Normal Creatinine Clearance Research Articles

Impact of the Preservation of Residual Kidney Function on Hemodialysis Survival: Results from the BISTRO Trial.

Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.

#1647 Clinical insights into incremental hemodialysis: a retrospective analysis of patient persistence and outcomes

Abstract Background and Aims Incremental haemodialysis has been proposed as an alternative to standard thrice-weekly haemodialysis for incident patients with significant residual kidney function. Definition is not unique, but it is mostly intended as twice weekly dialysis. Its diffusion is not known since there are no public registers in Europe, but it is adopted in some dialysis facilities, while in others is not, with geographical differences. In our centre incremental haemodialysis in adopted for some patients, based on the clinical judgement, without a strict protocol. We retrospectively analysed clinical outcomes of the incident patients of the last 36 months, to understand which patients may benefit more from this approach, how long it is viable and the clinical outcomes. Method Retrospective observational analysis of incident patients of the last 36 months, without serious rapidly evolving disease. Focus was on persistence in twice-weekly dialysis, nutritional parameters, residual kidney function, hospital admissions and economic considerations. 36 patients started haemodialysis with a 2-times per week schedule while 13 with full dose dialysis. At baseline, there were no significant differences on age, sex, serum albumin or vascular access. 5 patients in full dose group were anuric for bilateral nephrectomy or rapidly progressive kidney disease, while all patients in incremental group had significant residual kidney function (average creatinine clearance: 7.1 ml/min). Results During the follow up period, 19/36 patients’ weekly dialysis sessions were incremented to three after a median time of 280 days, and 17/36 were still on 2-dialysis with a median follow-up time of 228 days. The reason for transition to three dialysis per week was residual kidney function loss except for a case of pericarditis. Persistence in incremental dialysis was >80% at 6 months and 44% at 1 year (Fig. 1a). We observed a significantly reduced persistence in patients with low ultrafiltration at 2nd month of dialysis (<1.7% of weight per session – 1 kg for a 60 kg patient-) and a reduced persistence with pre-dialysis systolic blood pressure <150 mmHg at 2nd month (Fig. 1b-c). Persistence was not different in more frail patients (elderly, dialyzed with a central venous line or with lower baseline albumin). Serum albumin increase was higher in patients in incremental haemodialysis at 6 months, with a borderline statistically significant difference, and similar at 1 year (Fig. 2a-b). The average weight was stable in both groups (Fig. 2). Hospital admissions were lower in the incremental group, and number of days of hospitalization per 1000 patients’ days were lower (24 vs 41 days). Thanks to the incremental approach, about 1600 dialysis sessions were avoided for the patients included in the analysis, with significant reduction of economic impact for the public healthcare and the possibility to treat more patients. Data was insufficient to make conclusions on kidney function preservation. Conclusion Incremental approach is valid in our experience. These data give useful information on how long we can expect patients to persist in 2-weekly dialysis and on which patients might benefit more and longer of this approach. The patients with better volume control, which reflect in adequate blood pressure control and low ultrafiltration rate, show a significantly longer persistence in incremental dialysis. The approach is valid also for frail patients. We also found better albumin and lower hospital admission rates that could be related with a reduced health-care exposition and better overall patients’ well-being, with adequate uremic symptoms control. The reduction on the hospital admissions has been already observed, while the albumin better rise is a new finding and should be confirmed in a randomized or at least larger study. Waiting for the results of the on-going randomized clinical trials, incremental haemodialysis might be the new standard-of-care for a subset incident haemodialysis patients.

Changes of PK/PD of Meropenem in patients with abdominal septic shock and exploration of clinical rational administration plan: a prospective exploratory study

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

Increased Exceptional Response and Overall Survival Advantage for Patients with Multiple Myeloma Receiving Melphalan 200mg/m 2 Vs 140 Mg/m 2 Conditioning for Autologous Hematopoietic Stem Cell Transplantation

