Acute kidney injury in Turkey: epidemiological characteristics, etiology, clinical course, and prognosis.

BACKGROUND: This study aimed to evaluate the etiologies, comorbidities, and outcomes of acute kidney injury (AKI) in Turkey and determine any potential differences among different geographical parts of the country. METHODS: This prospective observational study was conducted by the Acute Kidney Injury Working Group of the Turkish Society of Nephrology. Demographical and clinical data of patients with AKI at the time of diagnosis and at the 1st week and 1st, 3rd, and 6th months of diagnosis were evaluated to determine patient and renal survival and factors associated with patient prognosis. RESULTS: A total of 776 patients were included (54.7% male, median age: 67 years). Prerenal etiologies, including dehydration, heart failure, and sepsis, were more frequent than other etiologies. 58.9% of the patients had at least one renal etiology, with nephrotoxic agent exposure as the most common etiology. The etiologic factors were mostly similar throughout the country. 33.6% of the patients needed kidney replacement therapy. At the 6th month of diagnosis, 29.5% of the patients had complete recovery; 34.1% had partial recovery; 9.5% developed end-stage kidney disease; and 24.1% died. The mortality rate was higher in the patients from the Eastern Anatolian region; those admitted to the intensive care unit; those with prerenal, renal, and postrenal etiologies together, stage 3 AKI, sepsis, cirrhosis, heart failure, and malignancy; those who need kidney replacement therapy; and those without chronic kidney disease than in the other patients. CONCLUSION: Physicians managing patients with AKI should be alert against dehydration, heart failure, sepsis, and nephrotoxic agent exposure. Understanding the characteristics and outcomes of patients with AKI in their countries would help prevent AKI and improve treatment strategies.

Acute renal infarction in Turkey: a review of 121 cases.

PURPOSE: Renal infarction is a clinical condition which is caused by renal artery occlusion and leads to permanent renal parenchymal damage. In the literature, there are generally case reports on this subject, and few studies that include a large group of patients. Therefore, we aimed to present the data of a large group of patients who were diagnosed with acute renal infarction in our country in this retrospective study. METHODS: The data of patients who were diagnosed with acute renal infarction according to clinical and radiological findings in Turkey in the last 3 years were examined. For this purpose, we contacted with more than 40 centers in 7 regions and obtained support from clinically responsible persons. Demographic data of patients, laboratory data at the time of diagnosis, tests performed for etiologic evaluation, given medications, and patients' clinical status during follow-up were obtained from databases and statistical analysis was performed. RESULTS: One-hundred and twenty-one patients were included in the study. The mean age was 53 ± 1.4 (19-91) years. Seventy-one (58.7%) patients were male, 18 (14.9%) had diabetes, 53 (43.8%) had hypertension, 36 (30%) had atrial fibrillation (AF), and 6 had a history of lupus + antiphospholipid syndrome (APS). Forty-five patients had right renal infarction, 50 patients had left renal infarction, and 26 (21.5%) patients had bilateral renal infarction. The examinations for the ethiologies revealed that, 36 patients had thromboemboli due to atrial fibrillation, 10 patients had genetic anomalies leading to thrombosis, 9 patients had trauma, 6 patients had lupus + APS, 2 patients had hematologic diseases, and 1 patient had a substance abuse problem. Fifty-seven (57%) patients had unknown. The mean follow-up period was 14 ± 2 months. The mean creatinine and glomerular filtration rate (GFR) values at 3 months were found to be 1.65 ± 0.16 mg/dl and 62 ± 3 ml/min, respectively. The final mean creatinine and GFR values were found to be 1.69 ± 0.16 mg/dl and 62 ± 3 ml/min, respectively. CONCLUSIONS: Our study is the second largest series published on renal infarction in the literature. More detailed studies are needed to determine the etiological causes of acute renal infarction occurring in patients.

Neutrophil gelatinase-associated lipocalin reflects the severity of anemia without iron deficiency and secondary hyperparathyroidism in hemodialysis patients.

