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1.
Nephrology (Carlton) ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38626950

RESUMO

Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady-state oral clearance (CL/F), elimination half-life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%-60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate-lowering therapy.

2.
Intern Med J ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38665051

RESUMO

Calcium-sensing receptors (CaSRs) are G protein-coupled receptors that help maintain Ca2+ concentrations, modulating calciotropic hormone release (parathyroid hormone (PTH), calcitonin and 1,25-dihydroxyvitamin D) by direct actions in the kidneys, gastrointestinal tract and bone. Variability in population calcium levels has been attributed to single nucleotide polymorphisms in CaSR genes, and several conditions affecting calcium and phosphate homeostasis have been attributed to gain- or loss-of-function mutations. An example is autosomal dominant hypercalciuric hypocalcaemia, because of a missense mutation at codon 128 of chromosome 3, as reported in our specific case and her family. As a consequence of treating symptomatic hypocalcaemia as a child, this female subject slowly developed progressive end-stage kidney failure because of nephrocalcinosis and nephrolithiasis. After kidney transplantation, she remains asymptomatic, with decreased vitamin D and elemental calcium requirements, stable fluid and electrolyte homeostasis during intercurrent illnesses and has normalised urinary calcium and phosphate excretion, reducing the likelihood of hypercalciuria-induced graft impairment. We review the actions of the CaSR, its role in regulating renal Ca2+ homeostasis along with the impact of a proven gain-of-function mutation in the CaSR gene resulting in autosomal dominant hypercalciuric hypocalcaemia before and after kidney transplantation.

3.
Can J Kidney Health Dis ; 8: 20543581211022207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178361

RESUMO

BACKGROUND: Patient involvement in dialysis decision-making is crucial, yet little is known about patient-reported outcomes over time on dialysis. OBJECTIVE: To examine health-related outcomes over 24 and 36 months in an older cohort of dialysis patients. DESIGN: The "Dialysis outcomes in those aged ≥65 years study" is a prospective longitudinal cohort study of New Zealanders with kidney failure. SETTING: Three New Zealand nephrology units. PATIENTS: Kidney failure (dialysis and predialysis) patients aged 65 or above. We have previously described outcomes after 12 months of dialysis therapy relative to baseline. MEASUREMENTS: Patient-reported social and health factors using the SF-36, EQ-5D, and Kidney Symptom Score questionnaires. METHODS: This article describes and compares characteristics of 120 older kidney failure patients according to whether they report "Same/better" or "Worse" health 24 and 36 months later, and identifies predictors of "worse health." Modified Poisson regression modeling estimated relative risks (RR) of worse health. RESULTS: Of 120 patients at 12 months, 47.5% had worse health or had died by 24 months. Of those surviving at 24 months (n = 80), 40% had "Worse health" or had died at 36 months. Variables independently associated with reduced risk of "Worse health" (24 months) were as follows: Maori ethnicity (RR = 0.44; 95% CI = 0.26-0.75), Pacific ethnicity (RR = 0.39; 95% CI = 0.33-0.46); greater social satisfaction (RR = 0.57; 95% CI = 0.46-0.7). Variables associated with an increased risk of "Worse health" were as follows: problems with usual activities (RR = 1.32; 95% CI = 1.04-1.37); pain or discomfort (RR = 1.48; 95% CI = 1.34, 1.63). At 36 months, lack of sense of community (RR = 1.41; 95% CI = 1.18-1.69), 2 or more comorbidities (RR = 1.21; 95% CI = 1.13-1.29), and problems with poor health (RR = 1.47; 95% CI = 1.41-1.54) were associated with "Worse health." LIMITATIONS: Participant numbers restricted the number of variables able to be included in the multivariable model, and hence there may have been insufficient power to detect certain associations. CONCLUSIONS: In this study, the majority of older dialyzing patients report "Same/better health" at 24 and 36 months. Maori and Pacific people report better outcomes on dialysis. Social and/or clinical interventions aimed at improving social satisfaction, sense of community, and help with usual activities may impact favorably on the experiences for older dialysis patients. TRIAL REGISTRATION: Australian and New Zealand clinical trials registry: ACTRN12611000024943.


