The impact on patients of the tertiary-primary healthcare interface in kidney failure: a qualitative study.

BACKGROUND: Clinicians and patients have reported fragmentation in the primary and tertiary healthcare interface. However, perspectives of service navigation and the impacts of fragmentation are not well defined, particularly for patients transitioning to dialysis. This study aimed to define patient perspectives of the functioning of the health service interface and impacts on healthcare experiences and engagement, informing patient-centred and outcomes-focused service models. METHODS: A qualitative study was conducted through semi-structured interviews with 25 dialysis patients (16 males) aged 34-78 receiving dialysis across a multi-site tertiary service. Transcripts were analysed thematically. RESULTS: Three main themes were identified: (1) The Changing Nature of General Practitioner (GP) Patient Relationships; (2) Ownership and Leadership in Kidney Care; and (3) The Importance of Nephrologist-GP Communications. Patients perceived an unreliable primary-tertiary service interface which lacked coordinated care and created challenges for primary care continuity. These impacted perceptions of healthcare provider expertise and confidence in healthcare systems. Patients subsequently increased the healthcare sought from tertiary kidney clinicians. The fractured interface led some to coordinate communication between health sectors, to support care quality, but this caused additional stress. CONCLUSIONS: A fragmented primary-tertiary healthcare interface creates challenges for patient service navigation and can negatively impact patient experiences, leading to primary care disengagement, reduced confidence in health care quality and increased stress. Future studies are imperative for assessing initiatives facilitating health system integration, including communication technologies, healthcare provider training, patient empowerment, and specific outcomes in health, economic and patient experience measures, for patients transitioning to dialysis.

Gastrointestinal symptom burden and dietary intake in patients with chronic kidney disease.

BACKGROUND: Gastrointestinal (GI) symptoms can present a significant burden to patients with chronic kidney disease (CKD) but the reported prevalence is inconsistent. OBJECTIVE: To examine the GI burden and dietary intake in patients with CKD with or without dialysis. METHODS: This was a cross-sectional study of 216 adults, recruited from outpatient and dialysis clinics, with CKD stage 4 or 5 not receiving dialysis (CKD-ND), or receiving haemodialysis (HD) or peritoneal dialysis (PD). Three questionnaires were administered: the Bristol Stool Form Scale (BSFS); a modified Gastrointestinal Symptom Rating Scale and a short Food Frequency Questionnaire. Outcomes were stool frequency and consistency, GI symptoms and dietary intake. RESULTS: Data were collected from 216 patients (mean age, 63 years [95% CI: 61, 65]; 63% males; CKD-ND: n = 134; HD: n = 67; PD: n = 15). Mean stool frequency for all groups was one bowel action per day (p = .45) and consistency was normal (BSFS type 4, p = .95). Overall GI symptom burden was low but several symptoms occurred at least "most of the time" including "tiredness/lethargy" (54% of participants), "reduced appetite" (29%), "early satiety" (25%) and "change in taste" (15%). Low intakes of fresh fruit, vegetables, whole-grains and legumes were found. No associations were observed between diet and GI symptoms. CONCLUSION: The overall GI symptom burden was low, but >15% of participants reported several symptoms as occurring most to all of the time. Low intakes of fresh fruit, vegetables, whole-grains and legumes were observed in all CKD patients.

Arginine Metabolites as Biomarkers of Myocardial Ischaemia, Assessed with Cardiac Magnetic Resonance Imaging in Chronic Kidney Disease.

