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Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus, mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO), and few studies have investigated its potential link with proteinuria. Renin-angiotensin system inhibitors (RASis) are recommended in these patients to decrease proteinuria, slow CKD progression and reduce cardiovascular risk, but whether these drugs influence kynurenine levels in humans is unknown. We evaluated serum tryptophan and kynurenine in patients suffering from CKD with or without type 2 diabetes mellitus, their correlations with markers of reduced kidney function, and their relationship with RAS-inhibiting therapy. Of 72 adult patients enrolled, 55 were receiving RASis, whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography); kynurenine was measured using an enzyme-linked immunosorbent assay kit; IDO activity (%) was calculated with the formula (kynurenine/tryptophan) × 100. Kynurenine levels were significantly lower in the group under RASis compared to the untreated group (1.56 ± 0.79 vs 2.16 ± 1.51 µmol/l; P = 0.0378). In patients not receiving RASis, kynurenine was inversely related to estimated glomerular filtration rate (eGFR) (r = - 0.4862; P = 0.0478) and directly related to both proteinuria (ρ = 0.493; P = 0.0444) and albuminuria (ρ = 0.542; P = 0.0247). IDO activity was higher in patients with history of cardiovascular disease compared to patients with no such history, and it negatively correlated with eGFR (ρ = - 0.554; P = 0.0210) in the same group. These findings may contribute to explain the well-known beneficial effects of RAS inhibition in CKD population, especially considering that kynurenine is emerging as a potential new biomarker of CKD.

Chronic kidney disease (CKD) represents a major public health issue worldwide and entails a high burden of cardiovascular events and mortality. Dyslipidaemia is common in patients with CKD and it is characterized by a highly atherogenic profile with relatively low levels of HDL-cholesterol and high levels of triglyceride and oxidized LDL-cholesterol. Overall, current literature indicates that lowering LDL-cholesterol is beneficial for preventing major atherosclerotic events in patients with CKD and in kidney transplant recipients while the evidence is less clear in patients on dialysis. Lipid lowering treatment is recommended in all patients with stage 3 CKD or worse, independently of baseline LDL-cholesterol levels. Statin and ezetimibe are the cornerstones in the management of dyslipidaemia in patients with CKD, however alternative and emerging lipid-lowering therapies may acquire a central role in near future. This position paper endorsed by the Italian Society of Nephrology aims at providing useful information on the topic of dyslipidaemia in CKD and at assisting decision making in the management of these patients.

Indole-3-acetic acid is a protein-bound indolic uremic toxin deriving from tryptophan metabolism. Increased levels are associated with higher thrombotic risk and both cardiovascular and all-cause mortality. An emerging biomarker of cardiovascular disease is the monocyte-to-high-density lipoprotein ratio (MHR). The main purpose of this study was to investigate the association of indole-3-acetic acid with MHR and other markers of cardiovascular risk in patients with chronic kidney disease (CKD).We enrolled 61 non-dialysis CKD patients and 6 dialysis patients. Indole-3-acetic acid levels were measured with ELISA technique.In the whole cohort of 67 patients, indole-3-acetic acid was directly related to Ca × P (ρ = 0.256; P = 0.0365) and MHR (ρ = 0.321; P = 0.0082). In the 40 patients with previous cardiovascular events, indole-3-acetic acid correlated with uric acid (r = 0.3952; P = 0.0116) and MHR (ρ = 0.380; P = 0.0157). MHR was related with fibrinogen (ρ = 0.426; P = 0.0010), arterial hypertension (ρ = 0.274; P = 0.0251), C-reactive protein (ρ = 0.332; P = 0.0061), gender (ρ = - 0.375; P = 0.0017; 0 = male, 1 = female), and CKD stage (ρ = 0.260; P = 0.0337). A multiple regression analysis suggested that indole-3-acetic acid might be an independent predictor of MHR.This study shows a significant association between indole-3-acetic acid and MHR. Prospective studies are required to evaluate if decreasing indole-3-acetic acid concentrations may reduce MHR levels and cardiovascular events and improve clinical outcomes.

