Gabriela Corrêa Souza

Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis.

Background The effects of obesity on outcomes reported after kidney transplantation have been controversial. The purpose of this systematic review and meta-analysis was to elucidate this issue. Methods MEDLINE, EMBASE, Cochrane Library, and gray literature were searched up to August 6, 2013. Studies that compared obese and nonobese patients who underwent kidney transplantation and evaluated one of these outcomes—delayed graft function (DGF), acute rejection, graft or patient survival at 1 or 5 years after transplantation, or death by cardiovascular disease (CVD)—were included. Two independent reviewers extracted the data and assessed the quality of the studies. Results From 1,973 articles retrieved, 21 studies (9,296 patients) were included. Obesity was associated with DGF (relative risk, 1.41; 95% confidence interval, 1.26–1.57; I2=8%; Pheterogeneity=0.36), but not with acute rejection. Graft loss and death were associated with obesity only in the analysis of studies that evaluated patients who received a kidney graft before year 2000. No association of obesity with graft loss and death was found in the analysis of studies that evaluated patients who received a kidney graft after year 2000. Death by CVD was associated with obesity (relative risk, 2.07; 95% confidence interval, 1.17–3.64; I2=0%; Pheterogeneity=0.59); however, most studies included in this analysis evaluated patients who received a kidney graft after year 2000. Conclusion In conclusion, obese patients have increased risk for DGF. In the past years, obesity was a risk factor for graft loss, death by CVD, and all-cause mortality. However, for the obese transplanted patient today, the graft and patient survival is the same as that of the nonobese patient.

Phase Angle as a Prognostic Marker in Patients With Critical Illness

BACKGROUND Phase angle (PA) is interpreted as an indicator of cell membrane integrity and a prognostic indicator in some clinical situations. This study aims to evaluate PA as a prognostic marker in critically ill patients admitted to the intensive care unit (ICU) and associate this marker with length of hospital stay, mortality, and clinical scores. METHODS A cohort study was conducted with 95 patients aged ≥18 years admitted to the ICU, who were assessed in terms of prognostic indexes (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment [SOFA]), clinical evolution (ICU discharge, death, and length of ICU stay), and PA. RESULTS Patients were predominantly male (63.1%) and had a mean age of 63.7 ± 14.6 years; length of stay of 4 days (range, 3-9 days); mortality of 15.8%; mean APACHE II and SOFA scores of 17.3 ± 8.2 and 6.1 ± 3.1 points, respectively; and mean PA of 4.91 ± 1.36°. An association was observed between females and PA <5.1° (P = .035), which was the cutoff point determined from the receiver operating characteristic curve. PA was correlated with APACHE II score (r = -0.241; P = .02). This correlation became moderate only when patients without sepsis were considered (r = -0.506; P < .001). CONCLUSIONS PA seems to be a good prognostic marker for patients without sepsis. The weak correlation between PA and APACHE II score and the lack of association with other clinical outcomes are limitations for interpreting the prognostic value of PA in the entire study sample.

Serum Leptin, Insulin Resistance, and Body Fat After Renal Transplantation

OBJECTIVE Our objective was to evaluate serum levels of leptin, body mass index (BMI), body-fat percentage (BF%), and insulin resistance in the first year after renal transplantation. DESIGN This study involved a prospective, observational cohort. SETTING The setting was a transplant unit of a university teaching hospital in Porto Alegre, Brazil. PATIENTS Thirty-two patients who underwent renal transplantation were prospectively followed for 1 year. A control group of 19 healthy individuals, matched by sex, age, and BMI, was included in the study. METHODS Body mass index and BF% were measured according to anthropometric measures, serum leptin was measured by radioimmunoassay, and the homeostasis model assessment (HOMA) was used as an index of insulin resistance. Anthropometric measures and biochemical markers were evaluated prospectively, starting at transplant time and then every 3 months for up to 1 year. RESULTS Leptin levels were increased before transplantation, and decreased significantly in the first year (median, 11.9 [interquartile range, 9.2 to 25.2] to 9.3 [4.9 to 16.4] ng/mL; P < .001). The HOMA values presented a similar pattern, decreasing from 2.4 +/- 1.5 (mean +/- SD) before transplantation, to 1.5 +/- 1.1 (P = .001) at 3 months after transplantation, but increasing to 2.0 +/- 1.7 at month 12 after transplantation (P = not significant). The BMI and BF% increased significantly in the first year after transplantation (23.3 +/- 2.7 kg/m(2) vs. 24.4 +/- 2.7 kg/m(2), P = .001, and 23.71% +/- 7.79% vs. 25.63% +/- 7.68%, P = .002, respectively). According to multivariate regression analysis, HOMA levels and BF% independently predicted leptin levels after transplantation. CONCLUSIONS We found that leptin serum levels decreased significantly over the first posttransplant year. However, the effect of transplantation on insulin resistance appears to be transitory, and BF% also increases steadily in this period. The beneficial profile of leptin levels is counterbalanced by the detrimental effects of insulin resistance and BF% that may be related to the elevated cardiovascular risk observed after transplantation.

