Bolignano D.,Dialysis and Transplantation Unit |
Rastelli S.,Dialysis and Transplantation Unit |
Agarwal R.,Indiana University |
Fliser D.,Saarland University |
And 21 more authors.
American Journal of Kidney Diseases | Year: 2013
Pulmonary arterial hypertension is a rare disease often associated with positive antinuclear antibody and high mortality. Pulmonary hypertension, which rarely is severe, occurs frequently in patients with chronic kidney disease (CKD). The prevalence of pulmonary hypertension ranges from 9%-39% in individuals with stage 5 CKD, 18.8%-68.8% in hemodialysis patients, and 0%-42% in patients on peritoneal dialysis therapy. No epidemiologic data are available yet for earlier stages of CKD. Pulmonary hypertension in patients with CKD may be induced and/or aggravated by left ventricular disorders and risk factors typical of CKD, including volume overload, an arteriovenous fistula, sleep-disordered breathing, exposure to dialysis membranes, endothelial dysfunction, vascular calcification and stiffening, and severe anemia. No specific intervention trial aimed at reducing pulmonary hypertension in patients with CKD has been performed to date. Correcting volume overload and treating left ventricular disorders are factors of paramount importance for relieving pulmonary hypertension in patients with CKD. Preventing pulmonary hypertension in this population is crucial because even kidney transplantation may not reverse the high mortality associated with established pulmonary hypertension. © 2013 National Kidney Foundation, Inc.
PubMed | Dialysis and Transplantation Unit and Molecular Virology Unit
Type: Journal Article | Journal: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology | Year: 2014
Human cytomegalovirus (HCMV) is the most common opportunistic virus infection in solid organ transplant recipients. The analysis of HCMV-specific T-cell immunity after organ transplant is of relevant clinical interest.To analyze HCMV-specific CD4(+) and CD8(+) T-cell responses in healthy subjects and kidney transplant recipients (KTR).HCMV-specific T-cell responses were evaluated by interferon- (IFN-) enzyme-linked immunospot (ELISPOT) using overlapping 15-mer peptide pools of immediate early (IE)-1, IE-2, phosphoprotein 65 (pp65) (for stimulation of both CD4(+) and CD8(+) T-cell responses) and a pool of 34 short peptides (8-12 amino acids in length, for stimulation of CD8(+) T-cell responses). ELISPOT results were normalized to T-cell subset counts and their correlations with a reported dendritic cell (DC)-based assay, which simultaneously quantifies HCMV-specific CD4(+) and CD8(+) T-cell responses, were analyzed.HCMV-seropositive KTR showed higher ELISPOT responses compared to HCMV-seropositive healthy subjects. IE-1 and pp65 ELISPOT responses were mediated mainly by CD8(+) T-cells and, to a lesser extent, CD4(+) T cells; IE-2 peptides appear to stimulate CD56(+) cells (natural killer cells). In HCMV-seropositive healthy subjects, ELISPOT results (expressed either as net spots/million cells or normalized to the corresponding T-cell count) significantly correlated with the DC assay. However, in HMCV-seropositive KTR, only normalized ELISPOT responses to overlapping 15-mer peptide pools significantly correlated with DC-assay responses.The normalized ELISPOT represents a novel and simple approach for quantifying and monitoring HCMV-specific CD4(+) and CD8(+) T-cell responses in KTR.
Signorini L.,University of Milan |
Belingheri M.,Dialysis and Transplantation Unit |
Ambrogi F.,University of Milan |
Pagani E.,Laboratory of Microbiology and Virology |
And 9 more authors.
Journal of Clinical Virology | Year: 2014
Background: Polyomavirus (PyV) infection is common, ranging from 60% to 100% depending on the virus. The urinary excretion rates of JC virus (JCV) and BK virus (BKV) have been extensively studied, but less is known about the more recently discovered PyVs. Objectives: To investigate the urinary excretion of Merkel cell PyV (MCPyV), which is associated with Merkel cell carcinoma (MCC), in kidney transplant recipients and healthy subjects, as well as those of lymphotropic polyomavirus (LPV), which was isolated from the B-cells of African green monkeys but has also been found in human blood, JCV and BKV. Study design: Urine samples were collected from 62 adult (ATP) and 46 pediatric (PTP) kidney transplant recipients and from 67 adult (AHC) and 40 pediatric (PHC) healthy controls. DNA was isolated and analyzed using real-time PCR (Q-PCR) to determine the viral loads of MCPyV, LPV, JCV and BKV. Results: MCPyV DNA was more frequently detected (p<. 0.05) in the PTP (36.9%) and PHC (30.0%) groups compared to JCV (8.7% in PTP, 12.5% in PHC), BKV (6.5% in PTP, 2.5% in PHC), and LPV (2.2% in PTP, 5% in PHC) and in the AHC (47.8%) group compared to BKV (13.4%) and LPV (0%). Conclusions: Based on the results, it could be concluded that: (a) Despite the rarity of MCC, MCPyV is a common infection; (b) MCPyV demonstrates an excretion pattern similar to those of JCV and BKV, persisting in the kidney and infecting skin cells upon reactivation, with subsequent integration and transformation. © 2014 Elsevier B.V.