OBJECTIVE: Secondary hyperparathyroidism (SHPT) and anemia are the primary and most common complications in patients receiving hemodialysis (HD). Neutrophil gelatinase-associated lipocalin (NGAL) is a new marker to assess iron deficiency and manage iron therapy for HD patients. The aim of this study was to determine any association between serum NGAL level and anemia without iron deficiency in patients with SHPT on chronic HD. METHODS: Total of 61 SHPT patients on chronic HD were enrolled in the study and divided into 3 groups: mild SHPT group (n=17), moderate SHPT group (n=21), and severe SHPT group (n=23). Hemogram, biochemical assays, and level of ferritin, high sensitivity C-reactive protein (hs-CRP), and NGAL were evaluated in all groups. RESULTS: Serum NGAL level was significantly higher and hemoglobin (Hb) level was significantly lower in severe SHPT patients compared with both mild and moderate SHPT patients. Furthermore, in severe SHPT group, serum NGAL level was significantly positively correlated with serum parathyroid hormone (r=0.79; p=0.00) and hs-CRP (r=0.52; p=0.01) level and negatively correlated with serum Hb (r=-0.56; p=0.00) level. CONCLUSION: SHPT was important factor affecting anemia in HD patients. Even when iron deficiency anemia is excluded in patients with SHPT, there was significant negative correlation between serum NGAL and Hb.

Relationships between plasma pentraxin 3 levels and inflammation markers patients with tunneled permanent catheter in hemodialysis.

PURPOSE: Vascular access (VA) devices may contribute to chronic inflammation in hemodialysis (HD). Pentraxin 3 (PTX3) is a recently discovered acute phase protein that responds more rapidly than other inflammatory markers. This study compared PTX3 and other markers between HD patients and healthy controls. METHODS: The study population included 30 patients with tunneled permanent catheter (TPC), 30 patients with arteriovenous fistula (AVF) and 30 healthy controls. Hemogram, biochemical assays, ferritin, high sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and PTX3 were evaluated in all groups. RESULTS: PTX levels were highest in HD patients with TPC, intermediated in HD patients with AVF and lowest in healthy controls (5.2 + 2.4 vs. 3.1 + 1.3 vs. 1.8 + 0.7, p<0.001 for all comparisons). PTX3 levels correlated strongly to hs-CRP (r = 0.857) and moderately to TNF-α, NLR, ferritin and total neutrophil count. PTX3 and albumin levels had a negative correlation. PTX3 levels were higher in patients with 8 months of TPC than those with 7 months or less. CONCLUSIONS: PTX3 levels are significantly elevated in all patients on HD, but presence and extended duration of TPC are associated with incrementally higher levels of PTX3 and other inflammatory markers. PTX3 and NLR may be useful in assessing chronic inflammatory states in HD.

The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity.

The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7 mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100 mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p<0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p<0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p<0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p<0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p<0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.

Can serum NGAL levels be used as an inflammation marker on hemodialysis patients with permanent catheter?

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of lipocalin family and released from many tissues and cells. We aimed to investigate the relationship among serum NGAL levels, the inflammation markers (IL-6, hs-CRP, TNF-α) and different vascular access types used in dialysis patients. METHODS: The study population included 90 patients and 30 healthy age-matched controls. The patients were divided into three groups (I, II, III) and group IV included the controls. In group I and II, the patients were with central venous permanent catheter and arterio-venous fistula, respectively. Group III included 30 patients with chronic renal failure. Hemogram, biochemical assays, ferritin, IL-6, hs-CRP, TNF-α, and NGAL were evaluated in all groups. RESULTS: Serum NGAL levels were markedly higher in group I than in group II (7645.80 ± 924.61 vs. 4131.20 ± 609.87 pg/mL; p < 0.05). Positive correlation was detected between NGAL levels and duration of catheter (r: 0.903, p: 0.000), hs-CRP (r: 0.796, p: 0.000), IL-6 (r: 0.687, p: 0.000), TNF-α (r: 0.568, p: 0.000) levels and ferritin (r: 0.318, p: 0.001), whereas NGAL levels were negatively correlated with serum albumin levels (r: -0.494, p: 0.000). In multiple regression analysis, duration of catheter hs-CRP and TNF-α were predictors of NGAL in hemodialysis patients. CONCLUSION: Inflammation was observed in hemodialysis patients and increases with catheter. Our findings show that a strong relationship among serum NGAL levels, duration of catheter, hs-CRP and TNF-α. NGAL may be used as a new inflammation marker in hemodialysis patients.

Bone marrow uptake in parathyroid scintigraphy is a consequence of extremely high parathyroid hormone levels.

