bluuebunny/crossref_metadata_2025_split huggingface dataset:
400-P: KidneyIntelX Impact on ADA DKD Prevention Model Metrics
Authors: TOKITA JOJI , MCNICHOLAS TONY , NADKARNI GIRISH N. , COCA STEVEN , DONOVAN MICHAEL J. 
Published: June 2024

The ADA DKD Prevention Model was developed to define key concepts for DKD prevention and treatment. We sought to describe and quantify specific outcome measures outlined in the ADA model following deployment of a system-wide interdisciplinary approach that centered around KidneyIntelX, a prognostic test that utilizes combines prognostic biomarkers and clinical variables to generate patient-specific risk assessment for kidney function decline. We assessed the changes in various process measures, including clinical assessments, referrals, and changes in short- and intermediate-term metrics. 6258 patients were tested with KidneyIntelX across the Mount Sinai Health System between 2021 and 2023. The median age was 67 years, with 51% females and 25% identified as African American. Baseline eGFR was 65 ml/min/1.73 m2, UACR 56 mg/g, and HbA1c 7.2%. Among tested patients scoring intermediate (40%) or high (10%) risk, UACR testing increased by 25%, NSAID prescriptions decreased by 11%, and use of SGLT2i and GLP1-RAs increased by 14-37%. Hypertension control and control of HbA1c improved by 12 to 27%, and albuminuria decreased by 19%.
In conclusion, risk assessment in patients with stages G1-3b DKD resulted in improvements in several process measures including UACR testing, guideline-recommended therapies, less nephrotoxin usage, and better control of hypertension, glycemia, and albuminuria.

Disclosure
J. Tokita: Research Support; Renalytix. T. McNicholas: None. G.N. Nadkarni: Stock/Shareholder; Renalytix. S. Coca: Stock/Shareholder; Renalytix. Consultant; Bayer Inc., Takeda Pharmaceutical Company Limited, 3ive Labs, Vifor Pharma Management Ltd., Boehringer-Ingelheim. M.J. Donovan: Employee; Renalytix.

Funding
Renalytix
404-P: Characterization of the Differential Effects of Oxyntomodulin (GLP-1/Glucagon) and GLP-1 on Body Weight, Glucose Metabolism and Renal Function in db/db Mice
Authors: ANVARI GOLNAZ , POCAI ALESSANDRO 
Published: June 2024

Introduction: Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR). Because GLP-1 agonism has been reported to have a renoprotective effect in animal models and humans, we compared the effect of simultaneous GCGR and GLP-1 activation to matched GLP-1 agonism on kidney function in mice.
Methods: Male 16 wk old db/db BLKS/J mice (n=30) with increased serum creatinine (~3-fold) were selected and treated once daily with saline, OXM or OXM-Q3E (a peptide analog to OXM without GCGR activity) for 6 weeks. Body weight and food intake were monitored weekly. An intraperitoneal glucose tolerance test (IPGTT) was performed on week 1 after food was removed for 6h. Plasma levels were collected before and at the end of the study to evaluate plasma creatinine and ketone bodies. OXM, but not OXMQ3E, activates the GCGR in vivo as shown by increased plasma ketone bodies (OXM 7.7±0.4, OXMQ3E 4.1±0.3, Vehicle 3.5±0.4 mg/dL). During the IPGTT, OXM and OXMQ3E had similar improvement in glucose tolerance while OXM reduced body weight and serum creatinine to a greater extent than OXMQ3E.
Results: OXM, but not OXMQ3E, activates the GCGR in vivo as shown by increased plasma ketone bodies (OXM 7.7±0.4, OXMQ3E 4.1±0.3, Vehicle 3.5±0.4 mg/dL). During the IPGTT, OXM and OXMQ3E had similar improvement in glucose tolerance while OXM reduced body weight and serum creatinine to a greater extent than OXMQ3E.
Conclusions: Our results provide new insights into the mechanism of action of OXM and suggest that activation of GCGR may have beneficial effect on kidney function when delivered together with GLP-1.