PubMed | University of Calgary, Dialysis and Hypertension, GGZ inGeest, Copenhagen University and 8 more.
Type: Journal Article | Journal: The journals of gerontology. Series A, Biological sciences and medical sciences | Year: 2016
The rate of senescence can be inferred from the acceleration by which mortality rates increase over age. Such a senescence rate is generally estimated from parameters of a mathematical model fitted to these mortality rates. However, such models have limitations and underlying assumptions. Notably, they do not fit mortality rates at young and old ages. Therefore, we developed a method to calculate senescence rates from the acceleration of mortality directly without modeling the mortality rates. We applied the different methods to age group-specific mortality data from the European Renal Association-European Dialysis and Transplant Association Registry, including patients with end-stage renal disease on dialysis, who are known to suffer from increased senescence rates (n = 302,455), and patients with a functioning kidney transplant (n = 74,490). From age 20 to 70, senescence rates were comparable when calculated with or without a model. However, when using non-modeled mortality rates, senescence rates were yielded at young and old ages that remained concealed when using modeled mortality rates. At young ages senescence rates were negative, while senescence rates declined at old ages. In conclusion, the rate of senescence can be calculated directly from non-modeled mortality rates, overcoming the disadvantages of an indirect estimation based on modeled mortality rates.
Tataranni T.,Dialysis and Transplantation Unit |
Biondi G.,Dialysis and Transplantation Unit |
Cariello M.,Dialysis and Transplantation Unit |
Mangino M.,Dialysis and Transplantation Unit |
And 6 more authors.
American Journal of Transplantation | Year: 2011
Rapamycin, an immunosuppressive drug used to prevent rejection after kidney transplantation, influences phosphate homeostasis, induces insulin resistance and has been shown to prolong lifespan in animal models. Because Klotho is an aging-suppressor gene controlling phosphate metabolism and insulin sensitivity, we investigated the influence of rapamycin on Klotho expression. A total of 100 kidney transplant recipients, 50 chronically treated with rapamycin and 50 with calcineurin inhibitors, were enrolled; 20 healthy subjects were employed as control. In the rapamycin group, serum phosphate was lower than in the CNI group with an increase in phosphate excretion and a reduction in its reabsorption. In addition, rapamycin increased insulin resistance as shown by HOMA index. Rapamycin treatment of an immortalized proximal tubular cell line induced the expression of Klotho, the phosphorylation of AKT in Ser473, downstream target of mTORC2 and the expression of RICTOR, mTORC2 main component. AKT inhibition reduced the rapamycin-induced expression of Klotho. In vivo rapamycin treatment induced higher degree of RICTOR and AKT Ser 473 expression directly correlating with long-term rapamycin exposure, FE PO4 and HOMA index. In conclusion, our data would suggest that rapamycin may influence phosphate homeostasis and insulin resistance modulating Klotho expression through mTORC2 activation. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
Vavallo A.,University of Bari |
Simone S.,Dialysis and Transplantation Unit |
Lucarelli G.,University of Bari |
Rutigliano M.,University of Bari |
And 10 more authors.
Medicine (United States) | Year: 2014
Malignancies are one of the main causes of mortality in diabetic patients; however, to date, very limited data have been reported on the specific influence of type 2 diabetes mellitus (T2DM) on the survival of patients with renal cell carcinoma (RCC). In the present longterm retrospective study, we investigated whether T2DM may influence the overall survival (OS), cancer-specific survival (CSS), and progression- free survival (PFS) in patients with surgically treated RCC. Medical records of 924 patients treated by radical or partial nephrectomy for sporadic, unilateralRCCwere reviewed. Patients with type-1DM and with T2 DM receiving insulin treatment were excluded. Survival estimates were calculated according to the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were performed using the Cox regression model. Of the 924 RCC patients, 152 (16.5%) had T2DM. Mean follow-up was 68.5months. Mean OS was 41.3 and 96.3 months in T2DMand non- T2DM patients, respectively (P<0.0001). The estimated CSS rates at 1, 3, and 5 years in T2DM versus non- T2DM patients were 63.4% versus 76.7%, 30.4% versus 56.6%, and 16.3% versus 48.6%, respectively (P=0.001). Mean PFS was significantly lower (31.5 vs 96.3 months; P<0.0001) in the T2DM group. At multivariate analysis, T2DM was an independent adverse prognostic factor for OS (hazard ratio [HR]=3.44; 95% confidence interval [CI]: 2.40-4.92), CSS (HR=6.39; 95% CI: 3.78-10.79), and PFS (HR=4.71; 95% CI: 3.11-7.15). In conclusion, our findings suggest that patients with RCC and preexisting T2DMhave a shorterOS, increased risk of recurrence, and higher risk for kidney cancer mortality than those without diabetes. Copyright © 2014 Wolters Kluwer Health / Lippincott Williams & Wilkins.
Zoccali C.,Dialysis and Transplantation Unit |
Zoccali C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy |
Ruggenenti P.,Mario Negri Institute for Pharmacological Research |
Perna A.,Mario Negri Institute for Pharmacological Research |
And 6 more authors.
