Nephrology and Hypertension

Cardiovascular disease in children with chronic kidney disease Purpose of review Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in children with chronic kidney disease (CKD). The cause of CVD in children with CKD is multifactorial and there are new and emerging data regarding prevalence and risk factors for CVD in this population. Recent findings A number of recent publications from longitudinal cohort studies of children with CKD have greatly increased our knowledge about the prevalence and risk factors for CVD including hypertension, obesity and dyslipidaemia. Masked hypertension and isolated nocturnal hypertension both correlate with surrogate markers of CVD in children. Obesity and adiposity are associated with an increased risk of CVD. Markers other than BMI such as waist to height ratio and fat-free tissue to fat tissue ratio better correlate with the presence of CVD in children. Dyslipidaemia is extremely prevalent in the paediatric CKD population, but there is a lack of consensus on treatment. More data on the relationship between bone mineral disease and CVD continue to emerge including an association between hyperparathyroidism and isolated nocturnal hypertension. Summary Children with CKD have multiple potentially modifiable risk factors for CVD. Research focused on CVD outcomes in children is needed. Correspondence to Michelle N. Rheault, MD, Division of Pediatric Nephrology, 2450 Riverside Ave, MB680, Minneapolis, MN 55454, USA. Tel: +1 612 626 2922; fax: +1 612 626 2791; e-mail: rheau002@umn.edu Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Disparities in chronic kidney disease-the state of the evidence Purpose of review The purpose of this review was to assess the prevalence of United States chronic kidney disease (CKD) health disparities, focusing on racial/ethnic groups, immigrants and refugees, sex or gender, and older adults. Recent findings There are major racial/ethnic disparities in CKD, with possible contributions from the social determinants of health, socioeconomics, and racial discrimination. Racial/ethnic minority patients experience faster progression to end-stage kidney disease (ESKD) and higher mortality predialysis, however, once on dialysis, appear to live longer. Similarly, men are quicker to progress to ESKD than women, with potential biological, behavioral, and measurement error factors. There is a lack of substantial evidence for intersex, nonbinary, or transgender patients. There are also strikingly few studies about US immigrants or older adults with CKD despite the fact that they are at high risk for CKD due to a variety of factors. Summary As providers and scientists, we must combat both conscious and unconscious biases, advocate for minority patient populations, and be inclusive and diverse in our treatment regimens and provision of care. We need to acknowledge that sufficient evidence exists to change treatment guidelines, and that more is required to support the diversity of our patient population. Correspondence to Maya N. Clark-Cutaia, PhD, ACNP-BC, RN, NYU Meyers College of Nursing, 433 First Avenue, Room 664, New York, New York 10010, USA. Tel: +212 998 5280; fax: +212 995 3143; e-mail: MC7009@NYU.EDU Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Gut–kidney axis in oxalate homeostasis Purpose of review The gut–kidney axis plays a critical role in oxalate homeostasis, and better understanding of oxalate transport regulatory mechanisms is essential for developing novel therapies. Recent findings Oxalate potentially contributes to chronic kidney disease (CKD) progression, CKD - and end stage renal disease (ESRD)-associated cardiovascular diseases, polycystic kidney disease (PKD) progression, and/or poor renal allograft survival, emphasizing the need for plasma and urinary oxalate lowering therapies. One promising strategy would be to enhance the bowel's ability to secrete oxalate, which might be facilitated by the following findings. Oxalobacter formigenes (O. formigenes)-derived factors recapitulate O. formigenes colonization effects by reducing urinary oxalate excretion in hyperoxaluric mice by inducing colonic oxalate secretion. Protein kinase A activation stimulates intestinal oxalate transport by enhancing the surface expression of the oxalate transporter SLC26A6 (A6). Glycosylation also stimulates A6-mediated oxalate transport. The colon adapts to chronic acidosis in rats through increased colonic oxalate secretion as previously reported in CKD rats, and A6-mediated enteric oxalate secretion is critical in reducing the body oxalate burden in CKD mice. Intestinal oxalate transport is negatively regulated by proinflammatory cytokines and cholinergic, purinergic, and adenosinergic signaling. Summary These findings could facilitate the development of novel therapeutics for hyperoxalemia, hyperoxaluria, and related disorders if similar regulatory mechanisms are confirmed in humans. Correspondence to Hatim A. Hassan, MD, PhD, Section of Nephrology, Department of Medicine, The University of Chicago, 5841S. Maryland Ave, MC5100, Chicago, Illinois 60637, USA. Tel: +773 834 0374; fax: +773 702 5818; e-mail: hhassan@medicine.bsd.uchicago.edu Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Regulation of vascular tone and blood pressure by singlet molecular oxygen in inflammation Purpose of review The principle aim of this