[Show abstract][Hide abstract]ABSTRACT: During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreas-kidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donor-specific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti-HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non-DSA (p < 0.05) or to negative patients (p < 0.001). Contrasting with the kidney, pancreas graft survival did not differ between patients with or without anti-HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non-DSA positive patients (100% for pancreas and 92% for kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failures were significantly higher in positive than in negative anti-HLA patients (32.5% vs. 11%; p < 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients.
Full-text · Article · Sep 2011 · American Journal of Transplantation
[Show abstract][Hide abstract]ABSTRACT: Lupus nephritis (LN) seldom recurs in a grafted kidney. By contrast, primary membranoproliferative glomerulonephritis (MPGN), which has been included, along with hemolytic uremic syndrome and age-related maculopathy, among the complement dysregulation diseases, has a high recurrence rate and is considered a contraindication to living-donor kidney transplant because of the poor prognosis. We report the case of a young girl with LN-related chronic renal failure who underwent a living donor transplant from her mother. After four months she had a recurrence that did not match the criteria for LN. Graft biopsies and revision of the clinical course pointed to type II MPGN on the basis of a lack of ARA criteria, persistent isolated low C3 levels, and response to plasma therapy. If confirmed by genetic analysis, the patient might benefit from treatment with the monoclonal antibody against the C5-C9 complex, eculizumab.
Full-text · Article · Nov 2010 · Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia
[Show abstract][Hide abstract]ABSTRACT: Complement factor H (CFH)-associated hemolytic uremic syndrome (HUS) is a genetic form of atypical HUS characterized by deficient CFH levels or activity, which cause a disorder of the regulation of the alternative pathway, leading to uncontrolled complement activation. This genetic disorder, which frequently leads to end-stage renal failure, often recurs in kidney transplants, resulting in the poorest graft outcomes among all atypical HUS forms, due to a mutation in genes encoding complement components and regulatory proteins. Herein we have report our experience with a 40-year-old woman, suffering from a clearly defined sporadic form of genetic atypical HUS, consisting of a heterozygous missense mutation in factor H gene. She underwent cadaveric kidney transplantation. At the moment of surgery she displayed positive hemolysis indices and C3 consumption. A calcineurin inhibitor (CNI)-free immunosuppressive regimen was based on sirolimus, mycophenolic acid and steroids after basiliximab induction. An early and intense prophylactic course of plasma exchange (PE), and fresh frozen plasma (40 mL/kg) was prescribed, starting before surgery and continuing daily for the first week. The frequency of PE slowly reduced over the following 2 weeks. After that, just plasma infusion at the same dose was performed once a week until 12 weeks after transplantation. There was prompt graft function and in third week there were no signs of hemolysis or of C3 consumption. More than 3 years after transplantation, the graft is still functioning well and there was no recurrence. In our opinion, this case indicates that, although evidence is lacking, avoidance of CNI and intensive prophylactic plasma therapy are essential to achieve good results in this peculiar type of kidney transplantation. Nevertheless, controlled, prospective studies are necessary to establish the actual role of these two therapeutic procedures in renal transplantation of patients with CFH-associated HUS.
No preview · Article · May 2010 · Transplantation Proceedings
[Show abstract][Hide abstract]ABSTRACT: In Italy, referral of diabetic patients for pancreas transplantation (PT) is an unstructured process, resulting in a low rate of activity and late referrals, often when the patient has already undergone dialysis. In addition, the continuous improvement in pancreas transplant alone, offering the opportunity to reduce cardiovascular risk due to proteinuria and reduced glomerular filtration rate (GFR), is rarely appreciated. We therefore analyzed (1) referral activity to PT during the time frame 2001-2005 in Emilia-Romagna, Italy (four million inhabitants), by collecting ICD 9 CM codes (55.69 + 52.80; 52.86 and 52.80 alone) by residence of the patient; (2) demand for PT among a sample population of 1670 diabetes patients, whose charts were reviewed for the type of diabetes and presence of overt diabetic nephropathy (DN: proteinuria >300 mg/24 h and/or GFR <60 mL/min); (3) potential pancreas availability as the ratio between pancreas and hearts utilized (UP/HR) in different areas of our country. As a results, (1) referral activity reached 8.4 PT per million people in 5 years in the whole region, ranging from 2.6 in the province where a PT program is active, to a maximum value of 20.7 in the province where a devoted outpatient clinic is operated by nephrologists. (2) Prevalence of overt DN was 6% in our cohort, corresponding to 510 D1 patients worthy of evaluation for PT inside Emilia-Romagna region. (3) During 2006, UP/HR was 0.58 in Associazione Inter-Regionale Trapianti agency, 1.16 in Tuscany, 0.30 in Piedmont, and 0.26 in our region. Taken together, our data showed that (1) the referral of D1 to PT has to be empowered, keeping in touch with all patients suffering from diabetic nephropathy; (2) the outpatient clinic devoted to evaluation and recruitment of D1 with nephropathy plays the key role in this program of timely and widespread referral; (3) the availability of pancreata can be increased by utilizing broader criteria for harvesting, increased consent rate to donation and increased the demand for PT (recipient pool). Pancreas grafts need to increase, since the current low demand produces underutilization of the pancreas resource, due to the frequent lack of a suitable recipient.
No preview · Article · Jul 2008 · Transplantation Proceedings
[Show abstract][Hide abstract]ABSTRACT: Great improvements in water treatment technology and the spread of ultrafiltration for cold sterilization have been the basic support for the development and diffusion of on-line dialysis treatments. Some 20 years ago, nephrologists recognized that the official standards for dialysis fluids were insufficient with respect to these new treatment modalities, and ultrapure water (bacteria <0.1 CFU/ml; endotoxin <0.03 EU/ml) was proposed as a reference. Today, ultrapure water is included in most guidelines and recommended standards, but there remains a need for harmonization between standards. To achieve and ensure these levels of purity, technology must be supported by commitment of resources to an active quality assurance programme with adequate maintenance, monitoring, cleaning, sanitizing and problem analysis procedures.
Full-text · Article · Aug 2007 · Contributions to nephrology