Progression of coronary artery calcification in conventional hemodialysis, nocturnal hemodialysis, and kidney transplantation.

INTRODUCTION: Cardiovascular disease is the leading cause of death in end-stage renal disease (ESRD) and is strongly associated with vascular calcification. An important driver of vascular calcification is high phosphate levels, but these become lower when patients initiate nocturnal hemodialysis or receive a kidney transplant. However, it is unknown whether nocturnal hemodialysis or kidney transplantation mitigate vascular calcification. Therefore, we compared progression of coronary artery calcification (CAC) between patients treated with conventional hemodialysis, nocturnal hemodialysis, and kidney transplant recipients. METHODS: We measured CAC annually up to 3 years in 114 patients with ESRD that were transplantation candidates: 32 that continued conventional hemodialysis, 34 that initiated nocturnal hemodialysis (≥4x 8 hours/week), and 48 that received a kidney transplant. We compared CAC progression between groups as the difference in square root transformed volume scores per year (ΔCAC SQRV) using linear mixed models. Reference category was conventional hemodialysis. RESULTS: The mean age of the study population was 53 ±13 years, 75 (66%) were male, and median dialysis duration was 28 (IQR 12-56) months. Median CAC score at enrollment was 171 (IQR 10-647), which did not differ significantly between treatment groups (P = 0.83). Compared to conventional hemodialysis, CAC progression was non-significantly different in nocturnal hemodialysis -0.10 (95% CI -0.77 to 0.57) and kidney transplantation -0.33 (95% CI -0.96 to 0.29) in adjusted models. CONCLUSIONS: Nocturnal hemodialysis and kidney transplantation are not associated with significantly less CAC progression compared to conventional hemodialysis during up to 3 years follow-up. Further studies are needed to confirm these findings, to determine which type of calcification is measured with CAC in end-stage renal disease, and whether that reflects cardiovascular risk.

Geriatric Assessment and the Relation with Mortality and Hospitalizations in Older Patients Starting Dialysis.

BACKGROUND AND OBJECTIVES: A geriatric assessment (GA) is a structural method for identifying frail patients. The relation of GA findings and risk of death in end-stage kidney disease (ESKD) is not known. The objective of the GA in OLder patients starting Dialysis Study was to assess the association of GA at dialysis initiation with early mortality and hospitalization. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients ≥65 years old were included just prior to dialysis initiation. All participants underwent a GA, including assessment of (instrumental) activities of daily living (ADL), mobility, cognition, mood, nutrition, and comorbidity. In addition, a frailty screening (Fried Frailty Index, [FFI]) was applied. Outcome measures were 6- and 12-month mortality, and 6-month hospitalization. Associations with mortality were assessed with cox-regression adjusting for age, sex, comorbidity burden, smoking, residual kidney function and dialysis modality. Associations with hospitalization were assessed with logistic regression, adjusting for relevant confounders. RESULTS: In all, 192 patients were included, mean age 75 ± 7 years, of whom 48% had ≥3 geriatric impairments and were considered frail. The FFI screening resulted in 46% frail patients. Mortality rate was 8 and 15% at 6- and 12-months after enrolment, and transplantation rate was 2 and 4% respectively. Twelve-month mortality risk was higher in patients with ≥3 impairments (hazard ratio [HR] 2.97 [95% CI 1.19-7.45]) compared to less impaired patients. FFI frail patients had a higher risk of 12-month mortality (HR 7.22 [95% CI 2.47-21.13]) and hospitalization (OR 1.93 [95% CI 1.00-3.72]) compared to fit patients. Malnutrition was associated with 12-month mortality, while impaired ADL and depressive symptoms were associated with 12-month mortality and hospitalization. CONCLUSIONS: Frailty as assessed by a GA is related to mortality in elderly patients with ESKD. Individual components of the GA are related to both mortality and hospitalization. As the GA allows for distinguishing between frail and fit patients initiating dialysis, it is potentially of added value in the decision-making process concerning dialysis initiation.

Association of Initiation of Maintenance Dialysis with Functional Status and Caregiver Burden.

