Effect of timing of the first cannulation on survival of arteriovenous hemodialysis grafts.

The use of an arteriovenous graft as vascular access for hemodialysis is associated with a high rate of patency loss. The influence of timing of the first cannulation of the graft on graft survival has not been sufficiently studied. The purpose of this study was to investigate an association between the timing of the first cannulation of the polytetrafluoroethylene arteriovenous graft and the incidence of 12-month failure. This is a retrospective study on a cohort of chronic hemodialysis patients treated in a single center. According to the time, in weeks, between graft construction and its first successful cannulation, the grafts were divided into six groups: 2nd, 3rd, 4th, 5th, 6th and 7th or more week after surgery. The primary outcome was primary graft failure at 12 months, defined as the first occurrence of graft thrombosis or any invasive access procedure. The secondary outcome was cumulative graft failure at 12 months, defined as complete loss of the access site for dialysis. Fifty-eight patients with 64 newly-created arteriovenous grafts were included in the study. In the whole cohort, the incidence of primary graft failure at 12 months was 72.2%, and the incidence of cumulative graft failure at 12 months was 40.7%. The incidences of primary graft failure and cumulative graft failure at 12 months did not differ significantly between the study groups. In our study, timing of the first cannulation of a new arteriovenous polytetrafluoroethylene graft had no significant impact on graft survival.

Comparison analysis of nutritional scores for serial monitoring of nutritional status in hemodialysis patients.

BACKGROUND AND OBJECTIVES: This study aimed to compare the longitudinal performance of the malnutrition-inflammation score (MIS) and the geriatric nutritional risk index (GNRI), two nutritional scores for patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Nutritional scores, dietary intake, biochemical markers, and body composition analysis were performed at baseline and at 6, 12, and 18 months after enrollment (which took place from January through December 2006) on 75 prevalent hemodialysis patients (43% women, mean age 64.8 ± 11.9 years). The patients underwent simultaneous MIS and GNRI assessments calculated by two independent examiners from baseline. The study period was 46.8 ± 16.4 months. RESULTS: GNRI had higher interobserver agreement (weighted κ-score 0.98) than MIS (weighted κ-score 0.62). Longitudinally, a 1-unit increase in MIS was associated with a 0.41 kcal/kg per day reduction in daily energy intake (P<0.001) and with a 0.014 g/kg per day reduction in nPNA (P=0.02). GNRI did not correlate with the change over time of dietary intake. Longitudinal changes of both scores were associated with appropriate changes over time in levels of nutritional biomarkers, inflammation (IL-6), and body composition parameters. Both scores expressed significant associations with prospective hospitalization, whereas only MIS was associated with mortality in this cohort. The multivariate Cox proportional hazard ratio was 1.15 for death for each 1-unit increase in the MIS (95% confidence interval, 1.03-1.3; P=0.02). CONCLUSIONS: Both MIS and GNRI are valid tools for longitudinal assessment of hemodialysis patients' nutritional status. MIS has lower interobserver reproducibility than GNRI; however, MIS is more comprehensive than GNRI.

N-acetylcysteine use for amelioration of aminoglycoside-induced ototoxicity in dialysis patients.

Use of aminoglycoside antibiotics is associated with significant ototoxicity, especially on patients with decreased renal function. The risk of aminoglycoside ototoxicity may approach 60%. Oxidative stress has been suggested as a general mechanism of aminoglycoside ototoxicity and is prevalent in dialysis population. N-acetylcysteine (NAC) is an effective antioxidant and has been safely used in dialysis patients. New experimental and clinical data, explored in this review, provide a good case to recommend NAC administration to all dialysis patients, receiving aminoglycosides.

Hyperglycaemia, inflammation, RAS activation: three culprits to blame for acute kidney injury emerging in healthy rats during general anaesthesia.

