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.

Chronic kidney disease mineral bone disorder in childhood and young adulthood: a 'growing' understanding.

Chronic kidney disease (CKD) mineral and bone disorder (MBD) comprises a triad of biochemical abnormalities (of calcium, phosphate, parathyroid hormone and vitamin D), bone abnormalities (turnover, mineralization and growth) and extra-skeletal calcification. Mineral dysregulation leads to bone demineralization causing bone pain and an increased fracture risk compared to healthy peers. Vascular calcification, with hydroxyapatite deposition in the vessel wall, is a part of the CKD-MBD spectrum and, in turn, leads to vascular stiffness, left ventricular hypertrophy and a very high cardiovascular mortality risk. While the growing bone requires calcium, excess calcium can deposit in the vessels, such that the intake of calcium, calcium- containing medications and high calcium dialysate need to be carefully regulated. Normal physiological bone mineralization continues into the third decade of life, many years beyond the rapid growth in childhood and adolescence, implying that skeletal calcium requirements are much higher in younger people compared to the elderly. Much of the research into the link between bone (de)mineralization and vascular calcification in CKD has been performed in older adults and these data must not be extrapolated to children or younger adults. In this article, we explore the physiological changes in bone turnover and mineralization in children and young adults, the pathophysiology of mineral bone disease in CKD and a potential link between bone demineralization and vascular calcification.

Effects of nutritional supplementation stabilizing muscle mass loss in older patients on hemodiafiltration.

BACKGROUND & AIMS: Malnutrition is common in older individuals with end-stage renal disease on maintenance dialysis. Whether nutritional supplementation may improve skeletal muscle mass (SMM) and survival rate in this population is uncertain. We aimed to analyze the effect of a year of nutritional supplementation on muscle mass and survival rate in older patients on hemodiafiltration. METHODS: In this observational study, older patients (≥65 years old) on maintenance hemodiafiltration were selected to receive nutritional counselling + nutritional supplementation (N = 85, Supp+) or nutritional counselling alone (N = 47, Supp-) and followed for 1 year. The outcomes were a change in SMM and sarcopenia diagnosis. The secondary outcome was 1-year mortality rate. Nutritional parameters included calf circumference, body mass index, anthropometric measurements, subjective global assessment, and handgrip strength (HGS). Data were evaluated using GLM for repeated measures with adjustment for covariates (age and diabetes). RESULTS: Malnutrition was found in 50.8% of patients. At baseline, patients from the Supp+ group were older and had worse nutritional parameters including hand grip strength, calf circumference, anthropometric findings and sarcopenia (all p values < 0.05). During the follow-up, there was no significant change in sarcopenia (from 50.8% to 58.3%, p = 0.108), and there was a more pronounced decrease in the SMM index in the Supp-group (p = 0.049), with a significant intervention interaction (p = 0.030). Twenty deaths occurred, 7 (35%) in the Supp- and 13 (65%) in the Supp+ group (p = 0.540). SMM index (relative risk 0.90, p = 0.030) and age (relative risk 1.07, p = 0.046) were independently associated with higher mortality rates. CONCLUSION: Nutritional supplementation in older and malnourished individuals undergoing hemodiafiltration mitigates the loss of the SMM index and benefits survival rate.

Corneal and Coronary Calcification in Maintenance Hemodialysis: The Face Is No Index to the Heart.

Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly evaluated in this population. Whether CCC correlates with coronary artery calcification remains unknown since studies so far have relied on methods with low sensitivity. Our objective was to test the relationship between CCC and coronary calcification based on tomography. This was a cross-sectional study that included patients on maintenance dialysis. Clinical, demographic, and biochemical data (calcium, phosphorus, parathormone, alkaline phosphatase, and 25(OH)-vitamin D) were recorded. Hyperparathyroidism was defined as parathyroid hormone (PTH) > 300 pg/mL. CCC was evaluated by anterior segment optical coherence tomography (AS-OCT), and coronary calcium scores (Agatston method) were assessed by computed tomography. We compared no/mild with moderate/severe CCC. Twenty-nine patients were included (49.6 ± 15.0 years, 62.1% female, on hemodialysis for 5.7 [2.7-9.4] years, 17.2% with diabetes mellitus, 75.9% with hyperparathyroidism). CCC was found in 82.7% of patients, with median scores of 9 (3, 14.5), ranging from 0 to 16. CCC was classified as absent/mild, moderate, and severe in 27.6%, 20.7%, and 51.7%, respectively. Coronary calcification was found in 44.8% of patients, with median scores of 11 (0, 464), varying from 0 and 6456. We found no significant correlation between coronary calcium scores and CCC (r = 0.203, p = 0.282). Hyperphosphatemia was more frequent in patients with moderate/severe CCC than in those with absent/mild CCC. We concluded that CCC was frequent in patients with CKD on dialysis and did not correlate with coronary calcium scores. Hyperphosphatemia appears to contribute to CCC. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Older patients are less prone to fast decline of renal function: a propensity-matched study.

PURPOSE: Despite CKD is common among older patients, and although factors associated with CKD progression have been explored over decades, little is known about the decline of renal function specifically in older individuals. METHODS: We included adult patients with CKD on conservative management in a propensity-score matched study 1:1 older (> 65 year) and young (≤ 65 yr). Factors associated with the slope of the decline of eGFR such as proteinuria, initial eGFR, diabetes, sex, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor block (ACEI/ARB) were analyzed. Inclusion criteria were at least two consultations in the service and an initial eGFR lower than 45 ml/min/m2, in the period between January 2012 and December 2017. RESULTS: Crude analysis of eGFR decline shows a slower progression of older patients when compared to younger patients in both absolute change [- 2.0 (- 4.5, - 1.0) vs. -3.0 (- 7.0, - 1.0) ml/min/1.73m2, p < 0.001] and slope of eGFR reduction [- 2.2 (- 4.4, - 1.0) vs. 3.1 (- 6.7, - 1.2)) ml/min/1.73m2, p < 0.001]. Patients considered fast progressors (> 5 ml/min/1.73 m2/year decline in eGFR) were less likely to be older (35.2% young vs. 22.0% older, p < 0.001). Adjusted logistic multivariate regression confirmed that older patients had less odds ratio of eGFR decline, independently of the presence of proteinuria, diabetes, ACEI/ARB use, sex, baseline eGFR, baseline phosphate and baseline 25(OH) vitamin D. CONCLUSION: Older patients present slower CKD progression even after multiple adjustments. This information should be taken into consideration while treating these patients on conservative management and should be kept in mind while planning dialysis start.

Self-reported and objective sleep duration in patients with CKD: are they telling the same story? / Duração do sono autorrelatada e objetiva em pacientes com DRC: contam a mesma história?

Abstract Introduction: There is disagreement between data on sleep duration obtained from questionnaires and objective measurements. Whether this is also true for individuals with CKD is unknown. Here we compared self-reported sleep duration with sleep duration obtained by actigraphy. Methods: This prospective study included adult individuals with stage 3 CKD recruited between September/2016 and February/2019. We evaluated subjective sleep duration by asking the following question: "How many hours of actual sleep did you get at night?" Results: Patients (N=34) were relatively young (51 ± 13 years). Self-reported and measured sleep duration were 7.1 ± 1.7 and 6.9 ± 1.6 hours, respectively, with no correlation between them (p=0.165). Although the mean difference between measurements was 0.21 h, the limits of agreement ranged from -3.7 to 4.1 h. Conclusion: Patients with CKD who are not on dialysis have an erroneous sleep perception. Data on sleep duration should be preferentially obtained from objective measurements in patients with CKD.

