Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis.

Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

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.

Prognostic value of glomerular C4d staining in patients with IgA nephritis.

INTRODUCTION: Mesangial IgA deposition is the initiative factor in the pathogenesis of IgA nephropathy (IgAN). Glomerular IgA depositon leads to activation local complement system. C4d positivity shows that complement activation occurs via alternative pathway. C4d positivity at the time of renal biopsy can be associated with poor prognosis in IgA nephropathy. We aimed to evaluate C4d deposition and renal outcome in patients with IgA nephritis. METHODS: Between January 2005 and December 2009, 40 patients with IgA nephritis were enrolled. Renal biopsy specimens of 33 patients have been evaluated. C4d immunohistochemical staining was performed 3-µm deparaffinized and rehydrated sections of formaldehyde-fixed renal tissues, using rabbit polyclonal anti-human C4d as the antibody. Baseline demographical, clinical and laboratory data were recorded retrospectively. RESULTS: Mean age of the patients was 35.9 ± 12.9 years and female/male ratio was 19/21. Mean duration of follow-up was 32.8 (12-60) months. Baseline glomerular filtration ratio (GFR) and proteinuria were 55.8 ml/min and 2.44 gr/day respectively at the time of renal biopsy. Eleven patients were C4d positive. Presence of hypertension (p=0.133), proteinuria (p=0.007), serum creatinine levels (p=0.056) and glomerulosclerosis (p=0.004), mesengial hypersellularity (p=0.0001) and interstitial fibrosis (p=0.006) at the time of renal biopsy were higher in C4d positive group rather than negative group. Evolution to renal failure were 63.6% in C4d positive group and 13.6% in negative group (p=0.006). Renal survival at 3 years was 39% in C4d-positive patients versus 66.7% in the C4d-negative patients (log rank- p=0.0072).

Quantitative evaluation of interstitial fibrosis with Sirius Red in IgA nephritis.

OBJECTIVE: Tubulointerstitial fibrosis is one of the strongest independent predictive factors in determining the prognosis in IgA nephritis. Recently, software-based quantitative measurement of interstitial fibrosis with Sirius Red staining has entered the practice. The objective of this study was to investigate the prognostic value of measurement of interstitial nephritis with this method in IgA nephritis. METHOD: Forty-three patients diagnosed with IgA nephritis with renal biopsy between the years 2005 and 2009 were included in this retrospective observational study. The diagnostic biopsies of 37 patients were examined. Basal data included age, gender, creatinine level, glomerular filtration rate (GFR), presence of proteinuria, hypertension, glomerulosclerosis, mesangial proliferation, and interstitial fibrosis and fibrosis index calculated by the measurement of computed images of Sirius Red positive areas. Final visit included evaluation of development of end-stage renal disease (ESRD), and GFR (whether = 60 mL/min or <60 mL/min). RESULTS: Numbers of patients with hypertension (75% vs. 34.5%; p = 0.050), ESRD development (62.5% vs. 20.7%, p = 0.035), GFR <60 mL/min (87.5% vs. 31%; p = 0.007) were greater; and basal GFR (34.25 ± 25.29 vs. 64.14 ± 35.34; p = 0.048) was lower in high-intensity interstitial fibrosis group (>1000 µm2) compared to low-intensity interstitial fibrosis group (≤1000 µm(2)). CONCLUSION: Quantitative analysis of computed imaging of areas of Sirius Red positive tubulointerstitial fibrosis might serve as an effective novel method to determine the prognosis in IgA nephritis.

Association between hyperlactatemia and occult cardiac failure in diabetic patients on maintenance hemodialysis.

