Geriatric considerations in older persons with end-stage kidney disease.

Decision-making in older persons with end-stagebkidney disease (ESKD) regarding dialysis initiation is highly complex. While some older persons improve with dialysis and maintain a good quality of life, others experience less benefit and multiple complications due to a high morbidity burden and (early) mortality. Geriatric impairments are highly prevalent among this population and these impairments may complicate the care of an older person with ESKD. Knowledge of these impairments can potentially help improve care and decision-making regarding dialysis initiation and advance care planning. Therefore, the aim of this review is to give healthcare providers an insight into the existing literature on geriatric impairments in older persons with ESKD. Furthermore, specific areas of concern will be discussed, in combination with some practical advice.

Thoracic vertebral fractures and hyperkyphosis in elderly patients with end-stage kidney disease; do these patients have different clinical outcomes?

BACKGROUND AND OBJECTIVES: Elderly patients with end-stage kidney disease (ESKD) are at high risk for fractures. However, the prevalence of vertebral fractures and hyperkyphosis is not studied well. This is relevant, because in the general population, both vertebral fractures and hyperkyphosis are associated with poor outcome. Therefore, the primary aim of our study was to assess the prevalence of vertebral fractures and hyperkyphosis in the ESKD population. The secondary aim was to assess if patients with vertebral fractures and/or hyperkyphosis more often have poor outcome after starting dialysis, such as accidental falling, functional decline and mortality compared to the patients without vertebral fractures and/or hyperkyphosis. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: This study included patients ≥65 years with ESKD who were enrolled in the Geriatric assessment in Older patients starting Dialysis (GOLD) study of whom a lateral chest radiograph was available. Chest radiographs were scored independently by two observers for vertebral fractures (Genant ≥1) and hyperkyphosis (≥50 degrees). The relation between vertebral fractures and hyperkyphosis with clinical outcomes (falls, decline in ADL and IADL, mortality) was studied using the Chi-square test. RESULTS: Of the 196 enrolled patients, chest radiographs were available for 160 patients. Mean age was 75.3 (SD ±6.9), and 35% were female. The prevalence of vertebral fractures was 43% and of hyperkyphosis 22%. Patients with hyperkyphosis had a higher one-year mortality compared to patients without hyperkyphosis (20% vs. 8%, p = 0.04). No differences were observed between patients with and without hyperkyphosis, vertebral fractures and the remaining outcomes after six months of follow-up. CONCLUSIONS: In patients ≥65 years old with ESKD starting dialysis, vertebral fractures are highly prevalent. In contrast to the general population, patients with vertebral fractures did experience poor outcome as often as patients without vertebral fractures. Remarkably, patients with hyperkyphosis did have a higher one-year mortality. However, these patients did not experience more functional decline or accidental falls.

Quality of life after the initiation of dialysis or maximal conservative management in elderly patients: a longitudinal analysis of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study.

BACKGROUND: Maximal conservative management (MCM) may be an appropriate alternative option for dialysis in some elderly patients with end-stage kidney disease (ESKD). Evidence about the impact of dialysis or MCM on quality of life (QoL) in older patients is sparse. In the GOLD (Geriatric assessment in OLder patients starting Dialysis) Study the trajectory of QoL was assessed in patients starting dialysis or MCM. METHODS: Patients ≥65 years old were included just prior to dialysis initiation or after decision for MCM. Baseline data included demographics, frailty as measured with a geriatric assessment, comorbidity (CIRS-G) and QoL, measured with the EQ-5D-3 L (EQ-5D Index and overall self-rated health). Six months follow-up data included QoL, hospitalizations and mortality. Change of QoL was assed with paired t-tests. Cox-regression was used to assess survival of MCM and dialysis patients. RESULTS: The cohort comprised 192 dialysis and 89 MCM patients. The MCM patients were older (mean age 82 ± 6 vs. 75 ± 7 years, p <  0.01) and mean kidney function was better (eGFR 11.5 ± 4.0 vs. 8.0 ± 2.9 ml/min/1.73m2, p <  0.01). Baseline QoL did not differ significantly between the groups. After six months, EQ-5D Index did not improve significantly in the dialysis group with mean ± standard error (SE) 0.026 ± 0.014 (p = 0.10; not clinically relevant), but a small but clinically relevant decline was seen in the conservative group: 0.047 ± 0.022 (p < 0.01; between group difference p < 0.01). Hospitalization occurred in 50% of dialysis patients vs. 24% of conservative patients (p < 0.01). In patients over 80 years old, no survival benefit could be found for dialysis patients starting dialysis vs. MCM. CONCLUSION: A small decline of QoL was found for conservative patients, while QoL did not change in dialysis patients. However, hospitalization rate was higher in patients starting dialysis. In patients over 80 years, no survival benefit was found.

