Cockcroft-Gault Formula Research Articles

Carboplatin dosing in obese patients.

The study aimed to: 1) Describe the carboplatin dosing criteria in obese patients in routine clinical practicein a general university hospital. 2) Evaluate toxicity based on the dosing criterion used. 3) Assess effectiveness in major diagnoses according to the dosing criterion employed. An observational, retrospective, descriptive study, including all obese patients (BMI ≥ 30 kg/m2) who started carboplatin treatment between 1st January 2012 and 31st January 2015. Data on patient characteristics, disease and treatment were collected. As a result variables were collected: carboplatin dosing methods, dosage criteria, alternative dosing approaches, treatment delays, dose reductions, relative dose intensity, adverse reactions and severity (CTCAE v. 4.0) as well as overall survival and progressive free survival for major diagnoses. 1) Carboplatin dosing at the centre used Calvert's formula for calculating AUC and Cockcroft-Gault's formula for estimating glomerular filtration rate. 2) Cockcroft-Gault's formula employed actual body weight and ideal adjusted body weight in similar proportions. 3) The ideal adjusted body weight was more commonly used in patients with higher obesity and diabetes. 4) In the general population, the developmental trend of toxicity during treatment was greater in the group dosed by actual body weight, reaching significant differences in thrombopenia, neutropenia, GOT elevation, hyporexia and myalgias. 5) Major diagnoses in the present study were ovarian cancer and non-small cell lung cancer. The effectiveness in terms of overall survival and progression-free survival, comparing the groups dosed by actual body weight and ideal adjusted body weight within each pathology did not show statistically significant differences.

Safety profile of tenofovir amibufenamide therapy extension or switching in patients with chronic hepatitis B: a phase Ⅲ multicenter, randomized controlled trial

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated. Results: 666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion: CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

A study on comparison of Tc-99m DTPA renal dynamic imaging with Mayo quadratic, Cockcroft-Gault, MDRD, and CKD-EPI formulas for estimation of glomerular filtration rate among South Indian live-related kidney donors

Introduction: Glomerular filtration rate (GFR) is calculated using various prediction equations. These equations are derived from the Western population, and extrapolating to our population subgroups may yield inaccurate results. Objectives: To study the correlation of measured GFR to estimated GFR using four different equations and to analyse how much proximity lies between the GFR calculated by above formulas correlates with DTPA renal scan among South Indian renal donors. Patients and Methods: An observational study was conducted among prospective renal donors undergoing evaluation. Donors underwent a DTPA scan as per protocol. Downloadable calculators calculated the glomerular filtration rate. Results that were descriptive were presented as mean and standard deviation. Correlation and comparisons were made by calculating Pearson’s correlation coefficient and student’s t test respectively. Results: A total of 151 patients were included; 24.5% were males and 75.5% were females. The majority of donors (37.09%) were in the 45-54 years age group. The mean of measured GFR by DTPA was 105.64 mL/min/1.73 m2 whereas estimated GFR was 100.95, 102.34, 109.35, 97.44 mL/min/1.73 m2 in MDRD, CKD-EPI, Mayo, and Cockcroft Gault (CG) formulae respectively with a maximum mean difference for CG of 8.2. Weighted kappa agreement between measured and estimated GFR shows 82.96% agreement with CKD-EPI compared to 78.09% agreement with the MDRD formula. Overall, CKD-EPI performed better in GFR estimation in our study subjects. Conclusion: We found that the CKD-EPI formula performed better in precision, correlation, and accuracy compared to other formulae in GFR estimation among healthy South Indian renal donors. Therefore, the CKD-EPI formula is best suited to pick-up subnormal GFR in clinical practice, as well as in epidemiological studies among the South Asian population.

Tasa de filtración glomerular estimada para la pesquisa de enfermedad renal crónica desde la Atención Primaria de Salud.