PURPOSE: Lactic acidosis as a consequence of high serum lactate levels may deepen the metabolic acidosis in patients with end-stage renal failure. Besides, certain antidiabetic may also cause raised lactate levels in diabetic patients. Therefore, it is obvious that the risk of hyperlactatemia is increased by folds in diabetic patients on chronic hemodialysis program. In this study, it is aimed to evaluate the frequency and the impact of increased serum lactate levels in prevalent diabetic hemodialysis patients. METHODS: A total of 100 diabetic patients who were under maintenance hemodialysis in five different dialysis centers were included in this study. All biochemical parameters, blood gas measurements, echocardiographic data and antidiabetic treatments were statistically analyzed in terms of serum lactate levels. RESULTS: Out of 100 patients, 12 patients had serum lactate levels over normal limits. When the patients with normal or high serum lactate levels were defined as two different groups, statistical significance was detected between serum lactate levels and serum sodium (p = 0.019), potassium (p = 0.037) and bicarbonate levels (p = 0.028). Moreover, in patients with hyperlactatemia, the ejection fraction value was found significantly low (p = 0.005). CONCLUSIONS: The frequency of hyperlactatemia was not rare in prevalent diabetic hemodialysis patients. We additionally found that serum lactate level measurement may particularly help to diagnose the occult cardiac failure. However, further large scale studies are required to define the clinical significance of hyperlactatemia in the end-stage renal failure patients with diabetes mellitus.

The impact of membrane permeability and dialysate purity on cardiovascular outcomes.

The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high- or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high- and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

Prognostic value of NGAL staining in patients with IgA nephropathy.

BACKGROUND: Renal tubulointerstitial injury plays an important role in disease progression of IgAN. Neutrophil gelatinase-associated lipocalin (NGAL) is a stress protein released by tubular cells. NGAL is a promising biomarker of acute kidney injury. There is a growing literature suggesting that NGAL is also a marker of chronic kidney disease and severity. Our aim was to evaluate the prognostic value of NGAL staining in patients with IgAN. METHODS: This retrospective study included all consecutive patients who underwent a renal biopsy at our center between January 2005 and December 2009. Forty-five patients with IgA nephritis were enrolled, and renal biopsy specimens of 29 patients were evaluated. We evaluated baseline age, sex, hypertension, serum creatinine, glomerular filtration rate (GFR), urine protein, NGAL staining, glomerulosclerosis, interstitial fibrosis, and extracapillary proliferation. The primary endpoint of this study was doubling of baseline serum creatinine and/or the onset of ESRD in the course of the study. At the end of the follow-up, patients whose estimated GFR (eGFR) was ≤15 mL/min/1.73 m(2) and/or baseline serum creatinine doubled, were defined as the progressor group. RESULTS: Nineteen patients (65.5%) were NGAL positive and 10 patients (34.5%) were NGAL negative. Female gender and hypertension were associated with NGAL-positive staining. Urinary protein excretion and serum creatinine levels were more elevated in the NGAL-positive group, but the difference was not significant. We found NGAL-positive staining in major proportion in the progressor group (88.9%) than the non-progressor group (55%) (p = 0.076). CONCLUSION: NGAL staining can be a new histological marker in IgAN progression.

Glomerular c4d staining can be an indicator of disease activity in lupus nephritis.

BACKGROUND: Abnormalities in complement activation and clearance of immune complexes by erythrocytes are the central pathogenic mechanisms in systemic lupus erythematosus (SLE). Serum C4d level, which is a degradation product of complement factor C4, was found to be a sensitive indicator of SLE activity. Our aim was to determine whether glomerular C4d staining could be a useful marker of disease activity in patients with lupus nephritis. METHODS: This retrospective study included all consecutive patients who underwent a renal biopsy at our center between January 2005 and December 2009. A total of 29 patients with IgA nephritis were enrolled, and renal biopsy specimens of 24 patients have been evaluated. We evaluated baseline age, sex, hypertension, serum creatinine level, glomerular filtration rate (GFR), urine protein, and glomerular C4d staining. The primary endpoint of this study was the onset of end-stage renal disease (ESRD) in the course of study. RESULTS: Fourteen (58%) patients were C4d+ and 10 (42%) patients C4d-. Urinary protein excretion was more elevated in C4d+ group (p = 0.0001). The renal biopsy showed that activity index score >12 was a higher proportion in C4d+ patients. The patients were followed up for 3.5 years. Four patients in the C4d+ group evolved to ESRD in the follow-up, but none of the patients in the C4d- group (p = 0.064). DISCUSSION: We found a relationship between glomerular C4d staining and activity of lupus nephritis. C4d staining may be a useful marker to predict the prognosis of lupus nephritis.

