Identifying Specific Causes of Kidney Allograft Loss

Abstract

The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 ± 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes.

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

“…In 2009, El-Zoghby et al differentiated the reasons for chronic transplant loss. These authors identified CAMR as a main cause in adults [1]. The same has been shown in children [51].…”

“…The last decades have been very successful regarding the prevention and treatment of acute cellular rejection. However, chronic antibodymediated rejection (CAMR) remains a leading cause of the late loss of kidney transplants in adults [1]. The prevalence of CAMR could even be higher in pediatric nephrology.…”

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

“…After censoring for death, however, similar findings remain, and it is likely that chronic alloimmune damage is a major cause of graft loss in this cohort as reported elsewhere. [28][29][30][31][32] Finally, HLA typing methods have evolved, such that the HLA antigens identified in one donor may be more fully resolved than the other donor or in the recipient. 33 Where this resolution discrepancy existed, we classified the antigens as equivalent.…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…IF/TA is detectable in about 40% of kidney allografts at 3-6 months (6,7) and increases to about 65% at 2 years (8). IF/TA is a non-specific lesion induced by various immune and non-immune injuries to the graft (9,10) and an independent risk factor for late graft loss, particularly in grafts from expanded criteria donors, irrespective of whether a specific disease was diagnosed in the allograft or not (11)(12)(13)(14)(15). However, ''IF/TA'' should only be diagnosed if the underlying etiology of fibrosis and tubular atrophy is not clear (5).…”

“…However, ''IF/TA'' should only be diagnosed if the underlying etiology of fibrosis and tubular atrophy is not clear (5). With protocol biopsies and detailed clinical information a cause of graft dysfunction can be recognized in most cases, with the majority being due to chronic rejection (9,10,12,16). Therefore, within this review we will use not use the term IF/TA but rather discuss renal fibrosis in general given that there is little to no evidence that the allograft fibrosis as part of IF/TA or any other allograft pathology differs significantly from the fibrosis observed in other progressive diseases of native kidneys.…”