OBJECTIVE: We retrospectively evaluated patients with end-stage renal disease (ESRD) who were referred to our department for parathyroid scintigraphy. The aim of this study was to investigate the causes of bone marrow uptake observed on parathyroid scintigraphy. METHODS: We included 18 ESRD patients (10 F, 8 M; mean, 52 ± 13 years old; range, 45-59) in the study. The disease duration of the patients was mean 7.7 ± 4.7 years. The patients' mean plasma calcium and parathormone (PTH) levels were 9.7 ± 1.4 mg/dL and 1,553.3 ± 691.7 pg/mL, respectively. Dual-phase technetium-99m 2-methoxyisobutyl-isonitrile (Tc-99m MIBI) parathyroid imaging and, if necessary, additional Tc-99m pertechnetate scintigraphy were performed. Quantification of the planar early phase parathyroid images was performed for various regions (sternum, humerus, ribs) with the same size rectangular region of interest (ROI, 176 × 176 pixels). Average counts were compared with paired samples Student's t tests, and P<.05 was considered statistically significant. RESULTS: Tc-99m MIBI parathyroid imaging revealed parathyroid hyperplasia, adenoma, and ectopic adenoma in 7, 3, and 2 patients, respectively. The other 7 patients had normal scintigraphy results with regard to parathyroid pathologies. Bone marrow uptake in the sternum, ribs, and humerus was observed in 6 patients. The difference between the average quantitative value obtained from the ROIs drawn on the sternum and humerus was also statistically significant compared to patients without bone marrow uptake (P<.05). All 6 patients' exhibited extremely high PTH levels (>2,000 pg/mL; mean, 2,413.7 ± 150 pg/mL) compared to the other 12 patients (mean, 1,342.8 ± 249 pg/mL). CONCLUSION: Our results show that bone marrow uptake on parathyroid scintigraphy is a consequence of extremely high PTH levels in ESRD patients; no further analysis is required.

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney. METHODS: Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis. RESULTS: The increased NF-κß p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (P < 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic rats. CONCLUSION: Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κß p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.

Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury.

In previous studies, we have demonstrated the biological activity of thymoquinone (TQ), an active compound extracted from the Nigella sativa plant, against cisplatin-induced neurotoxicity. Recenty, it was observed that there is an inherent lack in regulation of renal organic anion and cation transporters in cisplatin-induced nephrotoxicity. Here, we report, for the first time, the effect of TQ on alterations in the renal expression of organic anion transporters (OATs) and organic cation transporters (OCTs), as well as multidrug resistance-associated proteins (MRPs) in rats treated with cisplatin. Twenty-eight 8-week-old male Wistar rats were divided into four groups of control, TQ treated (10 mg/kg b.w. in drinking water for 5 days), cisplatin (7 mg/kg b.w., i.p.) and TQ and cisplatin combination treatment. Cisplatin-induced malondialdehyde (MDA) and 8-isoprostane increase was found to be markedly reduced in rats treated with TQ. In cisplatin only treated rats, the induced renal injury increased protein levels of the efflux transporters MRP2 and MRP4 while expression of OAT1, OAT3, OCT1 and OCT2 was reduced. In combination TQ- and cisplatin-treated rats, expression of MRP2 and MRP4 proteins was decreased in the kidneys. Conversely, TQ treatment increased levels of OCT1, OCT2, OAT1 and OAT3 and decreased levels of 8-isoprostane and MDA levels in cisplatin-treated rats. In conclusion, the present study shows that the TQ synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.

A tomato lycopene complex protects the kidney from cisplatin-induced injury via affecting oxidative stress as well as Bax, Bcl-2, and HSPs expression.

Cisplatin-induced nephrotoxicity is related to an increase in oxidative stress in the kidney. Lycopene, a carotenoid found in tomatoes, is a potent dietary antioxidant. In the present study, we investigated the effect of the tomato lycopene complex against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. Male Wistar rats (n = 28, 8 wk old, between 200-215 g) were divided into 4 groups: (a) control, (b) tomato lycopene complex (6 mg/kg, daily; consisting of 6% lycopene, 1.5% tocopherols, 1% phytoene and phytofluene, and 0.2% ß-carotene), (c) cisplatin (7 mg/kg i.p., single dose), and (d) cisplatin + tomato lycopene complex. Cisplatin administration increased serum urea-N (171 vs. 37 mg/dl) and creatinine (1.80 vs. 0.42 mg/dl) and decreased body weight in comparison with the control rats (P < 0.001). Serum creatinine and urea-N levels were lower in rats treated with tomato lycopene complex + cisplatin compared with rats treated with cisplatin alone (P < 0.001). The renal tissue from the cisplatin-treated rats had greater malondialdehyde (MDA; 172 vs. 93 nmol/g) and 8-isoprostane levels (1810 vs. 610 pg/g) than that from the control rats (P < 0.001). Tomato lycopene complex prevented the rise of MDA and 8-isoprostane (P < 0.001). No measurable lycopene could be detected in the serum of the control and cisplatin-treated rats, whereas lycopene was observed in the serum of rats supplemented with tomato lycopene complex. Renal Bax protein expression was significantly higher in the cisplatin-treated rats than in the control rats, and tomato lycopene complex treatment significantly reduced Bax expression (P < 0.001). The expression of Bcl-2 was higher in tomato lycopene complex/cisplatin-treated rats than in the cisplatin-injected rats (P < 0.05). The expression of renal HSP60 and HSP70 was significantly lower in tomato lycopene complex + cisplatin-treated rats than in rats treated with cisplatin alone (P < 0.001). These results suggest that tomato lycopene complex has protective effects against cisplatin-induced nephrotoxicity and lipid peroxidation in rats.