CONTEXTE: La participation des patients à la prise de décisions est essentielle en contexte de traitements de dialyse. On en sait toutefois peu sur les résultats observés par les patients en cours de traitement. OBJECTIF: Examiner les résultats liés à la santé sur une période de 24 et de 36 mois dans une cohorte de patients âgés suivant des traitements de dialyse. TYPE D'ÉTUDE: Cette étude intitulée Dialysis outcomes in those aged ≥65 years est une étude de cohorte prospective et longitudinale menée auprès de Néo-Zélandais atteints d'insuffisance rénale. CADRE: Trois unités de néphrologie en Nouvelle-Zélande. SUJETS: Des patients âgés de plus de 65 ans atteints d'insuffisance rénale (dialyse et prédialyse). Nous avions antérieurement décrit les résultats observés après 12 mois de dialyse par rapport au début de l'étude. MESURES: Les facteurs sociaux et l'état de santé déclarés par les patients par l'entremise des questionnaires SF-36, EQ-5D et Kidney Symptom Score. MÉTHODOLOGIE: Dans cet article, nous décrivons et comparons les caractéristiques de 120 patients âgés atteints d'insuffisance rénale selon qu'ils avaient déclaré un état de santé « inchangé/meilleur ¼ ou « empiré ¼ après 24 et 36 mois. Nous discutons également des facteurs prédictifs d'un état de santé jugé « empiré ¼. Un modèle de régression de Poisson corrigé a servi à estimer le risque relatif (RR) de progresser vers un état de santé « empiré ¼. RÉSULTATS: Des 120 patients évalués après 12 mois, 47,5 % avaient déclaré un état de santé « empiré ¼ ou étaient décédés après 24 mois. Parmi les survivants à 24 mois d'étude (n = 80), 40 % avaient déclaré un état de santé « empiré ¼ ou étaient décédés après 36 mois. Les variables associées de façon indépendante à un risque réduit de voir l'état de santé empiré (24 mois) étaient : le fait d'être Maori (RR = 0,44; IC 95% = 0.26-0.75) ou issu d'une population du Pacifique (RR = 0.39; IC 95% = 0.33-0.46) et une satisfaction sociale plus élevée (RR = 0.57; IC 95% = 0.46-0.7) constituent les variables qui ont été associées de façon indépendante à un risque réduit de voir un état de santé empiré après 24 mois. Parmi les variables associées à un risque accru d'aggravation de l'état de santé, on compte des difficultés à pratiquer les activités quotidiennes (RR = 1.32; IC 95% = 1.04-1.37) et la douleur ou l'inconfort (RR = 1.48; IC 95% = 1.34-1.63). Après 36 mois de traitement, l'absence d'un sentiment de communauté (RR = 1,41; IC 95% = 1.18-1.69), le fait de présenter au moins deux maladies concomitantes (RR = 1.21; IC 95% = 1.13-1.29) et des problèmes liés à une mauvaise santé (RR = 1.47; IC 95% = 1.41-1.54) ont été associés à un état de santé jugé « empiré ¼. LIMITES: Le faible nombre de participants a restreint le nombre de variables pouvant être incluses dans le modèle multivarié, il est donc possible que la puissance de détection de certaines associations soit insuffisante. CONCLUSION: Dans cette étude, la majorité des patients âgés sous dialyse ont déclaré avoir un état de santé « inchangé/meilleur ¼ après 24 et 36 mois de traitement. Les patients Maoris et ceux qui sont originaires du Pacifique ont déclaré de meilleurs résultats de dialyse. Les interventions sociales ou cliniques visant à améliorer la satisfaction sociale, le sentiment d'appartenance à la communauté et l'aide aux activités quotidiennes pourraient avoir un effet bénéfique sur le vécu des patients âgés suivant des traitements de dialyse.

4.
Br J Clin Pharmacol ; 87(12): 4868-4876, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34004027

RESUMO

This research explored the intact nephron hypothesis (INH) as a model for metformin dosing in patients with chronic kidney disease (CKD). The INH assumes that glomerular filtration rate (GFR) will account for all kidney drug handling even for drugs eliminated by tubular secretion like metformin. We conducted two studies: (1) a regression analysis to explore the relationship between metformin clearance and eGFR metrics, and (2) a joint population pharmacokinetic analysis to test the relationship between metformin renal clearance and gentamicin clearance. The relationship between metformin renal clearance and eGFR metrics and gentamicin clearance was found to be linear, suggesting that a proportional dose reduction based on GFR in patients with CKD is reasonable.


