Calculated Creatinine Clearance Research Articles

Development of normal reference intervals for renal function in pregnancy: a secondary analysis of clinical trial data

Background Due to its potential nephrotoxicity, screening for pre-existing renal function disorders has become a routine clinical assessment for initiating Tenofovir diphosphate fumarate (TDF)-containing antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) in pregnant and non-pregnant adults. We aimed to establish reference values for commonly used markers of renal function in healthy pregnant women of African origin. Methods Pregnant women ≥18 years, not living with HIV, and at 14–28 weeks gestation were enrolled in a PrEP clinical trial in Durban, South Africa between September 2017 and December 2019. Women were monitored 4-weekly during pregnancy until six months postpartum. We measured maternal weight and serum creatinine (sCr) at each visit and calculated creatinine clearance (CrCl) rates using the Cockcroft–Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Reference ranges for sCr and CrCl by CG and MDRD calculations were derived from the mean ± 2SD of values for pregnancy and postdelivery. Results Between 14-–and 40 weeks gestation, 249 African women not exposed to TDF-PrEP contributed a total of 1193 renal function values. Postdelivery, 207 of these women contributed to 800 renal function values. The normal reference range for sCr was 30–57 and 32–60 umol/l in the 2nd and 3rd trimesters of pregnancy. Normal reference ranges for CrCl using the MDRD calculation were 129–282 and 119–267 ml/min/1.73m2 for the 2nd and 3rd trimesters, respectively. Using the CG method of calculation, normal reference ranges for CrCl were 120—304 and 123–309 ml/min/1.73m2 for the 2nd and 3rd trimesters respectively. In comparison, the normal reference range for sCr, CrCl by MDRD and CG calculations postpartum was 40–77 umol/l, 92–201, and 90–238 ml/min/1.73m2, respectively. Conclusions In African women, the Upper Limit of Normal (ULN) for sCr in pregnancy is approximately 20% lower than 6 months postnatally. Inversely, the Lower Limit of Normal (LLN) for CrCl using either MDRD or CG equation is approximately 35% higher than 6 months postnatally. We provide normal reference ranges for sCr and CrCl for both methods of calculation and appropriate for the 2nd and 3rd trimesters of pregnancy in African women.

A prospective audit on adult thromboprophylaxis and therapeutic anticoagulation prescribing and administration practices in Galway University Hospitals

Abstract Introduction Anticoagulants are high-alert medications that can cause significant patient harm if used inappropriately.[1] These preparations have been identified as a significant medication safety concern in Galway University Hospitals and are one of the most frequently reported medication incidents in Ireland.[2] A key performance indicator agreed by the local Medication Safety Subgroup and Drugs and Therapeutics Committee was to conduct an anticoagulation audit against local guidelines to identify patterns and develop quality improvements. Methods A prospective audit was conducted over six weeks from September to November 2022 by five interprofessional data collectors using a data collection tool and accessing drug records and clinical notes. Development of the tool was guided by national[1] and local guidelines as well as design input from local expert specialist doctors and pharmacists. Adult inpatients on all wards receiving thromboprophylaxis (after 24 hours of admission) or therapeutic anticoagulation were included. Paediatrics and psychiatry were excluded. The protocol and tool were approved by the local Clinical Audit Committee, piloted with three inpatients, and communicated to all data collectors prior to commencement. Generated data were anonymous and securely stored. Data analysis was carried out by two independent researchers to confirm reliability of results. Results A total of 242 inpatients were audited on 26 wards: -Patients prescribed thromboprophylaxis (52%; 126/242). -Patients prescribed therapeutic anticoagulation (26%; 63/242) -Patients not prescribed anticoagulants (22%; 54/242) Most patients (92%; 216/234) did not have a thromboprophylaxis risk assessment form completed/signed. Nineteen patients (35%; n=54) not prescribed thromboprophylaxis or therapeutic anticoagulation should have been prescribed anticoagulation. High compliance with guidelines (>80%) included: i) anticoagulants prescribed in correct section of drug record, ii) appropriate agents prescribed, iii) correct dose and frequency, iv) few dose delays and omissions, and v) indication mostly documented. Low compliance with guidelines (<35%) included: -Patient height and weight not documented: unable to calculate creatinine clearance to determine accurate dose. -Incorrect administration times for once daily therapeutic dosing (should be in morning to facilitate surgery next day) and twice daily dosing (mostly 8am and 10pm = gap of 14 hours and 10 hours). Conclusion Results have identified varying levels of compliance with local anticoagulation guidelines. To date, there has been continuous targeted education and training on appropriate anticoagulation use for doctors, nurses, and pharmacy staff inclusive of the development and implementation of a new bespoke eLearning module for high-alert medications (which includes the appropriate use of anticoagulants specific to Galway University Hospitals). High leverage strategies, such as electronic prescribing, is a current consideration to standardise practices. Strengths include study robustness, interprofessional collaboration, and transferability to other hospitals. Perhaps reducing the scope in a re-audit which will be conducted in 2024 to identify any improvements in medication safety and patient care with these agents may allow for further in-depth analysis.