The standard conditioning regimen for multiple myeloma patients undergoing autologous hematopoietic stem cell transplant (HSCT) is intravenous melphalan dosed at 200mg/m 2 (mel200). Prior retrospective studies indicated that dose reduction to melphalan 140 mg/m 2 (mel140) confers similar progression-free (PFS) and overall survival (OS), leading to increased use of mel140 in patients with comorbidities or advanced age. A recent single-center retrospective study (Sharma et al, Leukemia Lymphoma 2023) identified an OS advantage yet similar PFS for mel200 vs mel140, suggesting that certain patient cohorts may benefit from mel200. These findings require confirmation and better understanding of the risks and benefits to different dosing strategies. We performed a single-center retrospective study of mel dosing and transplant outcomes at the University of Nebraska Medical Center between 2008-2018. Three hundred and sixty-two patients underwent a first autologous HSCT with mel conditioning; 95 received mel140 while 267 received mel200. Nearly all patients received maintenance therapy (n= 357, 99%). Patient demographic and disease factors were largely comparable between mel140 and mel200 cohorts including sex, response prior to HSCT (both 73% for very good partial response or better), and presence of high-risk cytogenetics (t(4;14), t(14;16), t(14;20), del17p; 15% vs 14%). The mel140 group was older (65.1 years vs 59.7 years), had higher hematopoietic cell transplantation-specific comorbidity index (HCT-CI) scores (64% vs 40% at ³3), and International Staging System (ISS) stages (40% vs 22% at stage III) than the mel200 group. Average creatinine clearance at transplant was 71 vs 91 mL/min/m 2 in the mel140 vs mel200 cohorts, respectively. OS favored mel200 with a median survival time of 94.4 vs 69.1 months (mel200 vs mel140, Figure 1, p = 0.002). There was no statistical difference in PFS between mel200 vs mel140 (median PFS 73.0 vs 60.5 months, p = 0.43, respectively). With Cox proportional hazards regression, we performed a multivariate analysis of risk factors on PFS and OS. For OS, age ( p = 0.02) retained statistical significance within the model. Mel dosing and high-risk cytogenetics (both p = 0.09) did not retain significance. HCT-CI may have an effect ( p = 0.04), but due to missing data on n= 125/362 subjects this could not be well evaluated. Response prior to HSCT, creatine clearance at transplant, and ISS stage were not statistically significant. Given the multiple variables assessed and missing data for HCT-CI we separately analyzed mel dosing together with the most significant variable in the model, age. In this subset OS model, mel200 was associated with an improved OS (hazard ratio (HR) 0.64, p = 0.03) while age was associated with an adverse effect (HR 1.11 per 5-year increase, p = 0.06). For the multivariate PFS model, only high-risk cytogenetics (HR 1.82 yes vs no, p = 0.004) retained statistical significance. Median engraftment was faster in mel200 cohort (67% vs 92% engraftment starting at ³D+12, p <0.001). We next examined the impact of mel dosing on the rate of exceptional response (Paquin et al, Blood Cancer Journal 2020), defined as alive and progression-free for 8 or more years. Twenty-nine of 362 patients (8%) met the requirements for exceptional response. Two (7%) received mel140 while 27 (93%) received mel200. Exceptional responders were younger and split evenly between male and female. The majority had at least a very good partial response prior to HSCT (79%). Only 2 exhibited high-risk cytogenetics; one received bortezomib and lenalidomide maintenance, the other only bortezomib. On multivariate analysis, only two factors contributed to exceptional response: mel dose (mel200 odds ratio (OR) 5.22, Table 1, p = 0.01) and HCT-CI (OR 0.66 for increasing score, Table 1, p = 0.02. High-risk cytogenetics was not associated with exceptional responders (OR 0.43 yes vs no, p = 0.38) which may be due to low sample size. We conclude that mel dosing impacts OS but not PFS in our cohort, though this effect is confounded by increasing age and potentially comorbidity. We report for the first time that mel200 dosing increases the rate of exceptional response compared to mel140. Overall, these data support recent conclusions by Sharma et al and challenge the previous reports of similar OS outcomes between mel200 and mel140 dosing.

Abstract P204: Acute Kidney Injury Prior To Pregnancy Induces Renal And Endothelial Dysfunction Which Predisposes Pregnant Rats To Adverse Pregnancy Outcomes