Protective role of zinc picolinate on cisplatin-induced nephrotoxicity in rats.

OBJECTIVE: Cisplatin-induced nephrotoxicity is related to an increase in lipid peroxidation, oxygen-free radicals, and inflammation in kidney. Zinc is an antioxidant and has anti-inflammatory action. To date, the protective role of zinc picolinate on cisplatin-induced renal injury has not been investigated. The purpose of the present study was to examine the effect of zinc picolinate on cisplatin-induced renal injury. METHODS: Male Wistar rats (n = 28, 8-week-old, weighing 200 to 220 g) were divided into four groups consisting of 7 rats each: control, zinc picolinate (6 mg Zn kg(-1) BW i.p.), cisplatin (7 mg kg(-1)BW i.p., single dose) and cisplatin plus zinc picolinate. RESULTS: A single dose of cisplatin resulted in an increase in malondialdehyde, 8-isoprostane, and tumor necrosis factor-α levels of kidney and significantly deranged renal function (urea-N and creatinine; P < .0001). Zinc picolinate treatment significantly reduced urea-N, creatinine, malondialdehyde, 8-isoprostane, and tumor necrosis factor-α -α levels. Concentration of zinc in kidney was increased significantly after zinc picolinate supplementation; however, Fe and Cu levels did not change. Expression of Bax in kidney increased with cisplatin administration, and this could be prevented by zinc picolinate treatment (P < .001). However, bcl-2 expression did not change by zinc or cisplatin treatment (P > .05). The expression of heat shock proteins 60 and 70 in kidney was increased after cisplatin treatment compared with the levels in the control (P < .01), and this increase could be prevented by the zinc picolinate treatment (P < .05). CONCLUSIONS: These results suggest that zinc picolinate may be a potential preventive agent in cisplatin-induced renal injury through decreasing oxidative stress and inflammation.

Epigallocatechin-3-gallate activates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats.

AIMS: Cisplatin-induced nephrotoxicity is associated with increased oxidative stress and inflammatory cytokines in the kidney. Epigallocatechin-3-gallate (EGCG) has anti-oxidant, anti-inflammatory, and anti-tumorigenic properties. In this study, we investigated the effects of EGCG on cisplatin-induced nephrotoxicity and potential mechanisms by which it enhances antioxidant activities and resolves inflammation after EGCG treatment during cisplatin-induced nephrotoxicity. MAIN METHODS: Twenty-eight rats were divided into four groups as control (group 1; no treatment; n=7), EGCG (group 2; n=7), cisplatin (group 3; n=7) or cisplatin and EGCG (group 4; n=7). After 2 days of EGCG treatment at a dose of l00 mg/kg BW, rats were treated with a single i.p. injection of cisplatin (7 mg/kg BW). On day 12 (10days after the cisplatin treatment), all rats were sacrificed by cervical dislocation. The level of protein was examined by Western blotting. KEY FINDINGS: Cisplatin caused a significant decrease in the expression nuclear levels of NF-E2-related factor-2 (Nrf2), heme oxygenase-1(HO-1), and an increase in the levels of nuclear factor-kappa B (NF-kappaB p65) and 4-hydroxynonenal (HNE) an oxidative stress marker. EGCG supplementation significantly improved the changes associated with cisplatin nephrotoxicity by increasing levels of Nrf-2 and HO-1, and decreasing levels of NF-kappaB and HNE. Renal activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione were significantly lower in cisplatin-treated rats compared with control rats, and EGCG treatment significantly increased the activities of antioxidant enzymes and glutathione (P<0.001). SIGNIFICANCE: The results suggest that Nrf2/HO-1 signaling pathway may be the primary target for prevention of cisplatin-induced nephrotoxicity by EGCG, and that reduces it inflammation by inhibiting NF-kappaB.