Disclosure
G. Anvari: None. A. Pocai: None.
405-P: Pharmacological Activation of Kidney AMPK Promotes Diuresis and Natriuresis in Rats
Authors: ANVARI GOLNAZ , POCAI ALESSANDRO 
Published: June 2024

Introduction: In vitro and in vivo genetic studies have demonstrated that AMP-activated protein kinase (AMPK) controls renal epithelial electrolyte transport stimulating renal sodium and water reabsorption. Using a selective small molecule pan AMPK activator, cpd 1, we characterize the contribution of AMPK to the regulation of renal transport, the final composition of excreted urine and potential mechanisms involved.
Methods: Sprague-Dawley (SD) rats were injected subcutaneously with vehicle (20% Hydroxypropyl-beta-cyclodextrin), cpd 1, or the loop diuretic furosemide as a diuretic positive control, dissolved in 5ml/kg injection volume. Urine and blood samples were collected for measurement of creatinine, sodium, blood urea nitrogen (BUN). Transcutaneous glomerular filtration rate (GFR) was assessed at 5-7 hours post treatment using fluorescein-isothiocyanate-(FITC)-sinistrin clearance in conscious rats. Glycoprotein non-metastatic melanoma protein B (GPNMB) and pAMPK were evaluated in plasma and kidney lysate, respectively.
Results: Sustained elevation of renal AMPK and upregulation of plasma GPNMB were observed in rats treated with cpd 1 (10 mg/kg). After 24 hours, similar to furosemide, cpd 1 increased the urine output and BUN/creatinine ratio. Natriuresis was also increased for both treatments while GFR was reduced.
Conclusion: Pharmacological activation of renal AMPK resulted in a strong effect on diuresis and natriuresis in rats.

Disclosure
G. Anvari: None. A. Pocai: None.
406-P: Kidney Disease and Risk of Diabetic Ketoacidosis in Type 1 Diabetes
Authors: BAKHSH ABDULMOHSEN M.K. , BUDHRAM DALTON R. , BAPAT PRIYA , ABUABAT MOHAMMAD I. , VERHOEFF NATASHA , MUMFORD DOUG , ORSZAG ANDREJ , CHERNEY DAVID , FRALICK MICHAEL , WEISMAN ALANNA , ERIK LOVBLOM LEIF , PERKINS BRUCE A. 
Published: June 2024

Introduction & Objective: Sodium glucose linked transporter inhibitors (SGLTi) in T1D raise DKA risk but hold potential for kidney protection, especially with impaired renal function [eGFR &lt;60 ml/min/1.73m2]. We aimed to determine if those with eGFR impairment have higher DKA risk, perhaps owing to lower buffering capacity, thereby reducing safety of SGLTi use.
Methods: Previously collected data from the DCCT/EDIC Study was obtained through the NIDDK central repository. We assessedtime-varying eGFR over 34 years as exposures and subsequent time-to-first DKA event as the outcome in Cox proportional hazard models.
Results: Of 1441 participants, 297 experienced 488 DKA events over 34-year follow-up. Unadjusted nonlinear association between eGFR categories indicated a “J-shaped” relationship (Figure). Using eGFR of 100 ml/min/1.73m2 as the reference, there were no differences in the relative hazard for eGFR ≤ 110 ml/min/1.73m2 while eGFR &gt; 110 ml/min/1.73m2 had progressively higher risk of DKA. This relationship was only partially explained by covariates in an adjusted model.
Conclusion: Impaired kidney function did not increase DKA risk, implying that use of interventions that increase DKA risk (such as SGLTi) should not cause greater concern than in those with normal eGFR. However, hyperfiltration (eGFR ≈ &gt;120ml ml/min/1.73m2) may impart greater DKA risk and requires further study.

