Is It Time to Give Peritoneal Dialysis Its Due Place in Managing Acute Kidney Injury: Lessons Learnt from COVID-19 Pandemic.

Despite comparable outcomes with the extracorporeal dialysis modalities, peritoneal dialysis (PD) is seldom considered a viable option for managing acute kidney injury (AKI) in developed and resource-rich countries, where continuous renal replacement therapies (CRRTs) are the mainstay of treating AKI. PD has fewer infrastructure requirements and has been shown to save lives during conflicts, natural disasters, and pandemics. During the ongoing COVID-19 pandemic, the developed world was confronted with a sudden surge in critically ill AKI patients requiring renal replacement therapy. There were acute shortages of CRRT machines and the trained staff to deliver those treatments. Some centres developed acute PD programmes to circumvent these issues with good results. This experience re-emphasised the suitability of PD for managing AKI. It also highlighted the need to review the current management strategies for AKI in developed countries and consider incorporating PD as a viable tool for suitable patients. This article reviews the current evidence of using PD in AKI, attempts to clarify some misconceptions about PD in AKI, and argues in favour of developing acute PD programmes.

Real-World Experience of Using Etelcalcetide for Secondary Hyperparathyroidism in Community-Based Hemodialysis Centers in Singapore.

Introduction Chronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD). The treatment for SHPT includes synthetic vitamin D analogs, calcitriol or calcimimetics. Recently, intravenous etelcalcetide was introduced as a second-generation calcimimetic. This article provides the real-world experience of using etelcalcetide in multiethnic Asian patients receiving hemodialysis at community-based hemodialysis centers in Singapore. Methods This study was real-world evidence, generated by a retrospective clinical audit of routine clinical care of hemodialysis patients in community-based centers in Singapore who received etelcalcetide for treating SHPT. The information on the starting and maximum dose of etelcalcetide, duration of treatment on hemodialysis, parathyroid hormone (PTH) levels, dialysate calcium, concomitant medications, and reasons for discontinuation were collected from the medical records. PTH levels were collected at four-, eight-, and twelve-month intervals. Results A total of 148 patients received etelcalcetide during the study period. Ten patients died and twenty discontinued their treatment, with 118 patients remaining on treatment. Demographically, the patients included Chinese, Malay, Indians, and those belonging to other racial groups. The starting dose of etelcalcetide ranged from 2.5 mg once per week to 7.5 mg three times a week. There was a 16.8% reduction (p=<0.001) in intact-PTH after four months of therapy. Target intact-PTH level of less than 60 pmol/L, was reported as 1.4% at baseline, with 22.3% at four months (p<0.001) and 25.9% at eight months (p=0.028). Calcium and phosphate levels were also tracked as part of the safety and efficacy measures of using etelcalcetide. No symptomatic hypocalcemia was noted and phosphate levels were noted to decline significantly. Overall, the calcium-phosphate product reduced at four months (13.2%, p=<0.001) and eight months (12.7%, p<0.05). An analysis of concomitant medication usage, dialysate calcium utilized, and the side effects of etelcalcetide were also recorded. Finally, a brief descriptive analysis of the patient's subjective feedback regarding etelcalcetide was also reported, especially regarding the reduction in pill burden and overall compliance to medications. Conclusion Etelcalcetide is safe and effective for treating SHPT in multi-ethnic Asian hemodialysis patients and can be considered an alternative to oral cinacalcet. Our study showed no side effects, which was one of the key reasons for non-compliance to traditional calcimimetics. A favorable compliance profile with reduced pill burden was noted by using this intravenous calcimimetic.

A Real-World Experience of Hyperkalemia Management Using Sodium Zirconium Cyclosilicate in Chronic Hemodialysis: A Multicenter Clinical Audit.

