Explore the vast range of titles available.

This review discusses unique aspects of kidney transplantation in children that necessitate specialized approaches and have resulted in clinical advances so that kidney transplantations in young children have higher success rates than in any other age group. Since the first successful kidney transplantation in 1954, 1 kidney transplantation has become the best treatment for adult patients with kidney failure. However, early pediatric kidney transplantation was complicated by technical, immunologic, and logistic problems, all leading to worse patient and graft survival among children than had been observed among adults. Over the past 15 years, a number of advances have greatly improved patient and graft survival among children with kidney transplants. 2 , 3 Some aspects of clinical kidney transplantation are similar in children and adults. The immunosuppressive medications and regimens used are similar, creatinine is the major serum biomarker, acute rejection . . .

In this international randomized, controlled trial, one kidney from each pair from 336 consecutive deceased donors was randomly assigned to machine perfusion and the other to cold storage. All recipients were followed for 1 year. Hypothermic machine perfusion was associated with a reduced risk of the primary end point — delayed graft function — and improved graft survival in the first year after transplantation. In this trial, one kidney from each pair from deceased donors was randomly assigned to machine perfusion and the other to cold storage. Hypothermic machine perfusion was associated with a reduced risk of the primary end point — delayed graft function — and improved graft survival in the first year after transplantation. Two different forms of organ preservation — static cold storage and hypothermic machine perfusion — are used clinically for renal allografts obtained from deceased donors. In static cold storage, the kidney is flushed, cooled with one of several cold preservation solutions, and transported on ice. In hypothermic machine perfusion, after an initial washout of blood, the kidney is connected to a perfusion device, and a solution is pumped continuously through the renal vasculature at temperatures between 1 and 10°C. 1 The typical deceased kidney donor today is older and has been exposed to more concomitant disease than donors were several decades . . .

This study demonstrates that switching from calcineurin inhibitors to sirolimus had an antitumoral effect in kidney-transplant recipients with cutaneous squamous-cell carcinomas and may have implications concerning immunosuppressive treatment of such patients. Skin cancers affect more than half of organ-transplant recipients during their long-term course. 1 Several studies have shown that after a first cutaneous squamous-cell carcinoma, multiple subsequent skin cancers develop in 60 to 80% of kidney-transplant recipients within 3 years. 2 , 3 Transplant recipients share common risk factors with the nonimmunosuppressed population, 4 but the specific tumor burden of such patients is linked to the immunosuppressive medications used. 5 , 6 A decrease in cutaneous carcinogenesis after the reduction of immunosuppression has been reported. 7 Consequently, changes in immunosuppression are frequently made in patients with skin cancer, although there is currently no consensus on the level . . .

In this trial of kidney transplantation involving HIV-infected patients, rates of patient and graft survival were high at 1 and 3 years, with no HIV-associated complications. However, unexpectedly high rejection rates were an important concern. An increasing number of persons living with human immunodeficiency virus (HIV) infection who have end-stage renal disease (ESRD) are seeking renal transplantation. Despite the efficacy of highly active antiretroviral therapy (HAART) in reducing the risk of HIV-related renal disease, the incidence of ESRD continues to increase among patients with HIV infection. 1 – 5 In the United States and Europe, nearly 1% of patients with ESRD are infected with HIV, and HIV-associated nephropathy is the third most common cause of ESRD among blacks in the United States who are between 20 and 64 years of age. 6 – 9 We conducted a multicenter, prospective . . .

Five patients with end-stage renal disease received bone marrow and kidney transplants from HLA-mismatched living related donors. Transient hematopoietic chimerism developed in all five. In one patient, irreversible humoral rejection occurred. In the other four recipients, immunosuppressive therapy was discontinued after 9 to 14 months and renal function has subsequently remained stable. Five patients with end-stage renal disease received bone marrow and kidney transplants from HLA-mismatched living related donors. In four recipients, immunosuppressive therapy was discontinued after 9 to 14 months and renal function has subsequently remained stable. Long-term results of organ transplantation remain unsatisfactory, mainly because of chronic rejection and complications associated with immunosuppressive medications. 1 , 2 Immune tolerance, which has been achieved in animal models, might provide a means for avoiding both of these problems. However, the results of attempts to extend such studies from laboratory animals to humans have been disappointing. 3 – 7 Tolerance of allografts has been induced in mice 8 and larger animals 9 by first transplanting hematopoietic stem cells from the prospective donor into the recipient, thereby creating a lymphohematopoietic chimera in which donor and recipient hematopoiesis coexist (“mixed chimera”). Using a nonmyeloablative perioperative regimen, we . . .