The value of serum immunoglobulin free light chain assessment in patients with monoclonal gammopathies and acute renal failure.

OBJECTIVE: Immunoglobulin free light chain (FLC) abnormalities are common in patients with monoclonal gammopathies and the kidneys are the most affected organs. Immunoassays that provide quantitative measurement of FLC in serum indicate monoclonal FLC production based on the presence of an abnormal FLC kappa:lambda (κ:λ) ratio. The aim of this study was to assess the utility of serum FLC measurement as a diagnostic tool for detecting plasma cell dyscrasias in comparison to standard assays, and to ascertain its sensitivity and specificity in patients with acute renal failure (ARF). MATERIAL AND METHODS: Sera from 82 patients with ARF were assessed using serum protein electrophoresis (SPE), serum immunofixation electrophoresis (SIFE), and FLC measurement. The sensitivity and specificity of the FLC ratio in identifying which ARF patients had multiple myeloma (MM) was compared to those of SPE and SIFE. RESULTS: Among the 82 patients with ARF, 7 were diagnosed as MM using SPE, SIFE, and bone marrow biopsy techniques. In total, 8 patients did not have a FLC κ:λ ratio that was within the published reference range (0:26-1:65); the FLC κ:λ ratio based on FLC measurement had a specificity of 96% and sensitivity of 71%, and positive and negative predictive values of 62.9% and 97.3%, respectively, for the diagnosis of MM. CONCLUSION: The sensitivity and specificity of the FLC κ:λ ratio for diagnosing MM in patients that presented with ARF were lower than those of SPE and SIFE. To further delineate the utility of the FLC κ:λ ratio additional prospective, well-designed large-scale studies are needed. CONFLICT OF INTEREST: None declared.

The impact of low serum sodium level on mortality depends on glycemic control.

BACKGROUND: Low serum sodium levels have been associated with mortality both in patients with and without chronic kidney disease. In this study, we investigated this association in relation to glycemic control in hemodialysis (HD) patients. MATERIALS AND METHODS: Between March and September 2005, 697 prevalent HD patients were enrolled in this prospective observational study and followed up for all-cause and cardiovascular mortality. The associations of serum sodium concentration with both overall and cardiovascular survival rates were studied. RESULTS: At baseline, mean predialysis serum sodium concentration was 138.4 ± 2.3 mEq/L (range: 130-145 mEq/L). Mild hyponatremia (< 135 mEq/L) was present in only 41 subjects (5.9%), and no patient had serum sodium level < 130 mEq/L. During 20.2 ± 6.2 months of follow-up, 119 patients (15.9%) died, 68 from CV causes. In adjusted Cox regression analysis, lowest sodium quartile was associated with 2.13-fold increased risk of overall mortality (95% confidence interval (CI) 1.14-3.98, P = 0.01, model chi-square 114.6, P < 0.001). As a continuous variable, each 1 mEq/L increase in predialysis sodium concentration was associated with a hazard ratio (HR) of 0.87 for overall mortality (95% CI 0.81-0.95, P = 0.002) and 0.86 for cardiovascular mortality (95% CI 0.78-0.96, P = 0.007). The predictivity of low serum sodium was prominent in diabetic subjects but not in nondiabetics. However, relationship between serum sodium and patient survival in diabetics was lost after adjustment for the HbA1c level: HR 0.91 (95% CI 0.78-1.05, P = 0.20). CONCLUSIONS: Low serum sodium concentration is associated with mortality only in those with diabetes. Furthermore, the impact of serum sodium on survival in these patients seems to be derived from poor glucose control.