BACKGROUND AND OBJECTIVES: Little is known about the functional course after initiating dialysis in elderly patients with ESKD. The aim of this study was to assess the association of the initiation of dialysis in an elderly population with functional status and caregiver burden. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: This study included participants aged ≥65 years with ESKD who were enrolled in the Geriatric Assessment in Older Patients Starting Dialysis study. All underwent a geriatric assessment and a frailty screening (Fried Frailty Index and Groningen Frailty Indicator) at dialysis initiation. Functional status (activities of daily life and instrumental activities of daily life) and caregiver burden were assessed at baseline and after 6 months. Decline was defined as loss of one or more domains in functional status, stable as no difference between baseline and follow-up, and improvement as gain of one or more domains in functional status. Logistic regression was performed to assess the association between the combined outcome functional decline/death and potential risk factors. RESULTS: Of the 196 included participants functional data were available for 187 participants. Mean age was 75±7 years and 33% were women. At the start of dialysis, 79% were care dependent in functional status. After 6 months, 40% experienced a decline in functional status, 34% remained stable, 18% improved, and 8% died. The prevalence of high caregiver burden increased from 23%-38% (P=0.004). In the multivariable analysis age (odds ratio, 1.05; 95% confidence interval, 1.00 to 1.10 per year older at baseline) and a high Groningen Frailty Indicator compared with low score (odds ratio, 1.97; 95% confidence interval, 1.05 to 3.68) were associated with functional decline/death. CONCLUSIONS: In patients aged ≥65 years, functional decline within the first 6 months after initiating dialysis is highly prevalent. The risk is higher in older and frail patients. Loss in functional status was mainly driven by decline in instrumental activities of daily life. Moreover, initiation of dialysis is accompanied by an increase in caregiver burden.

Geriatric Assessment in Elderly Patients with End-Stage Kidney Disease.

BACKGROUND/AIMS: Decision-making in elderly patients considering dialysis is highly complex. With the increasing number of elderly with end-stage kidney disease (ESKD), it may be important to assess geriatric impairments in this population. The aim of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study was to assess the prevalence of geriatric impairments and frailty in the elderly ESKD population by means of a geriatric assessment (GA), which is a comprehensive tool for overall health assessment. METHODS: This study included 285 patients ≥65 years: 196 patients at the time of dialysis initiation and 89 patients who chose maximal conservative management (MCM). The GA assessed cognition, mood, nutritional status, (instrumental) activities of daily living (ADL), mobility, comorbidity burden, quality of life and overall frailty. RESULTS: The mean age of the participants was 78 years and 36% were women. Of the incident dialysis patients, 77% started haemodialysis and 23% started peritoneal dialysis. Geriatric impairments were highly prevalent in both dialysis and MCM patients. Most frequently impaired geriatric domains in the dialysis group were functional performance (ADL 29%, instrumental ADL (iADL) 79%), cognition (67%) and comorbidity (41%). According to the GA, 77% in the dialysis group and 88% in the MCM group had 2 or more geriatric impairments. In the MCM group, functional impairment (ADL 45%, iADL 85%) was highly prevalent. CONCLUSIONS: Geriatric impairments are highly prevalent in the elderly ESKD population. Since impairments can be missed when not searched for in regular (pre)dialysis care, the first step of improving nephrologic care is awareness of the extensiveness of geriatric impairment.

Coronary Artery Calcification in Hemodialysis and Peritoneal Dialysis.

