Yunus Erdem

Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension

Abnormalities in fibrinolysis have been reported in hypertension. Angiotensin converting enzyme (ACE) inhibitors have been shown to improve altered fibrinolytic balance in hypertensive patients. It has not been documented, however, whether this is due to a decrease in angiotensin II (Ang-II) generation or is a consequence of elevated local levels of bradykinin. Accordingly, the aim of this study was to determine the effects of an ACE inhibitor (perindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic kinetics. We have examined the serum levels of the plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity, soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) before and after reaching the target blood pressure (<140/90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40+/-11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38+/-9 years, 6 women, 6 men). We also compared the baseline fibrinolytic activity of hypertensive patients with that of 12 normotensive control persons (mean age 40+/-9 years, 6 women, 6 men). The mean basal plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in the hypertensive patients than in normal controls (P<.005). The values of other analytes were similar in both groups. Increased plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P<.005); the reductions in losartan-receiving group were more pronounced (P<.05). There were no significant effects on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patients receiving the two therapeutic regimens (P>.05). In conclusion, chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to play a major role.

The relationship between hypertension and salt intake in Turkish population: SALTURK study

Abstract This population-based epidemiological study was aimed to evaluate the daily salt intake and its relation to blood pressure in a representative group of Turkish population. The enrolled normotensive and hypertensive individuals (n = 1970) completed a questionnaire including demographics, dietary habits, hypertension awareness and drug usage. Blood pressure was measured and to estimate salt consumption, 24-h urine samples were collected. The daily urinary sodium excretion was 308.3 ± 143.1 mmol/day, equal to a salt intake of 18.01 g/day. Salt intake was higher in obese participants, rural residents, participants with lower education levels and elderly. A positive linear correlation between salt intake and systolic and diastolic blood pressures was demonstrated (r = 0.450, p = 0.020; r = 0.406, p = 0.041; respectively), and each 100 mmol/day of salt intake resulted in 5.8 and 3.8 mmHg increase in systolic and diastolic blood pressures, respectively. Salt intake and systolic blood pressure was significantly correlated in normal weight individuals (r = 0.257, p < 0.01). The Turkish population consumes a great amount of salt; salt intake and blood pressure was positively correlated. Efforts in sodium restriction are therefore crucial in the management of hypertension as part of national and global health policies.

Hypertension incidence in Turkey (HinT): a population-based study.

Objective Hypertension incidence is an important determinant of hypertension prevalence and progression. Few studies have been published on hypertension incidence in developing countries despite the high prevalence observed. The aim of this study was to investigate the incidence of hypertension in Turkey. Methods The study was designed as an epidemiological cohort study which included the population of the Prevalence, awareness, treatment and control of hypertension in Turkey (PatenT) Study which had 4910 volunteers. Blood pressure measurements were performed three times and a questionnaire was used to obtain data on the present status of hypertension with regards to distributions and alterations of risk factors. Results In the present study, 4008 (81.6%) participants of the PatenT Study population were contacted after 4 years. After excluding 173 dead and 67 pregnant individuals, the study cohort comprised of 3768 individuals. The overall 4-year incidence rate of hypertension was 21.4%; it reached a maximum of 43.3% in individuals over 65 years of age. Age, initial blood pressure category, and body mass index were the best predictors of the hypertension incidence rate. Multivariate logistic regression analysis revealed that age, obesity, alcohol consumption, and living in rural areas were significant predictors of hypertension. Conclusion Follow-up periods scheduled considering age, initial blood pressure category, and body mass index are important for the early determination of hypertension. As there are limited data regarding hypertension incidence in developing countries, the results of data collected in this study might serve as a model.

