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Belda Dursun

Publications and source records attributed to Belda Dursun.

13 recordsLinked to original sources
PubMed2006

Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury.

Clinical studies demonstrate that acute renal failure (ARF) is associated with increased mortality, which may be due to pulmonary complications. ARF may affect the lung via increased renal production or impaired clearance of mediators of lung injury, such as proinflammatory cytokines. Bilateral nephrectomy is a method to examine directly the deleterious systemic effects of absent renal clearance in ARF without the confounding effects that are associated with ischemia-reperfusion injury (e.g., ischemic ARF) or systemic toxicity (e.g., cisplatin-induced ARF). This study contrasts the effects of ischemic ARF and bilateral nephrectomy on serum cytokines and lung injury. It demonstrates that the acute absence of kidney function after both ischemic ARF and bilateral nephrectomy is associated with an increase in multiple serum cytokines, including IL-6 and IL-1beta, and that the cytokine profiles were distinct. Lung injury after ischemic ARF and bilateral nephrectomy was similar and was characterized by pulmonary vascular congestion and neutrophil infiltration. For investigation of the role of proinflammatory cytokines in pulmonary injury after ARF, the anti-inflammatory cytokine IL-10 was administered before bilateral nephrectomy. IL-10 treatment improved pulmonary architecture and was associated with a reduction in inflammatory markers, including bronchoalveolar lavage fluid total protein, pulmonary myeloperoxidase activity (a biochemical marker of neutrophils), and the chemokine macrophage inflammatory protein 2. These data demonstrate for the first time that the acute absence of kidney function results in pulmonary injury independent of renal ischemia and highlight the critical role of the kidney in the maintenance of serum cytokine balance and pulmonary homeostasis.

Acute Kidney Injury↗
PubMed2006

Caspases and calpain are independent mediators of cisplatin-induced endothelial cell necrosis.

The role of caspases and calpain in cisplatin-induced endothelial cell death is unknown. Thus we investigated whether caspases and calpain are mediators of cisplatin-induced apoptosis and necrosis in endothelial cells. Cultured pancreatic microvascular endothelial (MS1) cells were exposed to 10 and 50 microM cisplatin. Apoptosis or necrosis was determined by Hoechst 33342 and propidium iodide (PI) nuclear staining. Cells treated with 10 microM cisplatin had normal ATP levels, increased caspase-3-like activity, excluded PI and demonstrated morphological characteristics of apoptosis at 24 h. Cells treated with 50 microM cisplatin had severe ATP depletion, increased caspase-3-like activity, and displayed extensive PI staining indicative of necrosis at 24 h. There was a dose-dependent increase in caspase-2-like activity and Smac/DIABLO protein. Calpain activity increased significantly with 50 microM, but not 10 microM cisplatin at 24 h. With 50 microM cisplatin, ATP levels were significantly reduced starting at 18 h, caspase-2- and caspase-3-like activities were significantly increased starting at 18 h, and LDH release started at 8 h with maximum increase at 18-24 h. Calpain activity was not increased before 24 h. The increase in LDH release and the nuclear PI staining with 50 microM cisplatin at 24 h was reduced by either the pancaspase inhibitor, Q-VD-OPH, or the calpain inhibitor, PD-150606. Calpain inhibitor had no effect on caspase-3-like activity. In conclusion, in cisplatin-treated endothelial cells, caspases, the major mediators of apoptosis, can also cause necrosis. A calpain inhibitor protects against necrosis without affecting caspase-3-like activity suggesting that calpain-mediated necrosis is independent of caspase-3.

Acrylates↗
PubMed2006

Ischemic acute renal failure following nephrectomy impairs long-term renal function.