Clinical data report an increase in adverse pregnancy outcomes in women with a history of AKI despite clinical recovery prior to pregnancy. We developed a rat model of pregnancy post-AKI in which female Sprague-Dawley (SD) rats recover normal creatinine clearance 30 days post-AKI, however, exhibit endothelial dysfunction, elevated plasma creatinine and fetal growth restriction (FGR) during pregnancy compared to sham. We hypothesized that AKI-induced endothelial dysfunction predisposes pregnant rats to adverse pregnancy events including renal dysfunction and FGR, and further, that sildenafil will ablate endothelial dysfunction and prevent AKI-induced FGR. Female SD rats were randomized to 45-minute warm bilateral renal ischemia reperfusion or sham (N=6-8/grp) and 15 days post-surgery were put on vehicle or sildenafil chow (50 mg/kg/day) and mated 30 days post sham/AKI surgery. Gestational day 1 (GD1) was determined via vaginal smear. Plasma and 24-hour urine collection, vascular and renal injury were analyzed in pre-pregnancy (30 days post-AKI/Sham) or late pregnancy (GD20). Although previous cohorts show creatinine clearance normalizes 30 days post-AKI, urine kidney injury marker-1 (KIM-1) was greater in AKI rats compared to sham after 30 days (580±169 pg/24hrs vs 257±17, P=0.09) which remained elevated at GD20 of pregnancy (283±28 vs 216±12, P=0.06). Mason Trichrome revealed increases in glomerular (0.93±0.08 vs 0.04±0.04 score, *P<0.05) and tubular fibrosis (1.7±0.19 vs 0.0±0.0, *P<0.05) in post-AKI pregnant rats at GD20 compared to sham. Endothelial-dependent relaxation to acetylcholine (ACh) in 3 rd order mesenteric arteries, measured by wire myography, was impaired in both 30-day post-AKI rats (concentration-response, 1nM-10μM, 2-w ANOVA, RM, *P<0.05) and in post-AKI GD20 groups (*P<0.05) compared to respective shams. Sildenafil treatment restored endothelial function at GD20 (P>0.05) and restored pup weights in post-AKI pregnant GD20 rats (1.18g±0.23 g vs 2.11±0.19, *P<0.05). Collectively, these data indicate that AKI induces endothelial dysfunction in female rats predisposing them to adverse renal adaptations and FGR in pregnancy, which is potentially prevented by improvement of endothelial function with sildenafil.

680. Utility of Cefoxitin for the Treatment of ESBL-producing E. coli Urinary Tract Infections

Abstract Background Carbapenems are regarded as first-line agents for the treatment of ESBL-producing bacterial infections, even when in vitro activity to other beta lactams is demonstrated. However, overuse is associated with the selection of beta-lactamases that can hydrolyze carbapenems. Patients with isolated urinary tract infections due to ESBL–producing E. coli potentially have a lower burden of infection ("low inoculum"). These patients are frequently less ill and may benefit from non-carbapenem therapy. Cephamycins have in vitro activity against ESBL–producing Enterobacterales, and may be useful in the treatment of ESBL E. coli urinary tract infections as a carbapenem sparing agent. Methods Patients 18 years of age and older, hemodynamically stable with negative blood cultures and who demonstrated signs and symptoms of a urinary tract infection with a urine culture showing ESBL E. coli, were eligible to participate. Patients were started on initial antimicrobial therapy at the discretion of the admitting physician, and if the urine culture showed ESBL E. coli with an MIC of less than 8, the antimicrobial stewardship team requested to switch the patient to Cefoxitin 2 g intravenously every 6 hours, via extended infusion. The dose was renally adjusted as appropriate, and patients with beta-lactam allergies were excluded. Results 46 patients were evaluated between May 2017-April 2022. Patients received antibiotics for 2.6+1 day before the switch to Cefoxitin. The mean duration of therapy with Cefoxitin was 4.5+2.2 days. All 46 patients had resolution of fever and dysuria. Six patients were readmitted within 30 days, but none were due to a urinary tract infection. 30 patients had a repeat urinalysis at 48 hours, and all demonstrated reduction in pyuria. 39 patients had a repeat urine culture following completion of therapy, and 36 had converted to culture-negative status. Conclusion Cefoxitin is a useful agent for the treatment of ESBL E. coli urinary tract infections. The optimal dose appears to be 2 g intravenously every 6 hours, via extended infusion, in patients with normal creatinine clearance. Further larger studies, involving patients with pyelonephritis, are needed to validate these findings. Disclosures Ramesh V. Nathan, MD, Eli Lilly: Grant/Research Support|PPD: Grant/Research Support.

Ureteral Inflammatory Myofibroblastic Tumor as a Cause of Gross Hematuria in Adults

At his first urological appointment, a 44-year-old male patient presented with gross hematuria and right lower back pain for one week. He had no history of smoking, occupational risks, trauma, urinary lithiasis, or any other comorbidities. The patient had no family history of malignancies. Laboratory tests revealed normal creatinine clearance, hemogram, coagulation tests, and negative urinary culture. Computed tomography imaging is shown in Figure 1. A diagnostic right ureteroscopy was performed, followed by a biopsy of the visible tumor and a double J stent placement.