BACKGROUND: Vascular calcification is seen in most patients on dialysis and is strongly associated with cardiovascular mortality. Vascular calcification is promoted by phosphate, which generally reaches higher levels in hemodialysis than in peritoneal dialysis. However, whether vascular calcification develops less in peritoneal dialysis than in hemodialysis is currently unknown. Therefore, we compared coronary artery calcification (CAC), its progression, and calcification biomarkers between patients on hemodialysis and peritoneal dialysis. METHODS: We measured CAC in 134 patients who had been treated exclusively with hemodialysis (n = 94) or peritoneal dialysis (n = 40) and were transplantation candidates. In 57 of them (34 on hemodialysis and 23 on peritoneal dialysis), we also measured CAC progression annually up to 3 years and the inactive species of desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, osteoprotegerin. We compared CAC cross-sectionally with Tobit regression. CAC progression was compared in 2 ways: with linear mixed models as the difference in square root transformed volume score per year (ΔCAC SQRV) and with Tobit mixed models. We adjusted for potential confounders. RESULTS: In the cross-sectional cohort, CAC volume scores were 92 mm3 in hemodialysis and 492 mm3 in peritoneal dialysis (adjusted difference 436 mm3; 95% CI -47 to 919; p = 0.08). In the longitudinal cohort, peritoneal dialysis was associated with significantly more CAC progression defined as ΔCAC SQRV (adjusted difference 1.20; 95% CI 0.09 to 2.31; p = 0.03), but not with Tobit mixed models (adjusted difference in CAC score increase per year 106 mm3; 95% CI -140 to 352; p = 0.40). Peritoneal dialysis was associated with higher osteoprotegerin (adjusted p = 0.02) but not with dp-ucMGP or fetuin-A. CONCLUSIONS: Peritoneal dialysis is not associated with less CAC or CAC progression than hemodialysis, and perhaps with even more progression. This indicates that vascular calcification does not develop less in peritoneal dialysis than in hemodialysis.

Health-related quality of life compared between kidney transplantation and nocturnal hemodialysis.

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome measure in patients with end-stage renal disease. HRQOL is assumed to improve with kidney transplantation and also with nocturnal hemodialysis compared to conventional hemodialysis. However, there is no evidence regarding HRQOL to support the optimal treatment choice for patients on nocturnal hemodialysis who hesitate opting for transplantation. We therefore compared HRQOL between patients who were treated with kidney transplantation or nocturnal hemodialysis for one year. METHODS: We assessed HQROL using the Kidney Disease Quality of Life-Short Form questionnaire in a cross-sectional sample of patients who were treated with kidney transplantation (n = 41) or nocturnal hemodialysis (n = 31) for one year. All patients on nocturnal hemodialysis were transplantation candidates. Using linear regression, we compared HRQOL between kidney transplantation and nocturnal hemodialysis, and adjusted for age, sex, dialysis duration, cardiovascular disease, and presence of residual urine production. RESULTS: At one year follow-up, mean age of the study population was 54 ±13 years, and median dialysis duration was 3.2 (IQR 2.1-5.0) years. Kidney transplantation was associated with significantly higher HRQOL on the domain "effects" compared to nocturnal hemodialysis (adjusted difference 12.0 points, 95% CI 3.9; 20.1). There were potentially clinically relevant differences between kidney transplantation and nocturnal hemodialysis on the domains "burden" (adjusted difference 11.1 points, 95% CI -2.6; 24.8), "social support" (adjusted difference 6.2, 95% CI -6.6; 19.1), and the physical composite score (adjusted difference 3.0, 95% CI -2.0; 8.1), but these were not significant. CONCLUSIONS: After kidney transplantation, HRQOL is especially higher on the domain "effects of kidney disease" compared to nocturnal hemodialysis. This can be useful when counseling patients on nocturnal hemodialysis who may opt for transplantation.

Frailty Screening Tools for Elderly Patients Incident to Dialysis.

