Publications by authors named "Annarita Plati"

7 Publications

  • Page 1 of 1

Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial.

PLoS Med 2021 06 24;18(6):e1003668. Epub 2021 Jun 24.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Background: We compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression.

Methods And Findings: ATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat. Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m2, p = 0.50], and adverse events (AEs) were not significantly different between groups. Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design.

Conclusions: In this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression.

Trial Registration: ClinicalTrials.gov NCT00494741; EUDRACT 2006-005604-14.
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http://dx.doi.org/10.1371/journal.pmed.1003668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224852PMC
June 2021

Long-Term Outcomes of Kidney Transplants from Older/Marginal Donors: A Cohort Study.

Nephron 2021 Jun 15:1-11. Epub 2021 Jun 15.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Introduction: To safely expand the donor pool, we introduced a strategy of biopsy-guided selection and allocation to single or dual transplantation of kidneys from donors >60 years old or with hypertension, diabetes, and/or proteinuria (older/marginal donors). Here, we evaluated the long-term performance of this approach in everyday clinical practice.

Methods: In this single-center cohort study, we compared outcomes of 98 patients who received one or two biopsy-evaluated grafts from older/marginal donors ("recipients") and 198 patients who received nonhistologically assessed single graft from ideal donors ("reference-recipients") from October 2004 to December 2015 at the Bergamo Transplant Center (Italy).

Results: Older/marginal donors and their recipients were 27.9 and 19.3 years older than ideal donors and their reference-recipients, respectively. KDPI/KDRI and donor serum creatinine were higher and cold ischemia time longer in the recipient group. During a median follow-up of 51.9 (interquartile range 23.1-88.6) months, 11.2% of recipients died, 7.1% lost their graft, and 16.3% had biopsy-proven acute rejection (BPAR) versus 3.5, 7.6, and 17.7%, respectively, of reference-recipients. Overall death-censored graft failure (rate ratio 0.78 [95% CI 0.33-2.08]), 5-year death-censored graft survival (94.3% [87.8-100.0] vs. 94.2% [90.5-98.0]), BPAR incidence (rate ratio 0.87 [0.49-1.62]), and yearly measured glomerular filtration rate decline (1.18 ± 3.27 vs. 0.68 ± 2.42 mL/min/1.73 m2, p = 0.37) were similar between recipients and reference-recipients, respectively.

Conclusions: Biopsy-guided selection and allocation of kidneys from older/marginal donors can safely increase transplant activity in clinical practice without affecting long-term outcomes. This may help manage the growing gap between organ demand and supply without affecting long-term recipient and graft outcomes.
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http://dx.doi.org/10.1159/000516534DOI Listing
June 2021

[Goodbye old creatinine: time to change?].

Authors:
Annarita Plati

G Ital Nefrol 2010 Nov-Dec;27(6):564

Unita' di Nefrologia e Dialisi, Fondazione Orizzonte, Ospedale Bolognini, Seriate, Bergamo, Italy.

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March 2011

[MICA antigen: HLA system is still enough?].

Authors:
AnnaRita Plati

G Ital Nefrol 2008 Mar-Apr;25(2):156

Unita' di Nefrologia e Dialisi, Ospedale ''Bolognini'', Seriate (BG) - Italy.

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August 2008

Renal function and functional reserve in healthy elderly individuals.

J Nephrol 2007 Sep-Oct;20(5):617-25

Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Pavia - Italy.

Background: Aging is characterized by a decline in renal function and by a susceptibility to renal diseases. However it is not clear whether the observed changes are solely hemodynamic, structural or both. We evaluated renal function, functional reserve (RFR) and morphology in healthy elderly individuals.

Methods: Healthy participants (n=19) were divided into young (n=6, age range 25-37 years), middle-aged (n=6, 44-74 years) and elderly (n=7, 81-96 years). Nitric oxide (NO), plasma renin activity (PRA) and aldosterone, renal plasma flow (RPF) by p-aminohippurate clearance (CPAH) and glomerular filtration rate (GFR) by inulin clearance (CIN) were determined before and during maximal vasodilating stimuli, induced with the infusion of dopamine and amino acids. Glomerular sclerosis, lumen area and wall thickness of afferent arterioles were determined by kidney biopsy from 36 healthy kidney donors and from 6 nephrectomies for renal carcinoma.

