Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy

Bonsib, Stephen M.; Abul-Ezz, Sameh R.; Ahmad, Irfan; Young, Scott M.; Ellis, Eileen N.; Schneider, Daniel L.; Walker, Patrick D.

doi:10.1111/j.1523-1755.2000.00395.x

Cited by 45 publications

(16 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Up-regulation of matrix metalloproteases can also contribute to rupture of the tubular membrane, a critical event in EMT. These data agree with those previously described by Bonsib et al (19). During this process, the epithelial tubular cells gain migratory properties and invade the surrounding tissues.…”

Section: The Epithelial-to-mesenchymal Transition In Renal Tubular Cellssupporting

confidence: 83%

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

Câmara¹,

Williams

Pacheco-Silva³

2009

Braz J Med Biol Res

View full text Add to dashboard Cite

New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF) development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as α-1-microglobulin, Nacetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, β-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.

show abstract

Section: The Epithelial-to-mesenchymal Transition In Renal Tubular Cellssupporting

confidence: 83%

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

Câmara¹,

Williams

Pacheco-Silva³

2009

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…Late loss of CrCl after early rejection could reflect late recurrent or smoldering rejection after early rejection, possibly as a result of subclinical rejection (18,19). However, late deterioration after early rejection may be an intrinsic response to injury to key renal components such as damaged tubule basement membranes (20) or arterial injury (21).…”

Section: Discussionmentioning

confidence: 99%

The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving

Gourishankar¹,

Hunsicker

Jhangri

et al. 2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. The 6-mo function and the stability of function posttransplantation in 429 cadaver renal transplants was investigated from 1990 to 2000. The 6-mo creatinine clearance (CrCl) and the rate of change of CrCl beyond 6 mo posttransplantation were calculated. The mean 6-mo CrCl was 64.6 Ϯ 1.1 ml/min and was stable between 1990 and 2000. The net slope of CrCl was Ϫ1.4 Ϯ 0.5 ml/min per yr. The slope has improved in recent years, such that the mean slopes in the period after 1997 are actually positive (ϩ3.5 ml/min per yr). The slope of CrCl beyond 6 mo was not related to the actual value of the 6 mo CrCl, i.e., there was no accelerated loss of function at low CrCl levels. The 6-mo CrCl was independently determined by donor factors (age, gender), recipient factors (age, gender), and immune factors (rejection episodes, regraft status). The slope of the CrCl correlated independently with the transplant year, recipient gender, rejection episodes, diastolic BP, and the choice of immunosuppressive drugs. Cytomegalovirus infection and mismatch status and lipid levels and treatment were not independently associated with slope or 6-mo CrCl. Thus, the most striking change in the course of renal transplants over the past decade is the new stability of function, correlating with reduced rejection and probably due at least in part to the new immunosuppressive agents. Despite continued calcineurin inhibitor use, late improvement in function now occurs in many cadaver kidney transplants, suggesting a previously unappreciated capacity for functional adaptation.With improved control of early rejection and graft loss (1), the emphasis in renal transplantation has now shifted to improving the long-term transplant course. This includes a focus on reducing late graft loss by stabilizing and improving renal function, controlling immunosuppressive side effects, and reducing risk factors for patient survival. The frequency of late graft loss remains excessive: approximately 7% of renal transplants currently functioning in Canada and the United States will fail each year, with approximately half of the losses being due to patient death and the remainder being due to loss of function. In studying the failures that are due to loss of renal function, transplant population studies have usually examined outcomes such as graft survival and half-life. However, these approaches are limited because they give information only about grafts that have failed completely and do not distinguish grafts with poor function from the outset from grafts with excellent function that subsequently deteriorate.Additional information can be gained by looking at renal function outcomes and change in function, permitting examination of the whole population, not just failures. Renal function has long been recognized as a critical determinant of the probability of graft survival (2), and its critical role as a predictor of survival has recently been confirmed in the United Network for Organ Sharing (UNOS) database (3). Serum creatinine and calculated and measured cr...

show abstract

“…Thus loss of nephrons damaged by rejection may progress after the immune response has been successfully reversed, due to failure of repair. One proposal is that basement membrane disruption secondary to tubulitis may lead to continued late progression (34). Nephron loss is a normal event in the kidney with age, and the mechanisms of nephron loss after injury may share path- ways with normal nephron loss due to the stresses of time.…”

Section: Implications Of the New Approachmentioning

confidence: 99%

Call for Revolution: A New Approach to Describing Allograft Deterioration

Halloran¹

2002

American Journal of Transplantation

View full text Add to dashboard Cite

I propose a set of definable entities in the renal transplant course, eliminating the need for the term 'chronic rejection'. The status of a renal transplant can be defined by the presence and extent of rejection (T-cell-mediated or antibody-mediated); allograft nephropathy (parenchymal atrophy, fibrosis, and fibrous intimal thickening in arteries); transplant glomerulopathy; specific diseases; and factors which could accelerate progression. The level of function and the slope of the loss of function should be separately determined. This approach can be applied both in research and in clinical practice, and can be adapted to other organ transplants.

show abstract

Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy

Cited by 45 publications

References 33 publications

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving

Call for Revolution: A New Approach to Describing Allograft Deterioration

Contact Info

Product

Resources

About