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.

Associations of platelet indices with proteinuria and chronic kidney disease.

OBJECTIVES: Platelet (PLT) indices are predictive in many diseases and conditions. The relationships of these indices with proteinuria and progression of renal disease are not well known. This study aimed to assess PLT indices in patients with primary glomerular nephrotic range proteinuria (PGNRP), with and without chronic kidney disease (CKD), and to compare these indices with those of healthy individuals (His). METHODS: This cross-sectional study was performed from January 2015 to May 2015. HIs (n = 57) and patients with PGNRP (n = 41) were enrolled. PLT indices and blood biochemistry parameters were compared between HIs and patients with PGNRP, as well as between subgroups of patients with PGNRP who had CKD (n = 23) and those who did not have CKD (n = 18). RESULTS: There were no statistically significant differences in any PLT indices (i.e., platelet number, mean platelet volume, plateletcrit, and platelet distribution width) between HIs and patients with PGNRP, or between the subgroups of patients with PGNRP. However, patients with PGNRP who had CKD exhibited higher median C-reactive protein and mean albumin levels, compared with patients who did not have CKD. CONCLUSIONS: Pathological processes in proteinuria and CKD are not associated with PLT indices.

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.

The effects of Mucuna pruriens on the renal oxidative stress and transcription factors in high-fructose-fed rats.

In the present study, we evaluated the effects of M. pruriens administration on metabolic parameters, oxidative stress and kidney nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways in high-fructose fed rats. Male rats (n = 28) were divided into 4 groups as control, M. pruriens, fructose, and M. pruriens plus fructose. All rats were fed a standard diet supplemented or no supplemented with M. pruriens (200 mg/kg/d by gavage). Fructose was given in drinking water for 8 weeks. High fructose consumption led to an increase in the serum level of glucose, triglyceride, urea and renal malondialdehyde (MDA) levels. Although M. pruriens treatment reduced triglyceride and MDA levels, it did not affect other parameters. M. pruriens supplementation significantly decreased the expression of NF-Ò¡B and decreased expression of Nrf2 and HO-1 proteins in the kidney. This study showed that the adverse effects of high fructose were alleviated by M. pruriens supplementation via modulation of the expression of kidney nuclear transcription factors in rats fed high fructose diet.

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.

Evaluation of nutritional status using anthropometric measurements and MQSGA in geriatric hemodialysis patients.

OBJECTIVE: Malnutrition is common among hemodialysis patients and is associated with higher rates of morbidity and mortality. The aim of this study was to evaluate nutritional status of geriatric hemodialysis patients. METHODS: Total of 163 hemodialysis patients were initially screened, and 55 patients (28 males, 27 females; mean age: 72.9±8.4 years) met the criteria for inclusion. Patients were divided into 3 groups according to modified quantitative subjective global assessment (MQSGA) scores: Group I (n=22) normal nutrition, Group II (n=20) mild-to-moderate malnutrition, and Group III (n=13) severe malnutrition. RESULTS: When we assessed the correlation between MQSGA nutrition score and data of malnourished patients (n=33), positive significant correlation was found between age, C-reactive protein level, and malnutrition-inflammation score. Negative significant correlation was found between body mass index, bicep skinfold, tricep skinfold, mid-arm circumference, mid-arm muscle circumference, and phosphate and albumin levels. CONCLUSION: Malnutrition is very common and increasing with aging in geriatric hemodialysis patients. MQSGA score and anthropometric measurements can be used to assess nutritional status in geriatric hemodialysis patients.

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.

Once-monthly continuous erythropoietin receptor activator (CERA) for haemoglobin maintenance in haemodialysis patients with chronic renal anaemia.

BACKGROUND: This study was conducted to evaluate the efficacy and safety of once-monthly continuous erythropoietin receptor activator (CERA) for maintenance of stable haemoglobin (Hb) levels in adult chronic renal anaemia patients on dialysis according to local clinical judgment in Turkey. METHODS: This was a prospective, open-label, single-arm, multi-centre study conducted in 20 centres in Turkey. After a 4-week screening period, eligible patients receiving conventional erythropoiesis-stimulating agents were converted to monthly intravenous CERA and entered a 16-week CERA dose-titration period (DTP) followed by an 8-week efficacy evaluation period (EEP) and a 4-week safety follow-up. The primary endpoint was the proportion of patients whose Hb concentration remained stable within ±1.0 g/dL of their reference Hb and within the range of 10.0-12.0 g/dL during the EEP. RESULTS: A total of 173 patients were screened, 132 entered the DTP and 84 completed the study. Thirty-nine patients [46.4% (95% confidence interval: 35.5-57.7%)] maintained stable target Hb concentrations. The mean change in time-adjusted average Hb concentration was 0.29 ± 1.08 g/dL between baseline and the EEP. The mean CERA monthly dose was 112.4 ± 76.78 µg during the EEP, and the CERA dose was adjusted in 39 patients (36.4%). Eleven patients (8.4%) reported 13 treatment-related adverse events, the most frequent adverse events being infections and infestations, gastrointestinal and vascular disorders. CONCLUSIONS: Once-monthly CERA maintains stable Hb concentrations in chronic renal anaemia patients on dialysis in Turkey. The study results confirm the known efficacy and safety profile of CERA.

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.

Effects of chromium histidinate on renal function, oxidative stress, and heat-shock proteins in fat-fed and streptozotocin-treated rats.

