Relationship between renal function and physical performance in elderly hospitalized patients.

Chronic kidney disease (CKD) is increasingly recognized as a cause of worsening physical functioning in older patients. The Short Physical Performance Battery (SPPB) is highly reliable in older populations, but no data on older hospitalized patients with different degrees of kidney function are available. We aimed at testing the association between estimated glomerular filtration rate (eGFR) and SPPB, either global score (range 0-12) or its individual components (muscle strength, balance, and walking speed, each ranging from 0 to 4), in a sample of older hospitalized patients. Our series consisted of 486 patients aged 65 or more consecutively enrolled in 11 acute care medical wards participating to a multicenter observational study. eGFR was obtained by the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) equation. Physical performance was objectively measured by the SPPB. The relationship between eGFR and SPPB was investigated by multiple linear regression analysis. Physically impaired patients (SPPB total score<5) were older, had lower serum albumin and Mini-Mental State Examination (MMSE) scores as well as higher overall co-morbidity, prevalence of stroke, cancer, and anemia compared to those with intermediate (SPPB=5-8) and good physical performance (SPPB=9-12). Fully adjusted multivariate models showed that eGFR (modeled as 10 mL/min per 1.73 m(2) intervals) was independently associated with the SPPB total score (B=0.49; 95% confidence interval [CI]=0.18-0.66; p=0.003), balance (B=0.30; 95% CI=0.10-0.49; p=0.005), and muscle strength (B=0.06; 95% CI=0.01-0.10; p=0.043), but not with walking speed (B=-0.04; 95% CI=-0.09-0.11; p=0.107). In conclusion, reduced renal function is associated with poorer physical performance in older hospitalized patients. SPPB is worthy of testing to monitor changes in physical performance in elderly CKD patients.

Geriatric conditions and adverse drug reactions in elderly hospitalized patients.

OBJECTIVES: To investigate the relationship between clinical conditions typically observed in the geriatric patients (geriatric conditions) and adverse drug reactions in older patients admitted to acute care hospitals. DESIGN AND SETTING: Prospective observational study conducted in 11 acute care medical wards throughout Italy. PARTICIPANTS: Five hundred six patients aged 65 years or older consecutively admitted to participating wards. MEASUREMENTS: The outcome of the study was the occurrence of any adverse drug reactions during the hospital stay. Geriatric conditions considered in the analysis were basic activities of daily living, history of falls, slow walking speed, malnutrition, dementia, depression, 1 or more unplanned admissions in the previous 3 months, history of stroke, unintentional weight loss, and exhaustion. The relationship between risk factors and outcomes was assessed using logistic regression. RESULTS: Female gender (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.18-4.45) and number of medications taken during hospitalization (OR 1.12; 95% CI 1.06-1.18), but not individual Geriatric conditions, were associated with the outcome after correction for potential confounders. However, the simultaneous presence of history of falls and dependency in at least 1 activities of daily living (OR 2.18; 95% CI 1.13-4.19) was associated with adverse drug reactions during stay. CONCLUSION: The simultaneous presence of history of falls and dependency in at least one activity of daily living defines a condition of particular vulnerability of elderly hospitalized patients to adverse drug reactions. Physicians should be aware of this high-risk condition when prescribing new drugs to disabled older people.

Prognostic significance of the short physical performance battery in older patients discharged from acute care hospitals.

We investigated the prognostic role of the Short Physical Performance Battery (SPPB) in elderly patients discharged from the acute care hospital. Our series consisted of 506 patients aged 70 years or more enrolled in a multicenter collaborative observational study. We considered three main outcomes: 1-year survival after discharge, functional decline, and hospitalization during follow-up. Independent predictors/correlates of the outcomes were investigated by Cox regression or logistic regression analysis when appropriate. The diagnostic accuracy of SPPB in relation to study outcomes was investigated by receiver operating characteristic (ROC) curve. SPPB score was associated with reduced mortality (hazard ratio [HR]=0.86, 95% confidence interval [CI] 0.78-0.95). When the analysis was adjusted for functional status at discharge, such an association was still near significant only for SPPB values >8 (HR=0.51; 95% CI 0.30-1.05). An SPPB score<5 could identify patients who died during follow-up with fair sensitivity (0.66), specificity (0.62), and area under the ROC curve (0.66). SPPB also qualified as independent correlate of functional decline (odds ratio [OR]=0.82; 95% CI 0.70-0.96), but not of rehospitalization or combined end-point death or rehospitalization. An SPPB score <5 could identify patients experiencing functional decline during follow-up with lower sensitivity (0.60), but higher specificity (0.69), and area under the ROC curve (0.69) with respect to mortality. In conclusion, SPPB can be considered a valid instrument to identify patients at major risk of functional decline and death after discharge from acute care hospital. However, it could more efficiently target patients at risk of functional decline than those at risk of death.