Assuntos
Metformina , Insuficiência Renal Crônica , Creatinina , Taxa de Filtração Glomerular , Humanos , Rim , Testes de Função Renal , Néfrons , Insuficiência Renal Crônica/tratamento farmacológico
5.
PLoS One ; 16(2): e0246247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33600406

RESUMO

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Nefropatias/complicações , Metformina/administração & dosagem , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Testes de Função Renal , Masculino , Metformina/efeitos adversos , Metformina/farmacocinética , Metformina/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem
6.
Physiol Meas ; 41(5): 055003, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32272458

RESUMO

OBJECTIVE: To test the reliability of immediate replication of muscle cramp characteristics induced with different electrical stimulation protocols. APPROACH: Five (age 33.8 ± 5.7 y, 60% male) and ten (age 47.4 ± 11.7 y, 60% male) participants completed independent discovery and validation cohorts, respectively. This was to identify a protocol that resulted in consistent muscle cramp characteristics (discovery), and to examine the test-retest reliability of the identified protocol (validation). Electrical stimulation (150 burst) at abductor hallucis motor-point was used to induce muscle cramps with 4 Hz increments in stimulation frequency (8-32 Hz) or until muscle cramp was first evident, followed by refinement (2 and 1 Hz) until at least two muscle cramps occurred. This defined the cramp threshold frequency, and concurrent electromyogram activity and duration of the cramp were quantified. The discovery cohort involved three separate randomised sessions where intervals between stimulation was 60, 90, and 120 s respectively. In each session, four randomised electrical stimulation protocols were completed. Stimulation current was fixed at 10, 20, and 30% higher than m-wave stimulation current (protocols 1-3 respectively), or randomised within 4 Hz steps (protocol 4) to minimise any order effect. MAIN RESULTS: We were able to immediately replicate tolerable muscle cramp at least twice. Discovery cohort demonstrated (i) incremental changes in stimulation frequency (protocols 1-3 vs. protocol 4, i.e. order effect), and (ii) changes in stimulation current with differing protocols did not significantly alter the prevailing muscle cramp characteristics, and (iii) defining the muscle cramp characteristics elicits good-to-excellent inter-observer reliability. The validation cohort's test-retest reliability and the minimum detectable change were improved for all muscle cramp characteristics when immediately replicated more than twice at the lowest stimulation frequency. SIGNIFICANCE: This study provides evidence for a reliable method for inducing repeatable muscle cramps in abductor hallucis.


Assuntos
Estimulação Elétrica/métodos , Cãibra Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Am Soc Nephrol ; 31(5): 1078-1091, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32188697

RESUMO

BACKGROUND: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. METHODS: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. RESULTS: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. CONCLUSIONS: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.


Assuntos
Ventrículos do Coração/efeitos dos fármacos , Soluções para Hemodiálise/farmacologia , Hemodiálise no Domicílio/métodos , Hipertrofia Ventricular Esquerda/patologia , Diálise Renal/efeitos adversos , Sódio/administração & dosagem , Idoso , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/terapia , Feminino , Hemodiálise no Domicílio/efeitos adversos , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Hipotensão/etiologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Ambulatório Hospitalar , Autocuidado , Resultado do Tratamento , Equilíbrio Hidroeletrolítico , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/prevenção & controle
8.
Eur J Clin Pharmacol ; 76(2): 239-247, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31814045

RESUMO

OBJECTIVE: We analysed the pharmacokinetics of meropenem and piperacillin-tazobactam in patients undergoing a standardised session of sustained low efficiency haemodiafiltration (SLED-HDF) to inform the dosing of these drugs in an acute setting. PARTICIPANTS: Six stable patients with end-stage kidney disease. METHODS: An open-label pilot pharmacokinetic study of meropenem and piperacillin-tazobactam. SLED-HDF was undertaken for 4 h. Plasma drug concentrations were measured pre- and post-filter and in the effluent at multiple time points. The pharmacokinetic data was analysed using non-compartmental methods. The fraction of time that individual plasma concentration profiles were predicted to remain above the MIC break-points for commonly isolated gram-negative pathogens during a prolonged SLED-HDF session was assessed using two targets; fT > MIC (fraction of time above the MIC) and the more aggressive fT > 4 × MIC (fraction of time above 4 × MIC). RESULTS: Meropenem total and SLED-HDF clearance ranged from 141 to 180 mL/min and 126-205 mL/min, respectively. Piperacillin total and SLED-HDF clearance values ranged from 131 to 252 mL/min and 135-162 mL/min, respectively. Our results suggest that prolonged SLED-HDF (12 h) will only maintain a sufficient meropenem and piperacillin-tazobactam plasma concentration to achieve a target of fT > MIC for gram-negative pathogens (MIC 2 mg/L-meropenem, 8 mg/L-piperacillin-tazobactam) for less than 40% of the time. Plasma concentrations would be inadequate to achieve the more aggressive target of 100 % fT > 4xMIC target recommended for critically unwell patients. CONCLUSIONS: The pharmacokinetic data obtained from this pilot study demonstrate significant quantities of meropenem and piperacillin are removed during a SLED-HDF session. This may lead to subtherapeutic concentrations of piperacillin and meropenem over the duration of HDF session. TRIAL REGISTRATION: Australasian Clinical Trials Registry Network (ACTRN12616000078459).