Abstract P418: Pre-Stroke Use of Loop Diuretics in Elderly Patients Aggravates Renal Function at the Onset of Acute Stroke: A Propensity Score-Matched, Retrospective Cohort Study

Introduction: Renal function is often impaired in elderly patients experiencing acute stroke (AS) due to pre-existing chronic kidney disease (CKD), which can progress to severe renal dysfunction (SRD). SRD can limit pharmacological treatments, such as anticoagulants, antiplatelets, diabetes medicines, or antihypertensives during the AS phase. Therefore, preventing CKD progression to SRD and minimizing the use of renal-impairing agents before SRD development is crucial. Loop diuretics, commonly prescribed for heart failure, have been reported to exacerbate renal function. Sex-based differences in renal function due to gonadal hormones exist. However, the impact of loop diuretics on the risk of SRD before AS in both sexes remains unclear. Hypothesis: The pre-stroke use of loop diuretics in elderly patients aggravates renal function at the onset of AS in both sexes. Methods: We conducted a propensity score-matched, retrospective cohort study involving patients admitted within 24 hours of AS onset between January 2013 and March 2019 with available pre-stroke medication information. We defined SRD as a calculated creatinine clearance (Ccr) of <30 ml/min. We analyzed logistic regression using variables for pre-stroke loop diuretics initiation, calculated propensity scores for pre-stroke loop diuretics usage, and implemented a one-to-one propensity score matching (PSM) by sex. We compared the incidence of SRD between loop diuretics users and non-users within each sex group. Results: Among 4294 patients with AS, 3472 met the inclusion criteria. Among these, 129 male and 143 female loop diuretic users were matched with non-users using the one-to-one PSM. After the PSM, median ages were 80 years in males and 86 years in females, respectively. The SRD incidence was 38.0% (49/129) versus 16.8% (21/129) in males (p<0.0001) and 50.4% (78/143) versus 23.1% (48/143) in females (p<0.0001), comparing users to non-users. Conclusions: The pre-stroke use of loop diuretics in elderly patients may increase the risk of SRD at the onset of AS in both sexes. Therefore, cautious utilization of loop diuretics in elderly patients is recommended to prevent SRD before AS. A possible option is to switch loop diuretics to other medications, which have been shown to have better renal protective effects. Further prospective studies are needed to validate our findings and establish the appropriate usage of loop diuretics in elderly patients before AS.

P09 Lancashire and South Cumbria Critical Care Network Vancomycin Project

Abstract Background This project was a collaborative piece of work across a critical care network that included specialist advice from colleagues including aseptic/technically trained pharmacists and microbiology to optimize care for critical care patients in Lancashire and South Cumbria. We used several members of our workforce including pharmacists, nursing staff, microbiologists, rotational doctors and consultants to work towards a harmonized guideline. Methods During our initial meeting, we identified that different centres were using different glycopeptides and administering them differently: East Lancashire Hospitals (ELHT)—continuous vancomycin infusion; Blackpool Cardiac and Blackpool General—continuous vancomycin infusion, with no formal guideline in place but adopted from ELHT; Lancashire Teaching Hospitals—intermittent vancomycin infusions; and University Hospitals Morecambe Bay—teicoplanin is glycopeptide of choice. Our consultant microbiologist discussed the use of glycopeptides and what infections they are used for in critical care. The pharmacokinetics of vancomycin and the benefit of using a continuous infusion was also discussed. We decided to undertake a clinical audit of our vancomycin guidelines at ELHT to ensure that we had an evidence base to implement our guideline and provide assurance to the working group. We agreed to reconvene the working group after this audit was completed and after the concerns of colleagues had been addressed. Results and conclusions We presented the results of our audit and highlighted the opportunities harmonizing this guideline would provide. We discussed various scenarios such as stepping up from a ward protocol to a continuous infusion and the different methods of calculating creatinine clearance and if this would influence the first 24 h of the infusion. One comment was concerning the administration of vancomycin and the number of times nurses will be changing bags for patients requiring higher doses, i.e. the majority of patients would usually be on 3 g/day or more depending on concentrations. This would mean changing the bag more than twice a day; as much as there is a therapeutic benefit to continuous vancomycin infusions, considering the max. concentration for peripheral and central lines allows for larger volumes, it would be beneficial (except in fluid restricted cases) to have a slightly larger volume to reduce the number of bag changes and plastic consumption. We considered this comment and discussed it with our aseptic services lead pharmacist. We attended a meeting of the ICS Aseptics Working Party across Lancashire and South Cumbria. WE discussed the proposed guideline and requested that aseptic units across Lancashire and South Cumbria developed worksheets to manufacture 5 g in 600 mL or 10 g in 1.2 L for central use to stop breaking the line when changing a bag and reducing plastic consumption. We also met with critical care practice educators across the network to discuss how we can promote this guideline and ensure nursing staff and prescribers are aware of how to prescribe and administer continuous vancomycin infusions. One of our units noted that they have had a few incidents with incorrect concentrations of vancomycin being made up for patients. We developed an e-learning package to educate our workforce.