The role of nebivolol in the prevention of contrast-induced nephropathy in patients with renal dysfunction.

OBJECTIVE: This prospective study was designed to evaluate the potential protective effect of nebivolol compared with metoprolol on the development of contrast-induced nephropathy (CIN) following coronary angiography in patients with renal dysfunction. METHODS: Ninety patients with stable coronary angina pectoris with renal insufficiency (creatinine value ≥1.2 mg/dl) were included for this prospective study. Patients were divided into two groups. Patients in group 1 (n=55) received oral administration of nebivolol 5 mg/daily for coronary artery disease and/or hypertension. Group 2 consisted of 35 patients who received metoprolol 50 mg/daily for the same indications. All patients were hydrated with 0.9% NaCl at a rate of 1 mL/kg/hr for 12 hours before and 24 hours after the procedure. Patients were also given N-acetylcysteine (NAC) 600 mg twice a day, beginning 24 hours before and continuing 48 hours after the procedure. All patients underwent routine coronary angiography. Serum creatinine was assessed just before, immediately after and 48 hours after the procedure. CIN was defined as an increase in serum creatinine concentration of ≥25% within 48 hours after the procedure compared to the patient's baseline value. Tests for significance between groups were conducted using the independent sample t-test for continuous variables and Chi-square test for categorical variables. RESULTS: Baseline serum creatinine levels were statistically comparable in two groups. Following angiography, serum creatinine levels increased in both groups. Post-angiographic creatinine levels were not statistically different in the nebivolol and the metoprolol groups. Contrast induced nephropathy developed in 13 patients (24%) of the nebivolol group and in 12 patients (33%) of the metoprolol group. The incidence of CIN was statistically significantly lower in the nebivolol group comparing with the metoprolol group (p=0.03). CONCLUSION: The use of oral nebivolol for one week at a dose of 5 mg per day may decrease the incidence of contrast-induced nephropathy in patients who underwent coronary angiography with renal dysfunction. The small numbers of this study do not allow to draw final conclusion on the use of nebivolol in the prevention of CIN. Therefore, larger studies may be necessary to address the definite role of nebivolol in this setting.

Statin use is associated with lower inflammation and erythropoietin responsiveness index in hemodialysis patients.

Patients with end-stage renal disease are prone to inflammation and inflammation is related to erythropoietin-stimulating agent hyporesponsiveness and mortality in this population. Statins have been demonstrated to reduce cardiovascular mortality in selected populations of end-stage renal disease patients. These drugs have pleiotrophic effects such as anti-inflammation. In this retrospective analysis, we determined whether the use of statins improves inflammation and inflammation-related anemia in a cohort of hemodialysis patients. Data were analyzed from Fresenius Medical Care Dialysis Clinics in Turkey between 2005 and 2007. Seventy prevalent hemodialysis patients who were on statins at the start of the study and have been on statins during follow-up (statin users) and 1293 patients who were not on statin at the start of the study and had never been prescribed any lipid-modifying drugs during follow-up (statin nonusers) were included in the study. High-sensitive C-reactive protein levels were significantly decreased in statin users (1.50±1.49 vs. 1.33±1.11 mg/L, P=0.05) compared with nonusers (1.93±3.22 vs. 2.05±2.77 mg/L). Hemoglobin levels and the rate of erythropoietin-stimulating agent users were similar. However, the prescribed erythropoietin-stimulating agent dose (31.6±27.5 vs. 47.3±45.2 U/kg/week, P<0.05) and the erythropoietin response index (2.90±2.73 vs. 4.51±4.48 U/kg/week/Hb, P=0.001) were lower in statin users compared with statin nonusers. On stepwise multiple regression analysis, gender, high-sensitive C-reactive protein, duration of hemodialysis, serum ferritin, and statin use were independent determinants of the erythropoietin responsiveness index. Our results suggest that statin treatment leads to lower inflammation and improves hematopoiesis in hemodialysis patients.

