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Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome—coronavirus-2 (SARS-CoV-2)—is an ongoing pandemic with high morbidity and mortality rates. Preliminary evidence suggests that acute kidney injury (AKI) is uncommon in patients with COVID-19 and associated with poor outcomes. Study aims and design: we performed a systematic review of the literature with a meta-analysis of clinical studies to evaluate the frequency of AKI and dialysis requirement in patients who underwent hospitalization due to COVID-19. The incidence of AKI according to the death risk was calculated in these patients. The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. Results: thirty-nine clinical studies (n = 25,566 unique patients) were retrieved. The pooled incidence of AKI was 0.154 (95% CI, 0.107; 0.201; p < 0.0001) across the studies. Significant heterogeneity was found (p = 0.0001). The overall frequency of COVID-19-positive patients who underwent renal replacement therapy (RRT) was 0.043 (95% CI, 0.031; 0.055; p < 0.0001); no publication bias was found (Egger’s test, p = 0.11). The pooled estimate of AKI incidence in patients with severe COVID-19 was 0.53 (95% CI, 0.427; 0.633) and heterogeneity occurred (Q = 621.08, I2 = 97.26, p = 0.0001). According to our meta-regression, age (p < 0.007) and arterial hypertension (p < 0.001) were associated with AKI occurrence in hospitalized COVID-19 positive patients. The odds ratio (OR) for the incidence of AKI in deceased COVID-19 positive patients was greater than among survivors, 15.4 (95% CI, 20.99; 11.4; p < 0.001). Conclusions: AKI is a common complication in hospitalized COVID-19 positive patients. Additional studies are under way to assess the risk of AKI in COVID-19 patients and to deepen the mechanisms of kidney injury.

Chronic kidney disease (CKD) is an important problem in public health and has significant morbidity and mortality implications. Mineral and bone disorders are common during CKD and occur in the early stages of the disease. During CKD a progressive reduction of the excretion of many substances, including phosphorus, is reported. The phosphorus balance is altered from the early stages of disease, and its variation has been related both to mineral bone disorders and cardiovascular disease. Of note, phosphate levels, which are frequently high in late stages of CKD, do not represent the total phosphate balance, which is influenced also by dietary phosphate intake, intestinal absorption and renal excretion.Correct phosphate control in CKD patients can be obtained by operating at different levels: 1) optimization of dialysis: type of dialysis (hemodialysis versus peritoneal dialysis), vascular access characteristics, modalities and duration of dialysis; 2) reduction of dietary phosphate intake, obtained by the c...

Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal complications.

Autosomal dominant polycystic kidney disease (ADPKD) is the first genetic cause of end-stage renal disease (ESRD) and the number of these patients who are listed for or receive a kidney transplant (KTx) is continuously increasing over time. Hence, nephrologists are involved not only in the handling of ADPKD patients during the long course of the disease, but also in programming and performing a renal transplant. The handling of all these processes implies the complete awareness of a number of critical points related to the decisions to be taken both before and after the transplant intervention. In the present review, we will briefly deal with the main critical points related to the clinical handling of the patients both before and after KTx.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic disorder of the kidney and accounts for over 95% of all cystic diseases involving loss of kidney function. The diagnosis of ADPKD is confirmed by mutational analysis of PKD1 and PKD2 genes, which is complex, because of the significant allelic heterogeneity and the presence of six pseudogenes presenting highly homologous sequences with an extended region of the PKD1 gene (exons 1–33). The aim of this study was to develop a rapid and reliable method for the molecular diagnosis of ADPKD using the technology of Next Generation Sequencing (NGS), that could be used for a diagnostic purpose. We first validated the test on two cohorts of ADPKD patients previously characterized by traditional Sanger sequencing method; then we analyzed a cohort of 58 patients not characterized and we achieved a mutation detection rate of 84.7%.

The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4 – 5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group ( n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients undergoing HCV treatment, particularly for chronic kidney disease patients who have a heavy burden of comorbidities.