Uninephrectomy is associated with increased glomerular filtration rate in both the donated and the remaining contralateral kidney. The long-term effects of ischemic acute renal failure (ARF) following uninephrectomy are unknown. This study examined renal function, histology and proteinuria 52 weeks after an episode of reversible ischemic ARF. Ischemic ARF was induced in uninephrectomised mice by renal pedicle clamping. At 52 weeks inulin clearance (muL/min/g) was 7.2+/-0.2 in sham, 5.0+/-0.1 in uninephrectomy (P<0.01 vs. sham) and 3.9+/-0.1 in uninephrectomy + ischemia (P<0.01 vs. sham, P<0.05 vs. uninephrectomy). Thus, mice subjected to uninephrectomy alone demonstrated compensatory hyperfiltration following reduction in renal mass. This response was prevented by ischemic ARF. At 52 weeks there was no difference in urine protein/creatinine, mean arterial pressure or scores of glomerulosclerosis or interstitial fibrosis. In conclusion, ischemic ARF following uninephrectomy in mice impairs long-term renal function.

Acute Kidney Injury↗
PubMed2006

Treatment with an inhibitory monoclonal antibody to mouse factor B protects mice from induction of apoptosis and renal ischemia/reperfusion injury.

Complement activation in the kidney after ischemia/reperfusion (I/R) seems to occur primarily via the alternative complement pathway. The ability of an inhibitory mAb to mouse factor B, a necessary component of the alternative pathway, to protect mice from ischemic acute renal failure was tested. Treatment with the mAb prevented the deposition of C3b on the tubular epithelium and the generation of systemic C3a after renal I/R. Treated mice had significantly lower increases in serum urea nitrogen and developed significantly less morphologic injury of the kidney after I/R. For gaining insight into potential mechanisms of protection, the activity of caspases within the kidney also was measured, and it was found that caspases-2, -3, and -9 increased in a complement-dependent manner after renal I/R. Apoptotic cells were detected by terminal deoxynucleotidyl transferase catalyzed labeling of DNA fragments, and mice in which the alternative pathway was inhibited demonstrated significantly less apoptosis than control mice. Thus, use of an inhibitory mAb to mouse factor B effectively prevented activation of complement in the kidney after I/R and protected the mice from necrotic and apoptotic injury of the tubules.

Analysis of Variance↗
PubMed2005

Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure.

BACKGROUND: Ischemia reperfusion injury leading to acute renal failure (ARF) and delayed graft function is an important problem in organ transplantation. CD4+ T cells, essential for transplant rejection, may mediate ischemic ARF. We have demonstrated that the caspase-1 mediated production of IL-18 is pathogenic in ischemic ARF in mice. A potential source of IL-18 in ischemic ARF is the CD4+ T cell. We therefore examined the effect CD4+ T cell depletion on the development of ischemic ARF and the activation of IL-18. METHODS: Functional and histological correlates were examined in two groups of mice with ischemic ARF: 1) CD4 T-cell depleted with the antibody GK1.5, and 2) T-cell receptor alpha-chain deficient (TCRalpha -/-) mice. TCRalpha -/- mice lack the alpha chain of the T-cell receptor and therefore lack functional CD4+ and CD8+ T cells. RESULTS: Flow cytometry of lymph nodes and immunohistochemistry of kidneys demonstrated complete depletion of CD4+ T cells in mice with ischemic ARF treated with GK 1.5. CD4+ T-cell depletion did not confer functional (serum creatinine, BUN and FITC-labeled inulin clearance) or histological protection against ischemic ARF. Likewise, TCRalpha -/- mice were not protected against ischemic ARF. Renal caspase-1 activity and IL-18 protein were similar in CD4+ T-cell depleted and wild-type postischemic reperfusion. CONCLUSIONS: Ischemic ARF can occur in the absence of classical T-cell function. The evaluation of other inflammatory mediators (e.g., macrophages or NK cells) as a source of IL-18 and mediator of ischemic ARF warrants further investigation.

Acute Kidney Injury↗
PubMed2005

An atypical case of POEMS syndrome with IgG kappa M protein and end stage renal failure.

