RESUMO
A male aged in his mid-60s was diagnosed with xanthogranulomatous pyelonephritis after a left nephrectomy for a renal mass that was detected during the investigation of weight loss and drenching night sweats. Past medical history includes type 2 diabetes mellitus, transient ischaemic attack, hypertension, non-alcoholic fatty liver disease, dyslipidaemia, osteoarthritis and active smoking. Three years after the initial diagnosis, the patient represented with abdominal pain. CT imaging demonstrated new pulmonary and pancreatic lesions, which were histologically confirmed to be xanthogranulomatous disease. The patient was too unstable for surgical intervention so was commenced on glucocorticoids with marked improvement in his clinical condition with resolution of inflammatory markers and radiographic improvement. Weaning of prednisolone led to a relapse of disease, which was managed with re-introduction of high-dose prednisolone and the initiation of azathioprine. The patient is now 2 years post initiation of immunosuppressive therapy with stable renal function and no active inflammation.
Assuntos
Diabetes Mellitus Tipo 2 , Pielonefrite Xantogranulomatosa , Humanos , Masculino , Pielonefrite Xantogranulomatosa/diagnóstico , Pielonefrite Xantogranulomatosa/tratamento farmacológico , Pielonefrite Xantogranulomatosa/patologia , Nefrectomia/métodos , Terapia de Imunossupressão , Prednisolona/uso terapêuticoRESUMO
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.
Assuntos
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: 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.
Assuntos
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
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.
Assuntos
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.
Assuntos
Hiperfosfatemia/sangue , Lantânio/uso terapêutico , Fosfatos/sangue , Insuficiência Renal Crônica/sangue , Calcificação Vascular/diagnóstico por imagem , Idoso , Aorta Abdominal , Método Duplo-Cego , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Lantânio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/urina , Análise de Onda de Pulso , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
Chronic kidney disease (CKD) is associated with excess cardiovascular morbidity and mortality compared to the general population. Hyperphosphataemia, associated with vascular calcification and arterial stiffness, may play a key role in the pathogenesis of cardiovascular disease (CVD) associated with CKD, although phosphate reduction strategies have not consistently proven to beneficially affect clinically relevant outcomes. The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) study is an international, multi-centre, randomized, placebo-controlled trial investigating the effect of the phosphate binder lanthanum carbonate on intermediate cardiovascular markers in patients with stage 3b-4 CKD. The primary end-point is change in carotid-femoral pulse wave velocity (PWV, SphygmoCor) after 96 weeks. Secondary outcomes include change in abdominal aortic calcification (AAC, computed tomography), serum phosphate and fibroblast growth factor 23 (FGF-23). In total, 278 participants were recruited and randomized, mean age 63 ± 13 years, 69% male, 45% diabetes, 32% CVD, 33% stage 3b CKD and 67% stage 4 CKD. Mean estimated glomerular filtration rate and serum phosphate were 26.6 ± 8.3 mL/min/1.72 m2 and 1.25 ± 0.20 mmol/L, respectively. Median (interquartile range) intact and c-terminal FGF-23 levels were 133.0 (89.1-202) pg/mL and 221.1 (154.3-334.1) RU/mL, respectively. Mean PWV was 10.8 ± 3.6 m/s and 81% had AAC (median Agatston score 1,535 [63-5,744] Hounsfield units). PWV ≥10 m/s was associated with older age, diabetes, CVD, presence of AAC, higher systolic blood pressure (BP), larger waist circumference and higher alkaline phosphatase. AAC was associated with older age, male sex, diabetes, CVD, higher diastolic BP, dyslipidaemia (and use of statins), smoking, larger waist circumference and increased PWV. In conclusion, IMPROVE-CKD participants had high baseline risk for cardiovascular events, as suggested by high baseline PWV and AAC values.
