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Kidney transplantation in people living with HIV (PLWHIV) is occurring with increasing frequency. Limited international data suggest comparable patient and graft survival in kidney transplant recipients with and without HIV. All PLWHIV aged ≥18 years who received a kidney transplant between 2000 and 2020 were identified by retrospective data initially extracted from Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), with additional HIV-specific clinical data extracted from linked local health-care records. Twenty-five PLWHIV and kidney failure received their first kidney transplant in Australia between January 2000 and December 2020. Majority were male (85%), with median age 54 years (interquartile range, IQR 43-57). Focal segmental glomerulosclerosis was the most common primary kidney disease (20%), followed by polycystic kidney disease (16%). 80% of patients underwent induction with basiliximab and none with anti-thymocyte globulin (ATG). Participants were followed for median time of 3.5 years (IQR 2.0-6.5). Acute rejection occurred in 24% of patients. Two patients lost their allografts and three died. Virological escape occurred in 28% of patients, with a maximum viral load of 190 copies/mL. In conclusion, kidney transplantation in PLWHIV in Australia is occurring with increasing frequency. Acute rejection is more common than in Australia's general transplant population, but this does not appear to be associated with higher rates of graft failure or mortality out to four years.
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Infecções por HIV , Transplante de Rim , Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , HIV , Estudos Retrospectivos , Rejeição de Enxerto/prevenção & controle , Diálise Renal , Austrália/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Sobrevivência de EnxertoRESUMO
BACKGROUND: Disparities in aspects of chronic kidney disease progression and management exist for patients from culturally and linguistically diverse (CALD) backgrounds, including with treatment and outcomes for kidney transplantation. OBJECTIVE: This study aimed to explore factors that impact kidney transplant outcomes from the perspective of kidney transplant recipients (KTRs) from CALD backgrounds and their family caregivers. METHODS: A descriptive qualitative design was utilised. Participants were recruited from two tertiary hospitals in Victoria, Australia. Semi-structured interviews were conducted with KTRs who were born overseas in countries where English is not the primary language. Interviews were also conducted with family caregivers. Analysis was guided by the Framework Method, and emergent subcategories were mapped into the categories identified in Andersen's Health Service Utilisation Model. RESULTS: Data from 21 KTRs and five caregivers were grouped under the categories of Population Characteristics, Environment, Health Behaviour and Outcomes. KTRs believed that neither culture nor religious beliefs impacted how they managed their transplant or healthcare utilisation. KTRs expressed satisfaction with their care, felt no inequity with how they were treated by health professionals and expressed gratitude for the Australian healthcare system. Language did not necessarily impact transplant outcomes, but there was a reliance on interpreters for non-English-speaking patients as most written information was in English. Caregivers were instrumental in providing support but discussed the challenges involved. CONCLUSION: This study explored factors influencing kidney transplantation for KTRs from a CALD background. The study provided insight into how to deliver quality healthcare to these patients, highlighting the importance of health services providing information that is written in the patient's own language and respectively asking KTRs about their health beliefs or customs. Caregivers were instrumental in supporting KTRs, but there is a need to better prepare them for this role. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement was integrated into the design and delivery of the study. KTRs from CALD backgrounds assisted with framing the research questions and offering advice on the recruitment and data collection process.
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Transplante de Rim , Pesquisa Qualitativa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Vitória , Cuidadores/psicologia , Entrevistas como Assunto , Idioma , Idoso , Diversidade CulturalRESUMO
RATIONALE & OBJECTIVE: Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD. STUDY DESIGN: Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023. SETTING & STUDY POPULATIONS: Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded. SELECTION CRITERIA FOR STUDIES: RCTs with≥3 months of follow-up evaluating a vitamin D compound. DATA EXTRACTION: Data were extracted independently by three investigators. ANALYTICAL APPROACH: Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE. RESULTS: Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium. LIMITATIONS: Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality. CONCLUSIONS: Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain. TRIAL REGISTRATION: Registered at PROSPERO with study number CRD42017057691. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.