INTRODUCTION:  Hyperkalemia, a common condition among hemodialysis (HD) patients, is associated with adverse health outcomes. Evidence of the safety and efficacy of a potassium-binder, sodium zirconium cyclosilicate (SZC), has been limited among Asian (HD) patients beyond phase 3 trials. This article demonstrates real-world evidence of SZC usage in an Asian cohort of HD patients. METHODS:  A retrospective clinical audit was conducted among 293 patients who received maintenance HD at community-based dialysis centers in Singapore. Patients received SZC for either management of hyperkalemia or hyperkalemia prevention during anticipated disruption to dialysis, such as during traveling. Among patients treated for hyperkalemia (N = 147), serum potassium (K+) prior to SZC initiation and at the endpoint was compared using a paired Student's t-test. Changes in K+ from baseline to endpoint were compared across various categories within each demographic and health-related variables using either Student's t-test or one-way ANOVA. Patients who experienced adverse events after SZC initiation or were deceased during the audit were reviewed to provide a descriptive account. RESULTS:  Among patients who received SZC for hyperkalemia treatment, SZC use was associated with a significant reduction of 0.812 mmol/L in serum potassium. Patients with ethnicities other than Chinese, Malay, or Indian had a nominal reduction in K+ of 0.7 mmol/L and this can be accounted for the small sample size of this sub-group. The three main ethnicities which represented more than 95% of the sample showed a significant reduction in K+ levels (all three p<0.001). This is consistent with other studies with SZC which showed efficacy across various ethnicities. Patients who received SZC for hyperkalemia treatment or prevention had a significant lowering of mortality rate. This mortality reduction may have inherent biases and confounders, due to the retrospective clinical audit study design.  Conclusions: Overall, SZC was safe and effective among the audited patients. The efficacy in the real-world setting was similar to previous trials. The novel use of SZC to manage serum potassium when HD sessions are missed, such as during traveling, warrants further investigation due to potentially significant life-saving implications.

The Impact of COVID-19 Infection Control Measures on End-Stage Renal Disease Patients in a Community Hemodialysis Setting.

INTRODUCTION: Several non-pharmaceutical infection control measures have been implemented at community-based hemodialysis centers to reduce the risk of Coronavirus Disease of 2019 (COVID-19) transmission, caused by the SARS-CoV-2 virus. However, there have been concerns that such measures may disrupt the routine and timely care required by patients, with adverse effects on their health outcomes. This cross-sectional study aims to determine the unintended consequences of COVID-19 infection control measures on hemodialysis patients. METHODS:  Electronic medical records were extracted from patients enrolled in community-based hemodialysis centers in Singapore. A baseline group prior of patients consisted of those enrolled in 2017, which was three years prior to the SARS-CoV-2-related pandemic (n = 548). This was compared with the study group of patients enrolled in 2019 (n = 426), just before the COVID-19 pandemic started. Medical records for these two groups were extracted from January to July 2018 for the baseline group and from January to July 2020, respectively. Three regression models were built to study dialysis adherence, kidney disease biomarkers, and hospitalization episodes. RESULTS:  There was no statistically significant difference in hospitalization and mortality outcomes, adherence to dialysis management, laboratory results for dialysis-related clearance, and anemia outcomes. There was a higher proportion of patients hospitalized for vascular access-related reasons in the study group as compared to the baseline group (OR 1.6, 95% CI: 1.10 to 2.29, P = 0.014). Patients in the study group had albumin levels 2.13% higher (95% CI: 0.88 to 3.39, P < 0.001) and alkaline phosphatase levels 7.3% lower (95% CI: 1.17 to 13.02, P = 0.020) than those in the baseline group. CONCLUSIONS:  From this community-based hemodialysis study in Singapore, it was shown that the COVID-19 pandemic did not disrupt regular healthcare services for these patients. With strategies instituted for a coordinated health delivery workflow, ensuring sufficient capacity in the various healthcare delivery sites and overall pandemic preparedness, the patient clinical outcomes measures continued to be met with no adverse consequences noted. Some improvements in dialysis-related laboratory values and quality of care targets may be due to more stringent measures instituted to protect these vulnerable patients in the community.