Background and Aims Indole-3-acetic acid (IAA, also called auxin) is a protein-bound indolic uremic toxin deriving from tryptophan metabolism by the intestinal bacteria. Previous studies have shown that increased IAA is associated with enhanced tissue factor synthesis in endothelial and peripheral blood mononuclear cells, oxidative stress and endothelial inflammation with resulting higher risk of thrombotic events and both cardiovascular and all-cause mortality. An emerging biomarker of cardiovascular disease is the monocyte to high-density lipoprotein (HDL) ratio (MHR). Its prognostic value is related to the ability of monocytes to release several cytokines involved in inflammation and atherogenesis and to the protective role of HDL through removal of cholesterol from peripheral tissues and suppression of both monocyte progenitor cell proliferation and differentiation and monocyte activation. In this single-centre cross-sectional observational study, we investigated the potential association of IAA with MHR and other markers of cardiovascular risk in a cohort of patients with CKD and evaluated the effect of a single midweek dialysis session with AFB (Acetate-free Biofiltration) technique on IAA serum concentrations. Method We enrolled 61 non-dialysis CKD adult patients and 6 dialysis patients treated with AFB technique. IAA levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit (Cat. number abx150354; Abbexa Ltd, Cambridge, UK). Post-dialysis IAA levels were corrected for haemoconcentration. Results In the whole cohort of 67 patients, IAA was directly related to creatinine (ρ = 0.247; P = 0.0441), potassium (r = 0.2871; P = 0.0185), Ca x P product (ρ = 0.256; P = 0.0365) and MHR (ρ = 0.321; P = 0.0082). After adjustment for creatinine, the correlation between IAA and potassium became not significant (r = 0.1968; P = 0.1133). Stratifying patients according to the history of cardiovascular disease, in the 40 patients with previous cardiovascular events IAA levels correlated significantly with uric acid (r = 0.3952; P = 0.0116) and MHR (ρ = 0.380; P = 0.0157). In the remaining 27 patients without history of cardiovascular disease, IAA only correlated with potassium (r = 0.3912; P=0.0481) and, though borderline significantly, with creatinine (ρ = 0.349; P = 0.0805). To assess whether IAA would independently predict MHR values, we evaluated potential correlations of MHR with risk factors for cardiovascular disease. MHR was related with fibrinogen (ρ = 0.426; P = 0.0010), arterial hypertension (ρ = 0.274; P = 0.0251), C-reactive protein (ρ = 0.332; P = 0.0061), gender (ρ = -0.375; P = 0.0017; 0 = male, 1 = female), and CKD stage (ρ = 0.260; P = 0.0337). A multiple regression analysis identified IAA as an independent predictor of MHR. Lastly, IAA levels were higher in dialysis patients compared to non-dialysis CKD patients (97.44 ± 21.58 versus 65.08 ± 24.38 ng/ml respectively; P = 0.0026) and it was significantly removed by a single AFB session (97.44 ± 21.58 versus 54.59 ± 21.74 ng/ml; P = 0.0028) with a reduction ratio of 43.80 ± 17.47%. Conclusion This study shows a statistically significant association between IAA and MHR. Based on previous experimental studies, such relationship could be explained by the activation of the transcription factor aryl hydrocarbon receptor. Indeed, IAA is a potent ligand of aryl hydrocarbon receptor and the latter has proinflammatory and proatherogenic activities and can reduce HDL levels. Moreover, AFB efficiently removes IAA during a single dialysis session. Prospective studies with appropriate sample size and sufficiently long period of observation are required to evaluate if decreasing IAA levels, through targeted therapeutic strategies in non dialysis CKD patients or by optimization of dialysis techniques and prescriptions in patients receiving renal replacement therapy, may reduce MHR levels and cardiovascular events and improve clinical outcomes and survival.

