Modification Of Diet In Renal Disease Research Articles

Consistency of metabolite associations with measured glomerular filtration rate in children and adults

Abstract Background and hypothesis There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation. Methods We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study, and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite-mGFR correlation association with metabolite class, molecular weight, assay platform, and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r < −0.5), we assessed additional variation by age (height in children), sex, race, and BMI. Results A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race, and BMI categories (correlation of metabolite-mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates, and nucleotides were more often negatively correlated with mGFR compared to lipids, but there was no association with metabolite molecular weight, LC/MS platform, and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r<−0.5), 27 were consistently not associated with age (height in children), sex, or race. Conclusions The majority of metabolite-mGFR correlations were negative and consistent across sex, race, BMI, and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of GFR.

UroAngel: a single-kidney function prediction system based on computed tomography urography using deep learning.

Accurate estimation of the glomerular filtration rate (GFR) is clinically crucial for determining the status of obstruction, developing treatment strategies, and predicting prognosis in obstructive nephropathy (ON). We aimed to develop a deep learning-based system, named UroAngel, for non-invasive and convenient prediction of single-kidney function level. We retrospectively collected computed tomography urography (CTU) images and emission computed tomography diagnostic reports of 520 ON patients. A 3D U-Net model was used to segment the renal parenchyma, and a logistic regression multi-classification model was used to predict renal function level. We compared the predictive performance of UroAngel with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and two expert radiologists in an additional 40 ON patients to validate clinical effectiveness. UroAngel based on 3D U-Net convolutional neural network could segment the renal cortex accurately, with a Dice similarity coefficient of 0.861. Using the segmented renal cortex to predict renal function stage had high performance with an accuracy of 0.918, outperforming MDRD and CKD-EPI and two radiologists. We proposed an automated 3D U-Net-based analysis system for direct prediction of single-kidney function stage from CTU images. UroAngel could accurately predict single-kidney function in ON patients, providing a novel, reliable, convenient, and non-invasive method.

ASSESSMENT OF COMPLETE BLOOD COUNT AND LIVER ENZYMES IN CHRONIC KIDNEY DISEASE PATIENT

Chronic renal failure (CRF) poses a significant global health challenge, with chronic kidney disease (CKD) characterised by kidney damage or a glomerular filtration rate (GFR) persistently below 60 ml/min for over three months. This observational study, conducted in Faisalabad from January to July 2023, aimed to evaluate haematological variables and liver enzymes across different stages of CKD. Using non-probability purposive sampling, 144 CKD patient files and 48 healthy control files were collected, excluding specific conditions. CKD staging was determined using the Modification of Diet in Renal Disease (MDRD) algorithm, categorizing patients into mild (Group A), moderate (Group B), severe (Group C) CKD, and controls (Group D). Data analysis was performed using SPSS v23. Mean ± SD values were presented for each parameter across the four groups. Haemoglobin levels (Hb g/dl) exhibited a decreasing trend in CKD patients compared to the control group, with values of 13.7 ± 1.50 in controls, 11.7 ± 0.64 in Group 1, 9.7 ± 0.57 in Group 2, and 6.7 ± 1.5 in Group 3. Red blood cell count (RBCs per million/mm3) also decreased progressively in CKD patients compared to controls, with values of 5.48 ± 0.59, 4.62 ± 0.15, 3.57 ± 0.28, and 2.81 ± 0.23 in the respective groups. Conversely, white blood cell counts (WBC thousand/mm3) increased with CKD progression, showing values of 8406 ± 1383 in controls, 10674 ± 1006 in Group 1, 12028 ± 643.5 in Group 2, and 13564 ± 741.29 in Group 3. Similarly, platelet counts (lakh/ul) exhibited a decreasing trend in CKD patients compared to controls, with values of 324708 ± 112970, 235458 ± 63853, 144979 ± 6935.8, and 126333 ± 4768.3, respectively. Analysis of liver enzymes revealed a progressive decrease in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as CKD advanced. AST levels (U/L) decreased from 29.104 ± 3.130 in controls to 7.5825 ± 1.543 in Group 3, while ALT levels (U/L) decreased from 48.145 ± 4.9679 in controls to 12.270 ± 3.3500 in Group 3. Our findings demonstrate that haemoglobin, red blood cell count, platelet count, and liver enzyme levels (AST and ALT) decrease as CKD progresses while white blood cell count increases. These insights into haematological and hepatic biomarkers underscore the dynamic nature of CKD pathology and may inform clinical management strategies.

The prevalence of acute kidney injury in patients with community-acquired pneumonia who required mechanical ventilation.