Disclosure
A.M.K. Bakhsh: None. D.R. Budhram: None. P. Bapat: None. M.I. Abuabat: None. N. Verhoeff: None. D. Mumford: None. A. Orszag: None. D. Cherney: Other Relationship; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK an. Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. M. Fralick: Consultant; singal1, proofdx. A. Weisman: None. L. Lovblom: None. B.A. Perkins: Advisory Panel; Abbott. Other Relationship; Novo Nordisk. Advisory Panel; Insulet Corporation, Nephris. Other Relationship; Medtronic. Advisory Panel; Sanofi, Vertex Pharmaceuticals Incorporated, Dexcom, Inc.

Funding
Diabetes Canada (Operating Grant OG-3-21-5572-BP)
409-P: Evaluating the Agreement between CKD-EPI Calculated eGFR and mGFR in People with Diabetes—An International Individual Participant Data Meta-analysis
Authors: KWOK RODNEY , KISHORE KARTIK , ZAFARI TINA , HACHEM MARIAM , KOYE DIGSU , BJORNSTAD PETTER , RESEARCH GROUP DCCT/EDIC , SCHAEFFNER ELKE , JEONG TAEDONG , MIN WON-KI , MACISAAC RICHARD , CHURILOV LEONID , EKINCI ELIF I. 
Published: June 2024

Introduction: Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide. We and others have shown that CKD-EPI equation is less accurate in estimating glomerular filtration rate (eGFR) in people with diabetes. This study aimed to assess the agreement between directly measured glomerular filtration rate (mGFR) and eGFR (2021 CKD-EPI) in individuals with type 1 or type 2 diabetes, especially in clinically relevant ranges of GFR.
Methods: Datapoints (n=16,182) were collected from people with type 1 and type 2 diabetes from six international cohorts (Diabetes Control and Complication Trial [DCCT, USA], Colorado [USA], Germany, Korea, Spain, and Australia), with mGFR assessed using exogenous filtration markers. The intra-class correlation coefficient between mGFR and eGFR was estimated using (a) a one-step intra-individual participant data meta-analysis approach, and (b) a four-level mixed-effect linear model which included studies and individual participants as first and second level random effects, method of measurement as third level fixed effect and time as fourth level random effect.
Results: Whilst overall mGFR and eGFR agreement was good (ICC: 0.82, 95%CI: 0.79, 0.84), subgroup analyses based on clinically relevant GFR ranges(&lt;30, 30-59, 60-89, ≥90 ml/min per 1.73m2) revealed poor agreement between mGFR and eGFR measurements (ICC: 0.38, 0.40, 0.29, 0.34 respectively).
Conclusion: Our data suggest the need for alternative methods to calculate eGFR in people with diabetes, particularly across clinically relevant GFR ranges, to improve early detection and management of kidney impairment and optimize intervention strategies for DKD.

Disclosure
R. Kwok: None. K. Kishore: None. T. Zafari: None. M. Hachem: None. D. Koye: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. E. Schaeffner: Consultant; AstraZeneca. Other Relationship; National Kidney Foundation. T. Jeong: None. W. Min: None. R. MacIsaac: None. L. Churilov: None. E.I. Ekinci: Advisory Panel; Lilly Diabetes. Research Support; Novo Nordisk, Boehringer-Ingelheim, Eli Lilly and Company. Board Member; Eli Lilly and Company. Advisory Panel; Abbott. Research Support; Endogenex, Versanis, AstraZeneca.

Funding
Australian Government Research Training Program (RTP) Scholarship
412-P: Kidney Shape in Magnetic Resonance Imaging—A Possible Biomarker for Diabetic Kidney Disease?
Authors: KYWE SOE KYWE , SHARMA KANISHKA , PERIQUITO JOAO , SHORE ANGELA , GOODING KIM M. , SELVARAJAH DINESH 
Published: June 2024