AIM: Major surgery under general anaesthesia might evoke acute kidney injury (AKI), sometimes culminating in end stage renal disease. We investigated the roles of hyperglycaemia, inflammation and renin-angiotensin system (RAS) activation in induction of AKI following anaesthesia by different anaesthetic drugs and/or regimens. METHODS: Ninety-four Sprague-Dawley rats underwent 1 h-anaesthesia by various protocols, including repeated blood glucose and insulin measurements. Blood samples and kidneys were allocated at sacrifice, for evaluation of renal function, inflammatory status and Angiotensin-II availability. RESULTS: Hyperglycaemia emerged in unconscious rats irrespective of anaesthetic drug choice or anaesthesia regimen. Insulin increase correlated with hyperglycaemia levels. Levels of Cystatin-C, as well as serum and urine neutrophil gelatinase-associated lipocain (NGAL), were significantly augmented. Serum transforming growth factor beta (TGF-ß) and interleukins (IL)-1ß, -4, -6, and -10 were significantly increased. Intra-renal Angiotensin-II, TGF-ß, IL-6 and-10 were significantly increased. IL-1 was decreased. IL-4 remained unaltered. CONCLUSIONS: Acute hyperglycaemia, systemic and intra-renal inflammation and RAS activation were independently triggered by induction of anaesthesia. Each confounder aggravated the impacts of the others, bringing about concomitant deterioration of renal function. Increased insulin secretion attenuated but did not abolish hyperglycaemia. Systemic inflammation was counterforced by anti-inflammatory cytokines, whereas intra-renal inflammation persisted, so that AKI progressed unopposed.

N-acetylcysteine may improve residual renal function in hemodialysis patients: a pilot study.

Clinical outcomes in chronic dialysis patients are highly dependent on preservation of residual renal function (RRF). N-acetylcysteine (NAC) may have a positive effect on renal function in the setting of nephrotoxic contrast media administration. In our recent study, we showed that NAC may improve RRF in peritoneal dialysis patients. The aim of the present study was to investigate the effect of NAC on RRF in patients treated with chronic hemodialysis. Prevalent chronic hemodialysis patients with a residual urine output of at least 100 mL/24 hours were included. The patients were administered oral NAC 1200 mg twice daily for 2 weeks. Residual renal function was assessed at baseline and at the end of treatment using a midweek interdialytic urine collection for measurement of urine output and calculation of residual renal Kt/V and glomerular filtration rate (GFR). Residual GFR was measured as the mean of urea and creatinine residual renal clearance. Each patient served as his own control. Twenty patients were prospectively enrolled in the study. Administration of NAC 1200 mg twice daily for 2 weeks resulted in significant improvement in RRF: urine volume increased from 320 ± 199 to 430 ± 232 mL/24 hours (P < 0.01), residual renal Kt/V increased from 0.19 ± 0.12 to 0.29 ± 0.14 (P < 0.01), and residual GFR increased from 1.6 ± 1.6 to 2.4 ± 2.3 mL/minute/1.73 m(2) (P < 0.01). N-acetylcysteine may improve RRF in patients treated with chronic hemodialysis.

Hyperglycaemia emerging during general anaesthesia induces rat acute kidney injury via impaired microcirculation, augmented apoptosis and inhibited cell proliferation.

AIM: Major surgery under general anaesthesia frequently triggers acute kidney injury by yet unknown mechanisms. We investigated the role of anaesthesia-triggered systemic hyperglycaemia in impairment of renal functioning, renal tissue injury, intra-renal Angiotensin-II synthesis and endogenous insulin production in anaesthetized rats. METHODS: Eighty-eight Sprague-Dawley rats underwent general anaesthesia for 1 h by different anaesthetic compounds. Some of the animals were either injected with high glucose, or received insulin prior to anaesthesia. Blood pressure, renal functioning estimated by cystatin-C and urea, renal perfusion evaluated by laser Doppler technique, blood glucose and insulin were surveyed. Subsequently, rat kidneys were excised, to be used for immunohistochemical examinations or preparation of renal extracts for intra-renal Angiotensin-II measurements. RESULTS: Elevated blood sugar was observed 5 min following induction of anaesthesia, concurrently with deterioration of renal functioning, drop of systemic blood pressure and decreased renal blood flow. Blood insulin concentrations positively correlated with glucose levels. Intra-renal Angiotensin-II was significantly augmented. Immunohistochemical examinations demonstrated enhanced staining for pro-apoptotic proteins and negligible cell proliferation in tubular tissues. Renal damage resultant from anaesthesia-induced hyperglycaemia could be attenuated by insulin injections. Rats challenged with glucose prior to anaesthesia demonstrated cumulative hyperglycaemia, further increase in insulin secretion, drop of renal blood flow and increased apoptosis. The effects were specific, since they could not be mimicked by replacing glucose with mannose. CONCLUSION: Anaesthesia-induced hyperglycaemia affects intra-renal auto-regulation via decreased renal perfusion, thus triggering renal function deterioration and tubular injury. Increased intra-renal Angiotensin-II aggravates the damage. Tight hypoglycaemic control might prevent or, at least, attenuate anaesthesia-induced renal injury.