Angiotensin II type 1 receptor, but no type 2 receptor, interferes with the insulin-induced nitric oxide production in HUVECs.

OBJECTIVE: Two subtypes of angiotensin II (ATII) receptor have been defined on the basis of their differential pharmacological and biochemical properties: ATII-type1 receptors (AT(1)-R) and ATII-type2 receptors (AT(2)-R). It has been hypothesized that part of the protective effects on the cardiovascular system of AT(1)-R blockers is mediated by an ATII-mediated overstimulation of AT(2)-R. We hypothesized that the inhibition of AT(1)-R has a stronger impact on insulin-induced nitric oxide (NO) production than ATII-mediated overstimulation of AT(2)-R. Therefore we studied the effect of the inhibition of AT(1)-R and AT(2)-R on ATII-mediated actions in Human Umbilical Vein Endothelial Cells (HUVECs). METHODS: We analyzed the phosphorylation state of IRS1 at Ser(616) and Ser(312) and on tyrosines after preincubation with PD123319, an inhibitor of AT(2)-R, alone and in combination with losartan, an inhibitor of AT(1)-R. In addition we measured eNOS and Akt activation through the evaluation of their phosphorylation at Ser(1177) and Ser(473) sites respectively. RESULTS: ATII induces IRS-1 phosphorylation at Ser(312) and Ser(616) through the activation of JNK and ERK 1/2, resulting in the inhibition of the insulin-induced phosphorylation of IRS1 tyrosines, Akt and eNOS. Treatment of HUVECs with AT(1)-R inhibitor restored the insulin signaling leading to NO production, whereas AT(2)-R inhibitor did not have effects on NO production in presence of ATII. CONCLUSION: Our results demonstrate that in presence of AT(1)-R antagonist, the AT(2)-R blockage does not modify the effect obtained with the AT(1)-R inhibition alone. Therefore, a possible positive role of an AT(2)-R overstimulation in condition of AT(1)-R antagonism seems to be irrelevant.

Agreement between equations estimating glomerular filtration rate in elderly nursing home residents and in hospitalised patients: implications for drug dosing.

BACKGROUND: detecting chronic kidney disease (CKD) may have important implications for the management of older and frail people. We aimed at investigating whether clinical setting (nursing home: NH versus hospital: H) affects the agreement between glomerular filtration rate (GFR) values estimated by Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations. DESIGN: observational study. SETTING: comparison between NH residents and H patients. SUBJECTS: we used data from 177 NH residents, and 439 H patients. METHODS: the agreement between estimating equations and the odds of a discrepancy >25% between formulas in relation to setting (NH versus H) were investigated. RESULTS: the agreement between MDRD and CKD-EPI formulas was good either in NH (k = 0.82) or H (k = 0.87) patients, while corresponding figures for CG indicate only a fair agreement with CKD-EPI (k = 0.50 for both populations). Setting (NH versus H) was associated with discordance between MDRD and CKD-EPI (OR = 3.97; 95% CI = 1.75-9.01), but not between CG and EPI (OR = 1.25; 95% CI = 0.87-1.81). CONCLUSIONS: in NH residents, MDRD and CKD-EPI formulas yield highly concordant GFR values, but CG behaves differently in up to one-third of patients. Such findings have important implications in dosing drugs cleared by the kidney. Setting should be taken into consideration in studies for validation of GFR equations.

Chronic kidney disease and 1-year survival in elderly patients discharged from acute care hospitals: a comparison of three glomerular filtration rate equations.

