Management considerations in the failing renal allograft

Lea‐Henry, Tom; Chacko, Bobby

doi:10.1111/nep.13165

Cited by 18 publications

(6 citation statements)

References 55 publications

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“…3,4,6 In Australia, immunosuppressive therapies are often reduced or withdrawn over time after kidney graft loss, with patients generally remaining on only low-dose prednisolone in the longer term. 12,13 This reduction in immunosuppression after graft loss may correlate with the lower cancer risk seen in those who experienced their first graft loss (SIR and SMR of 1.4–1.5) compared with patients with a functioning first or second transplant (SIR and SMR >2). Although the cancer incidence and mortality ratios for patients after second graft loss were less precise, as there were only few patients with cancer after second graft loss in our cohort, the overall cancer risk remained elevated in our cohort after return to dialysis with second graft loss.…”

Section: Discussionmentioning

confidence: 99%

Variations in Risk of Cancer and Death From Cancer According to Kidney Allograft Function, Graft Loss, and Return to Dialysis

Chapman

Teixeira‐Pinto

et al. 2023

Transplantation

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Background. Cancer incidence and mortality may change with varying kidney allograft function and after graft loss. We aimed to quantify cancer incidence and mortality during periods with a functioning graft and after graft loss. Methods. We included all adult Australians aged 20 and above who commenced kidney replacement therapy between 1982 and 2014 using data from Australia and New Zealand Dialysis and Transplant Registry. We calculated the standardized incidence ratios and standardized mortality ratios (standardized against the Australian general population) for dialysis patients and transplant recipients during periods with a functioning graft and after graft loss. Results. A total of 44 765 dialysis patients without transplants, 13 443 with first kidney transplants, 2951 after first graft loss, 1010 with second transplants, and 279 after second graft loss were followed for 274 660 patient-years. Cancer incidence and mortality (per 100 000 patient-years) were 1564 and 760 in dialysis patients, 1564 and 689 in recipients of first transplants, 1188 and 390 after first graft loss, 1525 and 693 after second transplants, and 1645 and 779 after second graft loss. Cancer standardized incidence ratios and standardized mortality ratios (95% confidence intervals) were 1.15 (1.11-1.20) and 1.29 (1.21-1.36) for dialysis patients, 2.03 (1.94-2.13) and 2.50 (2.33-2.69) for recipients following their first transplant, 1.55 (1.29-1.85) and 1.40 (1.00-1.90) after first graft loss, 2.18 (1.79-2.63) and 3.00 (2.23-3.96) for second transplants, 2.59 (1.56-4.04) and 3.82 (1.75-7.25) after second graft loss. Conclusions. In kidney transplant recipients, cancer incidence and mortality are highest during periods with a functioning graft and remained higher than in the general population even after graft loss.

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Section: Discussionmentioning

confidence: 99%

Variations in Risk of Cancer and Death From Cancer According to Kidney Allograft Function, Graft Loss, and Return to Dialysis

Chapman

Teixeira‐Pinto

et al. 2023

Transplantation

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“…Renal transplantation remains the optimal form of renal replacement therapy for patients with end stage renal disease. Despite exceptional short-term survival, long-term survival is limited by the development of chronic allograft dysfunction which in the kidney manifests with interstitial fibrosis and tubular atrophy [105]. Recently, novel approaches have been proposed to improve allograft outcomes [106].…”

Section: Cd39-adenosinergic Axis In Renal Transplantationmentioning

confidence: 99%

CD39-adenosinergic axis in renal pathophysiology and therapeutics

Kishore

Robson

Dwyer

2018

Purinergic Signalling

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Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis. In recent years, several studies have shown this axis to play critical roles in transport of water/sodium, tubuloglomerular feedback, renin secretion, ischemia reperfusion injury, renal fibrosis, hypertension, diabetic nephropathy, transplantation, inflammation, and macrophage transformation. Important developments include global and targeted gene knockout and/or transgenic mouse models of CD39 or CD73, biological or small molecule inhibitors, and soluble engineered ectonucleotidases to directly impact the CD39-adenosinergic axis. This review presents a comprehensive picture of the multiple roles of CD39-adenosinergic axis in renal physiology, pathophysiology, and therapeutics. Scientific advances and greater understanding of the role of this axis in the kidney, in both health and illness, will direct development of innovative therapies for renal diseases.

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“…Recently, two reviews discussing the management of a failed renal allograft were published. They mainly focus on the role of dialysis and the management of immunosuppression [12,13]. In the current review, we describe the clinical practices and surgical aspects of allograft nephrectomy, and provide an overview of the literature on the effect of allograft nephrectomy on retransplant outcome, with special reference to the role of HLA antibody sensitization.…”

Section: Introductionmentioning

confidence: 99%

Indications, risks and impact of failed allograft nephrectomy

Ghyselen

Naesens

2019

Transplantation Reviews

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In this review, we describe the indications, surgical aspects, benefits and risks of nephrectomy after graft failure. There is a great variation in the number of allograft nephrectomies performed among different centers. Nephrectomy of a failed allograft is associated with significant morbidity and mortality with a complication rate of 20-30% and mortality rates between 0% and 11%. A systematic review through Medline (Pubmed) and Embase identified thirteen retrospective studies that compared patients with and patients without allograft nephrectomy prior to retransplantation. Allograft nephrectomy associates with an increased risk of HLA antibody development. With two recent studies that used the more sensitive HLA antibody detection methods disproving the hypothesis of intragraft adsorption of HLA antibodies, the mechanism leading to the increased HLA antibody levels is not clear, but the role of immunosuppression withdrawal is becoming clear and needs further investigation. In nine of the thirteen studies that evaluated the impact of allograft nephrectomy on outcome in retransplantation, retransplant graft survival was not significantly different among patients with and patients without allograft nephrectomy. Only three studies showed significantly worse retransplant graft survival if prior allograft nephrectomy was performed. Most studies did not observe a significant difference in patient survival after retransplantation with versus without prior allograft nephrectomy. All studies were affected by the retrospective design, indication bias, and selection bias. On the basis of the available literature on this topic, we did not identify a clear advantage or disadvantage of allograft nephrectomy, in terms of outcome after repeat transplantation. Nevertheless, the significantly increased risk of HLA antibody sensitization, especially in patients at high immunological risk like high donor-recipientHLA epitope mismatch load and HLA-DQB1 mismatches, argues against routine allograft nephrectomy and immunosuppression withdrawal in asymptomatic patients who are eligible for repeat transplantation.

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Management considerations in the failing renal allograft

Abstract: Summary at a Glance This paper provides a balanced and thoughtful review of the management of patients with failing renal allografts, including the discussion relating to the adjustment and timely discontinuation of immunosuppression.

Cited by 18 publications

References 55 publications

Variations in Risk of Cancer and Death From Cancer According to Kidney Allograft Function, Graft Loss, and Return to Dialysis

Variations in Risk of Cancer and Death From Cancer According to Kidney Allograft Function, Graft Loss, and Return to Dialysis

CD39-adenosinergic axis in renal pathophysiology and therapeutics

Indications, risks and impact of failed allograft nephrectomy

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