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BACKGROUND: Calciprotein particles (CPPs), colloidal mineral-protein nanoparticles, have emerged as potential mediators of phosphate toxicity in dialysis patients, with putative links to vascular calcification, endothelial dysfunction and inflammation. We hypothesized that phosphate binder therapy with sucroferric oxyhydroxide (SO) would reduce endogenous CPP levels and attenuate pro-calcific and pro-inflammatory effects of patient serum towards human vascular cells in vitro. METHODS: This secondary analysis of a randomised controlled crossover study compared the effect of 2-week phosphate binder washout with high-dose (2000 mg/day) and low-dose (250 mg/day) SO therapy in 28 haemodialysis patients on serum CPP levels, inflammatory cytokine/chemokine arrays and human aortic smooth muscle cell (HASMC) and coronary artery endothelial cell (HCAEC) bioassays. RESULTS: In our cohort (75% male, 62 ± 12 years) high-dose SO reduced primary (amorphous) and secondary (crystalline) CPP levels {-62% [95% confidence interval (CI) -76 to -44], P < .0001 and -38% [-62 to -0.14], P < .001, respectively} compared with washout. Nine of 14 plasma cytokines/chemokines significantly decreased with high-dose SO, with consistent reductions in interleukin-6 (IL-6) and IL-8. Exposure of HASMC and HCAEC cultures to serum of SO-treated patients reduced calcification and markers of activation (IL-6, IL-8 and vascular cell adhesion protein 1) compared with washout. Serum-induced HASMC calcification and HCAEC activation was ameliorated by removal of the CPP-containing fraction from patient sera. Effects of CPP removal were confirmed in an independent cohort of chronic kidney disease patients. CONCLUSIONS: High-dose SO reduced endogenous CPP formation in dialysis patients and yielded serum with attenuated pro-calcific and inflammatory effects in vitro.
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Diálise Renal , Calcificação Vascular , Humanos , Masculino , Feminino , Diálise Renal/efeitos adversos , Interleucina-6 , Estudos Cross-Over , Interleucina-8 , Inflamação/tratamento farmacológico , Inflamação/etiologia , Citocinas/metabolismo , Calcificação Vascular/etiologia , Calcificação Vascular/prevenção & controle , FosfatosRESUMO
BACKGROUND: Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium-containing phosphate binders may reduce serum CPP in patients with kidney failure who require dialysis; however, it is unclear whether similar interventions are effective in patients with earlier stages of CKD. METHODS: The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) was a multi-centre, placebo-controlled, randomized trial of lanthanum carbonate on cardiovascular markers in 278 participants with stage 3b/4 CKD. In this pre-specified exploratory analysis, primary (CPP-I) and secondary CPP (CPP-II) were measured in a sub-cohort of participants over 96 weeks. Treatment groups were compared using linear mixed-effects models and the relationship between serum CPP and pulse wave velocity (PWV) and abdominal aortic calcification (AAC) was examined. RESULTS: A total of 253 participants had CPP data for baseline and at least one follow-up timepoint and were included in this analysis. The mean age was 62.4 ± 12.6 years, 32.0% were female and the mean estimated glomerular filtration rate (eGFR) was 26.6 ± 8.3 mL/min/1.73 m2. Baseline median serum CPP-I was 14.9 × 104 particles/mL [interquartile range (IQR) 4.6-49.3] and median CPP-II was 3.3 × 103 particles/mL (IQR 1.4-5.4). There was no significant difference between treatment groups at 96 weeks in CPP-I [22.8% (95% confidence interval -39.2, 36.4), P = 0.65] or CPP-II [-18.3% (95% confidence interval -40.0, 11.2), P = 0.20] compared with a placebo. Serum CPP were not correlated with baseline PWV or AAC, or with the progression of either marker. CONCLUSIONS: Lanthanum carbonate was not associated with a reduction of CPP at 96 weeks when compared with a placebo in a CKD cohort.