The Influence of Acute High Dose MitoQ on Urinary Kidney Injury Markers in Healthy Adults

IntroductionMitochondrial‐derived oxidative stress contributes to vascular dysfunction[1]. Chronic supplementation using the mitochondrial‐targeted antioxidant, MitoQ, in low doses (20 mg/day), improves vascular function in older adults and patients with chronic kidney disease [2, 3]. Furthermore, multiple studies have used acute high dose (>80mg/day) MitoQ, to examine the influence of mitochondrial oxidative stress on the vasculature [3, 4]. However, recent in vitro data suggest that MitoQ may induce nephrotoxicity which could contribute to kidney damage[5]. Therefore, we sought to determine whether acute, high dose MitoQ elicited changes across multiple urinary biomarkers associated with kidney injury in healthy adults.Methods15 healthy adults (10 females, mean ± SD, 28 ± 8 years, BMI: 25.3 ± 4.1 Kg/m2, BP: 112 ± 13/67 ± 7 mmHg) reported to our laboratory for two separate visits and were assigned MitoQ (100 – 160 mg based on body mass) or a placebo, in a randomized crossover design. Visits were separated by ≥ 72 hours. Venous blood was collected at baseline (prior to capsule ingestion) and urine was collected for 4‐6 hours after the study visits. We assessed serum and urine creatinine (Jaffe reaction) to determine 4‐6‐hour creatinine clearance. Regarding kidney injury biomarkers, we assessed multiple urinary biomarkers including the chitinase 3‐like‐1 gene product YKL‐40, kidney‐injury marker‐ 1 (KIM‐1), monocyte chemoattractant protein‐1 (MCP‐1), epidermal growth factor (EGF), neutrophil gelatinase‐associated lipocalin (NGAL), and uromodulin using multiplex. We calculated biomarker excretion rate (i.e., analyte concentration x 4–6‐hour urine flow rate [ml/min]) and performed a natural log transformation prior to parametric testing. We used a paired sample t‐test to compare creatinine clearance between conditions and Hotelling’s T2 to assess urinary markers between conditions.ResultsThere was a trend for acute MitoQ supplementation to reduce body surface area normalized creatinine clearance (placebo: 104.6 ± 16.6 vs MitoQ: 85.5 ± 24.4 mL/min/1.73m2, p = 0.069, η = 0.699). However, acute MitoQ supplementation did not influence urine flow rate (placebo: 1.9 ± 1.2 vs MitoQ: 1.5 ± 0.8 ml/min, p = 0.333) or urinary kidney injury markers (T21,20 = 16.776, p = 0.151). Using exploratory univariate analysis there were not any trends for any individual urine kidney injury marker (e.g., YKL‐40; placebo: 607 ± 386 vs. MitoQ 448 ± 241 pg/min, p = 0.544; KIM‐1; placebo: 79.01 ± 38.14 vs MitoQ 69.72 ± 44.26 pg/min, p = 0.362; NGAL; placebo: 20.8 ± 16.8 vs. MitoQ 18.9 ± 21.3 ng/min, p = 0.470).ConclusionsAcute MitoQ supplementation reduced normalized creatinine clearance without influencing flow rate and had no effect on urinary kidney injury markers. Future studies should include patient populations and longer‐term surveillance. However, based on our preliminary analysis using urinary kidney injury markers, acute high dose MitoQ supplementation does not elicit kidney injury in healthy adults.

Profil Klirens Kreatinin pada Pasien Penyakit Ginjal di RSUD Dr. Doris Sylvanus Kota Palangka Raya

Kidney disease is the loss of kidney function. This results in salt retention, nitrogen wastewater, and a decrease in urine volume. Kidney disorders are characterized by structural or functional abnormalities of the kidneys that last more than three months. Indicators to see the ability of renal glomerular filtration can be done by checking creatinine clearance. Creatinine clearance is the number of millimeters of plasma cleared of creatinine by the kidneys in one minute. This study aimed to determine the level of creatinine clearance in patients with kidney disease in RSUD dr. Doris Sylvanus City of Palangka Raya. This research was conducted by quantitative descriptive method, with the number of research samples as many as 15 outpatient kidney disease patients who had not performed hemodialysis at the Clinical Pathology Laboratory of RSUD dr. Doris Sylvanus Palangka Raya, with a sampling technique in the form of Accidental Sampling. The examination method used is the measurement of creatinine clearance as a marker of the glomerular filtration rate (GFR) using the Cockroft-Gault formula. The results showed that based on the value of normal creatinine clearance, as much as 7%, and the decreased value of creatinine clearance, as much as 93%.

