Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults.

BACKGROUND: Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults. METHODS: In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD. RESULTS: In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20-3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01-3.12). CONCLUSIONS: This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.

[Vaccination status and factors associated with pneumococcal vaccination in geriatric short-stay care]. / Statut vaccinal et facteurs associés à la vaccination antipneumococcique en court séjour gériatrique.

Nearly two-thirds of geriatric short-stay patients were eligible for pneumococcal vaccination. Among patients eligible for vaccination, less than 5 % had received at least one injection of pneumococcal vaccine on admission. We found no modifiable factors associated with vaccination status, but several avenues for improving vaccination coverage.

Diagnostic Validity of Chronic Kidney Disease in Health Claims Data Over Time: Results from a Cohort of Community-Dwelling Older Adults in Germany.

Purpose: The validity of ICD-10 diagnostic codes for chronic kidney disease (CKD) in health claims data has not been sufficiently studied in the general population and over time. Patients and Methods: We used data from the Berlin Initiative Study (BIS), a prospective longitudinal cohort of community-dwelling individuals aged ≥70 years in Berlin, Germany. With estimated glomerular filtration rate (eGFR) as reference, we assessed the diagnostic validity (sensitivity, specificity, positive [PPV], and negative predictive values [NPV]) of different claims-based ICD-10 codes for CKD stages G3-5 (eGFR <60mL/min/1.73m²: ICD-10 N18.x-N19), G3 (eGFR 30-<60mL/min/1.73m²: N18.3), and G4-5 (eGFR <30mL/min/1.73m²: N18.4-5). We analysed trends over five study visits (2009-2019). Results: We included data of 2068 participants at baseline (2009-2011) and 870 at follow-up 4 (2018-2019), of whom 784 (38.9%) and 440 (50.6%) had CKD G3-5, respectively. At baseline, sensitivity for CKD in claims data ranged from 0.25 (95%-confidence interval [CI] 0.22-0.28) to 0.51 (95%-CI 0.48-0.55) for G3-5, depending on the included ICD-10 codes, 0.20 (95%-CI 0.18-0.24) for G3, and 0.36 (95%-CI 0.25-0.49) for G4-5. Over the course of 10 years, sensitivity increased by 0.17 to 0.29 in all groups. Specificity, PPVs, and NPVs remained mostly stable over time and ranged from 0.82-0.99, 0.47-0.89, and 0.66-0.98 across all study visits, respectively. Conclusion: German claims data showed overall agreeable performance in identifying older adults with CKD, while differentiation between stages was limited. Our results suggest increasing sensitivity over time possibly attributable to improved CKD diagnosis and awareness.

NSAIDs for Pain Control During the Peri-Operative Period of Hip Fracture Surgery: A Systematic Review.

BACKGROUND: Hip fracture (HF) mostly affects older adults and is responsible for increased morbidity and mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) are part of the peri-operative multimodal analgesic management, but their use could be associated with adverse events in older adults. This systematic review aimed to assess outcomes associated with NSAIDs use in the peri-operative period of HF surgery. METHODS: This systematic review was conducted according to the PRISMA guidelines. Three databases (PubMed/EMBASE/Cochrane Central) were used to search for clinical trials and observational studies assessing efficacy, safety and impact of NSAIDs use on non-specific post-operative outcomes, such as functional status and post-operative complications. RESULTS: Among the 1320 references initially identified, four provided data on efficacy, four on safety and six on non-specific post-operative outcomes (three randomized controlled clinical trials, three observational studies). Mean study population ages ranged from 68 to 87 years. Two studies found that NSAIDs were effective on pain control, but two studies found conflicting results on opioid sparing. No increased risk of acute kidney injury was observed, while results concerning bleeding risk and delirium were conflicting. No study has found any effect of NSAIDs use on walk recovery. Quality of evidence was high for pain control, but low to very low for all the other studied outcomes. CONCLUSIONS: The use of NSAIDs may be effective for pain control in the peri-operative period of HF surgery. However, safety data were conflicting with low levels of certainty. Further studies are needed to assess their benefit-risk balance in this context. The research protocol was previously registered on PROSPERO (registration number: CRD42021237649).