(1) Background: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Myocardial oxygenation and perfusion response to stress, using oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) and stress T1 mapping respectively, are impaired in CKD patients with and without known coronary artery disease (CAD). Endothelial dysfunction, assessed by circulating levels of asymmetric dimethylarginine (ADMA) and homoarginine (HMA), promotes atherosclerosis. We hypothesized that in CKD patients, worsening endothelial dysfunction is associated with worsening myocardial oxygenation and perfusion as assessed by change in OS-CMR signal intensity (Δ OS-CMR SI) and stress T1 (ΔT1) values. (2) Methods: 38 patients with advanced CKD underwent cardiovascular magnetic resonance (CMR) scanning at 3 Tesla. OS-CMR and T1 mapping images were acquired both at rest and after adenosine stress and analyzed semi-quantitatively. Serum ADMA and HMA concentrations were assessed using mass spectrometry. (3) Results: There was no significant correlation between Δ OS-CMR SI and ADMA or HMA. Interestingly, there was a significant negative correlation seen between Δ T1 and ADMA (r = -0.419, p = 0.037, n = 30) but not between Δ T1 and HMA. (4) Conclusions: Stress T1 response is impaired in CKD patients and is independently associated with higher circulating ADMA concentrations.

Long-Term Impact of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients: A 5-Year Follow-Up Observational Cohort Study.

Background: The long-term effects of arteriovenous fistula (AVF) ligation on cardiovascular structure following kidney transplantation remain uncertain. A prospective randomized, controlled trial (RCT) examined the effect of AVF ligation at 6 months on cardiovascular magnetic resonance imaging (CMR)-derived parameters in 27 kidney transplant recipients compared with 27 controls. A mean decrease in left ventricular mass (LVM) of 22.1 g (95% CI, 15.0 to 29.1) was observed compared with an increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group (P<0.001). We conducted a long-term follow-up observational cohort study in the treated cohort to determine the evolution of CMR-derived parameters compared with those documented at 6 months post-AVF ligation. Methods: We performed CMR at long-term follow-up in the AVF ligation observational cohort from our original RCT published in 2019. Results were compared with CMR at 6 months postintervention. The coprimary end point was the change in CMR-derived LVM and LVM index at long-term follow-up from imaging at 6 months postindex procedure. Results: At a median of 5.1 years (interquartile range, 4.7-5.5 years), 17 patients in the AVF ligation group were studied with repeat CMR with a median duration to follow-up imaging of 5.1 years (IQR, 4.7-5.5 years). Statistically significant further reductions in LVM (-17.6±23.0 g, P=0.006) and LVM index (-10.0±13.0 g/m2, P=0.006) were documented. Conclusions: The benefit of AVF ligation on LVM and LVM index regression appears to persist long term. This has the potential to lead to a significant reduction in cardiovascular mortality.

A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD).

BACKGROUND: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism. RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings. CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.

BK virus-associated nephropathy in a lung transplant patient: case report and literature review.

BACKGROUND: BK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from reactivation of the latent and usually harmless BK virus (BK virus) due to immunosuppression and other factors including some that are unique to renal transplantation such as allograft injury. BKVAN is much rarer in non-renal solid organ transplantation, where data regarding diagnosis and management are extremely limited. CASE PRESENTATION: We report a case of a 58-year-old man found to have worsening renal dysfunction nine months after bilateral sequential lung transplantation for chronic obstructive pulmonary disease (COPD). He had required methylprednisolone for acute allograft rejection but achieved good graft function. Urine microscopy and culture and renal ultrasound were normal. BK virus PCR was positive at high levels in urine and blood. Renal biopsy subsequently confirmed BKVAN. The patient progressed to end-stage renal failure requiring haemodialysis despite reduction in immunosuppression, including switching mycophenolate for everolimus, and the administration of intravenous immunoglobulin (IVIG). CONCLUSIONS: This very rare case highlights the challenges presented by BK virus in the non-renal solid organ transplant population. Diagnosis can be difficult, especially given the heterogeneity with which BKV disease has been reported to present in such patients, and the optimal approach to management is unknown. Balancing reduction in immunosuppression against prevention of allograft rejection is delicate. Improved therapeutic options are clearly required.

Effects of Allopurinol on the Progression of Chronic Kidney Disease.

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).

Comprehensive evaluation of a prospective Australian patient cohort with suspected genetic kidney disease undergoing clinical genomic testing: a study protocol.

