Prognostic Impact of Post-Transplant Diabetes Mellitus in Kidney allograft recipients: A Meta-analysis.

BACKGROUND AND AIM: Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion, and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies. This meta-analysis was imperative to not only incorporate emerging evidence but also to delve into cause-specific mortality considerations. We aimed to comprehensively evaluate the association between PTDM and clinical outcomes, including all-cause and cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and graft loss, in kidney transplant recipients. MATERIALS AND METHODS: PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library databases were screened and studies evaluating the effect of PTDM on all-cause mortality, cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and overall graft loss in adult kidney transplant recipients were included. RESULTS: 53 studies, encompassing a total of 138,917 patients, to evaluate the association between PTDM and clinical outcomes were included. Our analysis revealed a significant increase in all-cause mortality (RR 1.70, 95% CI 1.53 to 1.89, P<0.001) and cardiovascular mortality (RR 1.86, 95% CI 1.36 to 2.54, P<0.001) among individuals with PTDM. Moreover, PTDM was associated with a higher risk of sepsis-related mortality (RR 1.96, 95% CI 1.51 to 2.54, P<0.001) but showed no significant association with malignancy-related mortality (RR 1.20, 95% CI 0.76 to 1.88). Additionally, PTDM was linked to an increased risk of overall graft failure (RR 1.33, 95% CI 1.16 to 1.54, P<0.001). CONCLUSION: These findings underscore the importance of comprehensive management strategies and the need for research targeting PTDM to improve outcomes in kidney transplant recipients.

Pancreatic steatosis is an independent risk factor for post-transplant diabetes mellitus in kidney transplant patients.

BACKGROUND AND AIM: Post-transplant diabetes mellitus (PTDM) is associated with an increased risk of post-transplant cardiovascular diseases, and several risk factors of PTDM have been shown in the literature. Yet, the relationship between hepatic and pancreatic steatosis with post-transplant diabetes mellitus remains vague. We aimed to evaluate pancreatic steatosis, a novel component of metabolic syndrome, and hepatic steatosis association with post-transplant diabetes mellitus in a single-center retrospective cohort study conducted on kidney transplant recipients. METHOD: We have performed a single-center retrospective cohort study involving all kidney transplant recipients. We have utilized pretransplant Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and abdominal computed tomography for the assessment of visceral steatosis status. RESULTS: We have included 373 kidney transplant recipients with a mean follow-up period of 32 months in our final analysis. Post-transplant diabetes mellitus risk is associated with older age (p < .001), higher body-mass index (p < .001), nonalcoholic fatty liver disease-fibrosis score (p = .002), hepatic (p < .001) or pancreatic (p < .001) steatosis on imaging and higher pre-transplant serum triglyceride (p = .003) and glucose levels (p = .001) after multivariate analysis. CONCLUSION: Our study illustrates that recipients' pancreatic steatosis is an independent predictive factor for post-transplant diabetes mellitus including in kidney transplant patients.

Effect of Bimagrumab on body composition: a systematic review and meta-analysis.

