Salt and Water: A Review of Hypernatremia.

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.

The small RNA RsaF regulates the expression of secreted virulence factors in Staphylococcus aureus Newman.

The pathogenesis of Staphylococcus aureus, from local infections to systemic dissemination, is mediated by a battery of virulence factors that are regulated by intricate mechanisms, which include regulatory proteins and small RNAs (sRNAs) as key regulatory molecules. We have investigated the involvement of sRNA RsaF, in the regulation of pathogenicity genes hyaluronate lyase (hysA) and serine proteaselike protein D (splD), by employing S. aureus strains with disruption and overexpression of rsaF. Staphylococcus aureus strain with disruption of rsaF exhibited marked down-regulation of hysA transcripts by 0.2 to 0.0002 fold, and hyaluronate lyase activity by 0.2-0.1 fold, as well as increased biofilm formation, during growth from log phase to stationery phase. These mutants also displayed down-regulation of splD transcripts by 0.8 to 0.005 fold, and reduced activity of multiple proteases by zymography. Conversely, overexpression of rsaF resulted in a 2- to 4- fold increase in hysA mRNA levels and hyaluronidase activity. Both hysA and splD mRNAs demonstrated an increased stability in RsaF+ strains. In silico RNA-RNA interaction indicated a direct base pairing of RsaF with hysA and splD mRNAs, which was established in electrophoretic mobility shift assays. The findings demonstrate a positive regulatory role for small RNA RsaF in the expression of the virulence factors, HysA and SplD.

DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity.

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.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

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 m2 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.

Kidney Physiology in Pregnancy.

A woman's body undergoes a myriad of changes throughout the course of a normal gestation. The kidneys play a central role in driving adjustments that guarantee maternal and fetal well-being, including a dramatic increase in glomerular filtration rate, alterations in tubular function, and changes in electrolyte and acid/base handling. Early in gestation, systemic vasodilation, driven by both a change in quantity of and response to various hormones, leads to increased renal blood flow and glomerular filtration rate. Vasodilation also results in activation of the renin-angiotensin-aldosterone axis, which combined with changing tubular handling causes alterations in total body stores of electrolytes and total body water, resulting in a lower serum sodium concentration. In addition, mild proteinuria, glucosuria, and a decrease in serum calcium and magnesium are common. The primary acid/base change seen in pregnancy is a mild respiratory alkalosis due to progesterone effects. This article provides an overview of the current understanding of the healthy response of the kidneys to pregnancy, an understanding of which is key to caring for the pregnant patient, and early identification of alterations that may indicate underlying kidney pathology in pregnancy.

Medical Education During the Coronavirus Disease-2019 Pandemic: Learning From a Distance.

As paradigms of clinical care delivery have been significantly impacted by the novel coronavirus disease-2019 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.

Current Paradigms and Emerging Opportunities in Nephrology Training.

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.

Apolipoprotein L1, Cardiovascular Disease and Hypertension: More Questions than Answers.

Ethnic disparities in health outcomes exist among multiple complex diseases especially cardiovascular disease, hypertension, and kidney disease. Recent discoveries in genetics have taught us that these disparities go beyond environmental and socioeconomic factors. The discovery of ethnic-specific risk variants in the Apolipoprotein L1 (APOL1) gene on chromosome 22 seen only in individuals of recent African ancestry explains a large proportion of kidney disease disparities. In addition, recent large-scale genotype-phenotype association studies have identified associations with cardiovascular disease and hypertension. This review aims to review the recent literature in this field and point toward future directions for research.

Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill Patients.

BACKGROUND AND OBJECTIVES: Hypernatremia is common in hospitalized, critically ill patients. Although there are no clear guidelines on sodium correction rate for hypernatremia, some studies suggest a reduction rate not to exceed 0.5 mmol/L per hour. However, the data supporting this recommendation and the optimal rate of hypernatremia correction in hospitalized adults are unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assessed the association of hypernatremia correction rates with neurologic outcomes and mortality in critically ill patients with hypernatremia at admission and those that developed hypernatremia during hospitalization. We used data from the Medical Information Mart for Intensive Care-III and identified patients with hypernatremia (serum sodium level >155 mmol/L) on admission (n=122) and hospital-acquired (n=327). We calculated different ranges of rapid correction rates (>0.5 mmol/L per hour overall and >8, >10, and >12 mmol/L per 24 hours) and utilized logistic regression to generate adjusted odds ratios (aOR) with 95% confidence intervals (95% CIs) to examine association with outcomes. RESULTS: We had complete data on 122 patients with severe hypernatremia on admission and 327 patients who developed hospital-acquired hypernatremia. The difference in in-hospital 30-day mortality proportion between rapid (>0.5 mmol/L per hour) and slower (≤0.5 mmol/L per hour) correction rates were not significant either in patients with hypernatremia at admission with rapid versus slow correction (25% versus 28%; P=0.80) or in patients with hospital-acquired hypernatremia with rapid versus slow correction (44% versus 40%; P=0.50). There was no difference in aOR of mortality for rapid versus slow correction in either admission (aOR, 1.3; 95% CI, 0.5 to 3.7) or hospital-acquired hypernatremia (aOR, 1.3; 95% CI, 0.8 to 2.3). Manual chart review of all suspected chronic hypernatremia patients, which included all 122 with hypernatremia at admission, 128 of the 327 hospital-acquired hypernatremia, and an additional 28 patients with ICD-9 codes for cerebral edema, seizures and/or alteration of consciousness, did not reveal a single case of cerebral edema attributable to rapid hyprnatremia correction. CONCLUSIONS: We did not find any evidence that rapid correction of hypernatremia is associated with a higher risk for mortality, seizure, alteration of consciousness, and/or cerebral edema in critically ill adult patients with either admission or hospital-acquired hypernatremia.