review is to prompt vascular researchers interested in vascular inflammation and oxidative stress to consider singlet molecular oxygen (1O2) as a potentially relevant contributor. A secondary goal is to propose novel treatment strategies to address haemodynamic complications associated with septic shock. Recent findings Increased inflammation and oxidative stress are hallmarks of a range of vascular diseases. We recently showed that in systemic inflammation and oxidative stress associated with models of inflammation including sepsis, the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase-1 (Ido1) contributes to hypotension and decreased blood pressure through production of singlet molecular oxygen (1O2). Once formed, 1O2 converts tryptophan bound to Ido1 to a vasoactive hydroperoxide which decreases arterial tone and blood pressure via oxidation of a specific cysteine residue of protein kinase G1α. Summary These works show, for the first time, that 1O2 contributes to arterial redox signalling and that Ido1 contributes to the regulation of blood pressure through production of a novel tryptophan-derived hydroperoxide, thus presenting a new signalling pathway as novel target in the treatment of blood pressure disorders such as sepsis. Correspondence to Roland Stocker, PhD, Heart Research Institute, Newtown, NSW 2042, Australia. E-mail: roland.stocker@hri.org.au Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Managing hyperuricemia and gout in chronic kidney disease: a clinical conundrum Purpose of review There is controversy regarding the impact of hyperuricemia on the progression of chronic kidney disease (CKD), and gout remains sub optimally managed in this population. We discuss the prescribing of drugs for the treatment of gout in patients with CKD. Recent findings There is a lack of consensus from expert guidelines, and prescribers have concerns regarding the risk of adverse reactions from medicines used to treat gout. These situations appear to contribute to suboptimal management of gout in this cohort. Recent data have challenged the role of urate lowering therapy (ULT) in the management of asymptomatic hyperuricemia in CKD. Summary ULT should be commenced in all patients with severe, recurrent disease, tophaceous gout and evidence of joint damage. Most international guidelines recommend a treat-to-target approach for the management of gout. In CKD, ULT should be started at low dose with up titration adjusted to serum urate levels, rather than being based on the creatinine clearance. If patients fail first-line therapy, alternative agents are utilized, the specific agent depending on ease of access, burden of disease and other comorbidities. This approach should be incorporated into routine practice to ensure optimal treatment of gout in CKD. More research is required to investigate whether treatment of asymptomatic hyperuricemia has clinical benefits. Correspondence to Darren M. Roberts, Department of Renal Medicine and Transplantation, St Vincent's Hospital, Darlinghurst, New South Wales, Australia. Tel: +61 283821111; fax: +61 283822032; e-mail: Darren.roberts@svha.org.au Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Cardiovascular autonomic nervous system dysfunction in chronic kidney disease and end-stage kidney disease: disruption of the complementary forces Purpose of review Several nontraditional risk factors have been the focus of research in an attempt to understand the disproportionately high cardiovascular morbidity and mortality in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) populations. One such category of risk factors is cardiovascular autonomic dysfunction. Its true prevalence in the CKD/ESKD population is unknown but existing evidence suggests it is common. Due to lack of standardized diagnostic and treatment options, this condition remains undiagnosed and untreated in many patients. In this review, we discuss current evidence pointing toward the role of autonomic nervous system (ANS) dysfunction in CKD, building off of crucial historical evidence and thereby highlighting the areas in need for future research interest. Recent findings There are several key mediators and pathways leading to cardiovascular autonomic dysfunction in CKD and ESKD. We review studies exploring the mechanisms involved and discuss the current measurement tools and indices to evaluate the ANS and their pitfalls. There is a strong line of evidence establishing the temporal sequence of worsening autonomic function and kidney function and vice versa. Evidence linking ANS dysfunction and arrhythmia, sudden cardiac death, intradialytic hypotension, heart failure and hypertension are discussed. Summary There is a need for early recognition and referral of CKD and ESKD patients suspected of cardiovascular ANS dysfunction to prevent the downstream effects described in this review. There are many unknowns in this area and a clear need for further research. Correspondence to David M. Charytan, MD, MSc, Chief, Nephrology Division, NYU Langone Medical Center, 462 1st Avenue C & D 689, New York, New York 10010, USA. Tel: +646 501 9086; e-mail: David.charytan@nyulangone.org Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Challenges in communication, prognostication and dialysis decision-making in the COVID-19 pandemic: implications for interdisciplinary care during crisis settings Purpose of review