Assuntos
Antibacterianos/farmacocinética , Hemodiafiltração/métodos , Meropeném/farmacocinética , Combinação Piperacilina e Tazobactam/farmacocinética , Adulto , Idoso , Antibacterianos/administração & dosagem , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Meropeném/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Combinação Piperacilina e Tazobactam/administração & dosagem
9.
BMC Nephrol ; 20(1): 137, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014261

RESUMO

BACKGROUND: Despite an increasing number of older people commencing dialysis the impact of dialysis on their quality of life and survival, remains unclear. The Dialysis Outcomes in those aged over 65 years or older study is an accelerated prospective cohort longitudinal design study, designed to obtain sufficient health related quality of life data, linked to clinical data, to inform clinicians' and patients' decision-making with respect to end stage kidney disease (ESKD), outcomes, and options for management in New Zealand (NZ). METHODS: The study has an accelerated prospective cohort longitudinal design, comprised of cross-sectional and longitudinal components. We report the baseline data on the 225 participants enrolled in the study. Dialysis duration was grouped in tertiles from less than one year (incident patients), 1-3 years and greater than 3 years. Health related quality of life data was obtained from self-reported questionnaires including KDQoL-36, EQ-5D-3 L, FACIT, WHODAS II, and the Personal Well-being Score. RESULTS: The median age of the cohort was 71 years and two thirds were male. Three quarters of the participants were on dialysis at the baseline, with 42% of those on home dialysis (haemodialysis or peritoneal dialysis). Maori and Pacific people were over represented (20% Maori and 24% Pacific) in the sample, when compared to the general NZ population of the same age group (where 5% are Maori and 2% are Pacific). At baseline, there were no differences observed in sociodemographic, quality of life or health characteristics between the dialysis groups either by modality or duration of dialysis. CONCLUSIONS: We report the baseline characteristics of participants enrolled prospectively into a longitudinal cohort observational study examining health related quality of life factors with clinical characteristics on dialysis outcomes in a group of New Zealanders aged 65 years or older who are either on dialysis or have been educated about dialysis (BMC Nephrol 14:175, 2013). Subsequent publications are planned, analysing the prospective longitudinal data to identify key factors that determine both outcome and quality of life for individuals of this age group. TRIAL REGISTRATION: ACTRN12611000024943 .


Assuntos
Falência Renal Crônica , Seleção de Pacientes , Qualidade de Vida , Diálise Renal , Idoso , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , Estudos Longitudinais , Masculino , Nova Zelândia/epidemiologia , Avaliação de Resultados da Assistência ao Paciente , Diálise Renal/métodos , Diálise Renal/psicologia , Diálise Renal/estatística & dados numéricos , Inquéritos e Questionários
10.
Kidney Int Rep ; 2(5): 856-865, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29270493

RESUMO

INTRODUCTION: Sympathetic neural activation is markedly increased in end-stage kidney disease (ESKD). Catheter-based renal denervation (RDN) reduces sympathetic overactivity and blood pressure in resistant hypertension. We investigated the effect of RDN on sympathetic neural activation and left ventricular mass in patients with ESKD. METHODS: Nine ESKD (6 hemodialysis and 3 peritoneal dialysis) patients with dialysis vintage of ≥11 months were treated with RDN (EnligHTN system). Data were obtained on a nondialysis day; at baseline, 1, 3, and 12 months post-RDN. RESULTS: At baseline sympathetic neural activation measured by muscle sympathetic nervous activity (MSNA) and plasma norepinephrine concentrations were markedly elevated. Left ventricular hypertrophy (LVH) was evident in 8 of the 9 patients. At 12 months post-RDN, blind analysis revealed that MSNAfrequency (-12.2 bursts/min1, 95% CI [-13.6, -10.7]) and LV mass (-27 g/m2, 95% CI [-47, -8]) were reduced. Mean ambulatory BP (systolic: -24 mm Hg, 95% CI [-42, -5] and diastolic: -13 mm Hg, 95% CI [-22, -4]) was also reduced at 12 months. Office BP was reduced as early as 1 month (systolic: -25 mm Hg, 95% CI [-45, -5] and diastolic: -13 mm Hg, 95% CI [-24, -1]). Both ambulatory and office BP had clinically significant reductions in at least 50% of patients out to 12 months. DISCUSSION: Catheter-based RDN significantly reduced MSNA and LV mass as well as systemic BP in this group of patients with ESKD.