Association between 276G/T adiponectin gene polymorphism and new-onset diabetes after kidney transplantation.

Background New-onset diabetes after transplantation (NODAT) is a well-recognized complication of kidney transplantation and is associated with poor outcomes. Both adiponectin and chemokine ligand 5 (CCL5) proteins are related to glucose metabolism and genetic variations in their genes can lead to development of NODAT. The aim of this study was to investigate the association of adiponectin and CCL5 genes polymorphisms with NODAT in a population of Caucasian kidney transplant recipients. Methods Two hundred seventy Caucasian kidney transplant recipients (83 with NODAT and 187 without NODAT) were included in a nested case-control study. Patients with pretransplantation diabetes mellitus and multiorgan transplantation were excluded. NODAT diagnosis was determined by American Diabetes Association criteria. Subjects were genotyped for 276G/T adiponectin gene polymorphism (rs1501299) and rs2280789 and rs3817655 CCL5 gene polymorphisms by real-time polymerase chain reaction. Results The TT genotype of 276G/T adiponectin gene polymorphism was significantly more frequent in NODAT than non-NODAT patients compared with GG/GT genotypes (recessive model; P=0.031). TT genotype was identified as an independent risk factor for NODAT in Caucasian kidney transplant recipients after adjusting for age at transplantation, pretransplantation body mass index, and use of tacrolimus (TT vs. GG/GT, hazard ratio=1.88, 95% confidence interval=1.03–3.45, P=0.041). There were no differences in genotype distribution and allele frequency of rs2280789 and rs3817655 CCL5 gene polymorphisms between NODAT and non-NODAT groups. Conclusions The 276G/T adiponectin gene polymorphism is associated with NODAT in Caucasian kidney transplant recipients.

Dynamic changes in bioelectrical impedance vector analysis and phase angle in acute decompensated heart failure

OBJECTIVES To evaluate whether changes in hydration status (reflecting fluid retention) would be detected by bioelectrical impedance vector analysis (BIVA) and phase angle during hospitalization for acute decompensated heart failure (ADHF) and after clinical stabilization. METHODS Patients admitted to ADHF were evaluated at admission, discharge and after clinical stabilization (3 mo after discharge) for dyspnea, weight, brain natriuretic peptide, bioelectrical impedance resistance, reactance, and phase angle. Generalized estimating equations and chi-square detected variations among the three time points of evaluation. RESULTS Were included 57 patients: Mean age was 61 ± 13 y, 65% were male, LVEF was 25 ± 8%. During hospitalization there were improvements in clinical parameters and increase in resistance/height (from 250 ± 72 to 302 ± 59 Ohms/m, P < 0.001), reactance/height (from 24 ± 10 to 31 ± 9 Ohms/m, P < 0.001), and phase angle (from 5.3 ± 1.6 to 6 ± 1.6°, P = 0.007). From discharge to chronic stability, both clinical and BIVA parameters remained stable. At admission, 61% of patients had significant congestion by BIVA, and they lost more weight and had higher improvement in dyspnea during hospitalization (P < 0.05). At discharge, more patients were in the upper half of the graph (characterizing some degree of dehydration) while at chronic stability normal hydration status was more prevalent (P < 0.001). CONCLUSIONS BIVA and phase angle were able to detect significant changes in hydration status during ADHF, which paralleled the clinical course of recompensation, both acutely and chronically. The classification of congestion by BIVA at admission identified patients with more pronounced changes in weight and dyspnea during compensation.

Leptin, Insulin Resistance, and Metabolic Changes 5 Years After Renal Transplantation

OBJECTIVE To evaluate leptin, insulin resistance (IR), and changes in body composition and lipid profile within 5 years after renal transplantation. DESIGN Longitudinal study. SETTING Hospital de Clínicas de Porto Alegre/RS, Brazil. SUBJECTS Thirty-two renal transplant recipients were followed up for 5 years after transplantation. METHODS Data were collected at transplantation time (T₁) and after 3 months (T₂), 1 year (T₃), and 5 years (T₄). Leptin serum levels, IR assessed by homeostasis model assessment (HOMA) index, lipid profile, and anthropometric measurements were analyzed. Data were compared with a control group at baseline. RESULTS At T₁, pretransplant patients had leptin levels (ng/mL) (11.9 [9.2 to 25.2]) higher than the control group (7.7 [5.2 to 9.9]; P < .0001). After transplantation, levels decreased at T₂ and T₃, but increased at T₄ to values similar to those seen at T₁ (T₄: 9.2 [5.7 to 21]; P = 1). HOMA also decreased at T₂, but increased at T₄ to identical levels (T₁: 2.1 [1.63 to 2.23], T₄: 2.1 [1.6 to 2.85]; P = 1). No significant changes in body fat percentage (BF%) were observed; however, the arm muscle circumference increased significantly at T₄ (P < .0001). At T₂, total cholesterol, triglycerides, and low-density lipoprotein cholesterol increased, whereas at T₄, lipid profile moved toward T₁ levels. By linear regression analysis, gender, BF%, and HOMA were independent predictors of leptin levels. A trend toward higher body mass index was observed in woman who also presented higher leptin and lower HOMA levels. CONCLUSION Leptin levels and HOMA decrease in the immediate posttransplant period and remain reduced for at least 1 year. Five years post transplantation, leptin, IR, BF%, and lipids have a profile similar to those in the pretransplant period. This metabolic profile is possibly associated with the elevated incidence of cardiovascular diseases observed in the late posttransplant period.