Tixagevimab and Cilgavimab Administration for Hemodialysis Patients at Community-Based Dialysis Centers in Singapore as Pre-Exposure Prophylaxis for SARS-CoV-2 Infection.

INTRODUCTION:  Hemodialysis patients are deemed to be immunosuppressed and may not be able to mount an adequate response to vaccination against the SARS-CoV-2 virus. Due to the higher morbidity and mortality in this vulnerable group, pre-exposure prophylaxis with monoclonal antibodies was introduced as an additional measure for protection in selected community-based hemodialysis patients in Singapore. Tixagevimab and cilgavimab, available as Evusheld, were used for this purpose. METHODS:  A government-sponsored clinical administration program with the provision of 200 doses of Evusheld at no cost to the patients was implemented. Patient selection criteria to further risk-stratify this vulnerable hemodialysis patient cohort was developed and 200 patients were finally selected. Evusheld administration was done over a period of two months, as two consecutive injections were given at two separate intramuscular sites, which constituted one administration. Data were collected as part of a retrospective clinical audit, as part of a routine quality monitoring process for this patient care program. Real-world evidence was generated to assess the impact on mortality, hospitalization rate, reason for hospitalization, and any associated morbidity. RESULTS:  No adverse events from the Evusheld administration were noted. All recipients had received COVID-19 vaccinations prior to Tixa-Cilga, with a range of one to five doses. A total of 198 (99%) completed two doses and 189 (95%) completed three doses, out of which, 14 (7%) patients contracted COVID-19 infection over three months. The overall hospitalization rate was 2% (four out of 200 patients). Severe illness that required intensive care unit stay was therefore seen in only 2 (1%) out of 200 patients. None of the infected patients died. DISCUSSION:  A significant reduction in severity of illness, hospitalization rate, and mortality was found with pre-exposure prophylaxis with tixagevimab and cilgavimab, in this real-world experience from Singapore. Evusheld administration reduced the hospitalization rate from 42.5% to 2%, which is a reduction of 95.3% (p<0.0001). Symptoms in infected patients were mild, with only 1% being admitted to the intensive care unit. The mortality rate from COVID-19 infection was reduced from 2.5% to 0% with Evusheld.  Conclusion: Mass administration of prophylactic treatments for vulnerable populations can be challenging in community-based settings and the successful implementation of such a program has been described. The findings can have health policy implications for the protection of such immunocompromised patients in the future. The combination of tixagevimab and cilgavimab, available as Evusheld in Singapore, was safe to use in hemodialysis patients, with no adverse events noted. There was a significant reduction in hospitalization rates and intensive care unit admissions with a zero-mortality rate due to COVID-19 infection, after pre-exposure prophylaxis.

Prevalence and trajectories of subjective cognitive complaints and implications for patient outcomes: A prospective study of haemodialysis patients.

OBJECTIVES: Cognitive impairment is common in haemodialysis patients and is associated with increased hospitalization and mortality. However, subjective cognitive complaints (SCCs), the self-experienced difficulties in everyday cognitive activities, remain poorly understood. This study examined the prevalence and course of SCCs in haemodialysis patients and its longitudinal associations with sociodemographic, clinical and patient-reported variables. DESIGN: Observational prospective study with baseline and 12-month follow-up assessment. METHODS: Based on a validated cut-off point on the Kidney Disease Quality of Life Cognitive Function subscale, haemodialysis patients (N = 159; 40.3% female, mean age 53.62) were classified into cognitive complaint trajectories: (1) resilient (60.4%; no/low SCCs throughout); (2) persistent (8.8%; stable high SCCs); (3) deterioration (17.6%; from no/low to high SCCs); and (4) recovery (13.2%; from high to no/low SCCs). Sociodemographic/clinical characteristics, self-efficacy, self-management skills, adherence, mood and biochemical assays were measured at both assessments and compared among trajectories using mixed ANOVAs. RESULTS: Interaction effects indicated significant improvements in the recovery group in clinical outcomes (i.e., decreased phosphorus and calcium-phosphorus product), self-efficacy and mood over time. Group effects indicated significantly poorer self-efficacy, self-management skills and adherence in the persistent group than other trajectories across both assessments. None of the sociodemographic/clinical characteristics was associated with SCC trajectories. CONCLUSIONS: The extent of SCCs vary over time across haemodialysis patients. Routine screening of SCCs in dialysis settings may help identifying patients at risk of poor self-management and worse prognosis. Strategies that compensate for cognitive lapses may mitigate the perceived cognitive burden of this population.