Background and Aims Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus (DM), mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO). Renin-angiotensin-aldosterone system inhibitors (RAASis) [angiotensin converting enzyme inhibitors (ACEis) and angiotensin II receptor antagonists (ARBs)] are recommended in these conditions to decrease proteinuria, slow CKD progression and reduce cardiovascular risk. The interactions between RAAS and the kynurenine pathway and the potential effects of RAASis have been reported in few experimental models but whether these drugs influence kynurenine levels in humans is unknown. We performed a single-centre cross-sectional observational study to evaluate tryptophan and kynurenine serum levels and IDO activity in CKD patients with and without type 2 DM, their correlations with markers of renal dysfunction, and their relationship with RAAS-inhibiting therapy. Method We enrolled 72 consecutive adult patients with CKD, of which 38 had DM, who were admitted to the Unit of Nephrology and Dialysis of our Hospital. Of them, 55 were receiving RAASis whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography) analysis with an UltiMateTM 3000 chromatograph (Thermo Fisher Scientific, 168 Third Avenue Waltham, MA, USA); kynurenine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (Catalogue n. K 7728; Immundiagnostik AG, Bensheim, Germany); IDO activity was calculated with the formula (kynurenine/tryptophan) x 100. Results Patients receiving RAASis and patients not under therapy only differed for frequency of arterial hypertension (100% vs 76.47%; P=0.002) and kynurenine levels, the latter being significantly lower in the treated group compared to the untreated one (1.56 ± 0.79 vs 2.16 ± 1.51 µmol/l; P=0.0378). Kynurenine did not correlate with estimated glomerular filtration rate (eGFR), proteinuria or albuminuria in the whole study cohort. Conversely, in patients not receiving RAASis it was inversely related to eGFR (r=-0.4862; P=0.0478) and directly related to proteinuria (ρ=0.493; P=0.0444) and albuminuria (ρ=0.542; P=0.0247); moreover, it varied across classes of albuminuria, being lower in patients with normoalbuminuria (0.98 ± 0.55 µmol/l) and higher in those with micro- (2.63 ± 1.53 µmol/l) and macroalbuminuria (3.09 ± 1.61 µmol/l) at the ANOVA test (F=4.008; P=0.042). In the same group, the relationship between IDO activity and eGFR was significant (ρ=-0.554; P=0.0210) and IDO activity differed across classes of albuminuria (F=3.702; P=0.05). Moreover, IDO activity was higher in patients with history of cardiovascular disease compared to those with no such history [10.22 (8.39 to 22.92) vs 7.57 (4.76 to 8.09) %; P=0.0343] whereas tryptophan had an opposite behaviour (17.00 ± 2.06 vs 22.00 ± 3.78 µmol/l; P=0.0036). Conclusion We observed lower kynurenine levels in CKD patients treated with RAASis compared to untreated patients, independently of the presence of DM, and a significant association between kynurenine and markers of renal damage only in the group not receiving RAASis. We could hypothesize that kynurenine may play a role in the pathophysiology of renal damage, as already suggested, and that drugs interfering with RAAS activation may act also by reducing kynurenine levels, in addition to their already known effects at the renal level. Indeed, kynurenine synthesis results to be higher in states of inflammation and RAAS has pro-inflammatory and pro-fibrotic actions; accordingly, RAASis could reduce the enzymatic activity responsible for kynurenine increase and this could be one of the mechanisms mediating the beneficial effects of RAAS inhibition on CKD progression. This may be relevant because kynurenine has shown pro-thrombotic effects and is emerging as a potential new biomarker of CKD.

According to many studies, extracorporeal dialysis with convective methods is associated with better clinical outcomes and a survival benefit compared to diffusive techniques. However, there is no full agreement on the actual superiority of this kind of renal replacement therapy on hard end-points such as mortality. We performed a retrospective epidemiological cohort study to provide "real-world" evidence on the impact of convective and non-convective dialysis techniques on all-cause and cardiac mortality and biochemical outcomes among dialysis patients in Sicily, the southernmost region of Italy. Data of all incident adult patients (N = 6529) who have started chronic extracorporeal dialysis over the period 2009-2015 were retrieved from the Sicilian Registry of Nephrology, Dialysis and Transplantation. There were 1558 patients receiving convective techniques (23.86%). Overall mortality rate was 45.21% with a significant difference between convective (31.39%) and non-convective (49.55%) groups (P

The purpose of this study was to assess depression and anxiety levels and possible correlations with levels of circulating catecholamines in maintenance hemodialysis (MHD) and Conservative care (CC) ERSD patients. Eighty ESRD patients, forty treated by MHD and forty by CC, were included in the study. Circulating catecholamines concentrations were measured; all subjects were assessed by Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Self-Rating Depression Scale, and Self-Rating Anxiety Scale. Statistical analysis showed significant differences in Noradrenaline (p

