Nephron Extra最新文献

Background/aims: Glutathione S-transferases (GSTs) are cytosolic enzymes excreted from renal tubules following tubular damage. α-GST primarily originates from proximal tubules, while π-GST from distal tubules and collecting ducts. We investigated if GST levels are associated with renal function in patients with type 1 diabetes.

Methods: We conducted a cross-sectional study including 189 Caucasian patients with type 1 diabetes and 16 nondiabetic controls. α- and π-GST were measured by ELISA and reported as GST/urinary creatinine excretion (μg/mmol).

Results: The subjects were 53 ± 14 years old, 66 (35%) were female and the estimated glomerular filtration rate was 85 ± 29 ml/min/1.73 m(2). Normo- (<30 mg/24 h), micro- (30-299 mg/24 h) and macroalbuminuria (≥300 mg/24 h) was present in 57, 61 and 71 patients, respectively. α- and π-GST/creatinine ratios in controls versus all patients were 0.07 (0-0.3) and 0.11 (0-0.8) μg/mmol versus 0.05 (0-2.3) and 0.16 (0-4.9) μg/mmol (p ≥ 0.16; adjusted for age and gender, p ≥ 0.18). The α-GST/creatinine ratio positively correlated with female gender (p = 0.04), while the π-GST/creatinine ratio was associated with age and female gender (p ≤ 0.016). Comparing normo-, micro- and macroalbuminuric patients, α- and π-GST levels were similar (p = 0.10; adjusted p = 0.11). Neither α- nor π-GST levels were significantly associated with renal function (p ≥ 0.34).

Conclusion: α- and π-GST/creatinine ratios were similar among controls and patients with type 1 diabetes. In addition, we did not find associations with albuminuria degree or level of renal function. The significance of increased or decreased excretion of α- and π-GST among patients with diabetes needs to be clarified.

Background: Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease and a major cause of cardiovascular disease (CVD) mortality. Inflammation is closely involved in the pathogenesis of T2DM, and reactive amyloidosis occurs in the presence of chronic inflammation. We hypothesized that patients with T2DM may have a higher prevalence of renal AA amyloidosis (RAAA) and that this could contribute to worse atherosclerosis and CVD.

Materials and methods: We analyzed 330 autopsy kidneys from patients with a previous T2DM diagnosis. The kidney tissue was evaluated in order to determine the presence of diabetic nephropathy and RAAA, and systemic vessels were evaluated for the presence of atherosclerosis.

Results: RAAA was detected in 9% of our study population and was associated with an increased risk for nodular sclerosis [OR (95% CI)] [11 (2.04-59.16)], for chronic ischemic cardiomyopathy [4.59 (2.02-10.42)], for myocardial infarction [3.41 (1.52-7.64)] as well as for aortic [4.75 (1.09-20.69)], coronary [3.22 (1.47-7.04)], and intrarenal atherosclerosis [3.84 (1.46-10.09)].

Conclusions: RAAA is prevalent in T2DM and is associated with worse CVD and renal disease, likely because RAAA is a marker of severe chronic inflammation.

Background: The clinical performance indicators (CPI) are important tools to assess and improve the quality of renal replacement therapy (RRT). The aim of the current study was to compare the results of a longitudinal set of CPI in RRT patients and to determine the extent to which the guidelines for anaemia, calcium phosphate management and other CPI are met in Estonian renal centres.

Methods: A long-term retrospective, observational, cross-sectional CPI analysis was undertaken in RRT patients from 2007 to 2011. The following CPI set of well-designed measures based on good evidence was analysed: anaemia management variables, laboratory analyses of mineral metabolism, nutritional status variables and dialysis adequacy variables.

Results: Relatively small changes in the analysed mean CPI values were noticed during the study period. In the course of the study, we noticed an improvement in anaemia control, but not all centres achieved the standard of >80% of the dialysis patients with a haemoglobin (Hb) level >100 g/l. There was a trend of decreasing Hb concentrations below 125 g/l in both haemodialysis (HD) and peritoneal dialysis (PD) patients. In 2011, hyperphosphataemia was present in 58% of the HD and 47% of the PD patients, whereas centre differences varied between 50 and 60% of both the HD and PD patients. HD adequacy was achieved in 77% of the HD patients.

Conclusion: An improvement in the data collection was noticed, and the analysis of CPI allows renal centres to assess and compare their practices with others. The collection and evaluation of CPI of RRT patients is an important improvement and significantly increases the awareness of nephrologists.