Background:Indications to repeat renal biopsy (RB) in lupus nephritis (LN) are not unanimously acknowledged.Objectives:To evaluate the renal outcome of patients with LN undergoing a second RB.Methods:We retrospectively analyzed prospectively collected data of patients with LN followed up in four Italian referral centres for systemic lupus eryhtematosus. Serological and clinical information were retrieved according to a shared database. RB were classified according to ISN/RPS 2003 classification; chronicity (CI) and activity indexes (AI) were defined according to Austin et al. The primary renal outcome was renal failure, defined as serum creatinine (SCr)>1.0mg/dL with eGFRResults:Four-hundred and thirty-eight patients were recruited. One-hundred and three patients repeated RB after 6.1±4.7 (mean± SD) years from the first due to: protocol biopsy due to renal remission (Group 1, n=8); proteinuric flare (Group 2, n=51); worsened renal function (Group 3, n=26); partial renal response (Group 4 n=18). Patients undergoing a second RB were younger (pConclusion:Patients undergoing a repeated RB had more aggressive clinical and histological features already at first RB and developed renal failure more frequently. Among baseline features, uncontrolled hypertension had the strongest association with renal failure, thus suggesting that control of blood pressure since early stages is highly advisable.References:[1]Austin HA, et al. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int 1994;45:544–50.Table .Comparison of patients undergoing 2nd RB according to development of renal failureRenal failure (n=26)No renal failure (n=69)*pTotal FU (years), mean (SD)21 (10.4)16.5 (9.39)0.002SCr (mg/dl) at 2° RB, mean (SD)1.7 (1)0.98 (0.35)0.001Proteinuria (g/24h) at 2° RB, mean (SD)4.7 (3.9)2.99 (2.63)0.022Class IV and IV+V at 2° RB, %76.954.50.07Hypertension at onset, %84.632.4HCQ intake at 2° RB, %9.552Glucocorticoids at 2° RB %8487nsImmunosuppressants at 2° RB %4058nsAI at onset, mean (SD)7.14 (3.95)7.02 (3.86)nsAI at 2° RB, mean (SD)5.37 (4.12)4.02 (3.71)nsCI at onset, mean (SD)2.05 (1.88)1.56 (1.64)nsCI at 2° RB, mean (SD)3.87 (3.08)3.52 (2.16)nsYears between 2° RB and end of FU, mean (SD)14.1 (10.5)9.3 (8.84)ns*Group 1 excludedRB, renal biopsy; AI, activity index; CI, chronicity index; SCr serum creatinine; FU, follow-up; SD, standard deviation.Disclosure of Interests:Mariele Gatto Speakers bureau: GSK, Francesca Saccon: None declared, Francesca Radice: None declared, Paolo Gilles Vercelloni: None declared, Renato Alberto Sinico: None declared, Giulia Frontini: None declared, Valentina Binda: None declared, Piergiorgio Messa: None declared, Federico Alberici: None declared, Gabriella Moroni: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies and a variable spectrum of clinical manifestations and disease severity. The 2019 criteria for SLE classification by the American College of Rheumatology and European League against Rheumatism define ANA positivity by immunofluorescence or by an equivalent solid-phase assay as the entry criterion (1). However, the prevalence of ANA positivity and the reliability of solid-phase assays in SLE are still a matter of controversy (2). Furthermore, the significance of ANA negativisation during follow-up is uncertain (3).Objectives:Our aim was to retrospectively analyse data on the frequency of ANA seroconversion during the follow-up in a cohort of SLE patients with renal involvement.Methods:Adult patients independent of age at SLE onset with a follow-up duration of at least 36 months starting from January 2009 (for standardization of ANA measurement) and with at least one ANA measurement per year were included in this retrospective longitudinal study. Data on demographic, clinical and laboratory characteristics of the study population are reported in table 1. ANA have been measured with Hep2 cell immunofluorescence assay.Table 1.Demographic, clinical and laboratory baseline characteristics of the 121 patients suffering from systemic lupus erythematosus (SLE).DemographicsGender,%F (n)93 (112)Age in years,mean±SD41.6±12.6Clinical featuresAge at SLE onset in years,mean±SD28.0±11.9SLE duration in years,mean±SD13.8±9.5SLEDAI,median (min-max)4 (0 – 27)Laboratory profileSerum creatinine mg/dL,median (min-max)0.8 (0.4 – 2)24h urine protein g/24h,median (min-max)0.5 (0 – 13.8)ANA,%pos (n)93 (112)Anti-ENA,%pos (n)49 (59)Anti-dsDNA,%pos (n)43 (51)Results:A total of 121 SLE subjects with renal involvement were enrolled. Mean follow-up ± standard deviation (SD) was 8 ± 2 years. Ten subjects (8.3%) with positive ANA at the beginning resulted ANA negative at the end of the follow-up. These subjects had different initial ANA titres: 1:1280 (n=1), 1:640 (n=2), 1:320 (n=2), 1:160 (n=3) and 1:80 (n=2); 48 subjects (39.7%) showed a decrease in ANA titre. Of the 9 patients (7.4%) that were negative at the beginning of follow-up, 6 remained negative, whereas 3 showed ANA positivity at the end of the follow-up with ANA titres 1:160 (n=2) and 1:320 (n=1). No differences between subjects with and without ANA titre variations in terms of age (p=0.551), disease duration (p=0.786), SLEDAI at the beginning (p=0.453) and at the end of follow-up (p=0.169) were observed. ANA negativisation and titre variations at the end of follow-up did not correlate with any of the treatments taken during follow-up, including a history of cyclophosphamide (p=0.788).Conclusion:In our cohort of patients with SLE and renal involvement, 10% of patients experienced negativisation and around 40% of patients showed a decrease in ANA titre during follow-up, independent of disease characteristics and previous treatment. Further studies are warranted to clarify the underlying mechanisms and clinical significance of ANA seroconversion and titre variation in SLE patients. However, based on our results, ANA positivity seems to be a relatively stable parameter further supporting its use as an entry classification criterion for SLE.References:[1]Aringer M et al. Arthritis Rheumatol. 2019; 71(9):1400-1412.[2]Pisetsky DS et al. Autoimmun Rev. 2019; 18(12):102400.[3]Frodlund M et al. Clin Exp Immunol. 2019. Epub ahead of print.Disclosure of Interests:None declared

The originally published article the co-author name Marco Heidempergher incorrectly spelled as Marco Hedemperger. The correct name given below.

Objective The efficacy of rituximab (RTX) in systemic lupus erythematosus (SLE) is a subject of debate. This study was undertaken to investigate the outcomes of RTX treatment in a European SLE cohort, with an emphasis on the role of RTX as a maintenance agent. Methods All patients with SLE who were receiving RTX as induction therapy in 4 centers were included. Patients who received a single course of RTX and those who received RTX maintenance treatment (RMT) were followed up after treatment. Disease flares during the follow-up period were defined as an increase in disease activity and the number or dose of immunosuppressive drugs. Results Of 147 patients, 27% experienced treatment failure at 6 months. In a multivariate analysis, a low number of previous immunosuppressive therapies (P = 0.034) and low C4 levels (P = 0.008) reduced the risk of treatment failure. Eighty patients received RMT over a median of 24.5 months during which 85 relapses, mainly musculoskeletal, were recorded (1.06 per patient). At the time of the last RTX course, 84% of the patients were in remission. Twenty-eight (35%) of 80 patients never experienced a flare during RMT and had low damage accrual. Active articular disease at the time of the first RTX administration was associated with a risk of flare during RMT (P = 0.011). After RMT, relapse-free survival was similar to that in patients receiving a single RTX course (P = 0.72). Conclusion RMT is a potential treatment option for patients with difficult-to-treat disease. Relapses occur during RMT and are more likely in those with active articular disease at the time of the first RTX administration. Relapse risk after RMT remains high and apparently comparable to that seen after a single RTX course.

