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Nicotinamide adenine dinucleotide (oxidized form, NAD(+)) is a critical coenzyme, with functions ranging from redox reactions and energy metabolism in mitochondrial respiration and oxidative phosphorylation to being a central player in multiple cellular signaling pathways, organ resilience, health, and longevity. Many of its cellular functions are executed via serving as a co-substrate for sirtuins (SIRTs), poly (ADP-ribose) polymerases (PARPs), and CD38. Kidney damage and diseases are common in the general population, especially in elderly persons and diabetic patients. While NAD(+) is reduced in acute kidney injury (AKI) and chronic kidney disease (CKD), mounting evidence indicates that NAD(+) augmentation is beneficial to AKI, although conflicting results exist for cases of CKD. Here, we review recent progress in the field of NAD(+), mainly focusing on compromised NAD(+) levels in AKI and its effect on essential cellular pathways, such as mitochondrial dysfunction, compromised autophagy, and low expression of the aging biomarker alpha Klotho (Klotho) in the kidney. We also review the compromised NAD(+) levels in renal fibrosis and senescence cells in the case of CKD. As there is an urgent need for more effective treatments for patients with injured kidneys, further studies on NAD(+) in relation to AKI/CKD may shed light on novel therapeutics., This review was funded by HELSE SØR-ØST (#2017056, #2020001, and #2021021), the Research Council of Norway (#262175), the National Natural Science Foundation of China (#81971327), Akershus University Hospital (#269901, #261973, and #262960), the Civitan Norges Forskningsfond for Alzheimers sykdom (#281931), the Czech Republic-Norway KAPPA programme (with Martin Vyhnálek, #TO01000215), and the Rosa sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society (#207819).

The effect of donor obesity on kidney transplantation success has long been an overlooked clinical research area. Even though there is no strict guideline in most countries prohibiting donation from obese individuals, most candidates with a body mass index >35-40 kg/m(2) are rejected due to concerns regarding long-term renal functional deterioration in the donor. The effects of excessive fat mass on renal function and allograft survival have been analysed by several longitudinal and follow-up studies. These studies have documented the deleterious effect on long-term graft outcomes of excessive body mass in living kidney donors and de novo obesity or pre-existing obesity worsening after transplantation on kidney outcomes. However, there is a paucity of clinical trials aimed at countering overweight and obesity in living and deceased kidney donors and in transplant patients. In this review we will briefly discuss the mechanism whereby fat excess induces adverse kidney outcomes and describe the effects on graft function and survival in living obese donors., NA

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Mitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between fusion and fission processes leading to mitochondrial fragmentation, oxidative stress, release of cytochrome c and mitochondrial DNA resulting in apoptosis, mitophagy, and defects in energy metabolism are the key pathophysiological mechanisms underlying the role of mitochondrial dysfunction in kidney diseases. Currently, various strategies target the mitochondria to improve kidney function and kidney treatment. The agents used in these strategies can be classified as biogenesis activators, fission inhibitors, antioxidants, mPTP inhibitors, and agents which enhance mitophagy and cardiolipin-protective drugs. Several glucose-lowering drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors are also known to have influences on these mechanisms. In this review, we delineate the role of mitochondrial dysfunction in kidney disease, the current mitochondria-targeting treatment options affecting the kidneys and the future role of mitochondria in kidney pathology., NA

Acute kidney injury (AKI) is common in hospitalized patients while common risk factors for the development of AKI include postoperative settings, patients with baseline chronic kidney disease (CKD) or congestive heart failure. Intravenous (IV) fluid therapy is a crucial component of care for prevention and treatment of AKI. In this narrative review, we update the approach to IV fluid therapy in hospitalized patients including the timing of fluid prescription, and the choice of fluid type, amount and infusion rate along with the potential adverse effects of various crystalloid and colloid solutions, addressing specifically their use in patients with acute kidney disease, CKD or heart failure, and their potential impact on the risk of hospital-acquired AKI., A.O. has received grants from Sanofi and consultancy or speaker fees or travel support from Advicciene, Astellas, AstraZeneca, Amicus, Amgen, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal Pharma, and is Director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra Astrazeneca-UAM of chronic kidney disease and electrolytes. A.O. is the former Editor-in-Chief of CKJ. M.K. is member of the CKJ Editorial Board. M.J.S. reports honorarium for conferences, consulting fees, and advisory boards from AstraZeneca, Novo Nordsik, Esteve, Vifor, Bayer, Mundipharma, Ingelheim Lilly, Jansen, Fresenius, ICU Medical, Travere Ther-apeutics, and Boehringer. M.J.S. also has received grants from Boehringer-Ingelheim. M.J.S. is Editor-in-Chief of CKJ.

