Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0.48 (range, 0.12 to 0.98) g/g. An extra-renal immune-related adverse event occurred prior to the onset of AKI in 7 patients. Median peak serum creatinine was 4.5 (interquartile range, 3.6-7.3) mg/dl with 4 patients requiring hemodialysis. The prevalent pathologic lesion was acute tubulointerstitial nephritis in 12 patients, with 3 having granulomatous features, and one thrombotic microangiopathy. Among the 12 patients with acute tubulointerstitial nephritis, 10 received treatment with glucocorticoids, resulting in complete or partial improvement in renal function in 2 and 7 patients, respectively. However, the two patients with acute tubulointerstitial nephritis not given glucocorticoids had no improvement in renal function. Thus, CPI-induced AKI is a new entity that presents with clinical and histologic features similar to other causes of drug-induced acute tubulointerstitial nephritis, though with a longer latency period. Glucocorticoids appear to be a potentially effective treatment strategy. Hence, AKI due to CPIs may be caused by a unique mechanism of action linked to reprogramming of the immune system, leading to loss of tolerance.

A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. Here we provide our overview of potassium homeostasis in health and disease and guidance for evaluation and management of dyskalemias in the context of kidney diseases, and indicate research priorities.

The proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.g., indoxyl sulfate), environmental toxins (e.g., mercury, aristolochic acid), metabolites (e.g., uric acid), dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters of the solute carrier (SLC) superfamily, including organic anion transporter (OAT) and organic cation transporter (OCT) subfamilies, and the ATP-binding cassette (ABC) superfamily. We review the basic physiology of these SLC and ABC transporters, many of which are often called drug transporters. With an emphasis on OAT1 (SLC22A6), the closely related OAT3 (SLC22A8), and OCT2 (SLC22A2), we explore the implications of recent in vitro, in vivo, and clinical data pertinent to the kidney. The analysis of murine knockouts has revealed a key role for these transporters in the renal handling not only of drugs and toxins but also of gut microbiome products, as well as liverderived phase 1 and phase 2 metabolites, including putative uremic toxins (among other molecules of metabolic and clinical importance). Functional activity of these transporters (and polymorphisms affecting it) plays a key role in drug handling and nephrotoxicity. These transporters may also play a role in remote sensing and signaling, as part of a versatile small molecule communication network operative throughout the body in normal and diseased states, such as AKI and CKD.

The glomerulus, the filtering unit of the kidney, is a unique bundle of capillaries lined by delicate fenestrated endothelia, a complex mesh of proteins that serve as the glomerular basement membrane and specialized visceral epithelial cells that form the slit diaphragms between interdigitating foot processes. Taken together, this arrangement allows continuous filtration of the plasma volume. The dynamic physical forces that determine the single nephron glomerular filtration are considered. In addition, new insights into the cellular and molecular components of the glomerular tuft and their contribution to glomerular disorders are explored.Clin J Am Soc Nephrol 9: 1461-1469, 2014. doi: 10.2215/CJN.09400913 The GlomerulusThe glomerulus, the filtering unit of the kidney, is a specialized bundle of capillaries that are uniquely situated between two resistance vessels ( Figure 1). These capillaries are each contained within the Bowman's capsule and they are the only capillary beds in the body that are not surrounded by interstitial tissue. Therefore, a unique support structure is needed to maintain flow in these essential capillary units. In fact, all of the major components of the filter itself are unique compared with related structures in other capillary beds. The proximal component layer of the glomerular filter itself is a fenestrated endothelium, characterized by the presence of individual fenestrae on the order of 70-100 nm in diameter. These cells drape the luminal aspect of the capillary and permit filtration. The second layer of the filter, the glomerular basement membrane (GBM), is a complex mesh of extracellular proteins, including type IV collagen, laminins, fibronectins, and proteoglycans. The distal layer of the glomerular filter is composed of the visceral epithelial cells, or podocytes. These remarkable cells help to create the filtration slit diaphragm and serve as support to help sustain the integrity of the free-standing capillary loops. A third cell type, the mesangial cells, also contributes to the integrity of the glomerular tuft and the dynamic nature of filtration. Together, this elegant structure permits the formation of the primary glomerular filtrate that enters a space delimited by the visceral and parietal epithelial cells before modification during transit through the tubule.

