Eray Eroglu

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.

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.

Endothelial Nitric Oxide Synthase Gene Expression Is Associated with Hypertension in Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Early occurrence of hypertension is the prominent feature of autosomal dominant polycystic kidney disease (ADPKD). The role of angiotensin-converting enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism in the clinical course of ADPKD is not well understood. However, data about the expression of these genes are lacking. Thus, we aimed to investigate the polymorphisms and expressions of both the ACE and eNOS genes that affect hypertension in ADPKD. Methods: Whole blood samples were obtained from all participants. ACE and eNOS gene polymorphisms and their expressions were analyzed in 78 ADPKD patients and 30 controls. Gene expressions were assessed by quantitative real-time PCR. Twenty-four-hour blood pressure monitoring was performed for the diagnosis of hypertension in all study participants. Results:eNOS expression and the estimated glomerular filtration rate were found to be significantly higher in ADPKD patients without hypertension than in those with hypertension. Each unit of increase in eNOS expression led to a 0.88-fold decrease (95% CI: 0.80-0.96) in the risk of hypertension in multiple logistic regression analysis. Conclusions:eNOS gene expression is independently predictive of hypertension in the ADPKD population. This study showed, for the first time, a novel link between eNOS gene expression and hypertension in ADPKD.

Evaluation of Fibrosis Markers: Apelin and Transforming Growth Factor-β1 in Autosomal Dominant Polycystic Kidney Disease Patients.

Renal interstitial fibrosis is an important pathological feature of autosomal dominant polycystic kidney disease (ADPKD), which progressively develops to end‐stage renal disease (ESRD). It has been shown that apelin and transforming growth factor‐β1 (TGF‐β1) play important roles in the renal fibrosis process. The aim of the present study is to evaluate the relationship of these fibrosis markers and ADPKD. Forty‐five patients with ADPKD and 28 healthy controls were studied cross‐sectionally. Estimated glomerular filtration rate (eGFR), apelin, TGF‐β1 were measured in all participants, using conventional methods. Apelin levels were lower (1.2 ± 0.9 ng/mL vs. 2.5 ±  1.3 ng/mL, P < 0.001), while TGF‐β1 levels were higher in the patient group according to healthy controls (466.5 ±  200.5 ng/L vs. 367.1 ± 163.45 ng/L, P = 0.031), respectively. Apelin was negatively correlated with TGF‐β1 and highly sensitive C‐reactive protein (hs‐CRP); and positively correlated with eGFR. In all subjects, eGFR was independently predicted by TGF‐β1 and apelin. Apelin and TGF‐β1 may be used as biomarkers of renal fibrosis that is an important pathological feature of ADPKD, which progressively develops to ESRD in ADPKD patients.

The role of platelet activation in determining response to therapy in patients with primary nephrotic syndrome

To test the role of platelet activation in the prognosis of nephrotic syndrome (NS), we evaluated the mean platelet volume (MPV) in patients with NS undergoing treatment. In this prospective, multicenter clinical study 156 patients with primary NS under treatment were assigned and followed for one year. Patients were divided into three groups for complete remission, partial remission, and resistance. Biochemical parameters, estimated glomerular filtration rate, proteinuria level, and MPV levels were compared at baseline and 12 months after treatment. MPV, proteinuria, total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, total protein, albumin, and hs-CRP levels significantly decreased in partial and complete remission group after 12 months compared to the baseline (p < 0.05). However, MPV levels significantly increased and only LDL cholesterol significantly decreased in the resistance group (p < 0.05). Univariate analyses demonstrated that ΔMPV was significantly associated with Δproteinuria (r = 0.41, p < 0.001), Δhs-CRP (r = 0.39, p < 0.001), and ΔAlbumin (r = −0.30, p < 0.001). We found that ΔAlbumin (β = −0.33, p < 0.001), ΔTotal cholesterol (β = −0.20, p = 0.011), and Δhs-CRP (β = 0.19, p = 0.018) were statistically significant predictors of the Δproteinuria in multiple regression analysis. In subjects with primary NS, MPV is associated with the prognosis or the disease. This study provides the background for longer trials and the role of platelet activation in NS.