Acute effect of standard heparin versus low molecular weight heparin on oxidative stress and inflammation in hemodialysis patients.

OBJECTIVE: Atherosclerotic cardiovascular diseases caused by traditional and non-traditional risk factors are the most common cause of morbidity and mortality in hemodialysis patients. Recently, much interest has been focused on non-traditional factors, such as oxidative stress, inflammation, and endothelial dysfunction. Hemodialysis patients are not only exposed to oxidative stress but also to inflammation. Although anticoagulants are the most frequently used drugs in hemodialysis patients, their effect upon oxidative stress and inflammation in dialysis patients are still unknown. METHODS: Thirty-three hemodialysis patients were randomized into three groups. Group 1 received standard heparin while group 2 received low molecular weight heparin during the dialysis therapy. Group 3 (control group) did not receive any anticoagulant agent. Investigators were blinded to the therapy. Serum concentrations of oxidative stress and inflammation markers, including C-reactive protein, tumor necrosis factor alpha, superoxide dismutase, and malondialdehyde, were measured before and after dialysis session. RESULTS: The oxidative stress and inflammation markers were significantly increased in groups 1 and 3 (p < 0.05 for each) compared to their baseline values. In contrast, baseline and end-treatment values of the oxidative stress and inflammation markers were comparable in the group 2 (p > 0.05). CONCLUSION: These findings indicate that the type of anticoagulants may take a role in the acute effect of hemodialysis upon oxidative stress and inflammation markers. A comparison of the groups revealed that low molecular weight heparin decreased the oxidative stress and inflammation, whereas standard heparin increased the oxidative stress and inflammation. Low molecular weight heparin appears to have an additive benefit for hemodialysis patients.

The effect of oxidative stress inhibition with trimetazidine on the peritoneal alterations induced by hypertonic peritoneal dialysis solution.

BACKGROUND: Chronic peritoneal dialysis (PD) can result in several peritoneal alterations of varying degree, which lead to progressive reduction in dialytic efficacy. Although its pathogenesis has not been clarified yet, it has been proposed that high glucose induced oxidative stress generation within the peritoneal membrane plays an important role in leading to membrane alterations. The aim of this study was to investigate the effect of oxidative stress inhibition on peritoneal alterations induced by hypertonic PD solutions in rats. METHODS: The rats were divided into three groups receiving no treatment (the control group), hypertonic PD solution intraperitoneally (ip) only (the hypertonic dextrose group) and hypertonic PD solution ip plus trimetazidine (TMZ) orally (TMZ group). After 4 weeks, a one-hour peritoneal equilibration test (PET) was performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D(1)/D(0) glucose), ultrafiltration volume (UF) and the level of dialysate protein were determined. The levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF) and the activity of glutathione peroxidase (GPx) were investigated in the peritoneal tissue lysates. The peritoneal membrane was evaluated histologically by light microscopy. RESULTS: Compared to the control group, peritoneal function tests (UF: 3.6 +/- 0.4 vs. 1.2 +/- 0.6 mL, D/P urea: 0.57 +/- 0.03 vs. 0.76 +/- 0.04, D(1)/D(0) glucose: 0.46 +/- 0.02 vs. 0.33 +/- 0.05) and morphology (thickness: 4.4 +/- 0.5 vs. 61 +/- 14 micro m and neovascularisation: 0.2 +/- 0.4 vs 2.4 +/- 0.8 number/field) were dramatically altered in the hypertonic PD solution-treated rats. Likewise, higher levels of VEGF, MDA and decreased activity of GPx were determined in the hypertonic PD solution-treated rats. Although peritoneal thickness (37 +/- 17 micro m) was not completely decreased, peritoneal functions were protected in the TMZ group (UF: 4.0 +/- 0.4 mL, D/P urea: 0.62 +/- 0.06, D(1)/D(0) glucose: 0.43 +/- 0.02). In the TMZ group, MDA and VEGF levels and neoangiogenesis were significantly less than those of the hypertonic dextrose group. In addition, GPx activity significantly increased in the TMZ group. CONCLUSIONS: These data demonstrated that not only generating oxidative stress but also attenuating antioxidative system and high glucose concentration can cause structural and functional alterations within the peritoneal membrane. TMZ can preserve these alterations by inhibiting the oxidative stress within the peritoneal membrane.