Community-acquired pneumonia (CAP) is a common reason for intensive care unit (ICU) admission and sepsis. Acute kidney injury (AKI) is a frequent complication of community-acquired pneumonia and is associated with increased short- and long-term morbidity and mortality and healthcare costs. Describe the prevalence of AKI in patients with CAP requiring mechanical ventilation and evaluate its association with inhospital mortality. Retrospective cohort. Intensive care unit. We included patients with CAP on mechanical ventilation. Patients were categorized according to the development of AKI in the first 24 hours of ICU admission using the Kidney Disease Improving Global Outcomes (KDIGO) classification from no AKI, stage 1 AKI, stage 2 AKI, and stage 3 AKI. The primary outcome was hospital mortality. Secondary outcomes were ICU mortality, hospital and ICU length of stay, ventilation duration, tracheostomy, and renal replacement therapy requirement. Of 1536 patients included in the study, 829 patients (54%) had no AKI while 707 (46%) developed AKI. In-hospital mortality was 288/829 (34.8%) for patients with no AKI, 43/111 (38.7%) for stage 1 AKI, 86/216 (40%) for stage 2 AKI, and 196/380 (51.7%) for stage 3 AKI (P<.0001). Multivariate analysis revealed that stages 1, 2, or 3 AKI compared to no AKI were not independently associated with in-hospital mortality. Older age, vasopressor use; decreased Glasgow coma scale, PaO2/Fio2 ratio and platelet count, increased bilirubin, lactic acid and INR were associated with increased mortality while female sex was associated with reduced mortality. Among mechanically ventilated patients with CAP, AKI was common and was associated with higher crude mortality. The higher mortality could not be attributed alone to AKI, but rather appeared to be related to multi-organ dysfunction. Single-center retrospective study with no data on baseline serum creatinine and the use of estimated baseline creatinine distributions based on the MDRD (Modification of Diet in Renal Disease)equation which may lead to an overestimation of AKI. Second, we did not have data on the microbiology of pneumonia, appropriateness of antibiotic therapy or the administration of other medications that have been demonstrated to be associated with AKI.

CHA2DS2-VASc Score, Fibrinogen, and Neutrophil to Lymphocyte Ratio as Predictors of In-Stent Restenosis in Patients with Severe Kidney Disease

Objective: This study examined the relationship between CHA2DS2-VASc score, fibrinogen (FIB), and neutrophil-to-lymphocyte ratio (NLR) with in-stent restenosis (ISR) in patients with severe kidney disease (SKD). Methods: Between January 2017 and January 2022, patients with SKD who underwent coronary stent implantation at the Second Hospital of Tianjin Medical University were retrospectively analyzed. According to whether ISR occurred within 2 years of postoperative follow-up, 164 patients were categorized into the ISR group (n = 62) and the non-ISR group (n = 102). According to the Modification of Diet in Renal Disease (MDRD) formula, SKD is defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/(min·1.73 m2). Angiographic ISR was defined as a stented coronary artery segment with more than 50% constriction during the follow-up angiography. Relevant clinical data and laboratory parameters were obtained from the hospital's medical records. Results: In total, 164 patients were included (mean age: 67.1 [10.2] years, 65.2% men), grouped into 62 patients with ISR and 102 patients without. A significant difference was found in the age, previous strokes, congestive heart failure (CHF), NLR, platelet-to-lymphocyte ratio (PLR), fibrinogen, CHA2DS2-VASc score, and risk classification of CHA2DS2-VASc score of patients in the ISR group as compared to those in the non-ISR group. In a multivariable logistic regression analysis, the CHA2DS2-VASc score, fibrinogen, and NLR were identified as independent predictors of ISR. The analysis of the receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) value was 0.714 (95% confidence interval (CI): 0.634–0.793) for the CHA2DS2-VASc score and 0.652 (95% CI: 0.565–0.739) for FIB, 0.707 (95% CI: 0.627–0.788) for NLR, and 0.797 (95% CI: 0.725–0.868) for the combination of CHA2DS2-VASc score, FIB and NLR. Conclusions: The combination of CHA2DS2-VASc score, FIB, and NLR can more accurately predict the occurrence of ISR in SKD patients.

Biological variation in the estimated glomerular filtration rate of healthy individuals within 24h calculated using 2021CKD-EPI equations.