Introduction: Primary health care (PHC) is fundamental in preventing and managing chronic kidney disease (CKD). By early detection of kidney disorders and providing comprehensive care to patients, PHC contributes to improving the quality of life of people with kidney disease and reducing the burden that this disease represents for health systems. This study aimed to determine the prevalence of chronic kidney disease in a primary care referral center in Holguín, Cuba. Methods: This analytical observational study was conducted at the “Máximo Gómez Báez” University Polyclinic, Cuba, from February to November 2021. Patients diagnosed with noncommunicable chronic disease without known CKD were included, subsequently Group 1 (G1): patients with CKD. Group 2 (G2): patients without CKD. The estimated glomerular filtration rate, comorbidities, nutritional status, and laboratory variables were recorded. Results: In Group 1 (CKD), 188 cases, and the control group, 348 cases. The prevalence of chronic kidney disease was 35% (95% CI 31-39%). The age in G1 was 61.6 ± 10.3 years in G2: 59.3 ± 11.6 (P =0.001). Women were the most affected by CKD (P =0.001). Of the total, 76% were hypertensive, with similar distributions between both groups (79% vs 74%). Type 2 diabetes was a risk factor for developing CKD (OR = 5.9; 95% CI: 3.9-8.9). 35%, 37% and 31% had an eGFR ≤ 60 mL/min/1.73 m2, by the CKD-EPI, MDRD-4 and Cockcroft-Gault formulas, respectively. The distributions of CKD stages were 76.1% for 3a, 16.5% for 3b, 6.9% for 4, and 0.5% for 5, by CKD-EPI. Conclusion: The eGFR by Cockcroft-Gault introduces erroneous results due to the patient's weight. CKD-EPI and MDRD-4 proved to be the most appropriate for diagnosing and staging CKD in the study population.

A 3-year follow-up analysis of renal function in elderly patients with type 2 diabetes mellitus and an estimated glomerular filtration rate

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.

Risk factors for renal impairment after liver transplantation in Mongolia: a retrospective single-center study.

Renal impairment (RI) is a frequent complication of liver cirrhosis and is associated with increased mortality and morbidity. Liver transplantation (LT) serves as an effective treatment method for patients with cirrhosis who have impaired renal function. However, renal function often declines after LT, influenced by various factors. This study aimed to investigate the factors contributing to RI following LT in our cases. We analyzed the demographic data, preoperative and perioperative parameters, and postoperative outcomes of patients who underwent LT at the First Central Hospital of Mongolia from September 2011 to December 2022. Renal function was assessed by measuring the glomerular filtration rate using the Cockcroft-Gault creatinine clearance formula pretransplantation and at 24 hours, 72 hours, 7 days, 14 days, and 28 days post-LT. Several factors increased the risk of RI among recipients. These included female sex (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.58-5.91), Child-Turcotte-Pugh (CTP) scores of B and C (OR, 4.23; 95% CI, 0.92-19.41 and OR, 7.68; 95% CI, 1.67-35.30, respectively), preoperative continuous renal replacement therapy (CRRT; OR, 5.86; 95% CI, 1.1-31.21), and a high graft-to-recipient weight ratio (GRWR; OR, 3.45; 95% CI, 1.23-9.63). Additionally, the survival rates for recipients with RI post-LT were 93.4% at 1 year and 78.1% at 3 years. Female sex, a high CTP score, preoperative CRRT, and high GRWR were identified as risk factors for RI after LT in Mongolia.

Switching to tenofovir alafenamide in patients with virologically suppressed chronic hepatitis B and renal or hepatic impairment: final week 96 results from an open-label, multicentre, phase 2 study

Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment. This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites. We recruited adults (≥18 years) with chronic hepatitis B who were virally suppressed on nucleoside or nucleotide analogues and had renal impairment (part A: moderate or severe in cohort 1 [estimated glomerular filtration rate by the Cockcroft-Gault formula (eGFRCG) 15-59 mL/min] or end-stage renal disease [eGFRCG <15 mL/min] on haemodialysis in cohort 2) or hepatic impairment including decompensation (part B: Child-Turcotte-Pugh score 7-12). Participants switched to 25 mg of tenofovir alafenamide given orally once daily for 96 weeks. The primary endpoint was the proportion of participants with viral suppression (HBV DNA <20 IU/mL) at week 24 by missing-equals-failure analysis. Efficacy (full analysis set) and safety (safety analysis set) analyses included all enrolled participants who received at least one dose of the study drug. Week 96 safety was assessed, including renal and bone parameters. This trial is registered at ClinicalTrials.gov, NCT03180619, and is completed. 124 participants (93 in part A [78 in cohort 1 and 15 in cohort 2] and 31 in part B) were enrolled between Aug 11, 2017, and Oct 17, 2018, and included in the full and safety analysis sets. 106 (85%) participants completed the study. There were 69 (74%) men and 24 (26%) women in part A and 21 (68%) men and ten (32%) women in part B. At week 24, 91 (97·8%, 95% CI 92·4 to 99·7) of 93 individuals in part A (76 [97·4%, 91·0 to 99·7] of 78 in cohort 1 and 15 [100·0%, 78·2 to 100·0] of 15 in cohort 2) and 31 (100·0%, 88·8 to 100·0) in part B had HBV DNA of less than 20 IU/mL. By week 96, the most common adverse event was upper respiratory tract infection, which occurred in 14 (15%) participants in part A and in six (19%) participants in part B. Serious adverse events occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment. No treatment-related deaths occurred. At week 96, median change in estimated glomerular filtration rate (Cockcroft-Gault method) was 1·0 mL/min (IQR -2·8 to 4·5) in cohort 1 and -2·4 mL/min (-11·4 to 10·7) in part B. Mean changes in spine and hip bone mineral density were 1·02% (SD 4·44) and 0·20% (3·25) in part A and -0·25% (3·91) and 0·28% (3·25) in part B. Tenofovir alafenamide might offer continued antiviral efficacy and a favourable safety profile for patients with renal or hepatic impairment and chronic hepatitis B switching from tenofovir disoproxil fumarate or other antivirals. Gilead Sciences.

