João Victor Salgado

How to understand the association between cystatin C levels and cardiovascular disease: Imbalance, counterbalance, or consequence?

The association of cystatin C with renal function has been studied for more than 25 years. Cystatin C has been described to have a better diagnostic performance than creatinine to assess renal function, particularly to detect small reductions in glomerular filtration rate. Recently, cystatin C has emerged as a strong predictor of incident or recurrent cardiovascular events and adverse outcomes in patients without kidney disease. Furthermore, it has been suggested that cystatin C concentrations are directly related to both inflammation and atherosclerosis. Nevertheless, the link between inflammation, atherogenesis, cardiovascular risk, and cystatin C is still poorly understood. This brief report discusses recent data, contrasting findings and possible mechanisms involved in this interaction.

Cystatin C, kidney function, and cardiovascular risk factors in primary hypertension*

OBJECTIVE To investigate the clinical usefulness of serum cystatin C (Scys) and cystatin C-based equations for the screening of chronic kidney disease in primary hypertensive patients, and correlate these markers with risk factors for cardiovascular disease. METHODS A cross-sectional study was performed in 199 middle-aged adults at a basic health unit. Kidney function assessment included measurements of serum creatinine (Scr) and Scys levels, 24-hour microalbuminuria (MA), as well as glomerular filtration rate (GFR) through Larsson and Modification of Diet in Renal Disease (MDRD) study equations. Bland- Altman plot analysis was used to calculate the agreement between equations. RESULTS High levels of Scys were found in 22% of the patients, even with normal values of GFR estimated by MDRD study equation. Systolic blood pressure and MA correlated better with Scys than Scr, but there was no correlation between Scys and diastolic blood pressure. Gender, age > 60 years, MA, and uric acid were significantly associated with high Scys levels. After multivariate analysis, only age > 60 yrs (RR = 6.4; p < 0.001) and male gender (RR = 3.0; p = 0.006) remained associated with high Scys levels. CONCLUSION Cystatin C can be used as a screening marker both for detecting mild declines of renal function and for preventing the risk of cardiovascular events in hypertensive subjects with presumably normal renal function.

Cystatin C and inflammatory markers in kidney transplant recipients

OBJECTIVE Kidney transplantation is the best option for patients with end-stage renal disease. This study evaluated the profile of cystatin C (CysC), interleukin 2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α) as inflammatory markers in 23 living donor kidney transplant recipients. METHODS A descriptive, analytical and prospective study was conducted between January 1st, 2007 and June 30th, 2008 on 23 living donor kidney transplant recipients. The biomarkers were evaluated before and 30 and 180 days after transplantation. RESULTS The mean age of the patients was 34.3 years (± 11.7), females (52%) and non-whites (61%). Significant difference was found in cystatin C and creatinine before and 30 days after transplantation (p < 0.0001) and before and 180 days after transplantation (p < 0.0001). There was a significant difference in IL-2 between 30 and 180 days post-transplant (p = 0.0418) and in TNF-α between pre-transplant and 30 days post-transplant (p = 0.0001). A negative correlation was observed between cystatin C and TNF-α at pre-transplant and between cystatin C and IL-6 at 180 days post-transplant. Comparison of biopsied and non-biopsied patients showed a significant difference in creatinine and cystatin C at 30 and 180 days post-transplant in biopsied patients. CONCLUSION Our results showed no significant correlations between CysC, IL-2, IL-6 and TNF-α levels in kidney transplant recipients at short-term follow-up. Moreover, CysC levels were very similar to creatinine levels in contrast to other inflammatory markers studied in biopsied and non-biopsied patients. Further studies are important to evaluate the long-term profile of these markers.

Cystatin C may better reflect the effect of obesity on renal function.

