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

Abstract

Conclusion. Damage to TBM develops in acute rejection asAcute rejection-associated tubular basement membrane changes a consequence of interstitial inflammation and tubulitis. These and chronic allograft nephropathy.lytic events correlate with the later development of clinical and Background. Acute rejection is a major risk factor for chronic morphologic evidence of chronic injury in the absence of arterial allograft nephropathy, although the link(s) between these events injury of chronic rejection. We suggest that chronic allograft is not understood. The hypothesis of this study is that alternephropathy may have an inflammatory interstitial origin. ations in tubular basement membranes (TBMs) that occur during acute rejection may be irreversible and thereby play a role in the development of chronic allograft nephropathy.Methods. Fourteen renal transplant patients were selected, Chronic rejection (CR) is the most common cause of each having had two or more biopsies performed (42 total). late-developing graft loss. The conventional view holds All biopsies were scored for acute and chronic rejection using Banff 1997 criteria. The initial biopsy showed only acute interthat CR has a vascular etiology [1-5]. Recently, attention stitial rejection (type I rejection). No biopsies contained sighas been directed toward interstitial contributions since nificant chronic arterial lesions of chronic vascular rejection.one of the strongest predictors of late graft failures isThe entire cortex was examined on Jones methenamine silverthe timing, number, and severity of acute rejection (AR) stained sections at ϫ400 for interruption in TBM staining. The episodes [5][6][7][8][9][10][11][12]. Even the presence of subclinical rejecnumber of tubules with TBM abnormalities was counted, and the renal cortical area was measured by image analysis. Periodic tion in early protocol biopsies, defined as the presence of acid-Schiff/immunoperoxidase stain was performed on 12 acute "borderline rejection" ("Banff 95"), has been associated rejection biopsies stained for laminin, cytokeratin 7, CD3, CD20,with elevated creatinine at one year compared with biopand CD68. Controls consisted of 11 biopsies (8 negative for sies free of all infiltrates [13][14][15]. The postulate of this rejection and 3 acute tubular necrosis).Results. Numerous TBM alterations in silver staining were

Immunologic risk factors and glomerular C4d deposits in chronic transplant glomerulopathy

“…Ten patients showed no or minor obliteration of the arterial lumen, indicating that ischemia is not a likely mechanism responsible for chronic transplant glomerulopathy. The observed chronic tubulointerstitial changes are most likely related to previous acute rejection episodes [20].…”

Chronic Allograft Nephropathy: Current Concepts and Future Directions

“…Adhesions (synecia) from segmentally injured glomeruli attached to Bowman's capsule, can misdirect ultrafiltrate into paraglomerular and paratubular channels leading to the interstitial space, with reduced overall functional efficiency (12)(13)(14). Inflammatory necrosis and healing favor local obliterative fibrosis, structural compromise, loss of basement membrane integrity (14) and a "leaky" transplanted kidney. Hence, functional failure of the transplanted kidney results from the summated loss of individual nephrons, combined with additional disruption of its internal structural integrity.…”

Pathogenesis of tubulointerstitial fibrosis in chronic allograft dysfunction

“…Disruptions of the tubular basement membrane are required for migration of cells from the tubular epithelium into the tubulointerstitial space. For example, Bonsib and colleagues examined 14 patients with at least two allograft biopsies and found a good correlation between the number of tubular basement disruptions and renal function (27). Destruction of tubular basement membranes is induced by invading lymphocytes, occurring mostly in phases of acute rejection and may explain in part why the number of acute rejection episodes is associated with increased fibrosis and reduced long-term function (28).…”