Nutritional state alters the association between free triiodothyronine levels and mortality in hemodialysis patients.

BACKGROUND: Serum free triiodothyronine (fT3) level is suggested to be a risk factor for mortality in unselected dialysis patients. We investigated the prognostic value of serum fT3 levels and also low-T3 syndrome on overall survival in a large cohort of hemodialysis (HD) patients with normal thyroid-stimulating hormone levels. METHODS: A total of 669 prevalent HD patients were enrolled in the study. Serum fT3 level was measured by enzyme immune assay in frozen sera samples at the time of enrollment. Overall mortality was assessed during 48 months of follow-up. RESULTS: Baseline fT3 was 1.47 ± 0.43 (0.01-2.98) pg/ml, and low-T3 syndrome was present in 71.7% of the cases. During a mean follow-up of 34 ± 16 months, 165 (24.7%) patients died. fT3 level was a strong predictor for mortality in crude and adjusted Cox models including albumin or high-sensitivity C-reactive protein (hs-CRP). Further adjustment for both albumin and hs-CRP made the impact of fT3 on mortality disappear. The presence of low-T3 syndrome was associated with mortality in only the unadjusted model. CONCLUSIONS: Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.

TLR polymorphisms in FMF: association of TLR-2 (Arg753Gln) and TLR-4 (Asp299Gly, Thre399Ile) polymorphisms and myeloid cell TLR-2 and TLR-4 expression with the development of secondary amyloidosis in FMF.

Amyloidosis is the major complication of familial Mediterranean fever (FMF). Toll-like receptors (TLR) are involved in the activation of an innate immune system TLR-2 and TLR-4 recognize lipoteichoic acid and lipopolysaccharides (LPS), respectively. While TLR-2 Arg753Gln polymorphism upregulates, TLR-4 Asp299Gly and Thre399Ile polymorphisms downregulate inflammation. We investigated the effect of these polymorphisms on the development of amyloidosis in FMF patients. We also investigated myeloid cell TLR-2 and TLR-4 expressions in these patients. We studied 26 FMF patients and 13 FMF patients with amyloidosis. TLR-2 Arg753Gln and TLR-4 Asp299Gly and Thr399Ile polymorphisms were analyzed with the polymerase chain reaction-restriction fragment length polymorphism method. Myeloid cell baseline TLR-2 and TLR-4 and LPS-induced TLR-4 expressions were evaluated. The TLR-2 and TLR-4 polymorphism rate was compared with the results of 100 healthy subjects in our previous study. In addition, 13 healthy controls were enrolled for leukocyte TLR-2 and TLR-4 expressions. Serum amyloid A (SAA) levels were measured in these 13 control cases and in FMF patients during attack-free periods. The frequency of TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms in healthy controls in our previous study were 1%, 3%, and 2%, respectively. The frequency of these polymorphisms were not different in FMF patients (with or without amyloidosis) compared to the control group. Likewise, myeloid cell TLR-2 and TLR-4 expressions were not different among the controls and FMF patients. However, LPS-induced TLR-4 expression in granulocytes was more prominent in FMF patients. There was no correlation between TLR-2 and TLR-4 expressions and SAA levels. Neither myeloid cell TLR-2 and TLR-4 expressions nor TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms seem to affect the development of secondary amyloidosis in FMF patients in our study population.

The renal effect of replacement fluids in controlled severe hemorrhagic shock: an experimental study.