BACKGROUND AND OBJECTIVES: A geriatric assessment is an appropriate method for identifying frail elderly patients. In CKD, it may contribute to optimize personalized care. However, a geriatric assessment is time consuming. The purpose of our study was to compare easy to apply frailty screening tools with the geriatric assessment in patients eligible for dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 123 patients on incident dialysis ≥65 years old were included <3 weeks before to ≤2 weeks after dialysis initiation, and all underwent a geriatric assessment. Patients with impairment in two or more geriatric domains on the geriatric assessment were considered frail. The diagnostic abilities of six frailty screening tools were compared with the geriatric assessment: the Fried Frailty Index, the Groningen Frailty Indicator, Geriatric8, the Identification of Seniors at Risk, the Hospital Safety Program, and the clinical judgment of the nephrologist. Outcome measures were sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: In total, 75% of patients were frail according to the geriatric assessment. Sensitivity of frailty screening tools ranged from 48% (Fried Frailty Index) to 88% (Geriatric8). The discriminating features of the clinical judgment were comparable with the other screening tools. The Identification of Seniors at Risk screening tool had the best discriminating abilities, with a sensitivity of 74%, a specificity of 80%, a positive predictive value of 91%, and a negative predictive value of 52%. The negative predictive value was poor for all tools, which means that almost one half of the patients screened as fit (nonfrail) had two or more geriatric impairments on the geriatric assessment. CONCLUSIONS: All frailty screening tools are able to detect geriatric impairment in elderly patients eligible for dialysis. However, all applied screening tools, including the judgment of the nephrologist, lack the discriminating abilities to adequately rule out frailty compared with a geriatric assessment.

A closer look at the trajectory of physical functioning in chronic hemodialysis.

Background: in chronic hemodialysis, physical functioning (PF) is known to be poor. We set out to assess to what extent chronic dialysis patients are able to maintain a good physical condition over time and what the influence of age is on the trajectory of PF. Methods: we used data form 714 prevalent hemodialysis patients, enrolled in the CONvective TRAnsport STudy (CONTRAST). The PF subscale of the KDQOL SF-36 was assessed at baseline (n = 679) and during 2 years of follow-up (n = 298). Baseline PF score (0-100) was categorized into tertiles (good, intermediate and low). Change of PF of ≥ 5 points was considered clinically relevant. A regression model was applied to assess factors related to 'decline of PF (≥5 points)/low PF (0-33) at follow-up'. Results: during follow-up, only 15.3 % (1 out of 6) of patients succeeded in maintaining a good physical condition, the remainder deteriorated or died. Of the older patients (≥75) only 3.6% remained in a good physical condition. Factors related to decline/low PF were increasing age (odds ratio [OR] = 1.96 [95% CI: 1.03-3.72] for 65-74 years and OR = 2.38 [95%CI: 1.17-4.84] for ≥75 years compared to <65 years) and albumin (OR = 1.10 [95%CI: 1.01-1.18] per g/L decrease). Conclusion: very few hemodialysis patients maintain a good physical condition over a 2-year time span. Especially in older patients, physical performance is poor and decline is faster than in the healthy population. These findings should be taken into account when considering dialysis in older patients and more emphasis should be placed to attempts for improving physical condition.

The Relevance of Geriatric Impairments in Patients Starting Dialysis: A Systematic Review.

BACKGROUND AND OBJECTIVES: With aging of the general population, patients who enter dialysis therapy will more frequently have geriatric impairments and a considerable comorbidity burden. The most vulnerable among these patients might benefit from conservative therapy. Whether assessment of geriatric impairments would contribute to the decision-making process of dialysis initiation is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic Medline and Embase search was performed on December 1, 2015 to identify studies assessing the association between risk of mortality or hospitalization and one or more geriatric impairments at the start of dialysis therapy, including impairment of cognitive function, mood, performance status or (instrumental) activities of daily living, mobility (including falls), social environment, or nutritional status. RESULTS: Twenty-seven studies were identified that assessed one or more geriatric impairments with respect to prognosis. The quality of most studies was moderate. Only seven studies carried out an analysis of elderly patients (≥70 years old). Malnutrition and frailty were systematically assessed, and their relation with mortality was clear. In addition, cognitive impairment and functional outcomes at the initiation of dialysis were related to an increased mortality in most studies. However, not all studies applied systematic assessment tools, thereby potentially missing relevant impairment. None of the studies applied a geriatric assessment across multiple domains. CONCLUSIONS: Geriatric impairment across multiple domains at dialysis initiation is related to poor outcome. However, information in the elderly is sparse, and a systematic approach of multiple domains with respect to poor outcome has not been performed. Because a geriatric assessment has proved useful in predicting outcome in other medical fields, its potential role in the ESRD population should be the subject of future research.