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Cagliari, Italy

Busnach G.,Science Nefrologia
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia | Year: 2012

Patients who are sensitized through pregnancy, previous blood transfusions, or organ transplantation produce donor-specific anti-HLA antibodies (DSA) that can result in an important obstacle in kidney transplantation. Sensitized patients wait longer on the cadaver donor transplant list, may not receive a transplant, and may have greater morbidity and mortality. Sensitized patients may have living donor candidates but transplantation cannot be performed because of cross-match positivity. Kidney transplant recipients with DSA are at higher risk of developing early acute antibody-mediated rejection (AMR) despite negative complement-dependent cytotoxicity (CDC) T-cell cross-match, and thus require desensitization. Desensitization protocols using the combination of apheresis (PE) or immunoadsorption to remove DSA and/or intravenous Ig (Iv-Ig) and rituximab to downregulate antibody-mediated immune responses have made kidney transplantation feasible by abrogating CDC T-cell cross-match positivity. All sensitized patients should be studied for DSA by sensitive methods and followed over time. The presence of DSA should be documented, and also the strength or titers of the alloantibodies should be determined to decide on the type of desensitization protocol. High-dosage Iv-Ig alone does not prevent AMR in patients with strong DSA, and the addition of peritransplantation PE as unselective plasma exchange, semiselective double filtration, or selective immunoadsorption significantly decreases the incidence of AMR. The effect of addition of monoclonal antibodies such as rituximab to desensitization protocols or of PE to patients with strong anti-HLA-II DSA on allograft outcomes requires further prospective studies.

Minetti E.,Science Nefrologia
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia | Year: 2010

Combined kidney-pancreas transplant is currently the best treatment option for patients with type 1 diabetes associated with chronic renal failure. The favorable results of simultaneous pancreas-kidney transplants (SPK), introduced in the early 1990s, led to the introduction of the pancreas after kidney transplant (PAK) and the pancreas transplant alone (PTA), a good option for patients with uncontrolled diabetes. The superior results of SPK over PAK are partly related to better donor selection and partly to immunological factors. In conclusion, PAK transplant is a good preemptive choice for patients for whom a living kidney donor is available, so that long-term uremia while the patient is waiting for a cadaver pancreas graft can be avoided. Despite a high surgical complication rate in all types of pancreas transplant (SPK, PAK, PTA), patient survival is good and graft survival is improving year by year.

Ponticelli C.,Humanitas Scientific Institute | Carmellini M.,Chirurgia Dei Trapianti Azienda Ospedaliera Universitaria | Tisone G.,University of Rome Tor Vergata | Sandrini S.,U.O. Nefrologia | And 4 more authors.
Transplantation Proceedings | Year: 2014

This multicenter, randomized, prospective, controlled trial (EVIDENCE study) aimed to determine short-term effects of early steroid withdrawal in renal transplant patients initially treated with everolimus, low-dose cyclosporine (CsA), and steroids. Patients were randomized to standard triple therapy with CsA, everolimus twice daily and steroids (group A), steroid-free immunosuppression (group B), or triple therapy once daily (group C). However, since patient enrollment was slower than expected, group C randomization was prematurely discontinued. The primary end point was treatment failure rate (composite end point of death, graft loss, biopsy-proven acute rejection, and loss to follow-up) between randomization and month 12. Patients evaluable for the primary end point included 139 randomized patients. According to intention-to-treat analysis, 2.8% of patients in group A and 14.7% in group B experienced treatment failure (95% upper confidence limit 19.7%). As this was higher than the predefined noninferiority limit of 10%, noninferiority could not be proved. No conclusive statements can be made on noninferiority of the steroid withdrawal regimen vs the standard regimen in these patients. Additional studies with longer follow-up are required to determine the efficacy of steroidfree immunosuppression in renal transplant recipients receiving everolimus.

Serraino D.,Irccs Centro Of Riferimento Oncologico | Segoloni G.P.,Science Nefrologia Dialisi Trapianto | Sandrini S.,Rheumatology and Clinical Immunology and Nephrology | Piredda G.B.,Azienda Ospedaliera G. Brotzu | And 12 more authors.
European Journal of Cancer | Year: 2013

To assess incidence and risk factors for de novo cancers (DNCs) after kidney transplant (KT), we carried out a cohort investigation in 15 Italian KT centres. Seven thousand two-hundred seventeen KT recipients (64.2% men), transplanted between 1997 and 2007 and followed-up until 2009, represented the study group. Person years (PY) were computed from 30 days after transplant to cancer diagnosis, death, return to dialysis or to study closure. The number of observed DNCs was compared to that expected in the general population of Italy through standardised incidence ratios (SIR) and 95% confidence intervals (CI). To identify risk factors, incidence rate ratios (IRR) were computed. Three-hundred ninety five DNCs were diagnosed during 39.598 PYs, with Kaposi's sarcoma (KS), post-transplant lymphoproliferative disorders (PTLD), particularly non-Hodgkin' lymphoma (NHL), lung, kidney and prostate as the most common types. The overall IR was 9.98/1.000 PY, with a 1.7-fold augmented SIR (95% CI: 1.6-1.9). SIRs were particularly elevated for KS (135), lip (9.4), kidney carcinoma (4.9), NHL (4.5) and mesothelioma (4.2). KT recipients born in Southern Italy were at reduced risk of kidney cancer and solid tumors, though at a higher KS risk, than those born in Northern Italy. Use of mTOR inhibitors (mTORi) exerted, for all cancers combined, a 46% significantly reduced risk (95% CI: 0.4-0.7). Our study findings confirmed, in Italy, the increased risks for cancer following KT, and they also suggested a possible protective effect of mTORi in reducing the frequency of post transplant cancers. © 2012 Elsevier Ltd. All rights reserved.

Piccoli G.B.,University of Turin | Grassi G.,SCDU Endocrinologia | Cabiddu G.,Science Nefrologia | Nazha M.,University of Turin | And 10 more authors.
Review of Diabetic Studies | Year: 2015

The term “diabetic kidney” has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting “glomerular diabetic nephropathy”, does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients. © 2015, Society for Biomedical Diabetes Research. All rights reserved.

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