Use the MDRD (Modification of Diet in Renal Disease) and 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation void of race coefficients (CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) to estimate the BV (Biological variation) of eGFR (estimated glomerular filtration rate) within 24h in a healthy population to help explain future studies using eGFR in the context of a known BV. Blood samples were collected from 30 healthy subjects at six time points within 24h. Serum creatinine (S-Crea) and serum cystatin C (S-Cys-C) were measured, and the BV of eGFR was calculated. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data. The eGFR CVI for the four equations (MDRD, CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) were 8.39% (7.50-9.51%), 3.90% (3.49-4.42%), 6.58% (5.88-7.46%), and 5.03% (4.50-5.71%), respectively. The corresponding II and RCVpos/neg values were 0.69, 0.48, 0.51, and 0.31, and (29.30%, - 22.66%), (12.69%, - 11.2 6%), (20.97%, - 17.33%), and (15.88%, - 13.70%), respectively; RCVpos /neg of eGFR was highest in the MDRD equation and lowest in the CKD-EPI Crea equation. Additionally, the RCVpos/neg values of the individual was highest in the MDRD equation and lowest in the CKD-EPICrea+Cys-C equation; they are (56.51%, - 36.11%) and (5.01%, - 4.77%), respectively. We present data on the 24h BV eGFR of the 2021 CKD-EPI equations. The presence of BV has impact on the interpretation of GFR results, affecting CKD disease grading. The RCVpos/neg differences were large among the individuals. When using eGFRs based on the MDRD and CKD-EPI equations, it is necessary to combine RCVpos/neg values before interpreting the results.

Associations of asymptomatic coronary heart disease in a cohort of stable type 2 diabetic subjects in a tertiary health center in south eastern Nigeria: A cross sectional study

Background: Coronary heart disease (CHD) is a type of heart disease where the lumina of the major arteries of the heart (coronary arteries) are narrowed by a build-up of plaque with a resultant limitation of blood flow to and oxygenation of the heart. Coronary heart disease can pose a diagnostic challenge in diabetic subjects due to the fact that it is often asymptomatic with a resultant lack of overt clinical complaint by the patients. It is an important cause of diabetes-associated morbidity and mortality and also a huge contributor to the cost of diabetes care. Objective: To determine the association between CHD and age, sex, cigarette smoking, duration of diabetes, central obesity, glycaemic control, hypertension, chronic kidney disease (CKD), stroke, transient ischaemic attack (TIA), dyslipidaemia, lack of exercise and metabolic syndrome in type 2 diabetic subjects attending the diabetes outpatient clinic of Nnamdi Azikiwe University Teaching Hospital, Nnewi in South Eastern Nigeria. Materials and Methods: This was a cross-sectional, observational study comprising 136 clinically stable T2DM subjects that were asymptomatic of coronary heart disease. The participants had two contacts with the researcher. Firstly, all the participants were evaluated with resting ECG for the diagnosis of CHD, 30 subjects had CHD while 106 had not. Next, the 30 subjects that had CHD and 98 of the 106 that had not, were met a second time on another clinic visit where medical history was extracted and anthropometric measurements were done. Next, biochemical tests, which included fasting blood glucose (FBG), glycated haemoglobin (HbA1c), fasting lipid profile (FLP) and serum creatinine were done and the glomerular filtration rate estimated using the Modification of Diet in Renal Disease (MDRD) calculator. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 25 (Chicago, IL, USA). The level of significance was set at p &lt; 0.05. Results: A total of 128 subjects completed the study and had their data analyzed. 30 subjects had CHD while 98 had not. There was significant association between CHD and TIA (p = 0.040), but no significant association between CHD and age (p = 0.959), sex (p = 0.679), educational status (p = 0.094), cigarette smoking (p = 1.000), duration of diabetes (p = 0.335), central obesity (p = 0.726), glycaemic control (p = 1.000), hypertension (p = 1.000), CKD (p = 0.570), stroke (p = 0.141), dyslipidaemia (p = 0.290), exercise (p = 0.641) and metabolic syndrome (p = 0.633) respectively among the subjects. Conclusion: There was a high prevalence of asymptomatic CHD among stable type 2 diabetic subject and with the exception of TIA, there was no significant association between CHD and all the other risk factors for CHD that were studied, although these risk factors were found more among the subjects that had CHD compared with those that had not.

