ANCA-associated pauci-immune necrotizing glomerulonephritis during the treatment with pembrolizumab.

Cancer immunotherapy is rapidly changing the treatment paradigm in oncology, and immune checkpoint inhibitors (ICPIs) have been used successfully in a variety of cancer types. Specific side effects termed immune-related adverse events (irAEs) have now been described in various organ systems, including the kidney. Renal complications have rarely been reported compared with other irAEs and mostly consist of acute interstitial nephritis. Only rare cases of ICPI-related glomerulonephritis have been described. Herein, we report the case of an adult patient treated with pembrolizumab (anti-PD-1) for squamous cell carcinoma (SCC), who developed infectious enterocolitis, and ANCA-related with diffuse necrotizing crescentic glomerulonephritis, both conditions potentially linked to treatment with pembrolizumab.

Cardiac evaluation prior to kidney transplantation.

Kidney transplantation is the treatment of choice for most patients with stage 5 chronic kidney disease and end-stage renal disease (ESRD), offering improved quality of life and overall survival rates. However, the limited supply of available organs makes this a scarce resource. Cardiovascular complications continue to be the leading cause of mortality in the kidney transplant population, accounting for over 30% of deaths with a functioning allograft. Thus, preoperative cardiac risk assessment is critical to optimize patient selection and outcomes. Currently there is no consensus for cardiovascular evaluation in the chronic kidney disease and ESRD population prior to kidney transplantation; the recommendations of the American Society of Nephrology and American Society of Transplantation differ from those of the American Heart Association and the American College of Cardiology. Previously developed risk scores have also been used to risk stratify this population. In this review, we discuss two cases that illustrate the difficulties of interpreting the prognostic value of current testing strategies. We also discuss the importance of different tests for cardiovascular evaluation as well as previous nonkidney transplant specific risk scores used in the pre-kidney transplant population.

Topics in transplantation medicine for general nephrologists.

Before transplantation, the general nephrologist is the primary resource for potential kidney transplantation recipients. After transplantation, the general nephrologist is increasingly managing transplant medications and complications. We provide evidence-based management strategies for common clinical issues. Linking our approach with the data allows the clinician to explore each subject in greater depth to tailor care to individual patients.

Langerhans cells are not required for efficient skin graft rejection.

The mechanism of skin allograft rejection has been thought to require presentation of graft antigen by resident epidermal Langerhans cells (LCs). We have previously engineered mice that have a selective and constitutive absence of epidermal LCs. By using donor skin from these LC-deficient mice, we show that LCs are not required for rejection of major (FVB --> B6) or minor (H-Y, male --> female on B6 background) antigen-mismatched skin grafts. On the FVB background, where H-Y mismatched grafts are normally maintained indefinitely, grafts lacking LCs are efficiently rejected. Thus, LCs in the donor graft are required for long-term skin engraftment, which supports a regulatory role for LCs in skin graft acceptance.

Effector T cell differentiation and memory T cell maintenance outside secondary lymphoid organs.

Naive T cell circulation is restricted to secondary lymphoid organs. Effector and memory T cells, in contrast, acquire the ability to migrate to nonlymphoid tissues. In this study we examined whether nonlymphoid tissues contribute to the differentiation of effector T cells to memory cells and the long-term maintenance of memory T cells. We found that CD4, but not CD8, effector T cell differentiation to memory cells is impaired in adoptive hosts that lack secondary lymphoid organs. In contrast, established CD4 and CD8 memory T cells underwent basal homeostatic proliferation in the liver, lungs, and bone marrow, were maintained long-term, and functioned in the absence of secondary lymphoid organs. CD8 memory T cells found in nonlymphoid tissues expressed both central and effector memory phenotypes, whereas CD4 memory T cells displayed predominantly an effector memory phenotype. These findings indicate that secondary lymphoid organs are not necessary for the maintenance and function of memory T cell populations, whereas the optimal differentiation of CD4 effectors to memory T cells is dependent on these organs. The ability of memory T cells to persist and respond to foreign Ag independently of secondary lymphoid tissues supports the existence of nonlymphoid memory T cell pools that provide essential immune surveillance in the periphery.

The role of toll-like receptors in solid organ transplantation.

Toll-like receptors (TLR) are critical sentinels of the host innate immune system. Prior evidence has clearly demonstrated that these receptors are essential to immune recognition of invading pathogens. However, there is emerging evidence that TLR signaling participates in inflammation that is not driven by microorganisms. In the setting of solid organ transplantation, there is accumulating evidence, both in experimental and clinical studies, that TLR signaling is involved in the immune recognition of allografts. Further investigation of how innate immunity impacts solid organ transplantation will likely lead to improved therapeutics for transplant recipients.