Background/aims: Diarrhea-associated hemolytic uremic syndrome is associated with the presence of Shiga toxin (Stx1, Stx2 and several variants) in the circulation. The aim of this study is to examine the possible triggering effect of Stx1 on the exocytosis of Weibel-Palade bodies (WPbs).

Methods: Cultured human umbilical venous endothelial cells (HUVECs) and glomerular microvascular endothelial cells (GMVECs) were stimulated by thrombin and Stx1 in both static and flowing conditions. The amount of secreted von Willebrand factor (VWF) in the supernatant as well as the remaining intracellular fraction was determined.

Results: In HUVECs and in 2 out of 4 GMVECs, the stimulation of Stx1 in flow at 1 dyne/cm(2) resulted in a decrease of intracellular VWF. This is contrary to the results of Stx1 applied in static conditions. At a higher flow rate of 5 dyne/cm(2), no effect in GMVECs was observed.

Conclusion: Stx1 can contribute, via an effect on WPbs, to the exocytosis of WPbs in flow conditions in HUVECs and probably in GMVECs. This results in the release of VWF, suggesting an initiating role of the coagulation system in the pathogenesis.

Background: Volume overload is the main factor responsible for the pathogenesis of hypertension in dialysis patients. Few studies have evaluated the interpretation of the parameters obtained by bioelectrical impedance (BIA) to manage these patients. The aim of this study was to assess the best cutoff level of volume overload obtained by BIA able to predict the absence of hypertension control in hemodialysis patients.

Methods: Volume overload was calculated as the difference between total body water (TBW) measured by bioimpedance and TBW estimated by the Watson formula in chronic stable hemodialysis patients. Inadequate control of blood pressure (BP) was defined as the mean of measurements obtained before five hemodialysis sessions ≥140 × 90 mm Hg. The best cutoff level of volume overload assessed by BIA able to predict the absence of BP control in patients on chronic hemodialysis was determined by the receiver operating characteristic (ROC) curve using the Youden method.

Results: We included 205 patients, 53% male, aged 56 ± 14.5 years. The largest area under the ROC curve was found for predialysis volume overload (0.660, 95% CI 0.556-0.765, p = 0.004). The ROC curve of postdialysis volume overload also reaches statistical significance. The best cutoff point was found for predialysis volume overload ≥1.4 liters with a sensitivity of 69% and a specificity of 67%.

Conclusion: The association of TBW and inadequate BP control highlights the importance of volume management in hemodialysis patients. Predialysis volume overload of 1.4 liters was the parameter that best discriminated the presence of inadequate BP control.

Background/aims: Vascular calcification (VC), a major complication in humans and animals with chronic kidney disease (CKD), is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC.

Methods: Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx) and 10 nonuremic control rats were studied.

Results: The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue) and phosphorus (20.6 ± 4.9 mg/g of tissue) content. Uremic rats had an increased pH level (7.57 ± 0.03) as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg) and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l) derangements. A high positive correlation between both anion gap (AG) and strong ion difference (SID) with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01) and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01) was detected.

Conclusions: In an experimental model of uremic rats, VC showed high positive correlation with AG and SID.

Background/aims: TSPAN8 encoding tetraspanin-8 was identified as a candidate gene for immunoglobulin A nephropathy (IgAN) by a genome-wide association study using microsatellites in the Japanese population. Tetraspanin-8 is a cell surface protein that contributes to the migration and invasion of epithelial cells.

Methods: We performed immunohistochemistry for tetraspanin-8 on human renal biopsy specimens associated with IgAN, antineutrophil cytoplasmic antibody-associated nephropathy and interstitial nephritis, as well as normal renal tissue. Furthermore, to study the potential function of tetraspanin-8, we performed cell migration and invasion assays using human renal tubule cells transfected with tetraspanin-8.

Results: Tetraspanin-8 was often expressed in vascular smooth muscle cells and occasionally in tubule cells in normal kidney. In the kidneys of all types of nephropathy, tetraspanin-8 staining in the arteries was unaffected, but that in the tubules was enhanced. The degree of tubular staining negatively correlated with the estimated glomerular filtration rate, independently of the type of nephropathy. Tetraspanin-8-expressing tubule cells were found predominantly in distal and collecting tubules, identified by cytokeratin 7 or aquaporin 2 staining. In vitro studies using cultured tubule cells revealed that tetraspanin-8 promoted migration by 2.7-fold without laminin, by 2.8-fold with laminin and invasion into Matrigel by 3.5-fold, suggesting that enhanced tetraspanin-8 may be involved in the repair of tubules.