Abstract 13242: One Day Intravenous Sotalol Loading for Treatment of Atrial Arrhythmia

Introduction: Sotalol is commonly used for the management of atrial arrhythmias Recently, sotalol was approved for intravenous administration. The intravenous loading protocol is based on a computer simulation of plasma concentration rather than clinical data Availability of IV sotalol offers an opportunity to shorten the loading time. We developed a One Day Sotalol Loading Protocol (ODSL) utilizing the IV sotalol formulation. Hypothesis: ODSL feasible & safe. It also results in significant health care cost reduction. Methods: Patients undergoing ODSL loading between June 2020 to Dec 2020 for management of AF were included in the analysis. The primary endpoint was successful initiation of sotalol therapy. The secondary endpoint was maintenance of sinus rhythm at 30 days. Safety endpoints included excessive prolongation of the QT C interval, ventricular arrhythmias and sinus bradycardia requiring dose adjustment. Patient co-morbidities and demographics were also evaluated. Cost savings analysis was performed to quantify health care savings Results: 55 patients were included in the analysis (30 paroxysmal AF and 25 persistent AF). The mean age was 70± 9.82 years old and 60.7% were men. The average ejection fraction was 52.91 ± 9.25% and average creatinine clearance was 83.58 ± 44.35mL/min. 51 patients (92.7%) underwent successful ODSL. Of these, 6 patients had dose reduction due to adverse events (fig 1). 7 (12.7%) patients had significant QT C prolongation during IV loading. ODSL was terminated in 4 patients: symptomatic bradycardia and prolonged QT C (1 pt) and failure of cardioversion (3 pts).42 (76%) of patients remained on sotalol and 32 (58%) maintained sinus rhythm at 30 day follow up. No ventricular arrhythmia was noted during the loading and monitoring period. Same day discharge led to an 18% reduction in health care costs. Conclusions: We present first real-world data demonstrating that abbreviated ODSL is feasible, safe, and leads to significant health care savings while freeing up resources and personnel. Further patient enrollment and data analysis is ongoing to further solidify this novel loading approach.

O004. Assessment of the impact of lupus nephritis on clinical, biological parameters, disease activity and mortality in pediatric Systemic Lupus Erythematosus

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Kidney involvement is one of the most frequent and severe manifestations of pediatric systemic lupus erythematosus (pSLE), seriously affecting the prognosis. It usually manifests as glomerulonephritis of varying severity. Objective: Knowledge of the correlation of lupus nephritis (LN) with clinical, biological, immunological parameters, disease activity and mortality in pediatric systemic lupus erythematosus is limited. This study aims to describe the impact of renal involvement with these different determinants. Methods This was a prospective, multicenter, descriptive 36-month study (January 2015 - December 2018) including patients less than 16 years of age with LN. The presence of LN was defined according to the American College of Rheumatology classification SLE criteria. The LN class was determined by renal biopsy and was classified according to the Morphology in Kidney International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2004 classification of lupus nephritis. The disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children. Means, percentages and Chi-square tests were specified. P values less than 0.05 were considered statistically significant. Results We included 83 patients in this study. 37/83 patients (44.6%) developed LN with the following urinary signs: 92% of proteinuria (mean 3366.147 mg ± 2785.93 / 24h) including 2/3 of cases of nephrotic syndrome, 81% of hematuria, 14% of acute renal failure with significant reduction in glomerular filtration rate (average creatinine clearance of 32.42 ml / min) and 12% high blood pressure. Out of a total of 30 renal biopsies interpreted at disease diagnosis, 73.4% diffuse proliferative glomerulonephritis forms were observed: (III (30%), IV (36.7%) and VI (6, 7%)). Lupus nephritis were significantly correlated with hypocomplementemia in its C3 (P = 0.00002) and C4 (P = 0.00005) fraction, lymphopenia (P = 0.02), anti-DNA antibodies (P = 0.026), SLEDAI (P = 0.00001) and mortality (P = 0.03). The most frequently used induction drugs for LN classes III, IV and VI were pulsed intravenous methylprednisolone (500 mg daily for 3 doses) in combination with low dose intravenous cyclophosphamide (23%) in the short term (500 mg/m2/15 days X 6) followed by mycophenolate mofetil (28%) (600mg/ m2 in two daily doses) as maintenance treatment associated with a daily dose of oral glucocorticoids with a gradual decrease until reaching the minimum amount necessary to control the disease. All of our SLE patients with nephritis were treated with HCQ with a significant correlation with the decrease in SLEDAI. During the first two years of disease progression, the frequency of LN increased to 43/83 (51.8%) mainly in these severe forms: (IV (41.7%), V (2.8 %). The progression to chronic renal failure had a prevalence of 6, 9% (3/43) of cases; these were mainly patients with severe lupus nephritis (III, and IV) Conclusion Nephritis is a major risk factor for morbidity and mortality in pSLE; LN in children is most often proliferating and more active. The early diagnosis and management of kidney damage are the only guarantee of a good course and prevention of the progression of chronic renal failure. Keywords lupus nephritis; child; systemic lupus erythematosus; disease activity, mortality.