Impaired kidney function and the risk of all-cause mortality and cardiovascular disease among Chinese hypertensive adults: Using three different equations to estimate the glomerular filtration rate

ObjectivesWe aimed to seek accurate assessments of the glomerular filtration rate (GFR) in a Chinese hypertensive population to identify individuals at high risk for chronic kidney disease (CKD) progression. Then, the risk of cardiovascular disease (CVD) and all-cause death due to kidney injury were further investigated under appropriate GFR-estimation equations. MethodsIn this prospective follow-up cohort study of 10,171 hypertensive patients, we compared the discrimination power of a trio of GFR-estimation equations using Harrell's C-index, measuring the model fit by calculating the Akaike information criterion. Univariate and multivariable logistic regression analyses were respectively used to calculate the hazard ratio (HR) and 95% confidence interval [CI] values for CKD progression. In addition, we also assessed the risk of CVD and all-cause death with impaired renal function using multivariable-adjusted Cox regression models. ResultsThe Modification of Diet in Renal Disease (MDRD) equation showed the highest C-index range for the predicted probability of CKD progression in the fully adjusted model. During MDRD analysis, a low eGFR (60–89 mL/min/1.73m2 or < 60 mL/min/1.73m2) was an independent risk factor for CVD, especially stroke (1.28 [95% CI, 1.05–1.55] and 1.89 [95% CI, 1.08–3.31]), as well as all-cause mortality (1.28 [95% CI, 1.09–1.50] and 1.68 [95% CI, 1.01–2.78]). ConclusionsThe MDRD equation seems to be more suitable for screening CKD progression in Chinese hypertensive populations, targeting potential risk factors for effective prevention to reduce renal impairment so as to further limit CVD morbidity and mortality.

Correlation between Neutrophil to Lymphocyte Ratio and Urine Albumin to Creatinine Ratio in Diabetic Nephropathy Patients: A Cross-sectional Study

Introduction: One of the microvascular complications of diabetes is known as Diabetic Nephropathy (DN). The clinical manifestation of DN is an increase in the amount of albumin excreted in the urine. Albuminuria is the inflammatory process that occurs before end-stage renal failure and is a diagnostic marker. The total White Blood Cell (WBC) count is a crude but sensitive measure of inflammation. It is examined as an inflammatory marker in various cardiac and non cardiac disorders, such as acute Myocardial Infarction (MI), stroke, and heart failure. Aim: To find a correlation between Neutrophil to Lymphocyte Ratio (NLR) and Urine Albumin to Creatinine Ratio (UACR) in DN patients. Materials and Methods: This was an analytical cross-sectional study done over a period of 18 months from January 2018 to June 2019 at Vydehi Institute of Medical Sciences and Research Centre in Bengaluru, Karnataka, India. on 104 subjects diagnosed with type 2 Diabetes Mellitus (DM) registered in present study. Spot albuminuria was tested by immune turbidimetry method. Urine creatinine was tested using Jaffe’s kinetic method, from which spot UACR was calculated. The patients with albuminuria and without albuminuria were grouped into cases and controls, respectively. NLR was calculated using complete blood count and correlated with UACR. The estimated Glomerulus Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation and correlated with UACR. Cases were further subgrouped into moderately increased albuminuria and severely increased albuminuria groups. Mean and standard deviation, independent sample t-test, Chi-square test, Odds Ratio (OR) were applied to find significance. A p-value of &lt;0.05 was considered statistically significant, and an OR more than one suggests a positive association. Results: A total of 104 diabetic subjects were registered, with 52 subjects having DN and 52 having normal urine albumin. The mean age was 56±11.3 years and 50.6±11.8 years in the case and control groups, respectively. Among the 52 subjects in the case group, 12 (23.1%) were female and 40 (76.9%) were male. In the 52 control group, 30.8% (n=16) were female, and 69.2% (n=36) were male. The mean urine albumin was 75.5±121.2 mg/dL and 1.2±1.2 mg/dL in the case and control groups, respectively (p&lt;0.001). A correlation was calculated between UACR and NLR, with a cut-off value for NLR of 2.92. The cutoff value for NLR was calculated using the Receivers Operating Curve (ROC). The Chi-square test was applied, showing statistical significance (p&lt;0.001), with an OR calculated at 4.34 (OR &gt;1). Conclusion: The present study showed a significant positive correlation between NLR and UACR. Therefore, NLR may be considered a novel surrogate marker of DN, as an alternative to UACR, which is expensive and requires special equipment.

Discrepancies among equations to estimate the glomerular filtration rate for drug dosing decision making in aged patients: a cross sectional study

BackgroundPatients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations.AimTo determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care.MethodThe Cockcroft–Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland–Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison.ResultsA total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations.ConclusionClinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average.