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Lantânio , Insuficiência Renal Crônica , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Lantânio/uso terapêutico , Análise de Onda de Pulso , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Fosfatos de CálcioRESUMO
BACKGROUND: Tunnelled central venous catheters (T-CVCs) are used globally as vascular access for patients on haemodialysis (HD) but are associated with increased sepsis, mortality, cost and length of hospitalisation compared with more permanent HD vascular access. The reasons for using T-CVC are varied and poorly understood. A significant and increasing proportion of incident HD patients in Victoria, Australia, have required T-CVC over the last decade. AIM: To explore reasons for a significant and increasing proportion of incident HD patients in Victoria, Australia, having required T-CVC over the last decade. METHODS: With rates of starting HD with definitive vascular access consistently below a Victorian quality indicator target of 70%, an online survey was developed to explore reasons why the rate remained lower than desired and to help inform future decisions about this quality indicator. The survey was completed by dialysis access coordinators over an 8-month period and involved all public nephrology services in Victoria. RESULTS: Of the 125 surveys completed, 101 incident HD patients had no attempt at permanent vascular access prior to T-CVC insertion. For almost half of these (48 patients), there was no active medical decision not to create permanent vascular access prior to commencing dialysis. Reasons for insertion of the T-CVC included deterioration of kidney function faster than anticipated, surgical referral being overlooked, complications related to peritoneal dialysis requiring a change in dialysis modality and changes to initial decisions regarding dialysis modality for kidney failure. CONCLUSIONS: These survey results provide an opportunity for quality improvement initiatives with respect to dialysis access planning and care.
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Cateteres Venosos Centrais , Falência Renal Crônica , Diálise Peritoneal , Humanos , Cateteres Venosos Centrais/efeitos adversos , Diálise Renal/efeitos adversos , Diálise Peritoneal/efeitos adversos , Vitória/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapiaRESUMO
BACKGROUND: There is increasing global incidence of acute kidney injury (AKI) and significant short- and long-term impacts on patients. AIMS: To determine incidence and outcomes of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) among inpatients in the Australian healthcare setting using modern health information systems. METHODS: A retrospective cohort study of adult patients admitted to a quaternary hospital in Melbourne, Australia, between 1 January 2018 and 31 December 2019 utilising an electronic data warehouse. Participants included adult patients admitted for >24 h who had more than one serum creatinine level recorded during admission. Kidney transplant and maintenance dialysis patients were excluded. Main outcomes measured included AKI, as classified by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, hospital length of stay and 30-day mortality. RESULTS: A total of 6477 AKI episodes was identified across 43 791 admissions. Of all AKI episodes, 77% (n = 5011), 15% (n = 947) and 8% (n = 519) were KDIGO stage 1, 2 and 3 respectively. HA-AKI accounted for 55.9% episodes. Patients required intensive care unit admission in 22.7% (n = 1100) of CA-AKI and 19.3% (n = 935) of HA-AKI, compared with 7.5% (n = 2815) of patients with no AKI (P = 0.001). Patients with AKI were older with more co-morbidities, particularly chronic kidney disease (CKD). Length of stay was longer in CA-AKI (8.8 days) and HA-AKI (11.8 days) compared with admissions without AKI (4.9 days; P < 0.001). Thirty-day mortality was increased with CA-AKI (10.2%) and HA-AKI (12.8%) compared with no AKI (3.7%; P < 0.001). CONCLUSION: The incidence of AKI detected by the electronic data warehouse was higher than previously reported. Patients who experienced AKI had greater morbidity and mortality. CKD was an important risk factor for AKI in hospitalised patients.