Secondary hyperparathyroidism (SHP) is a frequent complication of kidney diseases. At variance with all the other forms of SHP, which are compensatory conditions, renal SHP has many pathogenetic peculiarities, which have been only in part defined. Furthermore, in the long course of chronic kidney diseases (CKD), SHP sometimes transforms into a hypercalcemic condition resembling the autonomous form of hyperparathyroidism (tertiary hyperparathyroidism; THP). The clinical consequences of SHP in CKD patients are manifold, encompassing not only bone and mineral disorders, but also other metabolic and organic changes which frequently burden these patients. Although the medical therapeutic tools have substantially increased in number and improved in their efficacy in recent decades, we have as yet no demonstration of a clear benefit regarding the major clinical outcomes. Furthermore, some of these patients, particularly when the autonomous THP develops, still require a surgical approach.

Background/Aims: Uremic patients experience premature vascular ageing that causes cardiovascular morbidity. In this study, we investigated the relationship between uremic serum calcific potential induced by high phosphate (Pi) and vascular calcification score (VCS). Methods: Vascular smooth muscle cells (VSMCs) were cultured with 3.5 mM Na3PO4 (Pi) with 10% uremic serum and calcium deposition, markers of osteoblastic transformation, and apoptosis were evaluated. Results: Culture with uremic serum and high-Pi significantly induced calcification (0.21 ± 0.03 vs. 8.05 ± 0.6; ctr vs. Pi; OD/mg protein; p < 0.01). We next stratified patients with respect of the degree of VCS in 2 groups: absence of vascular calcification (VC) “no VC group” and presence of VC “VC group”. We found that there was a significant correlation between VCS and uremic serum calcific potential induced by high Pi in vitro (p < 0.01). Interestingly, uremic sera of the “VC group” were more effective than sera from the “no VC group”, in downregulating α-actin and SM22α, after treatment with high-Pi (41.3 ± 4.7 vs. 23.3 ± 2.9 and 25.6 ± 6.8 vs. 8.14 ± 2.3; VC vs. no VC group, α-actin and SM22α respectively; Δ intensity area; p < 0.01). Similarly, sera from “VC group” were more effective than sera from “no VC group” in adjuvanting the high-Pi effect of increasing osteoblastic markers, such as bone morphogenic protein 2 (BMP2), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2; 39.1 ± 11.3 vs. 5.0 ± 2.6 BMP2; 12.2 ± 4.2 vs. 1.7 ± 0.3 OC; 2.9 ± 0.4 vs. 1.2 ± 0.2 RUNX2; VC vs. no VC group respectively; p < 0.05). We found a similar pattern with significantly higher apoptosis and necrosis induction by sera from the “VC group” compared to the “no VC group” (2.05 ± 0.33 vs. 1.29 ± 0.13 and 54.1 ± 19.5 vs. 27.4 ± 10.6; Pi; VC group vs. no VC group; enrichment factor of apoptotic or necrotic fragments, respectively; p < 0.05). Conclusions: We conclude that VCS of end-stage renal disease patients significantly correlates with serum-calcific potential induced by high Pi. In addition, uremic patients with higher VCS have sera with a higher potential to induce VSMC osteoblastic trans-differentiation, apoptosis, and necrosis.

INTRODUCTION Hepatitis C virus (HCV) infection leads to important morbidity and mortality through liver disease and extra-hepatic manifestations. Recent evidence suggests the role of HCV in developing chronic kidney disease (CKD); also, HCV adversely affects cardiovascular (CV) disease both in the general population and in patients with CKD. Areas covered: All-oral, interferon-free direct-acting antiviral agents (DAAs) are currently available; anti-HCV regimens based on DAAs are provided with high efficacy and safety and short treatment duration. However, some difficult-to-treat populations still exist including patients with CKD and those who failed previous DAA regimen. Expert commentary: Two DAAs regimens (elbasvir/grazoprevir and glecaprevir/pibrentasvir) are now recommended for the treatment of HCV in patients with advanced CKD, these combinations have shown great efficacy, according to two multicenter phase-3 trials (C-SURFER and EXPEDITION-4). These trials reported a minimal impact of baseline resistance-associated substitutions (RASs) on treatment outcomes. The sofosbuvir/velpatasvir/voxaliprevir combination has been recommended as the first-line option for DAAs failures, on the basis of the results given by two randomized clinical trials involving patients who had been previously received DAA-containing regimens (POLARIS 1-4 studies). It has been suggested that clinicians should consider RASs upon the introduction of DAA-based antiviral therapy.

Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21-18% and 25%, moderate in 22-30% and 26% and severe in 30-18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD-. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.

IntroductionPrimary membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The disease may have different long-term outcomes. After 10 years of follow-up, 35%–50% of the untreated patients with persistent nephrotic syndrome may die or progress to end stage renal disease. The 2012 KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend that initial therapy should consist of alternating steroids and an alkylating agent for 6 months. Recent observational studies showed that the anti-CD20 antibody rituximab may be effective in inducing remission. We designed a pilot multicentre randomised trial to inform the design of a larger trial testing the efficacy and safety of treatment with steroids and cyclophosphamide versus rituximab in patients with primary MN and heavy proteinuria (>3.5 g/24 hours).Methods and analysisThis pilot, open-label, two-parallel-arm, randomised clinical trial will enrol 70 patients with primary MN and heavy proteinuria. Patients will be randomised in a 1:1 ratio to either the intervention arm (rituximab) or the active comparator arm (corticosteroid/alkylating-agent therapy). The study will provide estimates of the probability of complete remission of proteinuria and risk of serious side effects at 12 months to inform the design of a larger trial. We will also assess the recruitment potential of each participating centre to address study feasibility.Ethics and disseminationThe trial received ethics approval from the local ethics boards. We will publish pilot data to inform the design of a larger clinical trial.Trial registration numbersNCT03018535; 2011-006115-59.