A Randomized Phase III Study of Venetoclax-Based Time-Limited Combination Treatments (RVe, GVe, GIVe) Vs Standard Chemoimmunotherapy (CIT: FCR/BR) in Frontline Chronic Lymphocytic Leukemia (CLL) of Fit Patients: First Co-Primary Endpoint Analysis of the International Intergroup GAIA (CLL13) Trial

A Randomized Phase III Study of Venetoclax-Based Time-Limited Combination Treatments (RVe, GVe, GIVe) Vs Standard Chemoimmunotherapy (CIT: FCR/BR) in Frontline Chronic Lymphocytic Leukemia (CLL) of Fit Patients: First Co-Primary Endpoint Analysis of the International Intergroup GAIA (CLL13) Trial

Adolescents and adults with Fontan circulation: insights from the PREpArE-Fontan registry.

The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with "stable" Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial's eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in "stable" patients.

Trajectory of Change in Erectile Dysfunction Symptoms Following Coronary Artery Bypass Surgery in Malaysian Population

INTRODUCTION: Despite the advantages of Coronary artery bypass surgery (CABG), this procedure has been reported to have a significant impact on sexual activity. The study aims to assess the trajectory of change in erectile dysfunction (ED) symptoms following CABG.METHODS: 73 adult male participants were recruited. Participant primary data was measured using the International Index of Erectile Dysfunction (IIEF-5) at three-time points. RESULTS: Severe ED was most prevalent during 6 weeks following-operation (86.3%); however, the proportion of severe ED symptoms reduced after 4 months following-operatively (42.5%). There was a statistically significant difference in ED symptoms between pre-operatively and 6 weeks post- operatively (p&lt; 0.001). At 4 months, there was a marginally significant improvement in ED symptoms compared to baseline pre-operatively post CABG (p = 0.064). Age significantly increases the chance in odds of having abnormal ED symptoms by 22% at 4 months postoperatively (aOR=1.22, 95% CI=1.06, 1.41, p&lt;0.05). Other risk factors for abnormal ED symptoms following CABG, which include normal creatinine clearance, being a smoker, and having moderate to good LV function was not statistically significant. CONCLUSION: The present study has demonstrated a high prevalence of ED following CABG and the procedure caused a negative impact on the ED symptoms. However, there was a significant improvement in ED symptoms as the time from surgery increases and patients recovered. Further studies with larger sample size and longer recovery time are needed to assess the trajectory of recovery in ED symptoms in this population.&gt;&lt; 0.05). Other risk factors for abnormal ED symptoms following CABG, which include normal creatinine clearance, being a smoker, and having moderate to good LV function was not statistically significant. CONCLUSION: The present study has demonstrated a high prevalence of ED following CABG and the procedure caused a negative impact on the ED symptoms.

Blood pressure difference between regular hemodialysis and hemodialysis with hemoperfusion at Haji Adam Malik Hospital, Medan-Indonesia

Background: The differences of Hemodialysis and Hemoperfusion’s combination can increase of Uremic Toxin clearance, average creatinine clearance, and Angiotensin elimination optimally. The hemodialysis and hemoperfusion’s combination also can decrease blood pressure and reduce the use of Anti Hypertension drugs so that the number of cardiac events in CKD patients may decrease. The use of ABPM is chosen because this is the best method of automatic blood pressure which has the most accurate blood pressure measuring periodically.Objective: This study aims to determine the difference of regular Hemodialysis and Hemodialysis with Hemoperfusion on blood pressure measured by using ABPM in Medan, North of Sumatra.Methods: This study was a pre-experimental study which conducted since December 2013-March 2014 to the 20 regular hemodialysis patients. The measurement included anamnesis, height, weight, systolic and diastolic blood pressure among patients with regular hemodialysis and hemodialysis with hemoperfusion. Results: The study found that about 3 of 20 subjects were out of the study. There was no significant difference found in systolic and diastolic blood pressure between regular hemodialysis and hemoperfusion group (P = 0.807 and 0.906, respectively) based on the T-paired test and Wilcoxon test. Conclusion: There was no significant difference between blood pressure measured using ABPM on the combination of hemodialysis and hemoperfusion compared with regular hemodialysis