Results: GFR and RPF were slightly reduced in elderly individuals whereas filtration fraction (FF) was increased. GFR and RPF did not increase in the elderly after maximal vasodilating stimuli as in young and middle-aged subjects suggesting a reduction of RFR. NO, increased at baseline, did not increase further after vasodilating stimuli; while on the contrary, PRA, similar in the 3 groups at baseline, was not reduced by vasodilating stimuli in the elderly. Sclerotic glomeruli but not glomerular volume were significantly increased by aging. Afferent arteriole lumens were reduced by aging whereas wall thickness was unchanged.

Conclusions: Renal function is preserved with aging in healthy subjects at the expense of a complete reduction of RFR. RFR may be wasted to compensate for the increased number of sclerotic glomeruli. Vascular changes, suggested by reduced arteriolar lumen, may be so advanced that even in the presence of high levels of vasodilatory molecules, kidneys are not responsive anymore to maximal vasoactive stimuli.
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December 2007

Uremic serum induces proatherogenic changes in human endothelial cells.

J Nephrol 2006 Sep-Oct;19(5):599-604

Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Pavia-Italy.

Background: Cardiovascular complications are the main cause of death in uremic patients. Uremic angiopathy has been regarded as an accelerated form of atherosclerosis. However the mechanism leading to vessel wall injury is still unknown. We hypothesized that uremic serum affects endothelium inducing a proatherogenic state.

Methods: We studied the effects of uremic serum on human endothelial cells (HECs). Cell proliferation and adhesion of mononuclear cells to HEC monolayers were evaluated by cell counting, apoptosis and collagen production by ELISA, and nitric oxide (NO) by measuring the concentration of nitrite/nitrate in the cell supernatant. (alfa2)IV collagen, tissue inhibitor of metalloproteases-1 (TIMP-1) and transforming growth factor-beta (TGF-beta) mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR). In some experiments cells were preincubated with anti-receptor for advanced glycation end product (anti-RAGE) blocking antibodies.

Results: Uremic serum did not modify HEC proliferation but induced apoptosis after 72 hours of incubation. Adhesion of mononuclear cells to HEC monolayers was significantly increased by uremic serum. In addition, uremic serum increased (alfa2)IV collagen, TIMP-1 and TGF-beta mRNA levels. There was no increase in nitric oxide concentration in ure-mic serum-treated endothelial cells, and the expression of TGF-beta was neither modified by L-NAME nor by anti-RAGE antibodies.

Conclusions: Our results indicate that uremic serum affects HEC inducing a proatherogenic state that may be responsible for the accelerated atherosclerosis of uremic patients. Apparently uremic serum effect is not mediated by NO or by AGEs.
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June 2008

Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli.

Kidney Int 2005 Jun;67(6):2143-50

Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Background: The imbalance between synthesis and degradation of mesangial matrix causes glomerulosclerosis and leads to renal failure. Hepatocyte growth factor (HGF) has been shown to reduce the progression in murine models of chronic renal failure. The present study evaluated the effect of HGF on the extracellular matrix turnover and on c-met receptor in human glomeruli.

Methods: Human glomeruli microdissected from donor kidney biopsies before transplantation were incubated with culture media containing HGF (50 ng/mL). After 24 and 48 hours, the expression of c-met, (alpha2) IV collagen, transforming growth factor-beta (TGF-beta), metalloprotease (MMP) 2 and 9 and of the inhibitor of MMP-2, tissue inhibitors of metalloprotease-1 (TIMP-1), was evaluated by polymerase chain reaction (PCR). beta-actin was used as housekeeping gene. The production of collagen type IV and TGF-beta was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting and the activity of MMP by zymography.

Results: (alpha2) IV collagen, TGF-beta, and TIMP-1 mRNA levels were markedly decreased in glomeruli treated with HGF at 24 and 48 hours. The expression of c-met was up-regulated by HGF treatment. HGF reduced the production of collagen type IV and TGF-beta. MMP-2 but not MMP-9 mRNA level was increased in HGF-treated glomeruli, although the gelatinolytic activity of the supernatant was not changed. By light microscopic examination kidney biopsies neither showed glomerular hypercellularity nor mesangial expansion.

Conclusion: HGF reduced expression and synthesis of TGF-beta and collagen type IV and increased MMP-2 mRNA level in normal human glomeruli. These results suggest an antifibrotic effect of HGF on glomerular cells and may explain its beneficial role in glomerulosclerosis.
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http://dx.doi.org/10.1111/j.1523-1755.2005.00319.xDOI Listing
June 2005
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