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Injúria Renal Aguda , Insuficiência Renal Crônica , Adulto , Humanos , Tempo de Internação , Estudos Retrospectivos , Incidência , Mortalidade Hospitalar , Austrália/epidemiologia , Fatores de Risco , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Encaminhamento e Consulta , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , HospitaisRESUMO
AIM: Previous studies report an association between longer haemodialysis treatment sessions and improved survival. Worldwide, there is a trend to increasing age among prevalent patients receiving haemodialysis. This analysis aimed to determine whether the mortality benefit of longer haemodialysis treatment sessions diminishes with increasing age. METHODS: This was a retrospective cohort study of people who first commenced thrice-weekly haemodialysis aged ≥65 years, reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry from 2005 to 2015, included from 90 days after dialysis start. The primary outcome was all-cause mortality. Cox regression analysis was performed with haemodialysis session duration the exposure of interest. RESULTS: Of 8224 people who commenced haemodialysis as their first treatment for kidney failure aged ≥65 years during this period, 4727 patients died. Longer dialysis hours per session was associated with a decreased risk of death in unadjusted analyses [hazard ratio, HR, for ≥5 h versus 4 to <4.5 h: 0.81 (0.75-0.88, p < .001)]. Patients having longer dialysis sessions were younger but had greater co-morbidity. In an adjusted model including age and other variables, the survival benefit of longer hours was only partially attenuated [HR for previous comparison: 0.75 (0.69-0.82, p < .001)], and no interaction between age and hours was demonstrated (p = .89). CONCLUSION: The apparent survival benefit associated with longer haemodialysis session length appears to be preserved in patients 65 years or older. In practice, the benefit of longer dialysis hours should be carefully weighed against other factors in this patient group.
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Falência Renal Crônica , Diálise Renal , Humanos , Idoso , Diálise Renal/efeitos adversos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Falência Renal Crônica/epidemiologia , Estudos Retrospectivos , Comorbidade , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in CKD remain uncertain. METHODS: We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compared with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiologic methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. RESULTS: There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal. CONCLUSIONS: Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.
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Insuficiência Renal Crônica , Calcificação Vascular , Feminino , Humanos , Magnésio , Masculino , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/terapia , Calcificação Vascular/etiologiaRESUMO
BACKGROUND: Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of noncalcium-based phosphate-lowering treatment in nondialysis CKD. METHODS: We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared with placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow-up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik-Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes with common measurement units and Hedge's g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence. RESULTS: In total, 20 trials involving 2498 participants (median sample size 120, median follow-up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, noncalcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37; 95% CI, -0.58 to -0.15 mg/dl, low certainty evidence) and urinary phosphate excretion (eight trials, SMD -0.61; 95% CI, -0.90 to -0.31, low certainty evidence), but resulted in increased constipation (nine trials, log odds ratio [OR] 0.93; 95% CI, 0.02 to 1.83, low certainty evidence) and greater vascular calcification score (three trials, SMD, 0.47; 95% CI, 0.17 to 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR, 0.51; 95% CI, -0.51 to 1.17) and death were scant. CONCLUSIONS: Noncalcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.
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Hiperfosfatemia/prevenção & controle , Fosfatos/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Quelantes/uso terapêutico , Compostos Férricos/uso terapêutico , Humanos , Hiperfosfatemia/etiologia , Lantânio/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Sevelamer/uso terapêuticoRESUMO
BACKGROUND: Surgical parathyroidectomy may be required for severe and refractory secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD). Parathyroidectomy is associated with long-term survival benefit despite an increase in short-term morbidity and mortality. Global variation in practice exists, with limited Australian data on outcomes following parathyroidectomy. AIM: To evaluate clinical outcomes of patients with chronic kidney disease undergoing surgical parathyroidectomy for secondary hyperparathyroidism. METHODS: We conducted a retrospective study of patients who underwent parathyroidectomy for SHPT between January 2010 and December 2019 at a single tertiary referral centre in Melbourne, Australia. Biochemical markers and medications were assessed 12 months pre- and post-surgery. Clinical outcomes, including hospital readmission, cardiovascular events and mortality were assessed following surgery. RESULTS: During the 10-year study period, 129 patients underwent parathyroidectomy for SHPT (mean age 50.7 ± 15 years; 109 (85%) on dialysis). Significant immediate post-operative complications were seen in eight (6%) patients, requiring admission to the intensive care unit (n = 6) or return to theatre (n = 2). Within the first 6 months, 24 (19%) patients required hospital readmission. Within 12 months post-parathyroidectomy, 100 (78%) and 103 (80%) patients experienced at least one episode of hypercalcaemia (corrected calcium >2.6 mmol/L) or hypocalcaemia (corrected calcium <2.1 mmol/L) respectively. Over a 12-month period, there were six (5%) deaths and eight (6%) patients experienced a major cardiovascular event. CONCLUSION: Significant fluctuations in serum calcium levels are common post-parathyroidectomy; however, long-term morbidity and mortality in our cohort were lower than previously reported, highlighting that parathyroidectomy in a carefully selected cohort is safe for severe SHPT refractory to medical treatment.
