Daily Dialysis Research Articles

Open-label, controlled, phase 2 clinical trial assessing the safety, efficacy, and pharmacokinetics of INM004 in pediatric patients with Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome.

Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a severe condition mainly affecting children. It is one of the leading causes of acute kidney injury in the pediatric population. There is no established therapy for this disease. INM004 is an anti-Shiga toxin composed of equine polyclonal antibodies. This study is aimed at assessing the safety, pharmacokinetics, and efficacy of INM004 in pediatric patients with STEC-HUS. Phase 2, open-label clinical trial with an historical control arm. Patients in the treatment arm received two doses of INM004. The primary endpoints were the safety profile, pharmacokinetics, and efficacy (dialysis days) of INM004. Secondary endpoints included other kidney and extrarenal outcomes. Propensity score matching was used for efficacy comparisons between arms. Fifty-seven and 125 patients were enrolled in the treatment and control arm, respectively. After propensity score matching, 52 patients remained in each arm. INM004 was well-tolerated. Eight adverse events were considered possibly related, none of which were serious or severe. In the primary efficacy endpoint, patients of the treatment arm presented a non-statistically significant difference of two dialysis days. On secondary endpoints, non-statistically significant trends toward fewer patients needing dialysis and dialysis for more than 10days, and shorter time to glomerular filtration rate normalization, were observed favoring the treatment arm. INM004 showed an adequate safety profile. Efficacy non-statistically significant trends suggesting a beneficial effect in the amelioration of kidney injury were observed. These results encourage the conduction of a phase 3 study of INM004 in pediatric patients with STEC-HUS.

Effect of Age, Sex, Renal Impairment and Hepatic Impairment on the Safety, Pharmacokinetics and Pharmacodynamics of Asundexian.

Asundexian is a reversible and selective inhibitor of activated factor XI. It is currently under investigation for the prevention of secondary stroke in at-risk patients; these patients are often characterised by advanced age, impaired organ function and comorbidities. This article summarises results from three Phase I studies that investigated the effects of age and sex (study 1), chronic kidney disease including end-stage kidney disease (ESKD) on dialysis and dialysis-free days (study 2) and Child-Pugh A and B liver disease (study 3) on the safety, pharmacokinetics and pharmacodynamics of a single oral dose of asundexian 25mg. Study 1 was a multicentre, randomised, single-blind, placebo-controlled group-stratification design; study 2 was a single-centre, non-randomised, non-placebo-controlled, non-blinded group-stratification design; and study 3 had a non-randomised, non-blinded, non-placebo-controlled group-stratification design. Single doses of asundexian 25 mg were generally well tolerated in all three studies, with no asundexian-related bleeding events or treatment-emergent adverse events of special interest. Point estimates (geometric least squares [LS] means) (90% confidence intervals [CIs]) for the total asundexian area under the plasma concentration-time curve (AUC) for participants aged ≥65 to< 75 years versus ≥18 to <45 yearsand ≥75 to ≤80 years versus ≥18 to <45years were 1.257 (1.134-1.393) and 1.288 (1.158-1.433), respectively, and for females versus males, it was 1.084 (0.995-1.182). Point estimates (geometric LS means) (90% CIs) for unbound AUC in participants in estimated glomerular filtration rate (eGFR) categories G2 (60-89 mL/min/1.73 m2), G3 (30-59 mL/min/1.73 m2) and G4 (15-29 mL/min/1.73 m2) versus control were 1.003 (0.698-1.443), 0.791 (0.550-1.138) and 0.882 (0.606-1.285), respectively, and in participants with ESKD on dialysis-free day versus control was 0.597 (0.406-0.877). There was no effect of the dialysis procedure on the pharmacokinetics of asundexian. In participants deemed Child-Pugh class A and Child-Pugh class B, geometric LS means (90% CIs) for unbound AUC were 0.834 (0.597-1.164) and 1.143 (0.810-1.612), respectively, when compared to participants with normal liver function. Activated partial thromboplastin time (aPTT) was assessed as a pharmacodynamic variable of interest. Geometric mean maximum aPTT prolongation as a ratio to baseline after administration of asundexian 25 mg ranged from 1.45 to 1.55 in all age and sex groups, 1.49-1.59 in the control and eGFR G2 to G4 groups, 1.38-1.54 in the control and ESKD groups on dialysis and dialysis-free day and 1.38-1.89 in the healthy control and liver impairment groups. The effects of the investigated intrinsic factors on the exposure of asundexian were small and not considered clinically relevant. The impact of lower exposure in participants with ESKD requires further investigation. Pharmacodynamics were as expected. EudraCT 2022-000196-38 and 2020-000626-25.