Ingestion of coffee (which is a mixture of over 1000 hydrosoluble substances) is known to protect from type-2 diabetes mellitus and its complications, and other chronic disorders associated with increased oxidative damage in blood and tissues. This protection is generally attributed to polyphenols and melanoidins. Very few studies were conducted on the amelioration of classic blood markers of oxidative stress induced after a few days of caffeine administration, but results vary.To assess whether caffeine per se could account for antioxidant properties of coffee in the short-term, we tested the ability of pure caffeine ingestion (5â¯mg/kg body weight/day in two daily doses for seven consecutive days) to improve plasma levels of six biochemical indices in healthy male volunteers (nâ¯=â¯15). These indices were total antioxidant capacity (TAC), glutathione (GSH), oxidized glutathione (GSSG), GSH to GSSG ratio, lipid hydroperoxides (LOOH) and malondialdehyde (MDA).We found that all indices changed significantly (Pâ¯

Previous studies have investigated constructs that facilitate adaptation to chronic disease and improve quality of life and constructs that lead to psychopathological complications. The purpose of this research is to investigate the impact of coping and emotional regulation on the quality of life of patients on dialysis. Three questionnaires were administered to 78 patients on dialysis: Coping Orientations to Problems Experienced, Short Form (36), and Cognitive Emotion Regulation Questionnaire. Regressions analyses indicated that age, Rumination, Positive Refocusing, Avoidance Strategies, Approach to the Problem, and Transcendent Orientation predicted Physical Health. With regard to Mental Health, the predictors were gender, Self-Blame, Acceptance, Rumination, Positive Reappraisal, Catastrophizing, Avoidance Strategies, and Transcendent Orientation. This study confirms the relationship between emotional regulation, coping, and quality of life. The results highlight the need for total care of the patients, including an assessment of both physical state and psychological functioning in order to promote total well-being.

To evaluate the relation between CD34We enrolled 16 women that gave birth to newborns carrying congenital renal malformations over a 3-year period and 48 women with uncomplicated pregnancies (controls) in a 1:3 ratio (three controls per case).CD34CD34

To evaluate the relation between CD34+ cells count in maternal blood and potential development of fetal congenital renal abnormalities.We enrolled 16 women that gave birth to newborns carrying cong...

Renal diseases are distressing and it is, especially, the aspect of uncertainty that exerts an influence on patients’ emotional adjustment to illness. The present study investigates the relationship between uncertainty and trait emotional intelligence (EI), and the role of EI as mediator in the relationship between uncertainty, anxiety, and depression in nephropathy patients. Fifty patients were asked to complete a worksheet including the Hospital Anxiety and Depression Scale, Trait Emotional Intelligence Questionnaire—Short Form, and Mishel Uncertainty in Illness Scale. Structural equation modeling has been used to examine whether trait EI mediates the relationship between uncertainty, anxiety, and depression. Through structural equation modeling, it has been demonstrated that trait EI mediated the relationship between uncertainty, anxiety, and depression. These findings suggest to develop coaching programs aimed at strengthening nephropathy patients’ emotional responses to uncertainty; in this way, it could be possible to observe an improvement in patients’ quality of life.

Background: Gentamicin is an aminoglycoside antibiotic widely used in the treatment of infections caused by Gram-negative bacteria. The main limitation to its therapeutic effectiveness is the potential nephrotoxicity. Erythropoietin has a tissue protective effect widely demonstrated in the kidney. The aim of the present study was to evaluate the renoprotective effects of erythropoietin in a model of zebrafish (Danio rerio) after administration of gentamicin. Methods: Sixty adult zebrafish were subdivided into three groups: group A was treated with gentamicin; group B received gentamicin and, 24 h later, epoetin alpha; group C received drug diluent only. In order to analyze the renoprotective activity of erythropoietin, the expression of c-kit and ?-catenin was evaluated by immunohistochemistry. Results: Generally, the zebrafish renal tubule regenerates 15 days after an injury. Conversely, 7 days after gentamicin administration, animals treated with erythropoietin (group B) showed a better renal injury repair as documented by: increased expression of ?-catenin, less degenerated tubules, greater number of centers of regeneration, positivity for c-kit only in immature-looking tubules and lymphohematopoietic cells. Conclusion: The expression of c-kit and ?-catenin suggests that erythropoietin may exert a role in regeneration reducing the extent of tubular damage from the outset after gentamicin administration.

Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy.

