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Investigates the efficacy of muzolimine as a diuretic for persons with renal disease. Impact of muzolimine to urine volume and excretions of sodium, chloride and potassium ions; Reduction of body weight after administration of the drug; Restoration of normal blood pressure.

Presents the foreword to the June 2005 issue of "Nutrition Reviews," vol. 63, no. 6.

A letter to the editor is presented in response to the January 30, 2003 article "Peritoneal Dialysis and Epithelial-to-Mesenchymal Transition of Mesothelial Cells," by E. Lara-Pezzi and colleagues.

A response by Antonino Mazzone and colleagues to a letter to the editor about their article on hypercarotenemia in the March 14, 2002 issue is presented.

The article presents information on a 23-year-old woman who was admitted to a hospital for jaundice. She was found to have yellow-orange discoloration of her skin. It was observed that her sclerae were not discolored. Physical examination showed that her serum bilirubin level was normal. A marked increase in serum beta carotene levels was seen by high-performance liquid chromatography. The woman was a vegetarian. She was on a low-calorie diet with a high content of orange juice, pumpkin, and carrots. She was diagnosed with hypercarotenemia, for which other causes were also studied. However, other causes of hypercarotenemia like hyperlipidemia, diabetes mellitus, hypothyroidism, and porphyria were excluded.

Progressive hemodialysis is based on the simple idea of adjusting its dose according to residual renal function (RRF). The progressive, infrequent paradigm is slowly gaining a foothold among nephrologists, despite a lot of skepticism in the scientific world. Given the importance of RRF preservation in conservative therapy, it seems a contradiction to ignore the contribution of RRF when patients initiate hemodialysis (HD), especially when it is routinely considered with peritoneal dialysis. While a three-times-weekly HD regimen is broadly considered the standard starting regimen for new patients, twice-weekly HD has been used in selected patients and is currently a common practice in South-East Asia. Small studies indicate that a once-weekly HD regimen may be a viable starting option as well. Progressive hemodialysis still requires validation, yet it is promising. We share the belief that a randomized clinical trial to investigate progressive hemodialysis is much needed, but we also strongly recommend including a once-weekly HD starting dose as part of any such investigation. [ABSTRACT FROM AUTHOR]

Background. In the aftermath of large natural and manmade disasters, the need for continuing maintenance haemodialysis (HD) in end-stage renal disease patients of the disaster area and care including dialysis for patients suffering from acute kidney injury (AKI) due to crush syndrome are the two most important nephrological problems.Methods. We report on how renal patients and renal care personnel faced emergency in the aftermath of the earthquake that struck the Italian town of L'Aquila and a surrounding district, on Monday 6 April 2009, causing 308 deaths, some 1500 injured and 66 000 people to be displaced.Results. The Dialysis Centre in the town did not collapse but was seriously damaged and out of action, making it necessary to move 88 patients on regular dialysis treatment to the closest available facilities to continue treatment. This was all the more urgent in that 45 patients of the Monday–Wednesday–Friday batch were coming off the long interdialytic interval, with possible medical problems (i.e. high increase in weight gain, blood pressure, etc.). In spite of manifold difficulties (including road interruption and shortage of means of transportation, problems in establishing contact between patients and care personnel due to failure of phone and electronic communication and the limited number of available dialysis posts), no patient missed any scheduled HD session. This was obtained thanks to the transfer of patients to neighbouring functioning units, often with extra dialysis shifts. In 3 days, a provisional Dialysis Centre was set up in an inflatable military-style tent, enabling 780 dialysis sessions to be performed safely on patients who had opted to return to L'Aquila. The tent facility was replaced by a rigid modular structure, insulated as living accommodation, containing 13 dialysis machines (20 from 17 November) functioning in HD or on-line haemodiafiltration. Ten cases of crush-related AKI needing dialysis treatment were recorded, the ratio of dialysed victims to number of deaths (32.4: 10 cases/308 deaths, 1000×) being the highest value yet reported. Fasciotomy was performed in six patients but none of the patients had to be amputated. Intermittent HD was used in most cases as the single modality of renal replacement therapy. All patients survived and recovered renal function on discontinuing dialysis treatment. Serum creatinine returned to normal values upon discharge from hospital or during the follow-up period.Conclusions. Each earthquake is different and may pose issues that will require unanticipated response efforts. Advance planning and rescue coordination, flexibility and creativity in the emergency situation, as well as the hard work and dedication of the entire dialysis care community, contributed to the remarkably positive outcome of dialysis-needing patients in the aftermath of the Aquila earthquake. [ABSTRACT FROM AUTHOR]

