Inflammation, Diabetes, and Chronic Kidney Disease: Role of Aerobic Capacity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analysis of the association of polymorphism in the osteoprotegerin gene with susceptibility to chronic kidney disease and periodontitis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Oxidative stress, superoxide production, and apoptosis of neutrophils in dogs with chronic kidney disease

Oxidative stress is a key component in the immunosuppression of chronic kidney disease (CKD), and neutrophil function may be impaired by oxidative stress. To test the hypothesis that in uremic dogs with CKD, oxidative stress is increased and neutrophils become less viable and functional, 18 adult dogs with CKD were compared with 15 healthy adult dogs. Blood count and urinalysis were done, and the serum biochemical profile and plasma lipid peroxidation (measurement of thiobarbituric acid reactive substances) were determined with the use of commercial reagents. Plasma total antioxidant capacity (TAC) was measured with a spectrophotometer and commercial reagents, superoxide production with a hydroethidine probe, and the viability and apoptosis of neutrophils with capillary flow cytometry and the annexin V-PE system. The plasma concentrations of cholesterol (P = 0.0415), creatinine (P < 0.0001), and urea (P < 0.0001) were significantly greater in the uremic dogs than in the control dogs. The hematocrit (P = 0.0004), urine specific gravity (P = 0.015), and plasma lipid peroxidation (P < 0.0001) were significantly lower in the dogs that were in late stages of CKD than in the control group. Compared with those isolated from the control group, neutrophils isolated from the CKD group showed a higher rate of spontaneous (0.10 ± 0.05 versus 0.49 ± 0.09; P = 0.0033; median ± standard error of mean) and camptothecin-induced (18.53 ± 4.06 versus 44.67 ± 4.85; P = 0.0066) apoptosis and lower levels of superoxide production in the presence (1278.8 ± 372.8 versus 75.65 ± 86.6; P = 0.0022) and absence (135.29 ± 51.74 versus 41.29 ± 8.38; P = 0.0138) of phorbol-12-myristate-13-acetate stimulation. Thus, oxidative stress and acceleration of apoptosis occurs in dogs with CKD, the apoptosis diminishing the number of viable neutrophils and neutrophil superoxide production.

Calciphylaxis: a rare but potentially fatal event of chronic kidney disease. Case report

Calciphylaxis or calcific uremic arteriolopathy is a rare cutaneous-systemic disease occurring in patients with advanced chronic kidney disease. The classical clinical picture is that of a necrotic and progressive skin ulcer of reticular pattern, mostly in the lower legs and susceptible to local infection. It is a product of mural calcification and occlusion of cutaneous and sub-cutaneous arteries and arterioles. The authors report the case of a 73-year-old male patient in his late stage of renal disease presenting severe necrotic cutaneous ulcers on lower legs followed by local and systemic infection and death due to sepse after parathyroidectomy.

Assessment of physical activity by accelerometer and IPAQ-short version in patients with chronic kidney disease undergoing hemodialysis

To compare the short version of International Physical Activity Questionnaire (IPAQ) and the accelerometer measurement of physical activity (PA) in patients undergoing hemodialysis. Sample consisted of 40 patients (19 men) aged 45 ± 16 years. Patients reported their PA using the IPAQ during a face-to-face interview, and wore an Actigraph GT3-X accelerometer for 1 week to obtain minutes per day of light PA, moderate-to-vigorous PA (MVPA) and total PA as well as raw counts per day (vector magnitude). All PA-related variables were significantly correlated among instruments (r = 0.34-0.47) when analyzed as a group. However, when analyzed separately by gender, the relationships were present for women only (r = 0.46-0.62). IPAQ significantly underestimated light PA (IPAQ vs. accelerometer: 180.0 vs. 251.1 min/day, p = 0.019), but no differences were found between methods for MVPA and total PA. Modest correlations were found between self-reported PA time by IPAQ (short version) and accelerometer, but only in women. However, the IPAQ may underestimate light PA, which is the main form of PA in this population.

Cognitive impairment in chronic kidney disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Religious/spiritual coping in people with chronic kidney disease undergoing hemodialysis

The objective of the present study is to investigate the use of religious/spiritual coping mechanisms in patients with chronic kidney disease undergoing hemodialysis, by means of interviews using a sociodemographic questionnaire and the religious/spiritual coping scale. Data analysis was performed using descriptive statistics and multiple linear regression. A total of 123 individuals were interviewed, 79.6% of whom presented a high score for religious/spiritual coping and none of whom presented low or irrelevant scores. The variables that affected the religious/spiritual coping behavior were: gender, age group, treatment time, family income, and religious practice. In conclusion, the participants used religious/spiritual coping mechanisms as a strategy to cope with the disease, particularly women with a higher family income who attend church every week.

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-T-1306 and C-T-735 in the promoter region) were determined by TaqMan (R) 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-T-735 polymorphism and the C-T haplotype were associated with higher MMP-2 (but not TIMP-2) levels (p<0.05), whereas the C-T-1306 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. Copyright (C) 2012 S. Karger AG, Basel

The role of myocardial scintigraphy in the assessment of cardiovascular risk in patients with end-stage chronic kidney disease on the waiting list for renal transplantation

The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test. We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged epsilon 50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor). The incidence of CV events and death was 20 and 18, respectively (median follow-up 22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10, hazard ratio (HR) 2.37, confidence interval (CI) 1.693.33, P 0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR 2.8, CI 1.55.1, P 0.007). CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60 of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy.

Can we predict which patients will evolve to chronic kidney disease after nephrectomy for cortical renal tumors?

Introduction: While some studies show that patients submitted to radical nephrectomy have a higher risk of developing chronic kidney disease (CKD), some studies report that carefully selected living kidney donors do not present a higher risk for CKD. Here, we aim to study predictive factors of CKD after radical nephrectomy. Materials and Methods: Between January 2006 to January 2010, 107 patients submitted to radical nephrectomy for cortical renal tumors at our institution were enrolled in this study. Demographic data were recorded, modified Charlson-Romano Index was calculated, and creatinine clearance was estimated using abbreviated Modification of Diet in Renal Disease (MDRD) study equation. Pathological characteristics, surgical access and surgical complications were also reviewed. The end-point of the current study was new onset estimated glomerular filtration rate (eGFR) less than 60 and less than 45 mL/minute/1.73 m(2). Results: Age, preoperative eGFR, Charlson-Romano Index and hypertension were predictive factors of renal function loss, when the end-point considered was eGFR lower than 60 mL/minute/1.73 m(2). Age and preoperative eGFR were predictive factors of renal function loss, when the end-point considered was eGFR lower than 45 mL/minute/1.73 m2. Moreover, each year older increased 1.1 times the risk of eGFR lower than 60 and 45 mL/minute/1.73 m(2). After multivariate logistic regression, only age remained as an independent predictive factor of eGFR loss. Conclusion: Age is an independent predictive factor of GFR loss for patients submitted to radical nephrectomy for cortical renal tumors.