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Hiperparatireoidismo Secundário , Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Paratireoidectomia/efeitos adversos , Cálcio , Hormônio Paratireóideo , Estudos Retrospectivos , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Austrália/epidemiologia , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologiaRESUMO
BACKGROUND: Survivors of acute kidney injury (AKI) are at increased risk of major adverse kidney events and international guidelines recommend individuals be evaluated 3 months following AKI. AIM: We describe practice patterns and predictors of post-AKI care in an Australian tertiary hospital. METHODS: A retrospective analysis was undertaken of adults with AKI (defined by KDIGO criteria) admitted to a single centre between 2012 and 2016. The primary outcome was outpatient nephrology review at 3 months. Secondary outcomes included inpatient nephrology review, and outpatient serum creatinine and urinary protein measurements. Data were analysed using multivariable logistic and competing risk regression. RESULTS: Only 117 of 2111 (6%) patients with AKI were reviewed by a nephrologist at 3 months. Reviewed patients were more likely to have a higher discharge serum creatinine (odds ratio (OR) 1.20 per 10 µmol/L increase; 95% confidence interval (CI) 1.16-1.25) or a history of peripheral vascular disease (OR 1.77; 95% CI 1.00-3.14). They were less likely to be older (OR 0.66 per decade; 95% CI 0.57-0.76) or to have a history of liver (OR 0.47; 95% CI 0.26-0.87) or ischaemic heart (OR 0.50; 95% CI 0.27-0.94) disease. AKI stage did not predict follow up. The median time from discharge to outpatient serum creatinine testing was 12 days (interquartile range 4-47) and proteinuria was measured in 538 (25%) patients. CONCLUSIONS: A minority of admitted AKI patients receive recommended post-AKI care. Studies in other Australian institutions are required to confirm or refute these concerning findings.
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Injúria Renal Aguda , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Adulto , Assistência Ambulatorial , Austrália/epidemiologia , Atenção à Saúde , Humanos , Estudos RetrospectivosRESUMO
Excess sodium is a major modifiable contributor to hypertension and cardiovascular risk. Knowledge of sodium storage and metabolism has derived mainly from indirect measurements of dietary sodium intake and urinary sodium excretion, however both attempt to measure body sodium and fluid in a two-compartment model of intracellular and extracellular spaces. Our understanding of total body sodium has recently included a storage pool in tissues. In the last two decades, sodium-23 magnetic resonance imaging (23 Na MRI) has allowed dynamic quantification of tissue sodium in vivo. Tissue sodium is independently associated with cardiovascular dysfunction and inflammation. This review explores (i) The revolution of our understanding of sodium physiology, (ii) The development and potential clinical adoption of 23 Na MRI to provide improved measurement of total body sodium in CKD and (iii) How we can better understand mechanistic and clinical implications of tissue sodium in hypertension, cardiovascular disease and immune dysregulation, especially in the CKD population.