Secondary hyperparathyroidism (SHPT) is a frequent condition in the presence of chronic kidney disease (CKD). In CKD patients, SHPT is reported to increase both morbidity and mortality, especially cardiovascular. The difficulty in the treatment of SHPT in clinical practice is frequently encountered from a not always adequate conduct of the clinicians and a common non-compliance to the therapy of CKD patients. In this review, the greatest difficulties from clinicians and CKD-patients’ point of view in the treatment of SHPT will be addressed, with particular attention to those related to dialysis features, nutritional habits, and medical therapy.

Background: The evidence in the medical literature on the treatment of hepatitis C virus–associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety. Aims: We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus–associated glomerular disease. Methods: In the first phase of the study, patients with hepatitis C virus–associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively). Results: We enrolled 25 consecutive patients with hepatitis C virus–associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA Conclusion: Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus–related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.

Hepatitis C virus (HCV) infection has an estimated prevalence of 3% in the world population and is still frequent among patients undergoing long-term dialysis all over the world. The Dialysis Outcomes and Practice Patterns Study (DOPPS) found that the frequency of patients with HCV in developed

Chronic renal failure (CRF) is a frequent condition in elderly subjects, and it is associated with psychiatric comorbidity, especially depressive symptoms. Purpose of the present research was to compare patients with different severity of chronic kidney disease (CKD) in terms of psychiatric symptoms. One hundred CKD subjects were randomly selected among those attending the Department of Nephrology, University of Milan. The patients were evaluated through the following rating scales: Mini-Mental State Examination (MMSE), Beck Depression Inventory (BDI), Symptom Checklist (SCL-90), Kidney Disease Quality of Life- Short Form (KDQOL-SF) and Cumulative Illness Rating Scale (CIRS). A multivariable linear regression analysis was performed considering eGFR as continuous-dependent variable and rating scale scores as independent variables. A worse eGFR significantly correlated with the score about the effects of kidney disease on daily life (r = 0.25, p = 0.01) and the burden of kidney disease (r = 0.18, p = 0.05). Statistical significance of kidney disease on daily life persisted also in the final multivariate model (t = 2.04, p = 0.04). Severity of renal dysfunction seems to influence few psychiatric outcomes, particularly those related to quality of life and daily functioning. This result might depend on the over-worrying derived from the necessity to start a renal replacement therapy in the near future.

INTRODUCTION AND AIMS: The efficacy of rituximab (RTX) in Systemic Lupus Erythematosus (SLE) is debated, and there is a lack of data on its role in relapse prevention. We describe our experience in a European cohort of SLE patients with an emphasis on RTX use as a maintenance agent. METHODS: All the patients with SLE receiving RTX across 7 centers were included. Disease activity was assessed by the ECLAM score. RTX maintenance treatment (RMT) was defined as at least 3 RTX cycles with an interval between administrations of 3-12 months. A negative response (NR) 6 months after the first RTX and a flare during the follow-up were defined as an increase of disease activity and immunesuppressors. The evolution of damage and severe adverse events (SAEs) were collected during follow-up. RESULTS: 148 patients were identified: at 6 months 39(27%) experienced a NR. 80 received RMT with a median duration of 24.5 months and a median overall dose of RTX of 6g. ECLAM reduced from 3.5 (mean, 95%CI 3.1-3.9) to 1.86 (95%CI 1.5-2.2) after the first RTX (p

Kidney disease has become an important co-morbidity among human immunodeficiency virus-infected patients as they live longer in the era of highly effective antiretroviral therapy. It remains unclear how co-infection with hepatitis C virus impacts on the trajectory of kidney disease among HIV-infected patients. To evaluate the effect of co-infection with HCV on the risk of kidney disease in HIV-infected populations. We conducted a systematic review of the published medical literature to determine if hepatitis C co-infection is associated with increased likelihood of chronic kidney disease in HIV-positive adults. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis C virus across the published studies. Meta-regression and stratified analysis were also conducted. We identified 19 studies (146,151 unique patients with HIV) and separate meta-analyses were performed according to the outcome. Aggregation of longitudinal studies (n = 8, 105,462 unique patients) showed a relationship between HCV infection and increased risk of reduced glomerular filtration rate among HIV-infected individuals, the summary estimate for adjusted hazard ratio was 1.64 (95%CI, 1.28; 2.0, P

Background Hepatitis C virus (HCV) outbreaks among patients on hemodialysis are still an important health concern all over the world. Aims We performed a systematic review of reports on HCV outbreaks within dialysis units of developed and less-developed countries (between 1992 and 2015) to evaluate risk factors and practices associated with patient-to-patient transmission of HCV in this setting. Methods The research was performed using the PubMed Database and the Outbreak Database; studies were selected according to the PRISMA algorithm. Inclusion criteria were established before the papers were retrieved in order to avoid selection biases. Results 36 papers reported on 45 outbreaks that involved 335 unique patients on maintenance hemodialysis; no fatal cases were detected. Nosocomial transmission of HCV was confirmed by phylogenetic analysis in most (n = 31; 69%) reports. Sharing contaminated hemodialysis machines and multidose vials (heparin or saline solution) was suggested responsible for HCV transmission in 8 (18%) and 6 (13%) outbreaks, respectively. Breaches in environmental cleaning and disinfection practices, and failures in medication preparation and administration practices was considered in 29 (65%) outbreaks; however, the exact mechanism of transmission of HCV could not be ascertained in each facility where an outbreak occurred. Conclusions Our systematic review of reports on hepatitis C virus outbreaks shows that, although the full extent of HCV transmission in dialysis units is unknown, outbreaks continue to occur. Full compliance to standard/specific infection control procedures and routine serologic screening for HCV antibody play a pivotal role for preventing the transmission of HCV within hemodialysis units.

Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti–α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti–α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti–α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

The medical literature on mono-therapy with pegylated interferon for chronic hepatitis C in dialysis patients is mostly based on small clinical studies and the efficacy and safety of such approach is still unclear. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to evaluate the efficacy and safety of mono-therapy with pegylated interferon of chronic hepatitis C in patients on regular dialysis. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). The random-effects model of Der Simonian and Laird was used, with heterogeneity and sensitivity analyses. Twenty-four clinical studies (N = 744 unique patients) were retrieved; five (21%) being randomized controlled trials. The summary estimate for sustained viral response and drop-out rate was 0.40 (95% confidence interval [CI], 0.35; 0.46) and 0.14 (95% CI, 0.09; 0.20), respectively. The most frequent side-effects requiring discontinuation of treatment were hematological (31/83 = 37%) and gastrointestinal (9/31 = 10.8%). Meta-regression analysis showed a detrimental role of ageing on the frequency of sustained virological response (P = 0.01); drop-out rate was greater in diabetics (P

Hepatitis C virus (HCV) infection has been associated with a large spectrum of glomerular lesions in both native and transplanted kidneys. The most common HCV-associated renal disease is type I membranoproliferative glomerulonephritis usually, but not invariably, in the context of type II mixed cryoglobulinemia (MC). HCV infection is also the major cause of MC, a systemic vasculitis characterized by involvement of small and, less frequently, medium-sized vessels. Conflicting data exist on the treatment of HCV-associated glomerular disease.This review examines the drugs used for management of HCV-related kidney disease and discusses current and new strategies. All literature concerning treatment of HCV-associated kidney disease has been retrieved by electronic (Medline) and manual searches.Various approaches have been recommended for the treatment of HCV-related glomerular disease, including immunosuppressive therapy (corticosteroids, cytotoxic agents and mAbs) and antiviral therapy. These regimens should be considered according to the level or proteinuria and kidney failure. Immunosuppressive agents are recommended in patients with nephrotic syndrome and/or rapidly progressive kidney failure. Antiviral treatment based on IFN and/or ribavirin or triple antiviral therapy (PEGylated-IFN/ribavirin/telaprevir or boceprevir) has been adopted in patients with moderate proteinuria and slow loss of kidney failure; however, the number of patients enrolled was small. Some patients with HCV-related cryoglobulinemic glomerulonephritis have been treated with rituximab but some issues about its role remain to be clarified. The antiviral treatment of HCV-related glomerular disease is expected to improve in the near future with new agents provided with greater efficacy and safety. However, the affordability of these drugs remains a pivotal issue, particularly in low-income countries.

Chronic metabolic acidosis (CMA) is a common complication of the more advanced stages of chronic kidney diseases (CKD), and is associated with morbidity and mortality of CKD patients and possibly with the progression of renal disease. Nevertheless, there is limited evidence or information on the prevalence, the potential causal factors, the clinical impact and the effects of correction of CMA in kidney transplant recipients. In this review, we briefly look at the more relevant, though scanty, studies which have, over time, addressed the above-mentioned points, with the hope that in the future the interest of transplant nephrologists and surgeons will grow towards this unreasonably neglected issue.

Until the discovery of calcimimetics, the management of secondary hyperparathyroidism (SHPT) relied exclusively on treatment with phosphate binders, vitamin D derivatives or surgical parathyroidectomy with limited success. The therapeutic use of calcimimetic agents, together with a better understanding of the pivotal role of the calcium-sensing receptor (CaSR) in the physiological regulation of parathyroid gland function, substantially advanced the management of hyperparathyroidism in dialysis practice. Calcimimetics bind selectively to the CaSR receptor in parathyroid tissue and enhance the inhibitory effect of extracellular calcium ions on parathyroid hormone (PTH) secretion, thereby reducing PTH levels even when serum calcium concentrations are normal or low. The availability of calcimimetic agents for clinical use has opened a new era in the management of patients with SHPT. Indeed, calcimimetic compounds have been shown to reduce PTH levels and to lower serum calcium concentrations in all forms of hyperparathyroidism, including primary hyperparathyroidism (PHPT) and parathyroid carcinoma. Such findings underscore the critical importance of the CaSR as a therapeutic target in this family of clinical disorders. New calcimimetic agents are being developed that have the potential to offer improved efficacy and safety compared with currently available calcimimetic compounds.

Idiopathic focal segmental glomerulosclerosis (FSGS) is a progressive and proteinuric kidney disease that starts with podocyte injury. Podocytes cover the external side of the glomerular capillary by a complex web of primary and secondary ramifications. Similar to dendritic spines of neuronal cells, podocyte processes rely on a dynamic actin-based cytoskeletal architecture to maintain shape and function. Brain-derived neurotrophic factor (BDNF) is a pleiotropic neurotrophin that binds to the tropomyosin-related kinase B receptor (TrkB) and has crucial roles in neuron maturation, survival, and activity. In neuronal cultures, exogenously added BDNF increases the number and size of dendritic spines. In animal models, BDNF administration is beneficial in both central and peripheral nervous system disorders. Here we show that BDNF has a TrkB-dependent trophic activity on podocyte cell processes; by affecting microRNA-134 and microRNA-132 signalling, BDNF up-regulates Limk1 translation and phosphorylation, and increases cofilin phosphorylation, which results in actin polymerization. Importantly, BDNF effectively repairs podocyte damage in vitro, and contrasts proteinuria and glomerular lesions in in vivo models of FSGS, opening a potential new perspective to the treatment of podocyte disorders.