Contrast Induced Nephropathy- A Single Centre Observational Study

Background: CIN is an important cause of morbidity and mortality post cardiac procedures. Renal derangement and diabetes being the most important risk factors. Multifactorial causation of the disorder led us to study the risk factors associated with CIN.&#x0D; Methods: All patients who underwent cardiac procedures between March 2019 and March 2020 were screened for CIN and included in the study. Out of the 3192 patients screened 99 patients were diagnosed with CIN. Parameters such as diabetes mellitus, hypertension, CKD, anemia, duration of hospital stay, cardiogenic shock, number of stents, amount and type of contrast, Ejection Fraction, creatinine clearance before and after the procedure, concomitant nephrotoxic drugs were also recorded. &#x0D; Results: Ninety-nine patients developed CIN amounting to 3% of the total procedures, 11% expired, 18% required dialysis, average creatinine clearance before the procedure was 53.15 ml/min/1.73 m2 and post procedure it was 29.16 ml/min/1.73 m2, 51.5% of cases had creatinine clearance prior to procedure &lt;60 ml/min/1.73 m2, 60.6% were diabetic, 81.8% were hypertensive, 30.3% were anaemic, 15% had heart failure, 33% required ventilatory assistance, average haemoglobin level was 11.83 mg/dl, 33% received iso-osmolar contrast and 45% had EF of 35% or less.&#x0D; Conclusions: CIN has a multifactorial causation most common being prior renal derangement and diabetes mellitus. This is one of a kind study in this part of country among cardiac patients. Newer biomarkers of kidney injury could also be studied in future.

Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight.

Febuxostat is a xanthine oxidase inhibitor indicated for gout and hyperuricemia. This work investigates potential clinically relevant covariates for febuxostat pharmacokinetics with a special focus on Asian race and bodyweight. Febuxostat plasma concentrations from 141 male subjects were obtained from two phase II studies in patients with hyperuricemia/gout (NCT02246673, NCT02317861) and one study in healthy volunteers (NCT01883167). Subjects were administered febuxostat oral doses from 10 to 80mg. The pharmacokinetics of febuxostat was analyzed using non-linear mixed-effects modeling as implemented in NONMEM 7.3.0. The dataset consisted of racially diverse subjects, 40% being Japanese, 10% of unknown Asian origin, 39% Caucasian, and 10% Black. Most subjects (n = 92, 63%) had normal creatinine clearance (90mL/min), while 52 subjects (36%) had mild renal impairment (creatinine clearance > 60 to < 90) at baseline. The effect of disease state, body weight, and creatinine clearance on febuxostat pharmacokinetics was investigated using stepwise covariate modeling. Febuxostat pharmacokinetics was well described by a two-compartment disposition model. Asian race was the only covariate resulting in a potentially clinically important increase in febuxostat area under the curve (1.64-fold, 90% confidence interval 1.48-1.79) compared with Caucasian individuals. The difference in body weight between Asian and Caucasian subjects did not explain the difference in febuxostat exposure. Absorption was modeled as a sequential zero- to first-order process with lag-time. In this pooled analysis of three studies, we show that Asian individuals have a 1.64-fold higher febuxostat exposure than Caucasians, independent of bodyweight or other investigated covariates.These findings may be of importance when selecting starting febuxostat doses in Asian patients.

AB0932 FACTORS IN ACHIEVING TARGET SERUM URIC ACID LEVELS IN OUTPATIENT GOUT MANAGEMENT IN A MALAYSIAN TERTIARY RHEUMATOLOGY CENTRE

Background:Gout is one of the most common inflammatory arthropathies. A target serum uric acid of less than 300µmol/l is recommended when tophi are present, and less than 360µmol/l for non-tophaceous gout. Urate-lowering therapy (ULT) should be titrated until the target is achieved and long-term maintenance of the target concentration is recommended. Although ULT has been proven to reduce the uric acid level, less than half of treated patients achieved the target serum uric acid (sUA) in real-world clinical practice.Objectives:To assess the mean treat-to-target achievement in outpatient management of gout by the tertiary rheumatology centre and to identify factors influencing the success rate.Methods:Retrospective cross-sectional study of all patients with gout attending out-patient clinics in a rheumatology referral centre from 1stJanuary 2018 until 31stDecember 2018. Electronic medical records were reviewed. The successful target achievement is defined as mean of all available sUA in 2018 which is ≤360 and ≤300µmol/l for non-tophaceous and tophaceous gout respectively. Chronic kidney disease (CKD) is defined as glomerular filtration rate of less than 60ml/min.Results:There were 251 patients analysed with mean age of 56.3±13.8 years and disease duration of 10.5±9.2 years. Majority were males (215, 85.7%) and 133 (53%) patients had tophaceous gout. The rate of success achieving the target SUA level of ≤360 and ≤300µmol/l were 33.9% (40) and 15.8% (21) in non-tophaceous and tophaceous gout respectively. However, in patients who are compliant, the target sUA achieved is 52.4% (33) and 31.7% (19) in non-tophaceous and tophaceous gout respectively. Characteristics of patients who achieved the targeted sUA were patients of more than 50 years old (48, 78.7%), without family history of gout (29, 65.9%), were prescribed colchicine prophylaxis upon initiating ULT (46, 76.7%), with absence of joint erosions (34, 73.9%) and those with normal creatinine clearance (40, 65.5%). There were 120 (48.4%) patients who were compliant to ULT. In 42 compliant patients who achieved target sUA, the mean allopurinol dose is 289.66mg±101.2 and 369.23mg±175 in non-tophaceous and tophaceous gout respectively. Sub-analysis in 31 compliant CKD patients, revealed no difference in allopurinol dose between those who achieved versus non-achieved target sUA (mean 243mg versus 263mg respectively). However, we noted that 11 (61%) CKD patients with tophi did not achieved target sUA at dose less than 300mg allopurinol. Lower achievement of target sUA was significantly associated with presence of tophi (p=0.001), poor compliance (p= 0.000) and presence of more than one comorbidity (p=0.041).Conclusion:There are several challenges in achieving target uric acid level contributed by both patient and clinician factors such as compliance, presence of comorbidity and ULT dose. Our study suggests that higher dosage of allopurinol is required in patients with tophaceous gout, with or without renal impairment. However, the limitation of this study is, the small number of subjects which therefore needsfurtherinvestigation.

