Data on residual clinical damage after Coronavirus disease-2019 (COVID-19) are lacking. The aims of this study were to investigate whether COVID-19 leaves behind residual dysfunction, and identify patients who might benefit from post-discharge monitoring. All patients aged �18 years admitted to the Emergency Department (ED) for COVID-19, and evaluated at post-discharge follow-up between 7 April and 7 May, 2020, were enrolled. Primary outcome was need of follow-up, defined as the presence at follow-up of at least one among: respiratory rate (RR) >20 breaths/min, uncontrolled blood pressure (BP) requiring therapeutic change, moderate to very severe dyspnoea, malnutrition, or new-onset cognitive impairment, according to validated scores. Post-traumatic stress disorder (PTSD) served as secondary outcome. 185 patients were included. Median [interquartile range] time from hospital discharge to follow-up was 23 [20-29] days. 109 (58.9%) patients needed follow-up. At follow-up evaluation, 58 (31.3%) patients were dyspnoeic, 41 (22.2%) tachypnoeic, 10 (5.4%) malnourished, 106 (57.3%) at risk for malnutrition. Forty (21.6%) patients had uncontrolled BP requiring therapeutic change, and 47 (25.4%) new-onset cognitive impairment. PTSD was observed in 41 (22.2%) patients. At regression tree analysis, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO 2 /FiO 2) and body mass index (BMI) at ED presentation, and age emerged as independent predictors of the need of followup. Patients with PaO 2 /FiO 2 <324 and BMI �33 Kg/m 2 had the highest odds to require follow-up. Among hospitalised patients, age �63 years, or age <63 plus non-invasive ventilation or diabetes identified those with the highest probability to need follow-up. PTSD was independently predicted by female gender and hospitalisation, the latter being protective (odds ratio, OR, 4.03, 95% confidence interval, CI, 1.76 to 9.47, p 0.0011; OR 0.37, 95% CI

Abstract-The kidney plays an important role in salt and blood pressure (BP) homeostasis. In previous studies, variants in the genes for ␣-adducin (ADD1), WNK1, and NEDD4L, which all regulate renal sodium absorption, have been associated with increased BP. However, findings have been inconsistent. We tested whether this is because of physiological interactions between the effects of variants in these genes. We assessed the single and combined effects of the ADD1 (Gly460Trp), WNK1 (rs880054 A/G), and NEDD4L (rs4149601 G/A) polymorphisms on renal and BP response to an acute Na load (nϭ344 subjects), BP decrease after 1 month of treatment with 12.5 mg of hydrochlorothiazide (nϭ193), and ambulatory 24-hour BP (nϭ690). Individually, the variants showed modest effects on some of the studied phenotypes. We found the ADD1 Trp allele to be permissive for the effects of variants of the other genes. In combination, the same variants (ADD1 Trp/WNK1 GG/Nedd4L GAϩAA) showed a consistent effect on renal Na handling (Pϭ0.009) and acute BP response to a saline infusion (Pϭ0.021), BP lowering after thiazide treatment (Pϭ0.008), and nocturnal systolic BP (Pϭ0.044). Physiological interaction between the ADD1 and WNK1-NEDD4L pathways influences the effects of variants in these genes on sodium-related BP regulation. Relatively common alleles in the ADD1, WNK1, and NEDD4L genes when present in combination may have significant effects on renal sodium handling, BP, and antihypertensive response to thiazides. (Hypertension. 2008;52:366-372.)Key Words: hypertension Ⅲ genetic Ⅲ sodium transport Ⅲ kidney Ⅲ blood pressure Ⅲ tubular Ⅲ renal R egulation of body sodium and blood pressure (BP) is achieved through the interaction of several mechanisms, including sodium (Na) transport at the basolateral and luminal tubular cell membranes along specific nephron segments. Moreover, physical, nervous, and hormonal mechanisms modulate this constitutive capacity of tubular cells to transport Na according to the body's needs. 1 In fact, virtually all mendelian disorders leading to hypertension are caused by gene variants affecting salt reabsorption. 2 A comprehensive approach to the genetics of the regulation of body Na and BP should take into account the interactions among the underlying variety of gene polymorphisms. At present, this approach is not feasible globally for the prohibitive size of the cohort required. However, a contribution along this line may be provided by focusing on genes affecting luminal (WNK1 and NEDD4L) and basolateral transport of Na (Adducin) in patients whose BP is changed by maneuvers affecting body Na.These genes have been chosen for the following reasons: a missense mutation in the ␣-adducin (ADD1 Gly/Trp) gene has been shown to affect the function of the protein with the Trp allele resulting in greater renal Na-K pump activity in nephron segments proximal to the macula densa. 3,4 Results of association studies of the Trp allele with BP are conflicting when this allele is considered alone, 5 but they are much more consisten...