Efficacy of continuous glucose monitoring in people living with diabetes and end stage kidney disease on dialysis: a systematic review

BackgroundPatients with diabetes on dialysis experience wide variations in glucose levels and an increased risk of hypoglycaemia. Due to the inaccuracies of HbA1c in dialysis patients, JBDS-IP and KDIGO recommend the use of continuous glucose monitoring (CGM). We conducted a systematic review to examine the current evidence for CGM use and its impact on clinical outcomes in patients with diabetes on dialysis.MethodsA search of MEDLINE(R) ALL, Ovid Emcare, Journals@Ovid Full Text and Embase databases were conducted. Clinical or observational trials in adults with Type 1(T1D) or Type 2 (T2D) diabetes on dialysis and CGM intervention reporting on glycaemic outcomes were included.ResultsOf the 936 citations identified, 49 duplicates were removed. 887 citations were screened by title and abstract. 9 full texts were reviewed and a further 7 excluded due to duplications or failure to meet to selection criteria. Data was extracted for 2 studies, both prospective before-and-after interventional studies with no control group. Joubert et al. (2015) showed results for 15 participants with T1D. Mean CGM glucose level decreased from 8.37mmol/L at baseline to 7.7mmol/L at the end of the CGM period (p < 0.05) while HbA1c decreased from 6.9 to 6.5% (p < 0.05) during the same period. Mean CGM was lower on dialysis days (7.68mmol/L vs. 7.8mmol/L, p < 0.05). Képénékian et al. (2014) reported on data from 29 T2D patients. Following a 3 month CGM-adapted insulin regimen, HbA1c decreased from 8.4% at baseline to 7.6% (p < 0.01) by the end of study. Mean CGM values decreased from 9.9mmol/L to 8.9mmol/L (p = 0.05) and the frequency of glucose values > 10mmol/L decreased from 41 to 30% (p < 0.05), without a significant increase in hypoglycaemia frequency. Both studies were deemed to be of ‘good’ quality.ConclusionEvidence demonstrating the benefits of CGM in patients with diabetes receiving dialysis is lacking. There is a need for well-designed randomised controlled trials to ascertain the benefits of this technology in this patient group.Trail registrationPROSPERO registration number: CRD42023371635, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=371635.

8621 A Challenging Case of Preoperative Management of Pheochromocytoma Presenting With Recurrent Hypotension

Abstract Disclosure: N. Shripad: None. R. Osman: None. Introduction: Pheochromocytoma is a neuroendocrine tumor that clinically manifests due to the hypersecretion of catecholamines. Preoperative management typically involves alpha- and beta-adrenergic blockade. Patients commonly present with hypertension; however, in rare cases, patients may be hypotensive due to other comorbidities, posing a challenge to preoperative management. The following is a case of management of a pheochromocytoma with recurrent preoperative hypotension before the initiation of blood pressure-lowering agents. Case: A 47-year-old female presented to the hospital with dizziness and hypotension. The patient has a history of bilateral nephrectomy with left-sided adrenalectomy secondary to left-sided renal cell cancer and is hemodialysis-dependent. A right-sided pheochromocytoma was diagnosed a year ago on a follow-up CT scan done for monitoring renal cell cancer. The diagnosis was later confirmed with a DODATE scan and, eventually, a biopsy. Normetanephrine levels were between 581-735 pg/mL (0-88 pg/mL), with normal metanephrine levels. She denies having hyperadrenergic spells. She was started on metoprolol and doxazosin the year prior to presentation; however, she self-discontinued doxazosin after experiencing dizziness and palpitations on hemodialysis days. On admission, she was afebrile with a blood pressure of 103/66 mm Hg and a heart rate of 115 BPM. After an interdisciplinary decision was made for surgical resection, she was restarted on a lower dose of doxazosin (1 mg) and metoprolol was increased to the goal heart rate. Despite fewer hypotensive episodes on a reduced dose of doxazosin, the patient remained hypotensive on hemodialysis days. Salt tablets were started post-dialysis after clearance from nephrology, and an improvement in blood pressure was noted. She underwent a right adrenalectomy without receiving saline infusion before surgery due to concerns about volume overload. She was started on stress dose steroids due to her history of left adrenalectomy. She remained stable during and following surgery and did not require any vasopressor support. Discussion: Perioperative management of pheochromocytoma can be challenging in hypotensive patients and is poorly documented. Midodrine, an alpha-1 agonist that is typically used in dialysis-induced hypotension, is contraindicated in the setting of pheochromocytoma. We opted to manage our patient with a reduced dose of doxazosin and beta-blocker initially; however, with continued hypotensive episodes, the addition of salt tablets preoperatively on dialysis days helped to alleviate the hypotension. Although our patient did not require it, a preoperative overnight albumin infusion is a viable alternative to saline to prevent volume overload. Despite the limited literature, the patient was treated successfully through an interdisciplinary approach. Presentation: 6/3/2024

An investigation into the correlation between intraperitoneal teicoplanin concentrations and treatment outcomes in peritoneal dialysis-associated peritonitis.

