Hemodialysis without Systemic Anticoagulation: A Randomized Controlled Trial to Evaluate Five Strategies in Patients at a High Risk of Bleeding.

BACKGROUND: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach. AIM: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis. METHODS: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions. PRIMARY ENDPOINT: the successful completion of hemodialysis without clotting. SECONDARY OUTCOMES: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions. RESULTS: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed. CONCLUSIONS: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

Serum Creatinine and Tacrolimus Assessment With VAMS Finger-Prick Microsampling: A Diagnostic Test Study.

Rationale & Objective: Kidney transplant recipients require frequent venipunctures. Microsampling methods that use a finger-prick draw of capillary blood, like volumetric absorptive microsamplers (VAMS), have the potential to reduce the pain, inconvenience, and volume of blood loss associated with venipuncture. This study aimed to provide diagnostic accuracy using VAMS for measurement of tacrolimus and creatinine compared to gold standard venous blood in adult kidney transplant recipients. Study Design: Diagnostic test study. Prospective blood samples for measurement of tacrolimus and creatinine were collected using Mitra VAMS and venipuncture immediately before and 2 hours after tacrolimus dosing. Setting & Participants: A convenience sample of 40 adult kidney transplant participants in the outpatient setting. Tests Compared: Method comparison was assessed by Passing-Bablok regression and Bland-Altman analysis. The predictive performance of VAMS measurement compared to venipuncture was also assessed through estimation of the median prediction error and median absolute percentage prediction error. Results: A total of 74 tacrolimus samples and 70 creatinine samples were analyzed from 40 participants. Passing-Bablok regression showed a systematic difference between VAMS and venipuncture when measuring tacrolimus and creatinine with a slope of 1.08 (95% CI, 1.03-1.13) and a slope of 0.65 (95% CI, 0.6-0.7), respectively. These values were then corrected for the systematic difference. When used for Bland-Altman analysis, corrected values of tacrolimus and creatinine showed a bias of -0.1 µg/L and 0.04 mg/dL, respectively. Tacrolimus (corrected) and creatinine (corrected) microsampling values when compared to corresponding venipuncture values met median prediction error and median absolute percentage prediction error predefined acceptability limits of <15%. Limitations: This study was conducted in a controlled environment using a trained nurse to collect VAMS samples. Conclusions: In this study, VAMS was used to reliably measured tacrolimus and creatinine. This represents a clear opportunity for more frequent and less invasive sampling for patients.

Fingerprick Microsampling Methods Can Replace Venepuncture for Simultaneous Therapeutic Drug Monitoring of Tacrolimus, Mycophenolic Acid, and Prednisolone Concentrations in Adult Kidney Transplant Patients.

BACKGROUND: Kidney transplant patients undergo repeated and frequent venepunctures during allograft management. Microsampling methods that use a fingerprick draw of capillary blood, such as dried blood spots (DBS) and volumetric absorptive microsamplers (VAMS), have the potential to reduce the burden and volume of blood loss with venepuncture. METHODS: This study aimed to examine microsampling approaches for the simultaneous measurement of tacrolimus, mycophenolic acid, mycophenolic acid glucuronide (MPAG), and prednisolone drug concentrations compared with standard venepuncture in adult kidney transplant patients. DBS and VAMS were simultaneously collected with venepuncture samples from 40 adult kidney transplant patients immediately before and 2 hours after immunosuppressant dosing. Method comparison was performed using Passing-Bablok regression, and bias was assessed using Bland-Altman analysis. Drug concentrations measured through microsampling and venepuncture were also compared by estimating the median prediction error (MPE) and median absolute percentage prediction error (MAPE). RESULTS: Passing-Bablok regression showed a systematic difference between tacrolimus DBS and venepuncture [slope of 1.06 (1.01-1.13)] and between tacrolimus VAMS and venepuncture [slope of 1.08 (1.03-1.13)]. Tacrolimus values were adjusted for this difference, and the corrected values showed no systematic differences. Moreover, no systematic differences were observed when comparing DBS or VAMS with venepuncture for mycophenolic acid and prednisolone. Tacrolimus (corrected), mycophenolic acid, and prednisolone microsampling values met the MPE and MAPE predefined acceptability limits of <15% when compared with the corresponding venepuncture values. DBS and VAMS, collected in a controlled environment, simultaneously measured multiple immunosuppressants. CONCLUSIONS: This study demonstrates that accurate results of multiple immunosuppressant concentrations can be generated through the microsampling approach, with a preference for VAMS over DBS.

Pharmacokinetic and Pharmacodynamic Considerations in Relation to Calcineurin Usage in Elderly Kidney Transplant Recipients.