BACKGROUND: This experimental study examined the effects of resuscitation with Ringer's lactate (RL), 6% hydroxyethyl starch (130/0.4-HES), and the combination of RL and HES on renal function in hemorrhagic shock (HS). METHODS: Twenty-four male New Zealand white rabbits weighing 2198-3435 g were divided at random into four groups. HS was constituted by maintaining the mean arterial blood pressure at 30 mmHg and blood lactate at >4 mM/L. Subsequently, Group 1 (control) was not resuscitated, while the study rabbits' resuscitation was initiated with RL (Group 2), HES (Group 3), or the combination of RL and HES (Group 4). RESULTS: In all groups, the serum creatinine and blood urea nitrogen (BUN) levels were observed to be within normal limits, while the lactate dehydrogenase and alpha-1 microglobulin levels statistically significantly increased when time points were compared with beginning values (p<0.05). Furthermore, cystatin-C levels were observed to be increased after the HS (p<0.05), but returned to the normal level after resuscitation in all the study groups. Interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels were increased in all the rabbits after HS (p<0.05), and there were no significant differences among the study groups after resuscitation (p>0.05). There were no differences in the histological imaging between the groups (p>0.05). CONCLUSION: The 6% HES (130/0.4) did not have any harmful effects on the kidney when it was used alone or in combination with crystalloid for resuscitation of HS in rabbits.

Renal Behçet's disease: an update.

OBJECTIVE: The aims of this study are (1) to report 33 patients with Behçet's disease (BD) having various renal manifestations, and (2) to update current data using our patients and published papers about BD and renal manifestations. METHODS: The PubMed database was searched using the terms BD or Behçet's syndrome. We found reports of 94 patients (including ours) with BD and specific renal diseases (amyloidosis, 39; glomerulonephritis [GN], 37; renal vascular disease, 19; interstitial nephritis, 1). RESULTS: The presentation of renal disease was edema/nephrotic syndrome in 12 patients (36%). Renal disease was incidentally diagnosed by routine urine analysis and measurement of serum creatinine level in 20 patients (61%). Renal failure was present in 23 patients (70%) and 5 of them have had cyclosporine treatment. The frequency of renal disease among BD patients has been reported to vary from less than 1 to 29%. CONCLUSIONS: The clinical spectrum of renal BD shows a wide variation. Amyloidosis (AA type), GN, and macroscopic/microscopic vascular disease are the main causes of renal BD. Patients with vascular involvement have a high risk of amyloidosis and amyloidosis is the most common cause of renal failure in BD. Several types of glomerular lesions are seen in BD. Current treatment options for renal BD are not evidence based. Radiological vascular intervention combined with immunosuppressive drugs can be useful in selected cases. Routine urine analysis and measurement of serum creatinine level are needed for early diagnosis of renal BD.

Preventive effect of nebivolol on contrast-induced nephropathy in rats.

BACKGROUND: Altered renal vasodilatation and oxidative stress are important mechanisms of contrast-induced nephropathy (CIN). The aim of the present study was to assess the effect of nebivolol, a beta blocker, on prevention of CIN. We hypothesized that nebivolol may prevent CIN due to its renal vasodilatation and antioxidant effects. METHODS: Thirty-two Wistar-albino rats were divided into four groups (n = 8 each): control (C), contrast media (CM), nebivolol (N), and nebivolol + contrast media (NCM). CIN was induced by administration of intravenous high-osmolar contrast media diatrizoate (6 ml/kg) after 72 h of dehydration. Nebivolol (2 mg/kg) was given internally once daily for 5 days. Kidney function parameters, nitric oxide metabolites and oxidative stress markers were measured. Kidneys were excised for pathological evaluation. RESULTS: The decrease of creatinine clearance was 0.180 +/- 0.11 mg/dl in CM, and 0.030 +/- 0.10 mg/dl in NCM (P = 0.01). Microproteinuria was ameliorated using nebivolol (P = 0.001). Serum protein carbonyl content, malonyldialdehyde and kidney thiobarbituric acid-reacting substances levels were higher in CM than in C (P = 0.003, P < 0.001 and P = 0.034, respectively) and serum thiol was lower in CM than in C (P = 0.001). However, oxidative stress markers were similar in NCM and C. Diatrizoate decreased kidney nitrite levels, but nebivolol increased them (P = 0.027). Nebivolol attenuated the tubular necrosis, proteinaceous casts and medullary congestion, although significant protective effects, were observed in tubular necrosis (P = 0.001) and proteinaceous cast (P < 0.001). CONCLUSION: This study demonstrated the protective role of nebivolol against CIN.