Recently it has been demonstrated that Fetuin-A, an anti-inflammatory protein synthesized by the liver, is produced also in bone by an FGF23-regulated pathway. FGF23 has been also demonstrated to induce inflammatory cytokine production in the liver. This study aimed to explore if FGF23 plays a role in the Fetuin-A production in the liver cells too and the possible relationships with FGF23 pro-inflammatory effects. FGF23 and Fetuin-A were studied in liver, kidney and in plasma with immunochemistry, immunoprecipitation, western blot, chromatin immunoprecipitation, duolink, ELISA, qrtPCR methodology. FGF23 is produced, but not secreted by the liver cells. In hepatocytes and circulation, FGF23 was present only strictly linked to Fetuin-A, while Fetuin-A was found also in unbounded form. No link was observed in the kidney. FGF23 up to 600 pg/ml stimulates, while, at higher concentrations, reduces Fetuin-A expression. Notably, overall the range of concentrations, FGF23 stimulates Fetuin-A promoter, TNFα and IL6 expression. In the nucleus, FGF23 seems to act as a direct transcription factor of Fetuin-A promoter. These results suggest that FGF23 played a direct regulatory role in Fetuin-A expression in liver cells with a biphasic effect: Fetuin-A progressively increases when FGF23 increases up to 400-600 pg/mL, and declines at higher FGF23 concentrations. These results lead us to hypothesize: a) a possible epigenetic post-transcriptional regulation; b) a possible counter-regulatory effect of FGF23 induced inflammatory cytokines (TNFα/ NF-κB mechanism). This study could add an additional key for the interpretation of the possible mechanisms linking FGF23, Fetuin-A and inflammation in CKD patients and suggests a role for FGF23 as transcription factor.

The frequency of hepatitis C virus infection remains high in renal transplant recipients and plays a detrimental role on survival in this population. According to the latest evidence, the adjusted relative risk of mortality and graft loss for anti-HCV seropositive versus anti-HCV negative renal transplant recipients was 1.85 with a 95% confidence interval (CI) of 1.49 ; 2.31 (P0.0001) and 1.76 (95% CI, 1.46 ; 2.11) (P0.0001), respectively. Interferon-based regimens have been recommended for the treatment of hepatitis C after renal transplantation only in selected circumstances because of an increased risk of acute rejection due to the immuno-stimulatory properties of interferon. Limited data exist on the treatment of HCV with direct-acting antiviral agents among kidney transplant recipients. To date, the most important evidence comes from the European multicenter study where a large cohort (n=114) of patients with glomerular filtration rate of 40 mL/min/1.73m² received an interferon-free, ribavirin-free combination of direct-acting antivirals (Ledipasvir/Sofosbuvir) for 12 or 24 weeks. A high efficacy [SVR12 rate, 100% (114/114) ] was found even if three serious adverse were observed ; all were determined to be treatment related, one patient interrupted permanently treatment. Also, single-center single-arm observational studies have reported high efficacy and safety of sofosbuvir-based combinations for the treatment of HCV after renal transplant. A decline in through levels of calcineurin inhibitors after completion of antiviral therapy has been found in many patients; an enhanced metabolism of calcineurin inhibitors associated with resolution of liver injury has been suggested. An effective and safe therapy for HCV in kidney transplant recipients might improve the current suboptimal utilization of HCV-positive kidney donors and provide many patients with end-stage renal disease access to HCV-infected donor kidneys.

Context: The immunogenicity of the hepatitis B virus vaccine is reduced in patients with renal failure compared with the non-uraemic population. A variety of approaches have been suggested to improve the immune response in uraemic population including an increase in dose of the hepatitis B vaccine. Objective: To compare the efficacy and safety of hepatitis B vaccine schedules based on greater versus standard doses of HB vaccine in patients with chronic kidney disease stages 3 - 5. Evidence Acquisition: We carried out a systematic review of the medical literature with a meta-analysis of randomized trials comparing seroprotection rates after greater vs. standard doses of the HB vaccine. The odds ratio to obtain seroprotection among patients who received greater (study group) vs. standard (control group) doses was the end-point of interest. We used a random-effects approach, as described by DerSimonian and Laird, with heterogeneity and subgroup analyses. Results: We retrieved 11 clinical trials (n = 870 unique patients); 2 (n = 141 patients) and 8 studies (n = 689) included CKD patients on pre-dialysis and dialysis stage, respectively. Three trials (n = 368 patients) employed plasma-derived vaccine; 8 (n = 502) adopted recombinant vaccine. Aggregation of study results (n = 10 studies) showed that the seroprotection rate (short-term follow-up) towards HB virus was higher among patients receiving greater than standard doses of vaccine [pooled OR, 2.10, 95% confidence intervals, 1.15 - 3.82]. The P-value was 0.0001 for our test to study heterogeneity. The seroprotection rate towards HBV was much greater in the subset of trials (n = 2) based on plasma-derived vaccine (OR, 3.78; 95% CI, 2.35; 6.07), and no heterogeneity was found (NS). In the subset of RCTs (n = 8 studies), the seroprotection rate was higher among patients receiving greater doses of vaccine towards HBV, OR, 2.01 (95% CI, 0.92; 4.39), with significant heterogeneity (P = 0.002). Tolerance was satisfactory and no dropouts due to side effects were reported. Conclusions: Vaccine schedules based on greater than standard doses of HB vaccine offer higher immunogenicity in patients with chronic kidney disease. These results support the current recommendations to give higher doses of HBV vaccine to susceptible dialysis population in order to increase the sero-protection rate. Further research is needed to assess whether these findings apply to HB vaccines provided with novel adjuvants.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by platelet consumption, hemolysis, and organ damage. Eculizumab (ECU), a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule is not yet clear. Here, we report our experience with ECU maintenance treatment and the interval between subsequent doses being extended based on global classical complement pathway (CCP) activity aimed at

