Serum sodium disorders are generally a marker of water balance in the body. Thus, hypernatremia is most often caused by an overall deficit of total body water. Other unique circumstances may lead to excess salt, without an impact on the body's total water volume. Hypernatremia is commonly acquired in both the hospital and community. As hypernatremia is associated with increased morbidity and mortality, treatment should be initiated promptly. In this review, we will discuss the pathophysiology and management of the main types of hypernatremia, which can be categorized as either a loss of water or gain of sodium that can be mediated by renal or extrarenal mechanisms.

Kumar, Arjun; McCartney, Audrey; Zimmermann, Nives; Brathwaite, Latoya L.; Patel, Niralee Author Information

We are experiencing a revolution in nephrology education. In all phases of a learner's career—undergraduate medical education (UME), graduate medical education, and postgraduate education—shifts in priorities, funding, and patient care have dramatically altered how we teach.1Summer R. Wiener R.S. Carroll D. et al.Physician perception of the impact of productivity measures on academic practice.Arch Intern Med. 2012; 172: 967-969Crossref PubMed Scopus (13) Google Scholar,2Seifert W.E. Strobel H.W. Values, RVUs and teaching.Med Sci Educator. 2010; 20: 62-65Google Scholar Developing novel ways to teach nephrology, at all learner levels, will be critical to meet the needs of restructured UME curricula, the increased prevalence and treatment modalities for kidney disease, and the changing nature of renal fellowship. In this edition of the Advances in Chronic Kidney Disease (ACKD), we highlight innovative nephrology curricula, developed by leading educators, and share how to implement these tools more widely at other institutions. As of 2018, approximately half of medical schools had shifted from a 2-year preclerkship phase to an 18-month or shorter preclerkship phase, and data from the American Association of Medical Colleges (AAMC) show 85% of medical schools are planning or have implemented a new curriculum within the past 3 years, suggesting more schools are moving toward this timing.3Structure of pre-clerkship curriculum. AAMC.https://www.aamc.org/data-reports/curriculum-reports/interactive-data/structure-pre-clerkship-curriculumDate accessed: August 30, 2022Google Scholar,4Curriculum change in medical schools. AAMC.https://www.aamc.org/data-reports/curriculum-reports/interactive-data/curriculum-change-medical-schoolsDate accessed: August 30, 2022Google Scholar This shortening of the preclerkship years requires an emphasis on essential and clinically oriented topics, with a resultant reduction of content deemed less relevant to clinical practice.5Pock A.R. Durning S.J. Gilliland W.R. et al.Post-carnegie II curricular Reform: a North American survey of Emerging trends & challenges.BMC Med Education. 2019; 19: 1-12Crossref PubMed Scopus (16) Google Scholar Additionally, schools are placing a greater emphasis on small-group, active learning and shifting away from a lecture-heavy teaching strategy.5Pock A.R. Durning S.J. Gilliland W.R. et al.Post-carnegie II curricular Reform: a North American survey of Emerging trends & challenges.BMC Med Education. 2019; 19: 1-12Crossref PubMed Scopus (16) Google Scholar This, combined with the recognition of the vast impact of social determinants of health and racism on patient care, has dramatically altered the UME educational landscape.5Pock A.R. Durning S.J. Gilliland W.R. et al.Post-carnegie II curricular Reform: a North American survey of Emerging trends & challenges.BMC Med Education. 2019; 19: 1-12Crossref PubMed Scopus (16) Google Scholar, 6Borrell L.N. Elhawary J.R. Fuentes-Afflick E. et al.Race and Genetic Ancestry in medicine - a time for Reckoning with racism.N Engl J Med. 2021; 384: 474-480Crossref PubMed Scopus (187) Google Scholar, 7Hardeman R.R. Medina E.M. Kozhimannil K.B. Structural racism and Supporting Black Lives - the role of health Professionals.N Engl J Med. 2016; 375: 2113-2115Crossref PubMed Scopus (238) Google Scholar These changes can present a challenge to nephrology educators who have developed rich curricula with a heavy emphasis on glomerular and kidney physiology. Dr Stern and colleagues describe the challenges and opportunities for nephrology educators to adapt to a shorter preclerkship phase by focusing on more clinically relevant topics and replacing lectures with faculty-led small-group sessions. They propose innovative additions to the curriculum, including dialysis policy, and using the lessons of apolipoprotein L1(APOL1) to demonstrate the pitfalls of conflating race and biology. To help implement inquiry-based, active learning of complex renal physiology topics, Dr Hoenig and colleagues present their "hands-on" kidney physiology lab, where students review and interpret original data from seminal experiments to better understand kidney physiology. These laboratories exploit students' natural curiosity in order to teach fundamental kidney physiologic concepts while providing an opportunity for self-directed learning and enhancement of problem-solving skills. Finally, Paloma Orozco-Scott, MPH, Jerrel Cattlett, and others propose a framework for antiracist teaching, which provides educators with an actionable and stepwise plan for grappling with the social construct of race, which is often presented as a biologic fact. Taken together, these 3 articles provide UME educators with the necessary tools to create and teach a modern, antioppressive, exciting, hands-on, and clinically focused preclerkship nephrology course. For almost a decade, trends in graduate training of medical residents demonstrated a declining interest in nephrology, leading to a decrease in the number of nephrology applicants and eventually a relative reduction in the nephrology workforce.8Nair D. Pivert K.A. Baudy At Thakar C.V. Perceptions of nephrology among medical students and internal medicine residents: a national survey among institutions with nephrology exposure.BMC Nephrol. 