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43mg/L of the cured group and the 12.07 ± 2.68mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138mg/L) on day 5 after dosing.

Post-dialysis fatigue predicts all-cause mortality in patients on chronic hemodialysis.

Fatigue is reportedly associated with a poor prognosis in dialysis patients. The aim of the present study was to investigate whether fatigue on dialysis days or non-dialysis days is associated with mortality in patients on chronic hemodialysis. This was a prospective study of 134 hemodialysis patients. The level of fatigue was evaluated using a visual analog scale (VAS). The association between high fatigue evaluated by the highest quartile of the VAS value and all-cause death was investigated. The fatigue scale score was significantly higher on dialysis than on non-dialysis days. During the follow-up period (median 6.8 years), 42 patients died. Patients with high post-dialysis fatigue in the higher quartiles died more frequently compared to those with in the lower quartiles (p = 0.012). Multivariate Cox regression analysis showed that high post-dialysis fatigue was an independent predictor of all-cause death (adjusted hazard ratio 2.12, 95% confidence interval 1.10-4.07). Higher post-dialysis fatigue is related to increased mortality.

Assessment of Nutritional Intake in Patients With Kidney Failure Treated by Haemodialysis on Dialysis and Non-dialysis Days

Introduction/Aims/ObjectiveInadequate nutritional intake in haemodialysis (HD) patients increases the risk of muscle wasting, nutrient deficiencies, leading to an increased risk of additional morbidity and mortality. We aimed to assess nutritional intake on the dialysis and non-dialysis day of patients established on HD. MethodsWe employed a two-day dietary record, one on the day of dialysis and one on the non-dialysis day, and then determined nutritional intake using the Nutritics software. Muscle strength was assessed by hand grip strength (HGS) and body composition determined using multifrequency bioelectrical impedance recorded post-dialysis. ResultsWe recruited 51 established HD patients dialysing between May-July 2022, mean age 60±15 years, 52.9% male, and 51% diabetic. Only 25% achieved the calorie and protein intake recommended by Kidney Disease Outcomes Quality Initiative (KDOQI). Most patients had inadequate consumtion of fibre (96%), calcium (86%), iron (80%), zinc (82%), selenium (92%), folate (82%), vitamin A (88%), and (100%) vitamin D. On the other hand, the great majority followed the restriction guidelines for potassium (96%), phosphorus (86%), and sodium (84%), repectively. However, consumption was greater for potassium (P=0.007), phosphorus (P=0.015), and zinc (P=0.032) on non-dialysis vs dialysis days, but there was no difference in protein or calorie intake between days. ConclusionOur results suggest that many of our HD patients do not achieve the recommended nutritional targets. Patient compliance with restricting sodium, potassium and phosphate limits protein and calorie intake. HD patients are at increased risk of sarcopenia, so failure to achieve dietary protein intake will further increase this risk.

Pharmacokinetics of Sofosbuvir/Velpatasvir and efficacy of an alternate-day treatment in hemodialysis patients with chronic hepatitis C infection.

Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5-20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS-331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on- and off-dialysis studies. On the contrary, GS-331007 exhibited a 30% reduction in the area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24h) on dialysis days compared with non-dialysis days (AUC0-24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS-331007 was 9.35 (8.72-15.11) and 8.89 (8.52-14.07) mL/min, respectively. Subsequently, an alternate-day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen.

Predictive factors for acute kidney injury and amputation in crush injuries from the Kahramanmaraş earthquakes.