Recent increasing evidence supports a role for neuronal type signaling in bone. Specifically glutamate receptors have been found in cells responsible for bone remodeling, namely the osteoblasts and the osteoclasts. While most studies have focused on ionotropic glutamate receptors, the relevance of the metabotropic glutamate signaling in bone is poorly understood. Specifically type 1 metabotropic glutamate (mGlu1) receptors are expressed in bone, but the effect of its ablation on skeletal development has never been investigated. Here we report that Grm1crv4/crv4 mice, homozygous for an inactivating mutation of the mGlu1 receptor, and mainly characterized by ataxia and renal dysfunction, exhibit decreased body weight, bone length and bone mineral density compared to wild type (WT) animals. Blood analyses of the affected mice demonstrate the absence of changes in circulating factors, such as vitamin D and PTH, suggesting renal damage is not the main culprit of the skeletal phenotype. Cultures of osteoblasts lacking functional mGlu1 receptors exhibit less homogeneous collagen deposition than WT cells, and present increased expression of osteocalcin, a marker of osteoblast maturation. These data suggest that the skeletal damage is directly linked to the absence of the receptor, which in turn leads to osteoblasts dysfunction and earlier maturation. Accordingly, skeletal histomorphology suggests that Grm1crv4/crv4 mice exhibit enhanced bone maturation, resulting in premature fusion of the growth plate and shortened long bones, and further slowdown of bone apposition rate compared to the WT animals. In summary, this work reveals novel functions of mGlu1 receptors in the bone and indicates that in osteoblasts mGlu1 receptors are necessary for production of normal bone matrix, longitudinal bone growth, and normal skeletal development.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an inherited disorder that causes progressive kidney damage and renal failure. Mutations in the UMOD gene, encoding uromodulin, lead to ADTKD-UMOD related. Uromodulin is a GPI-anchored protein exclusively produced by epithelial cells of the thick ascending limb of Henle’s loop. It is released in the tubular lumen after proteolytic cleavage and represents the most abundant protein in human urine in physiological condition. We previously generated and characterized a transgenic mouse model expressing mutant uromodulin (Tg UmodC147W) that recapitulates the main features of ATDKD-UMOD. While several studies clearly demonstrated that mutated uromodulin accumulates in endoplasmic reticulum, the mechanisms that lead to renal damage are not fully understood. In our work, we used kidney transcriptional profiling to identify early events of pathogenesis in the kidneys of Tg UmodC147W mice. Our results demonstrate up-regulation of inflammation and fibrosis and down-regulation of lipid metabolism in young Tg UmodC147W mice, before any functional or histological evidence of kidney damage. We also show that pro-inflammatory signals precede fibrosis onset and are already present in the first week after birth. Early induction of inflammation is likely relevant for ADTKD-UMOD pathogenesis and related pathways can be envisaged as possible novel targets for therapeutic intervention.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance +/- SD: baseline, 328 +/- 96 m; 6 months, 367 +/- 113 m) but not in the control group (baseline, 321 +/- 107 m; 6 months, 324 +/- 116 m; P

Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels (≤11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value

Podocytes are postmitotic renal glomerular cells with multiple ramifications that extend from the cell body. Processes departing from a podocyte interdigitate with corresponding projections from neighboring cells and form an intricate web that enwraps the glomerular capillary completely. Podocyte processes are interconnected by the slit diaphragm, an adhesion junction mostly formed by Ig-like molecules, cadherins/protocadherins, ephrin/eph, and neurexin molecules organized in an assembly that resembles synaptic junctions. Podocyte failure is primarily or secondarily implicated in all forms of proteinuric glomerular diseases, as confirmed by the morphological changes of their elaborate cell architecture detectable by electron microscopy. Importantly, mutations of podocyte proteins are responsible for the most severe forms of congenital nephrotic syndrome. In the last 15 years, progressive technological advances have aided the study of podocyte biology and pathology, confirming the relevance of podocyte molecules and signaling pathways for the function of the glomerular filter. This review will examine the most important and newest discoveries in the field, which is rapidly evolving, hopefully leading to a detailed knowledge of this fascinating cell and to the development of specific therapeutic options for proteinuric diseases.

Summary Information on the antiviral treatment (pegylated interferon plus ribavirin) of chronic infection by hepatitis C virus (HCV) in patients on long-term dialysis is extremely limited. We evaluated the efficacy and safety of combination antiviral therapy (pegylated interferon plus ribavirin) in patients on long-term dialysis with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eleven clinical studies (287 unique patients), two of them being controlled clinical trials. The summary estimate for SVR and dropout rate was 0.60 (95% Confidence Intervals, 0.47; 0.71) and 0.18 (95% CI, 0.08; 0.35), respectively; studies being heterogeneous with regard to both the outcomes. Stratified analysis reported a higher SVR rate in controlled trials, 0.86 (95% CI, 0.27; 0.99). The most common sources of dropout were anaemia (11/46 = 23%) and infections (6/46 = 13%). Meta-regression analysis showed a detrimental impact of HCV genotype 1 (P = 0.036) and dropout (P = 0.0001) rate upon the frequency of SVR. Antiviral therapy based on pegylated interferon plus ribavirin for HCV gives encouraging results in terms of efficacy and safety among patients on long-term dialysis; such approach should be considered the current standard of care for HCV-infected individuals on regular dialysis.