BACKGROUND: Sarcopenia, a condition marked by progressive muscle mass and function decline, presents significant challenges in aging populations and those with chronic illnesses. Current standard treatments such as dietary interventions and exercise programs are often unsustainable. There is increasing interest in pharmacological interventions like bimagrumab, a monoclonal antibody that promotes muscle hypertrophy by inhibiting muscle atrophy ligands. Bimagrumab has shown effectiveness in various conditions, including sarcopenia. AIM: The primary objective of this meta-analysis is to evaluate the impact of bimagrumab treatment on both physical performance and body composition among patients diagnosed with sarcopenia. MATERIALS AND METHODS: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed, Ovid/Medline, Web of Science, and the Cochrane Library databases up to June 2024 using appropriate Medical Subject Headings (MeSH) terms and keywords related to bimagrumab and sarcopenia. Eligible studies were randomized controlled trials (RCTs) that assessed the effects of bimagrumab on physical performance (e.g., muscle strength, gait speed, six-minute walk distance) and body composition (e.g., muscle volume, fat-free body mass, fat body mass) in patients with sarcopenia. Data extraction was independently performed by two reviewers using a standardized form, with discrepancies resolved through discussion or consultation with a third reviewer. RESULTS: From an initial search yielding 46 records, we screened titles, abstracts, and full texts to include seven RCTs in our meta-analysis. Bimagrumab treatment significantly increased thigh muscle volume (mean difference [MD] 5.29%, 95% confidence interval [CI] 4.08% to 6.50%, P < 0.001; moderate heterogeneity χ2 = 6.41, I2 = 38%, P = 0.17) and fat-free body mass (MD 1.90 kg, 95% CI 1.57 kg to 2.23 kg, P < 0.001; moderate heterogeneity χ2 = 8.60, I2 = 30%, P = 0.20), while decreasing fat body mass compared to placebo (MD - 4.55 kg, 95% CI - 5.08 kg to - 4.01 kg, P < 0.001; substantial heterogeneity χ2 = 27.44, I2 = 89%, P < 0.001). However, no significant improvement was observed in muscle strength or physical performance measures such as gait speed and six-minute walk distance with bimagrumab treatment, except among participants with slower baseline walking speeds or distances. DISCUSSION AND CONCLUSION: This meta-analysis provides valuable insights into the effects of bimagrumab on sarcopenic patients, highlighting its significant improvements in body composition parameters but limited impact on functional outcomes. The observed heterogeneity in outcomes across studies underscores the need for cautious interpretation, considering variations in study populations, treatment durations, and outcome assessments. While bimagrumab shows promise as a safe pharmacological intervention for enhancing muscle mass and reducing fat mass in sarcopenia, its minimal effects on muscle strength and broader physical performance suggest potential limitations in translating body composition improvements into functional gains. Further research is needed to clarify its long-term efficacy, optimal dosing regimens, and potential benefits for specific subgroups of sarcopenic patients.

The risk for chronic kidney disease in metabolically healthy obese patients: A systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with obesity and metabolic syndrome. Nevertheless, the association of CKD with phenotype referred as metabolically healthy obese or overweight is unclear. In this this systematic review and meta-analysis, we investigate the relationships between obesity and CKD independent of metabolic syndrome by appraising published evidence in studies focusing on metabolically healthy obese people. MATERIALS AND METHODS: We performed a literature search through three databases Embase (Elsevier), the Cochrane Central Register of Controlled Trials (Wiley) and PubMed/Medline Web of Science up to March 2022 with the following terms: "chronic kidney disease", "kidney function", "obesity", "metabolic syndrome", "metabolically healthy obesity", "metabolically healthy overweight". Metabolically unhealthy was defined an individual having at least 3 of the following: abdominal obesity, high blood pressure, hypertriglyceridemia, low HDL cholesterol and hyperglycaemia. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for reporting. Prospective, retrospective, randomized and nonrandomized studies fitting the search criteria were included in our results. RESULTS: Our final analysis included 16 studies with a total number of 4.965.285 participants. There is considerable heterogeneity in terms of study design, participant characteristics and number of participants across individual studies. In comparison to healthy normal weight patients, the risk was progressively higher in overweight (RR 1.29, 95% CI 1.27 to 1.32, p < 0.001) and obese patients (RR 1.47, 95% CI 1.31 to 1.65, p < 0.001). CONCLUSION: Metabolically healthy overweight and obese individuals have higher risk of CKD compared to individuals without weight excess.

Effect of tirzepatide on blood pressure and lipids: A meta-analysis of randomized controlled trials.

