large cohort of patients with CKD, ABPV was not associated with adverse kidney and CV outcomes in adjusted models. Thus, in the context of the many cardiometabolic risk factors present in patients with CKD, ABPV is not an independent mechanism of adverse clinical outcomes in this high-risk population.

Long-Term Kidney Outcomes in Children with Posterior Urethral Valves: A Population-Based Cohort Study.

Posterior urethral valves represent the most common cause of lower urinary tract obstruction in male infants (∼1/4000 live births). Long-term kidney outcomes of posterior urethral valves remain uncertain. We aimed to determine the time-varying risk of major adverse kidney events (MAKE) following children with posterior urethral valves into adulthood. A population-based retrospective cohort study of all males (<2 years) diagnosed with posterior urethral valves between 1991-2021 in Ontario, Canada. Comparator cohorts were: 1) male general population and 2) male pyeloplasty patients (both <2 years). The primary outcome was MAKE (death, long-term kidney replacement therapy [dialysis or kidney transplant], or chronic kidney disease). Time-to-MAKE was analyzed using multivariable-adjusted Cox proportional hazards models. We censored for provincial emigration, or administrative censoring (March 31, 2022). We included 727 children with posterior urethral valves, 855 pyeloplasty comparators, and 1,013,052 general population comparators. Median follow-up time was 16.6 years (Q1-3 8.6-24.5) overall. Throughout follow-up, 32% of children with posterior urethral valves developed MAKE vs. 1% of the general population and 6% of pyeloplasty comparators. Their adjusted hazard ratio for MAKE was 36.6 (95%CI 31.6-42.4) vs. the general population. The risk of developing MAKE declined over the first 5 years after posterior urethral valves diagnosis but remained elevated for >30-year follow-up. Children with posterior urethral valves were also at higher risk of death, chronic kidney disease, long-term kidney replacement therapy, hypertension, and acute kidney injury than general population or pyeloplasty comparators. Children with posterior urethral valves are at higher risk of adverse long-term kidney outcomes well into adulthood.

Clinical Outcomes of Tirzepatide or GLP-1 Receptor Agonists in Individuals With Type 2 Diabetes

Despite its demonstrated benefits in improving cardiovascular risk profiles, the association of tirzepatide with mortality and cardiovascular and kidney outcomes compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) remains unknown. To investigate the association of tirzepatide with mortality and adverse cardiovascular and kidney outcomes compared with GLP-1 RAs in patients with type 2 diabetes. This retrospective cohort study used US Collaborative Network of TriNetX data collected on individuals with type 2 diabetes aged 18 years or older initiating tirzepatide or GLP-1 RA between June 1, 2022, and June 30, 2023; without stage 5 chronic kidney disease or kidney failure at baseline; and without myocardial infarction or ischemic or hemorrhagic stroke within 60 days of drug initiation. Treatment with tirzepatide compared with GLP-1 RA. The primary outcome was all-cause mortality, and secondary outcomes included major adverse cardiovascular events (MACEs), the composite of MACEs and all-cause mortality, kidney events, acute kidney injury, and major adverse kidney events. All outcomes were analyzed using Cox proportional hazards regression models. There were 14 834 patients treated with tirzepatide (mean [SD] age, 55.4 [11.8] years; 8444 [56.9%] female) and 125 474 treated with GLP-1 RA (mean [SD] age, 58.1 [13.3] years; 67 474 [53.8%] female). After a median (IQR) follow-up of 10.5 (5.2-15.7) months, 95 patients (0.6%) in the tirzepatide group and 166 (1.1%) in the GLP-1 RA group died. Tirzepatide treatment was associated with lower hazards of all-cause mortality (adjusted hazard ratio [AHR], 0.58; 95% CI, 0.45-0.75), MACEs (AHR, 0.80; 95% CI, 0.71-0.91), the composite of MACEs and all-cause mortality (AHR, 0.76; 95% CI, 0.68-0.84), kidney events (AHR, 0.52; 95% CI, 0.37-0.73), acute kidney injury (AHR, 0.78; 95% CI, 0.70-0.88), and major adverse kidney events (AHR, 0.54; 95% CI, 0.44-0.67). Treatment with tirzepatide was associated with greater decreases in glycated hemoglobin (treatment difference, -0.34 percentage points; 95% CI, -0.44 to -0.24 percentage points) and body weight (treatment difference, -2.9 kg, 95% CI, -4.8 to -1.1 kg) compared with GLP-1 RA. An interaction test for subgroup analysis revealed consistent results stratified by estimated glomerular filtration rate, glycated hemoglobin level, body mass index, comedications, and comorbidities. In this study, treatment with tirzepatide was associated with lower hazards of all-cause mortality, adverse cardiovascular events, acute kidney injury, and adverse kidney events compared with GLP-1 RA in patients with type 2 diabetes. These findings support the integration of tirzepatide into therapeutic strategies for this population.

Dihydropyridine Calcium Channel Blockers and Kidney Outcomes.