Dual Blockade of the Renin-Angiotensin System for Cardiorenal Protection: An Update

The renin-angiotensin system (RAS) has an important role in hypertension and the continuum of cardiovascular and kidney disease. The inhibition of this system, either with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), has been shown to be beneficial for cardiorenal protection. Dual blockade with an ACE inhibitor and ARB may have additional benefits due to the more complete inhibition of the system. Most published trials, including recent large studies and meta-analyses, have reported either limited or no additional benefit. Dual-blockade therapy seems to have some benefit on proteinuria and blood pressure reduction, and on morbidity and mortality in patients with heart failure, compared with monotherapy. The major issue arising from these published trials and meta-analyses is the increased frequency of dual therapy discontinuation and adverse effects on kidney function. There is a lack of hard end-point data for renal outcomes and long-term safety data in most published trials. Until the results of ongoing trials become available and as further safety data emerge, a wise approach would be to withhold use of ACE inhibitor and ARB combination therapy in general practice. When used in selected conditions, patients need to be closely monitored.

Effects of lowering dialysate sodium on flow-mediated dilatation in patients with chronic kidney disease

OBJECTIVE This study examined the effects of low dialysate sodium on endothelial dysfunction (ED) as measured by flow-mediated dilatation (FMD) of brachial artery in haemodialysis (HD) patients. METHODS Thirty HD patients (17 men; mean age: 48.4 ± 17.8 years) were studied. Subjects underwent two consecutive 6-week HD periods. Dialysate sodium was 143 mEq/L in the first period (standard Na HD) and 137 mEq/L in the second period (low Na HD). After each period, we performed FMD, echocardiographic evaluation and 24-h ambulatory blood pressure monitoring (ABPM). Interdialytic weight gain (IDWG), levels of pre- and post-dialysis blood pressure (BP), and dialysis-related symptoms were monitored during the study. RESULTS Per cent FMD was significantly greater (P < 0.05) after low Na HD (9.3 ± 6.2) compared with standard Na HD (5.7 ± 6.2). IDWG was significantly lower during low Na HD (2.35 ± 0.86 kg versus 2.71 ± 0.89 kg; P < 0.001). BP control was improved during low Na HD, as assessed by ABPM (128.2/77.5 mmHg versus 132.4/80.8 mmHg). Dialysis-related symptoms were more frequent during low Na HD (P < 0.05). There was no change in left ventricular mass after reducing dialysate sodium. CONCLUSIONS Reducing dialysate sodium concentration reduced ED, and provided better control of IDWG and BP, but increased dialysis-related symptoms.

Radiocontrast-induced nephrotoxicity and urinary alpha-glutathione S-transferase levels: Effect of amlodipine administration

Aims: The exact pathogenesis and prophylaxis concerning radiocontrast-induced nephrotoxicity (RCIN) was unclear. Short-acting calcium antagonists were used to prevent RCIN. This study was designed to evaluate the role of a long-acting calcium antagonist (amlodipine) administration by determining serum creatinine (SCre) levels and 24 hour urinary excretion rates of glutathione S-transferase alpha (GST-α) which has a selective localization only to proximal tubular epithelium.Methods: In a prospective trial, 29 outpatients (19 M, 10 F) undergoing coronary angiography were randomized and either amlodipine 10 mg/day (n = 15) or placebo (n = 14) were administered prior to angiography and continued thereafter. All patients had normal basal renal function and none of them had any risk factor for RCIN. A low osmolar, nonionic contrast media (iopamidol 76%) was administered to all patients. Creatinine clearance (CCre), SCre and 24-hour urinary GST-α levels were measured before, 24 hours and 7 days after angiography.Results: SCre and 24 hour urinary GST-α values increased on 24th hour following the angiography in both groups (p < 0.017 and 0.001, respectively). Pretreatment with amlodipine created no difference in both variables (p > 0.05).Conclusions: A reversible tubular dysfunction occurs following radiocontrast administration which was manifested by an increase in urinary GST-α excretion rates. Pretreatment with a long acting calcium antagonist amlodipine has no effect on the course of enzyme excretion and alteration observed in SCre

