Carlos Eduardo Poli de Figueiredo

Matrix Metalloproteinase (MMP)-2 Genetic Variants Modify the Circulating MMP-2 Levels in End-Stage Kidney Disease

Background: Matrix metalloproteinases (MMPs) play important roles in the pathophysiology of renal diseases, and imbalanced MMP-2 and its endogenous inhibitor (the tissue inhibitor of metalloproteinases-2; TIMP-2) are implicated in the vascular alterations of end-stage kidney disease (ESKD) patients. We have examined whether MMP-2 gene polymorphisms and haplotypes modify MMP-2 and TIMP-2 levels in ESKD patients as well as the effects of hemodialysis on the concentrations of these biomarkers. Methods: We determined MMP-2 and TIMP-2 plasma levels by gelatin zymography and ELISA, respectively, in 98 ESKD patients and in 38 healthy controls. Genotypes for two relevant MMP-2 polymorphisms (C–1306T and C–735T in the promoter region) were determined by TaqMan® allele discrimination assay and real-time polymerase chain reaction. The software program PHASE 2.1 was used to estimate the haplotype frequencies. Results: We found increased plasma MMP-2 and TIMP-2 levels in ESKD patients compared to controls (p < 0.05), and hemodialysis decreased MMP-2 (but not TIMP-2) levels (p < 0.05). The T allele for the C–735T polymorphism and the C-T haplotype were associated with higher MMP-2 (but not TIMP-2) levels (p < 0.05), whereas the C–1306T had no effects. Hemodialysis decreased MMP-2 (but not TIMP-2) levels independently of MMP-2 genotypes or haplotypes (p < 0.05). Conclusions: MMP-2 genotypes or haplotypes modify MMP-2 levels in ESKD patients, and may help to identify patients with increased MMP-2 activity in plasma. Hemodialysis reduces MMP-2 levels independently of MMP-2 genetic variants.

Acute renal failure needing dialysis in the intensive care unit and prognostic scores.

Background: Generic prognostic scores used in acute renal failure (ARF) give imprecise results; disease‐specific indices applied to distinct populations or intensive care practices becomes inaccurate. The current study evaluates the adequacy of prognostic scores, in patients with severe ARF needing dialysis. Methods: Known generic (APACHE II) and disease‐specific (ATN‐ISS) indices were applied to a cohort (n = 280) with ARF needing dialysis, under intensive care. Possible risk factors as causal factors, organ dysfunctions and clinical variables were examined, and a local index assembled by multivariate logistic regression analysis. Area under the receiver operating characteristics (ROC) curves evaluated the indices discriminating capacity. Goodness‐of‐fit testing and linear regression analysis appraised calibration. Validation was accomplished by the bootstrapping technique. The end‐point was hospital mortality. Results: Overall mortality was 85%. Female gender < 44 years (OR: 0.29; 95% CI: 0.10–0.84), liver/obstructive biliary disease (OR: 6.03; 95%CI: 1.65–22.08), being conscious (OR: 0.49; 95%CI: 0.21–1.14), use of vasoactive drug (OR: 3.13; 95%CI: 1.25–7.83), respiratory dysfunction (OR: 5.20; 95%CI: 1.25–7.83) or sepsis (OR: 2.62; 95%CI: 1.14–6.02) were associated with outcome. Areas under the ROC curve of 0.815, 0.652 and 0.814; Goodness‐of‐fit test P = 0.593, P < 0.001 and P = 0.002; and linear regression R2 = 0.973, R2 = 0.526 and R2 = 0.919 for the local index, APACHE II and ATN‐ISS, respectively, indicate better performance by the local index. The local index median area under the ROC curve, by bootstrapping, was 0.820 (95% CI: 0.741–0.907). Conclusions: APACHE II score was inaccurate, and ATN‐ISS poorly calibrated. When mortality or intensive care practices significantly deviate, local scores may better evaluate prognosis in severe ARF.

Influence of sodium profile in preventing complications during hemodialysis

Although a safe procedure, hemodialysis (HD) can cause numerous complications. The objective of this study was to evaluate the incidence of complications during dialysis, interdialytic weight gain, and the predialysis and postdialysis blood pressure in HD patients with and without variable sodium. Patients were observed during 12 HD sessions and those presenting with recurrent hypotension were selected for a step‐wise model of variable sodium profiling. A total of 53 patients were evaluated; the mean‐SD age was 53.7±16.3 years and 22 (41.5%) were male. Of these, 18 (34.0%) were selected to receive variable sodium profiling: the mean (SD) age was 59.9±12.6 years, and 10 (55.6%) were female. A significant decline in the occurrence of cramps (p<0.027), in the mean interdialytic weight gain (p<0.009), and a tendency to reduce the number of hypotensive episodes were detected in patients using variable sodium profiling. On the other hand, predialysis systolic blood pressure presented a significant increase (p<0.048). Using variable sodium, there was a statistically significant reduction in cramps and in the mean interdialytic weight gain. There was a significant increase in predialysis systolic pressure. Regarding hypotension episodes, only a tendency toward a reduction in the frequency of hypotension episodes could be detected.