Impella Versus Extracorporeal Membranous Oxygenation (ECMO) for Cardiogenic Shock: A Systematic Review and Meta-analysis.

The use of mechanical circulatory support (MCS) in cardiogenic shock (CS) is increasing. We conducted a systematic review and meta-analysis to compare the outcomes of Impella use with extracorporeal membranous oxygenation (ECMO) support in patients with CS. We searched the Medline, EMBASE, Cochrane, and Clinicaltrials.gov databases for observational studies comparing Impella to ECMO in patients with CS. Risk ratios (RRs) for categorical variables and standardized mean differences (SMDs) for continuous variables were calculated with 95% confidence intervals (CIs) using a random-effects model. Twelve retrospective studies and one prospective study (Impella n=6652, ECMO n=1232) were identified. Impella use was associated with lower incidence of in-hospital mortality (RR 0.88 [95% CI 0.80-0.94], P=0.0004), stroke (RR 0.30 [0.21-0.42], P<0.00001), access-site bleeding (RR 0.50 [0.37-0.69], P<0.0001), major bleeding (RR 0.56 [0.39-0.80], P=0.002), and limb ischemia (RR 0.42 [0.27-0.65], P=0.0001). Baseline lactate levels were significantly lower in the Impella group (SMD -0.52 [-0.73- -0.31], P<0.00001). There was no significant difference in mortality at 6-12 months, MCS duration, need for MCS escalation, bridge-to-LVAD or heart transplant, and renal replacement therapy use between Impella and ECMO groups. In patients with CS, Impella device use was associated with lower in-hospital mortality, stroke, and device-related complications than ECMO. However, patients in the ECMO group had higher baseline lactate levels.

Subjective cognitive complaints in end-stage renal disease: a systematic review and meta-analysis.

Cognitive impairment is common in patients with end-stage renal disease (ESRD) and is associated with compromised quality of life and functional capacity, as well as worse clinical outcomes. Most previous research and reviews in this area were focused on objective cognitive impairment, whereas patients' subjective cognitive complaints (SCCs) have been less well-understood. This systematic review aimed to provide a broad overview of what is known about SCCs in adult ESRD patients. Electronic databases were searched from inception to January 2022, which identified 221 relevant studies. SCCs appear to be highly prevalent in dialysis patients and less so in those who received kidney transplantation. A random-effects meta-analysis also shows that haemodialysis patients reported significantly more SCCs than peritoneal dialysis patients (standardised mean difference -0.20, 95% confidence interval -0.38 to -0.03). Synthesis of longitudinal studies suggests that SCCs remain stable on maintenance dialysis treatment but may reduce upon receipt of kidney transplant. Furthermore, SCCs in ESRD patients have been consistently associated with hospitalisation, depression, anxiety, fatigue, and poorer quality of life. There is limited data supporting a strong relation between objective and subjective cognition but preliminary evidence suggests that this association may be domain-specific. Methodological limitations and future research directions are discussed.

The role of subjective cognitive complaints in self-management among haemodialysis patients: a cross-sectional study.