Effect of captopril treatment on recuperation from ischemia/reperfusion-induced acute renal injury.

BACKGROUND: Ischemia/reperfusion triggers acute kidney injury (AKI), mainly via aggravating hypoxia, oxidative stress, inflammation and renin-angiotensin system (RAS) activation. We investigated the role of angiotensin-converting enzyme (ACE) inhibition on the progression of AKI in a rat model of ischemia/reperfusion. METHODS: Ninety-nine Sprague-Dawley rats were subjected to 1 h ischemia/reperfusion and/or left unilateral nephrectomy, with concurrent intraperitoneal implantation of Alzet pump. Via this pump, they were continuously infused with captopril 0.5 mg/kg/day, captopril 2 mg/kg/day or saline. The rats were sacrificed following 24, 48 or 168 h. Blood samples, 24-h urine collections and kidneys were allocated, to evaluate renal function, angiotensin-II, nitric oxide (NO), apoptosis, hypoxia, oxidative stress and inflammation. RESULTS: Serum creatinine and cystatin-C significantly increased in ischemic rats, coinciding with histopathologic intrarenal damage, decreased NO, augmented angiotensin-II, interleukin (IL)-6, IL-10, transforming growth factor-beta. At the acute reperfusion stage, captopril prevented excessive angiotensin-II synthesis, ameliorated renal dysfunction, inhibited intrarenal inflammation and improved histopathologic findings. Most of the renoprotective effects of captopril were limited predominantly to acute reperfusion stage. Concurrently, captopril significantly decreased NO availability, exacerbated intrarenal hypoxia and augmented oxidative stress. CONCLUSIONS: At the acute stage of renal ischemia/reperfusion-induced AKI, ACE inhibition substantially contributed to the amelioration of acute injury by improving renal function, inhibiting systemic and intrarenal angiotensin-II, attenuating intrarenal inflammation and preserving renal tissue structure. Later on, at the post-reperfusion stage, most of the beneficial effects of captopril administration on the recuperating post-ischemic kidney were no longer evident. Concurrently, ACE inhibition exacerbated intrarenal hypoxia and accelerated oxidative stress, indicating that renal adaptation to some consequences of ischemia does require bioavailability of RAS components.

IL-6 levels, nutritional status, and mortality in prevalent hemodialysis patients.