Mini-PCNL – a boon for CKD patients with nephrolithiasis

ABSTRACT Purpose The prevalence of urinary stone disease in ESRD is 3.2%, leading to renal damage due to obstructive uropathy, infection, and frequent surgical intervention. PCNL, the gold standard for complex renal stone disease, has evolved with smaller access sheaths (14–20 F), improved optics, and fluoroscopic equipments. This study aims to assess the safety and feasibility of mini- PCNL in CKD patients with respect to postoperative outcome and its effect on stage of CKD. Patients and methods This prospective study was conducted in the Department of Urology, Sher-I-Kashmir Institute of Medical Sciences, from January 2022 to October 2022. This study included adult patients with nephrolithiasis at CKD stage 3 or higher. The primary objective of this research was to assess the impact of mini-PCNL on renal function, specifically measuring changes in estimated glomerular filtration rate (eGFR) from baseline to a 6-month follow-up. The secondary objective was to evaluate the feasibility of mini-PCNL in CKD patients in terms of complications, stone clearance rate, and duration of hospital stay. Four variable Modification of Diet in Renal Diseases(MDRD) equation was used to calculate the estimated GFR(eGFR) of each patient and NKF/KDOQI classification system to classify the stage of CKD. Results A total of 46 patients were included in the study. We found that for management of nephrolithiasis in CKD patients, mini-PCNL leads to significant improvement in eGFR at 6 months follow-up (mean difference = 14.25 ml/min/1.73 m2; p-value <0.01) with high stone-free rates (89.5%). The complication rates were comparable to standard PCNL. Conclusions mini-PCNL is a bonanza for management of CKD patients with nephrolithiasis.

Association of high-estimated glomerular filtration rate with the severity of ischemic stroke during non-vitamin K antagonist oral anticoagulants therapy: a nationwide cohort study.

While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea. This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS2-VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft-Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation. The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054). The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS.

Prevalence and oncologic impact of chronic kidney disease for upper tract urothelial carcinoma in endemic area

ObjectiveThis study aimed to assess the impact of preoperative chronic kidney disease (CKD) on the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent standard radical nephroureterectomy (RNU). MethodsA total of 1172 UTUC patients who received RNU at a single center in Taiwan between February 2005 and August 2019 were included. The patients were categorized into two groups based on their preoperative CKD stage: CKD stage ≤3 (811 patients) and CKD stage >3 (361 patients). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. The study investigated the oncological outcomes, including intravesical recurrence, metastasis, and cancer-specific mortality, stratified by preoperative CKD status. ResultsThe main findings indicated that UTUC patients with CKD stage >3 in Taiwan exhibited a higher proportion of females (p < 0.001), a greater history of concurrent bladder cancer (p = 0.003), more multifocal tumor behavior (p < 0.001), a higher incidence of carcinoma in situ (p = 0.008), increased rates of intravesical recurrence (p < 0.001), a lower prevalence of smoking history (p = 0.003), lower utilization of adjuvant chemotherapy (p < 0.001), reduced occurrence of distant metastasis (p < 0.001), and lower cancer-specific mortality (p = 0.006) compared to patients with CKD stage ≤3. Multivariate Cox regression analysis revealed significant differences in intravesical recurrence (p = 0.014) and metastasis (p = 0.006) between the CKD stage >3 and CKD stage ≤3 groups. The study also demonstrated that patients with concurrent bladder cancer and variant histology had higher rates of intravesical recurrence, metastasis, and cancer-specific mortality. The CKD stage >3 group exhibited lower rates of intravesical recurrence (p = 0.0014), higher rates of metastasis (p < 0.0001), and increased cancer-specific mortality (p = 0.0091) compared to the CKD stage ≤3 group in the 5-year free survival analysis. ConclusionIn Taiwan, UTUC patients with CKD stage >3 exhibit distinct characteristics compared to the general population with urothelial carcinoma. They are associated with a non-smoking status, a higher proportion of females, and less aggressive pathological features. Additionally, CKD stage >3 can serve as a clinical indicator for intravesical and non-urothelial recurrence. Further investigation into molecular aspects and treatment modifications for these patients is warranted.

Methods of Estimating Renal Function for Use in Clinical Trial Eligibility Criteria Widely Vary in Phase II and III Clinical Trials in Acute Myeloid Leukemia