AIM: To perform a meta-analysis to quantify the effect of tirzepatide on blood pressure and lipids. METHODS: PubMed, Ovid/Medline, Web of Science, Scopus, Cochrane Library and CINAHL databases were screened and the randomized controlled trials evaluating the effects of tirzepatide on either blood pressure or lipid profiles were included. RESULTS: Seven randomized controlled trials have investigated the effects of tirzepatide on blood pressure and lipid profiles. Regardless of the dose administered, tirzepatide resulted in significant decreases in systolic blood pressure of median -4.20 (95% confidence interval [CI] -5.17 to -3.23) mmHg for 5 mg, -5.34 (-6.31 to -4.37) mmHg for 10 mg, and -5.77 (-6.73 to -4.81) mmHg for 15 mg. At all three once-weekly doses, tirzepatide treatment resulted in significant decreases in total cholesterol levels: median -3.76% (95% CI -5.20% to -2.31%) for 5 mg; -4.63% (-6.07% to -3.19%) for 10 mg; and -5.93% (-7.36% to -4.49%) for 15 mg. Additionally, tirzepatide treatment led to increased high-density lipoprotein (HDL) cholesterol levels and decreased low-density lipoprotein (LDL) cholesterol and triglyceride levels. CONCLUSIONS: Tirzepatide induced clinically meaningful reductions in the levels of systolic and diastolic blood pressure, total cholesterol, LDL cholesterol and triglycerides, along with increases in the level of HDL cholesterol.

A randomized multicenter trial on a lung ultrasound-guided treatment strategy in patients on chronic hemodialysis with high cardiovascular risk.

Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.

Effect of Coffee Consumption on Renal Outcome: A Systematic Review and Meta-Analysis of Clinical Studies.

OBJECTIVE: Drinking coffee is one of the most common daily habits, especially in the developed world. Along with caffeine, coffee has various ingredients that have been suggested to have beneficial effects, including antioxidant, antiinflammatory, anticarcinogenic, antithrombotic and antifibrotic effects. In this systematic review and meta-analysis, we investigated the relationship between coffee intake and chronic kidney disease (CKD) related outcomes. DESIGN AND METHODS: Literature search was performed through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from 1960 to February 2020. Incidence of CKD, the progression of CKD, and CKD-associated mortality have been evaluated in relation to coffee consumption and the amount of consumption. The Newcastle-Ottawa scale was used for quality assessment of included studies. RESULTS: 12 studies were included in the analysis (7 prospective, 5 cross-sectional) involving 505,841 subjects. 7 studies investigated the relationship between coffee consumption and incident CKD and showed that coffee consumption was associated with a significant decrease in the risk for incident CKD outcome (RR 0.86, 95% CI 0.76 to 0.97, P = .01) with a greater decrease in individuals taking ≥2 cups/day compared to those who drank ≤1 cup/day. There was a significantly lower risk of incident end stage kidney disease (ESKD) in coffee users (HR 0.82, 95% CI 0.72 to 0.94, P = .005). Coffee consumption was also associated with a lower risk of albuminuria (OR 0.81, 95% CI 0.68 to 0.97, P = .02). Overall, the risk of death related to CKD was lower in coffee users (HR 0.72, 95% CI 0.54 to 0.96, P = .02). CONCLUSION: Coffee intake was dose-dependently associated with lower incident CKD, ESKD, and albuminuria.

The Effect of Urine pH and Urinary Uric Acid Levels on the Development of Contrast Nephropathy.