11.
Am J Kidney Dis ; 70(6): 798-806, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28823582

RESUMO

BACKGROUND: Involving patients in dialysis decision making is crucial, yet little is known about patient-reported experiences and patient-reported outcomes of dialysis. STUDY DESIGN: A prospective longitudinal cohort study of older patients receiving long-term dialysis. Predictors of worse health status were assessed using modified Poisson regression analysis. SETTING & PARTICIPANTS: 150 New Zealanders 65 years or older with end-stage kidney disease dialyzing at 1 of 3 nephrology centers. PREDICTORS: Patient-reported social and health characteristics based on the 36-Item Short Form Health Survey, EQ-5D, and Kidney Symptom Score questionnaires and clinical information from health records. OUTCOMES: Health status after 12 months of follow-up. RESULTS: 35% of study participants had reported worse health or had died at 12 months. Baseline variables independently associated with reduced risk for worse health status were Pacific ethnicity (relative risk [RR], 0.63; 95% CI, 0.53-0.72), greater bother on the Kidney Symptom Score (RR, 0.78; 95% CI, 0.62-0.97), and dialyzing at home with either home hemodialysis (RR, 0.55; 95% CI, 0.36-0.83) or peritoneal dialysis (RR, 0.86; 95% CI, 0.79-0.93). Baseline variables independently associated with increased risk were greater social dissatisfaction (RR, 1.66; 95% CI, 1.27-2.17), lower sense of community (RR, 1.70; 95% CI, 1.09-2.64), comorbid conditions (RR, 1.70; 95% CI, 1.09-2.64), EQ-5D anxiety/depression (RR, 1.61; 95% CI, 1.07-2.42); poor/fair overall general health (RR, 1.60; 95% CI, 1.37-1.85), and longer time on dialysis therapy (RR, 1.03; 95% CI, 1.00-1.05). LIMITATIONS: Small sample size restricted study power. CONCLUSIONS: Most older dialyzing patients studied reported same/better health 12 months later. Home-based dialysis, regardless of whether hemodialysis or peritoneal dialysis, was associated with reduced risk for worse health, and older Pacific People reported better outcomes on dialysis therapy. Social and/or clinical interventions aimed at improving social satisfaction, sense of community, and reducing anxiety/depression may favorably affect the experiences of older patients receiving long-term dialysis.


Assuntos
Nível de Saúde , Falência Renal Crônica/terapia , Medidas de Resultados Relatados pelo Paciente , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Estudos de Coortes , Depressão/psicologia , Feminino , Humanos , Falência Renal Crônica/psicologia , Estudos Longitudinais , Masculino , Nova Zelândia , Diálise Peritoneal , Satisfação Pessoal , Distribuição de Poisson , Estudos Prospectivos , Análise de Regressão , Participação Social/psicologia
12.
BMJ Open ; 7(3): e014781, 2017 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-28360253

RESUMO

BACKGROUND: Issues related to renal replacement therapy in elderly people with end stage kidney disease (ESKD) are complex. There is inadequate empirical data related to: decision-making by older populations, treatment experiences, implications of dialysis treatment and treatment modality on quality of life, and how these link to expectations of ageing. STUDY POPULATION: Participants for this study were selected from a larger quantitative study of dialysis and predialysis patients aged 65 years or older recruited from three nephrology services across New Zealand. All participants had reached chronic kidney disease (CKD) stage 5 and had undergone dialysis education but had not started dialysis or recently started dialysis within the past 6 months. METHODOLOGY: Serial qualitative interviews were undertaken to explore the decision-making processes and subsequent treatment experiences of patients with ESKD.Analytical approach: A framework method guided the iterative process of analysis. Decision-making codes were generated within NVivo software and then compared with the body of the interviews. RESULTS: Interviews were undertaken with 17 participants. We observed that decision-making was often a fluid process, rather than occurring at a single point in time, and was heavily influenced by perceptions of oneself as becoming old, social circumstances, life events and health status. LIMITATIONS: This study focuses on participants' experiences of decision-making about treatment and does not include perspectives of their nephrologists or other members of the nephrology team. CONCLUSIONS: Older patients often delay dialysis as an act of self-efficacy. They often do not commit to a dialysis decision following predialysis education. Delaying decision-making and initiating dialysis were common. This was not seen by participants as a final decision about therapy. Predialysis care and education should be different for older patients, who will delay decision-making until the time of facing obvious uraemic symptoms, threatening blood tests or paternalistic guidance from their nephrologist. TRIAL REGISTRATION NUMBER: Australasian Clinical Trials Registry ACTRN 12611000024943; results.