TO THE EDITOR: We read with interest an article by Naour et al. titled “Potential Contribution of Adipose Tissue to Elevated Serum Cystatin C in Human Obesity” (1). advocating the elevation of serum cystatin C (Scys) with adiposity. However, we would like to draw attention to some issues that needs to be carefully reviewed. First, in order to confirm the association between obesity and elevated Scys, the authors attempted to discriminate the influence of reduced renal function by estimating glomerular filtration rate (GFR) based on serum creatinine (Scr). The authors found the GFR values of the participants in the range associated with normal to moderately impaired renal function. According to the K/DOQI guidelines this range concerns stage 1–3 of chronic kidney disease (CKD) (2). At stage 3, we already have a markedly affected kidney function. However, the authors reported none of the subjects had stage 3–5 of CKD. Second, the authors showed that three subjects with very low estimated GFR ( 60 ml/min, in which MDRD equation is not precise to estimate GFR (3). Finally, to determine cystatin C gene expression and secretion in adipose tissue, the authors did not mention the current renal status of the subjects recruited from the gastric surgery program. In response to hypoxic stress, the adipocytes secrete proinflammatory cytokines and adipokines. These adipokines are linked to the genesis of insulin resistance, endothelial dysfunction, metabolic syndrome, all of which have been connected with CKD and may explain the link between adipose tissue and Scys (4). Elevated Scys may be associated with the presence of early signs of atherosclerotic and end-organ damages (5). Moreover, Scys may identify an early stage defined as “preclinical kidney disease”, in which it is associated with an increased risk of CKD progression and cardiovascular mortality, more than creatinine or estimated GFR (3). A few epidemiological studies have reported positive associations of Scys with BMI in different populations and stages of CKD (6,7). However, none of these studies have used the direct measurement of GFR which means they were unable to determine if there is a bias in the estimation of GFR using creatinineor cystatin C-based equations. By contrast, other studies using direct measurement of GFR have found no association of BMI with Scys, and strong association of age with Scys and renal function, even in healthy individuals (8–10). Currently, there is no concrete evidence that would link elevated Scys to human obesity and adiposity other than its correlation with GFR. Therefore, we disagree with the authors that cystatin C may be dependent of body fat composition. DIsclOsuRE The authors declared no conflict of interest.

Occult hepatitis B among patients with chronic renal failure on hemodialysis from a capital city in northeast Brazil.

Occult hepatitis B (OHB) is characterized by the presence of HBV‐DNA in the absence of HBsAg in the serum of patients. Hemodialysis patients are at high risk for hepatitis B virus and there are few data on the prevalence of OHB in this population, mainly in Brazil. Thus, the aim of this study was to determine the prevalence of OHB in patients undergoing hemodialysis. A cross‐sectional study was performed, including 301 patients on chronic hemodialysis at two dialysis centers in São Luís (Maranhão), northeast Brazil. Serological tests were performed for HBsAg, anti‐HBc, anti‐HBs, and anti‐HCV using enzyme immunoassays (ELISA); HBV‐DNA and HCV‐RNA were studied by real‐time PCR. The mean age was 49 ± 15 years, and 128 (42%) were female. Serological tests confirmed that all samples were HBsAg negative. Anti‐HBc was positive in 114 (38%) patients, anti‐HBc and anti‐HBs were simultaneously positive in 104 (35%), and anti‐HBc alone was positive in 10 (3%). Tests were negative for anti‐HBc and anti‐HBs in 55 patients (18%). Anti‐HBs was the only positive marker in 132 (44%) patients. Anti‐HCV was positive in 15 (5%) patients with HCV‐RNA present in 14 of them (93%). HBV‐DNA was positive in seven cases (2.3%). There was no association of HBV‐DNA with age, gender, time on dialysis, previous kidney transplant, or HBV serological pattern, but there was a positive correlation with the presence of anti‐HCV (P < 0.001). OHB in chronic renal failure patients on hemodialysis appears to be a relevant finding, suggesting that studying HBV‐DNA in this population using sensitive molecular tests should be a recommended course of action, especially in candidates for renal transplant.

Exogenous lipoid pneumonia in children: a disease to be reminded of

1 Specialist in Pediatry; Pediatric Infectology Resident, Universidade Federal do Maranhão (UFMA), Parasitological and Infectious Diseases Service, Hospital Universitário Materno-infantil, UFMA, São Luís, MA, Brazil 2 Specialist in Neonatology, UFMA, Neonatology Service, Hospital Universitário Materno-infantil, UFMA, São Luís, MA, Brazil 3 MSc in Health Sciences, Universidade de Brasília (UnB); Clinical Analysis Service, Hospital Universitário, UFMA, São Luís, MA, Brazil 4 Medicine Student, UFMA, Hospital Universitário Materno-infantil, São Luís, MA, Brazil 5 MSc in Health Sciences, UFMA; Pediatric Pneumology Service, Hospital Universitário Materno-infantil, UFMA, São Luís, MA, Brazil 6 Specialist in Neonatology, UFMA; General Pediatry Service, Hospital Universitário Materno-infantil, UFMA, São Luís, MA, Brazil