The effect of baseline egfr on 6- month and 12-month mortality with CKD-EPI, MDRD and CG formulae in patients with advanced HIV

Background: HIV-associated renal disease was considered as an etiology of fatal condition in patients with HIV. Few equations (Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault) have been used in clinical for calculating creatinine clearance, however the prediction of these formulae in HIV patients have been different. Our goal was to evaluate the effect of baseline eGFR by three equations on 6- month and 12-month mortality in advanced HIV patients. Materials and method: We conduct a retrospective, observation cohort study of patients with HIV infection who firstly presented for care at selected HIV OPCs in Vietnam. Results: Of total of 1108 patients was eligible for analysis. HIV- positive patients with CKD stage 3 and 4 defined by CG and MDRD formula increased risk of 6- month and 12- month mortality. CKD-EPI were not correlated with 6-month and 12-month mortality in any stage of CKD. AUC (area unde curves) for 6-month mortality and 12-month with respect to eGFR calculated by CG formula was statistically higher than AUC by CKD-EPI and MDRD (p < 0.05, Delong test). Conclusion: Low eGFR calculated by CG were associated with higher mortality in patients with advanced HIV. Key words: HIV, eGFR, CKD-EPI, MRDR, CG.

KEYNOTE-905/EV-303: A phase 3 study to evaluate the efficacy and safety of perioperative pembrolizumab or pembrolizumab plus enfortumab vedotin (EV) for muscle-invasive bladder cancer (MIBC).

TPS4601 Background: Standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy + pelvic lymph node dissection (RC + PLND), but many patients with MIBC are ineligible for cisplatin-based chemotherapy. In the phase 1b/2 KEYNOTE-869/EV-103 study, combination therapy with the PD-1 inhibitor pembrolizumab and the Nectin-4–directed antibody-drug conjugate EV showed promising antitumor activity in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. KEYNOTE-905/EV-303 (NCT03924895) is a multicenter, randomized, open-label, phase 3 study to evaluate efficacy and safety of perioperative pembrolizumab alone or combined with EV versus RC + PLND alone in patients with MIBC who are ineligible for or decline cisplatin-based treatment. Methods: Patients with treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0) and predominantly (≥50%) urothelial histology who are cisplatin ineligible or decline cisplatin-based treatment and have an ECOG PS score of 0-2 are eligible. Cisplatin ineligibility will be defined as meeting ≥1 of the following criteria: impaired renal function with calculated creatinine clearance 30-59 mL/min; ECOG PS 2; grade ≥2 audiometric hearing loss per CTCAE v4.0; or NYHA class III heart failure. Patients will receive neoadjuvant pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for ≤3 cycles followed by RC + PLND and adjuvant pembrolizumab 200 mg IV Q3W for ≤14 cycles (arm A); RC + PLND followed by observation (adjuvant nivolumab permitted based on clinical indication and regulatory approval [arm B]); or neoadjuvant EV 1.25 mg/kg + pembrolizumab 200 mg IV Q3W for ≤3 cycles followed by RC + PLND and adjuvant EV + pembrolizumab for ≤6 cycles and adjuvant pembrolizumab 200 mg IV Q3W for ≤8 cycles (arm C). In the neoadjuvant and adjuvant phases of arm C, pembrolizumab will be administered on day 1 and EV will be administered on days 1 and 8 of each cycle. Enrollment is complete for arm A; patients will continue to be randomly assigned 1:1 to arm B or arm C. Stratification factors are tumor stage (T2N0 vs T3/T4aN0 vs T1-T4aN1), geographic region (United States vs Europe vs most of world), and cisplatin eligibility (cisplatin ineligible or cisplatin eligible but declines treatment). The primary end point is event-free survival between arm B and arm C. Secondary end points are event-free survival (arm A vs arm B) pathologic complete response, overall survival, disease-free survival, pathologic downstaging rates, and safety. Enrollment is planned for 308 patients, and recruitment is ongoing in Africa, Asia, Australia, Europe, North America, and South America. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO-GU Annual Meeting. All rights reserved. Clinical trial information: NCT03924895 .

Baseline characteristics of edoxaban treatment in routine clinical practice for patients with non-valvular atrial fibrillation in China (ETNA-AF-China)

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo (China) Holdings Co., Ltd, Shanghai, China. Background The effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) edoxaban for the treatment of patients with non-valvular atrial fibrillation (NVAF) have been investigated globally. Data from mainland China, however, is scarce. Purpose To report baseline characteristics of unselected NVAF patients receiving edoxaban in routine clinical practice. Methods ETNA-AF-China is a multi-center, prospective, observational study designed to evaluate effectiveness and safety of edoxaban for stroke preventions in 89 sites across mainland China with 2-year follow-up. Enrollment started on February 2021 and ended on October 2022. Patients having history of NVAF, prescribed edoxaban, and providing written informed consent were eligible. This descriptive analysis of the baselines data is based on a snapshot from November 2022. Results A total of 5,000 patients were enrolled and data of 4749 patients with full edoxaban treatment information at baseline were analyzed (60 mg: 2559, 30 mg: 2190). Overall, mean (SD) patient age was 70.2 (9.55) years, with 1660 (35.0 %) patients ≥ 75 years. Male patients constituted 57.0 %. The average calculated creatinine clearance rate, CHA2DS2-VASc scores and HAS-BLED scores were 71.3 (27.8) mL/min, 2.88 (1.41) and 1.83 (1.04), respectively. Patients with perceived frailty, history of stroke, history of bleeding comprised 6.46 %, 8.78 %, 2.21% of the overall population, respectively (Table). The majority of patients (79.0 %) received recommended dose according to label criteria, with similar percentages observed among economic regions (East, 81.5 %; Northeast, 78.4 %; Middle, 76.0 %; West, 76.8 %). A numerically larger percentage of patients receiving non-recommended 30 mg were categorised as high risk for either stroke or bleeding (presence of prior stroke, prior major bleeding or prior ICH, or a CHA2DS2-VASc score ≥ 4; 34.1 % vs 25.6 %), frail assessed by physician (10.6 % vs 3.3 %), and had stage 3 chronic renal disease (58.8 % vs 39.4 %) compared with patients receiving recommended 60 mg. Those prescribed a non-recommended 60 mg vs those with recommended 30 mg were less likely to be considered stroke or bleeding high risk (40.2 % vs 46.8 %), and advanced renal disease (≥ stage 4, 10.7% vs 13.8 %) (Figure). Conclusion In this real-world study, edoxaban was predominantly prescribed with elder NVAF patients, on dose of 60 mg. Most of Chinese patients adhered to edoxaban approved label and the deviation from dose recommendation appears to be influenced by physician’s consideration of patient’s characteristics (such as stroke or bleeding high risk). More data profiles of ETNA-AF-China concerning effectiveness and safety study are collecting at the follow-up period.