THE BOOSTER PHENOMENON IN 2-STEP TUBERCULIN SKIN TESTING OF PATIENTS RECEIVING LONG TERM HEMODIALYSIS

BACKGROUND Tuberculosis remains a significant health problem for patients receiving long-term hemodialysis (HD). The tuberculin skin test (TST) is an important method for detecting Mycobacterium tuberculosis infection. This study examined the significance and frequency of the booster phenomenon in serial TST of HD patients. METHOD Fifty-three outpatients in a hospital-based HD center in Turkey were screened for tuberculosis with the TST between August and October 1999. To determine the frequency of booster phenomenon, patients with less than 10 mm indurations to the initial TST were given a second test 7 days later. RESULTS Nineteen (35.8%) of 53 patients had a significant tuberculin reaction (> or = 10 mm) on the initial TST. The booster effect was detected in 10 (29.4%) of 34 patients who had a negative reaction (< 10 mm) to the initial test. Overall, 29 (54.7%) patients showed a significant reaction on both tests. CONCLUSIONS These results showed significant rates of TST positivity and the booster effect in this HD center.

Major Barriers against Renin–Angiotensin–Aldosterone System Blocker Use in Chronic Kidney Disease Stages 3–5 in Clinical Practice: A Safety Concern?

Renin–angiotensin–aldosterone system (RAAS) blockers are underutilized in patients with chronic kidney disease (CKD). We aimed to determine barriers against the use of RAAS blockers in these patients. Patients with stage 3–5 CKD referred to Hacettepe University Hospital Nephrology Unit during a 1 year period were evaluated for RAAS blocker use. Two hundred and seventy-nine patients (166 male, 113 female) were analyzed. The mean age of the patients was 56.7 ± 15.2 years, mean serum creatinine was 2.45 ± 1.44 mg/dL, and mean glomerular filtration rate was 33.3 ± 15.1 mL/min. The mean follow-up time was 22.0 ± 21.9 months and the clinical visit number was 4.0 ± 3.5. Angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers were used by 68.8% of all patients and 67.7% of diabetic patients at the time of analysis. In 82.1% of patients, RAAS blockers had either been used earlier or were being used. Hyperkalemia was the principal reason for both not starting and also discontinuing these drugs in patients with CKD. In 37.4% of patients, reasons for not starting RAAS blockers were unclear. This study showed that hyperkalemia is the major barrier against the use of RAAS blockers in patients with CKD. There was, however, a subset of patients who did not receive RAAS blockers even without clear contraindications.

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology.

BACKGROUND Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.

Daily Sodium Intake in Chronic Kidney Disease Patients during Nephrology Clinic Follow-Up: An Observational Study with 24-Hour Urine Sodium Measurement

Objective: To determine daily sodium intake in ‘real practice’ in a large group of chronic kidney disease (CKD) patients who were under regular follow-up in a nephrology clinic. Methods: A total of 373 consecutive outpatients with CKD stages 1–5 (not on dialysis; men: 52.3%, mean age: 51.6 ± 15.4 years) were included in the study. All patients had at least 3 or more nephrology visits and received information on reducing their sodium intake. Data for systolic and diastolic blood pressure, number of antihypertensive medications and 2 consecutive 24-hour urinary sodium levels were obtained from the patients’ medical records. Results: The mean 24-hour urinary sodium levels of 2 consecutive urine samples were 168.8 ± 70.3 and 169.3 ± 67.4 mEq/day (p > 0.05). Only 14.7% of the patients had a sodium excretion <100 mmol/day. There was no difference in daily sodium intake from stages 1 to 4, but it was significantly lower in stage 5 (126.6 ± 60.5 mEq/day, p < 0.05). No relation was found between 24-hour urinary sodium output, number of antihypertensives or thiazide use. Conclusions: This study showed that almost 85% of CKD patients under regular nephrologic care were consuming more sodium than the recommended level. More robust measures should be devised to increase patient and physician compliance with reducing sodium intake in CKD.