BACKGROUND: Glomerular filtration rate (GFR) is directly associated with survival. However, the prognostic significance of GFR might be different according to the formula used to estimate it. We aimed at comparing the association between GFR estimated using three different formulas and 1-year survival in elderly patients discharged from acute care hospitals. METHODS: Our series consisted of 439 patients aged 65 and older admitted to 11 acute care medical wards enrolled in a multicentre prospective observational study. GFR was estimated by body surface area-adjusted Cockcroft-Gault (CG-BSA), Modification of Diet in Renal Disease study (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. The relative risk of mortality in patients with estimated GFR = 30-59.9 or < 30 mL/min/1.73 m(2) compared to people with estimated GFR ≥ 60 mL/min/1.73 m(2) was calculated using Cox regression analysis. RESULTS: Participants with reduced GFR showed an increased mortality, regardless of the equation used, and the highest one was associated with CG-BSA-estimated GFR < 30 mL/min/1.73 m(2). After adjusting for potential confounders, CKD-EPI-estimated GFR remained significantly associated with the outcome [30-59.9 mL/min/1.73 m(2), hazard ratio (HR) = 1.70, 95% confidence interval (95% CI) = 1.02-2.98; < 30 mL/min/1.73 m(2), HR = 2.60, 95% CI = 1.20-5.66], while the strength of the association was clearly reduced for MDRD (30-59.9 mL/min/1.73 m(2), HR = 1.47, 95% CI = 0.83-2.38; < 30 mL/min/1.73 m(2), HR = 2.07, 95% CI = 1.01-4.30) and CG-BSA (30-59.9 mL/min/1.73 m(2), HR = 1.79, 95% CI = 0.67-4.53; < 30 mL/min/1.73 m(2), HR = 2.68, 95% CI = 0.92-7.55). CONCLUSION: GFR adds to the list of prognostic indicators in elderly and frail people, and CKD-EPI-derived GFR, which outperforms to some extent MDRD and CG-BSA-derived GFR in a multivariable predictive model, seems worthy of testing in wider populations.

Positive association between plasma IGF1 and high-density lipoprotein cholesterol levels in adult nondiabetic subjects.

AIMS: Low IGF1 levels have been associated with an increased cardiovascular risk. It is unknown however whether IGF1 mediates the atherosclerotic process by modulating high-density lipoprotein cholesterol (HDL-C) independently from confounders. To address this issue, we evaluated the association between IGF1 levels and HDL-C in nondiabetic subjects. METHODS: A cross-sectional analysis was used in the context of the CAtanzaro MEtabolic RIsk factors Study. One thousand and four participants (aged 20-69 years), for whom HDL-C and IGF1 measurements were available, were eligible for the study. RESULTS: After adjusting for gender and age, IGF1 levels were positively correlated with HDL-C, and negatively correlated with body mass index (BMI), waist circumference, blood pressure (BP), triglyceride, fasting insulin, and homeostasis model assessment (HOMA). In a logistic regression model adjusted for age and gender, IGF1 in the lowest tertile (<125 ng/ml) was associated with an increased risk of having low HDL-C (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.4-3.0; P=4x10(-5)) compared with the highest tertile (>186 ng/ml). When BMI, waist circumference, total cholesterol, triglyceride, and HOMA index were added to the model, IGF1 remained significantly associated with increased risk of low HDL-C (OR 1.52, 95% CI 1.01-2.31; P=0.04). A stepwise multivariate regression analysis in a model including age, gender, BMI, total cholesterol, triglycerides, IGF1, HOMA, and BP showed that the variables significantly associated with HDL-C were gender (P<0.0001), triglycerides (P<0.0001), total cholesterol (P<0.0001), BMI (P<0.0001), IGF1 levels (P<0.0001), and HOMA (P=0.001), accounting for 32.6% of its variation. CONCLUSIONS: These data provide evidence that IGF1 may be an independent modulator for HDL-C in nondiabetic individuals.

Renal function predicts cardiovascular outcomes in southern Italian postmenopausal women.