Assuntos
Tomada de Decisão Clínica , Falência Renal Crônica/terapia , Diálise Renal/psicologia , Idoso , Idoso de 80 Anos ou mais , Atitude Frente a Saúde , Feminino , Humanos , Falência Renal Crônica/psicologia , Tempo de Internação , Masculino , Nova Zelândia , Qualidade de Vida , Autoeficácia
13.
Clin Pharmacokinet ; 56(6): 671-678, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27943221

RESUMO

BACKGROUND AND OBJECTIVES: 51Cr EDTA clearance (CL) from plasma is used to estimate glomerular filtration rate (GFR). We propose that current methods for analysing the raw 51Cr EDTA measurements over-simplifies the disposition of 51Cr EDTA and therefore could produce biased GFR estimates. The aim of this study was to develop a population pharmacokinetic model for 51Cr EDTA disposition and to compare model-predicted GFR to other methods of estimating renal function. PATIENTS AND METHODS: Data from 40 individuals who received ~7.4 MBq of 51Cr EDTA, as an intravenous bolus, were available for analysis. Plasma radioactivity (counts/min) was measured from timed collection points at 2, 4, 6 and 24 h after the dose. A population analysis was conducted using NONMEM® version 7.2. Model-predicted GFR was compared with other methods for estimating renal function using mean prediction error (MPE). RESULTS: A two-compartment pharmacokinetic model with first-order elimination best fit the data. Compared with the model predictions, creatinine CL from 24 h urine data was unbiased. The commonly used 'slope-intercept' method for estimating isotopic GFR was positively biased compared with the model (MPE 15.5 mL/min/1.73 m2 [95% confidence interval {CI} 8.9-22.2]. The Cockcroft Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations led to negatively biased GFR estimates (MPE -19.0 [95% CI -25.4 to -12.7], -20.1 [95% CI -27.2 to -13.1] and -16.5 [95% CI -22.2 to -10.1] mL/min/1.73 m2, respectively). CONCLUSIONS: The biased GFR estimates were most obvious in patients with relatively normal renal function. This may lead to inaccurate dosing in patients who are receiving drugs with a narrow therapeutic range where dosing is adjusted according to GFR estimates (e.g. carboplatin). STUDY REGISTRATION: The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number: ACTRN 12611000035921.


Assuntos
Ácido Edético/farmacocinética , Rim/fisiologia , Modelos Biológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Radioisótopos de Cromo , Ácido Edético/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/sangue , Nefropatias/fisiopatologia , Masculino , Adulto Jovem
14.
Clin Kidney J ; 7(1): 3-10, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25859344

RESUMO

Endovascular renal denervation (sympathectomy) is a novel procedure developed for the treatment of resistant hypertension. Evidence suggests that it reduces both afferent and efferent sympathetic nerve activity, which may offer clinical benefit over and above any blood pressure-lowering effect. Studies have shown objective improvements in left ventricular mass, ventricular function, central arterial stiffness, central haemodynamics, baroreflex sensitivity and arrhythmia frequency. Benefits have also been seen in insulin resistance, microalbuminuria and glomerular filtration rate. In chronic kidney disease, elevated sympathetic activity has been causally linked to disease progression and cardiovascular sequelae. Effecting a marked reduction in sympathetic hyperactivity may herald a significant step in the management of this and other conditions. In this in-depth review, the pathophysiology and clinical significance of the sympatholytic effects of endovascular renal denervation are discussed.

