Raluca Dumea

Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Type 2 diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease and nephropathy—now the leading cause of end-stage renal disease and dialysis in Europe and the United States. Inflammation and oxidative stress play a pivotal role in the development of diabetic complications. Silymarin, an herbal drug with antioxidant and anti-inflammatory properties, may improve glycemic control and prevent the progression of the complications. In a systematic review and meta-analysis including five randomized controlled trials and 270 patients, routine silymarin administration determines a significant reduction in fasting blood glucose levels (−26.86 mg/dL; 95% CI −35.42–18.30) and HbA1c levels (−1.07; 95% CI −1.73–0.40) and has no effect on lipid profile. Benefits for silymarin on proteinuria and CKD progressions are reported in only one small study and are uncertain. However, being aware of the low quality of the available evidence and elevated heterogeneity of these studies, no recommendation can be made and further studies are needed.

Erythropoiesis-Stimulating Agents (ESA) for Preventing the Progression of Chronic Kidney Disease: A Meta-Analysis of 19 Studies

Background: The effect of anemia correction on kidney function in chronic kidney disease (CKD) patients remains unclear. As 19-40% of patients with CKD receive an erythropoiesis-stimulating agent (ESA), this is a potentially important consideration. Summary: We conducted a systematic review and meta-analysis of randomized trials to January 1, 2014 in adult patients with CKD stages 1 to 4. Selection criteria for studies: randomized controlled trials of at least 2 months duration. Patients were allocated to ESA versus placebo, no treatment, or different ESA doses with the purpose of achieving a higher versus a lower hemoglobin target. The analyzed outcomes were the need for renal replacement therapy, doubling of serum creatinine, change in GFR (ml/min), mortality and withdrawal of treatment due to adverse events. A total of 19 trials (n = 8,129 participants with CKD stage 1-4) were reviewed. There was no difference in the risk of end-stage kidney disease (RR, 0.97 [CI 0.83-1.20], 17 trials, 8,104 participants), change in GFR (Mean Difference [MD] -0.45 [-2.21, 1.31], 9 trials, 1,848 participants) or withdrawal of treatment due to adverse events (RR, 1.18 [CI 0.77-1.81], 10 trials, n = 1,958 participants) for patients at higher hemoglobin (Hb) targets. Furthermore, no statistically significant differences in mortality (Risk Ratio [RR] 1.10 [CI 0.90-1.35], 16 trials, n = 8,082 participants) were observed. Key Messages: There is no evidence that ESA treatment affects renal function in patients with CKD. Use of these agents should not therefore be influenced by considerations about influencing CKD progression.

Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Acute tacrolimus nephrotoxicity in kidney transplanted patients - from kidney biopsy to urinary markers of acute kidney injury: a case report

Calcineurin inhibitors (CNIs) play a major role in kidney transplant immunosuppressive regimens, but they also may cause acute and chronic kidney toxicity, which is an important cause of long-term graft failure if not recognized and treated promptly. Therapeutic approaches are different and sometimes even opposite in acute graft dysfunction, requiring detailed differential diagnosis. Current guidelines consider the renal biopsy to have the highest specificity and sensitivity in the diagnosis and correct therapy guidance of acute graft dysfunction. However, the renal biopsy is an invasive and expensive method that predisposes to complications. In the last decade, a number of studies were focused on the urinary levels of various biomarkers like kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interferon induced protein-10 (IP-10) or cystatin C (CysC) as potentially valuable non-invasive methods of allograft pathology diagnosis. We report the case of a 27 year-old male who underwent a kidney transplant and for which the urinary measurement of these biomarkers proved extremely useful in diagnosing the acute tacrolimus nephrotoxicity, which further allowed a correct therapeutic approach.