Mesangial proliferative glomerulonephritis in familial Mediterranean fever patient with E148Q mutation: the first case report

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease characterized by recurrent attacks of fever, usually accompanied by sterile polyserositis. Although amyloidosis is the most common renal involvement, non-amyloid renal lesions, such as glomerulonephritis, have been described in patients with FMF. In this report, we present the first case of an FMF patient with heterozygous mutation of E148Q, mesangial proliferative glomerulonephritis, and no amyloidosis. While the association of mutation E148Q with renal involvement is still obscure, colchicine treatment is useful in mesangial proliferative glomerulonephritis with FMF.

Levofloxacin-Induced Delirium: Is It a Dangerous Drug in Patients with Renal Dysfunction?

The central nervous system (CNS) toxicity of fluoroquinolones is well known but usually occurs benign. In the literature, there are a few number of severe CNS toxicity cases related to fluoroquinolones. Levofloxacin is a third-generation fluorinated quinolone antibiotic, is the active levo stereoisomer of ofloxacin, and has one of the most favorable adverse reaction profiles. We describe a case of delirium associated with levofloxacin in a 55-year-old man who was hospitalized in our medical clinic for pneumonia.

The effect of strict volume control on cardiac biomarker and arterial stiffness in peritoneal dialysis patients.

INTRODUCTION Arterial stiffness is a risk marker for cardiovascular events in peritoneal dialysis (PD) patients. Strict volume control strategy has been shown to result in better cardiac functions and control of hypertension in these patients. The aim of the study was to identify the determinants of arterial stiffness and evaluate the changes in cardiac biomarkers in PD patients under strict volume control strategy. METHODS 58 PD patients were enrolled into this prospective observational study. Arterial stiffness determined by aortic pulse wave velocity (PWV), echocardiography, ambulatory blood pressure and NT-pro-BNP levels were measured at baseline and at first year. RESULTS The mean age of the patients was 46.4 ± 14 years. 30 patients were on automated PD (APD) and 28 on continuous ambulatory PD (CAPD) group. In both groups, there were significant differences in PWV values at baseline and at the end of the study. A similar decrease was observed with NT-proBNP and PWV levels. In addition, a significant improvement was found in echocardiographic parameters in all patients. Comparison of APD and CAPD groups with respect to change in one year, showed no difference in echocardiographic findings, while the reduction in PWV, NTproBNP and blood pressure values was higher in the CAPD group. CONCLUSIONS In PD patients, strict volume control leads to a reduction in NT-pro-BNP levels, better control of blood pressure and significant improvements in cardiac functions and arterial stiffness.

The association of endothelial progenitor cell markers with arteriovenous fistula maturation in hemodialysis patients

AbstractAimsArteriovenous fistula (AVF) failure is one of the most important clinical problems in end-stage renal disease. Endothelial progenitor cells (EPCs) have a role on vascular angiogenesis and endothelialization. We aimed to investigate the association markers of EPCs on AVF maturation by measuring the surface expressions of CD34, CD309 and CD133 on the monocytes.MethodsThis prospective observational study was conducted in 54 voluntary patients with end-stage renal disease who were admitted for their first renal replacement therapy and were available for AVF creation. Venography was performed in all patients before AVF creation. Six patients were excluded due to inadequate veins after venographic imaging, and also seven patients were excluded due to postoperative thrombosis. The blood samples were analyzed a day before the fistula operation, and the expressions of CD34, CD133 and CD309 on the surface of monocytes were measured.ResultsPatients were divided into two groups after the evaluation of AVF maturation, as the mature group and the failure group. The CD309 expression level on the monocytes was 338.00 (35.00–479.00) in the mature group; however, it was 36.00 (5.50–237.00) (p 0.031) in the failure group. Multiple logistic regression analyses showed that both BMI and the mean fluorescence intensity level of CD309 expression on monocytes independently predicted AVF maturation.ConclusionsThe presence of DM and increased BMI negatively correlated with AVF maturation. High intensity of CD309 expression on monocytes was observed in patients with successful AVF maturation.