Conclusion: The obtained findings indicate that tetraspanin-8 expression is enhanced in injured distal tubules, which may be involved in the repair of tubules by facilitating migration and invasion.

Background/aims: The costs and the need for a specialist impair the implementation of ultrasonography for evaluating the inferior vena cava (IVC) to assess the volemic status in hemodialysis patients. We investigated whether a nephrologist with limited ultrasound training can accurately assess the IVC in patients undergoing hemodialysis.

Methods: A cardiologist and a nephrologist consecutively measured the indexed IVC expiratory diameter (VCDi) and the IVC collapsibility index (IVCCI) of 52 patients during hemodialysis sessions. In protocol I, the nephrologist used a regular ultrasound system (RUS) and the cardiologist used a cardiovascular ultrasound equipment; in protocol II, the machines were interchanged. Pearson and kappa coefficients and the interexaminer agreement by the Bland-Altman method were calculated.

Results: The VCDi measurements showed a strong correlation in both protocols (r = 0.88 and 0.84 in protocols I and II, respectively). The volemic classifications were excellent in protocol I (kappa = 0.82 and 0.93 by VCDi and IVCCI, respectively) and substantial in protocol II (kappa = 0.77 and 0.75 by VCDi and IVCCI, respectively). The interexaminer agreement on the VCDi measurements was very good in both protocols.

Conclusions: Ultrasound evaluation of the IVC can be performed by nephrologists using an RUS to assess the volemic status in hemodialysis patients.

Background: The number of dialysis patients has been increasing in Southeast Asia, but statistical data about these patients and on the quality of dialysates in Southeast Asian dialysis facilities are still imprecise. For this study, dialysis-related statistical data were collected in Southeast Asia.

Methods: A survey of the quality of dialysates was carried out at 4 dialysis facilities in Vietnam and Cambodia. The dialysis patient survey included the numbers of dialysis facilities and patients receiving dialysis, a ranking of underlying diseases causing the initiation of dialysis, the number of patients receiving hemodialysis (HD)/on-line hemodiafiltration/continuous ambulatory peritoneal dialysis, the number of HD monitoring devices installed, the cost of each session of dialysis (in USD), the percentage of out-of-pocket payments, and the 1-year survival rates of the dialysis patients (in percent). The dialysate survey covered the endotoxin (ET) level and bacterial count in tap water, in water filtered through a reverse osmosis system and in dialysate.

Results: In each of the countries, the most frequent reason for the initiation of dialysis is diabetes mellitus. HD is usually carried out according to the 'reuse' principle. The 1-year survival rates are 70% in Myanmar and about 90% in the Philippines and Malaysia. The ET levels in standard dialysates were satisfactory at 2 facilities. The bacterial counts in dialysates were not acceptable at any of the facilities investigated.

Conclusion: There is an urgent need to teach medical workers involved in dialysis how to prepare sterile and ET-free dialysates.

Background/aims: We examined whether regulation of hepcidin-25 by short- or long-acting recombinant human erythropoietin (rhEPO) is dependent on ferritin and predicts the response to rhEPO in hemodialysis (HD) patients.

Methods: Two studies with rhEPO were performed in 9 HD patients with a 2-year interval. Serum hepcidin-25 was measured at 0-18 h after intravenous epoetin-β (EPO) or methoxy polyethylene glycol-epoetin-β (PEG-EPO) administration and on days 3-7 after PEG-EPO. Hemoglobin (Hb), serum ferritin, transferrin, C-reactive protein (CRP), and interleukin (IL)-6 were analyzed before hepcidin measurement and 6 months after rhEPO. Based on the serum ferritin levels before hepcidin measurement, the patients in the two studies with EPO or PEG-EPO were combined into low (11; serum ferritin of <15.0 ng/ml) and high ferritin groups (7; serum ferritin of ≥15.0 ng/ml). The response of hepcidin-25 to rhEPO and the effect of rhEPO on anemia were compared between the groups.

Results: The serum hepcidin-25 levels rose at 6-9 h and returned to the baseline at 18 h after EPO. They rose at 6-9 h, returned to the baseline at 18 h, and decreased on day 5-7 after PEG-EPO. Serum hepcidin-25 levels were low (<5.0 ng/ml) in the low ferritin group, but rose at 6-9 h after rhEPO in the high ferritin group. Serum transferrin levels were similar, and CRP and IL-6 were normal in both groups. Hb tended to increase in the low ferritin group, but it significantly decreased in the high ferritin group after rhEPO.

Conclusion: Regulation of hepcidin-25 by rhEPO may be dependent on ferritin, affecting the response to rhEPO in HD patients.