2019; 20: 146Crossref PubMed Scopus (25) Google Scholar By changing the current paradigms of how we educate, we have the opportunity to reverse this disheartening trend and enhance recruitment of trainees into our discipline. This challenge can be tackled by those in academic institutions as well as by community-based nephrologists who may be an untapped resource to encourage trainees in pursuing nephrology as a career choice. There have been several initiatives by training programs to attract residents into nephrology, ranging from alterations to work schedules to subspecialization into focused career pathways. Additionally, compared to historical methods, there has been a new focus on how the nephrology community teaches and evaluates trainees. Our challenge is not only to kindle a love of nephrology in students but also to continue that excitement during the continuum of their training as internal medicine residents. Dr Hilburg and colleagues assert that our goal as nephrology educators in teaching residents should predominantly be centered on resident education rather than on recruitment. They describe their ambulatory nephrology curriculum for all internal medicine trainees at the University of Pennsylvania. This curriculum focuses on common renal disorders encountered in general medicine and prepares internists to deliver superb care to a growing population of CKD patients; it does so in non–hospital-based settings, a domain of kidney care delivery often overlooked when planning traditional nephrology electives during their internal medicine training. Dr Kwon describes how nephrologists in private practice—who comprise the majority of practicing nephrologists—can be a valuable yet an untapped resource in complementing nephrology education and recruitment, especially for residents in community programs.9Quigley L. Salsberg E. Collins A. Report on the 2018 Survey of Nephrology Fellows. American Society of Nephrology, WA, DC2018Google Scholar While there are many limitations compared to academic settings, including time, personnel, and resources, she presents a compelling argument for the many rewards inherent to resident teaching. She describes how to delicately balance teaching and patient care duties and provides substantial resources and ideas for other private practitioners interested in teaching medical residents. Other ideas to enhance interest in nephrology include broadening the curricular offerings in fellowship programs and preparing fellows for the future in addition to the present. Dr Greenberg and colleagues describe the modern nephrology fellowship, which includes formal curricula in home dialysis, palliative care, and point-of-care ultrasound. They provide actionable ideas on how such curricula can be designed, and how fellowship programs that do not have access to these resources can partner with other groups to create meaningful learning opportunities for their fellows. Other important areas, such as the necessity to develop stellar clinician educators, are explored by Dr Jain and colleagues who describe a novel fellow educator pathway concomitant with the nephrology fellowship. The need for robust kidney pathology education to complement clinical training cannot be overstated. Dr Kuperman and Dr Caza and colleagues provide a perspective on educating nephrology fellows and practicing nephrologists in nephropathology. This form of teaching expands beyond formal classroom didactics and ranges from online resources, educational courses/symposia, and mentorship opportunities. Education in nephrology expands beyond the fellowship training phase that includes more than nephrologists. An expansion of advanced practice providers (APPs) in nephrology has led to increased multidisciplinary approaches of care and, hence, different approaches to dissemination of knowledge. However, since the training of APPs is apprentice-based, most APPs will begin their nephrology career without prior exposure to nephrology. Amy Sears, DNP, Kim Zuber PA-C, and Jane Davis DNP present a much-needed discussion on the necessity, benefits, and limitations in training for APP in nephrology. They propose the ideal training platform that would be beneficial for a successful partnership between APPs and physicians and outline current and past initiatives. Finally, nephrologists are more than clinicians—they are medical directors of dialysis units and serve in executive as well as operational roles and as entrepreneurs.10"Dr. Paul Klotman's Biography." Baylor College of Medicine.https://www.bcm.edu/about-us/leadership/dr-paul-klotmans-biographyDate accessed: October 12, 2022Google Scholar Leadership skills are necessary to function as a nephrologist but are typically not a part of nephrology training. Dr Yau and Dr Auguste discuss how to incorporate such training into a fellow curriculum and in continuing medical education. We are excited to present this ensemble of work for this unique issue of ACKD. We thank all our authors and reviewers for their contributions and Dr Charuhas V. Thakar for inviting us to be guest editors.

