American Board of Internal Medicine Nephrology Procedure Requirements for Initial Certification: Time for a Change and Pursuing Consensus in the Nephrology Community.

In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically. In March 2021, the ABIM Nephrology Board embarked on a policy journey to revise the procedure requirements for nephrology certification. With the guidance of nephrology diplomates, training program directors, professional and patient organizations, and other stakeholders, the ABIM Nephrology Board revised the procedure requirements to reflect current practice and national priorities. The approved changes include the Opportunity to Train standard for placement of temporary dialysis catheters, percutaneous kidney biopsies, and home hemodialysis which better reflects the current state of training in most training programs, and the new requirements for home dialysis therapies training will align with the national priority to address the underuse of home dialysis therapies. This perspective details the ABIM process for considering changes to the certification procedure requirements and how ABIM collaborated with the larger nephrology community in considering revisions and additions to these requirements.

TXA2 attenuates allergic lung inflammation through regulation of Th2, Th9, and Treg differentiation.

In lung, thromboxane A2 (TXA2) activates the TP receptor to induce proinflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and TXA2 synthase inhibitors have been tested as potential asthma therapeutics in humans. Th9 cells play key roles in asthma and regulate the lung immune response to allergens. Herein, we found that TXA2 reduces Th9 cell differentiation during allergic lung inflammation. Th9 cells were decreased approximately 2-fold and airway hyperresponsiveness was attenuated in lungs of allergic mice treated with TXA2. Naive CD4+ T cell differentiation to Th9 cells and IL-9 production were inhibited dose-dependently by TXA2 in vitro. TP receptor-deficient mice had an approximately 2-fold increase in numbers of Th9 cells in lungs in vivo after OVA exposure compared with wild-type mice. Naive CD4+ T cells from TP-deficient mice exhibited increased Th9 cell differentiation and IL-9 production in vitro compared with CD4+ T cells from wild-type mice. TXA2 also suppressed Th2 and enhanced Treg differentiation both in vitro and in vivo. Thus, in contrast to its acute, proinflammatory effects, TXA2 also has longer-lasting immunosuppressive effects that attenuate the Th9 differentiation that drives asthma progression. These findings may explain the paradoxical failure of anti-thromboxane therapies in the treatment of asthma.

Sodium/Glucose Cotransporter 2 Inhibitors and Magnesium Homeostasis: A Review.

Magnesium (Mg2+), also known as "the forgotten ion," is the second most abundant intracellular cation and is essential in a broad range of intracellular physiological and biochemical reactions. Its deficiency, hypomagnesemia (Mg2+<1.8mg/dL), is a prevalent condition and routinely poses challenges in its management in clinical practice. Sodium/glucose cotransporter 2 (SGLT2) inhibitors have emerged as a new class of drugs with treating hypomagnesemia as their unique extraglycemic benefit. The beneficial effect of SGLT2 inhibitors on magnesium balance in patients with diabetes with or without hypomagnesemia has been noted as a class effect in recent meta-analysis data from randomized clinical trials. Some reports have demonstrated their role in treating refractory hypomagnesemia in patients with or without diabetes. Moreover, studies on animal models have attempted to illustrate the effect of SGLT2 inhibitors on Mg2+homeostasis. In this review, we discuss the current evidence and possible pathophysiological mechanisms, and we provide directions for further research. We conclude by suggesting the effect of SGLT2 inhibitors on Mg2+homeostasis is a class effect, with certain patients gaining significant benefits. Further studies are needed to examine whether SGLT2 inhibitors can become a desperately needed novel class of medicines in treating hypomagnesemia.

The evolution of social media in nephrology education: A mini-review.

Social media is defined as "a group of Internet-based applications that build on the ideological and technological foundations of Web 2.0, that allow the creation and exchange of user-generated content". Social media can be used in medical education to enhance knowledge sharing among peer groups and the public in general. The internet revolutionized learning by allowing easier dissemination of knowledge that did not depend on printing and physical distribution of books, journals, or magazines. According to a report from 2018, 95% of students have access to smartphones and 45% are online at any given time. Social media platforms are powerful tools to spread knowledge by the way of stories, videos, and educational games. Both formal and informal learning can be achieved with the use of social media. The microblogging website Twitter has become a popular social media platform by many in medical education including the nephrology community. Twitter, for example, is used to build communities, discuss journal articles, inform the community of conferences, share infographics and visual abstracts of original research work. As an example, it can be difficult for women in nephrology to connect and travel to make a physical presence. The use of social media allows women to connect via webinars and Women in Nephrology (WIN) India live Twitter chats. Thus, social media can help facilitate networking and collaboration with nephrologists all over the world. Social media has limitations as well. Insensitive posts can have a detrimental effect on one's career. A survey has shown that increased use of social media can contribute to addiction, anxiety, diminished self-esteem, and even depression. Hence, in order to effectively use social media to contribute positively to one's career, we recommend considering the positive and negative aspects of social media.This review will discuss the various social media platforms and how they have been applied to nephrology education.