Resumo Introdução: Há discordância entre os dados sobre duração do sono obtidos a partir de questionários e medições objetivas. Não se sabe se isto também é verdade para indivíduos com DRC. Aqui comparamos a duração do sono autorrelatada com a duração do sono obtida por meio de actigrafia. Métodos: Este estudo prospectivo incluiu indivíduos adultos com DRC estadio 3 recrutados entre Setembro/2016 e Fevereiro/2019. Avaliamos a duração subjetiva do sono, fazendo a seguinte questão: "Quantas horas de sono real você teve à noite?" Resultados: Os pacientes (N=34) eram relativamente jovens (51 ± 13 anos). A duração do sono autorrelatada e mensurada foi de 7,1 ± 1,7 e 6,9 ± 1,6 horas, respectivamente, sem correlação entre elas (p=0,165). Embora a diferença média entre as medições tenha sido de 0,21 h, os limites de concordância variaram de -3,7 a 4,1 h. Conclusão: Pacientes com DRC que não estão em diálise apresentam uma percepção equivocada do sono. Dados sobre a duração do sono devem ser obtidos preferencialmente a partir de medições objetivas em pacientes com DRC.

Self-reported and objective sleep duration in patients with CKD: are they telling the same story?

INTRODUCTION: There is disagreement between data on sleep duration obtained from questionnaires and objective measurements. Whether this is also true for individuals with CKD is unknown. Here we compared self-reported sleep duration with sleep duration obtained by actigraphy. METHODS: This prospective study included adult individuals with stage 3 CKD recruited between September/2016 and February/2019. We evaluated subjective sleep duration by asking the following question: "How many hours of actual sleep did you get at night?" RESULTS: Patients (N=34) were relatively young (51 ± 13 years). Self-reported and measured sleep duration were 7.1 ± 1.7 and 6.9 ± 1.6 hours, respectively, with no correlation between them (p=0.165). Although the mean difference between measurements was 0.21 h, the limits of agreement ranged from -3.7 to 4.1 h. CONCLUSION: Patients with CKD who are not on dialysis have an erroneous sleep perception. Data on sleep duration should be preferentially obtained from objective measurements in patients with CKD.

Calf Circumference Predicts Falls in Older Adults on Hemodialysis.

OBJECTIVE: Older patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis are at a higher risk of falling. However, there is no standard method to screen patients at higher risk. We have evaluated whether calf circumference (CC) measurement would be able to predict falls in this population. METHODS: This is a prospective study that enrolled patients aged ≥65 years on conventional hemodialysis, followed for 6 months. The presence of falls was associated with demographical, clinical, and biochemical data. Reduced CC was set at <34 cm for men and <33 cm for women. We evaluated physical status using Duke activity status index (DASI) and hand grip strength (HGS). RESULTS: Ninety-one patients were included (age 73.7 ± 5.4 years, 69.2% men, 56% with diabetes). Mean CC was 32.6 ± 3.7 cm, with a high prevalence of reduced CC (61.5%). During the follow-up, 13 falls were identified (1 had a fracture and died). These patients were older and heavier (P = .017 and P = .025, respectively). Most falls occurred in patients with sarcopenic obesity (BMI >27 kg/m2 plus reduced HGS or reduced CC). In a logistic regression model, reduced CC (hazard ratio (HR) 7.81, confidence interval (CI): 1.13-53.86, P = .037), higher age (HR 1.19, CI: 1.04-1.36, P = .011), and higher body weight (relative risk (RR) 1.13, CI: 1.04-1.22, P = .003) were independently associated with falls in a fully adjusted model. CONCLUSION: CC measurement, an easy and nonexpensive tool, was able to predict falls in older patients on HD. Further studies should test the inclusion of CC in a fall risk assessment in older patients on hemodialysis.

A randomized clinical trial to evaluate the effects of icodextrin on left ventricular mass index in peritoneal dialysis.