Assuntos
Aorta/patologia , Falência Renal Crônica/tratamento farmacológico , Lantânio/administração & dosagem , Calcificação Vascular/epidemiologia , Rigidez Vascular/efeitos dos fármacos , Fatores Etários , Idoso , Aorta/diagnóstico por imagem , Progressão da Doença , Feminino , Fator de Crescimento de Fibroblastos 23 , Taxa de Filtração Glomerular , Fatores de Risco de Doenças Cardíacas , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Análise de Onda de Pulso , Fatores Sexuais , Resultado do Tratamento , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico , Calcificação Vascular/etiologiaRESUMO
INTRODUCTION: Patients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlled clinical trials to guide management. Positive associations between serum phosphate and fibroblast growth factor 23 (FGF-23) and cardiovascular morbidity and mortality in both the general and CKD populations have resulted in clinical guidelines suggesting that serum phosphate be targeted towards the normal range, although few randomised and placebo-controlled studies have addressed clinical outcomes using interventions to improve phosphate control. Early preventive measures to reduce the development and progression of vascular calcification, left ventricular hypertrophy and arterial stiffness are crucial in patients with CKD. METHODS AND ANALYSIS: We outline the rationale and protocol for an international, multicentre, randomised parallel-group trial assessing the impact of the non-calcium-based phosphate binder, lanthanum carbonate, compared with placebo on surrogate markers of cardiovascular disease in a predialysis CKD population-the IM pact of P hosphate R eduction O n V ascular E nd-points (IMPROVE)-CKD study. The primary objective of the IMPROVE-CKD study is to determine if the use of lanthanum carbonate reduces the burden of cardiovascular disease in patients with CKD stages 3b and 4 when compared with placebo. The primary end-point of the study is change in arterial compliance measured by pulse wave velocity over a 96-week period. Secondary outcomes include change in aortic calcification and biochemical parameters of serum phosphate, parathyroid hormone and FGF-23 levels. ETHICS AND DISSEMINATION: Ethical approval for the IMPROVE-CKD trial was obtained by each local Institutional Ethics Committee for all 17 participating sites in Australia, New Zealand and Malaysia prior to study commencement. Results of this clinical trial will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ACTRN12610000650099.
Assuntos
Doenças Cardiovasculares/etiologia , Hiperfosfatemia/prevenção & controle , Fosfatos/sangue , Insuficiência Renal Crônica/complicações , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Protocolos Clínicos , Método Duplo-Cego , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Hiperfosfatemia/etiologia , Lantânio/uso terapêutico , Masculino , Hormônio Paratireóideo/sangue , Insuficiência Renal Crônica/sangueRESUMO
BACKGROUND: Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have a high risk of sudden cardiac death (SCD). A unique risk factor may be a longer interval between HD sessions (interdialytic period). Inherent in conventional HD (thrice-weekly) are two 48-hour short breaks (SIDP) and one 72-hour long break (LIDP) between HD sessions. OBJECTIVE: We used an implantable cardiac monitor (ICM) to define the incidence and timing of significant arrhythmias in an HD population. METHODS: Fifty CKD patients undergoing HD with left ventricular ejection fraction >35% had an ICM inserted, with intensive follow-up to record SCD events and predefined bradyarrhythmias and tachyarrhythmias. RESULTS: Mean age of the patients was 67 ± 11 years; 72% were male, and the mean follow-up was 18 ± 4 months. There were 8 unexpected SCDs (16%), all during the LIDP. The terminal event was severe bradycardia with asystole in each recorded case. No episodes of polymorphic ventricular tachycardia (VT) occurred. A total of 7686 arrhythmia events were recorded in 43 patients (86%), including bradycardia in 15 patients (30%), sinus arrest in 14 (28%), second-degree atrioventricular block in 4 (8%), nonsustained VT in 10 (20%), and new-onset paroxysmal atrial fibrillation in 14 (28%). The LIDP was the highest-risk period for all arrhythmias (P < .001). The arrhythmia event rate per hour was greatest during the first pre-HD period of the week compared with any other peri-HD period (P < .001). CONCLUSION: Risk of SCD and significant arrhythmias is greatest during the LIDP. SCD was attributable to severe bradycardia and asystole. Interventions to prevent this type of SCD or shorten the LIDP deserve further evaluation. CLINICAL TRIAL REGISTRATION INFORMATION: URL: https://www.anzctr.org.au (Unique identifier: ACTRN12613001326785).