Lung and kidney functions are intimately related in both health and disease. The regulation of acid-base equilibrium, modification of partial pressure of carbon dioxide and bicarbonate concentration, and the control of blood pressure and fluid homeostasis all closely depend on renal and pulmonary activities. These interactions begin in fetal age and are often responsible for the genesis and progression of diseases. In gestational age, urine is a fundamental component of the amniotic fluid, acting on pulmonary maturation and growth. Moreover, in the first trimester of pregnancy, kidney is the main source of proline, contributing to collagen synthesis and lung parenchyma maturation. Pathologically speaking, the kidneys could become damaged by mediators of inflammation or immuno-mediated factors related to a primary lung pathology or, on the contrary, it could be the renal disease that determines a consecutive pulmonary damage. Furthermore, non immunological mechanisms are frequently involved in renal and pulmonary diseases, as observed in chronic pathologies such as sleep apnea syndrome, pulmonary hypertension, progressive renal disease and hemodialysis. Kidney damage has also been related to mechanical ventilation. The aim of this review is to describe pulmonary-renal interactions and their related pathologies, underscoring the need for a close collaboration between intensivists, pneumologists and nephrologists.

Context: Available markers are not reliable parameters to early detect kidney injury in transplanted patients.Objective: Examine neutrophil gelatinase associated lipocalin (NGAL) in early detection of delayed graft function (DGF) and as a long-term predictor of graft outcome.Patients and methods: NGAL was evaluated in 124 transplanted patients.Results: Urinary NGAL levels were associated to a 10% (HR: 1.10; 95% CI: 1.04–1.25; p

Our aim was to evaluate the role of urotensin II, urantide (urotensin II receptor antagonist) and relaxin-2 on the cellular expression of fibronectin as a surrogate marker for renal fibrosis. We employed LLC-PK1 renal tubular epithelial cells and assessed the influence on the fibrotic process of the above-mentioned substances by using anti-fibronectin antibodies in western blot analysis. The addition of urotensin II increased fibronectin expression. Urantide reduced the positivity for fibronectin caused by urotensin II (P

Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, the treatment of adult primary MCD and FSGS should be based on immunosuppressants and antiproteinuric drugs. Recently, Rituximab, a humanized monoclonal antibody (mAb) has emerged as a potential treatment for steroid or calcineurin inhibitor-dependent patients; it has however demonstrated lower efficacy in those with nephrotic syndrome that is resistant to the above indicated drugs.Analysis of ongoing and already completed clinical trials, retrieved from clinicaltrials.gov, clinicaltrialsregister.eu and PubMed involving new therapies for nephrotic syndrome secondary to MCD and FSGS.The most promising drugs under investigation for MCD and FSGS are mAbs. We are hopeful that new therapeutic options to treat multi-drug resistant MCD and FSGS will emerge from currently ongoing studies. What appears certain is the difficulty in enrolling patients affected by orphan renal diseases and the selection of valid endpoints in clinical trials, such as kidney failure.

The use of glucose-lowering drugs in advanced stage diabetic nephropathic patients should be done very carefully. Some drugs are contraindicated or not recommended. The same insulin needs a dose reduction to avoid dangerous hypoglycemia. For some years the use of inhibitors of the DDP-4 has been approved in T2DM patients with CKD III and IV stage, proposing the use without limitations even in case of ESRD. We conducted a prospective observational study of a cohort of 60 patients with T2DM and CKD stage IV, selecting a sample of 15 patients taking an inhibitor of DPP-4 and comparing it with those who took therapy "old" drugs, despite having similar characteristics of CKD. In both groups, we found: 1) the effectiveness of therapy, through the assessment of glycated hemoglobin and glycemic profile; 2) the possible occurrence of "hypoglycemia", "side effects", accelerating the progression of CKD. No patients being treated with inhibitors of DPP-4 have experienced hypoglycemia, or adverse events, or adverse effects on the progression of CKD. The glycated hemoglobin, revealed more stability than the comparison group. Hypoglycaemic episodes were present only in the group receiving intensive insulin. Although kidneys and their dose, in case of high degree of CKD, primarily eliminate inhibitors of DPP-4, with some exceptions, should be reduced, in our experience they have proven beneficial drugs in diabetics with kidney disease, being effective and well tolerated in the case of ESRD, where the only treatment option was represented by insulin.