POEMS syndrome is a rare plasma cell dyscrasia which is characterized by small amounts of monoclonal protein, and a multisystem complex manifested by various combinations of polyneuropathy, organomegaly, endocrinopathy and skin changes. Here, we presented an atypical case of POEMS syndrome with IgG kappa monoclonal protein, chronic demyelinating polyneuropathy, hepatosplenomegaly, hypothyroidism, gynecomastia and severe renal impairment. The finding of IgG kappa type of monoclonal protein in our patient was interesting because the majority of cases were reported to have lambda light chain. Also, the absence of typical skin and bone lesions were atypical. Though speculative, these atypical features may account for the unusual presentation of this case. Our patient rapidly progressed to end-stage renal failure and died of cachexia. Renal involvement in POEMS syndrome is rare but may show substantial clinical and pathological variations. Proteinuria, hematuria, renal dysfunction and renal failure requiring hemodialysis can be seen. The pathogenesis of renal dysfunction is unclear. As a conclusion, POEMS syndrome may present with diverse clinicopathologic manifestations. In this syndrome, renal involvement may lead to end stage renal failure and the course may be fatal due to severe polyneuropathy and wasting.

Cachexia↗
PubMed2005

Benefits of low dose immunoglobulin in the treatment of refractory CAPD peritonitis and longevity of technical survival on CAPD.

In this study we investigated the long term results of intraperitoneal immunoglobulin (Ig) treatment in continuous ambulatory peritoneal dialyses (CAPD) patients with refractory or relapsing peritonitis. Sixteen CAPD patients (4 female, 12 male) with a mean age of 53 +/- 11 years (40-80), with a mean CAPD duration of 46.2 +/- 4.8 months (17-75) were included in the study. The patients included had a diagnosis of either refractory or relapsing peritonitis unresponsive to appropriate antibiotic therapy. 0.5 g of Ig was added to every exchange bag qid as an adjunctive therapy to the culture based antibiotherapy for 7 days. Intraperitoneal Ig treatment was found to be successful in treating peritonitis in all but one patient. Interestingly, following Ig treatment, long term peritonitis rate decreased significantly compared to the period before treatment (before: 2.2 +/- 0.6 episodes/patient/year vs. after: 0.6 +/- 0.17 episodes/patient/year; P = 0.019). The mean CAPD duration after Ig treatment was 30.5 +/- 5.4 (4-64) months. Out of 16 patients, one patient who was unresponsive, had his catheter removed and was switched to hemodialysis, and four patients with preexisting ultrafiltration failure or inadequate dialysis problems were transferred to hemodialysis after successful treatment of their peritonitis, one patient was transplanted and 10 patients continued on CAPD. We conclude that low dose Ig treatment may be beneficial in the treatment of refractory or relapsing CAPD peritonitis possibly through restoring impaired host defense within peritoneal cavity. This therapy, by preventing further peritonitis attacks, may prolong survival on CAPD.

Adult↗
PubMed2005

Carbonyl stress in chronic renal failure: the effect of haemodialysis.

Oxidative stress has been defined as a loss of balance between free radical production and the antioxidant systems. There have been many reports of increased production of oxidants and decreased levels of antioxidants in chronic renal failure (CRF) patients. An increase in oxidative stress may contribute to the development of oxidative protein damage in CRF. Our aim was to reveal oxidative modifications of plasma proteins by measuring 2,4-dinitrophenylhydrazine reactive carbonyl derivates (PCO), protein thiol (P-SH) and reduced glutathione (GSH) in predialytic uraemic and haemodialysed (HD) patients before and after dialysis. We included 20 predialytic uraemic patients, 20 HD patients and 20 healthy volunteers in our study. PCO concentration in predialytic uraemic patients increased compared with the concentration of the control group and this increase was more profound in HD patients. P-SH concentrations were significantly decreased in haemodialytic patients compared with those of controls. GSH level was higher in HD patients (both before and after dialysis). Increased PCO and decreased P-SH concentrations in all patient groups in comparison to the control subjects indicate increased protein oxidation. Our data in ESRD patients propose plasma protein carbonyl derivates and thiol concentrations as novel specific markers for oxidative protein damage.

Aged↗
PubMed2005

Can cystatin C be a better marker for the early detection of renal damage in primary hypertensive patients?