Machine Learning-Based Mortality Prediction in Chronic Kidney Disease among Heart Failure Patients: Insights and Outcomes from the Jordanian Heart Failure Registry

Background and Objectives: Heart failure (HF) is a prevalent and debilitating condition that imposes a significant burden on healthcare systems and adversely affects the quality of life of patients worldwide. Comorbidities such as chronic kidney disease (CKD), arterial hypertension, and diabetes mellitus (DM) are common among HF patients, as they share similar risk factors. This study aimed to identify the prognostic significance of multiple factors and their correlation with disease prognosis and outcomes in a Jordanian cohort. Materials and Methods: Data from the Jordanian Heart Failure Registry (JoHFR) were analyzed, encompassing medical records from acute and chronic HF patients attending public and private cardiology clinics and hospitals across Jordan. An online form was utilized for data collection, focusing on three kidney function tests, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and creatinine levels, with the eGFR calculated using the Cockcroft–Gault formula. We also built six machine learning models to predict mortality in our cohort. Results: From the JoHFR, 2151 HF patients were included, with 644, 1799, and 1927 records analyzed for eGFR, BUN, and creatinine levels, respectively. Age negatively impacted all measures (p ≤ 0.001), while smokers surprisingly showed better results than non-smokers (p ≤ 0.001). Males had more normal eGFR levels compared to females (p = 0.002). Comorbidities such as hypertension, diabetes, arrhythmias, and implanted devices were inversely related to eGFR (all with p-values &lt;0.05). Higher BUN levels were associated with chronic HF, dyslipidemia, and ASCVD (p ≤ 0.001). Higher creatinine levels were linked to hypertension, diabetes, dyslipidemia, arrhythmias, and previous HF history (all with p-values &lt;0.05). Low eGFR levels were associated with increased mechanical ventilation needs (p = 0.049) and mortality (p ≤ 0.001), while BUN levels did not significantly affect these outcomes. Machine learning analysis employing the Random Forest Classifier revealed that length of hospital stay and creatinine &gt;115 were the most significant predictors of mortality. The classifier achieved an accuracy of 90.02% with an AUC of 80.51%, indicating its efficacy in predictive modeling. Conclusions: This study reveals the intricate relationship among kidney function tests, comorbidities, and clinical outcomes in HF patients in Jordan, highlighting the importance of kidney function as a predictive tool. Integrating machine learning models into clinical practice may enhance the predictive accuracy of patient outcomes, thereby supporting a more personalized approach to managing HF and related kidney dysfunction. Further research is necessary to validate these findings and to develop innovative treatment strategies for the CKD population within the HF cohort.