Early trials of dihydropyridine calcium channel blockers (DCCBs) suggest a detrimental effect on intraglomerular pressure and an association with albuminuria. We sought to evaluate the associations of DCCB initiation with albuminuria and kidney failure with replacement therapy (KFRT) and to determine whether renin-angiotensin system (RAS) blockade modified these associations. We conducted a target trial emulation study using a new user, active comparator design and electronic health record data from Geisinger Health. We included patients without severe albuminuria or KFRT who were initiated on a DCCB or thiazide (active comparator) between January 1, 2004, and December 31, 2019. Using inverse probability of treatment weighting, we performed doubly robust Cox proportional hazards regression to estimate the association of DCCB initiation with incident severe albuminuria (urine albumin to creatinine ratio > 300 mg/g) and KFRT, overall and stratified by RAS blocker use. There were 11,747and 26,758 eligible patients initiating a DCCB and thiazide, respectively, with a weighted baseline mean age of 60 years, systolic blood pressure of 143 mm Hg, and eGFR of 86 mL/min/1.73 m2, and with a mean follow-up of 8 years. Compared with thiazides, DCCBs were significantly associated with the development of severe albuminuria (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.16-1.43), with attenuation of risk in the presence of RAS blockade (P for interaction < 0.001). The risk of KFRT was increased among patients without RAS blockade (HR, 1.66; 95% CI, 1.19-2.31), but not with RAS blockade (P for interaction = 0.005). DCCBs were associated with increased risk of albuminuria and, in the absence of RAS blockade, KFRT. These findings suggest coupling DCCB therapy with RAS blockade may mitigate adverse kidney outcomes.

Dietary Fiber Intake and Clinical Outcomes in Chronic Kidney Disease: A Report From the Chronic Renal Insufficiency Cohort Study

ObjectiveDietary interventions are the mainstay of chronic diseases prevention in general population, but the evidence to support such therapeutic approaches in patients with chronic kidney disease (CKD) is less robust. The objective of this study is to examine the association between dietary fiber intake and adverse cardiovascular and kidney outcomes and all-cause mortality in participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Design and MethodsA total of 3791 CRIC participants with self-reported dietary fiber intake were included in the analyses stratified by tertiles of dietary fiber at study baseline. Hazard Ratios for occurrence of all-cause mortality, composite cardiovascular events and composite kidney events were calculated using Cox Proportional Hazards models adjusted for demographic, clinical, and laboratory characteristics, including levels of inflammatory markers, C-reactive protein (CRP) and Interleukin-6 (IL-6). ResultsMean daily dietary fiber intake was 15.2 g/d. During a median (SD) follow up of 14.6 (4.4) years, 1074 deaths from any cause occurred. In multivariable adjusted models, participants in the middle and low dietary fiber tertiles had a 19% (HR [95%CI]), 1.19 [1.02, 1.39]) and 11% (1.11 [0.95, 1.31]) greater risk of death respectively, compared to those in the highest fiber intake tertile. No statistical significant associations were observed between dietary fiber intake and adverse cardiovascular and kidney outcomes. Higher dietary fiber intake was not significantly associated with lower levels of CRP and IL-6. ConclusionA lower intake of dietary fiber was not associated with all-cause mortality in participants with CKD after adjustments for kidney function and inflammatory biomarkers. There was no significant association between dietary fiber intake and adverse kidney and cardiovascular outcomes. Future randomized intervention trials are needed to identify whether a high dietary fiber intake translates into improved clinical outcomes in CKD.

Post-acute and Chronic Kidney Function Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Initiative.

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m2, End Stage Kidney Disease diagnosis, dialysis, or transplant.

Comorbidity and Medication Trends in Chronic Kidney Disease and Incident Atrial Fibrillation: A Nationwide Cohort Study.

Chronic kidney disease (CKD) is associated with an increased incidence of atrial fibrillation (AF). Also, patients with AF are prone to adverse kidney outcomes. We examined comorbidities and medication use in patients with CKD and incident AF. The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide retrospective register-linkage study including data from 168,233 patients with incident AF from 2007 to 2018, with laboratory data from 2010 onwards. Estimated glomerular filtration rate (eGFR) was available for 124,936 patients. The cohort was divided into 5 CKD stages with separate groups for dialysis and kidney transplantation. At AF diagnosis eGFR &lt;60 mL/min/1.73 m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded more comorbidities and medications. During 2010-2018 in patients with eGFR &lt;60 mL/min/1.73 m2 prevalence of hypertension, dyslipidaemia, and diabetes increased from 82 to 88%, from 50 to 66% and from 25 to 33%, respectively (&lt;0.001). Throughout the observation period, lipid-lowering medication was underused. More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR &lt;60 mL/min/1.73 m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but the use of survival-affecting medications, such as lipid-lowering medication, was suboptimal at all stages of CKD. More attention should be given to the optimal treatment of risk factors in this high CV risk population.