Kidney function estimators for drug dose adjustment of direct oral anticoagulants in older adults with atrial fibrillation.

Background: The Cockcroft-Gault equation (CrClC-G) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF). Methods: Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated CrClC-G and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status. Results: A total of 224 patients were included in the analysis (median age 87 years). Using CrClC-G, 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using CrClC-G and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using CrClC-G or eGFR. Conclusion: In older adults with AF, the association of DOAC dose status with adverse events did not differ when using CrClC-G or eGFR. Our results suggest that eGFR equations are not inferior to CrClC-G within this context.

Implementation of clinical medication review in a geriatric ward to reduce potentially inappropriate prescriptions among older adults.

PURPOSE: The impact of several pharmaceutical interventions to reduce the use of potentially inappropriate medications (PIMs) and potentially omitted medications (POMs) has been recently studied. We aimed to determine whether clinical medication review (CMR) (i.e. a systematic and patient-centred clinical assessment of all medicines currently taken by a patient) performed by a geriatrician and a pharmacist added to standard pharmaceutical care (SPC) (i.e. medication reconciliation and regular prescription review by the pharmacist) resulted in more appropriate prescribing compared to SPC among older inpatients. METHODS: A retrospective observational single-centre study was conducted in a French geriatric ward. Six criteria for appropriate prescribing were chosen: the number of PIMs and POMs as defined by the STOPP/STARTv2 list, the total number of drugs prescribed, the number of administrations per day and the number of psychotropic and anticholinergic drugs. These criteria were compared between CMR and SPC group using linear and logistic regression models weighted on propensity scores. RESULTS: There were 137 patients included, 66 in the CMR group and 71 in the SPC group. The mean age was 87 years, the sex ratio was 0.65, the mean number of drugs prescribed was 9, the mean MMSE was 21 and at admission 242 POMs, and 363 PIMs were prescribed. Clinical medication review did not reduce the number of PIMs at discharge compared to SPC (beta = - 0.13 [- 0.84; 0.57], p = 0.71) nor did it reduce the number of drugs prescribed (p = 0.10), the number of psychotropic drugs (p = 0.17) or the anticholinergic load (p = 0.87). Clinical medication review resulted in more POMs being prescribed than in standard pharmaceutical care (beta = - 0.39 [- 0.72; - 0.06], p = 0.02). Cardiology POMs were more implemented in the medication review group (p = 0.03). CONCLUSION: Clinical medication review did not reduce the number of PIMs but helped clinicians introduce underused drugs, especially cardiovascular drugs, which are known to be associated with morbidity and mortality risk reduction.

Gripwise Versus Jamar: The Challenge of a New Dynamometer Assessing Handgrip Strength.

BACKGROUND: Sarcopenia diagnosis is partly based on handgrip strength (HGS) assessment. The gold-standard dynamometer for this measurement is the Jamar. The electronic Gripwise is a smaller and lighter one, and its measurements are correlated with the Jamar's in laboratory tests. Our study aimed to confirm this correlation in aged patients. METHODS: This monocenter cross-sectional study was performed in patients of 65 years and older admitted at the University Hospital. Participants were assessed either in a seated or bedridden position, randomly allocated to begin the measurements with the Jamar or the Gripwise. RESULTS: Among 649 aged inpatients assessed for eligibility, 348 were included (mean age: 79 ±â€…9; 52% females). The intraclass correlation coefficient was 0.93 (95% confidence interval [CI] 0.92-0.94, p < .001) for the maximum value measured with both devices and 0.94 (95% CI 0.93-0.95, p < .001) for the mean values. However, there was a significant difference in detecting low values (<16 kg in women, <27 kg in men), found in 48% of patients with Jamar, and 71% with Gripwise (p < .001). Thus, we determined alternate cutoffs for diagnosing HGS low values with the Gripwise (<12 kg in women, <22 kg in men), further validated in a supplementary validation population (n = 70). The diagnostic performances of these alternative cutoffs were high (93% sensitivity and 87% specificity in women; 94% sensitivity and 96% specificity in men). CONCLUSIONS: The correlation of the Gripwise with the Jamar was confirmed in aged inpatients. However, lower values recorded with the Gripwise require alternate cutoffs for a relevant low HGS diagnosis.

