Metabolic Alkalosis.

Metabolic alkalosis is one of the four cardinal acid-base disorders and perhaps the least well understood by students. Taking a mechanistic approach to etiologies and management can be very helpful in such cases. Particularly, one should focus on the factors that generate the alkalosis (source of fluid loss and composition, less commonly alkali administration) and the factors (extracellular fluid volume status, hormonal systems) that maintain the abnormality.

American Society of Nephrology Kidney Tutored Research and Education for Kidney Scholars (TREKS) Program: A 10-Year Interim Analysis.

In response to decreasing numbers of individuals entering into nephrology fellowships, the American Society of Nephrology launched Kidney Tutored Research and Education for Kidney Scholars (TREKS) to stimulate interest in nephrology among medical students, graduate students, and postdoctoral fellows. The program combines a 1-week intensive exposure to kidney physiology with a longitudinal mentorship program at the participants' home institutions. Ten years in, an analysis was conducted to assess its effectiveness.

The times they are K+-changin': bringing the potassium curriculum out of the 20th century.

Purpose Of Review: Although most of the current medical education literature has focused on teaching strategies, little attention has been devoted to selecting appropriate course content. Despite elegant descriptions of physiologic mechanisms in recent decades, medical school curricula and students continue to rely on outdated textbooks and certification examination study aids composed to fit an antiquated exam blueprint.

Recent Findings: Advances in our understanding of potassium physiology offer multiple examples of key concepts that deserve to be included in the modern-day renal physiology curriculum, including the relationship of potassium to blood pressure and the potassium 'switch', the aldosterone paradox, and novel pharmacologic agents that target dietary potassium absorption and potassium handling in the kidney.

Acid Base Disorders in Cirrhosis.

Metabolic and respiratory acid-base disorders are common in individuals with liver disease and cirrhosis. The most common disorder is respiratory alkalosis, which may be related to dyspnea or respiratory stimulation. Primary metabolic disorders are less common.

Feasibility of a Nephrology Faculty Peer Observation of Teaching Pilot Program.

Awareness of being observed led to enhanced faculty preparation of teaching sessions. Any discomfort about being observed was generally outweighed by receiving observer input. Variable quality of feedback given to observed suggests need for more faculty development with next iteration of peer observation.

What's Old Is New Again: Harnessing the Power of Original Experiments to Learn Renal Physiology.

Although medical schools across the United States have updated their curricula to incorporate active learning techniques, there has been little discussion on the nature of the content presented to students. Here, we share detailed examples of our experience in using original experiments to lay the groundwork for foundational concepts in renal physiology and pathophysiology. We believe that this approach offers distinct advantages over standard case-based teaching by (1) starting with simple concepts, (2) analyzing memorable visuals, (3) increasing graphical literacy, (4) translating observations to "rules," (5) encouraging critical thinking, and (6) providing historical perspective to the study of medicine.

More than meets the I(ris): Use of manual urine microscopy to complement automated findings in acute kidney injury.

Evaluation of patients with acute kidney injury requires comprehensive assessment that includes a urinalysis, which features both semi-quantitative assessment with a urine dipstick and urine microscopy. This process is labor intensive for clinical laboratories, and availability of excellent automated instruments for urinalysis has prompted utilization and acceptance of this strategy by both by laboratories and clinicians. Recently, however, interest in provider performed microscopy has enjoyed a renaissance thanks to both improved microscopy techniques and the endorsement from social media in nephrology.

Incidence and risk factors of venous thromboembolism in ANCA-associated vasculitis: a metaanalysis and metaregression.

The incidence of venous thromboembolism (VTE) in ANCA-associated vasculitis patients varies in different populations. Moreover, the risk factors for VTE in these patients are poorly described due to the small number of events. Ovid MEDLINE, EMBASE, and the Cochrane Library were searched for eligible articles.

Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications.

Background And Objectives: Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging.

The Glomerular Disease Study and Trial Consortium: A Grassroots Initiative to Foster Collaboration and Innovation.