BACKGROUND: Subjective cognitive complaints refer to self-experienced difficulties with everyday cognitive tasks. Although there has been a fair amount of research on cognitive impairments and cognitive complaints in end-stage renal disease, the practical implications of these complaints remain unclear. The current study aims to examine the associations of cognitive complaints with sociodemographic and clinical variables, mood, as well as key patient-reported outcomes, i.e., self-efficacy, self-management skills, and treatment adherence. METHODS: A total of 305 haemodialysis patients (mean age = 53.97 years, 42.6% female) completed the Kidney Disease Quality of Life Cognitive Function subscale, a brief measure of cognitive complaints. The recommended cut-off point of 60 was used to identify probable cognitive impairment. Measures of self-efficacy, self-management skills (i.e., symptom coping, health monitoring, health service navigation), treatment adherence, and mood symptoms were also administered. Between-group comparisons and correlational analyses were performed to examine associations of cognitive complaints with sociodemographic, clinical, and health behaviour variables. Mediation analyses were also conducted to investigate the mediating role of self-efficacy on the relationship between cognitive complaints and treatment adherence. RESULTS: Nearly a quarter (23.0%) of haemodialysis patients reported cognitive complaints indicative of clinical impairments. Risk of probable impairments was higher for patients with hypertension, diabetes, those diagnosed with end-stage renal disease at an older age, and those with shorter time on dialysis. Subjective cognitive complaints (both rates of probable impairments as per cut-off and continuous scores) were significantly associated with lower disease and treatment self-efficacy, poorer self-management skills, lower treatment adherence, as well as higher symptoms of distress. Mediation analysis indicated that treatment self-efficacy mediated the relationship between cognitive complaints and treatment adherence. CONCLUSIONS: The current study demonstrated the clinical characteristics of haemodialysis patients who report cognitive complaints indicative of probable cognitive impairments and showed the associations of these complaints with self-management outcomes. Future studies should adopt more comprehensive measures of cognitive complaints and longitudinal designs to confirm the current findings.

Comparing outcomes of tunnelled dialysis catheter insertions and exchanges with or without fluoroscopy.

BACKGROUND/OBJECTIVE: To study the safety and outcome profiles of tunnelled dialysis catheter (TDC) insertions and exchanges with fluoroscopy versus without fluoroscopy. METHODS: This was a retrospective cohort study of all TDC insertions or exchanges performed at our centre, between January 2017 and December 2017. Patient demographics, laboratory results and catheter placement information were obtained from electronic records. Immediate technical success, early and late catheter associated complications were collected. Outcomes for TDC inserted with or without fluoroscopy were statistically analysed. RESULTS: A total of 351 TDC insertions and 253 TDC exchanges were performed. Out of 351 TDC insertions, 261 were done with fluoroscopy while 90 were done without. Out of 253 TDC exchanges, 219 were done with fluoroscopy while 34 were done without. For both TDC insertions and exchanges, there were no significant differences in complication rates when done with or without fluoroscopy. Mean duration of catheter patency was longer for TDC inserted without fluoroscopy, after adjusting for site of insertion and presence of previous TDC. CONCLUSIONS: The technique of inserting TDC in the right internal jugular vein (IJV) without fluoroscopy is a safe and effective method in selected patients. This supports the practice of performing the procedure without fluoroscopy, especially in institutions where fluoroscopy facilities are not readily available. This potentially translates into reduced healthcare resources and hospitalisation days, which is particularly valuable in times of limited resources such as the current Coronavirus Disease 2019 (COVID-19) pandemic.

Effectiveness of a brief positive skills intervention to improve psychological adjustment in patients with end-stage kidney disease newly initiated on haemodialysis: protocol for a randomised controlled trial (HED-Start).