BACKGROUND AND OBJECTIVES: The influence of serum IL-6 levels on nutritional status in chronic hemodialysis (HD) patients remains to be elucidated. The present report describes a prospective longitudinal study of IL-6 levels and nutritional parameters to determine whether high IL-6 levels are independently associated with nutritional status over time in a cohort of prevalent hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 85 clinically stable hemodialysis patients (37.6% women), with a mean age of 66.5 ± 10.6 years, were studied after exclusion of patients with BMI < 20 kg/m(2) and/or serum albumin <35 g/L. IL-6, dietary energy and protein intake, and biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18, and 24 months following enrollment. Observation of this cohort was continued over 2 additional years. RESULTS: IL-6 levels increased with time in both unadjusted (linear estimate: 2.57 ± 0.44 pg/ml per 2 yrs; P = 0.001) and adjusted models (linear estimate: 2.35 ± 0.57 pg/ml per 2 yrs; P = 0.049). Significant reductions of daily energy intake, laboratory markers (albumin, transferrin, cholesterol, creatinine), and body composition (fat mass) with higher IL-6 levels were observed over the duration of the longitudinal observation period. However, none of the studied parameters were associated with changes in IL-6 levels over time (IL-6-by-time interactions were NS). Furthermore, cumulative incidences of survival were correlated with the baseline serum IL-6 levels (P = 0.004 by log-rank test). Finally, for each pg/ml increase in IL-6 level, the hazard ratio for death from all causes was 1.06 (95% CI 1.01 to 1.10) after adjustment for demographic and clinical parameters. CONCLUSIONS: Our results suggest that higher serum IL-6 levels are associated with all-cause mortality without additional changes in clinical and laboratory markers of nutritional status in clinically stable HD patients.

Longitudinal study of leptin levels in chronic hemodialysis patients.

BACKGROUND: The influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients. METHODS: Leptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women) with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters. RESULTS: Significant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2 y; p < 0.001) with a more rapid decline in leptin levels in the highest leptin tertile in both unadjusted (p = 0.007) and fully adjusted (p = 0.047) models. A significant reduction in body composition parameters over time was observed, but was not influenced by leptin (leptin-by-time interactions were not significant). No significant associations were noted between leptin levels and changes in dietary protein or energy intake, or laboratory nutritional markers. Finally, cumulative incidences of survival were unaffected by the baseline serum leptin levels. CONCLUSIONS: Thus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.

N-acetylcysteine improves residual renal function in peritoneal dialysis patients: a pilot study.

BACKGROUND: Preservation of peritoneal membrane function and residual renal function is important for the optimal care of peritoneal dialysis patients. N-Acetylcysteine may ameliorate oxidative stress, which is thought to be involved in peritoneal membrane dysfunction. In addition, N-acetylcysteine may have a positive effect on renal function in the setting of nephrotoxic contrast media administration. The aim of this study was to investigate the effect of N-acetylcysteine on peritoneal and residual renal function in peritoneal dialysis patients. METHODS: Ten prevalent peritoneal dialysis patients were administered oral N-acetylcysteine 1200 mg twice daily for 4 weeks. At baseline and at the end of treatment, peritoneal membrane function and residual renal function were assessed using a 4.25% dextrose peritoneal equilibration test and 24-hour dialysate and urine collection for calculation of peritoneal and residual renal Kt/V and mean urea and creatinine residual renal clearance. RESULTS: No significant changes were demonstrated in peritoneal membrane function, including dialysate-to-plasma creatinine ratio, sodium sieving, and net ultrafiltration. Residual renal function improved significantly: urine volume increased from 633 ± 426 to 925 ± 552 mL/24 hours (p = 0.022), residual renal Kt/V increased from 0.56 ± 0.41 to 0.75 ± 0.47 (p = 0.037), and mean residual urea and creatinine clearance increased from 4.96 ± 3.96 to 5.95 ± 4.08 mL/min/1.73 m(2) (p = 0.059). CONCLUSIONS: N-acetylcysteine may improve residual renal function in patients treated with peritoneal dialysis.

Bowel preparation: comparing metabolic and electrolyte changes when using sodium phosphate/polyethylene glycol.