BACKGROUND: Postmenopausal women have an increased risk of adverse cardiovascular (CV) events. Similarly, chronic kidney disease (CKD) is a well established risk factor for CV disease and mortality. DESIGN: We evaluated the effect of renal function on the risk of death and CV events in 1500 southern Italian postmenopausal women. METHODS AND RESULTS: Renal function was estimated (e) by glomerular filtration rate (e-GFR) by Modification of Diet in Renal Disease equation. We classified postmenopausal women in two groups of e-GFR (ml/min per 1.73 m(2)): > or =60 (group 1) and less than 60 (group 2). The primary endpoint was major adverse CV events (MACE). The secondary endpoints were total events (MACE + death from any cause), coronary events, and stroke. During the follow-up (mean=72.6 months), there were 200 new CV morbid events. The rate of MACE (per 100 patient-years) was 1.88 and 2.98 in the two groups of e-GFR (P<0.0001). On univariate analysis, the incident risk of CV events was inversely related with the e-GFR values; similarly, in multiple Cox regression model, only the e-GFR maintained an independent association with MACE and secondary end-points. CONCLUSION: For the first time, we demonstrated that the reduction of e-GFR was associated with the increased risk of death and CV events, independently of traditional CV risk factors, menopause duration, and presence of metabolic syndrome.

Insulin-like growth factor-1 and glomerular filtration rate in hypertensive patients.

OBJECTIVE: Essential hypertension is a clinical condition associated with insulin resistance and progressive impairment of renal function that increases cardiovascular events. Insulin-like growth factor (IGF)-1, which is inversely related to insulin levels, increases renal blood flow and glomerular filtration rate (GFR). The aim of the present study was to investigate the relationship between circulating IGF-1 levels and GFR in a group of never treated hypertensive patients. METHODS: The study population consisted of 537 outpatients presenting at Catanzaro University Hospital. To participate in this study, patients have to had a systolic clinic blood pressure (BP) of more than 140 and less than 180 mmHg or a diastolic BP of more than 90 and less than 100 mmHg or both on at least two separate visits. Blood samples were at least obtained after 8-10 h in fasting conditions. The GFR was estimated by the modification of diet in renal disease equation. Serum creatinine was measured in the laboratory by an automated technique. Insulin sensitivity was estimated by using the homeostasis model assessment index calculated from the fasting glucose and insulin concentrations. RESULTS: Both fasting insulin and homeostasis model assessment significantly (P < 0.0001) show an inverse relationship with GFR decline, whereas IGF-1 presents a significant and direct relationship with it. As expected, IGF-1 and fasting insulin resulted in an inverse relationship between them (r = -0.318; P < 0.0001). The strongest predictor of GFR resulted IGF-1, accounting for a 9.8% of its variation; the addition of fasting insulin and systolic BP accounts for another 3.7% of the variation. CONCLUSION: We demonstrate a significant relationship between IGF-1 and GFR in a large sample of never treated hypertensive patients, probably as consequence of insulin resistance/hyperinsulinemia, which is a very frequent condition in high BP.

Low-plasma insulin-like growth factor-I levels are associated with impaired endothelium-dependent vasodilatation in a cohort of untreated, hypertensive Caucasian subjects.

CONTEXT: Accumulating evidence suggests that IGF-I has protective vascular effects, supporting the possibility that IGF-I deficiency may contribute to atherosclerosis. However, the relationship between plasma IGF-I levels and endothelium-dependent vasodilatation is still unsettled. OBJECTIVE: We designed this present study to test the hypothesis that low-plasma IGF-I levels are associated with reduced endothelial function independently classical cardiovascular risk factors. SETTING: Outpatients were included in the study. PATIENTS: A total of 100 never-treated hypertensive Caucasian subjects participating in the CAtanzaro MEtabolic RIsk factors Study was recruited. INTERVENTIONS: Subjects underwent forearm blood flow (FBF) evaluation by strain-gauge plethysmography in response to increasing doses of acetylcholine (ACh) (Sigma, Milan, Italy) and sodium nitroprusside (Malesci, Florence, Italy). Insulin sensitivity was estimated by the homeostasis model assessment index. RESULTS: Plasma IGF-I levels were significantly correlated with age (r = -0.300; P = 0.001), high-density lipoprotein serum cholesterol (r = 0.211; P = 0.017), homeostasis model assessment index (r = -0.355; P <0.0001), systolic blood pressure (r = -0.174; P = 0.042), glomerular filtration rate (r = 0.228; P = 0.011), and ACh-stimulated FBF (r = 0.565; P <0.0001). In a stepwise forward multivariate regression analysis, the strongest predictors of ACh-stimulated FBF response were plasma IGF-I levels, accounting for 31.9% of its variation. CONCLUSIONS: These results demonstrate, for the first time, that low-plasma IGF-I levels are highly associated with reduced endothelial function, an early step in atherogenesis process.