BACKGROUND: Hyperuricemia may cause acute kidney injury by activating inflammatory, pro-oxidative and vasoconstrictive pathways. In addition, radiocontrast causes an acute uricosuria, potentially leading to crystal formation. We therefore aimed to investigate the effect of urine acidity and urine uric acid level on the development of contrast-induced nephropathy (CIN) in patients undergoing elective coronary angiography. METHODS: We enrolled 175 patients who underwent elective coronary angiography. CIN was defined as a >25% increase in the serum creatinine levels relative to basal values 48-72 h after contrast use. Prior to coronary angiography and 48-72 h later, serum uric acid, urea, creatinine, bicarbonate levels, and spot uric acid to creatinine ratio (UACR) were measured. RESULTS: Of the 175 subjects included, 29 (16.6%) developed CIN. Those who developed CIN had a higher prevalence of diabetes, higher UACR (0.60 vs. 0.44, p = 0.014), higher contrast volume, and lower serum sodium level. With univariate analysis of a logistic regression model, the risk of CIN was found to be associated with diabetes (p = 0.0016, OR = 3.8 [95% CI: 1.7-8.7]), urine UACR (p = 0.0027, OR = 9.6 [95% CI: 2.2-42.2]), serum sodium (p = 0.0079, OR = 0.8 [95% CI: 0.77-0.96]), and contrast volume (p = 0.0385, OR = 1.8 [95% CI: 1.03-3.09]). In a multiple logistic regression model with stepwise method of selection, diabetes (p = 0.0120, OR = 3.2 [95% CI: 1.3-8.1]) and UACR (p = 0.0163, OR = 6.9 [95% CI: 1.4-33.4]) were the 2 risk factors finally identified. CONCLUSIONS: We have demonstrated that higher urine UACR is associated with the development of CIN in patients undergoing elective coronary angiography.

Bio-electrical impedance analysis for perioperative fluid evaluation in open major abdominal surgery.

Water retention and intercompartmental redistribution occur frequently in association with adverse postoperative outcomes, yet the available strategies for non-invasive assessment are limited. One such approach for evaluating body water composition in various circumstances is bio-electrical impedance analysis (BIA). This study aims to appraise the usefulness of the Body Composition Monitor (BCM, Fresenius Medical Care, Germany) in assessing body fluid composition and intercompartmental shifts before and after open major abdominal surgery. This prospective, clinician blinded observational study enrolled all the patients scheduled consecutively for elective major open abdominal surgery during a 1-year period starting from January 1st, 2016. BIA parameters-total body water (TBW), extracellular water (ECW), intracellular water (ICW), absolute fluid overload (AFO), and relative fluid overload (RFO) were measured before and after surgery. The results were compared with fluid balance and outcome parameters such as organ dysfunction, ICU-and hospital length of stay (-LOS). The study population included 71 patients aged 60.2 ± 12 of whom 60.6% men and with a BMI of 26.3 ± 5.1 kg/m2. Postoperative acute kidney injury, respiratory dysfunction, and infections occurred in 14.0%, 19.7% and 28.1% of cases, respectively. The median LOS in ICU was 20 h and the hospital-LOS was 10 days. Positive intraoperative fluid balance (2.4 ± 1.0 L) resulted in a significant increase of TBW (1.4 ± 2.4 L) and of ECW (1.4 ± 1.2 L). Intraoperative fluid balance significantly correlated with TBW change (r = 0.23, p = 0.04) and with AFO change (r = 0.31, p < 0.01). A significant correlation was found between pre- and postoperative AFO and RFO on one hand, and ICU-LOS on the other. BIA may be a useful tool for the perioperative assessment of volume status.

An analysis of the impact of fluid overload and fluid depletion for all-cause and cardiovascular mortality.