Recent Advances in Understanding the Molecular Pathophysiology of Angiotensin II Receptors: Lessons From Cell-Selective Receptor Deletion in Mice.

The renin-angiotensin system (RAS) is an essential hormonal system involved in water and sodium reabsorption, renal blood flow regulation, and arterial constriction. Systemic stimulation of the RAS with infusion of the main peptide angiotensin II (Ang II) in animals as well as pathological elevation of renin (ie, renovascular hypertension) to increase circulatory Ang II in humans ultimately lead to hypertension and end organ damage. In addition to hypertension, accumulating evidence supports that the Ang II type 1 receptor exerts a critical role in cardiovascular and kidney diseases independent of blood pressure elevation. In the past 2 decades, the identification of an increased number of peptides and receptors has facilitated the concept that the RAS has detrimental and beneficial effects on the cardiovascular system depending on which RAS components are activated. For example, angiotensin 1-7 and Ang II type 2 receptors act as a counter-regulatory system against the classical RAS by mediating vasodilation. Although the RAS as an endocrine system for regulation of blood pressure is well established, there remain many unanswered questions and controversial findings regarding blood pressure regulation and pathophysiological regulation of cardiovascular diseases at the tissue level. This review article includes the latest knowledge gleaned from cell type-selective gene deleted mice regarding cell type-specific roles of Ang II receptors and their significance in health and diseases are discussed. In particular, we focus on the roles of these receptors expressed in vascular, cardiac, and kidney epithelial cells.

Trainee Love and Breakup Letters to NephSIM: A Free, Mobile-Optimized, Nephrology Teaching Tool.

BACKGROUND: It is not known how learners feel about free open access medical education (FOAMed) as they progress through their training from medical school to fellowship. Love and breakup letter methodology (LBM) is a technique that has been used extensively in user experience technology-based research but has not previously been used in evaluating medical education tools. LBM asks participants to creatively write a "love" or "breakup" letter to a product under study to capture their thoughts and emotions when engaging with it. We conducted qualitative analysis of data from focus groups to explore how attitudes toward a learning platform change at various training stages and to broaden our understanding of how we meet learners' needs through a nephrology FOAMed tool, NephSIM. METHODS: Three virtual, recorded focus groups were conducted with second-year medical students, internal medicine residents, and nephrology fellows ( N =18). At the start of the focus group, participants composed and read their love and breakup letters. Semistructured discussions were then led by facilitator-driven questions and peer comments. After transcription, inductive data analysis was conducted using Braun and Clarke's six-step thematic analysis. RESULTS: Four main themes were seen across all groups: attitudes toward teaching tool, perception of nephrology, learning needs and approach, and application to practice. Preclinical students positively viewed the opportunity to simulate the clinical setting and unanimously wrote love letters. Reactions from residents and fellows were mixed. Residents were interested in brevity and speed of learning, preferring algorithms and succinct approaches to meet their practice-based learning needs. Fellows' learning needs were driven by a desire to prepare for the nephrology board examination and review cases uncommonly seen in practice. CONCLUSIONS: LBM provided a valuable methodology through which to identify trainee reactions to a FOAMed tool and highlighted the challenges of meeting learning needs of a continuum of trainees with a single learning platform.

Novel Concepts in Nephron Sodium Transport: A Physiological and Clinical Perspective.

