Aydin Turkmen

The evaluation of oxidative stress in patients with chronic renal failure

BACKGROUND Free radical-mediated changes are thought to be involved with atherosclerosis in patients with chronic renal failure. METHODS The protein carbonyl and malondialdehyde (MDA) levels in serum as the markers of radical-induced protein and lipid oxidations were measured in chronic renal failure patients. RESULTS Serum carbonyl and MDA levels in both hemodialysis and peritoneal dialysis patients were not found to be different as compared with healthy subjects. In both patient groups, the approximately twofold increment in total antioxidant activity (ferric reducing/antioxidant power; FRAP) and uric acid values in serum were found. The high uric acid levels in both patient groups might be partly responsible for the increment in FRAP values. In addition, all patients received multivitamin preparations including ascorbate, which was also a major antioxidant in serum. CONCLUSIONS Our data suggest that oxidative stress does not become the major threat for patients with chronic renal failure. The increment in endogenous and exogenous antioxidant capacities in serum might be thought to prevent any possible radical-induced damage in patients with chronic renal failure. In addition, the increased nitric oxide (NO) levels especially in hemodialysis patients might likely favor an antioxidant effect.

The effect of calcineurin inhibitors on endothelial function in renal transplant recipients.

Abstract:  Endothelial dysfunction is of vital importance, as it may cause ischemia and dysfunction in various organs. Despite, this problem has been well documented in patients with end‐stage renal disease (ESRD), there is not enough data considering this issue following renal transplantation. One of the potential causes of endothelial dysfunction in renal transplant recipients may be administration of calcineurin inhibitors. The aim of this study is to evaluate the effects of two different calcineurin inhibitors [cyclosporin A (CsA) and tacrolimus (FK506)] on endothelial function in renal transplant patients. Forty‐four renal transplant recipients [22 on FK506 (group I) and 22 on CsA (group II)] were studied. Endothelial functions of the brachial artery were evaluated by using high resolution vascular ultrasound. Endothelium‐dependent and ‐independent vasodilations were assessed by establishing reactive hyperemia and using sublingual nitroglycerine (NTG), respectively. Results are presented as percentage change from baseline values. Significant endothelial dysfunction was noted in renal transplant patients treated with CsA. While endothelium‐dependent vasodilation was 12.1 ± 5.1% in group I and it was 6.5 ± 3.7% in group II (p < 0.001). The increase in brachial artery diameter after sublingual NTG was 20.1 ± 6.3 and 12.7 ± 5.6% in groups I and II, respectively. This indicates that the endothelium‐dependent and ‐independent vasodilation of the patients on FK506 is better preserved than the patients on CsA therapy. Besides, blood flow volume (BFV) increase was 51.2 ± 39.4 and 43.9 ± 24.3%, in groups I and II, respectively, in reactive hyperemia period (p > 0.05). Post‐transplant course of renal transplant recipients is complicated by endothelial dysfunction. This problem is more prominent in patients on CsA therapy, which can predispose these patients to more frequent cardiac complications.

Efficacy of anakinra treatment in a patient with colchicine-resistant familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limited recurrent attacks of fever and serositis. The serious complication of FMF is AA-type amyloidosis, which can result in end-stage renal disease. Although colchicine is effective in the majority of patients, there is no established treatment for those who are resistant or intolerant to colchicine. We herein report the efficacy of anakinra in a 52-year-old Turkish patient with FMF, secondary amyloidosis and renal transplant, who was resistant to colchicine treatment.

Improvement of Uremic Autonomic Dysfunction after Renal Transplantation: A Heart Rate Variability Study

