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Background Classification of acute rejection (AR) based on etiology and timing may provide a means for enhancing therapeutic results and allograft survival. This study evaluated graft and patient survival after the first AR episodes among kidney transplant recipients with an early or late antibody-mediated rejection (AMR), acute cellular rejection (ACR) or mixed AR (MAR). Methods A prospective institutional review board-approved database was queried to identify biopsy-proven first AR episodes occurring from January 2005 to October 2012. The ACR was defined by Banff criteria; borderline AR was excluded. The AMR was defined as 3 of 4 criteria: renal dysfunction, donor specific antibody, C4d positivity on biopsy, and histological changes. The MAR met criteria for both ACR and AMR. Early AR occurred within six months post-transplant. AR episodes were then assigned to 1 of the 6 categories--early AMR, early ACR, early MAR, late AMR, late ACR, and late MAR. Results One hundred eighty-two kidney transplant recipients identified with a first AR episode. Mean follow-up was 773 days (± 715 days). No difference was observed in patient survival. Death-censored graft survival was 84%. Death-censored graft loss was higher with late versus early AMR (P = 0.01) and late versus early ACR (P = 0.03), but not late versus early MAR (P = 0.3). Conclusions The AR type demonstrated a hierarchy for graft survival with ACR better than MAR better than AMR, which persisted for both early and late AR. Improvement in long-term results of AR may require development of specific treatment for individual AR types.

Objectives and Methods: Guanylin and uroguanylin are peptides synthesized in the intestine and kidney that are postulated to have both paracrine and endocrine functions, forming a potential enteric-renal link to coordinate salt ingestion with natriuresis. To explore the in vivo role of guanylin and uroguanylin in the regulation of sodium excretion, we used gene-targeted mice in which the uroguanylin, guanylin or the peptide receptor guanylate cyclase C gene expression had been ablated. Results: Metabolic balance studies demonstrated that there was impaired excretion of a sodium load in uroguanylin (but not in guanylin or guanylate cyclase C) knockout mice. Uroguanylin-dependent natriuresis occurred without an increase in circulating prouroguanylin. A distinct morphological phenotype was present in the proximal convoluted tubules of uroguanylin knockout animals after an enteral salt loading. Marked vacuolization of the proximal convoluted tubule epithelial cells was observed by using light and electron microscopy. There was also a change in the distribution of the sodium hydrogen exchanger 3 (NHE3) after an enteral salt loading. In wild-type animals, there was a partial redistribution of NHE3 from the villus fraction to the less accessible submicrovillus membrane compartment, but this effect was less apparent in uroguanylin knockout animals, presumably resulting in greater Na+/H+ exchange. Conclusions: Together, these findings further establish a role for uroguanylin in fluid homeostasis and support a role for uroguanylin as an integral component of a signaling mechanism that mediates changes in Na+ excretion in response to an enteral salt loading. Proximal tubular NHE3 activity is a possible target for uroguanylin-mediated changes in Na+ excretion.

To examine the concordance between self-collected and clinician-collected samples for human papillomavirus (HPV) DNA.Sexually active adolescent and young adult women aged 14-21 years (N = 101) were enrolled in a prospective cohort study of HPV testing. Participants self-collected vaginal samples for HPV DNA, and clinicians collected cervicovaginal samples for HPV DNA and a cervical cytology specimen. We determined concordance between the results of self- and clinician-collected specimens using a kappa statistic and McNemar's test.Of the 51% of participants who were HPV positive, 53% had 1 type, 25% had 2 types, and 22% had 3 types or more; 25 different HPV types were identified. Self-collected samples detected more participants with HPV than clinician-collected samples (45% versus 42%, P =.65). When results were categorized into presence or absence of high-risk HPV types, agreement between self- and clinician-collected specimens was high (kappa 0.72) and the difference between test results was not significant (McNemar's P =.41). However, when all HPV types detected were considered, agreement was perfect in only 51% of those with 1 or more types of high-risk HPV type. There was no association between agreement and age or HPV type.Self testing for HPV DNA may be sufficiently sensitive for the detection of high-risk HPV DNA among adolescent and young adult women in clinical settings.

The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents. The kidney transplant was delayed by 6 hours after the liver transplant to allow more time to the liver allograft to “absorb” donor-specific antibodies (DSA). Interestingly, the liver allograft did not prevent immediate antibody-mediated injury to the kidney allograft in this highly sensitized recipient. Anti-HLA single antigen bead analysis of liver and kidney allograft biopsy eluates revealed deposition of both class I and II DSA in both liver and kidney transplants during the first 2 weeks after transplant. Afterward, both liver and kidney allograft functions improved and remained normal after a year with progressive reduction in serum DSA values.

We have cloned and characterized the gene and complementary DNA for a new kringle-containing protein. Although the function of this protein is not known, it has been called hepatocyte growth factor–like protein because it shares the same structural domains as hepatocyte growth factor, with four kringle structures followed by a region homologous to serine proteases. To determine if hepatocyte growth factor-like protein is synthesized by the same cells as hepatocyte growth factor, we surveyed adult mouse and developing mouse embryo tissues by in situ hybridization analysis using radiolabeled RNA for hepatocyte growth factor–like protein. Results of in situ hybridization analysis of adult mouse tissues show that among all surveyed tissues specific signal was restricted to the liver. Higher magnification of liver sections shows that hepatocytes were the only cell type expressing messenger RNA for hepatocyte growth factor–like protein, contrary to the reported presence of hepatocyte growth factor messenger RNA in fatstoring cells. A similar liver-restricted and hepatocytespecific pattern of messenger RNA expression was observed in the developing mouse embryo at 14 days of gestation. All other developing tissues that were analyzed, as well as liver hematopoietic cells, did not express messenger RNA for hepatocyte growth factor–like protein at levels detectable by this technique. We conclude that although structurally similar to hepatocyte growth factor, hepatocyte growth factor–like protein is a novel protein synthesized primarily in hepatocytes. (HEPATOLOGY 1993;18:394–399).