Effects of metabolic syndrome on kidney transplantation outcomes: a systematic review and meta-analysis.

Metabolic syndrome (MS) has been associated with proteinuria and reduced glomerular filtration rate. Immunosuppressive agents increase the incidence of traditional risk factors for cardiovascular disease (CVD) and have known effects on MS components after kidney transplantation. The purpose of this meta‐analysis was to evaluate the impact of MS on relevant outcomes after kidney transplantation. MEDLINE, EMBASE, and Cochrane Library were searched up to November 7, 2015. Papers that compared patients with and without MS and assessed one of the following outcomes, graft loss, death by cardiovascular disease, and all‐cause mortality, were included. Of 585 studies identified, five studies including 1269 patients were evaluated. MS was identified as a risk factor for graft loss [relative risk, 3.06; 95% confidence interval (CI), 2.17, 4.32; I² = 0%; P heterogeneity = 0.72] and death by CVD (relative risk, 3.53; 95% CI, 1.27, 9.85; I² = 0%; P heterogeneity = 0.40). Results on the association between MS and all‐cause mortality were inconclusive (relative risk, 2.61; 95% CI, 0.70, 9.81; I² = 58%; P heterogeneity = 0.09). Graft loss and death by CVD were associated with the presence of MS after transplantation. Randomized clinical trials should be conducted to define whether interventions on each MS component would result in better outcomes after transplantation.

Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial

Importance The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. Objective To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Design, Setting, and Participants Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015. Interventions Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Main Outcomes and Measures Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. Results We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74). Conclusions and Relevance Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias. Trial Registration clinicaltrials.gov Identifier: NCT02045992.

Vitamin D Insufficiency Is Associated with Lower Physical Function in Patients with Heart Failure and Diabetes

Vitamin D deficiency is frequent among patients with heart failure (HF) and diabetes, disorders associated with exercise intolerance and muscle weakness. This study aims to search for associations between vitamin D sufficiency and physical function indexes in patients with HF and diabetes. A cross-sectional study of 146 HF patients, 39.7% with diabetes, at a Brazilian tertiary outpatient clinic was performed. Patients underwent clinical evaluation, 6-minute walk test (6 MWT), handgrip strength, physical activity level (IPAQ), and biochemical evaluations including serum 25-hydroxyvitamin D. Classification was done according to vitamin D status (≥30 ng/dL, sufficient) and presence/absence of diabetes in vitamin sufficient, no diabetes (DS-C, n = 25), vitamin sufficient, diabetes (DS-DM, n = 18), vitamin deficient, no diabetes (DD-C, n = 63), and vitamin deficient, diabetes (DD-DM, n = 40). Patients age was 55.4 ± 8 yrs; 70.5% had vitamin D deficiency. Clinical characteristics were similar among groups. Total time expended in physical activity was similar among groups (P = 0.26). DS-C covered higher distances in the 6 MWT (392 ± 60 m) versus DD-DM (309 ± 116 m); P = 0.024. Handgrip strength was similar among groups but tended to lower levels in DD-DM (P = 0.074) even after being adjusted to physical activity (P = 0.069). Vitamin D deficiency can influence physical function in HF diabetic patients.

Triceps skinfold as a prognostic predictor in outpatient heart failure

Background Most reports regarding the obesity paradox have focused on body mass index (BMI) to classify obesity and the prognostic values of other indirect measurements of body composition remain poorly examined in heart failure (HF). Objective To evaluate the association between BMI and other indirect, but easily accessible, body composition measurements associated with the risk of all-cause mortality in HF. Methods Anthropometric parameters of body composition were assessed in 344 outpatients with a left ventricular ejection fraction (LVEF) of ≤50% from a prospective HF cohort that was followed-up for 30 ± 8.2 months. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. Results HF patients were predominantly male, of non-ischemic etiology, and had moderate to severe LV systolic dysfunction (mean LVEF = 32 ± 9%). Triceps skinfold (TSF) was the only anthropometric index that was associated with HF prognosis and had significantly lower values in patients who died (p = 0.047). A TSF ≥ 20 mm was present in 9% of patients that died and 22% of those who survived (p = 0.027). Univariate analysis showed that serum creatinine level, LVEF, and NYHA class were associated with the risk of death, while Cox proportional hazard regression analysis showed that TSF ≥ 20 was a strong independent predictor of all-cause mortality (hazard ratio = 0.36; 95% CI = 0.13-0.97, p = 0.03). Conclusion Although BMI is the most widely used anthropometric parameter in clinical practice, our results suggested that TSF is a better predictive marker of mortality in HF outpatients.