INTRODUCTION: Recent advances in genomic technology have allowed better delineation of renal conditions, the identification of new kidney disease genes and subsequent targets for therapy. To date, however, the utility of genomic testing in a clinically ascertained, prospectively recruited kidney disease cohort remains unknown. The aim of this study is to explore the clinical utility and cost-effectiveness of genomic testing within a national cohort of patients with suspected genetic kidney disease who attend multidisciplinary renal genetics clinics. METHODS AND ANALYSIS: This is a prospective observational cohort study performed at 16 centres throughout Australia. Patients will be included if they are referred to one of the multidisciplinary renal genetics clinics and are deemed likely to have a genetic basis to their kidney disease by the multidisciplinary renal genetics team. The expected cohort consists of 360 adult and paediatric patients recruited by December 2018 with ongoing validation cohort of 140 patients who will be recruited until June 2020. The primary outcome will be the proportion of patients who receive a molecular diagnosis via genomic testing (diagnostic rate) compared with usual care. Secondary outcomes will include change in clinical diagnosis following genomic testing, change in clinical management following genomic testing and the cost-effectiveness of genomic testing compared with usual care. ETHICS AND DISSEMINATION: The project has received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. All participants will provide written informed consent for data collection and to undergo clinically relevant genetic/genomic testing. The results of this study will be published in peer-reviewed journals and will also be presented at national and international conferences.

Effects of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients.

BACKGROUND: Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant. The persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodeling. The ability to reverse this maladaptive remodeling by ligation of this AVF is unknown. We conducted the first randomized controlled trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients. METHODS: In this randomized controlled trial, kidney transplant recipients (>12 months after transplantation with stable graft function) were randomized to AVF ligation or no intervention. All participants underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, left and right atrial areas, LV ejection fraction, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, cardiac output/index, brachial flows (ipsilateral to AVF), and pulmonary artery velocity. RESULTS: A total of 93 patients were screened, of whom 64 met the inclusion criteria and were randomized to the AVF ligation (n=33) or control (n=31) group. Fifty-four participants completed the study: 27 in the AVF ligation group and 27 in the control group. On the second cardiac magnetic resonance scan, a mean decrease of 22.1 g (95% CI, 15.0-29.1) was observed in LV mass in the AVF ligation group compared with a small increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group ( P<0.001). Significant decreases in LV end-diastolic volumes, LV end-systolic volumes, cardiac output, cardiac index, atrial volumes, and NT-proBNP were also seen in the AVF closure group ( P<0.01). No significant changes were observed in LV ejection fraction ( P=0.93) and pulmonary artery velocity ( P=0.07). No significant complications were noted after AVF ligation. No changes in estimated glomerular filtration rate or systolic and diastolic blood pressures were observed between cardiac magnetic resonance scans. CONCLUSIONS: Elective ligation of patent AVF in adults with stable kidney transplant function resulted in clinically significant reduction of LV myocardial mass. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au . Unique Identifier: ACTRN12613001302741.