Autonomic dysfunction in hemodialysis patients is one of the components of uremic neuropathy. In this prospective study, we investigated the effect of renal transplantation on uremic autonomic dysfunction with long-term time-domain and frequency-domain heart rate variability. Fourteen hemodialysis patients (10 male, 4 female; mean age 33 ± 11 (range 16–50) years) were examined before and at the early after transplantation period (mean 4.6 ± 1.5 (range 3–7.5) months). The mean time spent on hemodialysis was 16.7 ± 15.6 (range 6–65) months. In time-domain analysis, significant increases in all parameters except pNN50 (SD, SDANN, SDNN, rMSSD) were observed after renal transplantation (p < 0.01). In frequency-domain analysis, low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.40 Hz) spectral power were found to be significantly increased after renal transplantation (4.54 ± 1.04 vs. 12.58 ± 8.69 for LF (p = 0.005), 2.80 ± 1.0 vs. 6.50 ± 3.55 for HF (p = 0.005)), but the LF/HF ratio was not different from a pretransplant period (1.71 ± 0.349 vs. 1.85 ± 0.49, p = 0.26). It was concluded that autonomic dysfunction in hemodialysis patients is reversible and renal transplantation reverses the sympathetic and parasympathetic autonomic dysfunction simultaneously and at a relatively early stage.

Effects of zinc supplementation on the immune system and on antibody response to multivalent influenza vaccine in hemodialysis patients.

The depression of the immune system in chronic uremia is a well-known phenomenon but the role of serum zinc (Zn) levels on both cell-mediated and humoral immunity is still controversial. The aim of this study was to investigate the effect of Zn supplementation on the immune system and on antibody response to multivalent influenza vaccine (MIV) in hemodialysis patients (HP). Twenty-six HP and 11 healthy subjects (HS) were vaccinated with MIV. Hemodialysis patients were randomly divided into two groups. Group 1 (13 HP) was supplemented with 120 mg ZnS04 after each dialysis session. Group II (13 HP) and Grouip III (11 HS) were given placebo. In all cases, the serum Zn levels, CD3, CD4, CD8, CD19, HLA-DR+ cell percentages, CD4/CD8 ratio and CD3+HLA-DR+ cell percentages were determined before and 30 days after vaccination. Antibody levels to subgroups of MIV were also measured. All the baseline parameters studied were not statistically different between Group I and II. However, there was a significant difference between the basal parameters of Group III and the other two groups, except for CD3 and CD4 cell percentages. Serum Zn, CD19 cell percentage and antibody levels to MIV subgroups were significantly increased in Group I at the end of the first month of the study (p<0.01, p<0.05, p<0.001, p<0.001, and p<0.01, respectively), but the other parameters showed no significant changes. The only significant change observed in Groups II and III was an increase in antibody levels to MIV subgroups one month after vaccination. Antibody levels to MIV subgroups, were not statistically different between Groups I and II, but in Group III they were strikingly higher than those of HP (p<0.001). These results led us to conclude that Zn supplementation could not restore the immune parameters and enhance antibody response to MIV in HP.

Appetite-regulating Hormones in Chronic Kidney Disease Patients

OBJECTIVE Inflammation and loss of appetite is the most common problem in patients with chronic kidney disease (CKD). This comparative cross-sectional study aimed to characterize the changes in circulating levels of ghrelin, obestatin, leptin, all of which have an effect on food intake, and proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in patients with CKD who were undergoing different treatments. DESIGN AND SETTING Study participants included 36 patients who had undergone hemodialysis (body mass index [BMI]: 22.3 ± 4.17 kg/m(2)); 41 who had undergone peritoneal dialysis (BMI: 23.5 ± 3.10 kg/m(2)), 30 with early stage CKD (BMI: 24.4 ± 3.32 kg/m(2)), and 31 healthy subjects (24.3 ± 2.14 kg/m(2)). The patients with CKD were kept under a standard diet with restricted salt, potassium, and protein intake. INTERVENTION Levels of leptin, acylated ghrelin, obestatin, TNF-α, and IL-6 were measured by commercially available enzyme-linked immunosorbent assay kits. Total nitrite/nitrate was analyzed using colorimetric assay kit. RESULTS Significantly high leptin levels, accompanied by low acylated ghrelin levels, were observed in patients with CKD. Maintenance dialysis did not affect these levels. TNF-α and IL-6 levels were significantly higher in CKD patients than in healthy subjects, the highest being in dialysis patients. Obestatin levels were relatively low in patients who had undergone hemodialysis. CONCLUSION Low acyl-ghrelin levels, accompanied with high levels of TNF-α and IL-6 may be involved in the loss of appetite and poor nutritional status in CKD patients.