Comparative analysis of two-hour creatinine clearance and the C-G formula for renal function assessment in critically ill patients

Objective and rationaleTo investigate if the 2-h creatinine clearance (Ccr2) provides a more precise and timely assessment of renal function in critically ill patients compared to the Cockcroft-Gault formula (CrC-G). Materials and methodsThis cohort study incorporated 74 patients who were hospitalized for more than 48 h in the Intensive Care Unit over 6 months. A 24-h urine collection protocol was observed, and concurrently, 316 2-h urine specimens were obtained. Then calculated and analyzed the correlation and consistency between Ccr2, CrC-G, and 24-h creatinine clearance (Ccr24) values. The rates of change in Ccr2(ΔCcr2) and CrC-G(ΔCrC-G) were compared over two consecutive samples. ResultsThe R-values of Ccr2 and Ccr24 in the early, middle and late 24 h were 0.640, 0.886 and 0.854 (P < 0.001), with biases of −2.1, 1.7, and 6.3 ml/min/1.73 m2, respectively. Meanwhile, the R-values for CrC-G and Ccr24 at these time points were 0.618, 0.822, and 0.828(P < 0.001), with biases of −14.0, −5.2, and −1.8 ml/min/1.73 m2, respectively. For patients with Ccr24≥60 ml/min/1.73 m2, the R-value of Ccr2 and Ccr24 during the middle 2 h was 0.852(P < 0.001), while the R-values for CrC-G and Ccr24 were 0.763(P < 0.001), with biases of −2.3 ml/min/1.73 m2 and -14.2 ml/min/1.73 m2 respectively. For the group with Ccr24 ≥ 120 ml/min/1.73 m2 (n = 72), both Ccr2 and Ccr24 displayed a statistically significant elevation compared to CrC-G (P < 0.001), yet no significant difference was observed between Ccr2 and Ccr24 (P = 0.289). Out of 50 patients, 46(92 %) experienced a ΔCcr2≥20 % at least once, compared to 20(40 %) with a ΔCrC-G≥20 %(P < 0.001). 25(50 %) with a ΔCcr2≥50 %, compared to 3(6 %) with a ΔCrC-G≥50 %(P < 0.001). ConclusionCcr2 demonstrates a more accurate and more timely indicator of renal function in critically ill patients than CrC-G.

COMPARISON OF ANTI-PROTEINURIC EFFECTS OF AMLODIPINE AND CILNIDIPINE AS AN ADD-ON DRUG TO BASELINE MEDICATION IN HYPERTENSIVE CHRONIC KIDNEY DISEASE PATIENTS

Objectives: The objectives of the study were to compare the anti-proteinuric effects of amlodipine and cilnidipine in individuals with Chronic Kidney Disease (CKD) on baseline medication. Methods: This was a prospective observational study carried out in the Department of Nephrology at Government T.D. Medical College, Alappuzha spanning a duration of 1 year from January 2016 to December 2016. The study encompassed a total of 90 hypertensive CKD patients-45 were administered amlodipine and the remaining 45 were given cilnidipine in conjunction with their existing baseline medications. The inclusion criteria consisted of hypertensive CKD patients aged between 18 and 80 years possessing a Glomerular Filtration Rate (GFR) between 30 and 60 mL/min and exhibiting blood pressure readings surpassing 140/90 mmHg despite receiving a loop diuretic (Tab. Frusemide 80 mg BD), an α-blocker (Tab. Prazosin 10 mg BD) and a β-blocker (Tab. Metoprolol 50 mg BD) for a minimum duration of one month. The key parameters that were monitored were sitting systolic and diastolic blood pressure readings and proteinuria which was evaluated by determining the Urine Protein Creatinine (UPC) ratio using untimed random urine samples. The GFR was calculated utilizing the Cockcroft-Gault formula. Results: The number of patients who improved to stage 3A CKD from stage 3B CKD were more with cilnidipine which indicates its reno-protective action. Amlodipine was seen to have no effect on UPC ratio whereas cilnidipine decreased UPC ratio significantly. Conclusion: Unlike amlodipine, cilnidipine exhibits marked reduction in proteinuria and improved GFR thereby preventing progression of hypertensive CKD patients to end stage renal failure.

De-indexed estimated glomerular filtration rates for the dosing of oral antidiabetic drugs in patients with chronic kidney disease.