Background and objectivesHypertension is a common aging-related disorder. Salt intake is one of the main environmental factors contributing to the development of hypertension. Transgenic mice with one-half Klotho deficiency displayed a spontaneous BP increase and salt-sensitive hypertension in response to high sodium intake. Usually circulating levels of α-Klotho decrease with age, and this reduction may be stronger in patients with several aging-related diseases. This study aimed at exploring the association of Klotho with salt sensitivity in humans.Design, setting, participants, & measurementsThe role of Klotho polymorphisms and α-Klotho serum levels was evaluated in patients with hypertension who were treatment naive and underwent an acute salt-sensitivity test (discovery n=673, intravenous 2 L of 0.9% saline in 2 hours). Salt sensitivity was defined as a mean BP increase of >4 mm Hg at the end of the infusion. A total of 32 single nucleotide polymorphisms in the Klotho gene (KL), previously identified with a genome-wide association study, were used in the genetic analysis and studied for a pressure-natriuresis relationship.ResultsOf the patients with hypertension, 35% were classified as salt sensitive. The most relevant polymorphism associated with pressure natriuresis was the common missense single nucleotide polymorphism rs9536314, and the GG and GT genotypes were more represented among patients who were salt sensitive (P=0.001). Those carrying the G allele showed a less steep pressure-natriuresis relationship, meaning that a significant increase in mean BP was needed to excrete the same quantity of salt compared with patients who were salt resistant. KL rs9536314 also replicated the pressure-natriuresis association in an independent replication cohort (n=193) and in the combined analysis (n=866). There was an inverse relationship between circulating Klotho and mean BP changes after the saline infusion (r=−0.14, P=0.03). Moreover, circulating α-Klotho was directly related to kidney function at baseline eGFR (r=0.22, P<0.001).ConclusionsKL rs9536314 is associated with salt-sensitive hypertension in patients with hypertension who are treatment naive. Moreover, circulating α-Klotho levels were mainly related to diastolic BP changes at the end of a salt load and to eGFR as an expression of kidney aging.

Objective To evaluate whether the renin–angiotensin–aldosterone system (RAAS) and endogenous ouabain system differently affect renal Na handling and blood pressure. Methods Three hundred and one patients in whom we compared blood pressure, and renal Na tubular reabsorption in the basal condition and 2 h (T120) after saline infusion. Results Following multivariate-adjusted linear and quartiles analysis, baseline mean blood pressure (MBP) was significantly higher (113.7 ± 1.33 mmHg) in the fourth versus the first endogenous ouabain quartile (103.8 ± 1.04 mmHg) and the trend across the quartiles was highly significant (β=0.23, P =3.53e-04). In contrast, an inverse relationship was present in the renin activity (PRA) quartiles with MBP highest in the first (112.5 ± 1.26) and lowest in the fourth PRA quartile (107.6 ± 1.48, P =0.039). Following an acute saline load, changes in MBP and the slope of the pressure–natriuresis relationship were inversely related across the PRA quartiles. The fractional excretion of sodium (FENa) showed a negative linear trend going from the first to the third endogenous ouabain quartiles (2.35 ± 0.17 and 1.90 ± 0.14%, P =0.05). Patients in the fourth endogenous ouabain quartile (>323 pmol/l) showed increased FENa T120 (2.78 ± 0.18%, P < 0.01) and increased Na tubular rejection fraction (P =0.007) after Na load. After the saline load, there was a biphasic relationship between plasma endogenous ouabain and FENa favoring Na retention at low endogenous ouabain and Na excretion at high endogenous ouabain levels. Conclusion The RAAS and endogenous ouabain system are two independent and complementary systems having an inverse (RAAS) or a direct (endogenous ouabain system) relationship with hemodynamic parameters.