A patient received a kidney graft from his HLA-identical brother, followed by an infusion of CD34+ hematopoietic stem cells from the same donor. An apparent state of immunologic tolerance to the kidney allograft developed, allowing withdrawal of all immunosuppressive therapy within 6 months. A patient received a kidney graft from his HLA-identical brother, followed by an infusion of CD34+ hematopoietic stem cells from the same donor. Immunologic tolerance to the kidney allograft developed, allowing withdrawal of all immunosuppressive therapy within 6 months. Immune tolerance of organ transplants has been induced in laboratory animals when persistent mixed blood and immune-cell chimerism has been achieved by infusing hematopoietic cells from the organ donor before or after transplantation of the organ. 1 – 3 The continued presence of the organ donor's immune cells in the recipient's thymus and peripheral lymphoid tissue promotes and maintains immune tolerance by eliminating T-cell clones that can react to alloantigens of the graft. 1 – 3 We have attempted to achieve persistent mixed chimerism and tolerance in humans after transplantation of combined HLA-matched kidney and hematopoietic cells, using a low-intensity conditioning regimen of total . . .

This open-label, phase 1–2, single-center study examined the use of intravenous immune globulin and rituximab to reduce anti-HLA antibodies and improve transplantation rates in 20 highly sensitized patients. Sixteen patients (80%) subsequently received a transplant, and the 1-year survival rates for patients and allografts were 100% and 94%, respectively. Larger and longer trials are needed to assess the safety of this approach. This study examined the use of intravenous immune globulin and rituximab to reduce anti-HLA antibodies and improve transplantation rates in 20 highly sensitized patients. Sixteen patients (80%) subsequently received a transplant, and the 1-year survival rates for patients and allografts were 100% and 94%, respectively. Renal transplantation is considered the treatment of choice for patients with end-stage renal disease, since it offers improved survival and quality-of-life benefits as compared with dialysis and is considerably less costly to payers. 1 – 3 Currently, there are more than 74,275 patients with end-stage renal disease in the United States on the deceased-donor waiting list, and more than 30,000 new registrants are added each year. Despite this, there are fewer than 18,000 total kidney transplantations in the United States each year. 4 The waiting times for kidney transplants continue to increase, owing to the limited supply. This is especially true for patients . . .

The intrarenal resistive index is often measured to assess allograft status, but its value is unclear. This study showed that the resistive index, measured at predefined times after transplantation, reflects recipient factors but not intrinsic characteristics of the allograft. In many renal-transplantation centers, measurement of the intrarenal resistive index by means of Doppler ultrasonography is routinely used to evaluate renal allografts. 1 , 2 The resistive index is derived from the pulsatile flow-velocity waveform. In native kidneys, a higher resistive index, as compared with a lower resistive index, is a significant predictor of progressive renal dysfunction and adverse cardiovascular events. 3 – 9 A previous cross-sectional study linked an increased intrarenal resistive index after kidney transplantation with an increased risk of graft loss or recipient death. 10 Although these data suggest that the intrarenal resistive index reflects the intrinsic state of the allograft, it . . .

Adult kidney regeneration Fish can regenerate nephrons — the functional units of the kidney — following kidney injury, whereas adult mammals lack this ability. A previously unknown type of kidney cell responsible for this regeneration has now been discovered in adult zebrafish, where they are found in small aggregations throughout the kidney. When as few as 10–20 of these progenitor cells are transplanted into injured adult kidneys, they engraft and form new, functional nephrons. This suggests that it might be possible to identify an equivalent regenerative cell in humans for therapeutic purposes. Fish can regenerate nephrons (the functional units of the kidney) de novo after kidney injury, whereas adult mammals lack this ability. This study identifies a pool of self renewing nephron stem/progenitor cells that are responsible for nephrogenesis during kidney growth and regeneration in zebrafish. The findings might provide an insight into how mammalian renal regeneration may be therapeutically activated. Loss of kidney function underlies many renal diseases 1 . Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones 2 , 3 . By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury 4 , 5 , providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10–30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.

Renal-transplant recipients were given alemtuzumab induction therapy or conventional induction therapy as part of a program of early glucocorticoid withdrawal. Acute rejection was less frequent with alemtuzumab during the first year. In the United States between 1998 and 2007, a total of 78% of renal-transplant recipients received antibody induction therapy. The most frequently used agents have been rabbit antithymocyte globulin (Thymoglobulin, Genzyme), a lymphocyte-depleting polyclonal antibody, and basiliximab (Simulect, Novartis Pharmaceuticals), a non–lymphocyte-depleting monoclonal antibody targeting the interleukin-2 receptor. 1 More recently, alemtuzumab (Campath-1H, Berlex Laboratories), an anti-CD52 T-cell and B-cell–depleting monoclonal antibody, has been used for induction in renal transplantation. 2 – 5 Although a number of trials of early glucocorticoid withdrawal and calcineurin-inhibitor minimization have been conducted in renal-transplant recipients over the past decade, it is not clear which induction agent is . . .