Crush syndrome (CS) is characterized by high morbidity and mortality due to severe electrolyte disorders, circulatory dysfunction, and multiple organ failure, secondary to severe rhabdomyolysis and reperfusion injuries. Acute kidney injury (AKI) related to crush syndrome is one of the life-threatening complications and is the most frequent cause of death following earthquakes, other than trauma. We conducted a retrospective study to identify predictive parameters from clinical and laboratory data that aid in recognizing CS, assessing its severity, and evaluating acute kidney injury and amputation indications in patients. We retrospectively evaluated the clinical data and laboratory follow-up of 33 patients treated for crush syndrome within the first two weeks following the February 6, 2023 earthquake. Patients who underwent surgery for crush syndrome but could not be followed post-surgery were excluded. Laboratory parameters were analyzed upon admission and then daily over an average seven-day follow-up. A p-value of <0.05 was considered statistically significant. Data analysis was performed using IBM SPSS Statistics 26.0 and R Studio software. Of the 33 patients, 17 were male and 16 were female. The incidence of AKI was 35.7%, 66.7%, and 100% in patients with injuries to one, two, and three extremities, respectively. A significant correlation was observed between total entrapment time and the duration of required dialysis days; AKI risk significantly increased with more than six hours of total entrapment time. Regarding the initial blood values upon hospital admission, a myoglobin level exceeding 2330 mg/dL demonstrated the highest sensitivity for predicting AKI. An initial uric acid level (>6.36 mg/dL) on admission had the highest specificity for predicting AKI. The initial myoglobin level (>3450 mg/dL) showed the highest sensitivity in predicting the need for amputation. Meanwhile, the mean creatine kinase (CK) level (>34800 U/L) exhibited the highest specificity but the lowest sensitivity for amputation prediction. The study analyzed the effectiveness and predictability of clinical and laboratory findings concerning amputation and acute kidney injury in crush syndrome resulting from earthquakes. Effective amputation management is a crucial factor influencing prognosis and survival in patients with earthquake-induced crush syndrome.

Depression, Anxiety, and Stress in Patients Undergoing Hemodialysis: Assessment of Contributing Factors

Abstract: Background: The frequency of Chronic Kidney Disease (CKD) assessed worldwide is 13.4% (11.7-15.1%), and cases with ESKD demanding renal replacement therapy are calculated to be between 4.902 and 7.083 million. Several factors prompt anxiety and depression in hemodialysis cases. These include co-morbidities, frequent hospitalizations, habitual pain, sleep disturbances, chronic inflammation, increased fatigue, uremia, failure of family support, non-compliance to adjunctive therapeutics such as restrictions in diet and fluids, and dependence upon treatment and health professionals. Objective: To assess the frequency and contributing factors for incidents of depression, stress, and anxiety in hemodialysis patients. Materials and Methods: This is an observational, cross-sectional study conducted at the Karachi Institute of Kidney Diseases from February 2023 to March 2023, the obtained minimum sample size was 194. Data was collected with the help of DASS 10 questionnaire. The data was entered and analyzed by using Statistical Package of Social Sciences (SPSS) Version 22. Data significance was analyzed using Chi-Square test keeping P- value ≤0.05 as significant. Result: A total of 194 participants were recruited in the study, gender distribution recorded male dominance at 103 (53%) and females at 91 (46%). 139 (71.6%), the mean value of the length of dialysis was 15.4 ± 4.9 years while the mean days of dialysis were 2.7 ± 1.3. Moderate depression was reported in 101 (52%) of the study participants, while severe depression was reported in 25 (12.8%). Anxiety was reported as mild most frequently with 133 (68.5%) while stress was reported as mild in 48 (24.7%), moderate in 83 (42.7%), and severe in 63 (32.4%) with a p-value of 0.214. We identified a positive association of severe depression, anxiety, and stress with age ≤ 45 years in general, while participants from the upper middle class reported stress more frequently. Conclusion: This study concluded that compromised socio-economic status, young age, and higher prognosis rates are contributing factors for depression, anxiety, and stress in hemodialysis patients. Keywords: DASS, Depression, Hemodialysis, ESKD, Stress, Anxiety.

#1928 Stepwise incremental hemodialysis and low-protein diet supplemented with keto-analogues to preserve residual kidney function: a pilot study