Salt taste sensitivity threshold and exercise-induced hypertension

Salt taste sensitivity is the capacity to identify the flavour of salt. It is possible that salt taste sensitivity threshold (STST) can influence salt appetite, and sodium ingestion is associated with hypertension. The present study evaluates the relationship between salt taste sensitivity threshold (STST) and blood pressure (BP) response to exercise during a treadmill stress test. Two hundred and three normotensive individuals undergoing evaluation before starting an exercise training program were tested for STST, using concentrated saline solutions from 0.22 to 58.4g/L. Patients were divided into two groups according to the STST: normal (n-STST) and increased (i-STST); and into two groups according to their BP response to exercise: exercise-induced hypertension (EIH) or physiological blood pressure response (n-EIH). EIH was detected in 49 (24.1%) individuals. Initial systolic and diastolic BP and their areas under the curves during the test were higher in the EIH group. Initial systolic and diastolic BP areas under the curves were significantly higher in i-STST than n-STST. There was an association between STST of at least 1.8g/L (increased STST) and EIH (OR=6.71, 95% CI 1.5-29.99) independent of gender, body mass index and age. Occurrence of EIH was associated to i-STST, suggesting that a relationship between high STST and increased BP response to exercise is possible.

Imbalanced Matrix Metalloproteinases in Cardiovascular Complications of End-Stage Kidney Disease: A Potential Pharmacological Target

End-stage kidney disease (ESKD) is a major health problem associated with very high morbidity and mortality secondary to cardiovascular complications, especially in ESKD patients on dialysis. Therefore, exploring key mechanisms underlying cardiovascular alterations associated with ESKD may offer reasonable pharmacological targets that may benefit these patients. Imbalanced matrix metalloproteinases (MMP) activities have been implicated in many cardiovascular diseases, and growing evidence now indicates that excessive MMP activities contribute to cardiovascular complications in ESKD patients. However, there is no study on the effects of MMP inhibitors (MMPIs) in such patients. MMPIs may prevent against the vascular and cardiac changes associated with ESKD. In this MiniReview, we aimed at reviewing current evidence supporting the idea that pharmacological inhibition of imbalanced MMP activities in ESKD may decrease the morbidity and mortality associated with cardiovascular complications in ESKD patients. However, MMPs have variable effects during different phases of kidney disease, and therefore optimal timing for MMP inhibition during a disease process may vary significantly and is largely undetermined. While current research shows that MMPs play a role in the pathogenesis of the cardiovascular alterations found in ESKD patients, clinical studies are required to validate the idea of using MMPIs in ESKD.

Comparação entre duas técnicas de higienização das mãos em pacientes de diálise peritoneal

INTRODUCTION Hand hygiene is an important procedure in preventing peritoneal dialysis-related infections. OBJECTIVE To compare the effectiveness of two distinct techniques for hand hygiene in reducing the number of colony-forming units in patients on peritoneal dialysis. MATERIALS AND METHOD Controlled clinical trial. Thirty patients underwent three collections of microbiological flora from the hands in three different instances: before and after hand washing with glycerin soap and water, and after rubbing 70% glycerin gel-alcohol. Cultures were obtained by applying the fingers surface directly on agar-blood plates. RESULTS Cultures mean growth were 31, 30 e 12 colony-forming units prior to washing, after washing with glycerin soap and water, and following gel-alcohol, respectively (p < 0.001). Staphylococcus epidermidis was the predominant germ in culture, occurring in 93.7% of seeded plates. CONCLUSION Hand rubbing with gel-alcohol was more effective in reducing the number of colonies recovered than the other methods.INTRODUCTION: Hand hygiene is an important procedure in preventing peritoneal dialysis-related infections. OBJECTIVE: To compare the effectiveness of two distinct techniques for hand hygiene in reducing the number of colony-forming units in patients on peritoneal dialysis. MATERIALS AND METHOD: Controlled clinical trial. Thirty patients underwent three collections of microbiological flora from the hands in three different instances: before and after hand washing with glycerin soap and water, and after rubbing 70% glycerin gel-alcohol. Cultures were obtained by applying the fingers surface directly on agar-blood plates. RESULTS: Cultures mean growth were 31, 30 e 12 colony-forming units prior to washing, after washing with glycerin soap and water, and following gel-alcohol, respectively (p < 0.001). Staphylococcus epidermidis was the predominant germ in culture, occurring in 93.7% of seeded plates. CONCLUSION: Hand rubbing with gel-alcohol was more effective in reducing the number of colonies recovered than the other methods.

Intramuscular or intradermal hepatitis B vaccine administration in hemodialysis patients

3.3% in the ID group. The study was interrupted by the afety Monitoring Committee. Antibody titers to hepatitis B urface antigen during the observation period per group are hown in Fig 1. Contrary to previous studies assessing stable patients for a onger treatment period, our cohort comprised patients who ere starting on HD therapy. Moreover, it is possible that arly interruption of the study prevented detection of signifiant differences that eventually may have arisen later. It also s possible that the lower response to ID inoculation ocurred because of multiple factors; for example, there was ome evidence of inflammation in this group, an observation ith significance that cannot be discarded. Thus, to explain the different responses obtained in our tudy versus that of Barraclough et al, several possibilities ight be considered: revaccination versus initial immunizaion, prevalent versus incident individuals, patient clinical onditions, characteristics of the populations at risk, or erhaps the different interval between vaccine and doses.