Background Renal function is an important parameter to inform drug-dosing in oncology. In acute myeloid leukemia (AML), commonly used therapies or their metabolites are renally cleared. Several equations are commonly used to estimate renal function, such as Cockcroft-Gault (CG) to estimate creatinine clearance (CrCl) and the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations to calculate estimated glomerular filtration rates (eGFR). These equations frequently use endogenous serum markers, such as creatinine (Cr) and cystatin-C due to their ready availability but can have limitations. For example, Cr can be affected by muscle mass, diet, and age. Current ADDIKD international consensus guidelines recommend using the CKD-EPI creatinine formula to calculate eGFR to guide anti-cancer drug dosing unless direct GFR measurement is indicated. Renal function criteria are commonly used in clinical trial eligibility. In this study, we analyzed the types of reported renal eligibility criteria in phase II and III trials in AML and the methodology specified for renal function estimation, which can significantly impact treatment options for patients and potentially confound toxicity evaluation. Methods We examined the clinicaltrials.gov database to review publicly reported renal eligibility criteria for interventional phase II and III clinical trials recruiting adults with AML between 2021 to 2023. Trials including pediatric patients and exclusive phase I studies were excluded. Chi-square tests were used to evaluate for potential associations between eGFR cutoff criteria and disease variables. Results A total of 134 trials met criteria for review, including 84 (63%) trials specifically for AML and 50 (37%) allowing additional diagnoses. Of the total study cohort, 107 trials (80%) were evaluating chemotherapy, small molecule inhibitors, immunotherapy and/or combinations of these whereas 27 (20%) were evaluating primarily cell therapy and/or transplant-based regimens. Among the 134 trials, 21 (16%) did not mention renal or general organ function in eligibility criteria; 16 (12%) mentioned renal or organ function in inclusion/exclusion criteria but did not specify an eGFR cutoff value; and 15 (11%) specified a serum Cr cutoff value without a specific eGFR cutoff value. Among 82 (61%) studies specifying eGFR cutoffs: 18 required eGFR ≥60 ml/min and 64 specified cutoffs between 30 ml/min to 50 ml/min or greater (table 1). We found an association between studies requiring an eGFR of 60 ml/min or greater and studies investigating cell therapy or transplant-based regimens (p&amp;lt;0.01). We did not find associations between eGFR cutoff requirements and trials based on disease status (relapsed/refractory AML versus other AML states, p=0.24). We next evaluated methodologies reported in eligibility criteria to estimate renal function. Among the 113 trials commenting on renal function criteria: 15 (13%) did not report either an eGFR cutoff or methodology of determination; 67 (59%) specified eGFR cutoffs without specifying the methodology of determination and/or provided serum Cr-based cutoffs; and 31 (27%) specified either a method of direct measurement or equations to estimate eGFR (including CG-based in 25, CKD-EPI in 1, MDRD-based in 3 and radioisotope methodology in 1) (table 1). No trials mentioned cystatin-C as part of renal function determination. Conclusion In contemporary phase II/III clinical trials for adult patients with AML, we identified that while most trials include renal function in inclusion/exclusion criteria, there was tremendous heterogeneity in methodologies specified for determination of renal function which may make efficacy and toxicity comparisons challenging and impact patient eligibility across institutions. Several trials specified serum Cr cutoffs which can be impacted by factors besides renal function such as age or muscle mass. This study was limited by what trial criteria were publicly available and additional information specifying methodologies to calculate renal function may be available in full trial protocols. Further research is needed to determine the most suitable method for assessing eGFR in patients with AML to optimize treatment exposures for patients and to help reduce confounding of trial results or trial eligibility by institutional practice variation.

Impact of mildly reduced kidney function on 5-year mortality in patients with STEMI treated with primary PCI

Abstract PURPOSE Previous research associated renal failure (RF), as documented by estimated glomerular filtration rate (eGFR) &amp;lt;60 ml/min/1.73m2, with increased mortality risk following acute myocardial infarction. Our aim was to assess the impact of baseline mild RF (eGFR 60-89 ml/min/1.73m2) on mortality during 5-year follow-up after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods The study included 8378 STEMI patients undergoing primary PCI in the period from 2009 until 2019 for whom baseline eGFR data were available, according to the Modification of Diet in Renal Disease (MDRD) study equation. Cox regression models were created to assess the effect of different stages of renal failure on 30-day and 5-year mortality. Follow-up data were available for 8202 patients at 30 days and 5650 patients at 5 years. Results Renal function was impaired in 49% of patients (eGFR &amp;lt;30 ml/min/1.73m2 in 2.5%, eGFR 30-59 ml/min/1.73m2 in 16.2% and eGFR 60-89 ml/min/1.73m2 in 30%). Patients with eGFR &amp;lt;90 ml/min/1.73m2 had higher mortality rates at 30 days (10.0% vs. 1.7%, p&amp;lt;0.001) and at 5 years (44.1% vs 13.5%, p&amp;lt;0.001). Mortality increase was synchronous with the degree of renal failure at both 30 days and 5 years (Figure, panel A and B, respectively). At 30-days, patients with mild RF had higher adjusted mortality compared to patients with eGFR&amp;gt;90 ml/min/1.73m2 (HR 1.6, CI95% 1.1-2.4, p 0.027). At 5 years, eGFR 60-89 ml/min/1.73m2 was also associated with the higher adjusted mortality (HR 1.4, CI95% 1.2-1.6, p&amp;lt;0,001). As expected, severe (eGFR &amp;lt;30 ml/min/1.73m2) and moderate (eGFR 30-59 ml/min/1.73m2) renal failure was associated with a higher risk of mortality (30 days: HR 4.4 and 2.6 respectively; 5 years: HR 3.7 and 2.2 respectively). Conclusions The risk of short- and long-term mortality after STEMI increases proportionally with the degree of baseline renal failure. Compared with patients with a normal renal function, even mild renal failure (eGFR 60-89 ml/min/1.73m2) is associated with higher mortality at both 30 days and 5 years.

