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.).

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.

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.

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.

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.

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.

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.

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.

Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis.

BACKGROUND: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes. METHODS: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis. RESULTS: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events. CONCLUSIONS: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.

Beneficial cardiovascular remodeling following arterio-venous fistula ligation post-renal transplantation: a longitudinal magnetic resonance imaging study.

Despite improvements in survival following renal transplantation, high rates of cardiovascular morbidity and mortality remain. Persistence of arterio-venous fistulae (AVF) may contribute to maladaptive cardiovascular remodeling and poor health outcomes in this cohort. Utilizing recent advances in cardiovascular magnetic resonance imaging (CMR), we prospectively evaluated alterations in cardiac and vascular structure and function six months after elective ligation of AVF, following stable, successful renal transplantation. Eighteen subjects underwent CMR evaluation of cardiac structure and function, aortic distensibility and endothelial function prior to AVF ligation and at six months. At follow-up, while left ventricular ejection fraction was unchanged, mean cardiac output decreased by 15.6% (9.6 ± 2.9 L/min vs. 8.1 ± 2.3 L/min, p = 0.004) and left ventricular mass had regressed by 10% (166 ± 56 g vs. 149 ± 51 g, p = 0.0001). Significant improvements were also noted in right ventricular and biatrial structure and function. Aortic distensibility was unchanged at follow-up, but endothelial dependent vasodilatation had improved (2.5 ± 6.5% vs. 8.0 ± 5.9%, p = 0.04). Elective AVF ligation following successful renal transplantation is associated with improvements in left ventricular mass, right ventricular, and biatrial structure and function. Further randomized studies are warranted to determine the potential clinical improvement following AVF ligation in this cohort.

Dramatic improvement in decompensated right heart failure due to severe tricuspid regurgitation following ligation of arteriovenous fistula in a renal transplant recipient.

Arteriovenous (AV) fistulas with high blood flow rate are necessary for adequate hemodialysis, but they can also cause significant hemodynamic changes, including raised cardiac output, left ventricular hypertrophy and occasionally overt cardiac failure (Basile et al., Nephrol Dial Transplant, 23, 2008, 282; Unger et al., Am J Transplant, 4, 2004, 2038). We now report a case of rapid and dramatic improvement in symptomatic right heart failure due to severe tricuspid regurgitation following ligation of an arteriovenous fistula. Cardiac magnetic resonance imaging (MRI) performed before and after the ligation of fistula showed striking improvement in both the tricuspid regurgitation and right ventricular dimensions, with minimal impact on left ventricular mass, size, and function.

Implementation and Evaluation of a National Multidisciplinary Kidney Genetics Clinic Network Over 10 Years.

Introduction: Diagnostic genomic sequencing is the emerging standard of care in nephrology. There is a growing need to scale up the implementation of genomic diagnostics nationally to improve patient outcomes. Methods: This pragmatic study provided genomic or genetic testing to patients with suspected monogenic kidney disease through a national network of kidney genetics clinics (KGCs). We sought to evaluate the experiences of implementing genomic diagnostics across Australia and associated diagnostic outcomes between 2013 and 2022. Results: We successfully established and expanded a nationwide network of 20 clinics as of 2022; concurrently developing laboratory, research, and education programs to scale the clinical application of genomics in nephrology. We report on an Australian cohort of 1506 kidney patients, of whom 1322 received their test results. We assessed barriers to implementation in the nephrology context, and where possible, applied real-time solutions to improve clinical processes over 10 years. Conclusion: Developing a multidisciplinary kidney genetics model across multiple health services nationally was highly successful. This model supported optimal care of individuals with monogenic kidney disease in an economically responsible way. It has continued to evolve with technological and service developments and is now set to scale further as genomic testing for kidney patients transitions to health care system funding.

Post-transplant plasmablastic lymphoma of the skin.

Plasmablastic lymphoma (PBL) is a recently described rare variant of diffuse large B-cell lymphoma characterised by its aggressive nature and plasmacytic differentiation. It most frequently arises in the oral cavity of human immunodeficiency virus (HIV)-infected patients. However extra-oral involvement is becoming increasingly recognised, particularly in HIV-negative patients. We report a case of PBL presenting as multiple violaceous nodules and plaques on the leg of a HIV-negative patient, 13-years post-renal transplant. To date, 20 cases of PBL presenting in the skin have been reported. We review and compare the clinico-pathological features of these cases.

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.

Calcium supplements lower bone resorption after renal transplant.

AIM: Bone loss in renal transplant (RT) patients is a problem that begins during end-stage kidney disease and persists after transplantation. Suppression of parathyroid hormone (PTH) may decrease bone loss and improve fracture rate. METHODS: A single-group prospective intervention study involving 30 patients was performed at a large RT unit. Investigations included dual-emission X-ray absorptiometry scan, vertebral X-ray, calcium absorption test, 24-h urinary calcium and serum measurements of total and ionized calcium, PTH, C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, 25 hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D3. Patients were given 500 mg elemental calcium daily for seven d, and serum measurements were repeated. RESULTS: Two-tailed Wilcoxon rank-sum test showed significant decreases in PTH (p<0.01) and CTX (p<0.01) after calcium load. Dietary calcium, mean calcium absorption, and urinary calcium excretion were below desirable levels. Mean 25 hydroxyvitamin D (25(OH)D) was low, but levels of 1,25-dihydroxyvitamin D3 were normal. Calcium absorption significantly correlated with change in PTH (p<0.001), baseline 25(OH)D (p<0.001), and mycophenolate dose (p=0.024). CONCLUSIONS: Calcium malabsorption is prevalent in RT recipients, contributing to bone destruction and compounded by poor dietary intake and low 25(OH)D. Calcium supplementation appears to help overcome this deficiency and acutely suppress PTH. Calcium may be an effective and inexpensive therapy for bone loss in RT recipients.

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.