Abstract Background and Aims Studies have demonstrated that chronic dialysis with residual kidney function (RKF) had better survival rates in comparison to those with diminished or absent RKF and are also further associated with improved cardiovascular outcomes. Thus, the strategic preservation of RKF following the initiation of hemodialysis or during transitional periods emerges as a crucial consideration. Compelling evidence suggests that more frequent hemodialysis may contribute to an accelerated decline in RKF, contrasting with the beneficial effects of a low-protein diet (LPD) supplemented with keto-analogues, which has been shown to delay the progression of kidney function decline in the chronic kidney disease (CKD) non-dialysis population. Our pilot study aims to investigate the impact of a stepwise incremental hemodialysis with LPD supplemented with keto-analogues approach on the preservation of RKF after the need to initiate dialysis. Method This open-label, randomized controlled trial (RCT) pilot study employed a 1:1 allocation ratio (Groups 1 and 2) and included 30 patients in CKD stage V non-dialysis, aged ≥18 years, with an eGFR of 5-10 ml/min/1.73 m² as per the CKD-EPI equation, and a urine output of ≥800 ml/day. Exclusion criteria comprised patients with active infection or inflammation, indicated by C-reactive protein (CRP) levels exceeding 10 mg/L, individuals with cancer, or those with a body mass index (BMI) ≥35 kg/m². Group 1 underwent once-weekly hemodialysis (HD) initiation lasting 4 hours, coupled with a low-protein diet (LPD) of 0.6 g/kg/day supplemented with keto-analogues (0.12 g/kg/day) on non-dialysis days and a regular protein diet (1.0 g/kg/day) on dialysis days. In contrast, Group 2 underwent twice-weekly HD initiation (4 hours each) and maintained a regular protein diet (1.0 g/kg/day) every day. A stepwise incremental approach to HD frequency (once to twice per week in Group 1 and twice to thrice per week in Group 2) was implemented if renal kidney function (RKF) fell below 3 ml/min/1.73 m², eqKt/V was ≤1.2/session, Kru was &amp;lt;3 mL/min, ultrafiltration rate exceeded 15 ml/kg/hour, serum potassium was &amp;gt;5.5 mEq/L, and serum phosphate or serum albumin were outside the ranges of &amp;gt;5.5 mg/dL and &amp;lt;3.5 g/dL, respectively. The study spanned a duration of 12 months. Results A total of 30 patients were enrolled in the study and randomized into Group 1 (N = 15) and Group 2 (N = 15). There were no significant differences in baseline characteristics, including age (58.0 ± 19.3 vs 61.9 ± 16.8 years; p = 0.638), BMI (24.0 ± 3.8 vs 23.5 ± 3.6 kg/m²; p = 0.751), eGFR (6.9 ± 1.4 vs 6.2 ± 1.9 mL/min/1.73 m²; p = 0.241), urine volume (2226 ± 729 vs 1690 ± 986 mL/day; p = 0.128), and serum albumin (3.8 ± 0.3 vs 3.6 ± 0.3 g/dL; p = 0.123). In both groups, urine volume decreased over 12 months but Group 1 exhibited significantly higher urine volumes compared to Group 2 at M6 (1697 ± 442 vs 1063 ± 480; p = 0.01), M9 (1453 ± 522 vs 918 ± 404; p = 0.02), and M12 (1119 ± 429 vs 768 ± 367; p = 0.03). Consistent with urine volume, there were significant differences in creatinine clearance (CCr) at M6 (3.9 ± 0.5 in Group 1 vs 2.7 ± 1.8 in Group 2; p = 0.05) and M9 (3.5 ± 0.3 in Group 1 vs 1.9 ± 0.9 in Group 2; p = 0.01). In Group 1, there was a need to increase the rate of dialysis to twice/week in 5 patients at average of 3.6 months after start of study. No significant differences in hospitalization, adverse effects, and patient survival were observed between the two groups. The body weight of all participant were well maintained and no sign of malnutrition. Conclusion Stepwise incremental HD initiated as once-weekly hemodialysis coupled with LPD with keto-analogue supplementation better preserved urine output and CCr compared with twice weekly HD on a regular protein diet. In a period of 12 months after initiation of dialysis, we demonstrated that this stepwise strategy was feasible.

#1419 A single, easy-to-use question to assess pruritus intensity in daily dialysis practice

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) has been shown to negatively impact certain clinical outcomes and quality of life (QoL) in patients with kidney failure. However, regular screening for CKD-aP is not yet routine dialysis practice and no consensus on the preferred instrument exists. To facilitate implementation of regular screening for CKD-aP we assessed the performance of two different instruments validated in patients with CKD-aP. Method The Worst Itching Intensity Numerical Rating Scale (WI-NRS) asks patients to indicate the worst itch intensity in the past 24 hours (range 0 [no itch] to 10 [worst itch imaginable]). The 5-D Itch scale assesses itch-related QoL (range 5-25 where higher values indicate worse QoL) and includes one question on itch intensity over the past 2 weeks (5-D ‘degree’ domain, range 1 [not present] to 5 [unbearable]). Both instruments were included in two phase-3 clinical trials, KALM-1 and KALM-2, that established the favourable benefit-risk profile of difelikefalin over placebo in patients on haemodialysis with moderate to severe CKD-aP. WI-NRS was collected daily during the trial and 5-D Itch at the first dialysis visit in weeks 5, 9, 11 and 13. We assessed the correlations between both the 5-D total score and degree domain and a) the single WI-NRS measurement collected on the same day and b) the average of daily WI-NRS scores collected over the previous 2 weeks in all patients independent of treatment exposure. Results The two instruments demonstrated moderate to strong correlations (range 0.5635-0.7039, p &amp;lt; 0.0001) independent of whether the total 5-D Itch score or the 5-D itch degree question were compared with a single, same-day WI-NRS measurement or with the mean WI-NRS scores over the 2-week recall period of the 5-D Itch (Table). In addition, correlations remained consistent over time, supporting the reliability of the findings. Conclusion Using the WI-NRS to ask patients about their worst itch in the past 24 hours is a simple and swift approach for reliably identifying those with bothersome pruritus that also affects their itch-related QoL.