Mortality, Hepatic Decompensation, and Cardiovascular- and Renal-Related Outcomes in Lean Versus Non-lean Patients Hospitalized With Metabolic Dysfunction-Associated Steatohepatitis (MASH).

Metabolic dysfunction-associated steatohepatitis (MASH) is an important cause of cirrhosis and end-stage liver disease. In addition, there have been reports of worse extrahepatic outcomes, especially cardiovascular events, in patients with lean patients' fatty liver disease compared to the non-lean group.There is limited data on hepatic, cardiac, and renal outcomes in lean compared to non-lean patients with MASH. This study aims to evaluate the cardiovascular, renal, and hepatic outcomes in hospitalized US adults with MASH, focusing on a comprehensive comparison between lean and non-lean patients. The National Inpatient Sample (NIS) database was queried from 2016 to 2020 to identify hospitalizations with MASH. Hospitalizations with a history of overweight and obesity (lean body mass index (BMI) <25 vs. lean BMI >25) were also identified. The primary outcome was in-hospital mortality. Secondary outcomes were major adverse cardiovascular outcomes (MACE: a composite of acute myocardial infarction, cardiac arrest, stroke, heart failure, and atrial fibrillation); major adverse kidney outcome (MAKE: a composite outcome of acute kidney injury (AKI), renal replacement therapy, and renal cancer), and hepatic decompensation (esophageal varices with bleeding, ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and hepatorenal syndrome) Multivariate logistic regression analysis was used to derive risk ratios for clinical outcomes. We included 539,275 MASH patients in our sample; 324,330 (60%) were lean. The included patients were mostly female (61%), the mean age was 64 years, and 76% were White. At baseline, non-lean patients had a higher prevalence of heart failure, hypertension, and hyperlipidemia. There was no difference in the prevalence of smoking among both groups.In a multivariate analysis, with adjustment for age, sex, race, sarcopenia, cardiometabolic risk factors, hospital characteristics, admission type, socioeconomic factors, and all comorbidities (including 31 Elixhauser comorbidities), lean status was associated with a 40% increased risk of mortality(adjusted odds ratio (aOR) 1.40, confidence interval (CI) 1.29-1.53), 19% increased risk of MACE (aOR 1.19; 95% CI 1.14-1.24), 20% increased risk of renal decompensation (aOR 1.25; 95% CI 1.20-1.30), and 33% increased risk of hepatic decompensation (aOR 1.33 CI 1.28-1.38). Lean patients with MASH are at higher risk of cardiovascular and renal outcomes and may benefit from enhanced screening for early identification and treatment to improve outcomes.

#1200 Coronary artery calcium modifies the relationship between blood pressure and adverse kidney outcome: results from KNOW-CKD

Abstract Background and Aims Previous studies evidenced that elevated coronary artery calcium (CAC) score is associated with higher chronic kidney disease (CKD) progression. However, the use of CAC score to guide CKD management has not been adequately evaluated. Here, we evaluated whether presence of CAC modify the association between systolic blood pressure (SBP) and CKD progression in patients with CKD. Method We analyzed 1693 participants with CKD stages G1 to G5 from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Key exclusion criteria were kidney failure with replacement therapy (KFRT) and missing data for CAC and SBP information. We categorized participants according to baseline SBP and CAC score (Controlled BP, SBP &amp;lt; 120 mmHg; Elevated BP without CAC, SBP 120-140 mmHg and CAC score = 0; Elevated BP with CAC, SBP 120-140 mmHg and CAC score &amp;gt;0; Uncontrolled BP, SBP &amp;gt;140 mmHg) and compared the CKD progression. The CKD progression was defined as a composite of halving eGFR from baseline value or onset of KFRT. Results During 10,023 person-years of follow-up (median 6.2 years), the composite outcome occurred in 689 (40.7%) participants, and 108 (6.4%) participants died among the KNOW-CKD participants. There was significant interaction between CAC score and SBP for CKD progression (P &amp;lt; 0.001). There were 181/568 (31.9%), 167/424 (39.4%), 128/314 (40.8%) 213/387 (55.0%), composite outcomes in controlled BP, elevated BP without CAC, elevated BP with CAC, uncontrolled BP group, respectively. In crude Cox regression, compared to controlled BP, elevated BP with CAC group showed similar CKD progression risk (Hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.95-1.44), whereas other strata group showed increased risk of CKD progression (elevated BP with CAC; HR, 1.59; 95% CI 1.31-1.94 and uncontrolled BP, HR, 1.94; 95% CI 1.56-2.41). Similar elevated risk in elevated BP with CAC was observed even after adjustment of age, sex, diabetes mellitus, estimated glomerular filtration ratio, and proteinuria (HR, 1.26; 95% CI, 1.02-1.56). However, the risk of CKD progression in elevated BP without CAC group was comparable to controlled BP group (HR, 1.20; 95% CI, 0.87-1.66). Conclusion Elevated SBP was more strongly associated with an increased risk of adverse kidney outcomes in patients with coronary calcification.