Abstract: The Scatter Factors are two homologous proteins, named Scatter Factor/Hepatocyte Growth Factor and Macrophage Stimulating Protein. Their receptors are the products of two oncogenes, Met and Ron, respectively. The Scatter Factors induce movement, stimulate proliferation, regulate apoptosis and are morphogenic, i.e. operate an integrated program that seems tailored to drive organ development and to regenerate injured tissues. On the other hand, Scatter Factors may be responsible for pathologic tissue remodeling, infiltration of inflammatory cells, and tumor growth and diffusion. The review describes the involvement of Scatter Factors in renal disease, including acute renal failure, glomerulonephritis, chronic fibrosing nephropathies, dialysis, renal transplantation and renal tumors, and discusses the double-faced role of Scatter Factors, that play either a protective or a pathogenic role. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "A Randomized, Controlled Trial of Early Versus Late Initiation of Dialysis," by B. A. Cooper and colleagues in the August 12, 2010 issue.

A letter to the editor is presented in response to the article "Revascularization Versus Medical Therapy for Renal-Artery Stenosis" in the November 12, 2009 issue.

A letter to the editor is presented in response to the article "Role of T-regulatory cells in the response to hepatitis B vaccine in hemodialysis patients," by R. O. Mathew et al., in the 2016; 20 issue is presented.

Introduction. Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). In our study, we evaluated the association between RBP4 and IR in hemodialysis subjects (HD). We also assessed how circulating RBP4 could be influenced by kidney transplant or different dialytic techniques. Methods. RBP4 serum levels were evaluated in HD (n=16) and matched healthy controls (C; n=16). RBP4 and glucose transporter type 4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating RBP4 was evaluated after kidney transplant (n=7) and in hemodialysis patients (n=10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF). Results. HOMA index (P<0.05) and serum RBP4 (P<0.005) were higher in HD compared to C. RBP4 levels positively correlated with fasting serum glucose (P<0.05). RBP4 mRNA was lower in HD compared to C (P<0.05) and positively correlated with kidney function (P<0.05) and GLUT4 mRNA (P<0.001). Transplant or HDF reduced circulating RBP4 (P<0.01 and P<0.05, resp.). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels. [ABSTRACT FROM AUTHOR]

Background: Information on physical and mentalwellness in renal transplantation is limited. Therefore, we performed a crosssectional study to evaluate and describe the different components of physical performance and quality of life (QoL) in a cohort of kidney-transplanted patients. Methods: Physical performance and QoL were determined through the administration of validated tests and questionnaires [muscle strength, dynamometer handgrip, tactile sensitivity, visual analogue scale (VAS) for pain, Timed Up and Go (TUG) test, Fatigue Severity Scale (FSS) and the 36-item Short Form Health Survey]. The patients were divided into three groups based on time elapsed since transplantation: early (in the first 6 months), middle (from 7 to 60 months) and late (>60 months). Results: Of 132 enrolled patients, 11 patients (8.3%) presented a severe reduction of muscle strength, 63 patients (47%) had significant bilateral impaired handgrip and tactile sensitivity was altered in 23 patients (17.4%). TUG assessment showed significant mobility limitation in 29 patients (21.9%). The FSS presented a pathological value in 50 patients (37.3%), while the mean VAS was 1.8 ± 2.7. There were no significant differences in physical performance parameters among the three patient groups. There were inverse correlations among different components of physical performance and age, comorbidity and dialysis vintage, and therewas a direct correlation with renal function. During the first months after transplantation therewere limitations in physical, social and emotional activities. Overall, the self-perceived physical performancewas significantly lower in transplanted patients with respect to the normal reference level. Conclusion: Kidney-transplanted patientsmay present different degrees of impairment in physical performance and quality of life. Systematic functional assessment is essential to identify patients needing intensive and personalized rehabilitation programmes. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) is a pleiotropic cytokine which exerts a variety of effects on several cells, being involved in the regulation of many biological processes, such as inflammation, tissue repair, morphogenesis, angiogenesis, tumour propagation, immunomodulation of viral infections and cardio-metabolic activities. Patients undergoing regular hemodialysis (HD) present elevated levels of HGF, mainly due to the leukocyte activation associated with HD treatment. High HGF levels might account for specific clinical features of HD patients, i.e. mild liver damage in course of HCV-infection and high cardiovascular risk profile. Moreover, in patients with acute kidney injury, the induction of HGF may represent a crucial step to promote renal recovery, which can have important prognostic consequences in the short and long-term. In this review we discuss the mechanisms underlying HGF production in HD patients, the role of HGF in this particular patient population and the potential clinical implications derived from the study of HGF in HD patients. [ABSTRACT FROM AUTHOR]