BACKGROUND: Many patients with various types of colonic pathology undergo invasive procedures that require mechanical bowel preparation. The most commonly used medications for bowel preparation include phosphate-containing drugs which are low cost and enable this procedure to be performed in an outpatient setting, as opposed to other medications, such as polyethylene glycol. Recent studies have suggested that freely using phosphate-containing drugs might lead to renal function impairment in a small group of patients. Despite this, many surgeons still use these drugs to prepare their patients. We conducted a comparative study to check the side effects of phosphate-containing drugs compared to polyethylene glycol when used for bowel cleansing. METHODS: We conducted a double blind prospective randomized study that included 40 patients undergoing surgery for colonic pathology, all of whom underwent bowel cleansing (20 with sodium phosphate and 20 with polyethylene glycol). During the perioperative course, electrolyte parameters were collected from serum and urine and compared between the two groups of patients. RESULTS: Changes in electrolyte and metabolic parameters were shown in both groups, but more prominently in patients prepared with sodium phosphate. In addition, early signs of renal function impairment appeared in this group. The differences in metabolic and electrolyte changes between the two groups were statistically significant. CONCLUSIONS: On the basis of this study, we propose that the wide use of phosphate-containing drugs for colonic preparation might be dangerous for the specific group of patients that is prone to develop renal failure or electrolyte abnormalities.

Objective Score of Nutrition on Dialysis (OSND) as an alternative for the malnutrition-inflammation score in assessment of nutritional risk of haemodialysis patients.

BACKGROUND: Evaluation of nutritional risk, one of the strongest predictors of morbidity and mortality in maintenance haemodialysis (HD) patients, is a difficult process especially in patients with compounding conditions that prevent subjective assessment by subjective global assessment or malnutrition-inflammation score (MIS). METHODS: In this study, we developed and characterized a score for the assessment of nutritional status in dialysis patients based solely on objectively measurable criteria. Our prospective observational cohort included 81 prevalent HD patients (53 men and 28 women) with a mean age of 64.3 +/- 11.9 years. The study period encompassed 26.9 +/- 14.3 months. The quantitative and comprehensive scoring system, named Objective Score of Nutrition on Dialysis (OSND), was calculated by combining anthropometric measurements (the change in end-dialysis dry weight in the past 3-6 months, body mass index, skinfold thickness and mid-arm circumference) with three laboratory tests: albumin, transferrin and cholesterol levels. The sum of all seven components of OSND results in a score from 5 (severely malnourished) to 32 (normal). We compared our OSND system with the accepted MIS and phase angle (PA) measurements derived by bioelectric impedance analysis. RESULTS: The OSND correlated significantly with hospitalization days (r = -0.334; P = 0.002) and frequency of hospitalization (r = -0.373; P = 0.001), as well as with lean body mass and fat mass, MIS, PA and interleukin-6 levels. The Cox proportional hazard-calculated relative risk for death for each five-unit decrease in the OSND was 2.2 (95% CI, 1.3 to 3.8; P = 0.003) comparable with the predictions provided by MIS [for each five-unit increase in MIS, hazard ratio (HR) was 1.8 with 95% CI, 1.2 to 2.8; P = 0.007] and PA (for each 1-unit decrease in PA, HR was 2.9 with 95% CI, 1.5 to 5.6; P = 0.001). CONCLUSIONS: The OSND thus provides a comprehensive scoring system with significant associations with prospective hospitalization and mortality in chronic HD patients as well as measures of nutrition and inflammation.

Association between rosiglitazone use and decline in renal function in patients with type 2 diabetes mellitus.

BACKGROUND: Use of thiazolidinediones (TZDs) in treatment of type 2 diabetes mellitus (T2DM) has recently become a matter of major controversy regarding their cardiovascular and renal safety. The aim of this study is to investigate the association between rosiglitazone use and renal function in diabetic patients. METHODS: This is a retrospective cohort study conducted on a population of patients with T2DM treated at a large public health service organization. All patients who received continuous rosiglitazone therapy for at least 1 year were included in the study group. For each patient in the study group, control patients with T2DM never treated with rosiglitazone were selected from the same population and matched for age, sex, HbA1c% and date of study entry. Level of renal function was expressed as estimated glomerular filtration rate (eGFR), calculated by the simplified Modification of Diet in Renal Disease (MDRD) Study equation. RESULTS: In total, 5,666 patients were included in the study: 1,304 were treated with rosiglitazone, and 4,362 were matched controls. Baseline eGFR was similar in both groups (74.6 +/- 22.9 vs. 73.8 +/- 23.3 ml/min per 1.73 m(2), respectively; p=0.291). After 5 years of follow-up, eGFR was significantly lower in the rosiglitazone-treated group than in control group (67.7 +/- 23.6 vs. 73.8 +/- 25.2 ml/min per 1.73 m(2), p<0.001). CONCLUSION: The use of rosiglitazone may be associated with a decline of renal function in patients with T2DM. Further studies are needed to better quantify the risk-benefit trade-offs associated with rosiglitazone therapy.