[Pyoderma gangrenosum and hemopathies in older patients]. / Pyoderma gangrenosum et hémopathies chez la personne âgée.

Pyoderma gangrenosum (PG) belongs to neutrophilic dermatoses. PG can have different clinical presentations (ulcerated, bullous, pustular), is often painful, and preferentially affects the lower limbs. The diagnosis can be challenging, and a cutaneous biopsy is often necessary, which shows an aseptic cutaneous infiltrate of neutrophils. The association with inflammatory or hematologic conditions is frequent, especially in older patients. The hematologic diseases the most frequently associated with PG are myelodysplastic syndrome, followed by monoclonal gammopathy of undetermined significance. Because of the strong impact of its treatment, recognition of PG is crucial. The treatment is based on first-line corticosteroids and topical or systemic immunosuppressive drugs and most often leads to a favourable outcome. The management of an acute hematologic disease would further improve the prognosis of PG. The singularity of geriatric patients encourages to thoroughly balance the risks and benefits of the recommended drugs and to consider associated non-drug measures. Here, we propose a review of the scientific literature about the association between PG and hematologic diseases, with a special focus on older patients, accompanied by the report of two cases in geriatric ward.

[Validation of a method for detecting hospitalizations for falls related to adverse drug reactions in geriatric departments]. / Validation d'une méthode de détection des hospitalisations pour chute liées à un effet indésirable médicamenteux en service de gériatrie aiguë.

Fall is one of the five main causes of drug-related hospital admissions (DRA) in France. A standardized chart review method, to identify DRA adapted to elderly patients, has recently been developed by Thevelin et al. Our first aim was to assess the reliability of this method for detecting DRA for falls in elderly subjects. Our second aim was to assess the feasibility of this method and to evaluate its reliability for assessing causality, the contribution of DRA to hospitalization, and the avoidability of DRAs in elderly patients hospitalized for a medication-related fall. A retrospective observational study was conducted on 16 patient cases admitted to the hospital for falls in May 2022, in the geriatric department of a French university hospital. Six healthcare professionals (pharmacists, pharmacologists, and geriatricians) assessed a method for detecting DRA individually and then in multidisciplinary pairs of raters. Inter-rater agreement (individually and in pairs) was assessed for DRA detection, causality, avoidability, and contribution of the DRA to hospitalization. A κ > 0,4 was considered a satisfactory threshold for agreement. The mean age was 86 years. When the assessment was done individually, detection of DRA-related hospitalizations (κ = 0,46; p < ,001), and DRA contribution to hospitalization (κ = 0,50; p < ,001) were moderately concordant. The causality assessment (κ = 0,09; p = 0,24) did not agree, and the avoidability assessment (κ = 0,63; p < ,001) agreed substantially. When the evaluation was done in pairs, detection of DRA-related hospitalizations (κ = 0,47; p < ,001) was moderately concordant between pairs. Avoidability assessment (κ = 0,79; p < ,001) concurred substantially. The assessment of causality (κ = 0,29; p = 0,01) and DRA contribution to hospitalization (κ = 0,38; p < .001) agreed fairly well. This study validated, individually and in pairs, the reliability of the method to identify DRA in the context of falls. This method will be of great use in research and epidemiological studies.

Effectiveness and Tolerance of Renin-Angiotensin System Inhibitors With Aging in Chronic Kidney Disease.