Introduction: With advancement in medical imaging, magnetic resonance imaging (MRI) is considered as an alternative source of biomarkers. The aim of this study was to explore the potential of kidney shape factors measured by MRI as biomarkers for DKD progression as early DKD tends to have larger kidney volume due to hypertrophy and hyper-filtration.
Methods: Total 134 participants with type 2 diabetes and eGFR&gt;30 ml/min/1.73 m2 from iBEAt study were examined. This EU-funded, multi-centre renal imaging study seeks to identify novel biomarkers for DKD. All MRI data was acquired on 3T Siemens scanners. Each kidney was segmented using in-house software. Significant threshold was set at p&lt;0.01. Hierarchical cluster analysis (HCA) among 15 shape parameters was conducted by centroid clustering method (SPSS V29.0).
Results: The mean (SD) age of study participants was 70(8) years, eGFR 76.7(13.6) ml/min/1.73 m2, UACR 4.3(14.4) mg/mmol and 35.8% women. Several shape factors (mean (SD)) such as bounding box volume (495(126) ml), convex hull volume (212(48) ml), short (5.3(0.6) cm) and long axis length (12(1.2) cm) and surface area (227(36) cm2) correlated strongly with kidney volume (KV) (Range r = -0.54 to 0.99). Two distinct clusters were identified in HCA; cluster 1 include compactness and extent which were 3D shape features with low correlation to KV (r = 0.03 and -0.03 respectively, p&lt;0.01). Conversely, cluster 2 parameters mainly consisted of shape measures which were more closely correlated to KV.
Conclusion: Compactness and extent were statistically independent of KV.Extent is the ratio of KV to its bounding box volume; compactness is the surface area-to-volume ratio relative to that of an equivalent sphere, which has 100% compactness. Reduction in compactness indicates an irregular kidney shape secondary to ageing, cortical thinning and compression by surrounding structures. These measures may serve as independent prognostic markers that predict increased risk of future renal decline.

Disclosure
K. Soe: None. K. Sharma: Employee; Antaros Medical. J. Periquito: None. A. Shore: None. K.M. Gooding: None. D. Selvarajah: Research Support; Abbott. Speaker's Bureau; Grunenthal. Research Support; Impeto medical.

Funding
The Innovative Medicines Initiative 2 Joint Undertaking (115974)
413-P: Comparative Effectiveness of Glucose-Lowering Agents on Kidney Outcomes in Adults with Type 2 Diabetes at Moderate Cardiovascular Risk
Authors: NEUMILLER JOSHUA J. , HERRIN JEPH , SWARNA KAVYA , POLLEY ERIC , GALINDO RODOLFO J. , UMPIERREZ GUILLERMO , DENG YIHONG , MICKELSON MINDY , MCCOY ROZALINA G. 
Published: June 2024

Introduction & Objective: Guideline-directed care of people with type 2 diabetes (T2D) and high risk of cardiovascular disease (CVD) is informed by robust outcome trials. Little is known about the impact of T2D drugs in adults with T2D with moderate CVD risk, particularly on key kidney outcomes.
Methods: We used claims data from OptumLabs® Data Warehouse, linked to 100% sample of Medicare claims, for adults ≥21 years with T2D and moderate baseline CVD risk initiated on a GLP-1RA, SGLT2i, DPP4i, or sulfonylurea between 1/1/2014 and 12/31/2021. We used Cox models in a target trial framework to compare incident rates of a kidney composite outcome, including stage 3-5 chronic kidney disease, kidney failure, or initiation of kidney replacement therapy.
Results: We identified 364,714 adults with T2D, moderate CVD risk, and without stage 3 or greater CKD at baseline (mean age 65.5 years, 48.9% female). Compared to DPP4i, sulfonylurea therapy was associated with increased risk (HR:1.04; 95% CI:1.02-1.06), while SGLT2i (HR:0.70; 95% CI:0.67-0.73) and GLP-1RA (HR:0.87; CI:0.83-0.92) use were associated with lower risks for the kidney composite outcome (Figure).
Conclusion: SGLT2i and GLP-1RA are associated with lower risks, and sulfonylureas are associated with higher risk, for incident kidney disease in people with T2D and moderate CVD risk.