Background C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade is responsible for the development of the disease if triggered by several possible environmental conditions. We report the first case in literature of a patient affected by cystic fibrosis and C3GN. Case presentation Our case involves a young woman with cystic fibrosis, who had persistent microscopic hematuria, proteinuria and hypocomplementemia C3 for over three months. Renal biopsy confirmed the diagnosis of C3 glomerulopathy. Complement system dysregulation was tested and resulted in a strong terminal pathway activation proved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value

Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia-inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in-depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis-stimulating agents.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) è uno dei più promettenti biomarcatori utilizzati nella diagnosi di “Acute Kidney Injury” (AKI), dal momento che il suo incremento è un buon predittore a breve termine dello sviluppo di insufficienza renale acuta in notevole anticipo rispetto all'incremento dei valori della creatinia sierica. Riportiamo la nostra esperienza di un caso di Crush Syndrome di due pazienti vittime dell'alluvione che ha coinvolto Messina. Lo sviluppo di AKI in seguito a Crush Syndrome è la seconda causa più comune di morte in seguito a terremoti o altri disastri naturali ma allo stesso tempo è una complicanza disastro-correlata che può essere reversibile in particolar modo in caso di diagnosi precoce e di altrettanto precoce trattamento. In questo caso, l'NGAL ci ha permesso di fare una diagnosi precoce di AKI preannunciando le alterazioni dei classici marker come la creatinina, inoltre abbiamo notato la correlazione diretta tra i valori di NGAL, l'evoluzione del danno renale e la prognosi per le due pazienti.

Purpose: To evaluate the levels of peripheral blood CD34+ cells in women who subsequently had a spontaneous miscarriage (SM).Materials and methods: We enrolled 11 women who had SM, matching them for age, BMI and gestational age with 33 healthy pregnancies (controls). From a blood sample at 9th–11th weeks of pregnancy, we evaluated PAPP-A, free β-hCG, T (suppressor and helper), NK, B, CD34+ cells.Results: In peripheral blood of women who had SM, PAPP-A and CD34+ cells were significantly lower (p

At present, treatment of autosomal dominant polycystic kidney disease (ADPKD) is essentially supportive as there is still no specific therapy. However, recent advances with ADPKD pathophysiology have stimulated research for new therapeutic strategies.The aim of this systematic review is to analyze the experimental and early investigational therapies currently under evaluation in this field. Data from completed clinical trials were retrieved from the currently available scientific literature and from the ClinicalTrials.gov website.Among the drugs currently being explored, mammalian target of rapamycin inhibitors reduce kidney volume enlargement but their role remains uncertain. The most promising drug is the V2 receptor antagonist tolvaptan, which reduces the increased rate of total kidney volume and slows down glomerular filtration rate decline. The main candidates for the treatment of cysts growth, both in the kidney and in the liver whenever present, are the somatostatin analogues, such as lanreotide and octreotide and more recently pasireotide. As for other therapies, some favorable results have been achieved but data are still not sufficient to establish if these approaches may be beneficial in slowing ADPKD progression in the future.

Hyperphosphatemia is common in patients with chronic renal failure. Phosphate binders are associated with gastric intolerance, representing the main reason of drug discontinuation. The aim of this study was to compare the effects in vitro and in vivo of sevelamer hydrochloride (SH), sevelamer carbonate (SC) and lanthanum carbonate (LC) on gastric microenvironment. We have also evaluated the efficacy and tolerability of these drugs in hemodialysis (HD) patients. In vitro analysis: Dissolution time, ability to uptake phosphorus, changes in pH starting from gastric milieu and the amount of carbon dioxide (CO(2)) produced were the variables analyzed. In vivo analysis: 24-h esophago-gastric pH measurement was evaluated in 24 HD patients treated with phosphate binders and proton pump inhibitor (PPI). In vitro: LC dissolved over a longer time compared with SC (58 ± 2.4 vs. 12 ± 0.6 min; P