OBJECTIVES: Renin-angiotensin system inhibitors (RASi) are recommended for slowing chronic kidney disease (CKD) progression to kidney failure. Their effectiveness and tolerance as patients age remain uncertain because older patients have often been excluded from clinical trials. DESIGN: CKD-REIN cohort study. SETTING AND PARTICIPANTS: We studied 2762 patients with CKD stages 3 and 4 and a clinical indication for RASi enrolled between 2013 and 2016 in 40 nephrology clinics nationally representative in France. METHODS: The primary outcome was the occurrence of kidney failure or death. The secondary outcomes were the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. A propensity score analysis was performed. We used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age. RESULTS: Patients' mean age was 67 years, including 841 (30%) aged 75 years and older; 2178 (79%) were prescribed RASi's. During a median follow-up of 4.6 years, 33% of patients reached kidney failure or died. RASi prescription was associated with a lower risk of kidney failure or death (HR 0.79, 95% CI 0.66, 0.95), an association not modified by age (P for interaction = .72). It was not significantly associated with cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia, but risk was not higher among those prescribed RASi's (HR 0.75, 95% CI 0.55-1.02) and age did not modify its effect (P for interaction = .28). CONCLUSIONS AND IMPLICATIONS: This study shows that aging does not appear to modify either RASi's beneficial effects on major CKD outcomes or their potential adverse effects.

Chronic kidney disease and cognitive impairment.

Chronic kidney disease (CKD) affects 25% of people over the age of 70. Neurocognitive disorders (NCDs) are frequent in patients with CKD and affect 30% to 60% of patients treated by haemodialysis. The link between CKD and NCD is explained by common risk factors, such as hypertension and diabetes, but also by CKD-specific risk factors through vascular, degenerative, and toxic mechanisms. In patients with non-dialysed CKD, albuminuria is more strongly linked to the occurrence of NCD than glomerular filtration rate. Vascular dementia is the main cause of NCDs in patients with CKD, but the incidence of Alzheimer's disease has also been found to be higher in patients with end-stage renal disease (ESRD) than in the general population. Executive functions, orientation and attention are the most frequently affected cognitive domains in patients with CKD. The occurrence of NCDs in older patients with CKD could be prevented by controlling blood pressure or by using anticoagulant drugs in the case of atrial fibrillation, which is particularly frequent in patients with CKD, in order to prevent cerebrovascular lesions. Nephrological care could also influence the occurrence of neurological complications. Anticholinesterase drugs and memantine should be used with caution in patients with CKD, as most of these drugs accumulate due to a low glomerular filtration rate. Due to the poor prognosis of patients with NCD and ESRD treated by dialysis or kidney transplantation, a cognitive assessment should be proposed in older patients with severe CKD in order to discuss the initiation and type of renal replacement therapy with both patients and caregivers.

[Chronic kidney disease and cognitive impairment]. / Maladie rénale chronique et troubles neurocognitifs.

Chronic kidney disease (CKD) affects 25% of people aged over 70 years. Cognitive impairment (CI) is frequent in patients with CKD and affects 30% to 60% of patients treated by hemodialysis. The link between CKD and CI is explained by common risk factors, such as hypertension and diabetes, but also by CKD-specific risk factors through vascular, degenerative, and toxic mechanisms. In patients with non-dialyzed CKD, albuminuria is more strongly linked to CI occurrence than glomerular filtration rate. Vascular dementia is the main cause of CI in patients with CKD, but incidence of Alzheimer's disease has also been found higher in patients with end-stage of kidney disease than in the general population. Executive functions, orientation and attention are the most frequently affected cognitive domains in patients with CKD. Occurrence of CI in older patients with CKD could be prevented by controlling blood pressure or the use of anticoagulant drugs in case of atrial fibrillation, which is particularly frequent in patients with CKD, in order to prevent cerebrovascular lesions. Nephrological care could also influence the occurrence of neurological complications. Anticholinesterasic drugs and memantine should be used with caution in patients with CKD, because most of these drugs accumulates in case of low glomerular filtration rate. Due to the poor prognosis of patients with CI and end-stage of kidney disease treated by dialysis or kidney transplantation, a cognitive assessment should be proposed to older patients with severe CKD in order to discuss the initiation and the type of renal replacement therapy with both patients and caregivers.

Impact of age on cardiovascular drug use in patients with chronic kidney disease.