Analisis Farmakokinetik Klinik Dosis Obat Pasien Hipertensi Komplikasi Gagal Di RSUD Dr. Pirngadi Medan

Background: Hospitals are health service providers providing emergency care, outpatient and inpatient. Hypertension occurs when blood pressure is above normal. Clinical conditions that require dialysis treatment have a tendency to kidney failure. This effort is related to the field of clinical pharmacokinetics. Objective: The study was conducted to analyze the dose of drug administration in conditions complicated by kidney failure in hypertensive patients. Methods: The study went through a sampling stage of data from hypertensive patients complicated by kidney failure, data according to inclusion criteria, calculation of creatinine clearance, analysis of dose adjustments and creatinine clearance. Results: The study obtained 170 data, which met the inclusion criteria of 30 data. Drugs with a narrow therapeutic index and worsening kidney function that patients received included: digoxin, captopril, ranitidine, furosemide, ciprofloxacin, and cefriaxone in 2, 13, 9, 12, 3, and 8 cases respectively. Conclusion: According to dose adjustment calculations for patient creatinine clearance, it was found that the drug exceeded the individual dose in 6 out of 9; 8 of 13; and 2 cases each using ranitidine, captopril, digoxin

Современные маркеры определения функциональной способности почек в урологической практике.

Introduction. Over the past decade, there has been a progressive increase in the number of patients with chronic kidney disease (CKD). Early diagnosis of renal insufficiency allows to prevent irreversible consequences leading to disability and significant medical and economic costs. Purpose: to analyze modern markers for determining the functional ability of the kidneys. Materials and methods. A search was carried out in PubMed and Library, according to the keywords creatinine, urea, glomerular filtration rate (GFR), clearance, formulas for calculating creatinine clearance, cystatin C, β2-microglobulin, β-bound protein, NGAL, KIM-1, chronic kidney disease, chronic renal failure, urolithiasis. We found 389 sources no older than 10 years (published after 2012) that were relevant to the topic of the review. 80 articles were selected directly for citation in the review. Results. GFR assessment and detection of albuminuria are the most effective methods, but biomarkers used to calculate GFR are subject to a number of factors and do not allow assessing kidney function in real time. For early prediction of acute renal injury, the most suitable biomarkers are considered to be: NGAL and KIM-1 and IL-18. Equations combining cystatin C and creatinine r work better than equations using only cystatin C or creatinine, especially in situations where it is necessary to confirm chronic kidney disease. The combination of creatinine, cystatin C and the ratio of urine albumin to creatinine improves the stratification of the risk of progression of kidney disease and mortality. The latest developments in biomarkers allow us to hope that in the near future the assessment of the functional ability of the kidneys will be carried out in real time and will become a general clinical practice of a modern doctor. Conclusion. Modern biomarkers of the functional ability of the kidneys allow not only to evaluate the function, but also to screen for diseases, conduct differential diagnosis, and evaluate the effectiveness of the treatment. The modern approach to the diagnosis of renal dysfunction should be based not only on its diagnosis, but also on determining the topic of nephron damage.

Utilization of local treatment modalities and surveillance in veterans with early stage renal cell carcinoma.

