Phosphate is associated with frailty in older patients with chronic kidney disease not on dialysis.

PURPOSE: Frailty is common in older patients with chronic kidney disease (CKD) and has been considered an independent risk factor for adverse clinical outcomes in this population. CKD-associated mineral and bone metabolism (CKD-MBD) increases energy expenditure and causes malnutrition and inflammation leading to frailty. We investigated whether CKD-MBD markers and energy metabolism are associated with frailty in patients with advanced CKD on conservative management. METHODS: In this cross-sectional study, we investigated factors associated with frailty in a sample of 75 patients ≥ 65 years, with stage 4 or 5 CKD. Collected data included age, sex, body mass index, physical activity status, educational level, Charlson Comorbidity Index, and laboratory markers. Frailty was evaluated according to Fried's classification. RESULTS: Frailty was observed in 51.3% and pre-frailty in 47.3%. The frail population was significantly older, with a high proportion of females, more inactive, had lower educational levels, spent a long time sitting throughout the day, and had higher phosphate and fibroblast growth factor 21 (FGF-21). In the multivariate logistic analysis age (odds ratio 1.13, p = 0.026) and phosphate (odds ratio 3.38, p = 0.021) remained independently associated with frailty. CONCLUSION: Serum phosphate seems to be a toxin associated with the frailty phenotype in older patients with CKD. Whether strategies to decrease serum phosphate would reduce the risk of frailty in this population deserves further evaluation.

Glomerular filtration in the aging population.

In the last decades, improvements in the average life expectancy in the world population have been associated with a significant increase in the proportion of elderly people, in parallel with a higher prevalence of non-communicable diseases, such as hypertension and diabetes. As the kidney is a common target organ of a variety of diseases, an adequate evaluation of renal function in the approach of this population is of special relevance. It is also known that the kidneys undergo aging-related changes expressed by a decline in the glomerular filtration rate (GFR), reflecting the loss of kidney function, either by a natural senescence process associated with healthy aging or by the length of exposure to diseases with potential kidney damage. Accurate assessment of renal function in the older population is of particular importance to evaluate the degree of kidney function loss, enabling tailored therapeutic interventions. The present review addresses a relevant topic, which is the effects of aging on renal function. In order to do that, we analyze and discuss age-related structural and functional changes. The text also examines the different options for evaluating GFR, from the use of direct methods to the implementation of several estimating equations. Finally, this manuscript supports clinicians in the interpretation of GFR changes associated with age and the management of the older patients with decreased kidney function.

Hyperuricemia is associated with secondary hyperparathyroidism in patients with chronic kidney disease.

PURPOSE: Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism. METHODS: This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65 pg/ml. RESULTS: Our patients were mostly Caucasian women, with a mean age of 64 ± 16 years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol. CONCLUSION: Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated.

Design and methodology of the Aging Nephropathy Study (AGNES): a prospective cohort study of elderly patients with chronic kidney disease.

BACKGROUND: Renal replacement therapy (RRT) is usually indicated for patients with chronic kidney disease (CKD) with glomerular filtration rate below 10 ml/ml/min/1.73m2. However, the need for RRT and timing of dialysis initiation are debatable for patients aged 70 years or older. We here describe the study design and methodology of the Aging Nephropathy Study (AGNES) protocol that aims at evaluating to what extent geriatric-related conditions such as frailty, cognitive dysfunction, and presence of comorbidities have an impact on survival and RRT initiation in this group of patients. In this manuscript we provide detailed information about the AGNES study design and methodology. METHODS: AGNES is a prospective observational cohort that aim to investigate clinical, biochemical and demographic factors associated with RRT initiation and mortality of patients with CKD stage 4 or 5 who are aged 70 years and older. We plan to include 200 patients over 5 years. Clinically stable outpatients on conservative management for at least 6 months will be recruited from the Nephrogeriatric Clinic at the Hospital das Clinicas da Universidade de Sao Paulo, Brazil. Eligible patients are submitted to a full clinical examination, geriatric assessment, and blood test at baseline. Following the baseline visit the patients are being monitored during an observational follow up period of at least 12 months during which patients will be contacted in the clinic at their regular follow up or by phone until either RRT initiation or death occurs. This cohort includes evaluation of cognition by the education-adjusted 10-point Cognitive Screener (10-CS), frailty by Fried index score, a complete nutritional assessment (by body composition assessment, global subjective assessment and dietary intake), comorbidities by Charlson comorbidity index and biochemical markers including FGF-23 and Klotho. DISCUSSION: The AGNES cohort, a real-world study of current clinical practice in elderly patients with advanced CKD prior to dialysis initiation, will shed light into progression of CKD and its complications, indications of RRT and factors determining survival. This investigation will elucidate to what extent geriatric conditions, nutritional status and clinical factors are associated with survival, quality of life and RRT initiation in elderly CKD patients not yet on dialysis. TRIAL REGISTRATION: Registered on ClinicalTrials.gov on 18 October 2019 ( NCT04132492 ).