End-stage renal failure is associated with impaired coronary microvascular function.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. Studies investigating the disproportionate burden of cardiovascular disease have occurred predominantly in the peripheral vasculature, often used noninvasive imaging modalities, and infrequently recruited patients receiving dialysis. This study sought to evaluate invasive coronary dynamic vascular function in patients with end-stage renal failure (ESRF). PATIENTS AND METHODS: Patients referred for invasive coronary angiography prior to renal transplantation were invited to participate. Control patients were recruited in parallel. Baseline characteristics were obtained. Coronary diameter (via quantitative coronary angiography) and coronary blood flow (via Doppler Flowire) were measured; macrovascular endothelial-dependent and independent effects were evaluated in response to intracoronary acetylcholine infusion (10 and 10 mol/l) and intracoronary glyceryl trinitrate, respectively. Microvascular function was evaluated by response to adenosine and expressed as coronary flow velocity reserve. Mean values were compared. RESULTS: Thirty patients were evaluated: 15 patients with ESRF (mean age 52.1 ± 9, male 73%) and 15 control patients (mean age 53.3 ± 13, male 60%). Comorbidity profile, aside from ESRF, was well matched. Baseline coronary blood flow was similar between groups (101.6 ± 10.3 vs. 103.4 ± 9.1 ml/min, P = 0.71), as was endothelial-dependent response to acetylcholine (159.1 ± 16.9 vs. 171.1 ± 16.8 ml/min, P = 0.41). Endothelial-independent response to glyceryl trinitrate was no different between groups (14.3 ± 3.1 vs. 13.1 ± 2.3%, P = 0.73. A significantly reduced coronary flow velocity reserve was observed in the ESRF cohort compared to controls (2.34 ± 0.4 vs. 3.05 ± 0.3, P = 0.003). CONCLUSION: Patients with ESRF had preserved endothelial-dependent function however compared to controls, demonstrated significantly attenuated microvascular reserve. An impaired response to adenosine may not only represent a component of the pathophysiological milieu in patients with ESRF but may also provide a basis for the suboptimal diagnostic performance of vasodilatory stress in this population.

Do arteriovenous fistulas increase cardiac risk?

An effectively functioning arteriovenous fistula is the life line for patients on long-term hemodialysis, and for most an upper limb, native vessel fistula has significant short- and long-term advantages. There are, however, situations where a fistula has deleterious effects, including the relatively uncommon problem of severe heart failure exacerbated in particular by high-flow fistulas. There is also increasing evidence that a fistula can add to the already high burden of cardiovascular risk in patients with advanced kidney disease, including by promoting water and salt retention, and by inducing or worsening left ventricular hypertrophy. While cases periodically arise where a fistula needs to be ligated with some urgency, such as severe heart failure, an increasingly persuasive case can be made for electively ligating fistulas that are not being used. The most common example of this is in stable renal transplant recipients, where the risks of ligation are outweighed by the potential risks of maintaining an unused fistula. Surgically reducing the blood flow in large (usually upper arm) fistulas is also a legitimate maneuver in specific high-risk situations.

Gastrointestinal symptoms in patients receiving dialysis: A systematic review.

AIM: The aim of the present study was to describe the prevalence of all gastrointestinal (GI) symptoms reported by dialysis patients, as well as the tools being used for diagnosis. GI symptoms are commonly reported in patients having haemodialysis (HD) and peritoneal dialysis (PD), but there are multiple definitions and assessment tools reported in the literature. METHODS: A comprehensive systematic review was undertaken using five databases (Embase, Medline, CINAHL, Psycinfo and Web of Science) between 1996 and 2017. Articles were critically appraised using the Newcastle Ottawa Scale (NOS). Data collected were analyzed in a Microsoft Excel spreadsheet. RESULTS: Thirty studies (24 cross-sectional, six cohort) met the inclusion criteria. In total 5161 patients were studied (3804 HD and 1507 PD). Fifteen studies included HD, five included PD and 10 included both dialysis modalities. GI symptoms were heterogeneous, with the reported prevalence highly dependent on the definitions used, inclusion/exclusion criteria, assessment tools and methods used. The most prevalent symptoms were constipation, indigestion, abdominal pain and reflux. Medication use and dietary data were poorly reported. The most common tools used were Gastrointestinal Symptom Rating Scale (GSRS), Rome II and Rome III. Constipation was more common in HD patients than PD patients. Indigestion, abdominal pain and reflux were commonly reported in both dialysis modalities. CONCLUSIONS: Gastrointestinal symptoms are highly prevalent in people on dialysis; however, the evidence base is limited and further investigation of preventable causes and potential interventions such as medications and diet are required in future research.

Bowel health in chronic kidney disease: Patient perceptions differ from clinical definitions.

