Delirium accompanies kidney dysfunction in hospitalized elderly patients

Introduction. Delirium, defined as an acute mental status with altered level of consciousness, is a common geriatric syndrome and a typical complication in hospitalized elderly patients. We aimed to assess the occurrence of delirium and the possible relationship with renal impairment. Methods. Patients aged over 65 years admitted consecutively to a Geriatric Unit, were screened for a first diagnosis of delirium. Delirium was evaluated using the validated Assessment Test for Delirium and Cognitive Impairment (4AT). Results. Final analysis included 311 patients (182 women,129 men). Mean eGFR was 62.44 ± 28.84 mL/min/1.73 m2. Prevalence of Cognitive impairment or delirium was 5.4, 84.8 e 9.8% for 0, 1-3 and ≥ 4 4AT scores. At univariate analysis, prevalence of clear delirium was increased with the worsening of CKD, being 3.7% in stage IIIb up to 68% in stage IV-V (p < 0.001). At multivariable logistic analysis, adjusted for gender and smoking habit, higher eGFR levels were associated with a reduced risk for the presence of delirium (OR = 0.86 95% CI 0.82-0.91, p < 0.001) and for developing possible cognitive impairment (OR = 0.87 95% CI 0.83- 0.90, p < 0.001). Discussion. Mild to moderate delirium is a pervasive condition among geriatric patients with manifested renal function impairment

Physical performance and clinical outcomes in dialysis patients: a secondary analysis of the EXCITE trial.

Background/Aims: Scarce physical activity predicts shorter survival in dialysis patients. However, the relationship between physical (motor) fitness and clinical outcomes has never been tested in these patients. Methods: We tested the predictive power of an established metric of motor fitness, the Six-Minute Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296 dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov Identifier: NCT01255969). Results: During follow up 69 patients died, 90 had fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients had the composite outcome. In multivariate Cox models - including the study allocation arm and classical and non-classical risk factors - an increase of 20 walked metres during the 6MWT was associated to a 6% reduction of the risk for the composite end-point (P=0.001) and a similar relationship existed between the 6MWT, mortality (P<0.001) and hospitalizations (P=0.03). A similar trend was observed for cardiovascular events but this relationship did not reach statistical significance (P=0.09). Conclusions: Poor physical performance predicts a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients. Future studies, including phase-2 EXCITE, will assess whether improving motor fitness may translate into better clinical outcomes in this high risk populatio

Effect of a home based, low intensity, physical exercise program in older adults dialysis patients: A secondary analysis of the EXCITE trial

Background: Older adults dialysis patients represent the frailest subgroup of the End Stage Renal Disease (ESRD) population and physical exercise program may mitigate the age-related decline in muscle mass and function. Methods: Dialysis patients of the EXCITE trial aged > 65 years (n = 115, active arm, n = 53; control arm, n = 62) were submitted in random order to a home based, low intensity physical exercise program. At baseline and 6 months after exercise training 6-min walking distance (6MWD) and 5-time sit-to-stand test (5STS) were performed, and quality of life (QoL) was tested. Results: The training program improved both the 6MWD (6-months: 327 \ub1 86 m versus baseline: 294 \ub1 74 m; P < 0.001) and the 5STS time (6-months: 19.8 \ub1 5.6 s versus baseline: 22.5 \ub1 5.1 s; P < 0.001) in the exercise group whereas they did not change in the control group (P = 0.98 and 0.25, respectively). The between-arms differences (6 months-baseline) in the 6MWD (+ 34.0 m, 95% CI: 14.4 to 53.5 m) and in the 5STS time changes (- 1.9 s, 95% CI: -3.6 to - 0.3 s) were both statistically significant (P = 0.001 and P = 0.024, respectively). The cognitive function dimension of QoL significantly reduced in the control arm (P = 0.04) while it remained unchanged in the active arm (P = 0.78) (between groups difference P = 0.05). No patient died during the trial and the training program was well tolerated. Conclusions: This secondary analysis of the EXCITE trial shows that a home-based, exercise program improves physical performance and is well tolerated in elderly ESRD patients. Trial registration: The trial was registered in ClinicalTrials.Gov (Clinicaltrials.gov identifier: NCT01255969) on December 8, 2010