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m(2) were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.

In recent robust randomized control trials (RCTs), sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) have been shown to dramatically decrease both kidney and cardiovascular (CV) adverse outcomes in patients with diabetic kidney disease, nondiabetic proteinuric kidney disease, and heart failure with reduced ejection fraction—with and without the presence of diabetes (1–6). For decades, both the nephrologist’s and transplant nephrologist’s arsenal for the management of proteinuric kidney disease has been limited to renin-angiotensin-aldosterone system blockade (7). Although SGLT2 inhibitors have taken the nephrology community by storm, patients with kidney transplants (KTs) have been notably excluded from large RCTs (8–10). Pathophysiologically, it seems likely they would also benefit from these apparent wonder drugs, particularly as many patients with KT have proteinuric kidney disease or heart failure. Similar to patients with native kidney disease, CV mortality is the leading cause of death in the KT population (11). Is it time to allow patients with KT to benefit from proposed SGLT2 inhibitor mechanisms, including tubuloglomerular feedback restoration, decreased inflammation and fibrosis, and alteration in energy metabolism, that all culminate in improved CV and kidney outcomes (12)? Here, we review the available data for SGLT2 inhibitor use in patients with KTs and discuss potential benefits and risk of their use in this population. Since 2015, sequential RCTs have demonstrated efficacy of SGLT2 inhibitors in improving both kidney and CV outcomes. A 2020 meta-analysis included six of these RCTs that studied SGLT2 inhibitor use (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) in close to 47,000 patients with diabetes (2). In all of the studies included in the meta-analysis, SGLT2 inhibitor use led to a reduction in heart failure hospitalizations, with empagliflozin being the only drug with significant CV death risk reduction. A reduction in kidney outcomes was seen with all agents …

Dachshund homolog 1 (DACH1), a key cell-fate determinant, regulates transcription by DNA sequence-specific binding. We identified diminished Dach1 expression in a large-scale screen for mutations that convert injury-resistant podocytes into injury-susceptible podocytes. In diabetic kidney disease (DKD) patients, podocyte DACH1 expression levels are diminished, a condition that strongly correlates with poor clinical outcomes. Global Dach1 KO mice manifest renal hypoplasia and die perinatally. Podocyte-specific Dach1 KO mice, however, maintain normal glomerular architecture at baseline, but rapidly exhibit podocyte injury after diabetes onset. Furthermore, podocyte-specific augmentation of DACH1 expression in mice protects from DKD. Combined RNA sequencing and in silico promoter analysis reveal conversely overlapping glomerular transcriptomic signatures between podocyte-specific Dach1 and Pax transactivation-domain interacting protein (Ptip) KO mice, with upregulated genes possessing higher-than-expected numbers of promoter Dach1-binding sites. PTIP, an essential component of the activating histone H3 lysine 4 trimethylation (H3K4Me3) complex, interacts with DACH1 and is recruited by DACH1 to its promoter-binding sites. DACH1-PTIP recruitment represses transcription and reduces promoter H3K4Me3 levels. DACH1 knockdown in podocytes combined with hyperglycemia triggers target gene upregulation and increases promoter H3K4Me3. These findings reveal that in DKD, diminished DACH1 expression enhances podocyte injury vulnerability via epigenetic derepression of its target genes.

Abstract As paradigms of clinical care delivery have been significantly impacted by the novel coronavirus disease 2019 (COVID-19) pandemic, so has the structure, delivery, and future of medical education. Both undergraduate and graduate medical education have seen disruptions ranging from fully virtual delivery of educational content and limited clinical care for medical students to increased clinical demands with redeployment for residents and fellows. Adherence to social distancing has led to the adoption and implementation of already available technologies in medical education, including video conferencing softwares and social media platforms. Efficient and effective use of these technologies requires an understanding not only of these platforms and their features, but also of their inherent limitations. During a time of uncertainty and increased clinical demands, the approach to medical education must be thoughtful with attention to wellness of both the educator and learner. In this review, we discuss the influence of the pandemic on the existing medical education landscape, outline existing and proposed adaptations to social distancing, and describe challenges that lie ahead.