This review summarizes how possible age-related changes in tacrolimus and cyclosporine pharmacokinetics and pharmacodynamics may influence drug dosing and monitoring in the elderly, and highlights how micro-sampling may be useful in this cohort in the future. Advancing biological age leads to physiological changes that can affect drug absorption, distribution, metabolism and excretion, as well as immune system responsiveness. Some studies have shown that elderly recipients may have higher dose-adjusted exposure and/or lower clearance of the calcineurin inhibitors, suggesting that doses may need to be lowered in elderly recipients. Only one study has examined how aging effects drug target enzyme activity and demonstrated that age does not correlate with the calcineurin inhibitor half-maximal inhibitory concentration. Several studies have shown elderly kidney transplant recipients have increased risk of both morbidity and mortality, compared to younger adults due to increased susceptibility to immunosuppressant side effects, particularly cardiovascular disease, infection and malignancy. Current immunosuppressant dosing and monitoring protocols often make no adjustments for age. Lower maintenance immunosuppressant targets in elderly recipients may decrease patient susceptibility to drug side effects, however, further studies are required and appropriate targets need to be established. Blood draw by micro-sampling may be useful for drug monitoring in this cohort in the future, as blood collection is minimally invasive and less painful than venepuncture. Micro-sampling could also make further pharmacokinetic, pharmacodynamics and outcome studies in the elderly more feasible.

T-cell adoptive immunotherapy for BK nephropathy in renal transplantation.

INTRODUCTION: BK virus (BKPyV) nephropathy occurs in 1%-10% of kidney transplant recipients, with suboptimal therapeutic options. CASE: A 54-year-old woman received a transplant in March 2017. BKPyV was detected at 1.5 × 102  copies/mL within a month, necessitating halving of mycophenolate and addition of leflunomide. Allograft histology in December showed polyomavirus nephropathy treated with intravenous immunoglobulin and cessation of mycophenolate. In February 2018, cidofovir and ciprofloxacin were commenced. In April, tacrolimus was reduced while introducing everolimus. A second graft biopsy in August showed increasing polyoma virus infection and a subsequent biopsy in September for worsening renal function showed 30% of tubular reactivity for simian virus 40 (SV40). Allogeneic BKPyV-reactive T cells were generated from the patient's daughter and infused over 10 sessions starting late September. The fourth allograft biopsy in November 2018 demonstrated involvement of BKPyV in 50% of tubules. Allograft function continued to decline, requiring hemodialysis from December 2018. Allograft nephrectomy after 6 months showed <1% SV40 in preserved tubules and 80% interstitial fibrosis. DISCUSSION: We conclude that the T-cell adoptive immunotherapy reduced BKPyV load significantly despite extensive infection, but attendant fibrosis and tubular atrophy led to graft failure. Early intervention with T-cell therapy may prove efficacious in BKPyV nephropathy.

Kidney transplant recipient's perceptions of blood testing through microsampling and venepuncture.

A survey of kidney transplant recipients receiving two innovative microsampling methods, dried blood spot and volumetric absorptive microsampling using patient reported methodology. A total of 39 adult transplant patients underwent venepuncture and finger prick-based blood draws on two occasions. They completed a survey of blood test understanding, tolerability, preferences and the burden associated with venepuncture compared with microsampling. A total of 85% of participants (n = 33) preferred finger prick-based sampling and 95% (n = 37) were interested in blood collection using self sampling by finger prick at home; 33% (n = 13) of participants experienced blood test anxiety. To quantify time burden of providing venous samples a total of 44% (n = 17) spent greater than 1 hour to travel and provide venous samples. This study observed a patient preference for microsampling for blood sampling as an alternative to venepuncture in the management of their kidney transplant.

Experiences of medical dominance in pharmacist-doctor interactions - An elephant in the room?

BACKGROUND: The development of new roles by pharmacists supports the delivery of healthcare services but potentially also encroaches into other healthcare professions' domains of practice. Some novel pharmacy services are only reluctantly accepted by the medical profession and are surrounded by a discourse which expresses medical dominance, with pharmacists facing resistance to their closer involvement in patient care. OBJECTIVE: To investigate whether and how pharmacists may experience medical dominance in their practice. METHODS: For this qualitative study, pharmacists working in primary care settings were introduced to concepts of sociology in healthcare and medical dominance, then asked to reflect on personal experiences of potential medical dominance, and their emotional and behavioural response. The reflective texts were thematically analysed using a framework based on theories of medical dominance, self-regulation and the influence of emotions on cognition to interpret themes. RESULTS: Twenty-five pharmacists provided detailed reflective accounts. Most worked in a community pharmacy when they experienced medical dominance in interactions with doctors. They described how doctors demarcated territory, evaded scrutiny or disparaged pharmacists' professional expertise. Pharmacists perceived limited options in negotiating these experiences and often employed patients in resolving issues which were left unaddressed. They felt frustrated, undervalued and angry after their experiences and described apprehensiveness in future interactions with doctors. CONCLUSION: Although experiences of medical dominance by pharmacists working in primary care seem to be an infrequent though regular occurrence pharmacists do not seem to be well prepared to counter or negotiate around it. Perceived and actual dominance in interprofessional interactions with doctors are stressors which may affect pharmacists' ability to problem-solve, their role effectiveness and satisfaction.

Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia.

BACKGROUND: Urinary tract infections (UTI) are the most common of infections after renal transplantation. The consequences of UTIs in this population are serious, with increased morbidity and hospitalisation rates as well as acute allograft dysfunction. UTIs may impair overall graft and patient survival. We aimed to identify the prevalence and risk factors for post-transplant UTIs and assess UTIs' effect on renal function during a UTI episode and if they result in declining allograft function at 2 years post-transplant. Additionally, the causative organism, the class of antibacterial drug employed for each UTI episode and utilisation rates of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were also quantified. METHODS: This was a retrospective study of 72 renal transplant patients over a 5-year period who were managed at the Royal Brisbane and Women's Hospital. Patient charts, pathology records and dispensing histories were reviewed as part of this study and all UTIs from 2 years post transplantation were captured. RESULTS: Of these patients, 20 (27.8%) had at least one UTI. Older age (p = 0.015), female gender (p < 0.001), hyperglycaemia (p = 0.037) and acute rejection episodes (p = 0.046) were risk factors for developing a UTI on unadjusted analysis. Female gender (OR 4.93) and age (OR 1.03) were statistically significant risk factors for a UTI on adjusted analysis. On average, there was a 14.4% (SEM 5.20) increase in serum creatinine during a UTI episode, which was statistically significant (p = 0.027), and a 9.1% (SEM 6.23) reduction in serum creatinine after the UTI episode trending toward statistical significance. (p = 0.076). Common organisms (Escherichia coli and Klebsiella pneumoniae) accounted for 82% of UTI episodes with 70% of UTI cases requiring only a single course of antibiotic treatment. Furthermore, the antibiotic class used was either a penicillin (49%) or cephalosporin (36%) in the majority of UTIs. The use of TMP/SMX prophylaxis for Pneumocystis carinii pneumonia prophylaxis did not influence the rate of UTI, with > 90% of the cohort using this treatment. CONCLUSIONS: There was no significant change in serum creatinine and estimated glomerular filtrate rate from baseline to 2 years post-transplant between those with and without a UTI.

Using confidence assessment to explore physiotherapists, dieticians, speech pathologists and occupational therapists knowledge of medicines.

Medicines are the largest single intervention provided to patients on admission to hospital. Adverse effects of medicines may decrease the ability of patients to participate in clinical interventions from physiotherapists, dietitians, speech pathologists and occupational therapists (PDSOs), which in turn impacts on quality of care and length of hospital stay. PDSOs receive medicines education as part of their undergraduate degree but little education once commencing practice. Pharmacists' possess significant knowledge about medicines and are well placed to educate PDSOs about medicines which may benefit their interventions. This study used certainty- based scoring to evaluate an interprofessional workshop addressing medicines safety information for PDSOs. Scoping interviews established baseline knowledge. Interview data was then used to formulate the workshop and case study. Knowledge was assessed using a pre and post quiz including a certainty- based score. A two-hour pilot workshop attracted thirty-three attendees from the PDSO professions. A trend towards more correct answers and increased certainty they were correct was observed from pre to post quiz. This style of workshop measures PDSOs knowledge of, and competence with, medicines. The assessment for competence is an important consideration with increasing numbers of medicines and complexity of patients potentially increasing risk of adverse events.

The Kidney Supportive Care programme: characteristics of patients referred to a new model of care.

OBJECTIVES: For many people with advanced kidney disease, their physical, psychological and emotional needs remain unmet. Kidney supportive care, fully integrating specialist kidney and palliative care teams, responds to the emotional and symptom distress in this cohort who may be on a non-dialysis care pathway or on dialysis and approaching end of life. We aimed to analyse and describe the operation and patient characteristics of a new kidney supportive care programme (KSCp). METHODS: A multidisciplinary KSCp was introduced through a tertiary hospital in Brisbane, Australia. Operational information and characteristics of referred patients were collected from internal databases and electronic medical records and analysed descriptively. Patient data were collected using validated instruments to assess symptom burden, health-related quality of life, health state, functional status and performance at clinic entry and analysed descriptively. RESULTS: 129 people with advanced kidney disease were referred to the KSCp within the first year (median age 74 (range 27.7-90.5), 48.1% female, median Charlson Comorbidity Index score 7 (IQR 6-8) and mean Integrated Palliative care Outcome Scale Renal score 19.6±9.8). 59% were currently receiving dialysis. The leading reason for referral was symptom management (37%). While quality of life and health state varied considerably among the cohort, in general, these parameters were well below population norms. CONCLUSIONS: Results indicate that patients referred to the KSCp were those with a strong need for a patient-centred, integrated model of care. Shifting focus to co-ordinated, multidisciplinary care rather than discrete specialty silos appears key to addressing the challenging clinical problems in end-of-life care.