BACKGROUND: Elderly patients with chronic kidney disease (CKD) are often excluded from clinical trials; this may affect their use of essential drugs for cardiovascular complications. We sought to assess the impact of age on cardiovascular drug use in elderly patients with CKD. METHODS: We used baseline data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort including 3033 adult patients with CKD Stages 3 and 4. We studied the use of recommended drugs for coronary artery disease (CAD), stroke and atrial fibrillation by age, after adjusting for socio-demographic and clinical conditions. RESULTS: The patients' mean age was 66.8 years (mean estimated glomerular filtration rate 32.9 mL/min/1.73 m2). The prevalence of CAD was 24.5% [81.3% receiving antiplatelet agents, 75.6% renin-angiotensin system (RAS) blockers, 65.4% ß-blockers and 81.3% lipid-lowering therapy], that of stroke 10.0% (88.8% receiving antithrombotic drugs) and that of atrial fibrillation 11.1% (69.5% receiving oral anticoagulants). Compared with patients aged <65 years, older age (≥65 years) was associated with greater use of antithrombotic drugs in stroke [adjusted odds ratio (aOR) (95% confidence interval) = 2.83 (1.04-7.73) for patients aged (75-84 years)] and less use of RAS blockers [aOR = 0.39 (0.16-0.89) for patients aged ≥85 years], ß-blockers [aOR = 0.31 (0.19-0.53) for patients aged 75-84 years] and lipid-lowering therapy [aOR = 0.39 (0.15-1.02) for patients aged ≥85 years, P for trend = 0.01] in CAD. Older age was not associated with less use of antiplatelet agents in CAD or oral anticoagulants in atrial fibrillation. CONCLUSIONS: In patients with CKD, older age per se was not associated with the underuse of antithrombotic drugs but was for other major drugs, with a potential impact on cardiovascular outcomes.

Procalcitonin and C-Reactive Protein for Bacterial Infection Diagnosis in Elderly Patients After Traumatic Orthopedic Surgery.

BACKGROUND: Biomarkers prove valuable for diagnosing postoperative bacterial infection, but data in elderly patients are scarce. Here we analyze how procalcitonin and C-reactive protein (CRP) perform for bacterial infection diagnosis after traumatic orthopedic surgery in elderly patients. METHODS: We included all patients admitted to our perioperative geriatrics unit after traumatic orthopedic surgery. Patients on antibiotics, presenting preoperative bacterial infection, or without procalcitonin measurement were excluded. Clinical and biological data were collected prospectively. Medical charts were reviewed by three experts blinded to biomarker results to assess bacterial infection diagnosis. Areas under the curve and 90%-specificity thresholds were analyzed for baseline procalcitonin and CRP levels and relative variations. RESULTS: Analysis included 229 patients (median age 86 years, hip fracture 83%), of which 40 had bacterial infection (pneumonia [n = 23], urinary tract infection [n = 8]; median delay to onset: 2 days post-admission). For bacterial infection diagnosis, the computed areas under the curve were not significantly different (procalcitonin-baseline 0.64 [95% confidence interval: 0.57-0.70]; procalcitonin-relative variation 0.65 [0.59-0.71]; CRP-baseline 0.68 [0.61-0.74]; CRP-relative variation 0.70 [0.64-0.76]). The 90%-specificity thresholds were 0.75 µg/L for procalcitonin-baseline, +62% for procalcitonin-variation, 222 mg/L for CRP-baseline, +111% for CRP-variation. CONCLUSIONS: Diagnostic performances of procalcitonin and CRP were not significantly different. Baseline levels and relative variations of these biomarkers showed little diagnostic value after traumatic orthopedic surgery in elderly patients.

Prevalence of atheromatous and non-atheromatous cardiovascular disease by age in chronic kidney disease.