We thank Dr Parmar1Parmar M.S. COVID-19–associated acute kidney injury [letter].Kidney Med. 2020; 3: 128Google Scholar for his careful review of our article.2Patel N. Rein J.L. Sanchez-Russo L. Winston J. Uribarri J. COVID-19-associated acute kidney injury: a case series.Kidney Med. 2020; 2: 668-669Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar We do not agree that the serum urea nitrogen–creatinine ratio, as cited in reference 2, should become the standard definition of a hypercatabolic state.3Haines R.W. Zolfaghari P. Wan Y. Pearse R.M. Puthucheary Z. Prowle J.R. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma.Intensive Care Med. 2019; 45: 1718-1731Crossref PubMed Scopus (99) Google Scholar In that reference, the ratio was a prespecified outcome, their patients had a different phenotype compared with ours, most did not have acute kidney injury (AKI), and their work did not account for the influence of total parenteral nutrition on urea levels. It is widely known that parenteral nutrition is extensively and intensively used in intensive care units and may contribute significantly to increased serum urea nitrogen levels out of proportion to serum creatinine levels.4Gunst J. Vanhorebeek I. Casaer M.P. et al.Impact of early parenteral nutrition on metabolism and kidney injury.J Am Soc Nephrol. 2013; 24: 995-1005Crossref PubMed Scopus (81) Google Scholar Moreover, we have other data quantifying in a more precise way the inordinate levels of urea generation in COVID-19–associated AKI among patients similar to our cohort,5Uribarri J. El Shamy O. Sharma S. Winston J. COVID-19 associated AKI and quantified protein catabolic rate: a likely effect of cytokine storm on muscle protein breakdown.Kidney Med. 2021; 3: 60-63Scopus (8) Google Scholar strongly supporting a hypercatabolic state. We also disagree with Dr Parmar's interpretation of the meaning of near-normal creatinine kinase levels in our patients. We believe that these creatinine kinase values support our hypothesis that there was no actual loss of muscle cell integrity (rhabdomyolysis) but only increased muscle protein breakdown induced by the cytokine storm. We agree that there is much more to learn about the pathophysiology of this condition, both in COVID-19 and other critical illness. The authors declare that they have no relevant financial interests. Received October 14, 2020. Accepted October 25, 2020, after editorial review by the Editor-in-Chief. COVID-19–Associated Acute Kidney InjuryKidney MedicineVol. 3Issue 1PreviewIn their case series of acute kidney injury (AKI) associated with coronavirus disease 2019 (COVID-19), Patel et al1 proposed that a hypercatabolic state with muscle breakdown was the cause of AKI as they presented 3 cases that typify hypercatabolic state, with rapid increase in serum urea nitrogen levels, hyperuricemia, and hyperphosphatemia. However, in all 3 cases, the urea-creatinine ratio (UCR) was unchanged and was not elevated, as is observed in a hypercatabolic state.2 Serum urea nitrogen and creatinine levels (UCR initial/peak: case 1, 17.5/16.2; case 2, 12/13; case 3, 9.7/13) in all 3 cases were essentially unchanged and were not in keeping with a true hypercatabolic state. Full-Text PDF Open Access

Hospitalized patients with AKI rarely initiate peritoneal dialysis (PD) because of the limited availability of surgeons or interventionists with experience in placing PD catheters as well as of nephrologists and trained nursing staff who can manage and perform PD. Moreover, to minimize the incidence

Nephrology is facing a period of remarkable and unprecedented change. The pipeline of device and therapeutic drug development, the growing success of clinical trials, and the emergence of novel clinical practice and training pathways each hold the promise of transforming patient care. Nephrology is also at the forefront of health policy in the United States, given the recent Advancing American Kidney Health initiative. Despite these developments, significant barriers exist to ensure a robust pipeline of well-qualified nephrologists, including but not limited to trainees' declining trainee interest in the specialty, lower board pass rates, and a perceived erosion in stature of the subspecialty. There is a lack of consensus among training program directors regarding procedural training requirements, the number of fellowship positions needed, and the value of the match. There is widespread agreement, however, that any initiative to reassert the value of nephrology must include significant focus on reinvigorating the trainee experience before and during fellowship. We discuss the current state of education in nephrology (from medical school to beyond fellowship) and highlight ways to increase interest in nephrology to reinvigorate the specialty.