IDF23-0156 How much should insulin be reduced on dialysis days for Adults with Diabetes receiving Hemodialysis? A Systematic Review

IDF23-0156 How much should insulin be reduced on dialysis days for Adults with Diabetes receiving Hemodialysis? A Systematic Review

Arrhythmia and Time of Day in Maintenance Hemodialysis: Secondary Analysis of the Monitoring in Dialysis Study

Rationale & ObjectiveThe incidence of arrhythmia varies by time of day. How this impacts individuals on maintenance dialysis is uncertain. Our objective was to quantify the relationship of arrhythmia with the time of day and the timing of dialysis. Study DesignSecondary analysis of Monitoring in Dialysis study- a multicenter prospective cohort study. Settings & ParticipantsLoop recorders were implanted for continuous cardiac monitoring in 66 participants on maintenance dialysis with a follow up of 6 months. ExposureTime of day based on 6-hour intervals OutcomesEvent rates of clinically significant arrhythmia Analytical ApproachNegative binomial mixed effects regression models for repeated measures were used to evaluate data from the Monitoring in Dialysis study for differences in diurnal patterns of clinically significant arrhythmia among those with end stage kidney disease with heart failure and end stage kidney disease alone. We additionally analyzed rates according to presence of heart failure, time of dialysis shift, and dialysis vs. non dialysis day. ResultsRates of clinically significant arrhythmia peaked between 0:00 AM-<6:00 AM and were more than 1.5-fold as frequent during this interval compared with the rest of the day. In contrast, variations in atrial fibrillation peaked between 6:00 AM-<12: PM, but variations across the day were qualitatively small. Clinically significant arrhythmia occurred at numerically higher rate in individuals with end stage kidney disease and heart failure (5.9 events/month, 95% CI: 1.3-26.8) than those without heart failure (4.0 events/month, 95% CI: 0.9-17.9). Although differences in overall rate were not significant, their periodicity was significantly different (P<0.001) with a peak between 0:00 AM-6:00 AM with kidney failure alone and between 6:00 AM-<12:00 PM in those with heart failure. Although the overall clinically significant arrhythmia rate was similar with morning compared with evening dialysis shifts (P=0.43), their periodicity differed with a peak between 0:00 AM-<6:00 AM in those with AM dialysis and a later peak between 6:00 AM-<12:00 PM in those with PM shifts LimitationsPost hoc analysis, unable to account for unmeasured confounders ConclusionClinically significant arrhythmias showed strong diurnal patterns with a maximal peak between 0:00-<6:00 AM and noon. Although overall arrhythmia rates were similar the peak rate occurred overnight in individuals without heart failure and during the morning in individuals with heart failure. Further exploration of the influence of circadian rhythm on arrhythmia in the setting of hemodialysis is needed.

Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience

Abstract Sustained low-efficiency dialysis (SLED) is usually performed over 6–12 h among hemodynamically unstable patients. Conduction of 4-h SLED may spare time and manpower during hospitalization. Therefore, we conducted a retrospective observational study to explore the appropriateness and clinical outcomes of 4-h SLED among critically ill patients admitted to our center from 1/06/2016 to 1/06/2020. Renal parameters including blood urea nitrogen, serum creatinine, sodium, phosphorus, potassium, and bicarbonate were determined on the day of dialysis before SLED and within 24 h after SLED, and clinical outcomes including, acute kidney injury (AKI) recovery, in-hospital mortality, 30-day mortality, 180-day mortality, and re-admission with AKI, were evaluated. Of the 304 patients included, 69.4% were male. The majority of patients were from the Middle East (65.8%), followed by 28.6% from Asia. Four-hour SLED resulted in a significant improvement in the renal parameters. Recovery from AKI was observed in 25.4%, in-hospital mortality rate was 48.7%, while the 30- and 180-day mortality outcomes were 3.2 and 9.6%, respectively, and re-admission with AKI was observed in 16.9%. Our findings suggest that 4-h SLED significantly improved renal parameters and was associated with favorable clinical outcomes in terms of survival and AKI recovery, suggesting possible utilization of SLED shorter than 6 h in the acute settings to preserve time and manpower for procedures.

