Early Cyclosporine A Withdrawal in Kidney-Transplant Recipients Receiving Sirolimus Prevents Progression of Chronic Pathologic Allograft Lesions

Ruiz, J.C.; Campistol, Josep M.; Grinyó, Josep M.; Mota, A.; Prats, D; Gutiérrez, J; Henriques, António Castro; Pinto, J.R.; García, Javier Moreno; Morales, José; Gómez, Javier; Arias, Manuel

doi:10.1097/01.tp.0000137322.65953.0a

Cited by 68 publications

(48 citation statements)

References 25 publications

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“…Although the comparator arm uses combination CSA and sirolimus, which would now be expected to yield poor results, this cannot obviate significant improvements within the other arm. Similar histopathologic results have been seen in other smaller trials (104,105), supporting the view that the TORi lead to better long-term graft histology and reduced chronic allograft dysfunction.…”

Section: Therapeutic Strategies In Chronic Renal Dysfunctionsupporting

confidence: 77%

Chronic Renal Allograft Dysfunction

Chapman¹,

O’Connell²,

Nankivell³

2005

Journal of the American Society of Nephrology

386

288

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The major causes of renal transplant loss are death from vascular, malignant or infectious disease, and loss of the allograft from chronic renal dysfunction associated with the development of graft fibrosis and glomerulosclerosis. Chronic allograft nephropathy (CAN) is the histologic description of the fibrosis, vascular and glomerular damage occurring in renal allografts. Clinical programs rely on monitoring change in serum creatinine for identification of patients at risk of CAN, but this change occurs late in the course of the disease, and underestimates the severity of pathologic change. CAN has several causes: ischemia-reperfusion injury, ineffectively or untreated clinical and subclinical rejection, and superimposed calcineurin inhibitor nephrotoxicity, exacerbating pre-existing donor disease. Once established, interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerulosclerosis over the subsequent years. There have been a number of approaches to treatment aimed at reducing the impact of CAN, mostly centered around avoidance of calcineurin inhibitors through their elimination in all, or just selected, patients. These immunosuppression strategies combine corticosteroids with azathioprine or mycophenolate mofetil, and/or sirolimus and everolimus. Late identification of CAN in individual patients has meant that strategies for intervening to prevent chronic renal allograft dysfunction and subsequent graft loss tend to be "too little and far too late."

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Section: Therapeutic Strategies In Chronic Renal Dysfunctionsupporting

confidence: 77%

Chronic Renal Allograft Dysfunction

Chapman¹,

O’Connell²,

Nankivell³

2005

Journal of the American Society of Nephrology

386

288

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“…However, the prevalence of mild hyalinosis increased from (20) or re-operations (3). 3 Chronicity score equals the sum of Banff chronic scores (ah + eg + ci + ct + cv).…”

Section: Discussionmentioning

confidence: 99%

The Histology of Solitary Renal Allografts at 1 and 5 Years After Transplantation

Stegall

Park

Larson

et al. 2011

American Journal of Transplantation

125

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Previous studies suggest that the majority of renal allografts are affected by progressive, severe chronic histologic injury, yet studies using current protocols are lacking. The goal of this study was to examine the prevalence and progression of histologic changes using protocol allograft biopsies at 1 and 5 years after solitary kidney transplantation in patients transplanted between 1998 and 2004. Chronic histologic changes generally were mild at both 1 and 5 years and were similar in deceased and living donor kidneys. The overall prevalence of moderate or severe fibrosis was 13% (60/447) at 1 year and 17% (60/343) at 5 years. In a subgroup of 296 patients who underwent both 1-and 5-year biopsies, mild fibrosis present at 1 year progressed to more severe forms at 5 years in 23% of allografts. The prevalence of moderate or severe arteriolar hyalinosis was similar in tacrolimus and calcineurin inhibitor-free immunosuppression. These results in the recent era of transplantation demonstrate fewer, less severe and less progressive chronic histologic changes in the first 5 years after transplantation than previously reported.

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“…However, one of these studies compared tacrolimus and cyclosporine-treated patients, in both of whom the prevalence of CAN was approximately 70% at 2 yr (24). Finally, two recent studies reported the prevalence of CAN in protocol biopsies in patients who were on sirolimus (37,38). In one study (37), approximately 32% of patients who switched to sirolimus at 3 mo had new-onset CAN at 1 yr, as compared with 65% of those who were maintained on cyclosporine.…”

Section: Interstitial Fibrosis and Tubular Atrophy: Prevalence Risk mentioning

confidence: 99%

“…Finally, two recent studies reported the prevalence of CAN in protocol biopsies in patients who were on sirolimus (37,38). In one study (37), approximately 32% of patients who switched to sirolimus at 3 mo had new-onset CAN at 1 yr, as compared with 65% of those who were maintained on cyclosporine. In the other study (38), patients who were randomly assigned to sirolimus had a 34% prevalence of CAN at 2 yr as compared with almost 80% for those who were on cyclosporine.…”

Section: Interstitial Fibrosis and Tubular Atrophy: Prevalence Risk mentioning

confidence: 99%

Protocol Transplant Biopsies

Rush¹

2006

Clinical Journal of the American Society of Nephrology

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Early Cyclosporine A Withdrawal in Kidney-Transplant Recipients Receiving Sirolimus Prevents Progression of Chronic Pathologic Allograft Lesions

Cited by 68 publications

References 25 publications

Chronic Renal Allograft Dysfunction

Chronic Renal Allograft Dysfunction

The Histology of Solitary Renal Allografts at 1 and 5 Years After Transplantation

Protocol Transplant Biopsies

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