643 Background: Surgery represents the standard treatment for early stage renal cell carcinoma (RCC). For older patients, especially those with comorbidities including chronic kidney disease (CKD), there have been efforts made to spare renal function. The objective of this study was to evaluate the disease and treatment characteristics of Veterans with early stage RCC. Methods: We used the national Veterans Affairs’ Corporate Data Warehouse (CDW) database to identify patients diagnosed between 2000-2018 with early stage (cT1-2N0M0) RCC. Laboratory and diagnosis data were used to calculate creatinine clearance and Charlson comorbidity score. Chronic kidney disease (CKD) was defined as creatinine clearance < 60 milliliters per minute. The odds of receiving surveillance were evaluated with multivariable logistic regression. Results: Overall 19,555 Veterans with early stage RCC were included. The median age at diagnosis was 65, 90% range (48-82). 9,807 patients (50%) had at least 1 comorbidity and 4169 (21%) had multiple. Of 16,514 (84%) patients with available lab data, 1,359 (8%) patients had CKD. The treatments received were radical nephrectomy (RN) (N=4107, 21%), nephron sparing surgery (NSS) (N=5008, 26%), thermal ablation (N=489, 3%), and surveillance (N=9946, 51%). Compared to 2000-2010, from 2011-2018, there was a higher proportion of patients receiving NSS (29% vs. 20%, p < 0.01) and a lower proportion receiving surveillance (49% vs. 54%, p < 0.01). On multivariable logistic regression, predictors of receiving surveillance included older age (Odds Ratio [OR] 1.03 per year, p<0.01), T1 disease (OR 1.18, 95% CI 1.08-1.28), increasing number of comorbidities (OR 1.12 per comorbidity point, 95% CI 1.08-1.16), or CKD (OR 1.25, 95% CI 1.12-1.41). Compared to creatinine clearance before diagnosis, the median change in creatinine clearance at least 1 year after diagnosis was -46 for RN, -9 for NSS, -8 for ablation, and -24 for surveillance (p<0.01). Conclusions: A significant proportion of Veterans with early stage RCC undergo surveillance. Nephron sparing treatments are becoming increasingly common and are associated with more modest reductions in renal function than radical nephrectomy or surveillance. Further studies are warranted to assess the impact of surveillance on survival and cancer related outcomes.

Renal function and survival following treatment for cT1N0 renal cell carcinoma in a veteran population.

642 Background: Radical nephrectomy (RN), nephron sparing surgery (NSS) and thermal ablation (TA) are associated with similar oncologic control for early-stage renal cell carcinoma (RCC). However, the potential protective role of nephron sparing treatments on renal function and its impact on non-cancer related mortality remains undetermined. Methods: We employed the national Veterans Affairs Corporate Data Warehouse (CDW) to identify patients diagnosed with cT1N0 RCC between 2000-2018. Laboratory and diagnosis data were used to calculate creatinine clearance and Charlson comorbidity score. Chronic kidney disease (CKD) was defined as creatinine clearance < 60 milliliters per minute. Kaplan-Meier analysis and multivariable Cox regression analysis were used to evaluate overall survival. Results: Overall, there were 8279 Veterans with cT1N0M0 renal cell carcinoma diagnosed between 2000-2018 who received either RN (2946, 36%), NSS (4846, 59%) or TA (487, 6%). Median follow up time was 8 years (90% CI 2-15 years). Patients receiving RN were older than those receiving NSS (median age 64.0 vs 62.6 years, p<0.01) but younger than those receiving TA (median age 67.9 years, p<0.01). Patients receiving RN and TA had more comorbidities than patients receiving NSS (mean Charlson scores 0.76 vs. 1.00 vs. 0.66, p<0.01. More patients among the RN group had CKD before RCC diagnosis than the NSS and TA groups (10% vs. 6% vs. 7%, p<0.01). Among the subset of patients without CKD before treatment, 17% of RN, 8% of NSS, and 11% of TA developed CKD at least 1 year after treatment, (p <0.01). Median OS was 11.5 years with RN, 14.2 years with NSS, and 10.3 years with TA. On multivariable analysis considering age, comorbidities, CKD, race, and year of treatment, compared to RN, NSS was associated with better OS (HR 0.75, p<0.01) with a trend to improved survival with TA (HR 0.88, p=0.08). Conclusions: NSS or TA are associated with less post-operative renal dysfunction than RN in patients treated for cT1N0 RCC in the VAHCS. NSS is associated with improved OS compared to RN. Further studies are warranted to assess the impact of renal dysfunction in this population in relation to oncologic and survival outcomes.

Comparison of Jaffe Method and Enzymatic Method at Measuring Serum Creatinine Level, Creatinine Clearance and Estimated Glomerular Filtration Rate.

Correct measuring of blood and urine creatinine level is necessary for identification and tracking of chronic kidney disease (CKD). The aim of this study is a comparison of Jaffe and enzymatic methods for measuring creatinine in serum and in urine, in order to determine whether there are any statistical significant differences between them, and whether they are reflected on creatinine clearance calculation and estimated glomerular filtration rate (eGFR). Creatinine in serum and urine was measured for the group of patients (N=60; female=34, male=26) from 24 to 69 years of age by using Jaffe's method on Dimension RxL biochemical analyzer, and enzymatic method on integrated biochemical and immunochemical analyzer Architect ci8200, and obtained levels are used for creatinine clearance calculation and eGFR. The methods correlate well, both in measuring serum creatinine (r 1 = 0.990) and in measuring urine creatinine (r 2 =0.974). There are no statistically significant differences between them (p=0.57). Measuring creatinine using different methods showed no statistically significant differences in the calculated clearances (p=0.93), they significantly correlate (r=0.9722). eGFR, using the MDRD and CKD-EPI formulas, were not statistically significantly different, regardless of the used method. Apart from significant correlations between the used methods, the results of using the Jaffe and enzymatic methods showed no significant differences at measuring serum creatinine level, or creatinine clearance and glomerular filtration rate.