Aim Semaphorin 3A urinary levels represent an early, predictive biomarker of acute kidney injury and positively correlate with albumin-to-creatinine ratio and serum creatinine in hypertensive patients with chronic kidney disease. Our purpose has been to evaluate semaphorin 3A serum levels in a cohort of haemodialysis (HD) patients, the influence of a single HD session on its concentrations, and the potential correlation with clinical and biochemical parameters. Methods We enrolled 18 patients receiving HD with Acetate-Free Biofiltration technique and 16 healthy subjects as controls. Peripheral venous blood samples were obtained from patients at different intervals: start of dialysis (pre-HD), middle, and end of the treatment (post-HD). We also collected dialysate samples by the Quantiscan monitoring system (Hospal, Bologna, Italy). Results Semaphorin 3A was significantly lower in HD patients at baseline compared to controls (median 19.50 (interquartile range 1.00–65.00) versus 97.50 (23.50–161.00) ng/mL, P = 0.0237). A statistically significant reduction was seen during a single HD session (from 19.50 (1.00–65.00) to 0.86 (0.82–4.21) ng/mL, P

Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality in end-stage renal disease patients. It is not clear if this effect is related to the elevated ESAs dosage for targeting hemoglobin levels or underlying morbid conditions that lead to ESA resistance. We retrospectively evaluated from 2008 to death or December 2011, 28 consecutive incident hemodialysis patients. We identified 2 cohort of patients based on their mean annual ESAs dosage. The correlation between data was evaluated with the Spearman's rho test. Kaplan-Meier curves were generated to assess survival in subjects with high and low ESAs mean dose. Median ESAs dosage, used as a cutoff point between patients at high and low ESAs dose, was at 11.000 IU/week for epoetin alfa and beta, 55 mcg/week for darbopoietin, and 220 mcg/month for cera. Mean hemoglobin (Hb) level was 10.58 ± 0.13 g/dL. Of 28 patients, during follow-up, 6 (21,4%) died of all causes. High-dose ESA therapy was associated with increased all-cause mortality (P = .047). Moreover, there was a negative correlation between ESAs dose and Hb levels (rho = -0.825; P .001). Higher ESAs dose for the treatment of anemia in incident hemodialysis patients was associated with higher mortality risk. ESAs and Hb serum levels were inversely correlated with mortality. Together, these findings suggest that ESAs dosage and Hb level may play a role through an independent manner or an interactive effect that adversely affects mortality.

Nutritional support is one of the main factors in the management of patients with Chronic Kidney Disease (CKD) and it should be a substantial part of the treatment. Generally, the aim of the nutritional management for CKD patients is to control the protein content and the assumption of some micronutrients, such as potassium, sodium, calcium, and phosphorus, while there is little attention with regard to dietary lipids. Although their role in the progression of renal damage has not been clearly defined yet, many studies have reported that in the general population dyslipidemia is correlated with the increased cardiovascular risk associated with CKD, as well as with the progression of renal damage. In the literature, experimental and clinical data report that long chain n-3 fatty acids may protect patients on hemodialysis from sudden cardiac death. Moreover, the intake of dietary fibers may be effective for improving lipid profile in patients with CKD. Thus, nutritional management for patients with CKD shou...

Background: Accruing evidence suggests that Xanthine Oxidase inhibitors (XOis) may bring direct renal benefits, besides those related to their hypo-uricemic effect. We hence aimed at performing a systematic review of randomized controlled trials (RCTs) to verify if treatment with XOis may improve renal outcomes in individuals with chronic kidney disease (CKD). Methods: Ovid-MEDLINE, PubMed and CENTRAL databases were searched for RCTs comparing any XOi to standard therapy or placebo. The primary endpoint of interest was progression to End-Stage Kidney Disease (ESKD); secondary endpoints were changes in serum creatinine, glomerular filtration rate (eGFR), proteinuria and albuminuria. Results: XOis treatment significantly reduced the risk of ESKD compared to the control (3 studies, 204 pts; RR = 0.42; 95% CI, 0.22, 0.80) and also improved eGFR in data pooled from RCTs with long follow-up times (>3 mo.) (4 studies, 357 pts; mean difference (MD) 6.82 mL/min/1.73 m2; 95% CI, 3.50, 10.15) and high methodological quality (blind design) (3 studies, 400 pts; MD 2.61 mL/min/1.73 m2; 95% CI, 0.23, 4.99). Conversely, no definite effects were apparently noticed on serum creatinine, proteinuria and albuminuria. Conclusions: XOis may represent a promising tool for retarding disease progression in CKD patients. Future trials are awaited to confirm the generalizability of these findings to the whole CKD population.