Abdulkadir Unsal

Treatment of hypertension in dialysis patients by ultrafiltration : Role of cardiac dilatation and time factor

We retrospectively analyzed the blood pressure (BP) and cardiothoracic index (CTi) of 67 hemodialysis patients with hypertension who could be followed up for at least 8 months. A new treatment policy was adopted, aimed at strict volume control. Dietary salt restriction was strongly emphasized. Ultrafiltration (UF) was applied during regular dialysis sessions and sometimes in additional sessions, as long as BP and CTi remained at greater than normal values. All antihypertensive drugs were discontinued at the beginning of treatment. Average BP decreased from 173 +/- 17/102 +/- 9 to 139 +/- 18/86 +/- 11 mm Hg after 6 months and to 118 +/- 12/73 +/- 6 mm Hg after 36 months. Corresponding values for CTi were 52% +/- 4%, 47% +/- 3%, and 42% +/- 4%, respectively. Conventional relatively short dialysis (three times weekly for at least 4 hours) can achieve normal BPs with prolonged effort in most patients, whereas improvement in heart condition facilitates this.

Osteoprotegerin/RANKL Axis and Progression of Coronary Artery Calcification in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive. RESULTS Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15-0.46] versus 0.18 [0.12-0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model. CONCLUSIONS Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.

Coronary artery calcification and coronary flow velocity in haemodialysis patients

BACKGROUND Decreased coronary flow reserve (CFR) is a marker of endothelial dysfunction, coronary artery calcification and inflammation, well-known cardiovascular risk factors in haemodialysis (HD) patients. In this study, we aimed to investigate the correlation of coronary artery calcification scores (CACS) with CFR in HD patients. METHODS Sixty-four end-stage renal failure patients were enrolled in this study (38 males, 26 females). Thirty-nine healthy subjects (22 males, 17 females) were included in the control group. Biochemical parameters and acute-phase inflammation marker [high-sensitivity C-reactive protein (hs-CRP)] of patients were recorded before dialysis. The CACS were measured by electron beam computerized tomography method. CFR recordings were performed by trans-thoracic Doppler echocardiography. The relationship between CACS and CFR was evaluated. RESULTS The mean CACS was 281 +/- 589 and 29 patients had CACS < 10. Patients with CACS > 10 had significantly lower CFR values compared to patients with CACS < 10 (1.56 +/- 0.38 vs 1.84 +/- 0.53, P = 0.024). However, there was no difference in hs-CRP values between the groups. CFR was negatively correlated with CACS (r = -0.276, P = 0.030). In multiple stepwise regression analysis, CACS was found to be an independent variable for predicting CFR (P = 0.048). During a follow-up of 18 months, 10 patients had experience of cardiovascular events. Patients with CACS > 10 had significantly higher event rate [34.5% (10/29) vs 0% (0/24)] compared to those with CACS < 10 (P = 0.001). Patients who developed cardiovascular events had significantly higher mean CACS and lower CFR values than the remaining group (P = 0.019 and P = 0.039). All of four patients who died during follow-up were in the CFR < 2 and CACS > 10 groups. CONCLUSIONS CACS was associated with CFR in HD patients. However, we did not find any association of inflammation with CACS and CFR. This association between CFR and CACS might indicate two different (anatomical and functional) aspects of the common pathophysiology of the arterial system in HD patients.

FGF-23 associated with the progression of coronary artery calcification in hemodialysis patients

BackgroundDisordered mineral metabolism is implicated in the pathogenesis of vascular calcification in hemodialysis (HD) patients. Fibroblast growth factor 23 (FGF-23) is the main regulator of phosphate metabolism. In this prospective study, we aimed to investigate the association of serum FGF-23 with progression of coronary artery calcification in HD patients.MethodsSeventy-four HD patients (36 male/38 female, mean age: 52 ± 14 years) were included. Serum FGF-23 levels were measured by ELISA. Coronary artery calcification score (CACS) was measured twice with one year interval. Patients were grouped as progressive (PG) (36 patients-48%) and non-progressive (NPG).ResultsAge, serum phosphorus, baseline and first year CACS were found to be significantly higher in the PG compared to NPG group. Serum FGF-23 levels were significantly higher in PG [155 (80–468) vs 147 (82–234), p = 0.04]. Patients were divided into two groups according to baseline CACS (low group, CACS ≤ 30; high group, CACS > 30). Serum FGF-23 levels were significantly correlated with the progression of CACS (ΔCACS) in the low baseline CACS group (r = 0.51, p = 0.006), but this association was not found in high baseline CACS group (r = 0.11, p = 0.44). In logistic regression analysis for predicting the PG patients; serum FGF-23, phosphorus levels and baseline CACS were retained as significant factors in the model.ConclusionsSerum FGF-23 was found to be related to progression of CACS independent of serum phosphorus levels. FGF-23 may play a major role in the progression of vascular calcification especially at the early stages of calcification process in HD patients.

