Skeletal fractures in patients on renal replacement therapy: How large still is the knowledge gap?

aEuro broken vertical bar In Danish patients on dialysis and in those with a renal transplant, the risk of fractures is 3-fold and 2-fold higher, respectively, than in coeval subjects in the general populationaEuro broken vertical bar

Uso dei calciomimetici nell'iperaparatiroidismo secondario

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Alcune buone ragioni per le quali il nefrologo deve occuparsi della calcolosi urinaria

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HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population

Background: Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD. Aim: To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection). Methods: Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12 months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine. Results: One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers 65 10 mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9 \ub1 385 mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non- or low-responder patients to HBV-AS04 (P = 0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5 \ub1 269.6 mIU/mL, P = 0.001). No major side effects were observed. Conclusions: Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders

An unusual cause of gross hematuria, improved by recumbency

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Nuove terapie per l’epatite C nei pazienti nefropatici cronici

Gli studi effettuati nell\u2019ultima decade hanno evidenziato il ruolo sfavorevole che svolge l\u2019infezione da virus dell\u2019epatite C sulla sopravvivenza dei pazienti nefropatici (particolarmente i pazienti in dialisi ed i portatori di trapianto renale). In aggiunta, l\u2019infezione da virus dell\u2019epatite C sembra essere associata ad un aumentato rischio di nefropatia cronica nella popolazione adulta generale. Pertanto, c\u2019\ue8 urgente bisogno di terapie antivirali efficaci e sicure in questi pazienti. Recenti studi randomizzati e controllati hanno mostrato che la terapia antivirale basata su interferone peghilato e ribavirina pu\uf2 essere efficace (frequenza della risposta virale protratta, circa il 70%), e ben tollerata quando \ue8 usata da medici esperti in pazienti appropriati. Da qualche anno \ue8 iniziata la commercializzazione dei farmaci ad azione anti-virale diretta nella popolazione adulta con funzione renale normale, ma l\u2019uso di questi farmaci nei nefropatici cronici \ue8 ancora allo stato iniziale. Sono stati negli ultimi mesi pubblicati alcuni studi; il primo ha riguardato il trattamento antivirale di HCV nei pazienti (n=224) con malattia renale cronica (CKD stadio 4/ 5) che hanno ricevuto terapia con grazoprevir (inibitore di HCV NS3/4A) ed elbasvir (inibitore di HCV NS5A) per 12 settimane. La frequenza di SVR12 \ue8 stata pari a 94.3% (115/122); nessuno dei pazienti del gruppo di studio ha interrotto precocemente la terapia antivirale per eventi avversi. Il secondo studio riguarda la combinazione antivirale 3D (ombitasvir/paritaprevir/ritonavir/dasabuvir con e senza ribavirina) che \ue8 stata somministrata a 20 pazienti con malattia renale cronica (CKD, stadio 4/5, genotipo 1), la frequenza di SVR12 era 90% (18/20). Non sono stati riportati eventi avversi che hanno necessitato un\u2019interruzione precoce della terapia antivirale. Esistono inoltre alcuni studi preliminari riguardo la terapia antivirale sofosbuvir/simeprevir (n=38) in pazienti con malattia renale cronica di stadio 4/5; la frequenza di SVR12 era 89% (34/38). Altri studi clinici, di fase 2 o 3, basati sui farmaci ad azione antivirale diretta sono in corso. In conclusione, i nuovi farmaci ad azione anti-virale diretta promettono di eradicare l\u2019infezione da virus dell\u2019epatite C nei pazienti con insufficienza renale. Restano da chiarire alcuni punti cruciali quali il costo dei nuovi farmaci, che \ue8 un problema non trascurabile anche per i paesi industrializzati. Anche le interazioni tra farmaci sono un argomento di rilevanza clinica visto che i pazienti nefropatici cronici hanno una frequenza elevata di co-morbilit\ue0.Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions

Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism?

Background Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P. Methods The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300–799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n = 184) or a cinacalcet-based regimen (n = 368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (≤4.5 and ≤5.5 mg/dL) in relation to achievement of iPTH ≤300 pg/mL during the efficacy assessment phase (EAP; weeks 17–23). Results Patients who achieved iPTH ≤ 300 pg/mL (or a reduction of ≥30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH ≤ 300 pg/mL, 43% achieved P ≤4.5 mg/dL and 70% achieved P ≤5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH ≤ 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ≤300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ≤4.5 mg/dL during EAP in patients above this threshold at baseline. Conclusions This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received

Novel evidence on hepatitis C virus-associated glomerular disease

A large spectrum of renal pathology is associated with hepatitis C virus (HCV). According to novel evidence, occult HCV infection (HCV-RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) could be involved in the pathogenesis of glomerular nephropathy among patients negative for conventional markers of HCV. Additional studies with appropriate size and technology are in progress to confirm the relationship between occult HCV and glomerular disease, which has multiple implications from the clinical standpoint

Recent advances on Hepatitis C virus in dialysis population

Hepatitis C virus (HCV) infection remains common among patients undergoing regular dialysis and good evidence supports the detrimental role of HCV on survival in patients undergoing maintenance dialysis. According to an updated meta-analysis of clinical studies (n=15; 195,370 unique patients on maintenance dialysis), the summary estimate for adjusted relative risk (allcause mortality) with anti-HCV across the published studies was 1.32 with a 95% Confidence Intervals of 1.24; 1.42, homogeneity assumption was not rejected. Various mechanisms support the excess death risk of HCV-infected patients on regular dialysis, in addition to liver disease-related mortality. The adjusted relative risk for cardiovascular mortality among HCV-infected patients on regular dialysis was 1.26 (95% Confidence Intervals, 1.10; 1.45); the increased cardiovascular mortality in anti-HCV positive patients has been associated in part to malnutrition and chronic inflammation. The current standard of care for HCV in dialysis population is combined antiviral therapy (pegylated interferon plus ribavirin) with a rate of viral response of around 60%. Triple therapy with telaprevir proved to be effective and safe in dialysis patients with HCV but only anecdotal evidence exists. Antiviral treatment of HCV-infected patients on maintenance dialysis could lead to cure the liver damage and the extrahepatic complications. The future availability of all-oral interferon/ribavirin free regimens for antiviral treatment of HCV will help nephrologists to improve survival in this high-risk group