BACKGROUND: Both baseline fluid overload (FO) and fluid depletion are associated with increased mortality risk and cardiovascular complications in haemodialysis patients. Fluid status may vary substantially over time, and this variability could also be associated with poor outcomes. METHODS: In our retrospective cohort study, including 4114 haemodialysis patients from 34 Romanian dialysis units, we investigated both all-cause and cardiovascular mortality risk according to baseline pre- and post-dialysis volume status, changes in pre- and post-dialysis fluid status during follow-up (time-varying survival analysis), pre-post changes in volume status during dialysis and pre-dialysis fluid status variability during the first 6 months of evaluation. RESULTS: According to their pre-dialysis fluid status, patients were stratified in the following groups: normovolaemic with an absolute FO (AFO) compartment between -1.1 and 1.1 L, fluid depletion with an AFO below -1.1 L, moderate FO with an AFO compartment >1.1 but <2.5 L and severe FO with the AFO compartment >2.5 L. Baseline pre-dialysis FO and fluid depletion patients had a significantly elevated risk of all-cause mortality risk {hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.22-1.93], HR 2.04 (95% CI 1.59-2.60) and HR 1.88 (95% CI 1.07-3.39) for moderate FO, severe FO and fluid depletion, respectively}. In contrast, post-dialysis fluid depletion was associated with better survival [HR 0.71 (95% CI 0.57-0.89)]. Similar results were found when using changes in pre- or post-dialysis fluid status during follow-up (time-varying values): FO patients had an increased risk of all-cause [moderate FO: HR 1.39 (95% CI 1.11-1.75); severe FO: HR 2.29 (95% CI 2.01-3.31] and cardiovascular (CV) mortality [moderate FO: HR 1.34 (95% CI 1.05-1.70); severe FO: HR 2.34 (95% CI 1.67-3.28)] as compared with normohydrated patients. Using pre-post changes in volume status during dialysis, we categorized the patients into six groups: Group 1, AFO <-1.1 L pre- and post-dialysis; Group 2, AFO between -1.1 and 1.1 L pre-dialysis and <-1.1 L post-dialysis (the reference group); Group 3, AFO between -1.1 and 1.1 L pre- and post-dialysis; Group 4, AFO >1.1 L pre-dialysis and <-1.1 L post-dialysis; Group 5, AFO >1.1 L pre-dialysis and between -1.1 and 1.1 L post-dialysis; Group 6, AFO >1.1 L pre- and post-dialysis. Using the baseline values, only patients in Groups 1, 5 and 6 maintained an increased risk for all-cause mortality as compared with the reference group. Additionally, CV mortality risk was significantly higher for patients in Groups 5 and 6. When we applied the time-varying analysis, patients in Groups 1, 5 and 6 had a significantly higher risk for both all-cause and CV mortality risk. In the last approach, the highest risk for the all-cause mortality outcome was observed for patients with high-amplitude fluctuation during the first 6 months of evaluation [HR 2.75 (95% CI 1.29-5.84)]. CONCLUSION: We reconfirm the association between baseline pre- and post-dialysis volume status and mortality in dialysis patients; additionally, we showed that greater fluid status variability is independently associated with higher mortality.

Use of Lung Ultrasound for the Assessment of Volume Status in CKD.

Adequate assessment of fluid status is an imperative objective in the management of all types of patients in cardiology, intensive care, and especially nephrology. Fluid overload is one of the most common modifiable risk factors directly associated with hypertension, heart failure, left ventricular hypertrophy, and eventually, higher morbidity and mortality risk in these categories of patients. Different methods are commonly used to determine fluid status (eg, clinical assessment, natriuretic peptide concentrations, echocardiography, inferior vena cava measurements, or bioimpedance analysis). In recent years, lung ultrasonography (LUS), through the assessment of extravascular lung water, has received growing attention in clinical research. This article summarizes available studies that compare LUS with other methods for fluid status assessment in patients with kidney diseases. At the same time, it also presents the association of LUS with different outcomes (physical functioning, mortality, and cardiovascular events) in the same population. It appears that this simple bedside noninvasive technique has significant clinical potential in nephrology.

Primary Prevention of Stroke in Chronic Kidney Disease Patients: A Scientific Update.

BACKGROUND: Although chronic kidney disease (CKD) is an independent risk factor for stroke, official recommendations for the primary prevention of stroke in CKD are generally lacking. SUMMARY: We searched PubMed and ISI Web of Science for randomised controlled trials, observational studies, reviews, meta-analyses and guidelines referring to measures of stroke prevention or to the treatment of stroke-associated risk factors (cardiovascular disease in general and atrial fibrillation (AF), arterial hypertension or carotid artery disease in particular) among the CKD population. The use of oral anticoagulation in AF appears safe in non-end stage CKD, but it should be individualized and preferably based on thromboembolic and bleeding stratification algorithms. Non-vitamin K antagonist oral anticoagulants with definite dose adjustment are generally preferred over vitamin K antagonists in mild and moderate CKD and their indications have started being extended to severe CKD and dialysis also. Aspirin, but not clopidogrel, has limited indications for reducing the risk for atherothrombotic events in CKD due to its increased bleeding risk. Carotid endarterectomy has shown promising results for stroke risk reduction in CKD patients with high-grade symptomatic carotid stenosis. The medical treatment of arterial hypertension in CKD often fails to efficiently lower blood pressure values, but recent data regarding the use of interventional procedures such as renal denervation, baroreflex activation therapy or renal artery stenting are encouraging. Key Messages: In the absence of clear guidelines and protocols, primary prevention of stroke in CKD patients remains a subtle art in the hands of the clinicians. Nevertheless, refraining CKD patients from standard therapies often worsens their prognosis.