Evolução do peso durante o primeiro ano de transplante renal e a ocorrência de Diabetes Mellitus após 5 anos de seguimento

Introducao: O periodo pos-transplante tardio e marcado por uma serie de alteracoes nutricionais, os quais podem reduzir a sobrevida do orgao transplantado e do paciente. Objetivo: Avaliar a evolucao do peso durante o primeiro ano de transplante renal (TR) e o desenvolvimento de Diabetes Mellitus pos-transplante (DMPT) apos cinco anos de seguimento. Materiais e Metodos: Estudo de coorte retrospectiva, onde foram coletados dados de peso e outros parâmetros clinicos em prontuario do Setor de Nefrologia do Hospital Sao Lucas da PUCRS em Porto Alegre. Resultados: Dos 35 pacientes estudados, ao final do primeiro ano, descrito como T12, observamos ganho de peso medio de 8,2%, sendo que 29 deles (82,9%) ganharam peso. O aumento torna-se significativo a partir do sexto mes apos TR (T6) nas mulheres e apos nove meses (T9) nos homens. O ganho de peso promove impacto sobre o IMC, apresentando diferenca estatistica entre dados iniciais (T0) (23,2±4,3kg/m2) e em T12 (24,9±4,4 kg/m2) (p<0,001). Ao final do quinto ano, observa-se 6 obitos (17,1%) e 2 (5,7%) perdas de enxerto. Dos 27 pacientes, observa-se incidencia de 18,5% de DMPT, os quais apresentaram ganho de peso superior, apesar de nao serem dados estatisticamente diferentes, e aumento acentuado durante o primeiro ano de TR (13,6% do peso usual) em comparacao com o grupo que nao desenvolveu esta patologia (4,7% do peso usual). Conclusao: Observa-se aumento de peso apos um ano de TR e, os pacientes que desenvolveram DMPT apos 5 anos de seguimento apresentaram perfil de ganho de peso diferente do grupo que nao desenvolveu a doenca, apesar de serem dados sem diferenca estatistica.

Solutes transport characteristics in peritoneal dialysis: variations in glucose and insulin serum levels.

Background. Differences in small solutes transport rate (SSTR) during peritoneal dialysis (PD) may affect water and solutes removal. Patients with high SSTR must rely on shorter dwell times and increased dialysate glucose concentrations to keep fluid balance. Glucose absorption during peritoneal dialysis (PD), besides affecting glucose and insulin metabolism, may induce weight gain. The study aimed at examining acute glucose and insulin serum level changes and other potential relationships in PD patients with diverse SSTR. Methods. This cross-sectional study used a modified peritoneal equilibration test (PET) that enrolled 34 prevalent PD patients. Zero, 15, 30, 60, 120, 180, and 240-minute glucose and insulin serum levels were measured. Insulin resistance index was assessed by the homeostasis model assessment (HOMA-IR) formula. SSTR categories were classified by quartiles of the four-hour dialysate/serum creatinine ratio (D4/PCr). Demographic and clinical variables were evaluated, and the body mass index (BMI) was estimated. Correlations among variables of interest and categories of SSTR were explored. Results. Glucose serum levels were significantly different at 15, 30, and 60 minutes between high and low SSTR categories (p = 0.014, 0.009, and 0.022). Increased BMI (25.5 ± 5.1) and insulin resistance [HOMA-IR = 2.60 (1.40–4.23)] were evidenced overall. Very strong to moderate correlations between insulin levels along the PET and HOMA-IR (r = 0.973, 0.834, 0.766, 0.728, 0.843, 0.857, 0.882) and BMI (r = 0.562, 0.459, 0.417, 0.370, 0.508, 0.514, 0.483) were disclosed. Conclusions. Early glucose serum levels were associated with SSTR during a PET. Overweight or obesity and insulin resistance were prevalent. An association between insulin serum levels and BMI was demonstrated.

Mean Platelet Volume and Immature Platelet Fraction in Autoimmune Disorders

Mean platelet volume (MPV), measured using automated blood analysers, has been appraised as a potential biomarker in cardiovascular disease, diabetes mellitus, and cancer. The test, a useful tool in differentiation of thrombocytopenic states, has now been carried out for autoimmune disorders, but data are yet scarce. Controversial results have been obtained in systemic and organ-specific autoimmune disorders. Another test, the immature platelet fraction (IPF) reflects the amount of young, reticulated platelets. IPF is calculated by automated hematology analysis or flow cytometry, and it is usually high in patients with rapid platelet destruction. For both MPV and IPF, standardization of cutoff is a major need. In this review, we focus the current applicability of MPV and IPF as biomarkers in patients with autoimmune diseases.