High-efficiency Hemodiafiltration

The high mortality of hemodialysis (HD) patients is partly due to the limited capacity of diffusion-based HD to remove large uremic toxins. Hemodiafiltration (HDF) which combines convection with diffusion could enhance both large and protein-bound uremic toxin removal. Recently, there have been several randomized controlled trials demonstrating that high-efficiency post-dilution online HDF could improve survival. Indeed, high blood flow rate, which is the necessary requirement, could not be achieved in some patients. The alternative HDF techniques that could provide comparative efficacy would be considered. Pre-dilution online HDF could be performed without risk of hemoconcentration. Mid-dilution online HDF could be conducted via either simple way by using two dialyzers with the substitution fluid line in between or using special designed dialyzer. Mixed-dilution online HDF requires additional substitution pump for both pre- and post-dilution. There are interesting HDF techniques that could be performed with the conventional HD machine and these include HD with double high-flux, enhanced internal filtration, or super high-flux dialyzers. These modalities enhance the convective clearance in combination with internal backfiltration within the dialyzer in HD platform. All of these alternative high-efficiency HDF modalities are available and can potentially provide quite equivalent benefits with the high-efficiency post-dilution online HDF

Neutrophil gelatinase associated lipocalin (NGAL) in leptospirosis acute kidney injury: A multicenter study in Thailand

AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting

Cilostazol attenuates intimal hyperplasia in a mouse model of chronic kidney disease.

Intimal hyperplasia (IH) is a common cause of vasculopathy due to direct endothelial damage (such as post-coronary revascularization) or indirect injury (such as chronic kidney disease, or CKD). Although the attenuation of coronary revascularization-induced IH (direct-vascular-injury-induced IH) by cilostazol, a phosphodiesterase III inhibitor, has been demonstrated, our understanding of the effect on CKD-induced IH (indirect-vascular-injury-induced IH) is limited. Herein, we tested if cilostazol attenuated CKD-induced IH in a mouse model of ischemic-reperfusion injury with unilateral nephrectomy (Chr I/R), a normotensive non-proteinuria CKD model. Cilostazol (50 mg/kg/day) or placebo was orally administered once daily from 1-week post-nephrectomy. At 20 weeks, cilostazol significantly attenuated aortic IH as demonstrated by a 34% reduction in the total intima area with 50% and 47% decreases in the ratios of tunica intima area/tunica media area and tunica intima area/(tunica intima + tunica media area), respectively. The diameters of aorta and renal function were unchanged by cilostazol. Interestingly, cilostazol decreased miR-221, but enhanced miR-143 and miR-145 in either in vitro or aortic tissue, as well as attenuated several pro-inflammatory mediators, including asymmetrical dimethylarginine, high-sensitivity C-reactive protein, vascular endothelial growth factor in aorta and serum pro-inflammatory cytokines (IL-6 and TNF-α). We demonstrated a proof of concept of the effectiveness of cilostazol in attenuating IH in a Chr I/R mouse model, a CKD model with predominantly indirect-vascular-injury-induced IH. These considerations warrant further investigation to develop a new primary prevention strategy for CKD-related IH

A double-blind, randomized, placebo-controlled trial of combined calcitriol and ergocalciferol versus ergocalciferol alone in chronic kidney disease with proteinuria

Abstract Background KDOQI guideline suggests that nutritional vitamin D should be supplemented in chronic kidney disease (CKD) patients who have vitamin D insufficiency/deficiency. However, there are scarce data regarding the additional benefit of active vitamin D supplement in CKD patients who were receiving nutritional vitamin D supplement. This study was conducted to explore the effect of adding active vitamin D to nutritional vitamin D supplement on proteinuria and kidney function in CKD with vitamin D insufficiency/deficiency. Methods This double-blind, randomized placebo-controlled trial was performed to answer the above question. Sixty-eight patients with CKD stage 3\u20134, urine protein to creatinine ratio (UPCR)\u2009>\u20091\ua0g/g, and serum 25OH-D level\u2009<\u200930\ua0ng/mL were enrolled. Patients were randomly assigned to receive 12-week treatment with oral ergocalciferol plus placebo ( n \u2009=\u200936) or oral ergocalciferol plus calcitriol ( n \u2009=\u200932). Results The mean baseline values of UPCR of both groups were comparable (3.6\u2009\ub1\u20093.8\ua0g/g in combined group and 3.5\u2009\ub1\u20093.0\ua0g/g in ergocalciferol group). Following 12-week treatment, there were significant reductions in UPCR from baseline in both groups (2.3\u2009\ub1\u20092.1\ua0g/g in combined group and 2.4\u2009\ub1\u20092.0\ua0g/g in ergocalciferol group). The percentage reductions in UPCR of both groups were not significantly different. The mean eGFR and blood pressure did not differ between baseline and 12-week follow-up and between both groups. No severe hypercalcemia or serious side effects were noted in both groups. Conclusions The proteinuria lowering effect of ergocalciferol in CKD patients with vitamin D deficiency was demonstrated. Additional calcitriol supplement did not have more effects on proteinuria. Trial registration (Thai Clinical Trials Registry (TCTR) 20140929002 ). Date of registration: September 27, 2014