Homozygous SLC2A9 mutations cause severe renal hypouricemia.

Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 +/- 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout.

The cyclin kinase inhibitor p57kip2 regulates TGF-beta-induced compensatory tubular hypertrophy: effect of the immunomodulator AS101.

BACKGROUND: Compensatory tubular cell hypertrophy following unilateral nephrectomy is a cell cycle-dependent process. Our previous study showed that treatment of unilaterally nephrectomized rats with the immunomodulator AS101 partially inhibits compensatory hypertrophy of the remaining kidneys through the inhibition of IL-10-induced TGF-beta secretion by mesangial cells. The present study is focused on understanding the intracellular mechanism(s) of this phenomenon. METHODS: A total of 120 male Sprague-Dawley rats were unilaterally nephrectomized or sham-operated and treated with AS101 or PBS. Kidney weight and protein/DNA ratio were assessed for each experimental animal. The expression of TGF-beta, PCNA, CDK 2, pRb, ppRb, p21(Waf1), p27(kip1) and p57(kip2) proteins in renal tissues was determined by western blot analysis and immunohistochemistry, and the immunoprecipitation of cyclin E complexes was performed. RESULTS: Compensatory renal growth is initiated by proliferation of resident renal cells that precedes hypertrophy. Changes in TGF-beta expression were positively correlated with the amounts of p57(kip2), but not with p21(Waf1) and p27(kip1) expression in the remaining kidneys. Moreover, there was a marked abundance of p57(kip2) but not p21(Waf1) and p27(kip1) binding to the cyclin E complex in PBS-treated unilaterally nephrectomized rats compared to sham-operated animals. Treatment of uninephrectomized rats with AS101 reduced kidney weight and protein/DNA ratio, inhibited TGF-beta and p57(kip2) expression in the remaining kidneys, and decreased the level of p57(kip2) binding to cyclin E complexes. CONCLUSION: These results demonstrate that TGF-beta-induced compensatory tubular cell hypertrophy is regulated in vivo by p57(kip2) but not by the p21(Waf1) and p27(kip1) cyclin kinase inhibitor proteins.

Nutritional and inflammatory status of hemodialysis patients in relation to their body mass index.

OBJECTIVE: The study tested whether obese hemodialysis (HD) patients have a better nutritional and inflammatory state than those with overweight or normal body mass index (BMI). DESIGN: This was a single-center, cross-sectional study. SETTING AND PATIENTS: Ninety-six stable HD patients from a local HD unit were divided into 3 groups according to BMI (normal, overweight, and obese). MAIN OUTCOME MEASURES: Anthropometry, body composition by multifrequency bioelectrical impedance analysis, biochemical nutritional markers, as well as interleukins (IL-1, IL-6, and IL-10), tumor necrosis factor, leptin, and soluble leptin receptor (sOB-R) were measured. RESULTS: Serum creatinine was significantly elevated in the highest BMI category. Albumin and transferrin were significantly elevated in higher BMI groups after adjustment for age, sex, and diabetes status. The higher BMI group had greater lean body mass (P = .001) and fat mass (P = .0001), higher phase angle (PA), and lower extracellular mass-to-body-cell-mass ratio (ECM/BCM) (P < .05). Inflammatory cytokine levels were not different in the 3 BMI groups. In parallel with increasing BMI, a gradual increase in serum leptin and a trend for decreasing sOB-R were detected (P = .0001 and P = .055, respectively). Both PA (r = 0.295, P = .008) and ECM/BCM (r = -0.345, P = .002) significantly correlated with serum leptin concentration. According to a multiple linear regression analysis, with PA as the dependent variable, age (beta = 0.274, P = .008), creatinine (beta = 0.355, P = .001), and log sOB-R/leptin ratio (beta = -0.465, P = .008) were significant independent predictors of PA. CONCLUSION: HD patients with elevated BMI demonstrate better nutritional status compared to normal BMI or overweight patients, whereas the severity of inflammation is not related to BMI in HD patients.

Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction.

AIM: Peroxisome proliferator-activated receptor (PPAR)-gamma activation by rosiglitazone decreases manifestation of intrarenal inflammatory hallmarks. Inflammation significantly aggravates renal injury following urinary tract obstruction. The effect of rosiglitazone on renal inflammation following unilateral ureteral obstruction was investigated. METHODS: Ninety-six Sprague-Dawley rats were subjected to unilateral ureteral ligation, or to sham operation. Half of each group received rosiglitazone, 5 mg/kg bodyweight per day. The animals were killed and their kidneys allocated following 1 h, 24 h or 2 weeks, for pathological examination or for intrarenal transforming growth factor (TGF)-beta, interleukin (IL)-4, IL-6, IL-10 and nitric oxide (NO) assessment by specific enzyme-linked immunosorbent assays. Apoptosis rates, extracellular matrix deposition, PPAR-gamma, alpha-smooth muscle actin (alpha-SMA) expression and macrophage infiltration were assessed by specific immunohistological stainings. RESULTS: PPAR-gamma receptor expression was downregulated, and infiltration of macrophages decreased, in all rosiglitazone-treated kidneys. Rosiglitazone significantly decreased apoptosis, TGF-beta, IL-6, alpha-SMA expression and NO availability in obstructed kidneys. Synthesis of IL-10 was unaltered, while IL-4 augmented by Rosiglitazone. Rosiglitazone also affected NO and IL-4 production in sham-operated controls. CONCLUSION: (i) Rosiglitazone attenuates profibrotic and pro-inflammatory responses in a rat model of ureteral obstruction-induced renal inflammation; (ii) rosiglitazone stimulates counteractive anti-inflammatory responses in the damaged kidneys; (iii) in part, rosiglitazone exerts comparable anti-inflammatory effects on obstructed kidneys and unobstructed healthy controls. Taken together, this ascertains the importance of the anti-inflammatory role of rosiglitazone treatment in amelioration of ureteral obstruction-induced renal damage.

Hyperglycemia alters renal cell responsiveness to pressure in a model of malignant hypertension.

OBJECTIVE: Poor glycemic control contributes to development of diabetic nephropathy. However, for a majority of clinical situations, the mechanisms responsible for high glucose-induced aggravation of renal tissue injury are not fully elucidated. We investigated responsiveness to pressure of various renal cell subsets subjected to hyperglycemic environment in an in-vitro model of malignant hypertension. METHODS: Rat renal mesangium, epithelium and endothelium were exposed to high glucose-containing medium for 10 days and then subjected to high hydrostatic pressure for 1 h to simulate the incidence of malignant hypertension. In some cultures, renin-angiotensin system was experimentally suppressed prior to pressure application. Proliferation, apoptosis, intrarenal p53, H2O2 and angiotensin-II synthesis were subsequently assessed. RESULTS: By contrast to cultures not exposed to high glucose, in all hyperglycemic cells p53 expression, angiotensin-II synthesis and apoptosis were increased, whereas proliferation depressed, irrespective of pressure enforcement. H2O2 release was enhanced by high pressure per se, and increased further following exposure to high glucose. In all diabetic cultures, inhibition of p53 by a specific inhibitor pifithrin concomitantly significantly decreased apoptosis. CONCLUSION: Hyperglycemic environment alters responsiveness of renal cells to in-vitro simulation of malignant hypertension. The main consequence of either malignant hypertension or hyperglycemia is exaggerated apoptosis. However, the operating mechanisms differ: Malignant hypertension stimulates renal cell apoptosis via increased angiotensin-II, whereas hyperglycemia elicits apoptosis via augmented p53. By contrast to pressure-induced excessive proliferation of normoglycemic cells, hyperglycemia prohibits elevated proliferation in response to pressure. Angiotensin-II production is maximally augmented by hyperglycemic environment and is not stimulated further by pressure application.