Coenzyme Q Depletion Reshapes MCF-7 Cells Metabolism

Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells. Method: The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 enzyme, which catalyzes one of the final reactions in the biosynthetic pathway of CoQ. The bioenergetic and metabolic characteristics of control and coenzyme Q depleted cells were investigated using polarographic and spectroscopic assays. The effect of CoQ depletion on cell growth was analyzed in different metabolic conditions. Results: we showed that cancer cells could cope from energetic and oxidative stress due to mitochondrial dysfunction by reshaping their metabolism. In CoQ depleted cells, the glycolysis was upregulated together with increased glucose consumption, overexpression of GLUT1 and GLUT3, as well as activation of pyruvate kinase (PK). Moreover, the lactate secretion rate was reduced, suggesting that the pyruvate flux was redirected, toward anabolic pathways. Finally, we found a different expression pattern in enzymes involved in glutamine metabolism, and TCA cycle in CoQ depleted cells in comparison to controls. Conclusion: This work elucidated the metabolic alterations in CoQ-depleted cells and provided an insightful understanding of cancer metabolism targeting

Self-Reported Physical Inactivity and Mood Disturbances in End-Stage Kidney Disease (ESKD) Patients on Chronic Dialysis Treatment

Background: Physical inactivity and mood disturbances are key issues in individuals with end-stage kidney disease (ESKD) and may lead to poor clinical outcomes. Methods: We performed a pilot, observational study to explore the possible relationships between the self-reported level of physical activity (IPAQ) and the severity of mood disturbances (BDI score) in a cohort of 58 ESKD patients undergoing chronic hemodialysis (HD; n = 30) or peritoneal dialysis (PD; n = 28). Results: Overall, ESKD patients were severely inactive (median METs: 590 [460–1850]) and the intensity of overall and walking physical activity was mostly low to moderate. HD individuals appeared less active than PD (METs 550 [250–1600] vs. 1080 [750–1730]; p = 0.003) and were also less prone to walking (METs 180 ± 90 vs. 320 ± 100; p = 0.01), while a barely statistical difference was noticed for the time spent sitting. ESKD individuals displayed a median BDI score of 17 [12–21], which indicated, on average, the presence of borderline depression, which was apparently more evident among HD individuals. A strong, inverse correlation was found between self-reported METs and BDI scores (R = −0.78; p p = 0.0004) and a weekend day (R = 0.40; p = 0.002). Conclusions: In ESKD patients on chronic dialysis, physical inactivity and mood disturbances might be significantly inter-connected, thereby amplifying their relative impact on quality of life, dysautonomia and long-term outcomes. Future studies on larger populations are recommended to confirm these preliminary observations. Promoting strategies to improve fitness, along with greater attention to physiological aspects, should be incorporated into the clinical management of ESKD patients

Exploring the effects of DPP-4 inhibitors on the kidney from the bench to clinical trials

Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a relatively new class of non-insulin glucose-lowering agents, belonging to the incretin family, which are able to improve glycemic control with a favorable safety profile, since they are associated with a low risk of hypoglycemia, no weight gain, and good tolerability in patients with chronic renal failure. Some experimental and clinical studies suggest that these drugs may exert significant pleiotropic effects, in particular on chronic kidney disease (CKD) progression, but data from clinical trials are still controversial. In an effort to clarify the effects of DPP-4 inhibitors (DPP-4is) on diabetes-related renal damage, we performed a narrative review of available clinical trials and other experimental studies focusing on renal effects of DPP-4is. Currently, there is no conclusive evidence proving the usefulness of this drug class for improving diabetes-related renal damage. However, our literature review suggests that DPP-4is are safe and well tolerated in type 2 diabetes mellitus (T2DM) patients with CKD. More importantly, results from the reviewed studies indicate that DPP-4 inhibitor therapy may improve two major risk factors for diabetic nephropathy, such as hyperglycemia and albuminuria, resulting in potential renal benefits beyond glycemic control. Despite several limitations, the conclusions of our review corroborate previous evidence on the potential renal benefits of DPP-4is, highlighting the urgent need of future trials adequately powered and designed on hard renal outcomes to ascertain (or contradict) the therapeutic benefit of DPP-4is in T2DM and CKD patients