Abstract 14227: Fatty Acid-Binding Protein-3 and Renal Function Decline in Patients With Chronic Coronary Syndrome

Introduction: Renal dysfunction is common in patients with coronary artery disease. To delay the development of end-stage kidney disease and improve chronic kidney disease prognosis, early detection and management of chronic kidney disease are crucial, especially for high-risk populations. Hypothesis: We hypothesized that the fatty acid-binding protein-3 (FABP-3) is a novel biomarker associated with renal dysfunction. Methods: This is a multicentre prospective cohort study. Patients with chronic coronary syndrome were classified into three groups based on the initial serum FABP-3 levels. The Modification of Diet in Renal Disease (MDRD) equation was used to estimate the patient’s renal function. Renal events were defined as &gt;25% and &gt;50% decline in estimated glomerular filtration rate (eGFR). Multivariable Cox regression was employed to delineate the correlation between FABP-3 and renal dysfunction. Results: A total of 1606 subjects were included. During a mean follow-up of 35.9 months, there were 274 patients with eGFR &gt;25% reduction and 60 patients with &gt;50% reduction. The Kaplan-Meier survival curves showed that increased levels of FABP-3 were significantly correlated with eGFR &gt;25% reduction ( P &lt; 0.001) and &gt;50% reduction ( P &lt; 0.001). Multivariate Cox regression model revealed that subjects with higher FABP-3 exhibited a greater risk of eGFR &gt;25% reduction (Group 2: HR = 1.742, 95% CI = 1.222–2.483; Group 3: HR = 2.643, 95% CI = 1.847–3.784) and &gt;50% reduction (Group 2: HR = 3.818, 95% CI = 1.261–11.564; Group 3: HR = 9.769, 95% CI = 3.291–29.002). Conclusions: Serum FABP-3 may serve as a novel biomarker to predict eGFR decline in patients with chronic coronary syndrome. 1

Exploring an Unknown Corner of a Well-Known Topic: HIIE Influence on Renal Health and Filtration in Healthy Individuals Free of Cardiometabolic Diseases.

Aerobic exercise, specifically high-intensity interval exercise (HIIE), and its effects on renal health and filtration (RHF) are not well understood. Several studies support incorporating contemporary biomarkers serum cystatin C (CyC) and urine epidermal growth factor (uEGF) to combat the volatility of serum creatinine (sCr). Using these biomarkers, we examined the acute influences HIIE has on RHF to determine if there is a ceiling effect in healthy populations. The purpose was to determine the influence of an acute bout of HIIE on RHF. Thirty-six participants (n = 22 males; n = 14 females; age 37.6 ± 12.4 years.; BF% 19.2 ± 7.1%; VO2max 41.8 + 7.4 mL/kg/min) completed 30 min of HIIE on a treadmill (80% and 40% of VO2reserve in 3:2 min ratio). Blood and urine samples were obtained under standardized conditions before, 1 h, and 24 h post-exercise. CyC, sCR, uEGF, urine creatinine (uCr), uCr/uEGF ratio, and multiple estimates of glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations were used. The analysis employed paired sample t-tests and repeated measures ANOVAs. CyC, uEGF, uCr, and uCr/uEGF ratio concentrations were not altered between timepoints. sCr increased 1 h post-exercise (p > 0.002) but not at 24 h post-exercise. eGFR decreased in the MDRD and CKD-EPI equations at 1 h (p > 0.012) with no changes at 24 h post-exercise. CyC and sCr/CyC demonstrated no significant changes. CyC and uEGF are not altered by acute HIIE. The results demonstrate a potential ceiling effect in contemporary and traditional biomarkers of RHF, indicating improvements in RHF may be isolated to populations with reduced kidney function.