2541. Steady-state PK of Fixed Dose Dolutegravir+Rilpivirine in Hemodialysis

Abstract Background Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state PK of FDC DTG+RPV in those requiring hemodialysis (HD) has not been previously studied. Methods We performed a single-center, prospective evaluation of the steady-state PK of FDC DTG (50mg)+RPV(25mg) in HIV-negative adults either requiring HD (n=4; 2 men, 2 women) or with normal renal function, defined as CrCl ≥ 75mL/min (n=2; 1 man, 1 woman). All participants received DTG+RPV daily for 10-14 days with food before undergoing an intensive 24-hour PK evaluation (performed between dialysis days for those requiring HD). Plasma drug and metabolite concentrations were measured using a validated LC/MS/MS assay method (QTRAP 6500+LC-MS/MS system) with turboelectrospray source operating in both positive (confirmation) and negative (quantification) modes. We did not evaluate dialysis extraction of DTG+RPV. Descriptive PK parameters were calculated. Results No participant experienced serious or grade 3-4 adverse events; there were no study discontinuations. The 4 HD and 2 normal renal function participants were of similar ages (range, 50-60 vs 53-58 years) and BMI (range, 18.5-28.2 vs 20.3-24.0 kg/m2). The Table shows the PK parameters assessed in the study population for circulating plasma DTG, DTG-glucuronide (DTG’s primary metabolite), and RPV. Conclusion In this study, HD did not lead to clinically appreciable differential exposures to DTG and RPV; the markedly increased exposure to DTG-glucoranide (which is considered inert) in HD suggests increased UGT1A1 activation. All participants maintained exposures throughout the dosing interval greater than the reported IC90 efficacy values for DTG (64ng/mL) and RPV (12ng/mL). These data suggest no dosing modifications are needed for the FDC DTG+RPV regimen in HD. Disclosures Samir K. Gupta, MD, Gilead Sciences: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Allon Friedman, MD, Eli Lilly: Advisor/Consultant|Eli Lilly: Stocks/Bonds|GI Dynamics: Advisor/Consultant|Gila Therapeutics: Advisor/Consultant

Kidney sequelae in 281 Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome patients after a median follow-up of 12years.

A substantial proportion of patients with Escherichia coli-hemolytic uremic syndrome (STEC-HUS) evolve to chronic kidney disease (CKD). The objectives of this study were to evaluate long-term kidney outcomes and to identify CKD predictors. In this single-center retrospective study, long-term outcomes of patients were analyzed according to the presence of complete recovery (CR) or CKD at last visit. Then, they were grouped into favorable (CR + CKD1) or poor (CKD2-5) outcome to compare predictors at diagnosis (sex, age, leukocytes, creatinine, hemoglobin, HUS severity score), dialysis duration, and follow-up time between them. Of 281 patients followed up for a median of 12years, 139 (49%) had CR, 104 (37%) CKD1, 27 (10%) CKD2-4, and 11 (4%) CKD5. Thirty-eight patients progressed to CKD2-5 after a median of 4.8years, 7% in the first 5years, increasing to 8%, 10%, and 14% after 5-10years, 10-15years, and > 15years, respectively. They were younger, had higher baseline hemoglobin and leukocytes, and required longer dialysis and follow-up than those with favorable outcome. By multivariate analysis, days of dialysis and follow-up time remained as independent predictors of poor outcome. The best cutoff for days of dialysis was 10days. After 5years, 20% of those dialyzed ≥ 10days evolved to CKD2-5 versus 1% of those non-dialyzed or dialyzed < 10days. Fifty-one percent of patients evolved to CKD after 12years of follow-up and 14% to CKD2-5. Ten days of dialysis was the best cutoff to recognize outcomes. In some cases, kidney damage was evident after 15years of surveillance, highlighting the need for follow-up until adulthood in all STEC-HUS patients.

Duration of Dialysis in Acute Kidney Injury Donors and Transplant Outcomes.