15.
Am J Physiol Renal Physiol ; 304(3): F300-7, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23171555

RESUMO

There is a lack of suitable animal models that replicate the slowly progressive chronic interstitial fibrosis that is characteristic of many human chronic nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced renal fibrosis, with minimal active inflammation, which mimics chronic kidney interstitial fibrosis seen in the human kidney. Rats received lithium via their chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6 mo and the kidneys were processed for histological and immunohistochemical studies. Progressive interstitial fibrosis, characterized by increasing numbers of myofibroblasts, enhanced transforming growth factor-ß(1) expression and interstitial collagen deposition, and a minimal inflammatory cellular response was evident. Elucidation of the underlying mechanisms of injury in this model will provide a greater understanding of chronic interstitial fibrosis and allow the development of intervention strategies to prevent injury.


Assuntos
Rim/efeitos dos fármacos , Rim/patologia , Lítio/efeitos adversos , Lítio/farmacologia , Nefrite Intersticial/induzido quimicamente , Animais , Doença Crônica , Colágeno/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibrose , Rim/metabolismo , Masculino , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Ratos , Ratos Wistar , Fatores de Tempo , Fator de Crescimento Transformador beta1/metabolismo
17.
Nephrology (Carlton) ; 17(2): 182-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21883672

RESUMO

AIM: Due to altered red blood cell survival and erythropoietin therapy glycated haemoglobin (HbA1c) may not accurately reflect long-term glycaemic control in patients with diabetes and chronic kidney disease (CKD). Glycated albumin (GA) and fructosamine are alternative markers of glycaemia. The aim of this study was to investigate the accuracy of HbA1c, GA and fructosamine as indicators of glycaemic control using continuous glucose monitoring. METHODS: HbA1c, GA and fructosamine concentrations were measured in 25 subjects with diabetic nephropathy (CKD stages 4 and 5 (estimated glomerular filtration rate <30 mL/min per 1.73 m(2) )) matched with 25 subjects with diabetes and no evidence of nephropathy. Simultaneous real-time glucose concentrations were monitored by continuous glucose monitoring over 48 h. RESULTS: GA correlated significantly to mean glucose concentrations in patients with and without CKD (r = 0.54 vs 0.49, P < 0.05). A similar relationship was observed with fructosamine relative to glucose. A poor correlation between HbA1c and glucose was observed with CKD (r = 0.38, P = ns) but was significant in the non-CKD group (r = 0.66, P < 0.001). The GA/HbA1c ratio was significantly higher in diabetic patients with CKD compared with controls (2.5 ± 0.4 vs 2.2 ± 0.4, P < 0.05). HbA1c values were significantly lower in CKD patients, relative to non-CKD patients at comparable mean glucose concentrations. CONCLUSION: HbA1c significantly underestimates glycaemic control in patients with diabetes and CKD stages 4 and 5. In severe CKD, GA more accurately reflects glycaemic control compared with fructosamine and HbA1c and should be the preferred marker of glycaemic control.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Frutosamina/sangue , Hemoglobinas Glicadas/metabolismo , Monitorização Fisiológica , Albumina Sérica/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Estudos de Casos e Controles , Doença Crônica , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/terapia , Feminino , Produtos Finais de Glicação Avançada , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Diálise Peritoneal , Análise de Regressão , Diálise Renal , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Albumina Sérica Glicada
18.
Nephrology (Carlton) ; 17(3): 249-56, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22171802

RESUMO

BACKGROUND: Studies of dietary sodium on vascular function and blood pressure in normotensive volunteers have shown conflicting results. There are very limited data available on the effect of chronic sodium loading from a low-sodium diet to a high-sodium diet on vascular function and blood pressure in normotensive volunteers. OBJECTIVE: To assess the effect of modifying dietary sodium intake on arterial function and surrogate markers of arterial remodelling in normal healthy volunteers. DESIGN: Twenty-three normotensive volunteers met the inclusion criteria. After a 2 week run-in with a low-sodium diet (60 mmol/day), the participants maintained their low-sodium diets and were randomly assigned to receive sequentially one of three interventions for 4 weeks, with a 2 week washout between interventions: sodium-free tomato juice (A), tomato juice containing 90 mmol Na (B) and tomato juice containing 140 mmol Na (C). The outcomes measured were changes in pulse wave velocity (PWV), systolic blood pressure and diastolic blood pressure. RESULTS: There was no difference in PWV between interventions (B-A 0.00 m/s, 95% CI: -0.30, 0.31 m/s; C-A 0.01 m/s, 95% CI: -0.38, 0.40 m/s). There was also no change in pulse wave analysis, systolic or diastolic blood pressure between interventions. There was an appropriate increase in urinary sodium excretion in the added sodium interventions. CONCLUSION: Dietary salt loading did not produce significant increases in PWV and blood pressure in normotensive subjects with systolic blood pressure <130 mmHg. The lack of an observed effect supports Guyton's pressure-natriuresis hypothesis with appropriate renal excretion of the excess sodium load.