Basiliximab is associated with a lower incidence of De novo donor-specific HLA antibodies in kidney transplant recipients: A single-center experience

PurposeInduction immunosuppression has improved the long-term outcomes after kidney transplant. This study explores the association of different induction immunosuppression medications (Basiliximab vs. Alemtuzumab vs. rabbit Antithymocyte Globulin) used at the time of kidney transplant with the development of de novo donor-specific HLA antibodies (DSA) in the first 12 months post-transplant period. MethodsA total of 390 consecutive kidney transplant recipients (KTR), between 2016 and 2018, were included in the analysis. A 104 (26.6%) received Basiliximab, 186 (47.6%) received Alemtuzumab, and 100 (25.6%) received rabbit Antithymocyte Globulin (rATG) for induction. All recipients had a negative flow cytometry crossmatch before transplant. Serum samples at 4- and 12-months post-transplant were assessed for the presence of de novo HLA DSA. kidney allograft function was compared among the three groups with calculated Creatinine Clearance on 24 h urine collection. ResultsDe novo HLA DSA were detected in total of 81 (20.8%) patients within 12 months post-transplant. De novo HLA DSA were detected in 12/104 (11.5%), 43/186 (23.11%), and 26/100 (26%) KTR that received Basiliximab, Alemtuzumab, and rATG respectively (p = 0.006). KTR that received Basiliximab were significantly older, and the last follow-up creatinine clearance was significantly lower at 42 ml/min compared to KTR that received Alemtuzumab or rATG (p = 0.006). ConclusionInduction immunosuppression utilizing Basiliximab is associated with significant reduction in development of de novo DSA within the first 12-months post kidney transplant but had lower creatinine clearance with long-term follow up.

Overall agreement between eGFR estimates obtained with the CKDEPI, MDRD and CG formulae in patients with advanced HIV diseases

Background: Traditional CKD risk factors as well as HIV-related factors are major determinants of the prevalence of renal diseases among HIV patients. Few equations have been used in clinical practice for calculating creatinine clearance, however, the accuracy of these formulae in HIV patients has been different. Our goal was to evaluate the reliability of all three equations (Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease, and Cockcroft-Gault) to estimate GFR in HIV-infected patients. Materials and method: We conduct a retrospective, observational cohort study of patients with HIV infection who are first time in care at selected HIV OPCs in Vietnam. Results: In 1108 patients eligible for analysis, a major patient was in HIV clinical stage 3 and 4 with a median age of 36, and median serum creatinine of 0.89 mg/dL. eGFR calculated by CG equation was lower than CKD-EPI formulae in overall except overweight patients (p<0.05, paired t-test) while the similar results were observed in both CKD-EPI and MRDR (p=0.144, paired t-test). Conclusion: There was a substantial agreement between CKD-EPI and MDRD eGFR, agreement percentage of 90.1 and MDRD was reliable as CKD-EPI to calculate eGFR in the HIV population. Key words: HIV, eGFR, CKD-EPI, MRDR, CG.

Assessing safety of inpatient direct oral anticoagulant prescribing utilising an electronic prescribing system

Abstract Introduction Direct oral anticoagulants (DOACs) are favoured over oral vitamin K antagonists (VKA) due to their fixed-dose regimen and reduced thromboembolic and bleeding risk. Despite clear dose adjustments based on patient characteristics, several observational studies have demonstrated 15-20% of patients being overdosed or underdosed when compared to licensing.1,2 Inappropriate dosing can lead to harm e.g., bleeding or thrombosis which would prolong/escalate hospital stay. Aim To assess clinical appropriateness of inpatient DOAC prescriptions across multiple sites of a large London based NHS Trust. Methods This study was conducted retrospectively over a seven month-period across 4 sites from a large London based NHS Trust from November 2021. Electronic prescribing system was used to generate daily reports that enabled a specialist haematology pharmacist to assess all adult inpatient DOAC prescriptions for appropriateness as per product licensing for indication. The report included patient characteristics (age, gender, body weight), prescribed DOAC (agent, dose, indication), serum creatinine, hospital site. Queries were escalated for review by the pharmacy or medical teams. Type of intervention (dose, agent, or no change) was recorded, and allocated a clinical severity rating using IMPACCTS.3 This scale runs from a score of 1 indicating a good practice intervention to a score of 5 that prevents serious or major harm including death. This study was approved by the University College London (UCL) School of Pharmacy research ethics committee. Results A total of 1,761 inpatient DOAC prescriptions were reviewed, of which 10.1% had a clinical query requiring escalation. Results demonstrate that 77.0% (n=137) of all queries were dose-related, 33.2% overdosed and 43.8% underdosed compared to licensing, the most common agent requiring adjustment being apixaban. Renal-related queries were most frequently observed (50.6%), with 12.8% of patients on edoxaban having CrCl >110ml/min. We found that 2.3% of prescription queries raised required review and stopping antiplatelet agents co prescribed with anticoagulation. Most interventions made had a severity rating of 4 (74.2%), followed by 15.2%, and 10.7% had a score of 1 and 3, respectively. Following pharmacist recommendations, changes made were either dose (38.7 %) or agent (14.6%). Alternatively, it was not applicable due to a change in clinical status, i.e., renal function improved (1.1%) or patient re-weighed (6.2%). Changes to prescriptions did not apply to some patients as documentation of clinical reasoning were recorded (19.7%), or due to patients being discharged (13.5%). Discussion/Conclusion This study has demonstrated a significant number of DOAC prescriptions are inappropriate at the point of prescribing when compared to product summary of characteristics for the indications listed. The use of a centralised report to assess appropriateness of DOAC prescribing across several sites has facilitated a centralised mechanism led by a haematolgy specialist to improve safer DOAC prescribing. The most frequent interventions being made included dose amendments based on calculated creatinine clearance and amending (or adding) indications entered on the system. Further work is required to demonstrate effective change management strategies that have been implemented to further improve the safety of DOAC prescribing within the Trust.