Introduction: Adjusting drug dose levels based on equations that standardize the estimated glomerular filtration rate (eGFR) to a body surface area (BSA) of 1.73m2 can pose challenges, especially for patients with extremely high or low body mass index (BMI). The objective of the present study of patients with CKD and diabetes was to assess the impact of deindexing creatinine-based equations on estimates of kidney function and on the frequency of inappropriate prescriptions of oral antidiabetic drugs (OADs). Methods: The prospective CKD-REIN cohort is comprised of patients with eGFR <60mL/min/1.73m2. The inclusion criteria for this study were the use of OADs and the availability of data on weight, height and serum creatinine. We compared data for three BMI subgroups (group 1 <30kg/m2; group 2 30-34.9kg/m2; group 3 ≥35kg/m2). Inappropriate prescriptions (contraindicated or over-dosed drugs) were assessed with regard to the summary of product characteristics and the patient's kidney function estimated with the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the 2021 CKD-EPI equation, the Modification of Diet in Renal Disease (MDRD) equation, the European Kidney Function Consortium (EKFC) equation, their deindexed estimates, and the Cockcroft-Gault (CG) formula. The impact of deindexing the equations was evaluated by assessing 1) the difference between the indexed and deindexed eGFRs, and 2) the difference in the proportion of patients with at least one inappropriate OAD prescription between the indexed and deindexed estimates. Results: At baseline, 694 patients were receiving OADs. The median BMI was 30.7kg/m2, the mean BSA was 1.98m2, and 90% of patients had a BSA >1.73m2. Deindexing the kidney function estimates led to higher eGFRs, especially in BMI group 3. The proportion of patients with at least one inappropriate prescription differed greatly when comparing indexed and deindexed estimates. The magnitude of the difference increased with the BMI: when comparing BMI group 1 with BMI group 3, the difference was respectively -4% and -10% between deindexed 2021 CKD-EPI and indexed CKD-EPI. Metformin and sitagliptin were the most frequent inappropriately prescribed OADs. Conclusion: We highlight significant differences between the BSA-indexed and deindexed versions of equations used to estimate kidney function, emphasizing the importance of using deindexed estimates to adjust drug dose levels - especially in patients with an extreme BMI.

Carfilzomib, Daratumumab, and Dexamethasone (KdD) Vs Carfilzomib and Dexamethasone (Kd) for Relapsed/Refractory Multiple Myeloma (RRMM) in the Phase 3 Candor Study: Subgroup Analysis According to Renal Functioning