An unusual vascular involvement in a patient with Behcet's disease: renal artery stenosis.

Behcet's disease (BD) is a rare multisystem inflammatory disorder characterized by recurrent ulcers affecting the mouth and genitals, various skin lesions, relapsing iritis, and vasculitis. Vascular events may dominate the clinical presentation in some patients with BD. Hitherto three forms of vascular disease such as venous occlusions, arterial aneurysms, and arterial occlusions have been reported in BD. Renal vascular involvement has reported in less than 1% of the patients with vascular BD. A case of BD with renovascular hypertension is reported. To our knowledge, a case of BD with renovascular hypertension treated with angioplasty and stent implantation has not been reported previously.

Impact of diabetic and pre-diabetic state on development of contrast-induced nephropathy in patients with chronic kidney disease.

BACKGROUND: The aim of the present study was to assess the influence of diabetic and pre-diabetic state on the development of contrast-induced nephropathy (CIN) in chronic kidney disease patients undergoing coronary angiography. METHODS: A total of 421 patients with Cockcroft clearance between 15 and 60 ml/min were divided into three groups [diabetes mellitus (DM), n = 137; pre-diabetes (pre-DM), n = 140; and normal fasting glucose (NFG), n = 144]. CIN was defined as an increase of > or =25% in creatinine over baseline within 48 h of angiography, DM as glucose > or =126 mg/dl, pre-DM as glucose between 100 and 125 mg/dl and NFG as glucose <100 mg/dl. RESULTS: CIN occurred in 20% of the DM [relative risk (RR) 3.6, P = 0.001], 11.4% of the pre-DM (RR 2.1, P = 0.314) and 5.5% of the NFG group. The decrease of glomerular filtration rate (GFR) was higher in DM and pre-DM (P = 0.001 and P = 0.002, respectively). GFR < or =30 ml/min (RR 19.22), multivessel involvement (RR 7.59), hyperuricaemia (RR 3.95), use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker (RR 2.70) and DM (RR 2.34) were predictors of CIN. Length of hospital stay was 2.45 +/- 1.45 day in DM, 2.27 +/- 0.68 day in pre-DM and 1.97 +/- 0.45 day in NFG (P < 0.001, DM vs NFG and P = 0.032, pre-DM vs NFG). The rate of major adverse cardiac events was 8.7% in DM, 5% in pre-DM and 2.1% in NFG (P = 0.042, DM vs NFG). Haemodialysis was required in 3.6% of DM and 0.7% in pre-DM (P = 0.036, DM vs NFG), and the total number of haemodialysis sessions during 3 months was higher in DM and pre-DM (P < 0.001). Serum glucose > or =124 mg/dl was the best cut-off point for prediction of CIN. CONCLUSION: Our data support that patients with DM are at a higher risk of developing CIN, but patients with pre-DM are not at as high a risk for developing CIN as diabetes patients.

Risk factors and therapy strategies for contrast-induced nephropathy.

Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality, as well as increased costs for medical care, particularly in patients with diabetes mellitus and chronic renal failure. A key step to safer CIN is to identify patients at risk and applying proven preventive interventions. Extracellular volume expansion, minimizing the dose of contrast media, using low-osmolar non-ionic contrast media, stopping the intake of nephrotoxic drugs, and avoiding short intervals between procedures have all been shown to be effective in reducing CIN. The aim of the present review is to summarize the knowledge about the risk factors and prophylactic treatments of CIN.