Maternal and infant renal safety following tenofovir disoproxil fumarate exposure during pregnancy in a randomized control trial

BackgroundTenofovir disoproxil fumarate (TDF) in combination with other antiretroviral (ARV) drugs has been in clinical use for HIV treatment since its approval in 2001. Although the effectiveness of TDF in preventing perinatal HIV infection is well established, information about renal safety during pregnancy is still limited.Trial designThe IMPAACT PROMISE study was an open-label, strategy trial that randomized pregnant women to one of three arms: TDF based antiretroviral therapy (ART), zidovudine (ZDV) based ART, and ZDV alone (standard of care at start of enrollment). The P1084s substudy was a nested, comparative study of renal outcomes in women and their infants.MethodsPROMISE participants (n = 3543) were assessed for renal dysfunction using calculated creatinine clearance (CrCl) at study entry (> 14 weeks gestation), delivery, and postpartum weeks 6, 26, and 74. Of these women, 479 were enrolled in the P1084s substudy that also assessed maternal calcium and phosphate as well as infant calculated CrCl, calcium, and phosphate at birth.ResultsAmong the 1338 women who could be randomized to TDF, less than 1% had a baseline calculated CrCl below 80 mL/min. The mean (standard deviation) maternal calculated CrCl at delivery in the TDF-ART arm [147.0 mL/min (51.4)] was lower than the ZDV-ART [155.0 mL/min (43.3); primary comparison] and the ZDV Alone [158.5 mL/min (45.0)] arms; the mean differences (95% confidence interval) were − 8.0 mL/min (− 14.5, − 1.5) and − 11.5 mL/min (− 18.0, − 4.9), respectively. The TDF-ART arm had lower mean maternal phosphate at delivery compared with the ZDV-ART [− 0.14 mg/dL (− 0.28, − 0.01)] and the ZDV Alone [− 0.17 mg/dL (− 0.31, − 0.02)] arms, and a greater percentage of maternal hypophosphatemia at delivery (4.23%) compared with the ZDV-ART (1.38%) and the ZDV Alone (1.46%) arms. Maternal calcium was similar between arms. In infants, mean calculated CrCl, calcium, and phosphate at birth were similar between arms (all CIs included 0).ConclusionsAlthough mean maternal calculated CrCl at Delivery was lower in the TDF-ART arm, the difference between arms is unlikely to be clinically significant. During pregnancy, the TDF-ART regimen had no observed safety concerns for maternal or infant renal function.Trial Registration: NCT01061151 on 10/02/2010 for PROMISE (1077BF). NCT01066858 on 10/02/2010 for P1084s.

Phase 1 study of LP-108 as monotherapy and in combination with azacitidine in patients with relapsed or refractory myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML).

TPS7071 Background: BCL2 inhibition as a means of targeting intrinsic apoptotic pathways that confer a survival advantage to leukemic blasts has become a key therapeutic strategy for patients with myeloid malignancies. LP-108 is an oral highly potent and selective inhibitor of BCL-2 with comparable or more potent in vitro inhibitory activity as compared to the FDA approved oral BCL-2 inhibitor venetoclax. We propose to investigate LP-108 as monotherapy and in combination with azacitidine in patients with relapsed or refractory (r/r) MDS, CMML or AML. Methods: The primary objectives of the trial are 1.) To determine the safety, tolerability and determine the maximum tolerated dose (MTD) and the recommended phase 2 dose / optimal biological dose (OBD) of LP-108 as a single agent (Arm 1) and in combination with azacitidine (Arm 2) in patients with relapsed/refractory MDS/CMML/AML; 2.) To characterize the pharmacokinetic profile of LP-108 as monotherapy and in combination with a fixed dose of azacitidine. The secondary objectives of the trial are 1.) To evaluate the objective response rate of LP-108 (monotherapy or combination therapy) in r/r MDS/CMML/AML as well as progression free survival, duration of response and overall survival. In Arm 1 patients will be enrolled according to a 3+3 design with escalating doses of LP-108 for a 28 day cycle (firs table). DLTs will be determined in the first 28 days. In Arm 2 patients will be enrolled according to a 3+3 design with escalating doses of LP-108 in combination with a fixed dose of azacitidine (second table). DLTs will be determined in the first 28 days. DLT for both arms is defined as some ≥ Grade 3 non-hematological toxicities or prolonged myelosuppression. Patients may continue treatment until disease progression, unacceptable toxicity, or per investigator discretion. Patients age ≥ 18 years with r/r MDS with excess or blasts or with high or very-high risk disease per the R-IPSS, or r/r MDS for Arm 2, r/r AML, or frontline older and/or unfit AML for Arm 2, or r/r CMML may enroll. Patients with prior hypomethylating agents or venetoclax exposure may enroll. The blast count at the time of starting therapy must be ≤ 30 x 109 cells/L. Hydroxyurea is allowed prior to and during treatment. Ejection fraction ≥ 50% is required. Calculated creatinine clearance shall be ≥ 30 mL/min. Strong CYP3A4 inducers and inhibitors are prohibited. Patients on weak/moderate azole antifungals were allowed to enroll. Enrollment to Arm 1 is complete and there have been no DLTs to date. Enrollment to Arm 2 is pending. Arm 1 Dose Escalation Scheme (LP-108 monotherapy). Clinical trial information: NCT04139434. [Table: see text][Table: see text]

Estimation of Kidney Function in Patients With Multiple Myeloma: Implications for Lenalidomide Dosing.

