African-Americans with End Stage Renal Disease in the Early Years of Kidney Transplantation.

INTRODUCTION: The first successful kidney transplant in humans was performed in 1954. In the following 25 years, the biomedical, ethical, and social implications of kidney transplantation were widely discussed by both healthcare professionals and the public. Issues relating to race, however, were not commonly addressed, representing a "blind spot" regarding racial disparities in access and health outcomes. METHODS: Through primary sources in the medical literature and lay press, this paper explores the racial dynamics of kidney transplantation in the 1950-1970s in the United States as the procedure grew from an experimental procedure to the standard of care for patients in end-stage renal disease (ESRD). RESULTS & DISCUSSION: An extensive search of the medical literature found very few papers about ESRD, dialysis, or renal transplant that mentioned the race of the patients before 1975. While the search did not reveal whether race was explicitly used in determining patient access to dialysis or transplant, the scant data that exist show that African-Americans disproportionately developed ESRD and were underrepresented in these early treatment populations. Transplant outcome data in the United States failed to include race demographics until the late 1970s. The Social Security Act of 1972 (PL 92-603) extended Medicare coverage to almost all Americans with ESRD and led to a rapid increase in both dialysis and kidney transplantation for African-Americans in ESRD, but disparities persist today.

Living Kidney Donors Who Develop Kidney Failure: Excerpts of Their Thoughts.

BACKGROUND: Psychosocial data about living kidney donors have been collected for almost 5 decades now. To date, however, no study has provided any psychosocial follow-up of donors who developed a serious health problem such as end-stage renal disease (ESRD). METHODS: Donors who developed ESRD were invited to participate in a qualitative interview if they met one or both of the inclusion criteria: (1) developed ESRD within 10 years of donating and/or (2) lacked health insurance at the time of donation. We contacted 38 individuals who met these criteria, and 22 participated (58%). Two were subsequently excluded from analysis. RESULTS: Twenty qualitative interviews were analyzed. Five findings are described: (1) donors describe the decision-making process as spontaneous and fast; (2) donors describe lack of appreciation for the need for post-donation self-care; (3) donors do not regret donating despite the adverse outcome; (4) donors advise future donors to have in place emotional and physical support post donation; and (5) donors appreciate the opportunity to tell their story from being a living donor to living with ESRD, which virtually all perceive as 2 separate unrelated events. CONCLUSIONS: Most donors are positive about their donation decision and experience and would donate again, despite developing ESRD themselves. They propose some important changes to the decision-making and informed-consent processes. Our data are reassuring regarding lack of donor regret, but highlight the need for living donor transplant programs to ensure that living donors understand their long-term risks and receive appropriate life-long follow-up care to minimize these risks.

Adding Another Voice to the Living Donor Kidney Transplant Discussions at the CIBA Symposium of 1966.

In March 1966, the CIBA Foundation sponsored an international interdisciplinary conference on transplantation. Attendees included surgeons, physicians from many medical disciplines, legal professionals, a minister, and a science reporter. Although the main topic of discussion was the living donor, none was present. This article gives voice to the living donor through two qualitative interviews with men who donated at different centers in the United States in the early 1960s and subsequently developed end-stage renal disease (ESRD). These narratives contribute to five topics discussed at the CIBA meeting that are still relevant today: (1) pressure to donate; (2) special donor categories; (3) donor health; (4) socioeconomic consequences of donation; and (5) lack of regret.

Profiling CCK-mediated pancreatic growth: the dynamic genetic program and the role of STATs as potential regulators.

Feeding mice with protease inhibitor (PI) leads to increased endogenous cholecystokinin (CCK) release and results in pancreatic growth. This adaptive response requires calcineurin (CN)-NFAT and AKT-mTOR pathways, but the genes involved, the dynamics of their expression, and other regulatory pathways remain unknown. Here, we examined the early (1-8 h) transcriptional program that underlies pancreatic growth. We found 314 upregulated and 219 downregulated genes with diverse temporal and functional profiles. Several new identifications include the following: stress response genes Gdf15 and Txnip, metabolic mediators Pitpnc1 and Hmges2, as well as components of growth factor response Fgf21, Atf3, and Egr1. The genes fell into seven self-organizing clusters, each with a distinct pattern of expression; a representative gene within each of the upregulated clusters (Egr1, Gadd45b, Rgs2, and Serpinb1a) was validated by qRT-PCR. Genes up at any point throughout the time course and CN-dependent genes were subjected to further bioinformatics-based networking and promoter analysis, yielding STATs as potential transcriptional regulators. As shown by PCR, qPCR, and Western blots, the active phospho-form of STAT3 and the Jak-STAT feedback inhibitor Socs2 were both increased throughout early pancreatic growth. Moreover, immunohistochemistry showed a CCK-dependent and acinar cell-specific increase in nuclear localization of p-STAT3, with >75% nuclear occupancy in PI-fed mice vs. <0.1% in controls. Thus, the study identified novel genes likely to be important for CCK-driven pancreatic growth, characterized and biologically validated the dynamic pattern of their expression and investigated STAT-Socs signaling as a new player in this trophic response.

CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth.

Dietary protein can stimulate pancreatic growth in the absence of CCK release, but there is little data on the regulation of CCK-independent growth. To identify mechanisms whereby protein stimulates pancreatic growth in the absence of CCK release, C57BL/6 control and CCK-null male mice were fed normal-protein (14% casein) or high-protein (75% casein) chow for 7 days. The weight of the pancreas increased by 32% in C57BL/6 mice and 26% in CCK-null mice fed high-protein chow. Changes in pancreatic weight in control mice were due to both cell hypertrophy and hyperplasia since there was an increase in protein-to-DNA ratio, total DNA content, and DNA synthesis. In CCK-null mice pancreatic growth was almost entirely due to hypertrophy with both protein-to-DNA ratio and cell size increasing without significant increases in DNA content or DNA synthesis. ERK, calcineurin, and mammalian target of rapamycin complex 1 (mTORC1) are activated in models of CCK-induced growth, but there were no differences in ERK or calcineurin activation between fasted and fed CCK-null mice. In contrast, mTORC1 activation was increased after feeding and the duration of activation was prolonged in mice fed high-protein chow compared with normal-protein chow. Changes in pancreatic weight and RNA content were completely inhibited, and changes in protein content were partially abated, when the mTORC1 inhibitor rapamycin was administered during high-protein chow feeding. Prolonged mTORC1 activation is thus required for dietary protein-induced pancreatic growth in the absence of CCK.