Hypertension and obesity in the young population are major risk factors for renal and cardiovascular events, which could arise in adulthood. A candidate-gene approach was applied in a cohort observational study, in which we collected data from 2638 high school adolescent students. Participants underwent anthropometric and blood pressure (BP) measurements, as well as saliva and urine sample collection for genomic DNA extraction and renal function evaluation, respectively. We tested whether candidate genes previously implicated in salt-sensitive hypertension in adults impact BP also among adolescents. Since inflammatory mechanisms may be involved in pathophysiology of hypertension and in endothelial dysfunction and atherosclerosis through reactive oxygen species, the baseline urinary excretion of inflammatory and oxidative stress markers in a subgroup of adolescents stratified according to ADD1 (alpha adducin) rs4961 genotypes was assessed. Regression analysis of BP values with genetic polymorphisms, highlighted an association with a missense variant of LSS (lanosterol synthase, rs2254524), a gene coding for an enzyme involved in endogenous ouabain synthesis. Higher diastolic and systolic BP were associated with LSS A allele ( P =0.011 and P =0.023, respectively). BP resulted associated with 5 more SNPs. The KL (klotho) rs9536314 missense variant was associated with 24 hour urinary Na + excretion ( P =0.0083). Urinary protein tests showed a greater excretion of IL1β (interleukin 1β) and interleukin 10 ( P <0.0001) in carriers of the ADD1 rs4961 T allele. In conclusion, 3 missense gene variants already implicated in adult hypertension impact BP or Na + excretion among adolescents, and, together with activated pro-inflammatory pathways, might predispose to early cardiovascular damage.

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Among patients with essential hypertension, circulating endogenous ouabain and Aldo are typically coelevated and their BP is salt-sensitive. In conditions where Aldo is inappropriately elevated, both Aldo and endogenous ouabain may contribute to adverse cardiovascular and renal outcomes.

Anxiety affects many hemodialysis patients. The response to treatment varies and often requires patients to take therapeutics for long periods; thus, many patients look for complementary approaches. There have been reports of music alleviating anxiety in hemodialysis patients. However, the efficacy of music needs to be evaluated. The objective of this study was to conduct a systematic review and meta-analysis to compare the effects of participation in standard care combined with music with standard care alone. This was a systematic review and meta-analysis of randomized controlled trials to determine the efficacy of music to lower anxiety in hemodialysis patients. Five studies were included in the review (290 patients). Listening to music resulted, on average, in an anxiety reduction that was −0.52 standard deviation units greater (95% confidence interval, −1.02 to −0.03 lower, P = .003) than in the standard care group. No adverse events were identified. All trials contained a risk of bias due to lack of blinding. The heterogeneity showed an I 2 = 75%. The strength of evidence was very low. No adverse events were identified. Few trials were available for inclusion, with small sample sizes and significant heterogeneity. Within these considerable limitations there was a demonstrated decrease in anxiety for hemodialysis patients receiving standard care augmented with music. The effect size was moderate. Results were inconsistent across studies. We are uncertain about the estimate. The likelihood that effect will be substantially different is very high. Further research has a large potential for reducing uncertainty about the effects of the music interventions.