Assuntos
Arritmias Cardíacas/epidemiologia , Diálise Renal , Insuficiência Renal Crônica/complicações , Idoso , Arritmias Cardíacas/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Fatores de Tempo , Vitória/epidemiologiaAssuntos
Bradicardia/mortalidade , Morte Súbita Cardíaca/etiologia , Parada Cardíaca/mortalidade , Insuficiência Renal Crônica/mortalidade , Distribuição por Idade , Idoso , Bradicardia/complicações , Bradicardia/diagnóstico , Estudos de Coortes , Morte Súbita Cardíaca/epidemiologia , Eletrocardiografia , Feminino , Parada Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Diálise Renal/métodos , Diálise Renal/mortalidade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Medição de Risco , Distribuição por SexoRESUMO
BACKGROUND: Current clinical practice guidelines recommend a native arteriovenous fistula (AVF) as the vascular access of first choice. Despite this, most patients in western countries start hemodialysis therapy using a catheter. Little is known regarding specific physician and system characteristics that may be responsible for delays in permanent access creation. STUDY DESIGN: Multicenter cohort study using mixed methods; qualitative and quantitative analysis. SETTING & PARTICIPANTS: 9 nephrology centers in Australia and New Zealand, including 319 adult incident hemodialysis patients. PREDICTOR: Identification of barriers and enablers to AVF placement. OUTCOMES: Type of vascular access used at the start of hemodialysis therapy. MEASUREMENTS: Prospective data collection included data concerning predialysis education, interviews of center staff, referral times, and estimated glomerular filtration rate (eGFR) at AVF creation and dialysis therapy start. RESULTS: 319 patients started hemodialysis therapy during the 6-month period, 39% with an AVF and 59% with a catheter. Perceived barriers to access creation included lack of formal policies for patient referral, long wait times for surgical review and access placement, and lack of a patient database for management purposes. eGFR thresholds at referral for and creation of vascular accesses were considerably lower than appreciated (in both cases, median eGFR of 7 mL/min/1.73 m(2)), with median wait times for access creation of only 3.7 weeks. First assessment by a nephrologist less than 12 months before dialysis therapy start was an independent predictor of catheter use (OR, 8.71; P < 0.001). Characteristics of the best performing centers included the presence of a formalized predialysis pathway with a centralized patient database and low nephrologist and surgeon to patient ratios. LIMITATIONS: A limited number of patient-based barriers was assessed. Cross-sectional data only. CONCLUSIONS: A formalized predialysis pathway including patient education and eGFR thresholds for access placement is associated with improved permanent vascular access placement.
Assuntos
Derivação Arteriovenosa Cirúrgica , Competência Clínica/normas , Fidelidade a Diretrizes , Diálise Renal/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Cateteres de Demora , Feminino , Seguimentos , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
Studies have shown that dual therapy with angiotensin-converting enzyme inhibitors (ACEI) and either angiotensin II receptor blockers or aldosterone receptor antagonists is more effective in reducing proteinuria than either agent used alone. The questions that remain are as follows: (1) Which of these agents should be used as dual therapy with the ACEI? (2) Does a higher level of blockade of the renin-angiotensin-aldosterone system with triple therapy offer an advantage over dual blockade? A 3-mo randomized, double-blind, placebo-controlled study was performed in 41 patients with proteinuria >1.5 g/d. Four treatment groups were compared: (1) Ramipril + spironolactone placebo + irbesartan placebo, (2) ramipril + irbesartan + spironolactone placebo, (3) ramipril + irbesartan placebo + spironolactone, and (4) ramipril + irbesartan + spironolactone. The percentage change in protein excretion differed according to treatment arm (ANOVA: F(3,35) = 8.6, P < 0.001). Pair-wise comparison showed that greater reduction in protein excretion occurred in treatment regimens that incorporated spironolactone. The reduction in proteinuria at 3 mo was as follows: Group 1, 1.4%; group 2, 15.7%; group 3, 42.0%; and group 4, 48.2%. The reduction in proteinuria among patients who were taking spironolactone-containing regimens was sustained at 6 and 12 mo. This study suggests that aldosterone receptor blockade offers a valuable adjuvant treatment when used with ACEI therapy for the reduction of proteinuria. Results suggest no advantage of triple blockade over dual blockade of the renin-angiotensin-aldosterone system to reduce proteinuria.