INTRODUCTION: Initiation onto haemodialysis is a critical transition that entails multiple psychosocial and behavioural demands that can compound mental health burden. Interventions guided by self-management and cognitive-behavioural therapy to improve distress have been variably effective yet are resource-intensive or delivered reactively. Interventions with a focus on positive affect for patients with end-stage kidney disease are lacking. This study will seek (1) to develop a positive life skills intervention (HED-Start) combining evidence and stakeholder/user involvement and (2) evaluate the effectiveness of HED-Start to facilitate positive life skills acquisition and improve symptoms of distress and adjustment in incident haemodialysis patients. METHODS AND ANALYSIS: This is a single/assessor-blinded randomised controlled trial (RCT) to compare HED-Start to usual care. In designing HED-Start, semistructured interviews, a codesign workshop and an internal pilot will be undertaken, followed by a two-arm parallel RCT to evaluate the effectiveness of HED-Start. A total of 148 incident HD patients will be randomised using a 1:2 ratio into usual care versus HED-Start to be delivered in groups by trained facilitators between January 2021 and September 2022. Anxiety and depression will be the primary outcomes; secondary outcomes will be positive and negative affect, quality of life, illness perceptions, self-efficacy, self-management skills, benefit finding and resilience. Assessments will be taken at 2 weeks prerandomisation (baseline) and 3 months postrandomisation (2 weeks post-HED-Start completion). Primary analyses will use an intention-to-treat approach and compare changes in outcomes from baseline to follow-up relative to the control group using mixed-effect models. ETHICS AND DISSEMINATION: Ethics approval was obtained from Nanyang Technological University Institutional Review Board (IRB-2019-01-010). Written informed consent will be obtained before any research activities. Trial results will be disseminated via publications in peer-reviewed journals and conference presentations and will inform revision(s) in renal health services to support the transition of new patients to haemodialysis. TRIAL REGISTRATION NUMBER: NCT04774770.

The modality of choice, manual or automated, for urgent start peritoneal dialysis.

Over the last decade, urgent start peritoneal dialysis (USPD), defined as initiation of peritoneal dialysis (PD) before the traditionally recommended break-in period of 2-4 weeks, has increasingly been seen as a viable option for late-presenting end-stage renal disease patients, obviating the need for haemodialysis via central venous catheter. Different prescriptions and protocols involving both manual and automated exchanges have been published, but there is no head-to-head comparison of the two modalities and no consensus on the most suitable modality exists. Evaluation of the available evidence suggests that PD can be initiated urgently using either or both options without much difference in the outcome. The two most critical aspects dictating the success of a USPD programme are using low dwell volumes and keeping patients in a strict supine position during the dialysis exchanges in the first couple of weeks of the therapy. These measures are crucial in keeping the intraperitoneal pressure to a minimum and reduce the risk of mechanical complications, including catheter leaks and malpositioning.

Is surgical PD catheter insertion safe for urgent-start peritoneal dialysis?

Urgent-start peritoneal dialysis (USPD) is increasingly seen as a viable alternative to hemodialysis through a central venous catheter for late-presenting end-stage renal disease patients. However, concerns remain about starting dialysis early following the surgical implantation of the peritoneal dialysis (PD) catheter; urgent PD is often thought to be a safe option only after minimally invasive percutaneous catheter insertions. Analysis of the cumulative data from published literature presented in this review appears to negate this general perception and shows that compared to the percutaneous catheter insertions, starting PD urgently following surgically placed catheter is not associated with more catheter leaks, dysfunctions, or other complications. The outcome of USPD is independent of the mode of catheter insertion. Instead, measures to minimize intra-peritoneal pressure including using the low initial dwell volume based on patient's weight and body habitus and keeping patients in strict supine posture during exchanges in the first 2 weeks of treatment are the two most important factors ensuring a minimization of the risk of catheter-related complications.

Tumor lysis syndrome associated with reduced immunosuppression in a lung transplant recipient.

Tumor lysis syndrome usually occurs after Initiation of chemotherapy or radiation therapy in cancer patients with a moderate to high tumor burden. To our knowledge, the occurrence of this syndrome after discontinuation or reduction of an immunosuppressive regimen has not been reported in the literature. We describe a patient who had undergone lung transplantation and who was receiving immunosuppression and experienced an episode of acute pancreatitis. During the course of the work-up, the patient was found to have a B-cell lymphoma (posttransplantation lymphoproliferative disease). His tacrolimus dosage was decreased, and azathioprine was discontinued. The patient subsequently developed tumor lysis syndrome. Other than the decrease in immunosuppression, we found no other factor that could have accounted for this syndrome.