Renal impairment frequently occurs in patients (pts) with multiple myeloma (MM) and is associated with poor survival outcomes. In the phase 3 CANDOR trial, carfilzomib, dexamethasone, and daratumumab (KdD) met its primary endpoint of prolonged progression-free survival (PFS) vs carfilzomib and dexamethasone (Kd) (28.4 vs 15.2 mo; hazard ratio [HR]: 0.64; 95% CI: 0.49-0.83) after 50 months (mo) follow-up (Usmani Blood Adv 2023). The study aim was to perform a prespecified subgroup analysis of efficacy and safety by baseline renal function in pts with relapsed/refractory MM (RRMM) receiving KdD vs Kd in the CANDOR trial. Adult pts with RRMM were randomized 2:1 to KdD or Kd in the open-label, phase 3 CANDOR trial (NCT03158688) (Dimopoulos Lancet 2020). RRMM pts with measurable disease who had received 1-3 prior lines of therapy, with partial response or better to ≥1 line of therapy were eligible. Dialysis was an exclusion criterion. All pts received carfilzomib (K) as a 30-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m 2 on days 1 and 2 during cycle 1 and 56 mg/m 2 thereafter). Daratumumab (8 mg/kg) was administered IV on days 1 and 2 of cycle 1 and at 16 mg/kg once weekly for the remaining doses of the first 2 cycles, then every 2 weeks (wks) for 4 cycles (cycles 3 to 6), and every 4 wks thereafter. All pts received 40 mg dexamethasone oral or IV weekly (20 mg for pts &amp;gt;75 years). Pts were grouped according to baseline renal function (creatinine clearance [CrCl] ≥15-&amp;lt;60 mL/min, ≥60-&amp;lt;90 mL/min, and ≥90 mL/min (Dimopoulous J Clin Onc 2016). The Cockcroft-Gault formula was used to calculate baseline and on study renal function. PFS and overall response rates (ORRs) were protocol-derived/investigator-assessed. Median PFS was estimated using the Kaplan-Meier method, with HRs and corresponding 95% CIs estimated using a stratified Cox proportional hazards model. Response rates were summarized descriptively, with odds ratios (ORs) and corresponding 95% CIs estimated by Mantel-Haenszel methods using stratified randomization. Renal response was defined as pt CrCl improvement to ≥60 mL/min in any 2 consecutive study visits in pts with baseline CrCl of &amp;lt;50 mL/min. A total of 466 pts were randomized; renal subgroups were CrCl ≥15-&amp;lt;60 mL/min (renal impairment), n=67 and n=36; ≥60-&amp;lt;90 mL/min, n=112 and n=57; and ≥90 mL/min, n=132 and n=61 for KdD and Kd, respectively. One pt in the KdD arm with missing baseline CrCl was excluded. Baseline characteristics were generally balanced between treatment arms and renal subgroups ( Table 1). After a median follow-up of ~50 mo (data cutoff: April 15, 2022), pts treated with KdD vs Kd had improved median PFS across all renal subgroups; median PFS was 24.9 mo vs 8.4 mo (HR, 0.61; 95% CI, 0.35-1.06), 31.6 mo vs 19.9 mo (0.63; 0.41-0.96), and 27.4 mo vs 15.3 mo (0.64; 0.43-0.95) for pts with CrCl ≥15-&amp;lt;60 mL/min, ≥60-&amp;lt;90 mL/min, and ≥90 mL/min, respectively ( Table 2). Median overall survival (OS) for KdD vs Kd was 44.6 mo vs 25.2 mo (HR, 0.58; 95% CI, 0.32-1.03), 48.0 mo vs 43.7 mo (0.91; 0.58-1.43), and NE vs NE (0.74; 0.46-1.20), respectively. ORRs were 87% vs 50% (OR, 8.02; 95% CI, 2.84-22.65); 85% vs 82% (1.26; 0.49-3.27); and 86% vs 80% (1.59; 0.69-3.68), respectively. Complete response rates were 36% vs 8% (7.43; 1.85-29.74); 44% vs 21% (3.17; 1.47-6.87); and 38% vs 21% (2.20; 1.08-4.49), respectively. Among 38 KdD pts and 27 Kd pts with baseline CrCl &amp;lt;50 mL/min, the renal response rate was 21% vs 11% (OR, 2.65; 95% CI, 0.63-11.11), respectively. In pts with renal impairment, most common grade ≥3 TEAEs were thrombocytopenia (38% [25/66] vs 23% [8/35]), hypertension (24% [16/66] vs 20% [7/35]), anemia (24% [16/66] vs 29% [10/35]), and pneumonia (23% [15/66] vs 9% [3/35]) in the KdD arm vs Kd arm. Most common grade ≥3 TEAEs of interest in pts with renal impairment were respiratory tract infections (32% vs 14%), hypertension (26% vs 20%), and infusion reaction on the same date of any carfilzomib dosing (14% vs 11%), respectively. Grade ≥3 acute renal failure occurred in 6% vs 11%, 4% vs 7%, and 2% vs 3% of pts with baseline CrCl ≥15-&amp;lt;60 mL/min, ≥60-&amp;lt;90 mL/min, and ≥90 mL/min, respectively. Overall, the safety profile in each subgroups was consistent with the established carfilzomib safety profile (Usmani Blood Adv 2023). KdD showed consistent clinical benefit vs Kd in median PFS, ORR and OS irrespective of the baseline renal function. Safety findings were consistent with the overall study population.

Abstract P374: Greater Burden Of Chronic Kidney Disease Is Associated With Hypertension Prevalence And Management In South Africa

Introduction: Complications e.g., chronic kidney disease (CKD) are frequent with longstanding hypertension, particularly if poorly managed. Hypothesis: We assessed the hypothesis that prevalence and associations of CKD differed by hypertension prevalence, awareness, treatment and control in South Africa using five CKD estimates. Methods: In this randomly selected cross-sectional study, glomerular filtration rate (GFR) was estimated by CKD Epidemiology Collaboration (CKD-EPI) equations [CKD-EPI creatinine (CKD-EPIcr), CKD-EPI cystatin C, CKD-EPI creatinine-cystatin C], Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formula (CGF). Blood pressures were measured, and history of hypertension management collected. Results: Among 1092 participants, mean age 43.5 years, 64% women, the prevalence of hypertension was 42% with similar rates in men (41%) and women (43%). In participants with hypertension (n=460), awareness, treatment and control were 61.5% (283/460), 47.2% (217/460) and 27.0% (124/460), with better rates in women compared with men (p&lt;0.001). CKD prevalence (GFR&lt;60 mL/min/1.73m 2 ) was 2.0-5.9% overall using 5 formulae, and significantly higher in participants with (3.9-10.2%) compared to without hypertension (0.6-2.7%) (p&lt;0.001). In participants with hypertension, CKD was higher in those aware (5.7-13.8%) vs unaware (1.1-4.5%) of their diagnosis (p≤0.015), on treatment (6.9-14.3%) vs none (1.2-6.6%) (p≤0.016), and those with controlled (BP&lt;140/90 mmHg) vs uncontrolled hypertension (6.5-15.1% vs. 3-8%, p≤0.096). In models adjusted for age, sex and obesity, higher hypertension prevalence and awareness were significantly (p&lt;0.05) associated with CKD by CKD-EPIcr and MDRD equations; hypertension treatment was significantly associated with CKD by CKD-EPIcr, MDRD and CGF formulae, while hypertension control was not associated with CKD. Conclusions: This study highlights the higher prevalence and greater likelihood of CKD in participants with hypertension and those who were diagnosed and receiving treatment, likely due to the longer duration of their hypertension compared with their counterparts. Higher CKD in the diagnosed and treated reinforces the need for optimal control, which was low in this cohort.

Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration. Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula. Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes. This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.

Optimizing carboplatin dosing by an improved prediction of carboplatin clearance using a CT-enhanced estimate of renal function.

Carboplatin is generally dosed based on a modified Calvert formula, in which the Cockcroft-Gault-based creatinine clearance (CRCL) is used as proxy for the glomerular filtration rate (GFR). The Cockcroft-Gault formula (CG) overpredicts CRCL in patients with an aberrant body composition. The CT-enhanced estimate of RenAl FuncTion (CRAFT) was developed to compensate for this overprediction. We aimed to evaluate whether carboplatin clearance is better predicted by CRCL based on the CRAFT compared to the CG. Data of four previously conducted trials was used. The CRAFT was divided by serum creatinine to derive CRCL. The difference between CRAFT- and CG-based CRCL was assessed by population pharmacokinetic modelling. Furthermore, the difference in calculated carboplatin dose was assessed in a heterogeneous dataset. In total, 108 patients were included in the analysis. Addition of the CRAFT- and CG-based CRCL as covariate on carboplatin clearance led, respectively, to an improved model fit with a 26-point drop in objective function value and a worsened model fit with an increase of 8 points. In 19 subjects with serum creatinine <50 μmol/L, the calculated carboplatin dose was 233 mg higher using the CG. Carboplatin clearance is better predicted by CRAFT vs. CG-based CRCL. In subjects with low serum creatinine, the calculated carboplatin dose using CG exceeds the dose using CRAFT, which might explain the need for dose capping when using the CG. Therefore, the CRAFT might be an alternative for dose capping while still dosing accurately.

COMORBIDITY &amp; CLL DIFFERENT SCORES – DIFFERENT RESULTS

Introduction: Due to the implementation of the outpatient centres, our network provides care for 50% of the patients with hematological diseases in Vienna. Here we analyse the influence of our own CIRS Score on survival of CLL patients. Additionally we focus on renal comorbidities. Methods: 1150 CLL patients who were diagnosed, observed and treated between 2011 and 2021 within our haematological network were analysed. Study data was generated by reviewing electronic and paper medical records. Comorbidities were assessed with the conventional CIRS Score including utilizing our own Version where we did not focus on severity to detect more patients. We differentiated between 2 groups: low risk pts. without any or with just one existing co-morbidity and high-risk patients with 2 or more organ systems involved, regardless of the severity. Moreover we demonstrate a Composite Comorbidity Score “Severe4” with <3 or >3 points, validated in 4 Organ Systems as shown on ASH 2022 by Shouse et al. and the cut-off Score of 6 points as used by the German CLL Study Group. Furthermore the Cockcroft-Gault formula (GFR). Results: 55% of the patients were male. The median age at diagnosis was 68 years. IGHV was mutated in 53% of patients, del(17p) was present in 7,4% of patients. 27% of our 1150 patients received CLL specific treatment. As shown in Figure 1 our own interpretation of the CIRS-Score was able to identify 625 pts. classified as high risk with a significant lower OS. Regardless of the Severity, the involvement of 2 or more organ systems was more relevant than just one. Similarly to the Severe4 Score we could also show a significant OS difference in 167 pts. using a cut-off Score of 3 Points in at least one category. A highly significant OS difference can also be shown in 245 pts when using the established cut-off Score of 6 points. Emphasizing the weakness of the CIRS Score in detecting renal comorbidity due to the high threshold concerning the Serum Creatinine of 1,5 mg/dl we were able to demonstrate that 144 of our pts. had a GFR of <60 mL/min at time of diagnosis, which reflects Stage 3 CKD, resulting in a significant lower OS. When using the CIRS Score alone only 31 pts. would have been classified as renal impaired. Keyword: chronic lymphocytic leukemia (CLL) No conflicts of interests pertinent to the abstract.