BACKGROUND: Although chronic kidney disease (CKD) and age are major risk factors for cardiovascular disease (CVD), little is known about the relative proportions of atheromatous and non-atheromatous CVD by age in CKD patients. METHODS: We used baseline data from the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort of 3033 patients (65% men) with CKD Stages 3-4 to study crude and adjusted associations between age, the estimated glomerular filtration rate (eGFR), atheromatous CVD (coronary artery disease, peripheral artery disease and stroke) and non-atheromatous CVD (heart failure, cardiac arrhythmia and valvular heart disease). RESULTS: Mean age was 66.8 and mean Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR was 32.9 mL/min/1.73 m2. In the <65, (65-74), (75-84) and ≥85 year age groups, the prevalence was, respectively, 18.7, 35.5, 42.9 and 37.8% for atheromatous CVD, and 14.9, 28.4, 38.1 and 56.4% for non-atheromatous CVD. After adjusting for albuminuria, sex and CVD risk factors, the odds ratio (OR) [95% confidence interval (CI)] for (65-74), (75-84) and ≥85 age groups (compared with the <65 group) was, respectively, 1.99 (1.61-2.46), 2.89 (2.30-3.62), 2.72 (1.77-4.18) for atheromatous CVD and 2.07 (1.66-2.58), 3.15 (2.50-3.97), 7.04 (4.67-10.61) for non-atheromatous CVD. Compared with patients with an eGFR ≥30 mL/min/1.73 m2, those with an eGFR <30 mL/min/1.73 m2 had a higher OR for atheromatous CVD [1.21 (1.01-1.44)] and non-atheromatous CVD [1.16 (0.97-1.38)]. CONCLUSIONS: In this large cohort of CKD patients, both atheromatous and non-atheromatous CVD were highly prevalent and more frequent in older patients. In a given age group, the prevalence of atheromatous and non-atheromatous CVD was similar (except for a greater prevalence of non-atheromatous CVD after 85).

Relative prognostic impact of nutrition, anaemia, bone metabolism and cardiovascular comorbidities in elderly haemodialysis patients.

BACKGROUND: The prognostic impact of nutrition and chronic kidney disease (CKD) complications has already been described in elderly haemodialysis patients but their relative weights on risk of death remain uncertain. Using structural equation models (SEMs), we aimed to model a single variable for nutrition, each CKD complication and cardiovascular comorbidities to compare their relative impact on elderly haemodialysis patients' survival. METHODS: This prospective study recruited 3165 incident haemodialysis patients ≥75 years of age from 178 French dialysis units. Using SEMs, the following variables were computed: nutritional status, anaemia, mineral and bone disorder and cardiovascular comorbidities. Systolic blood pressure was also used in the analysis. Survival analyses used Poisson models. RESULTS: The population average age was 81.9 years (median follow-up 1.51 years, 35.5% deaths). All variables were significantly associated with mortality by univariate analysis. Nutritional status was the variable most strongly associated with mortality in the multivariate analysis, with a negative prognostic impact of low nutritional markers {incidence rate ratio [IRR] 1.42 per 1 standard deviation [SD] decrement [95% confidence interval (CI) 1.32-1.53]}. The 'cardiovascular comorbidities' variable was the second variable associated with mortality [IRR 1.19 per 1 SD increment (95% CI 1.11-1.27)]. A trend towards low intact parathyroid hormone and high serum calcium and low values of systolic blood pressure were also associated with poor survival. The variable 'anaemia' was not associated with survival. CONCLUSIONS: These findings should help physicians prioritize care in elderly haemodialysis patients with CKD complications, with special focus on nutritional status.

Bicarbonate Supplement Restores Urinary Klotho Excretion in Chronic Kidney Disease: A Pilot Study.

OBJECTIVE: We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum α-Klotho. DESIGN: This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum α-Klotho in these patients. SUBJECTS: The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age ≥ 18 years, CKD stage 3-5 non dialysis, Sbicar < 22 mmol/L, and not receiving bicarbonate supplementation. INTERVENTION: Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4 weeks. MAIN OUTCOME MEASURE: Patients were evaluated at two and 4 weeks by blood and urine measurements. RESULTS: Mean serum Klotho was 615 ± 287 pg/mL, and mean serum Sbicar was 19.3 ± 1.7 mmol/L at baseline. Sbicar increased from baseline at two (23.9 ± 2.9 mmol/L, P < .001) and 4 weeks (23.4 ± 1.9 mmol/L, P < .001). There was no change in serum Klotho at two (630 ± 333 mmol/L) and 4 weeks (632 ± 285 mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6 ± 31.6 pg/mmoL), increased by 320% at two weeks (P < .005) and by 280% at 4 weeks (P < .01). CONCLUSIONS: Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble α-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum α-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD.