Aydin Unal

The long‐term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients

The aim of this prospective study was to evaluate long‐term effects of arteriovenous fistula (AVF) on the development of pulmonary arterial hypertension (PAH) and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in the patients with end‐stage renal disease (ESRD). This prospective study was performed in 20 patients with ESRD. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in all patients. After mean 23.50 ± 2.25 months, the second evaluation was performed by echocardiography. Also, the blood flow rate of AVF was measured at the second echocardiographic evaluation. Pulmonary arterial hypertension was defined as a systolic PAP above 35 mmHg at rest. Mean age of 20 patients with ESRD was 55.05 ± 13.64 years; 11 of 20 patients were males. Pulmonary arterial hypertension was detected in 6 (30%) patients before AVF creation and in 4 (20%) patients after AVF creation. Systolic PAP value was meaningfully lower after AVF creation than before AVF creation (29.95 ± 10.26 mmHg vs. 35.35 ± 7.86 mmHg, respectively, P: 0.047). However, there was no significant difference between 2 time periods in terms of presence of PAH (P>0.05). Pulmonary artery pressure did not correlate with blood flow rate of AVF and duration after AVF creation (P>0.05). In hemodialysis patients, a surgically created AVF has no significant effect on the development of PAH within a long‐term period. Similarly, blood flow rate of AVF also did not affect remarkably systolic PAP within the long‐term period.

Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients.

Background/Aims: Cardiovascular disease is the main cause of morbidity and mortality in autosomal-dominant polycystic kidney disease (ADPKD) patients. To clarify temporal relationship between ADPKD, hypertension and the loss of renal function, we examined these factors in patients with early-stage ADPKD who did not yet have hypertension. Methods: Fifty patients with ADPKD (42% males, 36.6 ± 9.9 years, no blood pressure medication) and 50 healthy controls (44% males, 35.4 ± 6.4 years) were studied cross-sectionally. Pulse wave velocity (PWV), cardiac morphology and function, aortic elastic indexes, estimated glomerular filtration rate (eGFR), 24-hour ambulatory blood pressure, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and highly sensitive C-reactive protein (hs-CRP) were measured in all participants, using conventional methods. Results: Despite a normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls (6.8 ± 4.7 vs. 5.1 ± 3.3, p = 0.043 and 9.6 ± 1.3 vs. 5.8 ± 1.1 m/s, p < 0.001). In univariate analysis, IL-6, TNF-α, hs-CRP and eGFR were all significantly correlated with PWV. The independence of these correlations were analyzed in a regression model, and showed PWV to be significantly predicted by IL-6, TNF-α and hs-CRP. Conclusion: Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR. However, these vascular abnormalities are related to signs of systemic low grade inflammation, suggesting a common pathophysiological mechanism apparently present also in other vascular diseases but yet to be elucidated.

Role of neutrophil/lymphocyte ratio in prediction of disease progression in patients with stage–4 chronic kidney disease

BACKGROUND Chronic kidney disease (CKD) tends to progress to end-stage renal disease without any intervention. Neutrophil/lymphocyte (N/L) ratio may be indicative of an underlying inflammatory state. We aimed to investigate the role of N/L ratio for prediction of progression to dialysis in patients with stage 4 CKD. METHODS We included 105 patients with stage 4 CKD in the study. All patients were followed up from the first admission to dialysis. N/L ratio was measured during follow-up. Patients were divided into two groups as baseline N/L (N/Lb) ratio < 3 and N/Lb ratio =3 and rapid progression was defined as > 5 mL/minute/year loss of creatinine clearance and slow progression as < 5 mL/minute/year. RESULTS Patients with N/L ratio =3 demonstrated high progression rate compared to patients who had N/L ratio <3 (2.6 ± 1.6 and 5.4 ± 3.3, P<.001). hs-CRP levels were higher in patients who had rapid progression (5.6 ± 3.0 and 20.2 ± 10.6, P<.001). The sensitivity and specificity of N/Lb were 79% and 69%, respectively, when the cutoff level was accepted as N/L ratio =3 for determining rapid progression. Furthermore, patients with a high N/Lb ratio had worse prognosis and significantly faster progression to the dialysis compared with those with a low N/L ratio. CONCLUSION Our results suggest that N/L ratio may predict the progression rate of stage 4 chronic kidney disease to dialysis. It is an easily accessible and useful marker for monitoring CKD patients in clinical practice.

A Link between the Intrarenal Renin Angiotensin System and Hypertension in Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Early onset of hypertension and its consequences account for the great majority of deaths in patients with autosomal dominant polycystic kidney disease (ADPKD). Renin-angiotensin system (RAS) components have been shown in ADPKD kidneys independent of systemic RAS. Thus, we examined the urinary angiotensinogen (UAGT) levels as a biomarker of intrarenal RAS status in ADPKD patients with/without hypertension and healthy subjects. Methods: Eighty-four ADPKD patients (43 with hypertension and 41 without hypertension) and 40 healthy controls were studied cross-sectionally. Patients with glomerular filtration rate <60 ml/min were excluded from the study. Hypertension was diagnosed with ambulatory blood pressure monitoring. Urinary and plasma concentration of angiotensinogen, spot urine microprotein and creatinine (UCre) levels were recorded for each participant. Results: UAGT/UCre levels were higher in hypertensive ADPKD patients (23.7 ± 8.4) compared with normotensive ADPKD patients (16.6 ± 5.2) and healthy controls (6.9 ± 3.3; p < 0.001). In univariate analysis, UAGT correlated with systolic blood pressure, diastolic blood pressure (DBP) and proteinuria. The independence of these correlations was analyzed in a regression model, and UAGT was shown to be significantly predicted by proteinuria and DBP. Conclusion: Intrarenal RAS activation which is monitored by UAGT levels clinically may be a harbinger of hypertension and kidney disease in ADPKD patients.

Carotid‐jugular arteriovenous fistula and cerebrovascular infarct: A case report of an iatrogenic complication following internal jugular vein catheterization

Central venous catheterization is frequently performed for perioperative management and long‐term intravenous access. Although complications associated with central venous catheter insertion have been widely reported, there are few reports of carotid‐jugular arteriovenous fistula formation. Endovascular procedures are associated with a risk of immediate and delayed thromboembolic and ischemic complications. We describe a case of a carotid‐jugular arteriovenous fistula and a cerebrovascular infarct following the insertion of a double‐lumen catheter for hemodialysis access. We provide recommendations for the prevention and the early detection of this iatrogenic complication.

Occult HBV infection in continuous ambulatory peritoneal dialysis and hemodialysis patients.

Aim. Occult hepatitis B virus (HBV) infection can be defined as the presence of HBV DNA in the liver and/or blood in the absence of detectable serum hepatitis B surface antigen (HBs Ag). There is a high prevalence of occult HBV infection in dialysis patients. This study investigated the prevalence of occult HBV infection in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients and compared the prevalence of occult HBV infection in dialysis patients either with or without hepatitis C virus (HCV) infection. Methods. In this cross-sectional study, 71 CAPD patients and 71 HD patients were evaluated. HBV DNA testing was performed by polymerase chain reaction (PCR). We recorded general characteristics of the patients, duration of dialysis, HBs Ag, antibody to hepatitis B surface antigen (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), anti-HCV antibody (anti-HCV), HCV RNA, serum alanine aminotransferase (ALT), and aspartate aminotransferase levels (AST). Results. Twelve (16.9%) of the 71 HD patients and seven (9.8%) of the 71 CAPD patients were HBV DNA-positive. A statistically significant difference was not observed in the groups. Anti-HCV was negative and AST and ALT levels were normal in all of the HBV-DNA positive patients. Viral loads were low in both groups. Conclusion. This is the first study that analyzes occult HBV prevalence in CAPD patients. We conclude that the prevalence of the occult HBV may be common in CAPD patients as in HD patients, and HCV positivity is not a contributing factor to occult HBV infection in dialysis patients.

Serum Uric Acid Levels and Endothelial Dysfunction in Patients with Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit endothelial dysfunction (ED) despite normal levels of renal function. Hyperuricemia occurs in these patients and has been postulated to affect ED through the generation of oxidative stress. We therefore investigated the prevalence of ED and its association with serum uric acid levels in early-stage ADPKD. Methods: A cross-sectional design was used for the assessment of prevalent patients with early-stage (normal renal function) ADPKD (n = 91) from two academic medical centers. ED was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Serum uric acid levels were evaluated using an Olympus AU2700 autoanalyzer. Results: ADPKD patients with higher serum uric acid levels had a higher asymmetric dimethylarginine (ADMA) level (1.19 ± 0.2 vs. 1.47 ± 0.3, p < 0.001) and lower FMD rates (8.1 ± 1.3 vs. 6.8 ± 0.7, p < 0.001). In multiple regression analysis for predictors of cohort FMD, uric acid (β = -0.32, p < 0.001), ADMA (β = -0.36, p < 0.001), high-sensitivity C reactive protein (CRP; β = -0.32, p < 0.001) and estimated glomerular filtration rate (eGFR; β = 0.33, p < 0.001) all predicted FMD. Conclusions: In early-stage ADPKD patients, uric acid levels, serum ADMA and eGFR all independently predict ED in a similar manner. Future studies are needed to investigate the causes of elevated serum uric acid, ADMA and CRP in these patients.

Protective effect of N-acetylcysteine from drug-induced ototoxicity in uraemic patients with CAPD peritonitis

AIM Peritonitis is currently one of the leading complications of continuous ambulatory peritoneal dialysis (CAPD) treatment. Aminoglycosides and vancomycin are used in the treatment of CAPD peritonitis despite their potential risk for ototoxicity. N-acetylcysteine (NAC) is a molecule used in the treatment and prophylaxis of many diseases related to oxidative stress. The aim of this study was to examine whether ototoxicity due to antibiotics used in the treatment of CAPD peritonitis can be prevented by NAC. METHODS Sixty patients, who first developed CAPD peritonitis attacks from February 2008 to April 2010 were included in this study. Patients were divided into two groups, those taking an additional NAC treatment (n = 30) and a control group (n = 30). Low- and high-frequency hearing function tests were performed on the two groups before treatment (baseline), at the end of the first (early follow-up) and the fourth week after the treatment (late follow-up). Total doses of vancomycin and amikacin were recorded. RESULTS There was no statistically significant difference between the groups in terms of hearing functions at the beginning. However, patients taking NAC had better hearing function test results 4 weeks after the treatment compared with those of the control group (P < 0.05). There were no statistical differences between posttreatment low-frequency hearing function tests conducted at the baseline and the first and the fourth weeks in patients taking NAC. The first and the fourth weeks low-frequency hearing functions worsened when compared with the baseline low-frequency results in the control group (P < 0.001). It was found that NAC had a protective effect against ototoxicity on low-frequency (0.25-8 KHz) hearing functions. The first and the fourth weeks high-frequency hearing functions improved when compared with baseline high-frequency hearing functions in patients taking NAC (P < 0.05), while they worsened. The first and fourth weeks high-frequency tests worsened when compared with the baseline high-frequency tests in the control group (P < 0.001). CONCLUSIONS The present study suggests that intraperitoneal aminoglycoside and vancomycin administration in CAPD patients may cause low- and high-frequency hearing loss, and this ototoxic effect is related to the dose given. It was found that when the antioxidant NAC is administered alone, it prevents ototoxicity, associated with intraperitoneal amikacin and vancomycin in patients with CAPD peritonitis. In addition, it was revealed that NAC may also have a curative effect on impaired high-frequency hearing functions.

An Underappreciated Problem in Renal Transplant Recipients: Anemia

PURPOSE Posttransplant anemia (PTA) is associated with a higher risk of cardiac mortality, which is the most frequent cause of death among renal transplant recipients. In this study, we sought to determine the prevalence and causes of PTA among Turkish patients. PATIENTS AND METHODS The study included 75 (52 male, 23 female) adults. Anemia was defined as an hemoglobin (Hb) level < or = 13 g/dL for men and < or = 12 g/dL for women. RESULTS The prevalence of PTA was 49.3% at a mean duration of 60.45 months after renal transplantation. The most frequent causes of PTA were erythropoietin (EPO) and iron deficiency. The mean Hb level of 12.76 +/- 2.31 g/dL was significantly higher in male compared to female patients (13.26 +/- 2.31 g/dL vs 11.64 +/- 1.93 g/dL, P = .005). The Hb value was positively correlated with creatinine clearance and serum albumin level, and negatively correlated with serum creatinine level, the amount of proteinuria, and cyclosporine level. Creatinine clearance and serum albumin level were found to be an independent risk factors for PTA upon multivariate analysis. Only 12 of 37 anemic patients received treatment for anemia: 5 (13.5%) with EPO and 7 (18.9%) with iron preparations. CONCLUSION PTA a common complication was unfortunately neglected in this setting. Impaired renal allograft function and decreased serum albumin were major risk factors for PTA. Increased cyclosporine levels were also correlated with decreased Hb concentrations.

IMPACT OF ARTERIAL STIFFNESS ON ADVERSE CARDIOVASCULAR OUTCOMES AND MORTALITY IN PERITONEAL DIALYSIS PATIENTS

♦ Background: Cardiovascular (CV) disease is a major cause of morbidity and mortality in patients with end-stage renal disease. In recent years, arterial stiffness has taken on great importance in the pathophysiology of CV diseases. The independent predictive value of arterial stiffness for CV events and for all-cause and CV mortality has been demonstrated in the general population and in hemodialysis patients. Our aim in this study was to determine the relationship of arterial stiffness with mortality and fatal and nonfatal CV events in peritoneal dialysis (PD) patients. ♦ Methods: In this prospective observational cohort study with 2 years of follow-up, we studied a cohort of 156 PD patients with a mean follow-up of 19.2 ± 6.4 months. At baseline, echocardiography and standard clinical and biochemical analyses were performed in all patients and in 28 healthy subjects. Aortic stiffness index beta (ASIβ, a surrogate marker of arterial stiffness) was calculated as follows: ♦ Results: During the follow-up period, 25 of the patients (16.0%) died, and 10 of those deaths had CV causes. Nonfatal CV events occurred in 15 patients. The median ASIβ was greater in PD patients than in control subjects (4.2 vs. 3.5; interquartile range: 3.2 – 5.5 vs. 2.5 – 4.8; p = 0.028]. In the fully adjusted multivariate Cox regression analysis (co-variates: age, sex, albumin, hemoglobin, diabetes mellitus, comorbid CV disease, left ventricular mass index, residual glomerular filtration rate, dialysate-to-plasma ratio of creatinine, Kt/V urea, left ventricular ejection fraction, duration of dialysis, smoking), ASIβ independently predicted fatal and nonfatal CV events (hazard ratio: 1.239; 95% confidence interval: 1.103 to 1.392), but not all-cause mortality. ♦ Conclusions: Our results provide the first direct evidence that arterial stiffness is an independent risk predictor of adverse CV outcome in PD patients.