Home haemodialysis in the Netherlands: State of the art.

Home haemodialysis (HHD) has gained popularity in recent years, due to improved clinical outcomes associated with frequent or prolonged haemodialysis sessions, best achievable at home. However, several barriers to HHD are perceived by the physician and patient, among which lack of experience and education, logistic difficulties and reimbursement issues seem to be the most important ones. HHD, in particular when performed with intensified frequency or duration, is associated with improved quality of life, blood pressure control and survival. Serious adverse events are rare; however, more vascular access complications arise due to frequent needling. This emphasises the importance of comprehensive education and training. This review aims to provide the physician with a detailed state of the art overview on HHD in the Netherlands, discussing potential barriers and benefits, and offering practical advice.

Quality of life as indicator of poor outcome in hemodialysis: relation with mortality in different age groups.

BACKGROUND: Physical, cognitive and psychosocial functioning are frequently impaired in dialysis patients and impairment in these domains relates to poor outcome. The aim of this analysis was to compare the prevalence of impairment as measured by the Kidney Disease Quality of Life- Short Form (KDQOL-SF) subscales between the different age categories and to assess whether the association of these subscales with mortality differs between younger and older dialysis patients. METHODS: This study included data from 714 prevalent hemodialysis patients, from 26 centres, who were enrolled in the CONvective TRAnsport STudy (CONTRAST NCT00205556, 09-12-2005). Baseline HRQOL domains were evaluated for patients <65 years, 65-74 years and over 75 years. Multivariable Cox proportional hazards analyses were performed to assess the relation between the separate domains and 2-year mortality. RESULTS: Emotional health was higher in patients over the age of 75 compared to younger patients (mean level 71, 73 and 77 for increasing age categories respectively, p = 0.02), whilst physical functioning was significantly lower in older patients (mean level 60, 48 and 40, p < 0.01). A low level of physical functioning (Hazard Ratio (HR) 1.72 [95%Confidence Interval (CI) 1.02-2.73]), emotional health (HR 1.85 [95% 1.30-2.63]), and social functioning (HR 1.59 [95% CI 1.12-2.26]), was individually associated with an increased 2-year mortality within the whole population. The absence of effect modification suggests no evidence for different relations within the older age groups. CONCLUSIONS: In dialysis patients, older age is associated with lower levels of physical functioning, whilst the level of emotional health is not associated with age. KDQOL-SF domains physical functioning, emotional health and social functioning are independently associated with mortality in prevalent younger and older hemodialysis patients.

Groningen frailty indicator in older patients with end-stage renal disease.

