PTFE grafts versus tunneled cuffed catheters for hemodialysis: which is the second choice when arteriovenous fistula is not feasible?

Vascular access-related complications are still one of the leading causes of morbidity in hemodialysis patients. The aim of this study was to compare polytetrafluoroethylene (PTFE) grafts versus tunneled cuffed permanent catheters (TCCs) in terms of vascular access and patients' survival. An observational study was carried out with a 2-year follow-up. Eighty-seven chronic hemodialysis patients were enrolled: 31 with a PTFE graft as vascular access for hemodialysis versus 56 with a TCC. Patients' mean age was 63.8 ± 14.6 (grafts) versus 73.5 ± 11.3 years (TCCs), P = 0.001. Significantly more patients with TCC had atrial fibrillation than patients with grafts (30.3% versus 6.5%, P = 0.01). In an unadjusted Kaplan-Meier analysis, median TCC survival at 24 months was 5.4 months longer than that of PTFE grafts but not significantly (log-rank test = 1.3, P = ns). In a Cox regression analysis adjusted for age, gender, number of previous vascular accesses, diabetes, atrial fibrillation, smoking, and any complication, this lack of significant difference in survival of the vascular access between TCC and PTFE groups was confirmed and diabetes proved to be an independent risk factor for the survival of both vascular accesses considered (P = 0.02). In an unadjusted Kaplan-Meier analysis, a higher mortality was found in the TCC group than in the PTFE group at 24 months (log-rank test = 10.07, P < 0.01). The adjusted Cox regression analysis showed that patients with TCC had a 3.2 times higher risk of death than patients with PTFE grafts. When an arteriovenous fistula (AVF) is not possible, PTFE grafts can be considered the vascular access of second choice, whereas TCCs can be used when an AVF or PTFE graft are not feasible or as a bridge to AVF or PTFE graft creation.

Emerging drugs for chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is a worldwide health problem. Despite remarkable headway in slowing the progression of kidney diseases, the incidence of end-stage renal disease (ESRD) is increasing in all countries with a severe impact on patients and society. The high incidence of diabetes and hypertension, along with the aging population, may partially explain this growth. Currently, the mainstay of pharmacological treatment for CKD, aiming to slow progression to ESRD are ACE inhibitors and angiotensin II receptor blockers for their hemodynamic/antihypertensive and anti-inflammatory/antifibrotic action. However, novel drugs would be highly desirable to effectively slow the progressive renal function loss. AREAS COVERED: Through the search engines, PubMed and ClinicalTrial.gov, the scientific literature was reviewed in search of emerging drugs in Phase II or III trials, which appear to be the most promising for CKD treatment. EXPERT OPINION: The great expectations for new drugs for the management of CKD over the last decade have unfortunately not been met. Encouraging results from preliminary studies with specific agents need to be tempered with caution, given the absence of consistent and adequate data. To date, several agents that showed great promise in animal studies have been less effective in humans.

Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up.

Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.

Influence of the immunogenetic KIR and HLA systems on long-term renal transplant outcome.

BACKGROUND: Numerous studies have established the importance of innate immunity, particularly natural killer (NK) cells, in transplantation tolerance. NK cells express killer cell immunoglobulin-like receptors (KIRs) on their surface. By recognizing and binding major histocompatibility complex class I antigens, KIRs prevent autologous cell killing and promote lysis of non-self antigen-presenting cells. This study investigated the role of 16 KIR genes and donor-recipient KIR/HLA combinations on 5-year outcomes in a population of deceased donor kidney transplant recipients. MATERIAL/METHODS: We genotyped 126 renal transplant patients and their donors for HLA A, B, C, DR, and KIR genes. Patients underwent standardized transplantation and immunosuppressive protocols and were followed-up for 5 years. Graft function was evaluated by serum creatinine level and glomerular filtration rate calculated using the 4-variable modification of diet in renal disease (MDRD) equation. RESULTS: The presence of KIR2DS3 in the recipients was associated with better graft function indexes over time (p<0.05), but this effect was not confirmed by multivariate analysis. Conversely, the presence KIR2DS3 in the recipients combined with the presence of its HLA ligand in the donor had a detrimental effect on the trends of serum creatinine levels and eGFR trends, also confirmed by multivariate analysis. Kidney transplant recipients negative for the KIR2DL1 gene displayed higher creatinine levels after 5 years. Lastly, transplantation of HLA-A3/A11-negative donor kidneys into KIR3DL2-positive patients exerted a protective effect in terms of 5-years outcome (p<0.05). CONCLUSIONS: The present study demonstrates an important role of the KIR immunogenetic system in the long-term immune response to kidney transplantation.

Biochemical and molecular investigations on qualitative and quantitative Hb polymorphism in the river buffalo (Bubalus bubalis L. ) population reared in Southern Italy

On 398 river buffalo samples, randomly collected in distinct breeding areas of the Campania region, high-resolution analytical systems were used to identify both qualitative and quantitative variations of the Hb phenotype. Polyacrylamide gel isoelectric focusing and HPLC were used to determine the ratio between HBA1 and HBA2 globin chains; restriction endonuclease analysis was performed to assess whether quantitative variations in Hb bands were related to an unusual number of a-globin genes. In the two buffalo subpopulations, allele frequencies of the alpha and beta globin systems were calculated, and F statistics (FIS, FIT and FST) were estimated as parameters of genetic diversity. The results suggest that: i) as shown by RFLP analysis, only a couple of associated a globin genes account for the quantitative variations recorded at the phenotypic level; ii) as expected, in the a globin gene system (HBA), the frequency of haplotype B (HBA-B) largely exceeded that of haplotype A (HBA-A) (95.1 percent vs 4.9 percent); iii) the frequency of the usual allele at the beta locus is 0.6, as opposed to 0.4 of the slow variant; iiii) the most significant component of variation of the genetic system of hemoglobin is between individuals within the same location.

Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients.

Two loci for nonsyndromic recessive deafness located on chromosome 21q22.3 have previously been reported, DFNB8 and DFNB10. Recently a gene which encodes a transmembrane serine protease, TMPRSS3 or ECHOS1, was found to be responsible for both the DFNB8 and DFNB10 phenotypes. To determine the contribution of TMPRSS3 mutations in the general congenital/childhood nonsyndromic deaf population we performed mutation analysis of the TMPRSS3 gene in 448 unrelated deaf patients from Spain, Italy, Greece, and Australia who did not have the common 35delG GJB2 mutation. From the 896 chromosomes studied we identified two novel pathogenic mutations accounting for four mutant alleles and at least 16 nonpathogenic sequence variants. The pathogenic mutations were a 1-bp deletion resulting in a frameshift and an amino acid substitution in the LDLRA domain of TMPRSS3. From this and another study we estimate the frequency of TMPRSS3 mutations in our sample as 0.45%, and approximately 0.38% in the general Caucasian childhood deaf population. However, TMPRSS3 is still an important contributor to genetic deafness in populations with large consanguineous families.