Efficacy and outcome of intermittent peritoneal dialysis in patients with acute kidney injury: A single-center experience.

There are only a few reports on the role of peritoneal dialysis (PD) in critically ill patients requiring continuous renal replacement therapies (RRT). This study aimed to determine the efficacy and outcome of intermittent PD in acute kidney injury (AKI) patients in intensive care unit setting and to assess the procedure-related complications. This was a prospective, observational study conducted from March 1, 2015, to February 29, 2016, which included patients of either sex, aged ≥18 years, diagnosed with AKI, and undergoing RRT with intermittent PD sessions with more than 48 h of hospital stay. Patients were later shifted to sustained low- efficiency dialysis or hemodialysis, when they became hemodynamically stable. Hence, the patients who received at least 48 h of PD were included in the study. A total of 75 patients were enrolled. Overall, the mean age was 55.75 years, and around 64% were men. The most common indication to start PD was metabolic acidosis, and the most common cause of AKI was sepsis. A total of 21 patients survived, and the mortality rate was 72%. The average peritoneal urea clearance and creatinine clearance were 14.81 mL/min and 12.59 mL/min, respectively. Of the 66 patients on inotropes, 28 patients were tapered from inotropic support. Thirty-nine patients had hyperkalemia, and 27 patients had correction within 1 day of the start of PD. Forty-seven patients had correction of acidosis, and 33 of these achieved pH ≥7.25 within one day of PD. The most common complication that occurred was peri-catheter leaks followed by peritonitis. Acute PD can be an effective, simple, and safe bridge RRT in hemodynamically unstable patients until the achievement of hemodynamic stability to shift them to other modalities of RRT.

Evaluation of a modified vancomycin nomogram for obese adults.

The purpose of this study was to compare therapeutic vancomycin trough levels in obese adults when using an original nomogram (phase I) versus a modified nomogram (phase II). This study compared a vancomycin nomogram with a modified vancomycin nomogram for obese adults over 100kg. The primary endpoint compared the percentage of sub-therapeutic, therapeutic, and supra-therapeutic vancomycin trough concentrations between the nomograms. Patients were included if they were at least 18years of age, had a total body weight of 100-299kg, and had an initial vancomycin trough level collected. Patients were excluded if they had end-stage renal disease or were on continuous renal replacement therapy. Therapeutic trough levels occurred in 85 out of 171 patients (50%) in phase I and 98 out of 149 patients (66%) in phase II. The incidence of both sub-therapeutic and supra-therapeutic troughs was less in phase II (p = 0.013). In the subgroup of adults aged 18 to 49 with a normalized creatinine clearance of greater than 90mL/min, there was a trend in more therapeutic levels with the modified nomogram and less chance of sub-therapeutic levels (p = 0.088). In the subgroup of adults with a normalized creatinine clearance of 60-90mL/min, there was significant improvement in therapeutic levels and a decrease in supra-therapeutic levels without increasing the percent of sub-therapeutic levels (p = 0.001). The modified vancomycin nomogram at Cone Health showed significant improvement in therapeutic trough concentrations while reducing the rates of under and over dosing obese adults. The Cone Health-modified vancomycin nomogram could be a useful tool for initial dosing of vancomycin in the obese population.