Performance of Creatinine and Cystatin C-Based Equations to Estimate Kidney Function in Renal Transplant Recipients

Background: Numerous equations are applied in order to estimate the glomerular filtration rate (GFR). Objectives: This study aimed to spot the optimal equation that accurately estimates GFR and, therefore, the chronic kidney disease (CKD) stage in renal transplant patients. Methods: This cross-sectional study was conducted on 58 renal transplant patients. Their venous blood samples were obtained for serum creatinine and cystatin C determination used to calculate estimated GFR (eGFR). The average contrast of GFR in each equation was calculated using the Bland-Altman method. The correlation, bias, imprecision, and 10% and 30% accuracy were compared between the eGFR cystatin C and creatinine. Concordance between both equations for CKD staging was assessed. The classification of patients was also investigated. Results: Bland-Altman plots and bias demonstrated that eGFR by the abbreviated modification of diet in renal disease (Ab-MDRD) was the most accurate compared with chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C, followed by CKD-EPI eGFR creatinine. With reference to CKD-EPI cystatin C, the imprecision of the equations was approximately similar to Ab-MDRD, and CKD-EPI creatinine is still better than the Cockcroft-gault (CG) formula. They also showed good 30% accuracy. Finally, our finding suggested that Ab-MDRD and CKD-EPI eGFR creatinine might be the best-performing equation in the classification of the CKD stages in a cutoff of 60 mL/min/1.73 m2. Conclusions: Due to the high cost and potential delay in measuring cystatin C, it would be much more appropriate to measure Ab-MDRD; after that, CKD-EPI eGFR creatinine as an alternative approach in order to facilitate rapid clinical decision in renal transplant patients.

Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study

ObjectiveTo determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl). MethodsRetrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)—a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event. ResultsAUC statistics (range, 0.52–0.64) showed log(CrClJelliffe) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%–15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively. ConclusionThe formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials.

Clinical Associations with the differences in rivaroxaban dosing in patients with atrial fibrillation stratified by three renal function formulae.

Clinical trials used Cockcroft-Gault (CG) formula to calculate the estimated glomerular filtration rate (eGFR) in order to dose rivaroxaban for patients with atrial fibrillation (AF). The aim of this study is to evaluate rivaroxaban dosing appropriateness in patients with AF with or without renal impairment based on the CG formula and other formulae, including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the isotope dilution mass spectrometry (IDMS) traceable Modification of Diet in Renal Disease (MDRD) Study equation and the associated clinical outcomes. A retrospective cohort study conducted at Sultan Qaboos University Hospital (SQUH) from 1st January 2016 to 31st December 2020, included all adult patients (≥ 18 years) treated with rivaroxaban for AF and followed up for one year after starting the treatment. Based on the CG formula, the rivaroxaban dose was inappropriately prescribed in 27% of the patients (21% overdosed and 6% underdosed). Higher baseline creatinine (P=0.0014) and concurrent use of antiplatelet therapy (P<0.001) were associated with the tendency to rivaroxaban overdosing. Higher Body Mass Index (BMI) (P=0.002), female sex (P=0.032), and CKD (P=0.003) were associated with rivaroxaban underdosing. The degree of agreement between the renal function tests when comparing MDRD vs CG and CKD-EPI vs CG in terms of estimated glomerular filtration rate/creatine clearance (eGFR/CrCl) calculation was moderate (κ=0.46) and poor (κ=0.00), respectively, while, in terms of rivaroxaban dose appropriateness was almost perfect (κ=0.82) and substantial (κ=0.77). Clinical outcomes measured by stroke and bleeding events were not significantly different according to the appropriateness of the rivaroxaban dose. This study has shown a relatively high consistency with the gold standard in dosing rivaroxaban in AF patients using CG formula. Treatment efficiency and safety were not affected by the proportion of dose inappropriateness found in this cohort.