Disclosure
J.J. Neumiller: Advisory Panel; Bayer Inc., Boehringer-Ingelheim, Eli Lilly and Company, Proteomics International. J. Herrin: None. K. Swarna: None. E. Polley: None. R.J. Galindo: Consultant; Abbott. Other Relationship; Dexcom, Inc. Consultant; Bayer Inc. Other Relationship; Novo Nordisk, Eli Lilly and Company. Consultant; Boehringer-Ingelheim, AstraZeneca. G. Umpierrez: Research Support; Abbott, Bayer Inc., Dexcom, Inc., AstraZeneca. Advisory Panel; Dexcom, Inc. Y. Deng: None. M. Mickelson: None. R.G. McCoy: Research Support; American Diabetes Association. Other Relationship; American Diabetes Association. Consultant; Wolters Kluwer Health. Research Support; National Institutes of Health, Patient-Centered Outcomes Research Institute. Consultant; Yale New Haven Health System.

Funding
Patient-Centered Outcomes Research Institute (PCORI) award (PCS-1409-24099)
414-P: A Novel Mutation in HNF1B Promotes Ferroptosis-Mediated Renal Mesangial Cells Fibrosis
Authors: CHEN XIN , WEI QIANYING , HUANG MEI , LI YUXIAO , ZHANG MEI 
Published: June 2024

Objective: In this study, we identified a novel HNF1B gene mutation (c.445C&gt;A) in a young male MODY5 patient with and elevated serum creatinine levels and albuminuria.
Method: We constructed the HNF1B wild type (HNF1B-WT) and the novel missense mutation (c.445C&gt;A) Mutant (HNF1B-Mut) plasmid and no-loaded control plasmid (pCDH) were transfected into mouse mesangial cells (MMCs) and identified successfully by real-time fluorescent quantitative PCR (RT-qPCR). The changes of cell proliferation activity were detected by CCK-8, the changes of intracellular reactive oxygen species (ROS) were detected by DCFH-DA probe, and the expressions of fibronectin (FN) and iron death index 4-HNE were detected by immunofluorescence staining. The expression levels of long chain fatty acyl-CoA synthetase 4 (ACSL4) and GPX4, key regulatory proteins of iron death, were detected by RT-qPCR.
Results: RT-qPCR confirmed that compared with the control group, the expression levels of CycD1, FN, COLI and other indicators of proliferation and fibrosis decreased in the HNF1B-WT group, but increased in the HNF1B-Mut group. Immunofluorescence co-staining indicated that FN and 4-HNE decreased in HNF-WT cells and increased in HNF1B-Mut cells. CCK-8 assay confirmed that HNF1B-Mut plasmid restored the proliferation activity of MMCs inhibited by HNF-1B. After loading with DCFH-DA probe, it was found that HNF1B-Mut group had higher ROS level than HNF1B-WT group, suggesting that HNF1B-Mut promoted cellular oxidative stress. RT-qPCR showed that the expression of ACSL4 was
increased and GPX4 was decreased in HNF1B-Mut group compared with wild control group.
Conclusion: HNF1B c.445C&gt;A mutation can promote MMCs proliferation and fibrosis by improving intracellular oxidative stress and iron death sensitivity. These abnormal changes may be related to the abnormal renal function impairment of the clinical progenitor.

Disclosure
X. Chen: None. Q. Wei: None. M. Huang: None. Y. Li: None. M. Zhang: None.

Funding
National Natural Science Foundation of China (Approval No.81974103), the Improvement of Clinical Ability Project of Jiangsu Province Hospi-tal (JSPH-MA-2021-3), Jiangsu Provincial Medical Key Discipline (Laboratory) (ZDXK202202).
419-P: Association of Remnant Cholesterol (rem-C) with Kidney Disease Progression in People with Type 2 Diabetes (T2D)
Authors: YAMAMOTO YUI , HANAI KO , MORI TOMOMI , BABAZONO TETSUYA 
Published: June 2024