OBJECTIVE: Chromium is an essential element for carbohydrate, fat, and protein metabolism. The therapeutic potential of chromium histidinate (CrHis) in the treatment of diabetes has been elucidated. The present study investigated the effects of CrHis on serum parameters of renal function, on oxidative stress markers (malondialdehyde [MDA] and 8-isoprostane), and on the expression of heat-shock proteins (HSPs) in rats. METHODS: Male Wistar rats (n=60, 8 weeks old) were divided into four groups. Group 1 received a standard diet (12% of calories as fat). Group 2 received a standard diet, plus CrHis. Group 3 received a high-fat diet (40% of calories as fat) for 2 weeks, and was then injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg intraperitoneally). Group 4 was treated in the same way as group 3 (HFD/STZ), but was supplemented with 110 microg CrHis/kg/body weight/day. Oxidative stress in the kidneys of diabetic rats was evidenced by an elevation in levels of MDA and 8-isoprostane. Protein concentrations of HSP60 and HSP70 in renal tissue were determined by Western blot analyses. RESULTS: Chromium histidinate supplementation lowered kidney concentrations of MDA, 8-isoprostane levels, serum urea-N, and creatinine, and reduced the severity of renal damage in the STZ-treated group (i.e., the diabetes-induced group). The expression of HSP60 and HSP70 was lower in the STZ group that received CrHis than in the group that did not. No significant effect of CrHis supplementation was detected in regard to the overall measured parameters in the control group. CONCLUSIONS: Chromium histidinate significantly decreased lipid peroxidation levels and HSP expression in the kidneys of experimentally induced diabetic rats. This study supported the efficacy of CrHis in reducing renal risk factors and impairment because of diabetes.

The effect of strict volume control on cognitive functions in chronic hemodialysis patients.

Cognitive dysfunction is a well-known complication of chronic renal failure that is evident in 30% of hemodialysis (HD) patients. However, the pathogenesis of this dysfunction is unknown. Left ventricular hypertrophy could develop in hypertensive HD patients without establishing normovolemia. Our aim was to evaluate the effect of strict volume control by salt restriction and ultrafiltration on cognitive functions in HD patients. This cross-sectional study was composed of 22 HD patients who were normotensive by applying a strict volume control, 24 HD patients who were normotensive by receiving anti-hypertensive drugs, and 20 healthy controls. The strict volume control was defined as managing of blood pressure control by strict salt restriction and insistent ultrafiltration. P300 recording as an indicator of cognitive disfunction was measured when blood pressures were reached at target level at the end of six-month follow-up period. In all patients, dimensions of the heart were evaluated with echocardiography on an interdialytic day. The cardiothoracic ratio and echocardiographic dimensions were significantly lower in patients with strict volume control. P300 amplitudes were significantly lower in patients on antihypertensive drugs than in patients with strict volume control (9.5 +/- 5.1 versus 11.3 +/- 5.4 muV). P300 latency was longer in patients on antihypertensive drugs than in the control group and patients with strict volume control (359.9 +/- 39.6 versus 345.6 +/- 36.7 ms). Our results suggest that hypervolemia may be one of the causal and potentially modifiable factors of cognitive dysfunction. Strict volume control may have beneficial effects on cognitive functions in hemodialysis patients.

The effects of chromium histidinate on mineral status of serum and tissue in fat-fed and streptozotocin-treated type II diabetic rats.

The present study was conducted to investigate the effects of chromium histidinate (CrHis) against experimentally induced type II diabetes and on chromium (Cr), zinc (Zn), selenium (Se), manganese (Mn), iron (Fe), and copper (Cu) in serum, liver, and kidney of diabetic rats. The male Wistar rats (n = 60, 8 weeks old) were divided into four groups. Group I received a standard diet (12% of calories as fat); group II were fed standard diet and received CrHis (110 mcg CrHis/kg body weight per day); group III received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg i.p.; HFD/STZ); group IV were treated as group III (HFD/STZ) but supplemented with 110 mcg CrHis/kg body weight per day. The mineral concentrations in the serum and tissue were determined by atomic absorption spectrometry. Compared to the HFD/STZ group, CrHis significantly increased body weight and reduced blood glucose in diabetic rats (p < 0.001). Concentrations of Cr, Zn, Se, and Mn in serum, liver, and kidney of the diabetic rats were significantly lower than in the control rats (p < 0.0001). In contrast, higher Fe and Cu levels were found in serum and tissues from diabetic versus the non-diabetic rats (p < 0.001). Chromium histidinate supplementation increased serum, liver, and kidney concentrations of Cr and Zn both in diabetic and non-diabetic rats (p < 0.001). Chromium supplementation increased Mn and Se levels in diabetic rats (p < 0.001); however, it decreased Cu levels in STZ-treated group (p < 0.001). Chromium histidinate supplementation did not affect Fe levels in both groups (p > 0.05). The results of the present study conclude that supplementing Cr to the diet of diabetic rats influences serum and tissue Cr, Zn, Se, Mn, and Cu concentrations.

Atrial fibrillation due to oral methylprednisolone in a patient with membranoproliferative glomerulonephritis.

Cardiac adverse effects of intravenous pulse methylprednisolone administration are well known, but there is little information about the cardiac side effects of oral methylprednisolone in the literature. We present a 41 year-old man with membranoproliferative glomerulonephritis in whom developed atrial fibrillation after oral methylprednisolone therapy.