Aims: Cardiovascular autonomic dysfunction, evaluated as baroreflex sensitivity (BRS), could be acutely corrected by slow breathing or oxygen administration in patients with type 1 diabetes, thus suggesting a functional component of the disorder. We tested this hypothesis in patients with the type 2 diabetes with or without renal impairment. Methods: Twenty-six patients with type 2 diabetes (aged 61.0 ± 0.8 years, mean ± SEM; duration of diabetes 10.5 ± 2 years, BMI 29.9 ± 0.7 kg/m, GFR 68.1 ± 5.6 ml/min) and 24 healthy controls (aged 58.5 ± 1.0 years) were studied. BRS was obtained from recordings of RR interval and systolic blood pressure fluctuations during spontaneous and during slow, deep (6 breaths/min) controlled breathing in conditions of normoxia or hyperoxia (5 l/min oxygen). Results: During spontaneous breathing, diabetic patients had lower RR interval and lower BRS compared with the control subjects (7.1 ± 1.2 vs. 12.6 ± 2.0 ms/mmHg, p < 0.025). Deep breathing and oxygen administration significantly increased arterial saturation, reduced RR interval and increased BRS in both groups (to 9.6 ± 1.8 and 15.4 ± 2.4 ms/mmHg, respectively, p < 0.05, hyperoxia vs. normoxia). Twelve diabetic patients affected by chronic diabetic kidney disease (DKD) presented a significant improvement in the BRS during slow breathing and hyperoxia ( p < 0.025 vs. spontaneous breathing during normoxia). Conclusions: Autonomic dysfunction present in patients with type 2 diabetes can be partially reversed by slow breathing, suggesting a functional role of hypoxia, also in patients with DKD. Interventions known to relieve tissue hypoxia and improve autonomic function, like physical activity, may be useful in the prevention and management of complications in patients with diabetes. [ABSTRACT FROM AUTHOR]

We studied Mesenchymal Stromal Cells (MSC) effects in experimental Unilateral Ureteral Obstruction (UUO), a fibrogenic renal disease. Rats were divided in 5 groups: sham, UUO, MSC treated-UUO, ACEi treated-UUO, MSC+ACEi treated- UUO. Data were collected at 1, 7, 21 days. UUO induced monocyte renal infiltration, tubular cell apoptosis, tubular atrophy, interstitial fibrosis and overexpression of TGFβ, Renin mRNA (RENmRNA), increase of Renin, Angiotensin II (AII) and aldosterone serum levels. Both lisinopril (ACEi) and MSC treatment prevented monocyte infiltration, reduced tubular cell apoptosis, renal fibrosis and TGFβ expression. Combined therapy provided a further suppression of monocyte infiltration and tubular injury. Lisinopril alone caused a rebound activation of Renin-Angiotensin System (RAS), while MSC suppressed RENmRNA and Renin synthesis and induced a decrease of AII and aldosterone serum levels. Furthermore, in in-vitro and in-vivo experiments, MSC inhibit Human antigen R (HuR) trascription, an enhancer of RENmRNA stability by IL10 release. In conclusion, we demonstrate that in UUO MSC prevent fibrosis, by decreasing HuR-dependent RENmRNA stability. Our findings give a clue to understand the molecular mechanism through which MSC may prevent fibrosis in a wide and heterogeneous number of diseases that share RAS activation as common upstream pathogenic mechanism. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs), defined as CD4 + CD25 + highFoxP3 + CD127 − cells, could promote tolerance in renal transplantation (Tx). In an open-label, randomized, controlled trial 62 de-novo Tx recipients received induction with basiliximab and cyclosporine A (CsA) for the first month after Tx and then were assigned to treatment with sirolimus (SRL) or CsA and followed up for 2 years. The primary endpoint was to evaluate the effects of induction and maintenance treatments on circulating Tregs, while the secondary endpoint was the assessment of Treg renal infiltration and the relationship between Treg count and clinical outcomes. There were no significant differences in either circulating or tissue Treg number between the two groups. At 1 month post-Tx, all patients presented a profound Treg depletion, followed by a significant increase in Tregs that resulted stable during the follow-up. The same trend was also observed for non-activated Tregs (CD69 −) and for other immunocompetent cells (CD4 + and CD8 + T cells, B cells and NK cells). Moreover, the Treg count did not correlate either with renal function or with acute rejection and graft loss. Initial immunosuppression is crucial to regulate circulating Tregs, regardless of subsequent immunosuppressive maintenance regimens. Strategies aiming to promote tolerance should consider the effects of different induction regimens. [ABSTRACT FROM AUTHOR]

Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms ( C ortinarius speciosissimus, C . orellanus, C . orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little-known intoxication. [ABSTRACT FROM AUTHOR]

Costimulatory pathways play a key role in immunity, providing the second signal required for a full activation of adaptive immune response. Different costimulatory families (CD28, TNF-related, adhesion and TIM molecules), characterized by structural and functional analogies, have been described. Costimulatory molecules modulate T cell activation, B cell function, Ig production, cytokine release and many other processes, including atherosclerosis. Patients suffering from renal diseases present significant alterations of the costimulatory pathways, which might make them particularly liable to infections. These alterations are further pronounced in patients undergoing kidney transplantation. In these patients, different costimulatory patterns have been related to distinct clinical features. The importance that costimulation has gained during the last years has led to development of several pharmacological approaches to modulate this critical step in the immune activation. Different drugs, mainly monoclonal antibodies targeting various costimulatory molecules (i.e. anti-CD80, CTLA-4 fusion proteins, anti-CD154, anti-CD40, etc.) were designed and tested in both experimental and clinical studies. The results of these studies highlighted some criticisms, but also some promising findings and now costimulatory blockade is considered a suitable strategy, with belatacept (a CTLA-4 fusion protein) being approved as the first costimulatory blocker for use in renal transplantation. In this review, we summarize the current knowledge on costimulatory pathways in the setting of kidney transplantation. We describe the principal costimulatory molecule families, their role and clinical significance in patients undergoing renal transplantation and the new therapeutic approaches that have been developed to modulate the costimulatory pathways. [ABSTRACT FROM AUTHOR]

Background Knowledge on anaemia management in non-dialysis chronic kidney disease (ND-CKD) patients regularly followed in renal clinics is scarce although being essential to identifying areas of therapeutic improvement. Methods We prospectively evaluated anaemia management in two visits, performed 6 months apart, in 755 prevalent ND-CKD stage 3b-5 patients followed in 19 nephrology clinics from ≥6 months. Anaemia was defined as severe (Hb <11 g/dL) or mild (Hb: 11–13.5 in males and 11–12 g/dL in females); iron deficiency (ID) was defined as transferrin saturation (TSAT) <20% and/or ferritin <100 ng/mL. Primary endpoint was the change of anaemia and ID prevalence between baseline and 6-month visit. Secondary endpoint was the prevalence of clinical inertia to either ESA or iron supplementation, that is, the lack of ESA or iron prescription despite Hb <11 g/dL or ID. Results Age was 69 ± 13 years and GFR 27.5 ± 10.0 mL/min/1.73 m2; male gender, diabetes and prior cardiovascular disease were 57.2, 30.1 and 30.1%, respectively. Prevalence of severe and mild anaemia was 18.0 and 44.0% at baseline and remained unchanged at Month 6 (19.3 and 43.2%). ID was prevalent at both visits (60.1 and 60.9%). Clinical inertia to ESA was similar at baseline and at Month 6 (39.6 and 34.2%, respectively, P = 0.487) and it was less frequent than clinical inertia to iron therapy (75.7 and 72.0%, respectively). Conclusions This study shows that anaemia prevalence is unexpectedly high in the setting of tertiary nephrology care. This was due to a persistent clinical inertia in the anaemia management, remarkable for iron supplementation and less critical, but still significant, for ESA treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Acute kidney injury (AKI) is associated with a high mortality and morbidity rate. In this study we investigated whether dialysis membranes influence the recovery of renal function, through the regulation of hepatocyte growth factor (HGF). Design and methods: 21 patients were enrolled and assigned to hemodialysis (HD) with cellulose (CE, N =11) versus polymethylacrylate (PMMA, N =10) membranes in alternating order. HGF and IL-1 were measured in serum and in peripheral blood mononuclear cells (PBMC) supernatants collected immediately before the first HD session (T0), at 15minutes (T15), at 240minutes (T240) and after the last HD, when renal recovery occurred. Eight healthy volunteers were the controls (CON). Results: Time to renal function recovery was lower in CE than in PMMA patients. Serum HGF in HD patients was significantly higher than in CON. HGF levels were higher in CE than in PMMA patients at T15 (13.4±2.7 vs 8.9±3.0ng/mL, P =0.004) and T240. At recovery, HGF levels decreased. IL-1 serum levels showed a similar trend (at T15 CE: 20.5±2.9 vs PMMA: 16.9±3.2pg/mL, P =0.005). HGF release significantly increased in the course of HD, resulting in higher levels in CE than that in PMMA patients. Considering all the patients, basal HGF release negatively correlated with time to renal recovery (r2=0.42, P <0.01). Conclusions: Here we demonstrated that dialysis membranes influence the cytokine profile in AKI patients, HGF release being higher in patients treated with the CE membrane, in comparison to PMMA. Our results suggest that treatment with CE might improve clinical outcomes, possibly through increased release of HGF. [Copyright &y& Elsevier]