A spatial indicator of environmental and climatic vulnerability in Rome

Background: Urban areas are disproportionately affected by multiple pressures from overbuilding, traffic, air pollution, and heat waves that often interact and are interconnected in producing health effects. A new synthetic tool to summarize environmental and climatic vulnerability has been introduced for the city of Rome, Italy, to provide the basis for environmental and health policies. Methods: From a literature overview and based on the availability of data, several macro-dimensions were identified on 1,461 grid cells with a width of 1 km2 in Rome: land use, roads and traffic-related exposure, green space data, soil sealing, air pollution (PM2.5, PM10, NO2, C6H6, SO2), urban heat island intensity. The Geographically Weighted Principal Component Analysis (GWPCA) method was performed to produce a composite spatial indicator to describe and interpret each spatial feature by integrating all environmental dimensions. The method of natural breaks was used to define the risk classes. A bivariate map of environmental and social vulnerability was described. Results: The first three components explained most of the variation in the data structure with an average of 78.2% of the total percentage of variance (PTV) explained by the GWPCA, with air pollution and soil sealing contributing most in the first component; green space in the second component; road and traffic density and SO2 in the third component. 56% of the population lives in areas with high or very high levels of environmental and climatic vulnerability, showing a periphery-centre trend, inverse to the deprivation index. Conclusions: A new environmental and climatic vulnerability indicator for the city of Rome was able to identify the areas and population at risk in the city, and can be integrated with other vulnerability dimensions, such as social deprivation, providing the basis for risk stratification of the population and for the design of policies to address environmental, climatic and social injustice

Urinary Marinobufagenin in Patients with Non-Advanced Chronic Kidney Disease: A Cross-Sectional Study

Background and Objectives: The global prevalence of chronic kidney disease (CKD) is on the rise, posing important challenges for healthcare systems. Thus, the search for new factors potentially involved in the pathogenesis, progression and complications of early CKD remains urgent. Marinobufagenin (MBG) is a natriuretic endogenous cardiotonic steroid, and increased circulating levels of it may accelerate kidney damage. In this study, we explored the possible clinical significance of measuring urinary marinobufagenin (uMBG) in patients with non-advanced CKD. Materials and Methods: One hundred and eight adult CKD patients (mean age 71.6 ± 10 years, 70.4% male; mean eGFR 40.54 ± 17 mL/min/1.73 m2) were enrolled in this cross-sectional study. uMBG was measured together with a series of clinical, anthropometric, laboratory and instrumental analyses. Twenty-five healthy matched subjects served as controls for the uMBG measurement. Results: The uMBG values were lower in the patients with CKD as compared to those of the controls (0.37 [IQR: 0.25–0.45] vs. 0.64 [0.46–0.78] nmol/L. p = 0.004), and a significant trend in eGFR levels was noticed across the decreasing uMBG tertiles (p = 0.03). Regarding the correlation analyses, the uMBG values remained robustly associated with the eGFR in multivariate models employing either uMBG or eGFR as the dependent variable (β = 0.248; p = 0.01 and β = 0.139; p = 0.04, respectively). Besides the eGFR, the independent predictors of uMBG values in this population were the use of statins (β = −0.326; p = 0.001), the presence of diabetes (β = 0.243; p = 0.009) and urine sodium (β = 0.204; p = 0.01). Conclusions: Reduced uMBG excretion may reflect impaired renal clearance, which may contribute to the detrimental effects attributed to this hormone due to systemic accumulation. Future studies are needed to clarify the biological mechanisms placing uMBG at the crossroad of sodium intake and the presence of diabetes in CKD-suffering individuals and to verify whether a statin treatment may somewhat limit the detrimental effects of MBG in the presence of impaired renal function

Exploring the effects of DPP-4 inhibitors on the kidney from the bench to clinical trials

Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a relatively new class of non-insulin glucose-lowering agents, belonging to the incretin family, which are able to improve glycemic control with a favorable safety profile, since they are associated with a low risk of hypoglycemia, no weight gain, and good tolerability in patients with chronic renal failure. Some experimental and clinical studies suggest that these drugs may exert significant pleiotropic effects, in particular on chronic kidney disease (CKD) progression, but data from clinical trials are still controversial. In an effort to clarify the effects of DPP-4 inhibitors (DPP-4is) on diabetes-related renal damage, we performed a narrative review of available clinical trials and other experimental studies focusing on renal effects of DPP-4is. Currently, there is no conclusive evidence proving the usefulness of this drug class for improving diabetes-related renal damage. However, our literature review suggests that DPP-4is are safe and well tolerated in type 2 diabetes mellitus (T2DM) patients with CKD. More importantly, results from the reviewed studies indicate that DPP-4 inhibitor therapy may improve two major risk factors for diabetic nephropathy, such as hyperglycemia and albuminuria, resulting in potential renal benefits beyond glycemic control. Despite several limitations, the conclusions of our review corroborate previous evidence on the potential renal benefits of DPP-4is, highlighting the urgent need of future trials adequately powered and designed on hard renal outcomes to ascertain (or contradict) the therapeutic benefit of DPP-4is in T2DM and CKD patients