Left ventricular hypertrophy is a risk factor for cardiovascular mortality in patients on peritoneal dialysis (PD). Because icodextrin has a greater ultrafiltration power compared with glucose-based solutions for long dwell, it could improve left ventricular mass by reducing fluid overload. This was a randomized clinical trial that included patients on PD recruited from 2 teaching hospitals, in Sao Paulo-Brazil. Patients were allocated to the control glucose group (GLU) or the intervention icodextrin (ICO) group. Clinical and cardiac magnetic resonance image (MRI) parameters were evaluated at baseline and 6 months after randomization. The primary outcome was the change in left ventricular mass adjusted by surface area (ΔLVMI), measured by cardiac MRI. A total of 22 patients completed the study (GLU, N = 12 and ICO, N = 10). Baseline characteristics such as age, sex, underlying disease, and time on dialysis were similar in both groups. At baseline, 17 patients (77.3%) presented with left ventricular hypertrophy with no difference between groups (p = 0.748). According to the total body water (TBW)/extracellular water (ECW) ratio, 36.8% and 80% of patients from GLU and ICO groups, respectively, were considered hypervolemic (p = 0.044). During follow-up, ΔLVMI was 3.9 g/m (- 10.7, 2.2) in GLU and 5.2 (- 26.8, 16.8) in ICO group (p = 0.651). ΔLVMI correlated with change in brain natriuretic peptide (r = 0.566, p = 0.044), which remained significant in a multiple regression analysis. The use of the icodextrin-based solution in prevalent patients on PD compared with a glucose-based solution was not able to improve LMV. A larger randomized trial with a longer follow-up period may be needed to show changes in LVM in this patient population.Trial registration: this study has been registered at ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification #RBR-2mzhmj2, available at: https://ensaiosclinicos.gov.br/pesquisador .

Phosphate balance during dialysis and after kidney transplantation in patients with chronic kidney disease.

PURPOSE OF REVIEW: In patients with chronic kidney disease (CKD), hyperphosphatemia is associated with several adverse outcomes, including bone fragility and progression of kidney and cardiovascular disease. However, there is a knowledge gap regarding phosphate balance in CKD. This review explores its current state, depending on the stage of CKD, dialysis modalities, and the influence of kidney transplantation. RECENT FINDINGS: Adequate phosphate control is one of the goals of treatment for CKD-mineral and bone disorder. However, ongoing studies are challenging the benefits of phosphate-lowering treatment. Nevertheless, the current therapy is based on dietary restriction, phosphate binders, and optimal removal by dialysis. In the face of limited adherence, due to the high pill burden, adjuvant options are under investigation. The recent discovery that intestinal absorption of phosphate is mostly paracellular when the intraluminal concentration is adequate might help explain why phosphate is still well absorbed in CKD, despite the lower levels of calcitriol. SUMMARY: Future studies could confirm the benefits of phosphate control. Greater understanding of the complex distribution of phosphate among the body compartments will help us define a better therapeutic strategy in patients with CKD.

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.

Returning to PD after kidney transplant failure is a valuable option.

PURPOSE: There is a paucity of data on the prognosis for patients returning to peritoneal dialysis (PD) after a failed transplant. PD has an advantage over hemodialysis in preserving residual renal function, which is associated with better outcomes. METHODS: We have reviewed the electronic charts of patients on PD in a tertiary academic hospital for the last 8 years. We have compared technique survival, peritonitis-free survival, and residual diuresis in two groups: patients with graft failure which returned to PD (PD-KTx, N = 18) and patients starting PD for other causes (PD-not KTx, N = 163). RESULTS: The median follow-up was similar between groups [42(16,71) in PD-not KTx vs. 48(22,90) months in PD-KTx, p = 0.293]. Kaplan-Meier survival comparing PD-KTx and PD-not KTx showed no difference in technique survival (p = 0.196), and peritonitis-free survival (log-rank 0.238), which were confirmed in a fully adjusted Cox regression. Diuresis at baseline and at the end of the first year was similar between groups (p = 0.799 and p = 0.354, respectively). Six out of 18 patients from the PD-KTx group had the immunosuppression maintained and none of those had peritonitis. The reduction of diuresis across the first year of PD was significant for all patients, except for those on continued immunosuppressive therapy. CONCLUSION: PD is a worthy dialysis alternative after a failed kidney transplant, providing similar outcomes when compared to patients who started PD for other reasons.

Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis / Consequências esqueléticas e cardiovasculares de um balanço positivo de cálcio durante a hemodiálise

Abstract Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.

Resumo Pacientes em hemodiálise são expostos ao cálcio, por meio do dialisato, pelo menos três vezes por semana. As alterações no cálcio sérico variam de acordo com a transferência de massa de cálcio durante a diálise, que é dependente do gradiente entre a concentração de cálcio no plasma e no dialisato (d [Ca]) e o estado de renovação do esqueleto que altera a capacidade do osso de incorporar cálcio. Embora subestimado, o d [Ca] pode potencialmente causar balanço positivo de cálcio que leva a danos em órgãos sistêmicos, incluindo associações com mortalidade, disfunção miocárdica, tolerabilidade hemodinâmica, calcificação vascular e arritmias. A fisiopatologia desses efeitos adversos inclui alterações do cálcio sérico, supressão do hormônio da paratireóide e calcificação vascular por meio de efeitos diretos e indiretos. Alguns órgãos são mais suscetíveis a alterações na homeostase do cálcio. Nesta revisão, discutimos os dados existentes e os mecanismos potenciais que ligam o d [Ca] ao equilíbrio do cálcio com a consequente disfunção no esqueleto, miocárdio e artérias.

Effects of diuretics furosemide and hydrochlorothiazide on CKD-MBD: A prospective randomized study.

Although diuretics are often prescribed to control fluid overload, they can change Chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters. Previous studies have shown an association between diuretic prescription and changes in both calciuria and parathormone levels. However, the causal relationship could not be confirmed. In addition, the effects of diuretics on bone mineral density and turnover markers are yet to be established. To evaluate the effects of diuretics on CKD-MBD, we have performed a prospective randomized trial comparing hydrochlorothiazide with furosemide in a stage 3CKD population followed for 1 year. Furosemide increased bone remodeling and parathormone levels, whereas hydrochlorothiazide attenuated parathyroid hormone rise and decreased bone turnover markers.

The disparity of measuring bone mineral content using bioimpedance and dual-energy absorptiometry in the context of hyperparathyroidism.

INTRODUCTION: Body composition is critical for the evaluation of patients with Chronic Kidney Disease (CKD) and can be obtained from either multifrequency bioelectrical impedance analysis (BIA) or dual-energy absorptiometry (DXA). Although the discrepancy between the results obtained from both methods has already been described, reasons are unknown, and might be related to secondary hyperparathyroidism, which is associated with bone loss. METHODS: We have evaluated 49 patients (25 males and 24 females): 20 with CKD not on dialysis and 29 on maintenance hemodialysis [18 with severe hyperparathyroidism (HD-SHPT) and 11 submitted to parathyroidectomy (HD-PTX)]. All patients underwent DXA and BIA. RESULTS: The median age and body mass index (BMI) were 49 years and 25.6 kg/m2, respectively. Patients exhibited low bone mineral content (BMC) measured by DXA, particularly those from the HD-SHPT group. The largest BMC measurement disagreement between DXA and BIA was found in the HD-SHPT group (p=0.004). Factors independently associated with this discrepancy in BMC measurement were serum phosphate (p=0.003) and patient group (p=0.027), even after adjustments for age, BMI, and gender (adjusted r2=0.186). PTX attenuated this difference. DISCUSSION: BIA should be interpreted with caution in patients with SHPT due to a loss of accuracy, which can compromise the interpretation of body composition.

Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis.

Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.