Adjunct Hypertonic Saline in Patients with Diffuse Edema Due to Heart Failure: A Randomized Double-Blinded Clinical Trial.

In patients with diuretic resistance due to heart failure, higher doses or continuous furosemide infusion and adding hypertonic saline solution (HSS) to diuretics could be effective. The goal of this study was to assess the effectiveness of hypertonic saline solution administration in weight loss of hospitalized patients with diuretic-resistant edema due to heart failure. In a randomized double-blinded clinical trial, adult patients with diffuse peripheral edema due to heart failure who were unresponsive to 80 mg of oral furosemide were enrolled. The patients were randomized into two groups. In the intervention and control groups, patients received 150 mL of HSS and normal saline, respectively. Subjects in both groups received 250 mg IV furosemide every 12 h for 48 h. The change in body weight, urine output, blood pressure, uric acid, urine osmolality, blood biochemistry, and urinary cystatin C levels were assessed. Based on defined inclusion and exclusion criteria, 28 patients, 14 in each group, were recruited. The groups were similar in demographic and baseline laboratory characteristics. A significant decrease in body weight was observed in the intervention group (P = 0.002). The change in other measured parameters, including urine output and urinary cystatin C levels, was not reached statistical significance. Our findings suggest that the administration of HSS as an adjunct to loop diuretics could provide a safe and effective treatment for increasing urine output and decreasing weight in patients with heart failure.

A Randomized Double Blind Placebo Controlled Trial Examining the Effects of Pentoxifylline on Contrast Induced Nephropathy Reduction after Percutaneous Coronary Intervention in High Risk Candidates.

Contrast-induced nephropathy (CIN) (known as contrast-induced acute kidney injury) occurs as a result of acute worsening of renal function following a procedure with administration of iodine contrasts agent and remains a substantial concern in clinical practices. The purpose of this study is to investigate the preventive effect of Pentoxifylline supplementation on reduction of CIN occurrence after percutaneous coronary intervention among patients who were high risk of CIN according to Mehran score. In randomized, double-blind clinical trial patients who undergo coronary angiography with Mehran Score ≥ 11 consisted of our population. Patients in a ratio 1:1, divided into two groups received saline 0.9% plus N-acetyl cysteine and Pentoxifylline 400 mg three times per day 24 h before angiography until 48 h after angiography. In control group, the patients received placebo instead of PTX in a same manner as the control group. The endpoint was the incidence of CIN defined as creatinine increase of 0.5 mg/dL within 2 days after contrast. There were no significant differences in baseline characteristics. CIN occurred in 3 (5.5%) and 4 (7.3%) patients of the both groups (Pentoxifylline and control), respectively (p = 0.69; incidence odds ratio 1.36; 95% CI 0.29-6.38). No significant differences were seen in secondary outcome measures and changes in the level of creatinine (p = 0.54). In high-risk patients undergoing coronary angiography pentoxifylline supplementation had protection effect against contrast-induced nephropathy greater than placebo based hydration, but, not supported by our data.

1 H NMR-based metabolomics exploring urinary biomarkers correlated with proteinuria in focal segmental glomerulosclerosis: a pilot study.

Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic-range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non-invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy-proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and <3000 mg/day. In addition, random forest was performed to predict differential metabolites, and pathway analysis was performed to find the defective pathways responsible for proteinuria. Ten metabolites, significant in both statistical methods (orthogonal projection to latent structure discriminant analysis and random forest), were considered as prognostic biomarkers for FSGS: citrulline, dimethylamine, proline, acetoacetate, alpha-ketoisovaleric acid, valine, isobutyrate, D-Palmitylcarnitine, histidine, and N-methylnicotinamide. Pathway analysis revealed impairment of the branched-chain amino acid degradation pathways in patients with massive proteinuria. This study shows that metabolomics can reveal the molecular changes corresponding with disease progression in patients with FSGS and provide a new insight for pathogenic pathways. Copyright © 2016 John Wiley & Sons, Ltd.

Metformin toxicity: a report of 204 cases from Iran.

OBJECTIVE: The aim of this study was to evaluate the frequency of metformin-associated lactic acidosis in our metformin-intoxicated patients, the general approach for their management, and determine the frequency of hypoglycemia and outcome in these patients. We also wanted to see if there was a significant difference in the course and outcome of metformin poisoning between our patients and those reported in the literature. MATERIALS AND METHODS: Files of all patients diagnosed with metformin toxicity were retrospectively evaluated. A purposemade questionnaire containing the patients' demographic data, vital signs and lab tests on presentation, time of development of hypoglycemia and metabolic acidosis (if any), treatment modalities performed for the patients and their indications, and the patients' outcomes was filled. The patients were evaluated in total and then assigned into two groups of metformin alone (group 1) and multi-drug toxicity including metformin (group 2) and were compared. RESULTS: A total of 204 patients were reviewed. Fifty-five (26.9%) were in group 1 and 149 (73.1%) were in group 2. Sixteen and 52 patients in groups 1 and 2 had acidosis. Dialysis was performed in only four patients, all of whom belonged to group 1 (P = 0.005). They were all dialyzed only once. Two patients (1%) died both of whom were in group 2. Groups 1 and 2 were insignificantly different in all characteristics except for their aspartate transaminase and creatine phosphokinase. Almost 23% of the patients in group 1 had experienced hypoglycemia sometime during their course of hospitalization. CONCLUSIONS: Although lactic acidosis is considered to be a serious condition resulting in high mortality and morbidity rates, it seems that our patients can easily and safely be managed with conservative therapies. Most of them do not need aggressive treatments including hemodialysis. Metformin seems to cause hypoglycemia more than what was previously considered.

Effects of stem cells and granulocyte colony stimulating factor in reperfusion injury.

INTRODUCTION: Bone marrow-derived stem cells have a potential capacity to differentiate and accelerate recovery in injured sites of body. Also, factors like granulocyte colony stimulating factor (GCSF) can promote their mobilization to the injured sites. We aimed to investigate the role of GCSF as an alternative therapeutic option instead of mesenchymal stem cells (MSCs) in reperfusion injury. MATERIALS AND METHODS: Twenty-nine rats with induced reperfusion injury were divided into 3 groups to receive MSC, GCSF, or nothing (control). Kidney function was assessed by blood urea nitrogen and serum creatinine levels. Histological grading was performed to evaluate the extent of tubular injury and the rate of recovery. RESULTS: All the rats reached recovery after 14 days. Rats in the MSC group reached early functional and histological recovery compared to the controls on the 7th day of the study (P = .01 and P = .02, respectively). Compared to the control group, the GCSF group showed a more significant histological recovery on the 7th day (P = .04), but kidney function was ameliorated on the 14th day (P = .04). Both the GCSF and control groups had a significant number of CD34+ cells, which were detected by flow cytometry on the 7th day after reperfusion injury. CONCLUSIONS: We found therapeutic effects following administration of both MSC and GCSF which was more evident with MSC in the setting of reperfusion injury. More investigation is required to find optimal time, dose, and route of administration as well as other possible contributing factors.