Lenalidomide is an immunomodulatory drug used to treat multiple myeloma that requires renal dosing adjustment based on Cockcroft-Gault (CG). Various equations to estimate kidney function exist and pose a potential issue with lenalidomide dosing. The objective of this analysis was to evaluate the impact of estimating kidney function in newly diagnosed multiple myeloma patients with CG, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and their potential impact on lenalidomide dosing. Data from 1121 multiple myeloma patients at the time of diagnosis acquired from the Mayo Clinic were used to calculate creatinine clearance (CrCl) using Cockcroft-Gault with actual body weight (CGABW), ideal body weight (CGIBW), or adjusted body weight (CGAdjBW); MDRD; and CKD-EPI for each subject. Discordances in dosing were then analyzed, and lenalidomide exposure was calculated for each subject to assess impact on pharmacokinetics of lenalidomide for patients who received discordant doses. Overall, approximately 16% of patients received a discordant dose when using MDRD or CKD-EPI instead of CGABW. The most common dose discordance was the decrease of a full dose of lenalidomide 25 mg when using CGABW down to 10 mg and when using MDRD or CKD-EPI with 53.8% to 55.6% of all discordances in this category. When assessing different body weights, the most common discordance was a decrease from 25 to 10 mg when using CGIBW instead of CGABW; the same trend was observed when using CGAdjBW instead as well. Patients were also at risk of over- or underexposure based on area under the concentration versus time curve (AUC) for discordant dosing. A significant proportion of patients are at risk of under- or overdose of lenalidomide if CKD-EPI or MDRD are used instead of CGABW. Physicians should use CGABW when estimating renal function to dose lenalidomide.

Evaluation of standard dosing for selected broad-spectrum Hydrophilic antibiotics in critically ill patients with Augmented renal clearance: An Observational Study

Background: Inappropriate antibiotic dosing in critically ill patients with augmented renal clearance (ARC) may be associated with pathogens' resistance and worse outcomes. Unfortunately, studies regarding the relationship between ARC and clinical outcomes in patients treated with antibiotics are scarce. This study aims to evaluate selected broad-spectrum hydrophilic antibiotics' effectiveness and clinical outcomes in ARC critically ill patients with confirmed infections. Methods: A retrospective a retrospective cohort study in adult critically ill patients who were admitted to intensive care units at King Abdulaziz Medical City, Riyadh, and received standard dosing of selected broad-spectrum hydrophilic antibiotics (meropenem, imipenem, or piperacillin/tazobactam) with confirmed infection. All the patients who met our eligibility criteria during the study period (January 1, 2018, to December 31, 2019) were included. According to the calculated creatinine clearance using the Cockcroft-Gault equation, eligible patients had been classified into two groups: ARC versus non-ARC. The primary outcome was to assess pathogen eradication at 10–14 days; other outcomes were considered secondary. Multivariate logistic and generalized linear regression analyses were used. We considered P < 0.05 statistically significant. Results: A total of 133 patients were included in the study; 66 patients had ARC. The distribution of infections and types of pathogens between the groups were similar. The pathogen eradication at 10–14 days was similar between the two groups (odds ratio [OR] 1.08; 95% confidence interval [CI], 0.41–2.78; P = 0.88). Moreover, the odds of resistance development and persistence after three days were not significantly different between the two groups ([OR 0.78; 95% CI, 0.25–2.40; P = 0.66] and [OR 0.88; 95% CI, 0.35–2.18; P = 0.78], respectively). Conclusion: In terms of pathogen eradication, resistance, and persistence, ARC patients and non-ARC patients responded similarly to conventional doses of hydrophilic broad-spectrum antibiotics. To confirm our findings, further randomized controlled clinical trials are needed.

Evaluation and enhancement of standard equations for renal function estimation in individuals with components of metabolic disease

BackgroundThe primary objective of this study aims to test patient factors, with a focus on cardiometabolic disease, influencing the performance of the Cockcroft-Gault equation in estimating glomerular filtration rate.MethodsA cohort study was performed using data from adult patients with both a 24-h urine creatinine collection and a serum creatinine available. Creatinine clearance was calculated for each patient using the Cockcroft-Gault, Modified Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations and estimates were compared to the measured 24-h urine creatinine clearance. In addition, new prediction equations were developed.ResultsIn the overall study population (n = 484), 44.2% of patients were obese, 44.0% had diabetes, and 30.8% had dyslipidemia. A multivariable model which incorporating patient characteristics performed the best in terms of correlation to measured 24-h urine creatinine clearance, accuracy, and error. The modified Cockcroft-Gault equation using lean body weight performed best in the overall population, the obese subgroup, and the dyslipidemia subgroup in terms of strength of correlation, mean bias, and accuracy.ConclusionsRegardless of strategy used to calculate creatinine clearance, residual error was present suggesting novel methods for estimating glomerular filtration rate are urgently needed.