Differential effects of N-acetylcysteine, theophylline or bicarbonate on contrast-induced rat renal vasoconstriction.

BACKGROUND: Vasoconstriction and reactive oxygen species (ROS) accumulation following contrast media (CM) injection are the key factors triggering CM-induced nephropathy. We compared the effects of N-acetylcysteine (NAC), theophylline or sodium bicarbonate on intrarenal vasoconstriction and ROS generation in a rat model of CM-induced nephropathy. METHODS: Following a 3-day dehydration, Sprague-Dawley rats received CM (Telebrix) or sham 'CM' injection of 0.9% saline. Part of them received NAC, theophylline or bicarbonate prior to CM. Medullar renal blood flow was estimated by laser Doppler. The animals were sacrificed 1, 15 or 30 min after the respective treatments, their kidneys allocated and intrarenal STAT-8 isoprostane, PGE(2) and NO assessed. RESULTS: Vasoconstriction was significantly attenuated by NAC. Theophylline only mildly attenuated the perfusion drop at 15 min, and was ineffective following 30 min. Unlike theophylline or bicarbonate, NAC significantly augmented intrarenal PGE(2). NAC, theophylline but not bicarbonate, gradually increased intrarenal NO. In all experimental variables, CM-induced ROS accumulation, represented by STAT-8 isoprostane estimation, progressed undisturbed. CONCLUSIONS: (1) CM-induced intrarenal vasoconstriction was efficiently prohibited by NAC but not bicarbonate or theophylline; (2) the vasodilatory effect of NAC was mediated via increased PGE(2) synthesis, and (3) ROS accumulation was a primary renal response to CM-induced injury, not affected by any pharmacologic manipulations.

Application of normobaric hyperoxia therapy for amelioration of haemorrhagic shock-induced acute renal failure.

BACKGROUND: Hypoxia resultant from haemorrhagic shock is the primary cause of kidney damage. Application of normobaric hyperoxia therapy (NHT) is an acceptable treatment for acute haemorrhagic shock. We investigated the effect of NHT on amelioration of haemorrhagic shock-induced rat renal failure. METHODS: Twenty-four Sprague-Dawley rats were subjected to gradual blood withdrawal/reperfusion, followed by 12-h, 24-h or 48-h NHT. Verification/monitoring of intrarenal hypoxia was performed using Hypoxyprobe-TM-1. Subsequently, cystatin C, urea and creatinine were assessed in serum by a Hitachi autoanalyser, and NO, 3-nitro-tyrosine, STAT-8-isoprostane and NF-kB in renal medullae and cortices by specific ELISAs. RESULTS: In rats subjected to haemorrhagic shock, 12- to 48-h NHT significantly reduced intrarenal Hypoxyprobe-TM-1 stained areas and attenuated augmentation of urea, creatinine and cystatin C. Haemorrhagic shock resulted in a 10-fold drop of intrarenal NO availability. 12-h and 24-h, but not 48-h, NHT significantly increased cortical/medullar NO synthesis, the latter, however, not approaching the pre-shock values. Significant shock-induced accumulation of STAT-8-isoprostane and 3-nitro-tyrosine was further exacerbated by NHT. Haemorrhagic shock activated NF-kB in ischaemic tissues, which was not attenuated by NHT. CONCLUSIONS: (1) 12- to 48-h NHT decreased intrarenal hypoxia signs and ameliorated deterioration of renal functions in a rat model of haemorrhagic shock-induced renal failure. (2) 12- to 24 h NHT improved bioavailability of NO in cortices/medullae of kidneys recuperating from haemorrhagic shock. (3) If any anti-inflammatory activities were stimulated by NHT, they would not be mediated via the NF-kB pathway. (4) Despite NHT-associated elevation of reactive oxygen species (ROS), early oxygen supply proved mandatory for effective recuperation of ischaemic kidney from detrimental consequences of haemorrhagic shock.