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Imageamento por Ressonância Magnética , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/metabolismo , Sódio/análise , Sódio/metabolismo , HumanosRESUMO
OBJECTIVES: High dietary phosphate intake may lead to adverse outcomes including cardiovascular disease (CVD). Urinary phosphate excretion, a marker of intestinal phosphate absorption, may be a more reliable marker of phosphate homeostasis in steady state than serum phosphate. Studies report good agreement between urine phosphate-to-creatinine ratio (uPiCr) and 24-hour urinary phosphate; however, whether uPiCr is associated with increased risk of CVD or mortality remains uncertain. This study aimed to assess the relationship between uPiCr and all-cause and CVD mortality. DESIGN AND METHODS: This is an observational longitudinal cohort study using data from the population-based national Australian Diabetes, Obesity and Lifestyle study (n = 10,014 participants). Non-linear association between uPiCr and all-cause and CVD mortality was assessed using fractional polynomial transformations. Cox proportional hazards regression models were used to estimate adjusted hazard ratios for all-cause and CVD mortality. RESULTS: Median age [interquartile range] was 50 [41-62] years, and 46% were male. Median uPiCr was 1.38 [1.02-1.79] mmol/mmol. Median follow-up time was 16.9 years with 1,735 deaths. uPiCr was associated with all-cause and CVD mortality in univariate models and when adjusted for age and gender. However, associations were not significant in multivariate models. Sensitivity analyses excluding participants with chronic kidney disease (CKD) revealed a significant J-shaped association between uPiCr and all-cause mortality. Urine phosphate alone showed an association with increased all-cause mortality in a similar J-shape relationship. CONCLUSION: Although no association between uPiCr and all-cause and CVD mortality was observed in multivariate analyses in the whole cohort, a significant relationship between uPiCr and mortality in those without CKD suggests that uPiCr may have predictive validity for future adverse outcomes in people with no CKD.
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Doenças Cardiovasculares , Insuficiência Renal Crônica , Austrália/epidemiologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fosfatos , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Fatores de RiscoRESUMO
OBJECTIVE: Higher serum phosphate is associated with increased adverse outcomes including cardiovascular disease. Abnormalities of bone and mineral metabolism in chronic kidney disease (CKD), including higher serum phosphate, are important risk factors for increased cardiovascular disease. Associations between dietary phosphate intake and biochemical and cardiovascular parameters in non-dialysis CKD patients, however, have not been adequately studied. This study aimed to explore associations between phosphate intake and biomarkers of bone and mineral metabolism and intermediate cardiovascular markers in adults with stage 3-4 CKD. DESIGN AND METHODS: One hundred thirty-two participants enrolled in the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease trial were invited to participate in this sub-study. At baseline, dietary phosphate intake and its source (animal, plant, or a mixture of animal and plant) were determined using a 7-day self-administered diet food record, and measurements were made of serum and urinary phosphate, serum calcium, parathyroid hormone, fibroblast growth factor-23, and the intermediate cardiovascular markers pulse wave velocity (PWV) and abdominal aortic calcification. The relationships between dietary phosphate intake and these bone metabolism and cardiovascular markers were explored using Pearson's correlation and linear regression. The effect of source of phosphate intake was analyzed using compositional data analysis. RESULTS: Ninety participants (age 64 ± 12 years, 68% male, estimated glomerular filtration rate 26.6 ± 7.6 mL/min/1.73 m2, daily phosphate intake 1,544 ± 347 mg) completed the study. Correlations among dietary phosphate intake and biochemical measures, PWV, and abdominal aortic calcification ranged from r = -0.13 to r = +0.13. Linear regression showed no association between dietary phosphate measurements and biochemical or cardiovascular parameters. Source of phosphate intake was associated with PWV (P = .01), but not with other biomarkers of bone and mineral metabolism. Higher PWV values were associated with higher intake of plant-based relative to animal-based phosphate (1.058 [1.020-1.098], P = .003). CONCLUSION: Levels of total dietary phosphate intake measured by dietary food record show no statistically significant relationship with biochemical markers of bone and mineral metabolism or intermediate cardiovascular markers. Higher PWV levels associated with higher intake of plant-based relative to animal-based phosphate intake were an unexpected finding and further research is needed in this area.