BACKGROUND: Currently over 55% of end-stage renal disease (ESRD) patients are aged ≥60 years and patients >75 years represent the fastest growing segment of the dialysis population. We aimed to assess whether the Groningen frailty indicator (GFI) can be used to distinguish fit older ESRD patients, likely able to tolerate and benefit from dialysis, from frail older patients who need further evaluation with a geriatrician's comprehensive assessment. METHODS: All patients aged ≥65 years visiting the pre-dialysis unit at the Gelre hospital between 2007 and 2013 were included and underwent the GFI (n = 65). Patients with GFI ≥ 4 (frail) were referred for geriatric consultation (n = 13). Results of the GFI and nephrologists' evaluation were compared with geriatrician's assessment. Survival rates and outcomes after one year of follow up were recorded. RESULTS: Twenty patients (32%) were identified as frail. Of the problems identified by the geriatrician in 13 patients, 55% were not reported in the nephrologists' notes. The first year after inclusion, 30% of patients with a GFI ≥ 4 died, compared to 9% of fit patients (p = 0.04). Moreover, 90% of frail patients had been hospitalized one or more times, compared to 53% in the fit group (p = 0.005). CONCLUSION: Although the GFI can be a useful instrument to identify ESRD patients at risk, both the GFI and the nephrologists' assessment failed to identify specific geriatric impairments. Further research is needed to develop a specific frailty indicator for ESRD patients and to determine the value and effect of a comprehensive geriatric assessment in ESRD patients.

A national survey on the decision-making process of dialysis initiation in elderly patients.

BACKGROUND: The decision-making process of dialysis initiation in the elderly involves different considerations compared with younger patients. Cognitive, functional and psychosocial issues are likely to be more important than standard prognostic factors. To assess the role of these issues in the decision-making process regarding dialysis initiation in the elderly, a survey was conducted among nephrologists in the Netherlands. METHODS: An internet-based survey was sent to all members of the Netherlands Federation of Nephrology. RESULTS: Out of 298 invited, 94 Dutch nephrologists responded to the questionnaire. Reaching consensus with the patient and relatives and early withdrawal are difficult issues in the decision-making process in elderly end-stage renal disease patients. Geriatric impairments were considered (very) relevant issues (varying from 7- 0 on a scale from 1-10) in the context of dialysis initiation, with cognitive dysfunction being most relevant (median 10, range 6-10). The majority of nephrologists (56%) underlined the need for screening for geriatric problems when considering dialysis in the elderly. A total of 26% reported using some form of screening measurement for the determination of the presence of one or more geriatric impairments. CONCLUSIONS: Although cognitive, functional and psychosocial issues are considered relevant items in the context of dialysis initiation in the elderly, systematic assessment of these items is not standard of care in nephrology practice. Future research is needed to determine whether a more systematic screening for the presence of geriatric impairments can improve the decision-making process.

Effect of corticosteroids on nuclear factor-kappaB activation and hemodynamics in late septic shock.

OBJECTIVE: To describe the underlying pathophysiologic mechanisms of the effect of corticosteroids in a patient with late septic shock. DESIGN: Case report. SETTING: The medical intensive care unit at University Medical Center Utrecht. PATIENT: An 86-yr-old female patient with late septic shock requiring mechanical ventilation and vasopressive agents. INTERVENTIONS: Administration of hydrocortisone, 300 mg daily. MEASUREMENTS AND MAIN RESULTS: Within 3 days of corticosteroid treatment, the patient could be weaned of vasopressive agents and mechanical ventilation. Serum C-reactive protein levels normalized. Nuclear factor-kappaB activation in unstimulated and in vitro lipopolysaccharide-stimulated peripheral blood mononuclear cells decreased to background level within 5 days. Repeated functional tests of the hypothalamic-pituitary-adrenal axis were normal. CONCLUSION: Our data suggest that the pathophysiologic mechanism behind the clinical effects of supraphysiologic doses of corticosteroids in late septic shock is directly related to the inhibition of nuclear factor-kappaB in peripheral blood mononuclear cells.

Pharmacokinetics and dosing regimen of meropenem in critically ill patients receiving continuous venovenous hemofiltration.