The concept of homeostasis has been inextricably linked to the function of the kidneys for more than a century when it was recognized that the kidneys had the ability to maintain the "internal milieu" and allow organisms the "physiologic freedom" to move into varying environments and take in varying diets and fluids. Early ingenious, albeit rudimentary, experiments unlocked a wealth of secrets on the mechanisms involved in the formation of urine and renal handling of the gamut of electrolytes, as well as that of water, acid, and protein. Recent scientific advances have confirmed these prescient postulates such that the modern clinician is the beneficiary of a rich understanding of the nephron and the kidney's critical role in homeostasis down to the molecular level. This review summarizes those early achievements and provides a framework and introduction for the new CJASN series on renal physiology.

As the U.S. health care system changes and technology alters how doctors work and learn, medical schools and their faculty are compelled to modify their curricula and teaching methods. In this article, educational leaders and key faculty describe how the Pathways curriculum was conceived, designed, and implemented at Harvard Medical School. Faculty were committed to the principle that educators should focus on how students learn and their ability to apply what they learn in the evaluation and care of patients. Using the best evidence from the cognitive sciences about adult learning, they made major changes in the pedagogical approach employed in the classroom and clinic. The curriculum was built upon 4 foundational principles: to enhance critical thinking and provide developmentally appropriate content; to ensure both horizontal integration between courses and vertical integration between phases of the curriculum; to engage learners, foster curiosity, and reinforce the importance of student ownership and responsibility for their learning; and to support students’ transformation to a professional dedicated to the care of their patients and to their obligations for lifelong, self-directed learning. The practice of medicine is rapidly evolving and will undoubtedly change in multiple ways over the career of a physician. By emphasizing personal responsibility, professionalism, and thinking skills over content transfer, the authors believe this curriculum will prepare students not only for the first day of practice but also for an uncertain future in the biological sciences, health and disease, and the nation’s health care system, which they will encounter in the decades to come.

Background Acute kidney injury (AKI) is a sudden episode of kidney damage or failure affecting up to 15% of hospitalized patients and is associated with serious short- and long-term complications, mortality, and health care costs. Current practices to diagnose and stage AKI are variable and do not factor in our improved understanding of the biological and analytical variability of creatinine. In addition, the emergence of biomarkers, for example, cystatin C, insulin-like growth factor binding protein 7, and tissue inhibitor of metalloproteinases 2, and electronic notification tools for earlier detection of AKI, highlights the need for updated recommendations to address these developments. Content This AACC Academy guidance document is intended to provide laboratorians and clinicians up-to-date information regarding current best practices for the laboratory investigation of AKI. Topics covered include: clinical indications for further investigating potential AKI, analytical considerations for creatinine assays, the impact of biological variability on diagnostic thresholds, defining “baseline” creatinine, role of traditional markers (urine sodium, fractional excretion of sodium, fractional excretion of urea, and blood urea-to-creatinine ratio), urinary microscopic examination, new biomarkers, improving AKI-associated test utilization, and the utility of automated AKI alerts. Summary The previous decade brought us a significant number of new studies characterizing the performance of existing and new biomarkers, as well as potential new tools for early detection and notification of AKI. This guidance document is intended to inform clinicians and laboratorians on the best practices for the laboratory investigation of AKI, based on expert recommendations where the preponderance of evidence is available.

BackgroundWeb-based formative assessment tools have become widely recognized in medical education as valuable resources for self-directed learning.ObjectivesTo explore the educational value of formative assessment using online quizzes for kidney pathology learning in our renal pathophysiology course.MethodsStudents were given unrestricted and optional access to quizzes. Performance on quizzed and non-quizzed materials of those who used (‘quizzers’) and did not use the tool (‘non-quizzers’) was compared. Frequency of tool usage was analyzed and satisfaction surveys were utilized at the end of the course.ResultsIn total, 82.6% of the students used quizzes. The greatest usage was observed on the day before the final exam. Students repeated interactive and more challenging quizzes more often. Average means between final exam scores for quizzed and unrelated materials were almost equal for ‘quizzers’ and ‘non-quizzers’, but ‘quizzers’ performed statistically better than ‘non-quizzers’ on both, quizzed (p=0.001) and non-quizzed (p=0.024) topics. In total, 89% of surveyed students thought quizzes improved their learning experience in this course.ConclusionsOur new computer-assisted learning tool is popular, and although its use can predict the final exam outcome, it does not provide strong evidence for direct improvement in academic performance. Students who chose to use quizzes did well on all aspects of the final exam and most commonly used quizzes to practice for final exam. Our efforts to revitalize the course material and promote learning by adding interactive online formative assessments improved students’ learning experience overall.