Delirium and Adverse Outcomes in Hospitalized Patients with COVID-19.

BACKGROUND: Little is known about the association between acute mental changes and adverse outcomes in hospitalized adults with COVID-19. OBJECTIVES: To investigate the occurrence of delirium in hospitalized patients with COVID-19 and explore its association with adverse outcomes. DESIGN: Longitudinal observational study. SETTING: Tertiary university hospital dedicated to the care of severe cases of COVID-19 in São Paulo, Brazil. PARTICIPANTS: A total of 707 patients, aged 50 years or older, consecutively admitted to the hospital between March and May 2020. MEASUREMENTS: We completed detailed reviews of electronic medical records to collect our data. We identified delirium occurrence using the Chart-Based Delirium Identification Instrument (CHART-DEL). Trained physicians with a background in geriatric medicine completed all CHART-DEL assessments. We complemented our baseline clinical information using telephone interviews with participants or their proxy. Our outcomes of interest were in-hospital death, length of stay, admission to intensive care, and ventilator utilization. We adjusted all multivariable analyses for age, sex, clinical history, vital signs, and relevant laboratory biomarkers (lymphocyte count, C-reactive protein, glomerular filtration rate, D-dimer, and albumin). RESULTS: Overall, we identified delirium in 234 participants (33%). On admission, 86 (12%) were delirious. We observed 273 deaths (39%) in our sample, and in-hospital mortality reached 55% in patients who experienced delirium. Delirium was associated with in-hospital death, with an adjusted odds ratio of 1.75 (95% confidence interval = 1.15-2.66); the association held both in middle-aged and older adults. Delirium was also associated with increased length of stay, admission to intensive care, and ventilator utilization. CONCLUSION: Delirium was independently associated with in-hospital death in adults aged 50 years and older with COVID-19. Despite the difficulties for patient care during the pandemic, clinicians should routinely monitor delirium when assessing severity and prognosis of COVID-19 patients.

Longitudinal Pharmacokinetics of Everolimus When Combined With Low-level of Tacrolimus in Elderly Renal Transplant Recipients.

BACKGROUND: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. METHODS: We studied 12-hour everolimus (EVL) PK in 16 elderly renal transplant recipients (all whites; 10 men; mean age, 64 ± 2 years (61-71 years), in 4 separate timepoints (at 7, 30, 60, and 150 days) after EVL introduction, corresponding to a mean postrenal transplantation day: PK1 (43 ± 4 days), PK2 (65 ± 7 days), PK3 (106 ± 17 days), and PK4 (206 ± 40 days). Patients received EVL (target trough level (Ctrough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target Ctrough, 2-5 ng/mL). RESULTS: Mean TCL-Ctrough was 7.2 ± 3.8, 4.9 ± 2.2, 4.9 ± 2.2, and 4.5 ± 1.2 ng/mL at PK1, PK2, PK3, and PK4, respectively. There were no differences among timepoints for mean EVL daily dose (data shown as PK3) (3.5 ± 1.3 mg/d), Ctrough (4.7 ± 2.5 ng/mL), AUC0-12h (106 ± 51 ng/h per mL), Caverage (8.8 ± 4.2 ng/mL), Cmax (19.2 ± 9.7 ng/mL), apparent Half-life (11.7 ± 4.2 hours), estimated total body clearance (0.39 ± 0.27 L/h), or fluctuation (166 ± 65%). Also, none of those PK parameters differed statistically when adjusted for body weight. EVL-Ctrough showed a very high correlation (r = 0.849) with AUC0-12h. CONCLUSIONS: Our data indicate that elderly renal transplant recipients starting EVL 1 month after transplantation along with a steady-state TCL level, present stable EVL-PK parameters without significant changes in dose or exposure during the first 6 months after renal transplantation.