OBJECTIVE: To study the pharmacokinetics of meropenem in critically ill patients with acute renal failure receiving continuous venovenous hemofiltration (CWHF). DESIGN: Prospective, open-labeled study. SETTING: Medical intensive care unit of the University Medical Center Utrecht. PATIENTS: Five critically ill patients receiving CWHF for acute renal failure treated with meropenem for documented or suspected bacterial infection. INTERVENTION: All patients received meropenem (500 mg) administered intravenously every 12 hrs. Plasma samples and ultrafiltrate aliquots were collected during one dosing interval. MEASUREMENTS AND RESULTS: Mean age and body weight of the patients studied were 46.6 yrs (range, 28-61 yrs) and 85.8 kg (range, 70-100 kg), respectively. The following pharmacokinetic variables for meropenem were obtained: mean peak plasma concentration was 24.5 +/- 7.2 mg/L, mean trough plasma concentration was 3.0 +/- 0.9 mg/L, mean terminal elimination half-life was 6.37 +/- 1.96 hrs, mean total plasma clearance was 4.57 +/- 0.89 L/hr, mean CWHF clearance was 1.03 +/- 0.42 L/hr, mean nonrenal clearance was 3.54 +/- 1.06 L/hr, and mean volume of distribution was 0.37 +/- 0.15 L/kg. CONCLUSION: In critically ill patients with acute renal failure, nonrenal clearance became the main elimination route. CWHF substantially contributed to the clearance of meropenem (23% of mean total plasma clearance). We recommend meropenem to be dosed at 500 mg intravenously every 12 hrs in patients receiving CWHF, according to our operational characteristics. This dosing regimen resulted in adequate trough plasma levels for susceptible microorganisms.

Hemoperfusion is ineffectual in severe chloroquine poisoning.

OBJECTIVES: To study the toxicokinetics in severe chloroquine poisoning, and to evaluate the efficacy of hemoperfusion. DESIGN: Case report on one observation. SETTING: Medical intensive care unit (ICU) of the University Medical Center Utrecht, The Netherlands. PATIENT HISTORY: A previously healthy, 52-yr-old woman ingested 100 tablets containing 100 mg chloroquine base 1 hr before admission. At admission, she was drowsy, agitated, hypotensive, and in respiratory distress. Shortly thereafter, she was resuscitated from cardiac arrest. After hemodynamic and respiratory stabilization, the patient was transferred to the medical ICU. TOXICOKINETICS EVALUATION: During the course of her stay at the ICU, blood samples were taken for the determination of chloroquine and the metabolite desethylchloroquine concentration. Hemoperfusion was started 3.5 hrs after ingestion of the chloroquine tablets. MEASUREMENTS AND MAIN RESULTS: The following toxicokinetics data during this severe chloroquine poisoning were calculated: apparent volume of the central compartment 181 L, apparent volume of distribution 1137 L, half-life in the distribution phase 6.4 hrs, half-life in the elimination phase 392.8 hrs, and total body clearance 2.01 L/hour. The average extraction ratio during hemoperfusion was 0.07, 0.28, and 0.25, in plasma, erythrocytes and whole blood, respectively. The total amount of chloroquine removed by hemoperfusion was only 480 mg (5.3% of the amount ingested). Simulation of a hemoperfusion session over 5 hrs by using a column with an optimal extraction ratio of 1.0 would have removed 1,816 mg chloroquine, only 18.2% of the amount ingested. This limited contribution of hemoperfusion to the total clearance makes it ineffective. CONCLUSION: Hemoperfusion is not effective in severe chloroquine poisoning, even when started (relatively) early in the course of the intoxication. Toxicokinetic evaluation of a chloroquine poisoning should be based on the evaluation of plasma and whole blood concentrations.

Factors predicting survival for HIV-infected patients with respiratory failure.

BACKGROUND: Despite improved treatment modalities, the mortality of HIV infected patients admitted to the intensive care unit with respiratory failure remains high. To help ICU physicians in advising HIV infected patients whether to undergo mechanical ventilation, we retrospectively investigated prognostic factors predicting hospital outcome for HIV-infected patients, admitted to a medical intensive care unit with respiratory failure before the era of highly-active anti-retroviral therapy. METHODS: A retrospective chart review was carried out of all HIV-infected patients with respiratory failure admitted to the medical ICU of a Dutch University Hospital between 1991 and 1997. RESULTS: In the six year period, 29 HIV-infected patients were admitted to the ICU for respiratory failure. Mechanical ventilation, CD4 cell count, APACHE II score, APACHE III score, ARDS and length of ICU stay all differed significantly between survivors and non-survivors. However, a multivariate analysis only showed the need for mechanical ventilation as an independent risk factor for mortality. The only combination of factors able to accurately predict mortality for the individual patient was the development of ARDS and the requirement of mechanical ventilation. CONCLUSIONS: The combination of mechanical ventilation and ARDS accurately predicts hospital outcome in HIV-infected patients presenting with respiratory failure before the HAART era.

Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients.

OBJECTIVE: To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF). DESIGN: Open-label study. SETTING: Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht. MATERIALS AND METHODS: In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied. In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin. Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy. After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation. INTERVENTIONS++: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter. MEASUREMENTS AND RESULTS: The average sieving coefficient in vitro was 0.73 +/- 0.06, 0.86 +/- 0.11, and 0.80 +/- 0.06 for the PAN 03, 06, and 10 haemofilters, respectively. Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant. The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion. The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.8 l, terminal half-life time (t(1/2 term)) 15.4 h, total clearance (Cl(tot)) 2.5 l/h, CVVHF clearance (CL(CVVHF, form 1)) 1.4 l/h, and body clearance (Cl(body)) 1.1 l/h. The average sieving coefficient during the study period was 0.89 +/- 0.03. In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, (1/2 term) 20.3 h, Cl(tot) 1.4 l/h, Cl(CVVHF, form 1) 1.4 l/h, and Cl(body) < 0.1 l/h. The average sieving coefficient during the study period was 0.88 +/- 0. 03. The cumulative amount of vancomycin removed by means of CVVHF during the 12-h study period was 245 mg in patient 1 and 228 mg in patient 2. CONCLUSIONS++: CVVHF with a PAN 06 haemofilter effectively removed vancomycin in two critically ill patients. The amount of vancomycin removed with CVVHF was about 250 mg per 12 h. A clear difference in body clearance in the two patients was observed. Our dosage recommendation for vancomycin in critically ill patients receiving CVVHF is a loading dose of 15-20 mg/kg followed after 24 h by 250 to 500 mg twice daily with close monitoring of the serum and ultrafiltrate vancomycin concentration.

Graft flow as a predictor of thrombosis in hemodialysis grafts.

BACKGROUND: The effort to reduce the incidence of graft thrombosis is mainly based on predicting venous stenosis by measuring venous drip chamber pressures. In this study we evaluated whether graft flow measurements, using an ultrasound dilution technique, would be of additional value to identify patients at risk for thrombosis. METHODS: In fifty consecutive patients with a bridge graft we measured graft flow and venous drip chamber pressure at a dialyzer blood flow of 200 ml/min. The results of these flow measurements were not used for selection of patients, nor for a diagnostic or therapeutic procedure. All thrombotic events and (radiological or surgical) interventions were registered. RESULTS: A total of 17 patient-years were analyzed. In 17 patients an intervention was done, and in 18 patients thrombosis occurred. The incidence rate of thrombosis was higher in patients with a flow < 600 ml/min (N = 13) compared to patients with a flow > 600 ml/min (N = 37; rate ratio 7. 2; 95% CI, range 2.84 to 18.24, P < 0.001). In 4 patients with a flow < 600 ml/min an intervention was done within the first two months after the flow measurement. In the remaining 9 patients, 6 grafts thrombosed within this period. Five interventions were done in patients with a flow > 600 ml/min. In the remaining 32 patients only two developed spontaneous thrombosis. Remarkably, venous drip chamber pressure measurements did not discriminate between patients with graft flow > or < 600 ml/min, and showed a wide range in patients who developed spontaneous thrombosis within two months. CONCLUSION: We suggest that graft flow measurements are helpful in selecting patients at risk for graft thrombosis.

Nonaccidental endosulfan intoxication: a case report with toxicokinetic calculations and tissue concentrations.