BACKGROUND: The bowel health of those with chronic kidney disease (CKD) can be affected by medications, fluid/dietary allowances, reduced activity and pre-existing medical conditions. Patient perceptions of their bowel health can differ from those of health care professionals and the burden of gastrointestinal symptoms could be inaccurately reported. METHODS: Adults with CKD, including those undergoing haemodialysis, peritoneal dialysis and kidney transplant from four South Australian hospitals enrolled in the study. Participants completed a five-item questionnaire, to investigate their perception of bowel health compared with clinical criteria for 'normal and abnormal' bowel health using the Bristol Stool Form Scale, bowel frequency and reported symptoms. RESULTS: A total of 324 individuals completed the questionnaire. Of those with clinically defined 'abnormal' bowel health (n = 180), 50.6% perceived their bowels as 'normal' or 'more normal than abnormal'. Only 6% of this clinically 'abnormal' group perceived their bowel health as abnormal. Of those with clinically defined 'normal' bowel health (n = 144), 16% perceived their bowel health as 'abnormal', 'more abnormal than normal' or 'variable'. Fifty-seven percent of patients with clinically defined 'abnormal' bowel health were not taking any treatments. Peritoneal dialysis recipients were the highest users of treatments to improve bowel function, with 62% using 1 or more treatment. CONCLUSIONS: It is common for patients with CKD to experience signs and symptoms of abnormal bowel health. There is a disconnect between patient perceptions and clinical definitions of normal or abnormal bowel health. Clinical care team members must carefully obtain and clarify patient-reported symptoms related to bowel function in order to help ensure recommendations and use of appropriate treatments.

Developing the future Indigenous health workforce: The feasibility and impact of a student-led placement programme in remote Indigenous communities.

OBJECTIVE: To describe and evaluate a programme where medical students designed and implemented Indigenous health placements for students with an interest in rural/Indigenous health. DESIGN, SETTING AND PARTICIPANTS: In 2011, a student-led programme at the University of Adelaide was set up to give medical students the opportunity to undertake outreach trips and clinical placements in remote Indigenous communities. Twenty-four medical students attended trips to remote communities between 2012 and 2014. Here we evaluate our programme using a single-arm experimental design. MAIN OUTCOME MEASURES: Responses to questionnaire items before and after attending an outreach placement, scored on 6-point Likert scales. RESULTS: Following their remote Indigenous health placement, participants expressed a significantly higher mean likelihood of working in an Indigenous community in the future (3.17 (2.69-3.64) versus 4.00 (3.65-4.35); P < 0.007). Furthermore, after their placement participants felt better prepared to work in Indigenous communities (mean 1.79 (1.44-2.14) versus 3.21 (2.88-3.54); P < 0.001). CONCLUSIONS: A placement programme initiated and run by medical students can provide meaningful exposure to Indigenous health. Implementation of this student-led model in other medical schools may encourage nationwide development of the Indigenous health workforce.

The Impact of Arteriovenous Fistulae for Hemodialysis on the Cardiovascular System.

An arteriovenous fistula (AVF) is critical for the provision of optimal chronic hemodialysis. Its creation causes significant hemodynamic alterations in cardiovascular parameters, and can result in progressive left and right heart failure. Despite successful kidney transplantation, many patients retain a functional AVF indefinitely, which may contribute to ongoing adverse cardiovascular outcomes. A similar high risk:benefit ratio may exist in peritoneal dialysis patients with "backup" AVF.

Nocardiosis presenting as a lung mass in a kidney transplant recipient.

Nocardiosis is a potentially life-threatening disease in renal transplant recipients. It is an uncommon infection with high lethality if left untreated. We report a case of a 67 year-old kidney transplant recipient who developed pulmonary nocardiosis and presented with pleural effusion along with an underlying lung mass, which was successfully treated with trimethoprim-sulphamethoxazole in conjunction with a reduction in immunosuppressive therapy. Five months later, graft function remains stable with complete regression of radiological abnormalities and absence of symptoms. Nocardiosis should be suspected in the presence of pulmonary symptoms in a transplant patient with unusual radiological presentation.