Acute tubular injury is an important component in type I acute antibody-mediated rejection.

BACKGROUND: "Acute tubular necrosis (ATN)-like" changes in type I acute antibody- mediated rejection (AAMR) have been proposed since 2005, but the presence of "ATN-like" injury in AAMR has not well been established. The aim of this study was to confirm the presence of acute tubular injury in type I AAMR, using the specific proximal tubular injury marker, kidney injury molecule-1 (KIM-1). DESIGN: The study included 3 groups of cases, namely, a negative control group (normal nontransplantation renal parenchyma as group 1, n = 11), a positive control group (transplant ATN with negative C4d staining as group 2, n = 12), and study cases (type 1 AAMR as group 3, n = 19). Biopsy specimens from all groups were stained immunohistochemically for KIM-1 (monoclonal antibody) and KIM-1 staining intensity in proximal tubules was graded from 0.5 to 3+. Clinical indices were also correlated and analyzed. RESULTS: Group 1 demonstrated significantly lower serum creatinine levels (1.02 ± 0.10 mg/dL) when compared with both group 2 and group 3. Both groups 2 and 3 showed similar serum creatinine levels (4.02 ± 0.59 mg/dL in group 2 and 3.24 ± 0.34 mg/dL in group 3). The negative control group demonstrated negative proximal tubule staining for KIM-1, whereas both groups 2 and 3 showed positive KIM-1 staining in proximal tubules (intensity ranging from 1+ to 3+ in group 2 and from 0.5 to 3+ in group 3). CONCLUSION: Our results, using KIM-1 immunohistochemistry, demonstrated that acute tubular injury is an important component of type I AAMR.

Renal allograft outcome in recipients of positive-crossmatch combined liver-kidney transplantation.

BACKGROUND: Successful kidney transplantation despite positive crossmatch (+CXM) before transplantation is well recognized in combined liver-kidney transplant (CLKT) recipients. This is probably due to immunologic protection of the renal allograft (RA) conferred by the liver allograft. However, occurrences of antibody-mediated rejection and poor long-term RA outcome is also documented with +CXM CLKT recipients, suggesting that such immunologic protection may not be universal. METHODS: A total of 1,401 CLKT recipients with known status of pre-transplantation CXM were identified from the United Network for Organ Sharing registry from January 1, 1986, to December 31, 2006. Univariate analysis for significant differences in clinical variables and Kaplan-Meier estimate for patient and graft survivals were performed. The results were compared between positive and negative CXM groups. RESULTS: Pre-transplantation +CXM was seen in 17.3% (242/1401) of CLKT recipients studied. The demographic and clinical characteristics were similar between the groups, except for higher panel reactive antibody level and CXM positivity in female recipients. Outcome analysis showed higher RA rejection (19.3% vs 10.8%; P = .026) and increased hospital length of stay (37.3 ± 46.0 vs 28.8 ± 33.2 days; P = .028) in the +CXM group. RA survivals at 1, 3, and 5 years were 8%, 7%, and 6% lower in the +CXM group. The patient and liver allograft survivals were not different between the groups. CONCLUSIONS: In CLKT recipients with pre-transplantation +CXM, the immunologic protection of RA conferred by the liver allograft is less robust than previously perceived and may lead to higher rejection rate and poor RA outcome. This can be mitigated with routine pre-transplantation CXM.

Glomerulitis during acute cellular rejection may be a surrogate marker of vasculitis in renal allografts--better index for diagnosis of vasculitis.

BACKGROUND: The Banff criteria (from 2005 to 2009) use "T cell-mediated rejection" to indicate acute cellular rejection. Vasculitis in smaller arteries is an important diagnostic criterion for moderate and severe T cell-mediated rejection. The renal allograft endothelium is a significant target of inflammatory response-mediated tissue damage. Medium-size arteries (arcuate arteries) are mostly absent in routine allograft biopsies, so identification of vasculitis relies on its identification in small arteries (arterioles to interlobar arteries). Although inflammation in terminal vessels such as the glomerular capillaries has been previously recognized, their role in grading the rejection process is not well characterized. We therefore evaluated the expression of CD3-positive T lymphocytes and CD68-positive macrophages in glomeruli, small arteries, and arcuate arteries of nephrectomy specimens obtained from transplant and renal tumor patients. METHODS: The study group included 21 renal explant subjects with nonreversible moderate to severe T cell-mediated rejection (IIa to III) and/or severe chronic changes. The control group comprised 17 individuals with nephrectomy for renal tumors. In each case, a large renal section from cortex to medulla was stained for CD3 and CD68 by immunohistochemical method. CD3-positive T lymphocytes and CD68-positive macrophages per balanced high-power field were counted in glomeruli, interlobar arteries, and arcuate arteries. RESULTS: In control kidney sections, neither CD3-positive T lymphocytes nor CD68-positive macrophages were noted in glomeruli, interlobar arteries, or arcuate arteries. In the study group, 15/21 showed diffuse C4d positivity. Also in the study group, positive CD3 and CD68 counts in glomeruli were significantly correlated to both interlobar and arcuate artery counts by linear regression analysis. CONCLUSION: We conclude that in renal allograft biopsies, T lymphocytes and macrophages in the glomeruli not only represent a separate entity, "transplant glomerulitis," but also may be a surrogate marker of vasculitis present in larger vascular beds. Comparable amounts of T cells and macrophages imply that "acute cellular rejection" may be a better terminology to reflect the true inflammatory status.

Quality of life and psychosocial factors in renal transplant recipients.

An ideal method for quality of life (QOL) assessment in renal transplant recipients (RTR) has not yet been determined. Present assessments of QOL in RTR are lengthy, cumbersome to administer, and difficult to interpret. We used a previously validated single question QOL scale score (QLS) that directly asks about the patients' overall assessment of their QOL; "Considering all parts of my life-physical, emotional, social, spiritual, and financial--over the past 2 days the quality of my life has been ... ". The QLS ranges from 0 ("very bad") to 10 ("excellent"). Patients were contacted prior to their routine office visit when they were free of acute medical problems. Fifty RTR participated. Psychosocial and medical variables included the Beck Depression Inventory, Illness Effects Questionnaire, Multidimensional Scale of Perceived Social Support, time since transplant, age, creatinine, hemoglobin, and albumin levels. Of the patients, 64% were African-American and 48% were women; 94% of patients had a score>5. Mean QLS was 7.5+/-2.3. Perception of a better QOL correlated with less perception of depression and illness effects and with perception of greater social support and satisfaction with life (all P<.05). Perception of QOL did not correlate with age, time since transplantation, creatinine, hemoglobin or albumin levels. We concluded that QLS is a quick tool to measure subjective QOL in RTR for correlation with psychosocial factors of interest in this group. These studies should be replicated in larger multiethnic populations.