Background. Some difficult cases of idiopathic nephrotic syndrome (NS) have been treated with a HIV protease inhibitor provided with proteasome-inhibiting activity. The objective of this study was to limit nuclear factor κB (NF-κB) activation which is up-regulated in these patients, aiming at decreasing proteinuria and prednisone need. Methods. Ten cases with long-lasting (up to 15 years) history of NS with steroid dependence (six cases, of which three with secondary steroid resistance) or resistance to steroids (four cases) unsuccessfully treated with multiple immunosuppressive drugs, accepted a treatment with the protease inhibitor saquinavir. p50/p65 NF-κB nuclear localization and immunoproteasome/proteasome messenger RNA (mRNA) were monitored in peripheral blood mononuclear cells (PBMCs). The effects of saquinavir on NF-κB nuclear localization in cultured PBMCs and in immortalized human podocytes were assessed. Results. After a median follow-up of 14.7 months (6–68.7), 1/4 primary steroid-resistant NS (SRNS) and 5/6 steroid-dependent NS or secondary SRNS became infrequent (5) or frequent (1) relapsers, with 63% prednisone reduction (from 25.3 to 8.4 mg/kg/month, P = 0.015). Saquinavir was effective in association with low doses of calcineurin inhibitors (cyclosporine 2 mg/kg/day or tacrolimus 0.01–0.06 mg/kg/day). No side effects were observed apart from transitory mild diarrhoea. In PBMCs, NF-κB was down-regulated, while MECL-1 immunoproteasome/beta2 proteasome mRNA ratio was reversed to normal values. In culture, saquinavir blunted NF-κB activation in human podocytes and in PBMCs. Conclusions. In this pilot study, a HIV antiprotease drug reduced proteinuria and had a steroid-sparing effect in some multidrug-resistant/-dependent NS. This observation warrants further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative response and inflammation constitute a major defense against infections, but if not properly regulated they could also lead to a number of deleterious effects. Patients affected by different stages of acute and chronic kidney disease, particularly patients on hemodialysis, present a marked activation of oxidative and inflammatory processes. This condition exposes these patients to an elevated risk of morbidity and mortality. This Review is up to date and it analyses the newest notions about pathophysiological mechanisms of oxidative stress and inflammation in patients with renal diseases, also considering the different strategies studied to counterbalance this high risk state. [Copyright &y& Elsevier]

Hyponatremia is a marker of different underlying diseases and it can be a cause of morbidity itself; this implies the importance of a correct approach to the problem. The syndrome of inappropriate antidiuresis (SIAD) is one of the most common causes of hyponatremia: it is a disorder of sodium and water balance characterized by urinary dilution impairment and hypotonic hyponatremia, in the absence of renal disease or any identifiable non-osmotic stimulus able to induce antidiuretic hormone (ADH) release; according to its definition, it is diagnosed through an exclusion algorithm. SIAD is usually observed in hospitalized patients and its prevalence may be as high as 35%. The understanding of the syndrome has notably evolved over the last years, as reflected by the significant change in the name, once the syndrome of inappropriate secretion of ADH (SIADH), today SIAD. This review is up to date and it analyses the newest notions about pathophysiological mechanisms, classification, management and therapy of SIAD, including vaptans. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Dialysis treatment and regulatory T cells" by T. K. Hendrikx and colleagues in the February 17, 2010 issue is presented.

The article describes the case of Tenckhoff catheter obstruction in a 37-year-old woman with kidney failure secondary to nephronophthisis on continuous ambulatory peritoneal dialysis. Topics covered include presentation of impaired dialysate drainage and constipation after one month of dialysis and the need to consider tubaric fimbriae entrapment in female patients with a malfunctioning peritoneal dialysis catheter.