Glomerular kidney disorders account for a significant proportion of chronic kidney disease and end-stage renal disease worldwide. Nevertheless, major obstacles make breakthrough progress in diagnosis and cure an ongoing challenge. Here we report the creation of a "grassroots" initiative that aims to provide new opportunities for nephrologists, pathologists, basic and clinical scientists, patients, and industry partners to collaborate in the field of glomerular kidney disease.

The Interdialytic Creatinine Rise is a novel marker of volume overload and mortality risk in hemodialysis patients.

Background: Volume overload poses a major risk in hemodialysis patients but simple detection methods are lacking. We propose a novel marker, the Interdialytic Creatinine Rise (IDCR), readily calculated as the change in serum creatinine over time (in mg/dL/h), to assess volume overload and predict mortality risk in hemodialysis patients.

Methods: First, we calculated IDCR changes with volume in a prospective cohort of 35 hospitalized hemodialysis patients awaiting hemodialysis and 33 hospitalized patients undergoing hemodialysis every other day.

Analysis of skeletal muscle gene expression patterns and the impact of functional capacity in patients with systolic heart failure.

Background: Declining physical function is common among systolic heart failure (HF) patients and heralds poor clinical outcomes. We hypothesized that coordinated shifts in expression of ubiquitin-mediated atrophy-promoting genes are associated with muscle atrophy and contribute to decreased physical function.

Methods: Systolic HF patients (left ventricular ejection fraction [LVEF] ≤40%) underwent skeletal muscle biopsies (nondominant vastus lateralis) and comprehensive physical assessments.

Suppression of atrogin-1 and MuRF1 prevents dexamethasone-induced atrophy of cultured myotubes.

Objective: The mechanistic role of the ubiquitin ligases atrogin-1 and MuRF1 in glucocorticoid-induced muscle wasting is not fully understood. Here, we tested the hypothesis that glucocorticoid-induced muscle atrophy is at least in part linked to atrogin-1 and MuRF1 expression and that the ubiquitin ligases are regulated by compensatory mechanisms.

Methods: The expression of atrogin-1 and MuRF1 was suppressed individually or in combination in cultured L6 myotubes by using siRNA technique.

Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

Background: Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress.

Expression of the irisin precursor FNDC5 in skeletal muscle correlates with aerobic exercise performance in patients with heart failure.

Background: Exercise-induced increase in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression has been shown to increase the expression of the fibronectin type III domain containing 5 (FNDC5) gene and thereby its product, irisin, in mice. Given that exercise intolerance is a hallmark characteristic of heart failure (HF), and because PGC-1α and irisin promote exercise benefits in animals, we hypothesized that expression of these genes relates to aerobic performance in patients with HF.

Methods And Results: Systolic HF (left ventricular ejection fraction ≤40%) patients underwent cardiopulmonary exercise testing to evaluate aerobic performance.

Adiposity facilitates increased strength capacity in heart failure patients with reduced ejection fraction.

Background: Obesity is associated with relatively improved prognosis among heart failure (HF) patients. Mechanisms explaining this so-called "obesity paradox" have been unclear. We hypothesized that increased adiposity may contribute to increased strength capacity, and may thereby facilitate clinical benefits.

Proteolysis in illness-associated skeletal muscle atrophy: from pathways to networks.

Improvements in health in the past decades have resulted in increased numbers of the elderly in both developed and developing regions of the world. Advances in therapy have also increased the prevalence of patients with chronic and degenerative diseases. Muscle wasting, a feature of most chronic diseases, is prominent in the elderly and contributes to both morbidity and mortality.

Proteolysis by the ubiquitin-proteasome system and kidney disease.

Proteins in all cells turnover continuously such that rigorous control of proteolysis is required to govern levels of proteins with vastly different half-lives and actions including those regulating transcription, metabolic pathways, or the breakdown of muscle proteins to amino acids used in gluconeogenesis or the synthesis of new proteins. Critical cellular functions would be disrupted without precise regulation of protein degradation. Thus, it is surprising that the bulk of protein in all cells is degraded by the ATP-dependent, ubiquitin-proteasome system.