Clinical conditions and memory complaints in outpatient elderly.

Memory complaints are common in elderly, and may be associated with many clinical problems. OBJECTIVE: To identify clinical conditions and possible factors related to memory complaints in elderly outpatients presenting at a tertiary unit. METHODS: Patients with memory complaints and normal cognitive screening tests were submitted to clinical and laboratorial testing. Radiological evaluation was performed as needed for diagnosis. RESULTS: One hundred and seventy-seven subjects were initially evaluated, 12 were excluded because of poor and inconsistent memory complaints. Of the remainder, seventeen had criteria for dementia diagnosis. Ninety-two (55.4%) had one or more comorbid conditions possibly related to their complaints. Major depression was present in 26.0%. Sixteen patients (9.6%) had vitamin B12 deficiency, 8 were in use of inappropriate medications, and 7 (4.2%) had hypothyroidism. Other conditions diagnosed were: generalized anxiety disorder, obstructive sleep apnea syndrome, hyperparathyroidism, normal pressure hydrocephalus. Three patients had severe hearing loss (in 22 with hearing complaints); one had severe visual impairment (in 22 with visual complaints). CONCLUSIONS: Comprehensive evaluation was able to identify treatable conditions possibly related to memory complaints.

Queixas de memória são comuns em idosos, podendo estar associadas a diversos problemas clínicos. OBJETIVO: Identificar condições clínicas e fatores relacionadas a queixas de memória em pacientes idosos encaminhados a um serviço terciário. MÉTODOS: Pacientes com queixas de memória e testes de rastreio cognitivo normal foram submetidos a avaliação clínica detalhada e testes laboratoriais, além de avaliação radiológica quando necessário para o diagnóstico. RESULTADOS: Cento e setenta e sete pacientes foram inicialmente avaliados, sendo 12 excluídos devido a queixas frustras e inconsistentes de memória. Dos restantes, 17 preenchiam critérios clínicos para diagnóstico de demência. Noventa e dois (55,4%) apresentavam uma ou mais condições clínicas possivelmente relacionadas às queixas. Depressão maior estava presente em 26%. Dezesseis pacientes (9,6%) tinham deficiência de vitamina B12, 8 estavam em uso de medicações inapropriadas e 7 (4,2%), hipotireoidismo. Outras condições diagnosticadas foram: transtorno de ansiedade generalizada, síndrome da apnéia obstrutiva do sono, hiperparatireoidismo e hidrocefalia de pressão normal. Três pacientes apresentavam hipoacusia grave (em 22 com queixas auditivas), e 1 apresentava perda visual grave (em 22 com queixas visuais). CONCLUSÕES: Avaliação detalhada pode identificar diversas condições clínicas tratáveis, possivelmente relacionadas às queixas de memória.

Efeitos dos exercícios resistidos no desempenho cognitivo de idosos com comprometimento da memória: resultados de um estudo controlado / Effects of resistance training exercise on cognitive performance in elderly individuals with memory impairment: results of a controlled trial

Objetivo: Detectar os efeitos de um programa de exercíciosresistidos no desempenho cognitivo e na força muscular de idosossedentários com comprometimento da memória. Métodos: Trinta eum idosos sedentários sem demência ou depressão foram distribuídosaleatoriamente em dois grupos: Grupo Atividade Física e Grupo Controle.O programa de exercícios resistidos durou nove meses e consistiu detrês séries de seis exercícios por sessão, realizados em aparelhos comsistema de alavancas, por aproximadamente uma hora, duas vezespor semana. Ambos os grupos foram submetidos aos seguintes testescognitivos a cada três meses: Teste Comportamental de Memóriade Rivermead (RBMT), Amplitude de Dígitos Diretos e Indiretosdo Wechsler Adult Intelligence Scale (WAIS), Escala de Queixas deMemória e Teste Cognitivo de Cambridge (CAMCOG). Resultados:Após nove meses, o grupo que realizou os exercícios resistidos teve umaumento significativo do escore padronizado do RBMT (p = 0,021) eda força muscular (p < 0,001), sem diferença significativa dos demaisparâmetros avaliados. Conclusões: Estes resultados indicam que osexercícios resistidos supervisionados podem melhorar o desempenhoda memória em idosos sedentários com prévio comprometimento,além de determinar o aumento da força muscular.