CASE REPORT: A case of nonaccidental endosulfan intoxication in a previously healthy 43-year-old male patient is reported. On admission, the patient had few symptoms, but refractory seizures began 1 hour after ingestion. The patient died on the fourth day after admission showing clinical signs of cerebral herniation confirmed at autopsy. Blood, urine, and tissue samples were analyzed for alpha-endosulfan, beta-endosulfan, and endosulfan sulfate by capillary gas chromatography with electron capture detection. Concentration versus time data for endosulfan were fitted using the program MW/Pharm, assuming complete bioavailability although it is recognized that the bioavailability of endosulfan after ingestion may have been low and the calculated clearance was primarily due to redistribution. Hemoperfusion was shown to be ineffective.

Pressure or flow recordings for the surveillance of hemodialysis grafts.

Venous pressures (VP) measured by the dialysis machine are widely used for access surveillance and have significantly improved outcomes. VP reflect the resistance in the venous outflow tract, which will rise in the presence of stenosis. Low graft flow caused by high graft resistance predicts thrombosis. In this study we investigated whether high VP coincides with low graft flow (measured by ultrasound dilution technique). Of 70 forearm bridge grafts in 42 chronic hemodialysis patients, 31 had an angiographically proven outflow stenosis. VP at 200 ml/min blood flow (VP200), total graft resistance and venous outflow resistance were higher whereas graft flow was lower in patients with venous outflow tract stenosis as compared to patients without stenosis. Diagnostic power of the tests for identifying patients with venous stenosis showed no important differences. However, arterial inflow resistance, which is not reflected in VP measurements, represented a substantial and, more importantly, a highly variable percentage of total graft resistance. As a result graft flow showed no correlation with VP measurements. In conclusion, although patients with venous outflow stenosis may be identified accurately using venous pressure assessments, graft flow measurements seem to be more suitable for selecting patients at risk for thrombosis.

Access flow measurements in hemodialysis patients: in vivo validation of an ultrasound dilution technique.

In this study, access flow in hemodialysis patients with bridge grafts was measured by a newly developed device. The technique is based on the measurement of changes in the ultrasound characteristics of blood. These changes were initiated by an injection of isotonic saline and measured in the tubes of the extra-corporeal circuit. The access flow rate (mean +/- standard variation) was 880 +/- 440 mL/min (range, 166 to 1740) (N = 46). The mean coefficient of variation was 13.4 +/- 6.8% (median, 13.0%; range 3.5 to 29.4%). Measurements correlated well (r = 0.91, N = 22, P < 0.001) with flow rates determined by magnetic resonance angiography and by a technique based on intra-access flow-pressure curves (r = 0.84, N = 14, P < 0.001). In conclusion, access flow can be measured easily, noninvasively, and reliably by the ultrasound dilution device.

Epidemiology of hip fractures in The Netherlands: women compared with men.

In this retrospective study the epidemiology of hip fractures in The Netherlands was evaluated. The number of hip fractures over the period 1972-1987 was collected from the Dutch Centre for Health Care Information (Stichting Informatiecentrum voor de Gezondheidszorg, SIG). The demographic data were collected from the Dutch Centre for Statistics (Centraal bureau voor de Statistiek, CBS). The age-adjusted incidence of hip fractures for both women and men 50 years of age and over, increased linearly over the period 1972-1987. There was also a linear rise in the age-adjusted incidence of hip fractures in women and men 65 years of age and over, but the rise in incidence was equal in both sexes. After the age of 50 years women and men showed an equal proportional increase in the age-specific incidence of hip fractures by 5-year age groups. This proportional increase was independent of the calendar year studied during the period 1972-1987. The increase over time in the age-adjusted incidence of hip fractures in inhabitants 50 years of age and over is the result of changes that act well before the age of 50 years, because the proportional increase in the age-specific incidence of these fractures after the age of 50 years did not change over the period studied. The cohort analysis showed that the age-specific incidence of hip fractures in more recently born birth cohorts is higher than that in birth cohorts born long ago. This observation agrees with the other observations.(ABSTRACT TRUNCATED AT 250 WORDS)