Role of endothelial function determined by asymmetric dimethylarginine in the prediction of resistant hypertension: A subanalysis of ReHOT trial.

The authors conducted a subanalysis of the ReHOT (Resistant Hypertension Optimal Treatment) study to evaluate the association between endothelial dysfunction and resistant hypertension in a population of patients treated in a staged fashion for hypertension. One hundred and three hypertensive patients were followed for 6 months and participated in seven visits (V0-V6) 28 days apart. There was a first phase (V0-V3) of antihypertensive adjustment with three drugs and determination of resistant hypertension and a second randomized phase (V3-V6) of treatment with a fourth drug (clonidine or spironolactone) in the hypertensive patients characterized as resistant. Of the 103 patients included, 86 (83.5%) underwent the randomization visit (V3), 71 were characterized as non-resistant hypertensives (82.5%), and 15 as resistant hypertensives (17.5%). Serum asymmetric dimethylarginine (ADMA) was shown to be an independent predictor of resistant hypertension after adjustment for multiple variables (OR: 11.42, 95% CI: 1.02-127.71, P = .048), and in addition, there was a reduction in blood pressure levels and ADMA values during follow-up with a positive correlation in both groups and a greater reduction in the group of resistant hypertensives. We demonstrated that ADMA was an independent predictor of resistant hypertension, and we observed that the improvement in blood pressure levels obtained with the treatment was proportional to the reduction in ADMA values, suggesting a complementary role of ADMA not only as a stratification tool for the occurrence of resistant hypertension, but also as a possible therapeutic target in this population.

Chronic kidney disease induces inflammation by increasing Toll-like receptor-4, cytokine and cathelicidin expression in neutrophils and monocytes.

TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry. Cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 were analyzed via ELISA.TLR4 expression in neutrophils was higher in HD patients than in stage 3 and 4 CKD patients. In these cells, we observed a positive correlation between TLR4 and cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 levels. In monocytes, TLR4 expression was significantly higher in CKD 3 and 4 groups than in the control and HD groups and positively and negatively correlated with IL-6 and MCP-1 and cathelicidin, respectively. TNF-α, IL-6 and MCP-1 serum levels were higher in HD and CKD patients than in control. Cathelicidin and IL-10 levels were only higher in HD patients. IL-6 serum levels were positively correlated with all cytokines, and cathelicidin was negatively correlated with MCP-1 (r = - 0.35; p < 0.01) and positively correlated with IL-10 (r = 0.37; p = 0.001). These results suggest that a uremic environment induces high TLR4, cathelicidin and cytokine expression and may increase inflammation. Thus, future studies should be conducted to evaluate whether TLR4 and cathelicidin should be targets for anti-inflammatory therapeutic strategies.

Impact of metabolic syndrome on resting energy expenditure in patients with chronic kidney disease.

BACKGROUND & AIMS: Resting energy expenditure (REE) changes in patients with chronic kidney disease (CKD) may contribute to mortality increase. The obesity and inflammation is associated with high REE and when not compensated by adequate intake, may determine an unfavorable clinical outcome in this population. We aimed to evaluate the influence of metabolic syndrome (MetS) on REE in CKD patients. METHODS: One hundred eighty-three patients were stratified according to glomerular filtration rate (GFR) and divided in groups: without CKD (GFR > 60 ml/min/1.73 m2) and CKD (GFR < 60 ml/min/1.73 m2) and according to the presence or absence of MetS. REE was measured by indirect calorimetry; body composition was assessed by bioelectrical impedance analysis and blood and urine were collected for biochemical tests. RESULTS: REE was lower in the group with CKD compared with those without CKD (1293 ± 364 vs 1430 ± 370 kcal/d, P = 0.01). The group with CKD without MetS showed decrease in REE compared to the groups without CKD, regardless the presence of Mets, and those with CKD and MetS (1173 ± 315 vs 1392 ± 324 vs 1460 ± 410 vs 1424 ± 376 kcal/d, P < 0.05, respectively). Multivariate analysis showed an independent association of CKD in determining REE when adjusted for lean body mass. The inclusion of MetS as an independent variable in the same analysis model neutralized the impact of CKD on the REE (P = 0.19). Patients without MetS, REE correlated with estimated GFR and the protein equivalent (r = 0.33, P < 0.01, r = 0.21, P = 0.04, respectively), whereas in MetS patients, these correlations were not observed. CONCLUSION: The presence of CKD is independently associated with reduced REE. The observed decrease in REE is reversed in patients with MetS independent of renal function.