The 2011 report of the World Health Organization General Assembly on noncommunicable diseases identified chronic kidney disease as a worldwide health issue posing a heavy economic burden. Hepatitis C virus infection, which is responsible for over 1 million deaths resulting from cirrhosis and liver cancer, is linked to chronic kidney disease in several ways; some forms of renal disease are precipitated by hepatitis C and patients with end-stage chronic renal disease are at increased risk for acquiring HCV. The aim of this review is to update the evidence on the relationship between hepatitis C infection and chronic kidney disease. Information has been accumulated in the last decade indicating that HCV plays an adverse effect on the incidence and progression of chronic kidney disease; a novel meta-analysis of observational studies (seven longitudinal studies; 890,560 unique individuals) found a relationship between hepatitis C seropositivity and incidence of reduced estimated glomerular filtration rate (adjusted relative risk, 1.70; 95% CI, 1.20; 2.39;P=0.002) in the adult general population. In addition to conventional risk factors, hepatitis C may be an additional factor for the development of chronic kidney disease, and an atheromasic activity of hepatitis C virus has been mentioned. The link between hepatitis C and atherosclerosis could also explain the excess risk of cardiovascular mortality that has been observed among hepatitis C virus seropositive patients undergoing maintenance dialysis. A number of biologically plausible mechanisms related to hepatitis C virus have been hypothesized to contribute to atherosclerosis. Implementation of effective treatment intervention towards hepatitis C is required to decrease the healthcare burden of hepatitis C and to prevent the progression of chronic renal disease.

Background/Aims: Scarce physical activity predicts shorter survival in dialysis patients. However, the relationship between physical (motor) fitness and clinical outcomes has never been tested in these patients. Methods: We tested the predictive power of an established metric of motor fitness, the Six-Minute Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296 dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov Identifier: NCT01255969). Results: During follow up 69 patients died, 90 had fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients had the composite outcome. In multivariate Cox models - including the study allocation arm and classical and non-classical risk factors - an increase of 20 walked metres during the 6MWT was associated to a 6% reduction of the risk for the composite end-point (P=0.001) and a similar relationship existed between the 6MWT, mortality (PConclusions: Poor physical performance predicts a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients. Future studies, including phase-2 EXCITE, will assess whether improving motor fitness may translate into better clinical outcomes in this high risk population.

Glomerular disease is an extra-hepatic manifestation of hepatitis C virus infection (HCV) and membranoproliferative glomerulonephritis is the most frequent glomerular disease associated with HCV. It occurs commonly in patients with HCV-related mixed cryoglobulinemia syndrome. Patients with HCV-related glomerular disease have been historically a difficult-to-treat group. The therapeutic armamentarium for HCV-related glomerular disease now includes antiviral regimens, selective or non-specific immunosuppressive drugs, immunomodulators, and symptomatic agents. The treatment of HCV-associated glomerular disease is dependent on the clinical presentation of the patient. The recent introduction of all-oral, interferon (IFN)-free/ribavirin (RBV)-free regimens is dramatically changing the course of HCV in the general population, and some regimens have been approved for HCV even in patients with advanced chronic kidney disease. According to a systematic review of the medical literature, the evidence concerning the efficacy/safety of direct-acting antiviral agents (DAAs) of HCV-induced glomerular disease is limited. The frequency of sustained virological response was 92.5% (62/67). Full or partial clinical remission was demonstrated in many patients (n = 46, 68.5%) after DAAs. There were no reports of deterioration of kidney function in patients on DAAs. Many patients (n = 29, 43%) underwent immunosuppression while on DAAs. A few cases of new onset or relapsing glomerular disease in patients with HCV successfully treated with DAAs have been observed. In summary, DAA-based combinations are making easier the management of HCV. However, patients with HCV-induced glomerular disease are still a difficult-to-treat group even at the time of DAAs. Fil: Fabrizi, Fabrizio. No especifíca; Fil: Cerutti, Roberta. No especifíca; Fil: Porata, Giulia. No especifíca; Fil: Messa, Piergiorgio. Università degli Studi di Milano; Italia Fil: Ridruejo, Ezequiel. Universidad Austral. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina

Chronic kidney disease (CKD) is a disabling condition associated with different medical comorbidities including depression and cognitive impairment. We investigated the association between malnutrition, inflammation and depressive/cognitive symptoms in elderly subjects with advanced CKD.We evaluated cross-sectionally 132 elderly subjects (age ≥65 years) with advanced CKD (stage 4-5, non-dialytic-ND) in regular follow up at the outpatient clinic of nephrology. Blood and urinary samples were collected after an overnight fast. All patients were evaluated by Geriatric Depression Scale (GDS)-30 items for severity of depressive symptoms, Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT) for cognition. Nutritional status was assessed by Malnutrition Inflammation Score (MIS). Different linear regression models were performed to study the association between clinical variables, diet and inflammatory parameters with the above mentioned rating scale scores. A final linear regression model with only previous statistically significant variables was performed for GDS scores.Our cohort consisted of 95 males and 37 females with a mean age of 78 ± 7. Female gender (B = 3.20, p .01), higher MIS (B = 0.29, p = .02) and higher IL-12p70 serum levels (pg/mL) (B = 0.37, p = .03) were associated with severity of depressive symptoms. MIS was associated with the severity of cognitive impairment as assessed by MMSE (B = -0.19, p .01) and CDT (B = 0.10, p = .03).In elderly subjects affected by CKD the severity of depressive symptoms and cognitive impairment is associated with specific inflammatory and nutritional parameters. These results have to be considered as preliminary and need replication by further studies.