Effects of Volume Overload and Current Techniques for the Assessment of Fluid Status in Patients with Renal Disease.

Volume overload is an important, may be the foremost, independent prognostic factor determining the outcome of hemodialysis patients. Therefore, it is crucial to measure fluid status of these patients and avoid volume overload. This review aims to evaluate volume overload, its effects on patients with renal diseases and current methodologies measuring volume status in the body. These techniques will be first classified as clinical evaluation and non-clinical and/or instrumental techniques, which includes biomarkers, ultrasonography, relative blood volume monitoring, bioimpedance, echocardiography, pulmonary artery catheterization, esophageal and/or suprasternal Doppler, and blood viscosity. Advantages and limitations of these different techniques will be reviewed extensively by comparing each other. At last, insights gained from this review can highlight the future prospects in this active area of research.

Novel Faces of Fibroblast Growth Factor 23 (FGF23): Iron Deficiency, Inflammation, Insulin Resistance, Left Ventricular Hypertrophy, Proteinuria and Acute Kidney Injury.

FGF23 is a hormone that appears as the core regulator of phosphate metabolism. Great deal of data has accumulated to demonstrate increased FGF23 secretion from the bone to compensate for even subtle increases in serum phosphorus long before intact PTH. However, recent evidence points to the fact that actions and interactions of FGF23 are not limited solely to phosphate metabolism. FGF23 may be implicated in iron metabolism and erythropoiesis, inflammation, insulin resistance, proteinuria, acute kidney injury and left ventricular hypertrophy. In this review, we will summarize latest experimental and clinical data examining impact of FGF23 on aforementioned pathophysiologic pathways/disorders.

Colchicine in Renal Medicine: New Virtues of an Ancient Friend.

Colchicine is a plant-derived alkaloid that disrupts the cell microtubule system and accumulates in neutrophils, inhibiting neutrophil adhesion and recruitment. Colchicine has been used extensively in the prevention and treatment of gouty arthritis attacks, familial Mediterranean fever attacks and resultant AA amyloidosis, and recurrent pericarditis. Colchicine also disrupts the intracellular traffic of additional inflammatory and fibrosis mediators. Renal fibrosis is the final common pathway of chronic renal disease. Colchicine had anti-fibrotic effects in experimental diabetic nephropathy, renal mass reduction, and cyclosporine nephrotoxicity among others and is undergoing clinical trials for non-diabetic metabolic syndrome and diabetic nephropathy. In this review, we summarize the anti-inflammatory and anti-fibrotic properties of colchicine in experimental and clinical studies in renal diseases or other fibrotic disease processes with renal consequences. We also discuss the potential future uses of colchicine in renal medicine and challenges faced with its use in patients with impaired kidney function.

Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events.

Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.

Novel Masters of Erythropoiesis: Hypoxia Inducible Factors and Recent Advances in Anemia of Renal Disease.

Anemia seen in patients with chronic kidney disease is a particular form of 'anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population. Recognizing the pivotal roles of hypoxia inducible factors (HIFs) in orchestrating elements of erythropoiesis opened new avenues in the management of renal anemia. Several phase 1 and 2 studies confirmed the results of early experimental studies supporting the beneficial role of augmenting HIFs for erythropoiesis. In this review, we describe the physiologic functions of HIF in erythropoiesis with special emphasis on interactions with iron and hepcidin metabolism and inflammation.