Overview of the study of the ischemic-reperfusion injury with unilateral nephrectomy (Chr I/R) mouse model.

<p><b>(a)</b> Time-line of Chr I/R procedure and <b>(b)</b> the study schema was showed.</p

Renal pathology scoring at 20 weeks post-nephrectomy of the ischemic-reperfusion injury with unilateral nephrectomy (Chr I/R) mouse model.

<p><b>(a)</b> The representative figures of renal cortical staining by Periodic Acid-Schiff (PAS), and Masson’s trichrome among sham-operated, placebo (PB), and cilostazol-treated (CZ) mice were demonstrated. <b>(b)</b> Glomerulosclerosis, the percentage of the glomerular area that was sclerotic determined from PAS-stained sections, (left-side panel) and relative interstitial volume, the percentage of total surface area of the sampled cortical area in Masson’s trichrome stained sections that is occupied by interstitial space (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187872#sec002" target="_blank">method</a>), (right-side panel) from Chr I/R in sham-operated (n = 6), placebo (PB) (n = 10), and cilostazol-treated mice (CZ) (n = 10) were demonstrated. *<i>p</i>< 0.05, #<i>p</i>< 0.0001. Scale bar = 200 μm.</p

The correlation analysis between microRNAs (miRs) in aortic tissue and other serum parameters.

<p>The correlation between asymmetrical dimethylarginine <b>(</b>ADMA) and miR-143 <b>(a)</b>, miR-145, <b>(b)</b> miR-221 <b>(c)</b>; between vascular endothelium growth factor (VEGF) and these miRs <b>(d-f)</b> and between platelet-derived growth factor (PDGF) and these miRs <b>(g-i)</b> were demonstrated.</p

The role of intraoperative parameters on predicting laparoscopic abdominal surgery associated acute kidney injury

Abstract Background Laparoscopic abdominal surgery has been widely used to reduce the length of hospital stay and complications from open abdominal surgery. During the operation, the creation of pneumoperitoneum is used for better visualization of the operating field. However, the effect of pneumoperitoneum on kidney function is unknown. We aimed to identify risk factors and predictors associated with AKI development following laparoscopic abdominal surgery. Methods A single-center prospective cohort study of laparoscopic abdominal surgery patients between June 2012 and December 2013. Acute kidney injury (AKI) was identified by Kidney Disease Improving Global Outcome (KDIGO) criteria. Urinary neutrophil gelatinase associated lipocalin (uNGAL) was measured on the first 3 days after surgery as a surrogate marker of AKI. Results Of the 64 patients, 23 (35%) developed postoperative AKI. The mean age, initial blood pressure, and initial glomerular filtration rate were not different between AKI and non-AKI groups. Inflation time and exposure index were significantly higher in the AKI group compared to non-AKI group (192.0 vs 151.1 min, p = 0.045, and 2325.9 vs 1866.1 mmHg-minutes, p = 0.035). Operation time, mean intra-abdominal pressure, duration of intraoperative hypotension, amount of blood loss and intravenous fluid were not different between groups. In multivariable analysis adjusted for age, diabetes, baseline estimated glomerular filtration rate, and type of operation (urological surgery), exposure index was significantly associated with postoperative AKI, with odds ratio (95% CI) 1.47 (1.05–2.04), p = 0.024. By combining the intraoperative parameters with clinical model the area under the receiver operating characteristic curve was 0.71 (95% CI 0.58–0.84). Conclusions AKI was a common condition in laparoscopic abdominal surgery. Exposure index has been proposed as a novel predictor of laparoscopic abdominal surgery associated AKI