Relationship of Fibroblast Growth Factor 23 with Left Ventricle Mass Index and Coronary Calcificaton in Chronic Renal Disease

Background: to evaluate the relationship between FGF23 and changes in biochemical parameters, left ventricle mass index, coronary, aortic and, valve calcifications. Methods: Totally 185 patients with chronic renal disease were included in this prospective, cross-sectional study. The patients were stratified according to GFR levels (mL/min/1.73m2) into 5 groups: ≥60, 45-59, 30-44, 15-29 and <15 (group 1-5 respectively).Biochemical parameters, serum FGF23 levels were measured. Echocardiographic assessments and Coronary artery calcification (CAC) with multidetector computerized tomography (MDCT) were done, left ventricle muscle mass (LVMI) was measured all patients. Results: Left ventricular hypertrophy (LVH), aortic and valve calcification were detected in 27.8%, 25.3% and 12% of patients respectively. CAC was detected in 18 patients. LVMI and FGF23 levels were found to increase proportionally with the severity of renal failure. A significant positive correlation between FGF-23 level and serum phosphate, logPTH, and CaxP product was found. While a correlation between FGF-23 and valve calcification was detected, no correlation could be detected with LVMI, LVH, coronary and aortic calcification. Conclusion: In CKD, circulating FGF-23 and LVMI levels gradually increase with declining renal function such that by the time patients reach end-stage renal disease. Correlation between logFGF23 and valve calcification was significant, whereas no statistically significant relationship was found between logFGF23 and LVMI, LVH, aortic and coronary artery calcifications.

Neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio in evaluation of inflammation in end-stage renal disease.

OBJECTIVE To evaluate the relationship between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and inflammation in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). METHODS 100 ESRD patients on maintenance HD (mean ± SD age: 52.3 ± 1.7 years, 52% were males) were included in this cross-sectional study. Data on patient demographics, dry weight, body mass index, duration of HD (months), etiology of ESRD, delivered dose of dialysis (spKt/V), complete blood count, blood biochemistry and inflammatory markers including hs-CRP (mg/L), TNF-α (pg/mL), NLR, and PLR were recorded in all patients and compared in patients with hs-CRP levels of ≤ 3 mg/L vs. > 3 mg/L. other study parameters were also recorded. RESULTS Compared to patients with lower hs-CRP levels, patients with hs-CRP levels of > 3 mg/L had significantly higher values for NLR (3.7 ± 0.2 vs. 2.7 ± 0.2, p < 0.01) and PLR (150.7 ± 6.9 vs. 111.8 ± 7.0, p < 0.001). Both NLR and PLR were positively correlated with hs-CRP (r = 0.333, p = 0.01 and r = 0.262, p = 0.001, respectively) and negatively correlated with transferrin saturation (%) (r = -0.418, p = 0.001 and r = -0.309, p = 0.002, respectively). CONCLUSION Our findings in a cohort of ESRD patients on maintenance HD revealed higher values for NLR and PLR in patients with higher levels of inflammation along with a significant positive correlation of both NLR and PLR with hs-CRP levels. Being a simple, relatively inexpensive and universally available method, whether or not calculation of NLR and PLR offers a plausible strategy in the evaluation of inflammation in ESRD patients in the clinical practice should be addressed in larger scale randomized and controlled studies.

Duodenal biopsy for diagnosis of renal involvement in amyloidosis.

Amyloidosis results from extracellular deposition of a fibrillary protein in various organs, and renal biopsy is the best, but a complicated tool for diagnosis. Therefore, alternative biopsy sites have been proposed with varying degrees of sensitivity. We aimed to find the most appropriate biopsy site in patients with chronic kidney disease (CKD) in whom renal biopsy is contraindicated or unavailable. 42 patients (29 male; mean age 46 ± 16 y) with CKD in whom amyloidosis was suspected as the underlying etiology on clinical grounds, but renal biopsy was not available (Group I), and 36 patients (25 male; mean age 40 ± 16 y) with CKD in whom renal biopsy revealed AA-amyloidosis (Group II) were investigated. Upper and lower gastrointestinal tract (GIT) endoscopies were performed and multiple biopsies from gingiva, esophagus, antrum, duodenum and rectum were obtained. In Group I, no amyloidosis was detected in gingival and GIT biopsies among 13 patients. In the remaining 29 patients AA-amyloidosis was detected in various sites with the following frequencies: duodenum 100%, rectum 83%, antrum 79%, esophagus 44% and gingiva 29%. In Group II, frequency of amyloid deposition was 97% in duodenum, 76% each in antrum and rectum, 59% in esophagus and 32% in gingival mucosa. In conclusion, duodenal biopsy is sensitive for diagnosing amyloidosis in CKD patients, and highly correlates with renal amyloidosis.