Journal of the American Society of Nephrology | Year: 2011
Phosphate may promote the onset and progression of chronic nephropathies. Here we evaluated the relationships between baseline serum phosphate levels, disease progression, and response to ACE inhibition in 331 patients with proteinuric nephropathies in the prospective Ramipril Efficacy In Nephropathy (REIN) trial. Independent of treatment, patients with phosphate levels in the highest two quartiles progressed significantly faster either to ESRD or to a composite endpoint of doubling of serum creatinine or ESRD compared with patients with phosphate levels below the median (P < 0.001). Results were similar when we analyzed phosphate as a continuous variable (P ≤ 0.004). The renoprotective effect of ramipril decreased as serum phosphate increased (P ≤ 0.008 for interaction); this modification of the treatment effect by phosphate persisted despite adjusting for potential confounders such as GFR and urinary protein. In summary, these data suggest that phosphate is an independent risk factor for progression of renal disease among patients with proteinuric CKD, and high levels of phosphate may even attenuate the renoprotective effect of ACE inhibitors. Future trials should test whether reducing serum phosphate improves renal outcomes and optimizes the renoprotective effect of ACE inhibition. Copyright © 2011 by the American Society of Nephrology.
Lucarelli G.,Urology andrology and Kidney Transplantation Unit |
Bettocchi C.,Urology andrology and Kidney Transplantation Unit |
Battaglia M.,Urology andrology and Kidney Transplantation Unit |
Impedovo S.V.,Urology andrology and Kidney Transplantation Unit |
And 6 more authors.
Transplantation Proceedings | Year: 2010
Introduction: Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not suitable for single kidney transplantation (SKT), has been suggested to expand the kidney donor pool. Herein, we reviewed the long-term outcomes of DKT to assess its results versus a control group of 179 ECD SKTs. The allocation policy was based on a Remuzzi score obtained from a pretransplant biopsy. Materials and methods: We analyzed SKT in 179 (31.8%) and DKT in 41 (7.3%) of 563 cadaveric transplants from 2000 to 2008. Patients with DKT versus SKT showed mean recipient ages of 54 versus 51 years. We performed 17 ipsilateral and 24 bilateral DKT. The mean score was 2.78 for SKT and 4.3/4.6 for DKT. Results: Delayed graft function requiring dialysis occurred in 23 (56.1%) DKT and 70 (39.1%) SKT recipients. Primary nonfunction was observed in 1 (2.4%) DKT and 7 (3.9%) SKT recipients respectively. One DKT patient underwent monolateral transplantectomy. In the DKT versus SKT group, patient survivals were 92% versus 95%, 89% versus 93%, and 89 versus 91% at 12, 36, and 60 months, respectively (P = .3). Graft survivals were 100% versus 94%, 95% versus 90%, and 89% versus 78% at 12, 36, and 60 months, respectively (P < .001). We observed a lower incidence of chronic allograft nephropathy (P = .01) and a higher incidence of surgical adverse events (P = .04) in DKT. Conclusions: ECD graft survival using DKT provided better results compared with SKT, despite the use of organs from higher-risk donors. At 5 years follow-up, DKT was a safe strategy to face the organ shortage. To optimize the use of available kidneys, the criteria for DKT require further refinement and standardization. Preimplantation evaluation must maximize transplant success and protect recipients from receiving organs at increased risk of premature failure. © 2010 Elsevier Inc. All rights reserved.
Catalano C.,Dialysis and Transplantation Unit
BMJ case reports | Year: 2011
The authors report the case of a 33-year-old Italian man who had three episodes of hypokalaemia with paralysis linked to hyperthyroidism. Because of its low prevalence in western populations, the diagnosis of thyrotoxic hypokalaemic periodic paralysis can be easily missed in non-Asian countries.
PubMed | Dialysis and Transplantation Unit
Type: Case Reports | Journal: Biologicals : journal of the International Association of Biological Standardization | Year: 2013
Focal segmental glomerulosclerosis (FSGS) is the most frequent acquired renal condition resulting in end stage kidney disease in children. We describe a cell therapy treatment with human allogeneic bone marrow mesenchymal stem cells (MSC) in a 13-year-old patient developing recurrent FSGS after renal transplantation, which was not responding to conventional therapy. This treatment relied on the following measurements:clinical and laboratory evaluation of renal function, proteome array, biopsy, short tandem repeat assay. Before MSC treatment, the patient needed weekly plasmapheresis to achieve proteinuria-to-creatininuria ratio below 5. After three MSC infusions without adverse events, the patient has a stable renal function and the proteinuria target was reached without plasmapheresis. In addition, some circulating inflammatory factors decreased and their levels were still low after one year. This is the first report of an MSC treatment in an FSGS patient. Even though different factors may have contributed to the clinical results, after MSC infusion a stable reduction in the serum level of several inflammatory factors has been registered and the patient does not need anymore plasmapheresis to keep proteinuria under control. In addition, this encouraging single case let us identify some putative efficacy biomarkers that could be of clinical interest in chronic kidney diseases.