The kidneys play a critical role in maintaining total body sodium (Na+) balance across a wide range of dietary intake, accomplished by a concerted effort involving multiple Na+ transporters along the nephron. Furthermore, nephron Na+ reabsorption and urinary Na+ excretion are closely linked to renal blood flow and glomerular filtration such that perturbations in either of them can modify Na+ transport along the nephron, ultimately resulting in hypertension and other Na+-retentive states. In this article, we provide a brief physiological overview of nephron Na+ transport and illustrate clinical syndromes and therapeutic agents that affect Na+ transporter function. We highlight recent advances in kidney Na+ transport, particularly the role of immune cells, lymphatics, and interstitial Na+ in regulating Na+ reabsorption, the emergence of potassium (K+) as a regulator of Na+ transport, and the evolution of the nephron to modulate Na+ transport.

Targeting Glomerular Hemodynamics for Kidney Protection.

The kidney microcirculation is a unique structure as it is composed to 2 capillary beds in series: the glomerular and peritubular capillaries. The glomerular capillary bed is a high-pressure capillary bed, having a 60 mm Hg to 40 mm Hg pressure gradient, capable of producing an ultrafiltrate of plasma quantified as the glomerular filtration rate (GFR), thereby allowing for waste products to be removed and establishing sodium/volume homeostasis. Entering the glomerulus is the afferent arteriole, and the exiting one is the efferent arteriole. The concerted resistance of each of these arterioles is what is known as glomerular hemodynamics and is responsible for increasing or decreasing GFR and renal blood flow. Glomerular hemodynamics play an important role in how homeostasis is achieved. Minute-to-minute fluctuations in the GFR are achieved by constant sensing of distal delivery of sodium and chloride in the specialized cells called macula densa leading to upstream alternation in afferent arteriole resistance altering the pressure gradient for filtration. Specifically, 2 classes of medications (sodium glucose cotransporter-2 inhibitors and renin-angiotensin system blockers) have shown to be effective in long-term kidney health by altering glomerular hemodynamics. This review will discuss how tubuloglomerular feedback is achieved, and how different disease states and pharmacologic agents alter glomerular hemodynamics.

RheumMadness: Creating an Online Community of Inquiry in Rheumatology.

OBJECTIVE: To evaluate the educational impact of RheumMadness, an online tournament of rheumatology concepts grounded in social constructivist theory, as viewed through the community of inquiry (CoI) framework. METHODS: The curricular scaffold of RheumMadness was a bracket of 16 rheumatology concepts competing as "teams" in a tournament. Participants could create and review "scouting reports" about each team, listen to a RheumMadness podcast, discuss on social media, and submit a bracket predicting tournament outcomes according to the perceived importance of each team. Engagement was measured with direct analytics and through self-report on a survey. The survey also assessed participants' educational experience using an adapted 34-item CoI survey, which describes the cognitive, social, and teaching presences in a learning activity. RESULTS: One hundred brackets were submitted. On average, each scouting report was viewed 92 times, each podcast episode was downloaded 163 times, and 486 tweets were sent about #RheumMadness from 105 users. The survey received 58 of 107 responses (54%). Respondent agreement with prompts related to each CoI presence was: 70.3% cognitive, 61.7% social, 84.9% teaching. Reported engagement in RheumMadness correlated strongly with overall CoI survey scores (r = 0.72, P < 0.001). CONCLUSION: RheumMadness created an online CoI that fostered social constructivist learning about rheumatology.

Engagement in Free Open Access Medical Education by US Nephrology Fellows.

BACKGROUND: As free open access medical education (FOAMed) use increases, it is important to characterize how and why learners are using this educational material in nephrology. We describe the frequency, purpose, and type of FOAMed usage across US nephrology fellows. METHODS: In this cross-sectional survey, items were emailed to all US adult and pediatric nephrology fellows via the American Society of Nephrology (ASN) Fellow Survey in May 2022. The eight-item survey, developed to measure FOAMed engagement, had previously undergone instrument validation. The results were analyzed by descriptive statistics. RESULTS: In total, 43% (359/842) adult nephrology fellows and 51% (45/88) pediatric nephrology fellows completed the survey. Seventy-four percent (300/404) of fellows reported using FOAMed, and 72% (215/300) started using FOAMed within the past 2 years. Of FOAMed users, 41% (122/300) reported viewing FOAMed and 33% (99/300) reported applying knowledge gained from these resources daily or weekly. Common purposes for FOAMed engagement included searching Twitter to learn about others' opinions in the field (43%; 130/300), reading blogs to answer clinical questions (35%; 105/300), and listening to podcasts for the most up-to-date information (39%; 116/300). Compared with traditional educational resources, fellows preferred using FOAMed for staying up to date on nephrology topics (75%) and answering clinical questions (37%). Among all fellows, the greatest barriers to FOAMed use were unfamiliarity with FOAMed (27%; 111/404), validity concerns (22%; 90/404), and a lack of a local community of FOAMed users (22%; 87/404). CONCLUSIONS: Seventy-four percent of nephrology fellows used FOAMed resources in a variety of ways, and of them, 33% of fellows clinically applied knowledge gained from these resources. Reasons for engaging with FOAMed varied across resources.

Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II.

BACKGROUND: Ang II (angiotensin II) type 1 (AT1) receptors play a critical role in cardiovascular diseases such as hypertension. Rodents have 2 types of AT1 receptor (AT1A and AT1B) of which knock-in Tagln-mediated smooth muscle AT1A silencing attenuated Ang II-induced hypertension. Although vascular remodeling, a significant contributor to organ damage, occurs concurrently with hypertension in Ang II-infused mice, the contribution of smooth muscle AT1A in this process remains unexplored. Accordingly, it is hypothesized that smooth muscle AT1A receptors exclusively contribute to both medial thickening and adventitial fibrosis regardless of the presence of hypertension. METHODS: About 1 µg/kg per minute Ang II was infused for 2 weeks in 2 distinct AT1A receptor silenced mice, knock-in Tagln-mediated constitutive smooth muscle AT1A receptor silenced mice, and Myh11-mediated inducible smooth muscle AT1A together with global AT1B silenced mice for evaluation of hypertensive cardiovascular remodeling. RESULTS: Medial thickness, adventitial collagen deposition, and immune cell infiltration in aorta were increased in control mice but not in both smooth muscle AT1A receptor silenced mice. Coronary arterial perivascular fibrosis in response to Ang II infusion was also attenuated in both AT1A receptor silenced mice. Ang II-induced cardiac hypertrophy was attenuated in constitutive smooth muscle AT1A receptor silenced mice. However, Ang II-induced cardiac hypertrophy and hypertension were not altered in inducible smooth muscle AT1A receptor silenced mice. CONCLUSIONS: Smooth muscle AT1A receptors mediate Ang II-induced vascular remodeling including medial hypertrophy and inflammatory perivascular fibrosis regardless of the presence of hypertension. Our data suggest an independent etiology of blood pressure elevation and hypertensive vascular remodeling in response to Ang II.

Sodium-Glucose Cotransporter 2 Inhibitors and Management of Refractory Hypomagnesemia Without Overt Urinary Magnesium Wasting: A Report of 2 Cases.

Sodium-glucose cotransporter 2 (SGLT2) inhibitor have become widely used in patients with diabetes, heart failure, and kidney disease to improve clinical outcomes and diminish hospitalizations. They have also been associated with increased serum magnesium levels in patients with type 2 diabetes. The use of SGLT2 inhibitors resulted in improved magnesium homeostasis in a series of patients with refractory hypomagnesemia with urinary magnesium wasting. However, the role of SLGT2 inhibitors in patients with hypomagnesemia without urinary magnesium wasting remains unexplored. We report 2 cases with refractory hypomagnesemia without significant urinary magnesium wasting and dramatically improved serum magnesium levels after the initiation of SGLT2 inhibitors. Case 1 achieved independence from weekly intravenous magnesium infusions and reached sustainably greater serum magnesium levels with decreased oral magnesium supplementation and increased urinary fractional excretion of magnesium. Case 2 demonstrated improved serum magnesium levels with reduced oral magnesium supplementation without significant reduction in urinary fractional excretion of magnesium. These findings not only expand the use of SGLT2 inhibitors but also open the door for further studies to better understand the pathophysiology of how magnesium homeostasis is altered with inhibition of SGLT2.

Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.

Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids, prostaglandin E2 and its E-prostanoid receptor 4 receptor (EP4R) have been implicated in blood pressure control. Our previous study found that conditional deletion of EP4R from all tissues in adult mice exacerbates angiotensin II-dependent hypertension, suggesting a powerful effect of EP4R to resist blood pressure elevation. We also found that elimination of EP4R from vascular smooth muscle cells did not affect the severity of hypertension, suggesting nonvascular targets of prostaglandin E mediate this antihypertensive effect. Methods and Results Here we generated mice with cell-specific deletion of EP4R from macrophage-specific EP4 receptor knockouts or kidney epithelial cells (KEKO) to assess the contributions of EP4R in these cells to hypertension pathogenesis. Macrophage-specific EP4 receptor knockouts showed similar blood pressure responses to alterations in dietary sodium or chronic angiotensin II infusion as Controls. By contrast, angiotensin II-dependent hypertension was significantly augmented in KEKOs (mean arterial pressure: 146±3 mm Hg) compared with Controls (137±4 mm Hg; P=0.02), which was accompanied by impaired natriuresis in KEKOs. Because EP4R expression in the kidney is enriched in the collecting duct, we compared responses to amiloride in angiotensin II-infused KEKOs and Controls. Blockade of the epithelial sodium channel with amiloride caused exaggerated natriuresis in KEKOs compared with Controls (0.21±0.01 versus 0.15±0.02 mmol/24 hour per 20 g; P=0.015). Conclusions Our data suggest EP4R in kidney epithelia attenuates hypertension. This antihypertension effect of EP4R may be mediated by reducing the activity of the epithelial sodium channel, thereby promoting natriuresis.

Emerging Viral Infections and the Potential Impact on Hypertension, Cardiovascular Disease, and Kidney Disease.

Viruses are ubiquitous in the environment and continue to have a profound impact on human health and disease. The COVID-19 pandemic has highlighted this with impressive morbidity and mortality affecting the world's population. Importantly, the link between viruses and hypertension, cardiovascular disease, and kidney disease has resulted in a renewed focus and attention on this potential relationship. The virus responsible for COVID-19, SARS-CoV-2, has a direct link to one of the major enzymatic regulatory systems connected to blood pressure control and hypertension pathogenesis, the renin-angiotensin system. This is because the entry point for SARS-CoV-2 is the ACE2 (angiotensin-converting enzyme 2) protein. ACE2 is one of the main enzymes responsible for dampening the primary effector peptide Ang II (angiotensin II), metabolizing it to Ang-(1-7). A myriad of clinical questions has since emerged and are covered in this review. Several other viruses have been linked to hypertension, cardiovascular disease, and kidney health. Importantly, patients with high-risk apolipoprotein L1 (APOL1) alleles are at risk for developing the kidney lesion of collapsing glomerulopathy after viral infection. This review will highlight several emerging viruses and their potential unique tropisms for the kidney and cardiovascular system. We focus on SARS-CoV-2 as this body of literature in regards to cardiovascular disease has advanced significantly since the COVID-19 pandemic.

Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial.

BACKGROUND: Low-dose methotrexate (LD-MTX) is contraindicated in advanced CKD, but kidney safety in normal kidney function or mild-to-moderate CKD is less clear. METHODS: We performed a secondary analysis for eGFR and kidney AEs using the randomized double-blind, placebo-controlled Cardiovascular Inflammation Reduction Trial. Adults with cardiovascular disease and diabetes and/or metabolic syndrome were randomly allocated to oral LD-MTX (target dose 15-20 mg/week) or placebo. All participants took folic acid 1 mg 6 days/week. Exclusion criteria included systemic rheumatic disease and creatinine clearance <40 ml/min. The least-squares mean Δ eGFR from baseline was calculated at each study visit; the difference in eGFR between LD-MTX and placebo was compared. We used Cox proportional hazard models to compare rates of kidney AEs for LD-MTX versus placebo. RESULTS: A total of 2391 participants were randomized to LD-MTX and 2395 to placebo. At baseline, the mean age was 66 years, 19% were female, and mean eGFR was 80.0 ml/min per 1.73 m 2 (54% had Stage 2 CKD and 18% had Stage 3 CKD). Median follow-up was 23 months. The LD-MTX group had less decline in eGFR than placebo (difference in least-squares mean ΔeGFR from baseline to on-treatment visits: 0.93 ml/min per 1.73 m 2 , 95% confidence interval [95% CI], 0.45 to 1.40, P <0.001). There were 138 (incidence rate [IR], 2.97 per 100 person-years) kidney AEs in the LD-MTX group and 184 (IR, 3.99 per 100 person-years) among placebo (hazard ratio [HR] 0.73, 95% confidence interval [95% CI], 0.59 to 0.91) during safety laboratory monitoring. CONCLUSIONS: These results demonstrate the kidney safety of LD-MTX among patients with normal kidney function or mild-to-moderate CKD at baseline.