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C Esposito, C Migotto,
M Torreggiani,
N Maggi,
A Manini,
F Castoldi,
F Grosjean,
F Mangione,
M Abelli,
M L Scaramuzzi,
D Catucci,
A Dal Canton
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ABSTRACT: Although many variables may affect long-term graft survival no biomarker is available to identify donor kidney with poor quality and with inadequate short and long-term outcome. While in marginal donors pre-transplant renal biopsies are commonly performed to establish if donor kidneys are suitable for transplantation they are not performed in standard donors. In this study we assessed the relevance of pre-transplant morphological features on post-transplant renal function and evaluated the association between perioperative parameters with posttransplant histological and clinical findings. Kidney transplant recipients undergone pre-transplant and post transplant protocol biopsies at 1, 6, and 12 months were enrolled in the study. Perioperative and posttransplant clinical and biochemical parameters were recorded. Semiquantitative analysis of PAS stained kidney sections was used to determine the degree of lesions. Glomerular volume was measured by computed morphometry. A strong inverse correlation was found between donor age and renal graft function at 1, 6, and 12 months after transplantation. A prompt functional recovery was associated with a better renal function at 6 months and one year. Kidneys with higher glomerular volume demonstrated a lower serum creatinine at 1 month. Higher tubulo-interstitial grading at protocol biopsies was associated with a poor renal function at 1 month. Our findings confirm the importance of donor age in kidney transplant long-term outcome and demonstrate that pretransplant and protocol biopsies are valid options to determine graft outcome and to define therapeutic strategies and tailor immunosuppressive regimen for each patient.
Transplantation Proceedings 09/2012; 44(7):1889-91. · 1.00 Impact Factor
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C Esposito,
M Abelli,
G Sileno, C Migotto,
M Torreggiani,
N Serpieri,
N Maggi,
V Esposito,
F Grosjean,
M L Scaramuzzi,
F Montagna,
A D Canton
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ABSTRACT: Erythropoietin-stimulating agents (ESAs) are commonly used to treat anemia in kidney transplant recipients (KTRs). Since 2007, continuous erythropoietin receptor activator (CERA) has been one of the newest recombinant ESAs to treat anemia in dialysis and nondialysis patients with chronic kidney disease. The efficacy of CERA to manage anemia has not been extensively evaluated in KTRs. We evaluated safety, efficacy, and satisfaction among KTRs treated with CERA. We enrolled 19 anemic KTRs (60 ± 9.3 y) who were treated with short-acting ESA for ≥24 weeks. They were shifted to the equivalent dose of CERA and followed for 24 weeks. We measured serum hemoglobin, hematocrit, creatinine, iron, ferritin, and transferrin. To investigate tolerance to and satisfaction with short-acting ESA and CERA, questionnaires were administered to the patients before shifting to CERA and at the end of the follow-up. After 6 months, CERA induced an increase in hemoglobin levels (12.3 ± 0.8 vs 11.2 ± 1.1 g/dL; P = .002, CERA vs short-acting ESA, respectively). In 2 patients treatment was discontinued because the hemoglobin increased to >13 g/dL. No significant differences were observed in serum iron and creatinine between short-acting ESA and CERA throughout the study. The questionnaires showed better compliance to CERA treatment with reduced pain at the injection site, which led subjects to prefer CERA to short-acting ESA. In summary, CERA showed better control of anemia compared with short-acting ESA. It was preferred by the majority of patients, mainly because of the reduced number of monthly injections. Our results demonstrated CERA to be effective, safe, and well tolerated in the management of anemia in KTRs.
Transplantation Proceedings 09/2012; 44(7):1916-7. · 1.00 Impact Factor
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ABSTRACT: Asymmetric dimethylarginine (ADMA) has been identified as a marker of endothelial dysfunction and an independent risk factor for cardiovascular events in uremic subjects. This study evaluated ADMA plasma levels in kidney transplant recipients. ADMA levels were serially measured during the first year posttransplantation in 41 recipients treated with cyclosporine regimen (CY), sirolimus (SIR), or low-dose cyclosporine plus everolimus (E). Homocysteine, C reactive protein (CRP), nitric oxide (NO), and standard routine laboratory analyses were determined serially. ADMA significantly increased at 6 months posttransplantation, but was significantly lower among patients on SIR or E. NO was only slightly reduced in patients with increased ADMA levels. Interestingly, ADMA was significantly increased during the first 4 days posttransplantation in patients who experienced acute rejection during the first 6 months after transplantation. The same group of patients demonstrated higher levels of CRP and systolic blood pressure before transplantation. Our results demonstrated that ADMA was increased in patients on CY at 6 months. When increased soon after transplantation ADMA may be associated with episodes of acute rejection in kidney transplant recipients. The presence of elevated systolic blood pressure, as well as CRP and ADMA levels, suggested a role for endothelial dysfunction in the development of acute rejection episodes among deceased donor kidney transplant recipients.
Transplantation Proceedings 07/2009; 41(5):1570-3. · 1.00 Impact Factor
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C Esposito,
E Pertile,
F Grosjean,
F Castoldi,
R Diliberto,
N Serpieri,
M Arra,
L Villa,
F Mangione,
V Esposito, C Migotto,
R Valentino,
A Dal Canton
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ABSTRACT: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure in kidney transplantation; however, the mechanisms of kidney damage and repair are not yet clear. So far no treatment has been effective to prevent I/R injury. In the present study we evaluated the effect of erythropoetin (EPO) in I/R injury in rats. We investigated the role of bone marrow cells (BMC) in kidney repair and the effect of EPO on BMC recruitment.
Female Sprague Dawley rats transplanted with male BMCs underwent I/R injury. In the treatment group rats received 5000 IU of EPO 30 minutes before renal ischemia. At 2 and 4 weeks after I/R, rats were humanely killed and we measured creatinine clearance (glomerular filtration rate [GFR]), proteinuria, and body weight (BW). Renal tissue was harvested for histologic and molecular analysis. Fluorescein in situ hybridization (FISH) and TUNEL were used to determined the presence of male cell chimerism and apoptosis in renal tissue.
At 4 weeks after I/R, EPO significantly improved GFR (1.8 +/- 0.2 vs 1.2 +/- 0.14 mL/min; P < .05). No significant differences between EPO and control rats were observed in proteinuria, BW, and hemoglobin levels at 2 and 4 weeks. After death, the kidney showed only minimal tubulointerstitial changes, which were more marked in control rats. FISH analysis demonstrated a low degree of microchimerism, not significantly different between EPO and control rats. Apoptosis decreased between 2 and 4 weeks after I/R, in both EPO and control groups.
EPO improved GFR and injury at 4 weeks after I/R; however, it did not enhance the recruitment of BMC.
Transplantation Proceedings 05/2009; 41(4):1113-5. · 1.00 Impact Factor