Assuntos
Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Sódio na Dieta/administração & dosagem , Adulto , Feminino , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Fluxo Pulsátil , Sódio na Dieta/metabolismo
19.
J Pharmacokinet Pharmacodyn ; 38(6): 787-801, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21997468

RESUMO

Anaemia of chronic kidney disease (CKD) is a common complication in patients with renal impairment, especially in end-stage renal failure. As well as erythropoietin deficiency, decreased red blood cell survival is a contributing factor. However, it remains unclear which mechanism underlies the altered survival of red blood cells (RBCs). In this work a previously developed statistical model for RBC survival was applied to clinical data obtained from 14 patients with CKD undergoing hemodialysis as well as 14 healthy controls using radioactive chromium (5¹Cr) as random labelling method. A classical two-stage approach and a full population analysis were applied to estimate the key parameters controlling random destruction and senescence in the model. Estimating random destruction was preferred over estimating an accelerated senescence in both approaches and both groups as it provided the better fit to the data. Due to significant nonspecific random loss of the label from the cells that cannot be quantified directly only a relative RBC survival can be obtained from data using 5¹Cr as labelling method. Nevertheless, RBC survival was found to be significantly reduced in CKD patients compared to the controls with a relative reduction of 20-30% depending on the analysis method used.


Assuntos
Anemia/fisiopatologia , Sobrevivência Celular/fisiologia , Eritrócitos/fisiologia , Falência Renal Crônica/fisiopatologia , Modelos Biológicos , Anemia/sangue , Anemia/complicações , Anemia/diagnóstico por imagem , Estudos de Casos e Controles , Radioisótopos de Cromo , Eritrócitos/diagnóstico por imagem , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Cintilografia , Diálise Renal
20.
Am J Kidney Dis ; 58(4): 591-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21715072

RESUMO

BACKGROUND: Shortening of red blood cell (RBC) survival contributes to the anemia of chronic kidney disease. The toxic uremic environment accounts for the decreased RBC life span. The contribution of mechanical damage caused by hemodialysis to the shortened life span is unclear. Reductions up to 70% in RBC survival have been reported in uremic patients. To date, no accurate well-controlled RBC survival data exist in dialysis patients treated using different dialysis modalities and receiving erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to determine RBC survival in hemodialysis (HD) and peritoneal dialysis (PD) patients compared with healthy persons. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 14 HD patients and 5 PD patients were recruited from the dialysis unit. Healthy volunteers (n = 14) age- and sex-matched to HD participants were included. All dialysis patients received either ESA therapy or regular iron supplementation. PREDICTOR: Dialysis patients versus age- and sex-matched healthy controls. OUTCOMES: RBC survival. MEASUREMENTS: RBC survival was determined using radioactive chromium labeling. RESULTS: More than 85% of dialysis patients were anemic (hemoglobin, 12.0 ± 1.1 g/dL); hemoglobin concentrations were not significantly different between HD and PD patients. Median RBC survival was significantly decreased by 20% in HD patients compared with healthy controls: 58.1 (25th-75th percentile, 54.6-71.2) versus 72.9 (25th-75th percentile, 63.4-87.8) days (P = 0.02). No difference was shown between the PD and HD groups: 55.3 (25th-75th percentile, 49.0-60.2) versus 58.1 (25th-75th percentile, 54.6-71.2) days (P = 0.2). LIMITATIONS: Label loss from RBCs associated with the chromium 51 labeling technique needs to be accounted for in the interpretation of RBC survival data. CONCLUSIONS: Despite current ESA therapy, decreased RBC survival contributes to chronic kidney disease-related anemia, although the reduction is less than previously reported. There does not appear to be net mechanical damage associated with HD therapy resulting in decreased RBC life span.


Assuntos
Envelhecimento Eritrocítico , Falência Renal Crônica/sangue , Diálise Renal , Adulto , Idoso , Anemia/sangue , Anemia/tratamento farmacológico , Anemia/epidemiologia , Arteriolosclerose/sangue , Arteriolosclerose/complicações , Estudos de Casos e Controles , Radioisótopos de Cromo/sangue , Feminino , Hematínicos/uso terapêutico , Hemoglobinas/análise , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Diálise Peritoneal , Doenças Renais Policísticas/sangue , Doenças Renais Policísticas/complicações
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