Acute kidney injury (AKI) kidneys, including those from donors on dialysis, are often underutilized, although there is increasing data available demonstrating good transplant outcomes. To date, data on the duration of donor dialysis and transplant outcomes are limited. This was a single-center study of deceased donor kidney transplants from 2010 to 2022. The study cohort consisted of recipients of deceased donor kidney transplants from donors with AKI and on dialysis. Three groups were identified based on the predetermined interquartile range of donor dialysis duration: 1 to 2 dialysis days, 3 to 4 dialysis days, and 5 or more dialysis days. During this period, 765 AKI deceased donor transplants were performed, of which 230 were from donors on dialysis. The median dialysis duration was 2 days with a maximum of 13 days. Across the 3 groups, there were no differences in recipient age (p = 0.23) or dialysis vintage (p = 0.70). Donor age (p = 0.86) and kidney donor profile index (p = 0.57) were comparable between the groups. Recipients of deceased donor kidney transplants from donors on dialysis 5 or more days had lower terminal creatinine levels (p = 0.003) and longer cold ischemia times (p = 0.04). Posttransplant, the median length of hospital stay was 3 days for all groups (p = 0.75). There were no differences in delayed graft function occurrence (94.4% vs 86.8% vs 92.1%, p = 0.19), duration of delayed graft function (p = 0.56), or readmissions (p = 0.99). At 1 year posttransplant, the estimated glomerular filtration rate (p = 0.76), patient survival (p = 0.82), or death-censored graft survival (p = 0.28) were comparable. Excellent outcomes have been observed in AKI deceased donor kidney transplants, including those coming from donors on dialysis. In this small cohort, the duration of donor dialysis did not adversely affect outcomes. Cautious expansion of the donor pool, including donors on dialysis, should be considered given the ongoing organ shortage.

Assessment of Biomedical Waste Generation in Dialysis Units: A Prospective Observational Study-Is it Time for "Green Dialysis"?

Introduction: Chronic kidney disease and as a consequence end-stage kidney disease (EKSD) is increasing globally. More and more people across the world are requiring hemodialysis (HD). The HD procedure produces a large quantity of biomedical waste. In addition, HD consumes a large quantity of water. In this study, we estimated the waste generated from our government-funded HD unit. Materials and methods: It is a prospective study that was carried out in the dialysis unit in the nephrology department over a period of 1 year. The daily dialysis waste generated by the unit was measured using a spring balance. The proportion of plastic and nonplastic waste was determined. The quantity of biomedical waste generated per person in 1 year was calculated. Water input to the dialysis unit was noted. Water consumption per dialysis was calculated. Liquid chemical waste consumed was determined. Electricity consumed by the unit was measured by the electricity meter. The cost of waste disposal was calculated. The cost of electricity consumption and water consumption was also calculated. Results: The approximate weight of waste disposables generated in one dialysis was 0.75 kg. Approximately each person generates 1.29 kg of waste per dialysis. Each dialysis required 125 L of reverse osmosis (RO) water and to generate 125 L of RO water 250 L of raw water was used. This happens as 125 L of water are rejected during the generation of 125 L of RO water. Thus, the net water consumption for each dialysis was 250 L. Chemical waste generated per dialysis includes 90 mL citric acid per dialysis and 130 mL bleach. Each dialysis consumes 3 kWh (three units) of electricity. The cost of electricity for each dialysis was 25.5 INR and the cost of water was 25 INR per dialysis. The cost of waste disposal for each dialysis bed was 6 INR. Discussion: Each dialysis patient produced 1.29 kg of waste per dialysis which was like other studies. Unlike other studies, the waste was not being reprocessed or recycled. Conclusion: Hemodialysis produces substantial biomedical waste. Proper waste disposal techniques and policies to promote reduction, reuse, and recycling will go a long way toward promoting green dialysis and reducing environmental as well as economic burdens. How to cite this article: Sahay M, Sahay RK, Seshadri B, et al. Assessment of Biomedical Waste Generation in Dialysis Units: A Prospective Observational Study-Is it Time for "Green Dialysis"? J Assoc Physicians India 2023;71(10):49-52.

Novel Approach to Intradialytic Progressive Resistance Exercise Training

Physical activity levels are typically undesirably low in chronic kidney disease patients, especially in those undergoing haemodialysis, and particularly on dialysis days. Intradialytic exercise programmes could be a solution to this issue and have been reported to be safe and relatively easily implemented in dialysis clinics. Nevertheless, such implementation has been failing in part due to barriers such as the lack of funding, qualified personnel, equipment, and patient motivation. Intradialytic aerobic exercise has been the most used type of intervention in dialysis clinics. However, resistance exercise may be superior in eliciting potential benefits on indicators of muscle strength and mass. Yet, few intradialytic exercise programmes have focused on this type of intervention, and the ones which have report inconsistent benefits, diverging on prescribed exercise intensity, absent or subjective load progression, equipment availability, or exercise supervision. Commonly, intradialytic resistance exercise interventions use free weights, ankle cuffs, or elastic bands which hinder load progression and exercise intensity monitoring. Here, we introduce a recently developed intradialytic resistance exercise device and propose an accompanying innovative resistance exercise training protocol which aims to improve the quality of resistance exercise interventions within dialysis treatment sessions.