In order to present an antigen to T-cells, the antigen must first be degraded by proteasomes. Following exposure to interferons, some proteasome subunits (ß1,ß2,ß5) are replaced by others (LMP2, LMP7, MECL-1) that have more optimal catalytic properties for peptide presentation; this more efficient organelle is termed the immuno-proteasome. Here we measured gene expression of various subunits in peripheral mononuclear cells of patients with IgA nephropathy, a disease with features of immune dysregulation. We used quantitative PCR to measure the expression of proteasomal subunit mRNA in mononuclear cells from IgA nephropathy patients, a group of proteinuric control patients with idiopathic nephrotic syndromes, and healthy controls. A significant switch in the expression of trypsin- and chymotrypsin-like proteasome subunits to corresponding immuno-proteasome subunits was found in patients as compared to healthy controls. Further, we found that nuclear translocation of NF-κB p50 and p65 was significantly greater in the IgA nephropathy patients, but this did not correlate with the switch to the immuno-proteasome phenotype. Patients with proteinuria greater than 0.5 g/1.73 m2/day had a significant switch of the chymotryptic-like β5 protease to the LMP7 subunit, but this did not occur in patients with idiopathic nephrotic syndrome. The switch to an immuno-proteasome in peripheral blood mononuclear cells of patients with IgA nephropathy suggests an increased efficiency of antigen processing and presentation. This switch appears to be independent of a coincidental activation of the NF-κB pathway but is associated with high levels of proteinuria, a well known risk factor for progression of IgA nephropathy.Kidney International (2009) 75, 536–541; doi:10.1038/ki.2008.579; published online 26 November 2008 [ABSTRACT FROM AUTHOR]

Background: Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) is a nuclear receptor that regulates the transcription of genes associated with lipid and glucose metabolism. Recently, it has been shown that PPAR-γ modulates the activity of T cells, resulting in inhibition of T cell proliferation and IL-2 release. In this study we investigated whether the PPAR-γ ligand rosiglitazone (R) enhances in vitro the immunosuppressive effects of cyclosponne A (C5A). Methods: CD4+ T cells isolated from peripheral blood mononuclear cells of healthy donors were activated either with mitogens or by one-way mixed lymphocyte reaction. The activated T cells were treated with (I) CsA at low and high concentration (50, 150 nglml); (2) R (20 μM); (3) R (20 μM) in combination with CsA at low concentration (50 nglml). We studied the effects of the various treatments on cell proliferation (incorporation of [3H] thymidine), the cell-cycle phases (FACS analysis), IL-2 release (ELISA), and IL-2 receptor (CD25) expression (FACS analysis). Results: R used alone reduced T cell proliferation and CD25 expression. Low-dose CsA combined with R was significantly more powerful than either high-dose CsA alone or R alone in suppressing IL-2 release, arresting the T cell cycle, and blocking the growth of activated T cells. Conclusion: PPAR-γ ligand R potentiates in vitro the inhibitory action of CsA on activated T helper cells. The combined use of PPAR-γ ligands and low-dose CsA represents a rationale therapeutic approach aimed to prevent CsA nephrotoxicity while maintaining adequate immunosuppression. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli.Background.The imbalance between synthesis and degradation of mesangial matrix causes glomerulosclerosis and leads to renal failure. Hepatocyte growth factor (HGF) has been shown to reduce the progression in murine models of chronic renal failure. The present study evaluated the effect of HGF on the extracellular matrix turnover and on c-met receptor in human glomeruli.Methods.Human glomeruli microdissected from donor kidney biopsies before transplantation were incubated with culture media containing HGF (50 ng/mL). After 24 and 48 hours, the expression of c-met, (α2) IV collagen, transforming growth factor-β (TGF-β), metalloprotease (MMP) 2 and 9 and of the inhibitor of MMP-2, tissue inhibitors of metalloprotease-1 (TIMP-1), was evaluated by polymerase chain reaction (PCR).β-actin was used as housekeeping gene. The production of collagen type IV and TGF-β was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting and the activity of MMP by zymography.Results.(α2) IV collagen, TGF-β, and TIMP-1 mRNA levels were markedly decreased in glomeruli treated with HGF at 24 and 48 hours. The expression of c-met was up-regulated by HGF treatment. HGF reduced the production of collagen type IV and TGF-β. MMP-2 but not MMP-9 mRNA level was increased in HGF-treated glomeruli, although the gelatinolytic activity of the supernatant was not changed. By light microscopic examination kidney biopsies neither showed glomerular hypercellularity nor mesangial expansion.Conclusion.HGF reduced expression and synthesis of TGF-β and collagen type IV and increased MMP-2 mRNA level in normal human glomeruli. These results suggest an antifibrotic effect of HGF on glomerular cells and may explain its beneficial role in glomerulosclerosis. [ABSTRACT FROM AUTHOR]

Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC. Background. The changes induced on endothelial cells by a long-term exposure to high glucose, a situation that mimics the hyperglycemia of diabetics, have not yet been determined. We compared short- and long-term effects of elevated glucose on macrovascular and microvascular endothelial cells. Methods. Endothelial cells were grown in high-glucose media for 24 hours and for 8 weeks. Cell proliferation was evaluated by cell counting, apoptosis and expression of adhesion molecules by flow cytometry; nitric oxide (NO) by measuring the concentration of nitrite/nitrate in the cell supernatant; α2(IV) collagen mRNA and protein by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The adhesion of peripheral blood mononuclear cells (PBMCs) to endothelial cells was evaluated by adhesion assay. In some experiments, endothelial cells were preincubated with anti-vascular cell adhesion molecule-1 (VCAM-1) and anti-receptor for advanced glycation end product (RAGE) blocking antibodies. Results. At 24 hours, but not at 8 weeks, high glucose increased endothelial cell proliferation and apoptosis. High glucose did not modify NO synthesis at 24 hours and 8 weeks. Collagen production and expression were increased only after eight weeks. VCAM-1 but not intercellular adhesion molecule-1 was up-regulated after 8 weeks, a change not observed after 24 hours. The adhesion of PBMCs was significantly increased at eight weeks and was completely abrogated by anti–VCAM-1 and by anti-RAGE antibodies. After 24 hours, there was a modest increase of PBMC adhesion that was not blunted by anti-RAGE antibodies. Conclusions. Increased adhesion of PBMCs, caused by up-regulation of VCAM-1 with a mechanism involving advanced glycation end product (AGE) adducts, and augmented collagen deposition are critical effects of long-term high glucose on endothelial cells, and may eventually promote the atherosclerotic process. [ABSTRACT FROM AUTHOR]

Cyclosporine induces different responses in human epithelial, endothelial and fibroblast cell cultures. Background. Nephrotoxicity, accelerated atherosclerosis, and graft vascular disease are common complications of cyclosporine long-term treatment characterized by a wide disruption of organ architecture with increased interstitial areas and accumulation of extracellular matrix (ECM). How cyclosporine induces these changes is not clear, but it is conceivable that they are the sum of changes induced at the cell level. Methods. We studied the effects of cyclosporine on human endothelial (HEC), epithelial (HK-2), and fibroblast (MRC5) cells. Cell proliferation was evaluated by cell counting, apoptosis and collagen production by enzyme-linked immunosorbent assay, and nitric oxide by measuring the concentration of nitrite/nitrate in the cell supernatant. (α1)I and (α2)IV collagen, matrix metalloprotease-9 (MMP9), and tissue inhibitors of metalloprotease-1 (TIMP-1) mRNA levels were measured by reverse transcription-polymerase chain reaction. Proteolytic activity was evaluated by zymography. Results. Cyclosporine showed a marked antiproliferative and proapoptotic effect on endothelial and epithelial cells. Fibroblast growth was not affected by cyclosporine. Nitric oxide was up-regulated by cyclosporine in epithelial cells and fibroblasts but not in endothelial cells. (α1)I and (α2)IV collagen synthesis was increased in cyclosporine-treated endothelial and epithelial cells, respectively. Proteolytic activity was increased in endothelial and epithelial cells. TIMP-1 mRNA was up-regulated by cyclosporine in fibroblasts. Conclusions. Our results demonstrate that cyclosporine exhibits an antiproliferative effect on endothelial and epithelial cells. This effect is associated with induction of apoptosis probably via nitric oxide up-regulation in epithelial cell cultures. Cyclosporine treatment induces ECM accumulation by increasing collagen synthesis in... [ABSTRACT FROM AUTHOR]