Machine learning clinical prediction models for acute kidney injury: the impact of baseline creatinine on prediction efficacy

BackgroundThere are many Machine Learning (ML) models which predict acute kidney injury (AKI) for hospitalised patients. While a primary goal of these models is to support clinical decision-making, the adoption of inconsistent methods of estimating baseline serum creatinine (sCr) may result in a poor understanding of these models’ effectiveness in clinical practice. Until now, the performance of such models with different baselines has not been compared on a single dataset. Additionally, AKI prediction models are known to have a high rate of false positive (FP) events regardless of baseline methods. This warrants further exploration of FP events to provide insight into potential underlying reasons.ObjectiveThe first aim of this study was to assess the variance in performance of ML models using three methods of baseline sCr on a retrospective dataset. The second aim was to conduct an error analysis to gain insight into the underlying factors contributing to FP events.Materials and methodsThe Intensive Care Unit (ICU) patients of the Medical Information Mart for Intensive Care (MIMIC)-IV dataset was used with the KDIGO (Kidney Disease Improving Global Outcome) definition to identify AKI episodes. Three different methods of estimating baseline sCr were defined as (1) the minimum sCr, (2) the Modification of Diet in Renal Disease (MDRD) equation and the minimum sCr and (3) the MDRD equation and the mean of preadmission sCr. For the first aim of this study, a suite of ML models was developed for each baseline and the performance of the models was assessed. An analysis of variance was performed to assess the significant difference between eXtreme Gradient Boosting (XGB) models across all baselines. To address the second aim, Explainable AI (XAI) methods were used to analyse the XGB errors with Baseline 3.ResultsRegarding the first aim, we observed variances in discriminative metrics and calibration errors of ML models when different baseline methods were adopted. Using Baseline 1 resulted in a 14% reduction in the f1 score for both Baseline 2 and Baseline 3. There was no significant difference observed in the results between Baseline 2 and Baseline 3. For the second aim, the FP cohort was analysed using the XAI methods which led to relabelling data with the mean of sCr in 180 to 0 days pre-ICU as the preferred sCr baseline method. The XGB model using this relabelled data achieved an AUC of 0.85, recall of 0.63, precision of 0.54 and f1 score of 0.58. The cohort size was 31,586 admissions, of which 5,473 (17.32%) had AKI.ConclusionIn the absence of a widely accepted method of baseline sCr, AKI prediction studies need to consider the impact of different baseline methods on the effectiveness of ML models and their potential implications in real-world implementations. The utilisation of XAI methods can be effective in providing insight into the occurrence of prediction errors. This can potentially augment the success rate of ML implementation in routine care.

Is There Any Effect of Retrograde Intrarenal Stone Surgery on Renal Functions in Childhood?

Purpose In this study, we aimed to demonstrate whether retrograde intrarenal stone surgery (RIRS) performed due to renal stones during the childhood period has any detrimental impact on renal functions. Materials and methods We retrospectively analyzed 121 patients aged 2 to 16 years who underwent RIRS for renal stones between March 2018 and February 2023. Data were available for 41 patients. The estimated glomerular filtration rate (eGFR) was computed using the modification of diet in renal disease (MDRD) formula on the day preceding the surgery and the third month after the surgery. We employed the National Kidney Foundation's chronic kidney disease (CKD) classification to categorize the glomerular filtration rate (GFR) into five groups. Preoperative and postoperative eGFR values of pediatric patients were compared by analyzing changes in CKD groups. Results Of the patients included in the study, 21 (51.2%) were male, while 20 (48.8%) were female children. No significant difference was found between the preoperative median eGFR and the postoperative median eGFR values (p=0.958). In the 3rd month after surgery, it was observed that 5 (12.1%) patients showed an improvement in their CKD stage, while deterioration was noted in 1 (2.4%) patient. Although a negative correlation was observed between the median eGFR change and both the operation time and the stone volume in Pearson correlation analysis, it was determined that this change did not create a significant difference (p=0.213 and p=0.295, respectively). Conclusion Stone surgery conducted with RIRS appears to yield positive outcomes on kidney function in the pediatric population. Nevertheless, being particularly attentive to patients with prolonged operation times and larger stone volumes is essential.

Associations of meat, fish and seafood consumption with kidney function in middle-aged to older Chinese: a cross-sectional study based on the Guangzhou Biobank Cohort Study

ObjectiveTo examine the associations of red meat, poultry, fish and seafood and processed meat consumption with kidney function in middle-aged to older Chinese.DesignA cross-sectional study based on the Guangzhou Biobank...