Using case vignettes, we highlight challenges in communication, prognostication, and medical decision-making that have been exacerbated by the coronavirus disease-19 (COVID-19) pandemic for patients with kidney disease. We include best practice recommendations to mitigate these issues and conclude with implications for interdisciplinary models of care in crisis settings. Recent findings Certain biomarkers, demographics, and medical comorbidities predict an increased risk for mortality among patients with COVID-19 and kidney disease, but concerns related to physical exposure and conservation of personal protective equipment have exacerbated existing barriers to empathic communication and value clarification for these patients. Variability in patient characteristics and outcomes has made prognostication nuanced and challenging. The pandemic has also highlighted the complexities of dialysis decision-making for older adults at risk for poor outcomes related to COVID-19. Summary The COVID-19 pandemic underscores the need for nephrologists to be competent in serious illness communication skills that include virtual and remote modalities, to be aware of prognostic tools, and to be willing to engage with interdisciplinary teams of palliative care subspecialists, intensivists, and ethicists to facilitate goal-concordant care during crisis settings. Correspondence to Devika Nair, MD, MSCI, Instructor of Medicine, Vanderbilt University Medical Center, Division of Nephrology and Hypertension, Vanderbilt Center for Health Services Research, 2525 West End Avenue, Suite 450, Office 416, Nashville, Tennessee 37203, USA. Tel: +615 322 7285; e-mail: Devika.nair@vumc.org Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Angiotensin-converting enzyme 2: from a vasoactive peptide to the gatekeeper of a global pandemic Purpose of review We provide a comprehensive overview of angiotensin-converting enzyme 2 (ACE2) as a possible candidate for pharmacological approaches to halt inflammatory processes in different pathogenic conditions. Recent findings ACE2 has quickly gained prominence in basic research as it has been identified as the main entry receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This novel pathogen causes Coronavirus Disease 2019 (COVID-19), a pathogenic condition that reached pandemic proportion and is associated with unprecedented morbidity and mortality. Summary The renin–angiotensin system is a complex, coordinated hormonal cascade that plays a pivotal role in controlling individual cell behaviour and multiple organ functions. ACE2 acts as an endogenous counter-regulator to the pro-inflammatory and pro-fibrotic pathways triggered by ACE through the conversion of Ang II into the vasodilatory peptide Ang 1–7. We discuss the structure, function and expression of ACE2 in different tissues. We also briefly describe the role of ACE2 as a pivotal driver across a wide spectrum of pathogenic conditions, such as cardiac and renal diseases. Furthermore, we provide the most recent data concerning the possible role of ACE2 in mediating SARS-CoV-2 infection and dictating COVID-19 severity. Correspondence to Luca Perico, PhD, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87, 24126 Bergamo, Italy. Tel: +39 035 42131; fax: +39 035 319331; e-mail: luca.perico@marionegri.it Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Sodium bicarbonate therapy for acute respiratory acidosis Purpose of review Respiratory acidosis is commonly present in patients with respiratory failure. The usual treatment of hypercapnia is to increase ventilation. During the recent surge of COVID-19, respiratory acidosis unresponsive to increased mechanical ventilatory support was common. Increasing mechanical ventilation comes at the expense of barotrauma and hemodynamic compromise from increasing positive end-expiratory pressures or minute ventilation. Treating acute respiratory acidemia with sodium bicarbonate remains controversial. Recent findings There are no randomized controlled trials of administration of sodium bicarbonate for respiratory acidemia. A recent review concluded that alkali therapy for mixed respiratory and metabolic acidosis might be useful but was based on the conflicting and not conclusive literature regarding metabolic acidosis. This strategy should not be extrapolated to treatment of respiratory acidemia. Low tidal volume ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has beneficial effects associated with permissive hypercapnia. Whether the putative benefits will be negated by administration of alkali is not known. Hypercapnic acidosis is well tolerated, with few adverse effects as long as tissue perfusion and oxygenation are maintained. Summary There is a lack of clinical evidence that administration of sodium bicarbonate for respiratory acidosis has a net benefit; in fact, there are potential risks associated with it. Correspondence to David S. Goldfarb, MD, Clinical Chief, Nephrology Division, NYU Langone Health, Professor of Medicine and Physiology, New York University School of Medicine, Nephrology Section 111G, 423 E. 23 Street, New York, NY 10010, USA. Tel: +1 212 686 7500, x3877; fax: +1 212 951 6842; e-mail: david.goldfarb@nyulangone.org Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Controversies in nephrologic covidology No abstract available

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