Valor da equação Cockcroft-Gault na triagem de função renal reduzida em pacientes com hipertensão arterial sistêmica

INTRODUCTION Arterial hypertension is a worldwide public health problem and one of the major risk factors for chronic kidney disease development. METHODS In order to compare the Cockcroft-Gault (CG) equation with serum creatinine and 24-hour creatinine clearance (CrCl) for the screening of reduced renal function, a cross-sectional study of 198 hypertensive patients was undertaken at a basic health unit. The demographic, nutritional, and clinical laboratory data were analyzed. Renal function was assessed by serum creatinine and 24hour CrCl. Glomerular filtration rate (GFR) was also estimated according to Cockcroft-Gault equation. RESULTS The patients had a mean age of 60.6 ± 11.6 years-old, and 73.7% were female. The prevalence of serum creatinine > 1.2 mg/dL was 7.6% and the prevalence of GFR < 60 mL/minute was 24.2%, when evaluated by the CrCl and CG equation. Reduced GFR was observed in older male patients, with lower body mass index, normal values of fasting blood glucose, and higher levels of serum uric acid and of systolic blood pressure. DISCUSSION The prevalence of decreased renal function among hypertensive patients varies considerably, depending on the laboratory investigation used. CG-estimated CrCl has shown to be more accurate than serum creatinine for assessing GFR. CONCLUSIONS CG-estimated CrCl was highly similar to 24-hour CrCl, proving to be a reliable primary care screening test for the early diagnosis of renal impairment in hypertensives.

Increased urinary cystatin C level is associated with interstitial fibrosis and tubular atrophy in kidney allograft recipients.

AIM The objective of this study was to investigate the correlation between the urinary excretion of cystatin C (CysC) and the presence of interstitial fibrosis/tubular atrophy (IF/TA) in renal transplant (RT) recipients. METHODS This prospective study included 21 adult patients who had undergone renal biopsy and RT ≥6 months prior. According to the renal biopsy reports, the patients were divided into groups with (n=12) or without (n=9) IF/TA. Analytical parameters included the following: serum and urinary levels of CysC, creatinine (Cr) and sodium (Na), total urinary protein, urinary CysC/creatinine ratio [u(CysC/Cr)], fractional excretion of sodium (FENa) and estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS The values of uCysC, u(CysC/Cr), proteinuria, and FENa were significantly higher in patients with IF/TA than in patients without IF/TA. The values of eGFR were statistically lower in patients with IF/TA (p=0.001). Values of uCysC significantly correlated with those of serum Cr, FENa, and eGFR (p<0.001). Among the patients with IF/TA, 67% presented with glomerulosclerosis (segmental/global). CONCLUSION Elevated levels of urinary CysC are associated with interstitial fibrosis and tubular atrophy in RT recipients and may become a useful tool for monitoring kidney allografts.

Reductions in glycemic and lipid profiles in hypertensive patients undergoing the Brazilian Dietary Approach to Break Hypertension: a randomized clinical trial ☆,☆☆

Hypertensive patients often have an unfavorable lipid and glucose profile. The main goal of dietary treatment for these patients is to achieve adequate control of blood pressure and reducing cardiovascular morbidity and mortality. The aim of this study was to evaluate whether the Brazilian Dietary Approach to Break Hypertension (BRADA) based on Dietary Approaches to Stop Hypertension but with both low sodium and glycemic index foods could reduce lipid and glycemic profiles in hypertensive patients who were seeing primary health care providers in a low-income region of Brazil. A randomized study of 206 individuals were followed up for the duration of 6 months. The experimental group received orientation and planned monthly menus from the BRADA diet. In the control group, counseling was based on standard care and mainly focused on salt intake reduction. Differences in all biochemical parameters were compared at the baseline and at the 6-month follow-up period. The mean age was 60.1 (±12.9) years old, and 156 subjects (119 females) completed the study. An intention-to-treat analysis showed that both groups reduced fasting plasma glucose, glycated hemoglobin, total cholesterol, and low-density lipoprotein cholesterol concentrations; however, statistically significant between-group differences were found for these parameters. The mean difference in fasting glucose was -7.0 (P < .01), -0.2 for HbA1c (P < .01), -28.6 for TC (P < .01), and -23.8 for LDL-c (P < .01) for the experimental group compared with the control group. This study showed the efficacy of the BRADA diet to treat hypertension on biochemical parameters tested in a primary health care service setting.