Is cystatin C a useful marker in the detection of diabetic kidney disease?

BACKGROUND/AIMS: To evaluate cystatin C as a marker of diabetic kidney disease in normoalbuminuric diabetic patients without chronic kidney disease (CKD). METHODS: A cross- sectional study was carried out comprising 243 hypertensive patients, 61 of them with type 2 diabetes, presenting normoalbuminuria and an estimated glomerular filtration rate (eGFR) >or=60 ml/min/1.73 m(2). Renal function assessment included determinations of serum creatinine and cystatin C levels, microalbuminuria, as well as eGFR through Cockcroft-Gault and Modification of Diet in Renal Disease equations. RESULTS: Diabetic patients presented higher cystatin C levels than nondiabetic patients (0.95 +/- 0.19 vs. 0.89 +/- 0.17 mg/l; p < 0.05). In the binary logistic regression, the presence of diabetes and metabolic syndrome was significantly associated with elevated cystatin C levels. Diabetic patients also presented a slightly greater albuminuria (6.72 +/- 4.43 vs. 5.07 +/- 3.59 microg/min; p < 0.05). CONCLUSIONS: Our results suggest that elevated cystatin C levels in diabetic patients may identify a certain degree of renal dysfunction even when albuminuria and eGFR do not mirror CKD. Longitudinal studies with direct GFR measures need to be done in order to confirm the value of cystatin C as an indicative of worse renal outcomes in the diabetic population.

N-domain angiotensin I-converting enzyme with 80 kDa as a possible genetic marker of hypertension.

We have previously described angiotensin I-converting enzyme (ACE) forms in urine of normotensive (190 and 65 kDa) and hypertensive patients (90 and 65 kDa, N-domain ACEs). Based on the results described above, experimental and genetic models of hypertension were investigated to distinguish hemodynamic and genetic influence on the generation of ACE profile in urine: Wistar-Kyoto and Brown Norway rats (WKY and BN), spontaneously and stroke-prone spontaneously hypertensive rats (SHR and SHR-SP), one kidney/one clip rats (1K1C), deoxycorticosterone acetate (DOCA) salt-treated and untreated rats, and enalapril-treated SHR (SHRen). Two peaks with ACE activity were separated from the urine of WKY and BN rats submitted to an AcA-44 column, WK-1/BN-1 (190 kDa), and WK-2/BN-2 (65 kDa), as described for urine of normotensive subjects. The same results were obtained for urine of 1K1C and DOCA salt-treated and untreated rats, analyzed to evaluate the influence of hemodynamic factors in the ACE profile in urine. The urine from SHR, SHR-SP, and SHRen presented 80 (S-1, SP-1, Sen-1) and 65 (S-2, SP-2, Sen-2) kDa ACE forms, differing from the urine profile of normotensive rats, but similar to that described for hypertensive patients. The presence of 80 kDa ACE in urine of SHR, SHR-SP, and SHRen and its absence in urine of experimental hypertensive rats (1K1C and DOCA salt) support the hypothesis that this enzyme could be a possible genetic marker of hypertension. Taken together, our results provide evidence that ACE forms with 90/80 kDa isolated from the urine of hypertensive subjects and genetic hypertensive animals behaves as a possible genetic marker of hypertension and not as a marker of high blood pressure.