Hemodialysis prevents liver disease caused by hepatitis C virus: Role of hepatocyte growth factor. Background. Hemodialysis increases markedly the serum levels of hepatocyte growth factor (HGF) so that regular dialysis treatment (RDT) mimics the regular administration of HGF as a drug. Therefore, we have studied the effects of dialysis-associated HGF production on the severity of liver damage caused by hepatitis C virus (HCV). Methods. Biochemical tests of liver function and liver biopsy were performed in 10 patients on RDT and in 11 patients without renal disease (WRD) converted to anti-HCV serum-positive test for the same time (48 ± 4 months). The HGF serum concentration was measured by enzyme immunoassay. In patients on RDT, HGF was measured just before starting a dialysis session (T0), at 15 and 240 minutes of dialysis (T15 and T240), and 24 hours later (T24 hr). Results. Serum HGF was similar in WRD (average 0.17 ng/ml) as in RDT at T0 (0.25 ng/ml). In RDT serum HGF increased markedly at T15 and T240 (5.51 and 2.67 ng/ml, respectively, P < 0.001 vs. WRD and T0) and was still higher than baseline at T24 hr (0.41 ng/ml, P < 0.05). Both grade of necroinflammatory activity and stage of fibrosis were significantly lower in RDT than in WRD (both, P < 0.001). The number of apoptotic hepatocytes was also significantly reduced in patients on RDT compared with patients WRD. Conclusion. These results show that HCV-related liver disease is more benign in patients on RDT. The phenomenon may depend on the marked and prolonged HGF release caused by dialysis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 47-year-old man having a history of idiopathic myelofibrosis associated with jaundice and hepato-splenomegaly was admitted for ascites and asthenia. Blood tests revealed acute kidney injury (AKI) and a marked increase in bilirubin levels. Plasma bilirubin decreased progressively and serum creatinine levels after four cycles of plasma absorption perfusion (PAP).

A letter to the editor is presented in response to the article "Standard Hemodiafiltration Improves Diuretic Responsiveness in Advanced Congestive Heart Failure," by Carmelo Libetta, Vincenzo Sepe, Manuela Zucchi, Carlo Campana, and Antonio Dal Canton in the December 15, 2005 issue.

Presents a letter to the editor commenting on an article published in the periodical "Kidney International," concerning the association between C-reactive protein and risk of acute coronary events in patients with coronary heart disease.

The article reports that tumor infiltration by lymphocytes must be included in the differential diagnosis of acute renal failure in patients with chronic lymphocytic leukemia focusing on the treatment provided to patient who was admitted with severe renal failure and abnormal growth of kidneys.

Examines the effects of percutaneous renal embolization in renovascular hypertension in Italy. Usage of renal embolization for the treatment of severe hypertension on patients receiving hemodialysis; Clinical characteristics of patients with renovascular hypertension; Effectivity of renal embolization for the treatment of renovascular hypertension.

Examines the prevalence of symptoms in patients with simple renal cysts. Assumptions on the possible cause of hypertension; Definition of simple renal cysts; Use of ultrasonography in diagnosing renal cysts.

Early allograft calcifications after kidney transplantation (KT) have already been reported, but the clinical implications of this finding are not clear thus far. Patient-related factors such as age, gender, underlying renal disease, and dialytic modality, seem to be irrelevant. It has been postulated that factors promoting the development of metastatic calcifications, including elevated calcium phosphate product and severe secondary hyperparathyroidism, could play a causal role. Here we report a case of a KT patient who developed early kidney calcifications which were associated with severe allograft dysfunction. [ABSTRACT FROM AUTHOR]

A correction to the article "Peritonitis in type 2 diabetes mellitus due to Ochrobactrum anthropi complicating automated peritoneal dialysis" is presented.

A letter to the editor is presented in response to the article "Efficacy of folic acid supplementation in stroke prevention: a meta-analysis," by X. Wang and X. Qin et al. in the June 2, 2007 issue.

A correction to the article "Prevention of dialysis hypotension episodes using fuzzy logic control system" that was published in a previous issue is presented.

Presents a letter to the editor about the effectiveness of mycophenolate mofetil in immunoglobulin A nephropathy.

Discusses the inhibitory effect of homocysteine on angiogenesis. Upregulation of the vascular endothelial growth factor receptor (VEGFR) on human atherosclerotic plaques; Association of homocysteine to VEGFR serum levels; Consistency of the inverse association of serum homocysteine with circulating VEGFR.

Studies the prevalence of hyperhomocysteinemia in male hemodialysis patients. Risk factors for vascular disease in hemodialysis patients; Influence of sex on the prevalence of conventional risk factors; Dialysis and ration of urea clearance.

Discusses the correlation between hyperhomocysteinemia and interleukin-18 serum levels in maintenance hemodialyzed patients. Testing of total homocysteine by high-performance liquid chromatography with fluorometric detection; Analysis of interleukin-18 using a commercial enzyme-linked immunosorbent assay kit.