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Fosfatos , Insuficiência Renal Crônica , Idoso , Austrália , Biomarcadores , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Pessoa de Meia-Idade , Minerais , Análise de Onda de PulsoRESUMO
INTRODUCTION: Acute kidney diseases and disorders (AKD) encompass acute kidney injury (AKI) and subacute or persistent alterations in kidney function that occur after an initiating event. Unlike AKI, accurate estimates of the incidence and prognosis of AKD are not available and its clinical significance is uncertain. METHODS: We studied the epidemiology and long-term outcome of AKD (as defined by the KDIGO criteria), with or without AKI, in a retrospective cohort of adults hospitalized at a single centre for >24 h between 2012 and 2016 who had a baseline eGFR ≥60 mL/min/1.73 m2 and were alive at 30 days. In patients for whom follow-up data were available, the risks of major adverse kidney events (MAKEs), CKD, kidney failure, and death were examined by Cox and competing risk regression analyses. RESULTS: Among 62,977 patients, 906 (1%) had AKD with AKI and 485 (1%) had AKD without AKI. Follow-up data were available for 36,118 patients. In this cohort, compared to no kidney disease, AKD with AKI was associated with a higher risk of MAKEs (40.25 per 100 person-years; hazard ratio [HR] 2.51, 95% confidence interval [CI] 2.16-2.91), CKD (27.84 per 100 person-years); subhazard ratio [SHR] 3.18, 95% CI 2.60-3.89), kidney failure (0.56 per 100 person-years; SHR 24.84, 95% CI 5.93-104.03), and death (14.86 per 100 person-years; HR 1.52, 95% CI 1.20-1.92). Patients who had AKD without AKI also had a higher risk of MAKEs (36.21 per 100 person-years; HR 2.26, 95% CI 1.89-2.70), CKD (22.94 per 100 person-years; SHR 2.69, 95% CI 2.11-3.43), kidney failure (0.28 per 100 person-years; SHR 12.63, 95% CI 1.48-107.64), and death (14.86 per 100 person-years; HR 1.57, 95% CI 1.19-2.07). MAKEs after AKD were driven by CKD, especially in the first 3 months. CONCLUSIONS: These findings establish the burden and poor prognosis of AKD and support prioritisation of clinical initiatives and research strategies to mitigate such risk.
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Nefropatias/epidemiologia , Doença Aguda , Injúria Renal Aguda/complicações , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Calciphylaxis is a rare disease, predominantly affecting patients with chronic kidney disease (CKD) and associated with significant morbidity and mortality due to progressive cutaneous calcification, necrotic ulceration and infection. Clinical registries have been established to better understand the risk factors, optimal treatments and disease outcomes of calciphylaxis. METHODS: We established a prospective, Internet-based clinical registry for the online notification of calciphylaxis cases in Australia. Seven institutions participated, with data recorded on patient characteristics, biochemical parameters, treatments and disease outcomes. RESULTS: Between 2014 and 2019, 47 cases of calciphylaxis were registered. The mean patient age was 66 ± 11 years and body mass index was 35 ± 9 kg/m2, with a higher proportion of females (51%). Eighty-seven percent of patients had end-stage kidney disease (ESKD), with 61% on hemodialysis or hemodiafiltration, with a median dialysis vintage of 4.8 [interquartile range (IQR) 1.7-7.4)] years. Five patients had CKD not requiring dialysis and two were kidney transplant recipients. Diabetes was present in 76% of patients and the cause of ESKD in 60%; 34% received vitamin K antagonists (VKAs) before diagnosis. The median parathyroid hormone level at diagnosis was 32 (IQR 14-50) pmol/L. The most common site of calciphylaxis was the lower limbs (63%), with 19% of patients having more than one area involved. Ten patients (22%) had a resolution of calciphylaxis and 25 died, with 50% mortality at a median of 1.6 (IQR 0.2-2.5) years from diagnosis. CONCLUSIONS: The Australian Calciphylaxis Registry highlights risk factors for calciphylaxis, including diabetes, obesity and VKA use. Resolution of calciphylaxis is uncommon despite multimodal therapy and mortality from calciphylaxis in the first year following diagnosis remains high.