Objective: A study using diabetic mice demonstrated that cholesterol deposition in the kidneys provokes apoptosis of podocytes and albuminuria; however, most studies in people with diabetes have failed to demonstrate significant association of higher LDL cholesterol (LDL-C) levels with progression of diabetic nephropathy (DN). Accumulating evidences reveal a strong atherogenicity of cholesterol in triglyceride-rich lipoproteins, called rem-C. Currently, data on the association between rem-C and DN are limited. Here, we examined whether rem-C can predict kidney disease progression in people with diabetes.
Methods: This was a retrospective cohort study of 5161 Japanese adults with T2D (mean age: 61 years, women: 36.4%). The exposure was serum rem-C levels at baseline, treated as a categorical variable and classified into four categories based on the quartile of rem-C. Rem-C was calculated as total cholesterol minus LDL-C minus HDL cholesterol, referencing previous studies. The outcome was a composite of a ≥30% decline in eGFR or the initiation of kidney replacement therapy. The hazard ratios (HRs) for the outcome were estimated using the multivariable Cox proportional hazards model. In the analysis treating rem-C as a continuous variable, the multivariable-adjusted restricted cubic spline model was used.
Results: The median (interquartile range: IQR) baseline rem-C (mg/dL) was 25 (18-35). During a median (IQR) follow-up of 7.6 (3.0-11.6) years, 1172 people reached the outcome. In setting the first quartile group (n= 1257) as the reference, the HRs (95% CIs) of the second (n= 1302), third (n= 1304), and fourth quartile groups (n= 1298) were 1.13 (0.92-1.39), 1.38 (1.10-1.74), and 1.36 (1.01-1.81), respectively. A similar trend was also shown by the spline model.
Conclusion: Rem-C levels were identified as a risk factor for kidney disease progression in people with T2D. Future interventional studies are needed to clarify the potential of rem-C as a therapeutic target for DN.

Disclosure
Y. Yamamoto: None. K. Hanai: None. T. Mori: None. T. Babazono: None.
42-OR: A Small Intestinal Bile Acid Modulates the Gut Microbiome to Improve Glucose Regulation following Bariatric Surgery
Authors: CHEN YINGJIA , CHAUDHARI SNEHAL N. , HARRIS DAVID A. , TAVAKKOLI ALI , DEVLIN SLOAN , SHEU ERIC 
Published: June 2024

Bariatric surgical procedures such as sleeve gastrectomy (SG) provide the most effective and durable therapy for type 2 diabetes (T2D). This work is aimed at identifying molecule mediators of bariatric surgery’s metabolic effects, in order to develop non-invasive interventions for T2D. Our previous work demonstrated that gastrointestinal levels of the bacterial metabolite lithocholic acid (LCA) are decreased after SG in mice and humans. Here, we investigate the metabolic effects of LCA and the mechanisms of its downregulation post-SG. We find that LCA feeding to chow-fed mice worsens glucose tolerance, decreases respiratory exchange ratio, and increases adiposity. We also show that taurodeoxycholic acid (TDCA) is the only bile acid whose concentration is increased in the murine small intestine post-SG. Moreover, TDCA abundance is decreased in small intestinal tissue from patients with T2D. Treatment of cecal cultures with SG small intestinal contents or TDCA in vitro reduces the expression of bacterial bile acid-inducible (bai) operon and production of LCA. In vivo treatment of diet-induced obese mice with TDCA also suppresses the bai operon, reduces LCA levels and leads to improvements in host glucose handling. Abolishing gut microbiota or co-feeding LCA to TDCA-treated mice substantially diminishes the beneficial effects of TDCA on glucose regulation, demonstrating that TDCA’s glucoregulatory effects require the microbiota. This work has revealed that TDCA is an endogenous inhibitor of LCA production and suggests that TDCA may contribute to the glucoregulatory effects of bariatric surgery.

Disclosure
Y. Chen: None. S.N. Chaudhari: None. D.A. Harris: None. A. Tavakkoli: Consultant; AltrixBio. S. Devlin: None. E. Sheu: Other Relationship; Intuitive Surgical. Consultant; Vicarious Surgical Inc. Speaker's Bureau; Cine-Med.

Funding
National Institutes of Health (R01 DK126855R35, GM128618); Alfred P. Sloan Fellowship; National Institutes of Health (K99/R00 DK128503)