New insights into the effect of haemodiafiltration on mortality: the Romanian experience.

BACKGROUND: Haemodiafiltration (HDF), by successfully removing the larger solutes and protein-bound compounds, may offer a feasible approach to improve dialysis outcomes. Recently, three large, randomized, controlled trials have tested this hypothesis, but only one showed an improved survival associated with HDF treatment, when compared with haemodialysis (HD). METHODS: This is a retrospective analysis of the entire Romanian dialysed population from the European Clinical Database (EUCLID) Fresenius Medical Care Database. We conducted two types of analysis. First, we used an intention-to-treat approach including all patients who were in dialysis (either HDF or HD) at 1 March 2010--'prevalent cohort analysis'. We then considered only the incident patients who started dialysis (either HDF or HD) after 1 March 2010--'incident cohort analysis'. In both analyses, patients were followed until 31 April 2013. RESULTS: In the prevalent cohort, we included 1546 patients who were already performing dialysis at the first time point-1322 on HD and 224 on HDF. When compared with HD, HDF treatment was associated with reduced mortality in both univariate and multivariate survival analysis (HR = 0.67, 95% CI 0.46-0.96 and HR = 0.58, 95% CI 0.36-0.93, respectively). In the incident cohort, 2447 patients started dialysis (2181 HD and 266 HDF) during the observation period. Patients in the HDF group maintained a reduced risk for all-cause mortality (HR = 0.20, 95% CI 0.11-0.38 for the univariate and HR = 0.24, 95% CI 0.13-0.46 for the fully adjusted model). CONCLUSIONS: This study suggests that HDF treatment could reduce all-cause mortality in incident and prevalent patients even after correction for different confounders. Interestingly, an additional survival benefit could be observed in incident patients. However, as with any observational study, there could have been other unmeasured confounders that could have influenced our final results.

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease.

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Effects of allopurinol on endothelial dysfunction: a meta-analysis.

OBJECTIVE: Several studies have assessed the effect of allopurinol on endothelial function, but these studies were relatively small in size and used different methods of evaluating endothelial function. We conducted a meta-analysis to investigate the effect of allopurinol on both endothelial-dependent and -independent vasodilatation. METHODS: Electronic databases, Medline, PubMed, EMBASE, SCOPUS, EBSCO and the Cochrane Library Central Register of Clinical Trials were searched from January 1985 to July 2013 on clinical trials (randomized and non-randomized) which assessed the effect of allopurinol on endothelial function. We conducted a sensitivity analysis to assess the contribution of each study to the pooled treatment effect by excluding each study one at a time and recalculating the pooled treatment effect for the remaining studies. Treatment effect was significant if p < 0.05. We assessed for heterogeneity in treatment estimates using the Cochran Q test and the χ(2) statistic (with substantial heterogeneity defined as values >50%). RESULTS: The final analysis consisted of 11 studies (2 observational and 9 randomized). For the endothelial-dependent vasodilatation there were 6 studies, including 257 patients, that evaluated flow-mediated dilatation and 5 studies with 87 patients that reported data on forearm blood flow response to acetylcholine or flow-dependent vasodilatation. Overall, there was a significant increase in the endothelium-dependent vasodilatation with allopurinol treatment (MD 2.69%, 95% CI 2.49, 2.89%, p < 0.001; heterogeneity χ(2) = 319.1, I(2) = 96%, p < 0.001). There was only 1 study (100 patients) assessing nitrate-mediated dilatation and 4 studies (73 patients) evaluating forearm blood flow response to sodium nitroprusside as measures of endothelial-independent vasodilatation. The overall analysis (MD -0.08, 95% CI -0.50, 0.34, p = 0.70; heterogeneity χ(2) = 9.0, I(2) = 44%, p = 0.11) showed no effect of allopurinol treatment on endothelium-independent vasodilatation. CONCLUSIONS: We found that treatment of hyperuricemia with allopurinol is associated with an improvement in the endothelial-dependent, but not with the endothelial-independent vasodilatation.