Renal Involvement in AA Amyloidosis: Clinical Outcomes and Survival

Background: The natural history of AA amyloidosis is typically progressive, leading to multiple organ failure and death. We analyzed the etiology as well as clinical and laboratory features of patients with biopsy-proven AA amyloidosis and evaluated the ultimate outcome. Methods: Seventy-three patients (24 female; mean age 41.85±15.89 years) were analyzed retrospectively. Demographic, clinical and laboratory features were studied and the outcome was assessed. Results: Familial Mediterranean Fever and tuberculosis were the most frequent causes of amyloidosis. Mean serum creatinine and proteinuria at diagnosis were 4.65±4.89 mg/dl and 8.04±6.09 g/day, respectively; and stage I, II, III, IV and V renal disease were present in 19.2%, 13.7%, 16.4%, 11%, and 39.7% of the patients, respectively. ESRD developed in 16 patients during the follow-up period. All of the ESRD patients started a dialysis programme. Thirty patients (41%) died during the follow-up period; median patient survival was 35.9±6.12 months. Old age, tuberculosis etiology, advanced renal disease and low serum albumin levels were associated with a worse prognosis. Serum albumin was a predictor of mortality in logistic regression analysis. Conclusion: The ultimate outcome of the patients with AA amyloidosis is poor, possibly due to the late referral to the nephrology clinics. Early referral may be helpful to improve prognosis.

Impact of Volume Status on Blood Pressure and Left Ventricle Structure in Patients Undergoing Chronic Hemodialysis

In this study, we aimed to examine the impact of volume status on blood pressure (BP) and on left ventricular mass index (LVMI) in chronic hemodialysis (HD) patients. This study enrolled 74 patients (F/M: 36/38, mean age 53.5 ± 15.3 years, mean HD time 41.5 ± 41 months) that were on HD treatment for at least 3 months. Demographics, biochemical tests, hemogram and C-reactive protein levels, mean interdialytic weight gain (IDWG), mean percentage of ultrafiltration (UF), and intradialytic complications such as hypotension and cramps were determined. Mean values of predialysis and postdialysis BP measurements were recorded a month before echocardiographic examination. On the day after a midweek dialysis session, 24 h ambulatory BP monitoring (ABPM) and echocardiographic examination were made concurrently. The patients were classified into two groups according to volume status: normovolemic (group 1; 14F/24M, mean age 50 ± 16.7 years, mean dialysis time 47.7 ± 47.7 months) and hypervolemic (group 2; 15F/21M, mean age 57.3 ± 12.7 years, mean dialysis time 34.9 ± 32 months). HD duration, IDWG, UF, and interdialytic complication rates were similar between the two groups (p < 0.05). Eleven patients (28.9%) of group 1 and 8 patients (22.2%) of group 2 showed dipper (p = 0.50). Valvular damage was more common in group 2 (p = 0.002). Whereas 33 patients (91.7%) had left ventricular hypertrophy (LVH) in group 2, 21 patients of the group 1 (55.3%) had LVH (p < 0.001). Although LVMI showed a significant positive correlation with cardiothoracic index, predialysis and postdialysis BP, IDWG, UF, daytime and nighttime BP measurements of 24 h ABPM, a significant negative correlation was seen with Kt/V urea and serum albumin levels. In conclusion, increased IDWG and UF and elevated BP are independent predictors of LVH for HD patients. Increased volume status leads to IDWG and elevated BP and eventually causes severe LVMI increases.

Dilated uremic cardiomyopathy in a dialysis patient cured by persistent ultrafiltration.

A patient is presented who after 2 years of hemodialysis showed all of the features of congestive cardiomyopathy to a very severe degree: dilation of all cardiac compartments, increased left ventricular mass, low ejection fraction, diastolic disturbances, third- to fourth-degree mitral and tricuspid regurgitation, ascites, and low blood pressure. All of these abnormalities gradually but completely disappeared during 5 months of persistent ultrafiltration during or between dialysis sessions. It was concluded that chronic fluid overload was a major factor in the cardiac disease of this patient. Unrecognized hidden fluid overload has long been known (but also neglected), and its prevention deserves top priority in chronic dialysis patients.