Coronary flow reserve dysfunction in hemodialysis and kidney transplant patients

Abstract: Background:  The assessment of coronary flow reserve (CFR) by trans‐thoracic echocardiography has recently been introduced into clinical studies. Impairment of coronary microvascular functions and decreased CFR detected by trans‐thoracic Doppler harmonic echocardiography (TTDE) has recently been reported in hemodialysis (HD) patients, but there is no comparative study between HD patients and renal transplant recipients.

Renal transplantation in amyloidosis secondary to familial Mediterranean fever.

FAMILIAL Mediterranean fever (FMF) is an autosomal recessive disorder, common in some ethnic groups such as Sephardic Jews, Armenians, Turks, and Arabs. The disease is characterized by recurrent attacks of fever associated with serositis affecting the pleura, peritoneum, and/or large joints as well as systemic amyloidosis of the AA type causing nephropathy and end-stage renal failure (ESRF). There is a wide variation in the reporting of this disease as a cause of ESRF. Among the member countries of European Dialysis and Transplantation Association (EDTA), amyloidosis was responsible 1.6% of all ESRF patients. In 76% of these patients, chronic inflammatory diseases were the underlying etiology for amyloidosis, and FMF was the second cause. Most of the FMF patients were localized to Egypt, Israel, and Turkey. Even a lower incidence (0.3%) of amyloidosis as a cause of ESRF has been reported from the United States; however the underlying etiology of these cases was not defined in this report. In contradistinction, amyloidosis represents a more common cause of chronic renal failure among patients from the Middle East and the Mediterranean countries; and FMF has been identified as the most frequent underlying cause for the disease in these groups. Indeed, FMF amyloidotic patients represent 6% of the candidates for renal transplantation in Israel. In Turkey 4.2% of ESRF patients suffer from amyloidosis, although the underlying etiology was not identified in this report. Thus, at least in some countries, amyloidosis is an important etiologic factor for ESRF. As most of the patients with renal amyloidosis progress to ESRF, the selection of the renal replacement therapy modality (ie, hemodialysis, peritoneal dialysis, or renal transplantation) is a major concern. It has been reported that amyloidotic patients maintained on chronic hemodialysis experience higher rates of morbidity and mortality when compared to dialysis patients whose causes of ESRF were due to other diseases. There is not enough information regarding the patients on chronic peritoneal dialysis; because the effects of repeated peritoneal inflammation on peritoneal permeability has not been well defined. Considering kidney transplantation, many authors have concerns, because amyloidosis is a generalized disorder and most patients show systemic manifestations of the disease. There are four concerns when considering these patients for transplantation.

Effect of Cyclosporin A and Tacrolimus on Sister Chromatid Exchange Frequency in Renal Transplant Patients

Long-term use of Cyclosporin A (CsA) and Tacrolimus is known to yield serious untoward side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation. Sister chromatid exchange (SCE) is used to assess the genotoxic potential of various agents. A total of 37 postrenal transplant patients receiving either CsA (n = 20) or Tacrolimus (n = 17) were included in this study. The genotoxic effects of CsA and Tacrolimus were assessed by determination of SCE frequency. In patients receiving CsA, SCE frequency was increased significantly compared to that in the control group (p = 0.001), whereas Tacrolimus did not yield such a significant change (p = 0.801). SCE frequency was not correlated with drug dosage (p > 0.05). Our results indicate that the use of CsA, but not Tacrolimus 506, is associated with an increased genotoxic effect in postrenal transplant patients.

Clinical and molecular characterization of two adults with autosomal recessive Robinow syndrome

Autosomal recessive Robinow syndrome is caused by mutations in ROR2 and is characterized by short stature, mesomelic limb shortening, brachydactyly, vertebral abnormalities, and a characteristic “fetal face” dysmorphology. We report the clinical and molecular studies on two adults with this condition. Besides typical skeletal and facial features, one patient developed hydronephrosis, nephrocalcinosis, and renal failure. The second patient had characteristic skeletal manifestations including severe spinal involvement and showed endocrinological abnormalities including elevated gonadotropic hormones. The facial phenotype in both patients remained distinctive into adulthood. Analysis of the ROR2 gene revealed a homozygous c.1937_1943delACAAGCT mutation in Patient 1, and compound heterozygosity for c.355C > T (p.R119X). and c.550C > T (p.R184C) in Patient 2.