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Calciofilaxia/mortalidade , Falência Renal Crônica/complicações , Sistema de Registros/estatística & dados numéricos , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Idoso , Austrália/epidemiologia , Calciofilaxia/diagnóstico , Calciofilaxia/epidemiologia , Calciofilaxia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
AIM: Hyperphosphataemia is associated with increased adverse outcomes, including mortality. Re-examining this association using up-to-date data reflecting current and real-world practices, across different global regions and in both haemodialysis and peritoneal dialysis patients, is important. METHODS: We describe the association between serum phosphate and all-cause and cardiovascular mortality in incident dialysis patients between 2008 and 2018 using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Time-dependent Cox proportionate hazards models were used. Models were adjusted for available covariates and fitted for the overall cohort, and also each dialysis modality. RESULTS: 31 989 patients were followed over 97 122 person-years at risk (mean age at first dialysis 61 years, 38% female, 67% haemodialysis). We observed a U-shaped association between serum phosphate and all-cause mortality. In the fully adjusted model, categories of serum phosphate above and below 1.25-1.99 mmol/L were associated with progressively higher risk, reaching a hazard ratio of 2.13 (95% CI 1.93-2.36, p < .001) for serum phosphate ≥2.75 mmol/L, and 1.56 (95% CI 1.44-1.69, p < .001) for serum phosphate <1.00 mmol/L. Low and high levels of serum phosphate were also associated with increased risk of cardiovascular mortality, however the association with high serum phosphate was more pronounced ("J-shaped relationship"). The associations were consistent across sub-analyses of patients receiving haemodialysis and peritoneal dialysis treatment. CONCLUSION: In this large contemporary dialysis cohort, both high and low levels of serum phosphate were independently associated with increased risk of mortality. Future studies are required to determine whether treatment of abnormal serum phosphate levels improves mortality.
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Hiperfosfatemia/sangue , Fosfatos/sangue , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Austrália/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Hiperfosfatemia/diagnóstico , Hiperfosfatemia/mortalidade , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/mortalidade , Sistema de Registros , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Dietary phosphate modification is a common therapy to treat hyperphosphatemia in individuals with chronic kidney disease (CKD). However, current dietary intake and common food sources of phosphate typically consumed by individuals with CKD are not well characterized. This study examined a cohort of CKD patients to determine total dietary intake and common food sources of phosphate, including phosphate additives. DESIGN AND METHODS: Participants with CKD stages 3b and 4 recruited to a substudy of the "IMPROVE-CKD (IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease) Study" completed a 7-day self-administered diet record at baseline. Diet histories were analyzed and daily phosphate intakes determined using FoodWorks V.9 (Xyris). The proportion of phosphate contributed by each food group was determined using the AUSNUT 2011-2013 Food Classification System. Ingredient lists of packaged food items consumed were reviewed to determine frequency of phosphate-based additives. RESULTS: Ninety participants (mean eGFR 26.5 mL/min/1.73 m2) completed this substudy. Mean phosphate intake of participants was 1544 ± 347 mg/day, with 96% of individuals exceeding the recommended daily intake of phosphate (1000 mg/day). The highest sources of dietary phosphate were milk-based products (25%) and meat and poultry products/dishes (25%). Phosphate-based food additives were identified in 39% (n = 331/845) of packaged foods consumed by participants. CONCLUSION: Dietary phosphate intakes of Australians with CKD are high and come from a variety of sources. Managing dietary phosphate intake requires a patient-centered, tailored approach with an emphasis on maintaining nutritional adequacy and awareness of phosphate additives.
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Hiperfosfatemia , Insuficiência Renal Crônica , Austrália , Dieta , Humanos , FosfatosRESUMO
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.