In this study, we aimed to compare Cystatin C (Cys C) with other traditional glomerular filtration rate (GFR) markers and to evaluate its superiority over them in detecting early renal involvement in patients with primary hypertension. Fifty-one primary hypertensive patients and 29 healthy control subjects, who were similar in terms of age and gender, were included in the study. In all subjects serum levels of Cys C, beta-2 microglobulin, serum creatinine (SCr), uric acid, BUN, albumin; 24 h urinary levels of protein (Upro), albumin (Ualb) and creatinine were measured. The GFR was calculated according to Creatinine Clearance (CrCl), Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas. The MDRD was used as the reference method. A GFR<80 mL/min/1.73 m2 was considered as the lower cut-off limit. Mean levels of the serum parameters were found to be significantly higher in the patient group than they were in the control group (p<0.05). Mean CrCl, CG, and MDRD levels were lower in patients than they were in controls but the difference was statistically significant for CG and MDRD. The serum parameter having the best correlation with MDRD was SCr (r = -0.760) in patients and Cys C (r = -0.622) in controls. However, in ROC analysis; the area under curve (AUC) for Cys C was found to be superior (AUC = 0.900) to the other markers. The CrCl was the parameter having the worst diagnostic efficiency (AUC = 0.598). As a conclusion, compared to other traditional markers, measurement of Cys C may be a better parameter to estimate GFR, especially to detect mild reductions of GFR in primary hypertensive patients.

Adult↗
PubMed2004

Effects of different dialysis modalities on cardiac autonomic dysfunctions in end-stage renal disease patients: one year prospective study.

Cardiac autonomic dysfunction (CAD) is a common problem in patients with end-stage renal disease (ESRD) and may contribute to the risk of cardiac mortality. Long-term effects of dialysis modalities on CAD in ESRD patients are not clear. In this one-year prospective study, we studied the effects of different dialysis modalities on CAD in ESRD patients. The study consisted of 20 ESRD patients who had the indications for initiating dialysis therapy (13 hemodialysis and 7 CAPD patients) and 15 healthy controls (M/F: 5/10; age 30 +/- 4). In all the subjects, first at the beginning of study (in patient groups just before initiating dialysis therapy) and then after 12 months, we studied 24 hours ECG-Holter monitoring and heart rate variability parameters (time and frequency domain analysis parameters; SDNN: standard deviations of nn intervals, rMSSD: square root of the median of standard deviation, HRVI: heart rate variability index, LF/HF: low frequency/high frequency). In ESRD patients, before dialysis therapy, all the parameters of time domain analysis were significantly lower compared to control group (p = 0.001). In patient groups, after dialysis therapy (on the 12th month), significant improvement was observed in time domain analysis parameters (p = 0.001). When dialysis modalities were compared, the increase in the time domain analysis parameters was significantly greater in the CAPD group compared to hemodialysis (HD) group. Our findings suggest that CAD is frequent in ESRD patients, a dialysis therapy of 12 months can cause significant improvement on CAD and the ameliorative effect of CAPD is better than HD.

Adult↗
PubMed2004

Can a different priming process of the dialyzer affect dialysis adequacy in chronic hemodialysis patients?

In this study, we investigated whether a different priming process of the dialyzer could affect the dialysis adequacy in chronic hemodialysis (HD) patients. 20 HD patients (M/F:12/8) with a median age of 40 (20-74) were included in this study. All the patients were clinically stable and were on bicarbonate-based hemodialysis program 3 times in a week. During the study period of 6 months, we tried to keep the vascular accesses, types and surfaces of the membranes and also the blood and dialysate flow rates almost the same for all patients. For the first 3 months of the study we performed our routine priming process by flushing 1 L of saline from the bloodline without any dialysate passing through the dialyzer. For the next 3 months, we carried out a different priming process. While we passed 1 L of saline through the blood compartment of the dialyzer, we also started the dialysate pump to get a flow rate of 500 mL/min for 30 minutes. After a 3 month period of different priming process, significant increases were observed in Kt/V (1.19+/-0.14 to 1.35+/-0.14, p=0.000), URR (%) (62.3+/-1.1 to 66.9+/-1.25, p=0.000) and nPCR (1.09+/-0.04 to 1.25+/-0.04, p=0.002) parameters. Our findings show that a priming process of the dialyzer by passing both saline and dialysate from the dialyzer for half an hour before starting every dialysis session can improve dialysis adequacy parameters. We suggest that this procedure, by increasing dialysis adequacy, can provide great clinical benefits.

Adult↗
PubMed2002

Effect of hemodialysis on the oxidative stress and antioxidants.

Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.

Antioxidants↗