Chronic kidney disease (CKD) will become the fifth global case of death by 2040. Its largest impact is on premature mortality but the number of persons with kidney failure requiring renal replacement therapy (RRT) is also increasing dramatically. Current RRT is suboptimal due to the shortage of kidney donors and dismal outcomes associated with both hemodialysis and peritoneal dialysis. Kidney care needs a revolution. In this review, we provide an update on emerging knowledge and technologies that will allow an earlier diagnosis of CKD, addressing the current so-called blind spot (e.g. imaging and biomarkers), and improve renal replacement therapies (wearable artificial kidneys, xenotransplantation, stem cell-derived therapies, bioengineered and bio-artificial kidneys)., Research by A.O. is supported by IS/Fondos FEDER (PI18/01 366, PI19/00 588, PI19/00 815, DTS18/00 032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00 064) and PERSTIGAN AC18/00 071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Espanola de Nefrologia, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM, Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001) and SPACKDc PMP21/00 109, FEDER funds. RD16/0009.

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19-53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49-117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes., The authors acknowledge funding from the Nazarbayev University Collaborative Research Program (CRP) for 2020–2022 (Funder Project Reference: 091019CRP2105).

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of novel oral anti-hyperglycemic agents which are increasingly used in clinical practice. SGLT-2 inhibitors improve glycemic control and cardiorenal outcomes, promote weight loss, and reduce blood pressure. Randomized controlled trials have demonstrated that SGLT-2 inhibitors reduce proteinuria and delay progression of kidney disease in patients with albuminuria. However, whether SGLT-2 inhibitors have similar benefits in patients with nephrotic-range proteinuria has not been well established. Evidence to date has been limited to case reports, case series and secondary analyses of randomized controlled trials. This is the first comprehensive review on the effectiveness of SGLT-2 inhibitors for the treatment of patients with nephrotic-range albuminuria or proteinuria. Overall findings support a likely beneficial role of SGLT-2 inhibitors in reducing proteinuria and delaying chronic kidney disease progression in patients with nephrotic-range proteinuria. Lay Summary Sodium-glucose cotransporter-2 (SGLT-2) inhibitors might be a promising agent in non-diabetic kidney patients with proteinuria. Lowering proteinuria may help to improve kidney disease patients' outcome by slowing kidney disease progression and decreasing the risk of new cardiovascular events., NA

Improper hydration habits are commonly disregarded as a risk factor for the development of chronic diseases. Consuming an intake of water below recommendations (underhydration) in addition to the substitution of sugar-sweetened beverages (SSB) for water are habits deeply ingrained in several countries. This behavior is due to voluntary and involuntary dehydration; and because young children are exposed to SSB, the preference for a sweet taste is profoundly implanted in the brain. Underhydration and SSB intake lead to mild hyperosmolarity, which stimulates biologic processes, such as the stimulation of vasopressin and the polyol-fructose pathway, which restore osmolarity to normal but at the expense of the continued activation of these biological systems. Unfortunately, chronic activation of the vasopressin and polyol-fructose pathways has been shown to mediate many diseases, such as obesity, diabetes, metabolic syndrome, chronic kidney disease, and cardiovascular disease. It is therefore urgent that we encourage educational and promotional campaigns that promote the evaluation of personal hydration status, a greater intake of potable water, and a reduction or complete halting of the drinking of SSB., NIH; Fondos de Gasto Directo Autorizados a la Subdirección de Investigación Básica del Instituto Nacional de Cardiología Ignacio Chávez; Instituto Nacional de Cardiologia Ignacio Chavez

Air pollution is an emerging etiology of chronic kidney disease (CKD). Evidence regarding this causative relationship has been shown by several studies. Recently, Lin et al. conducted the first community-based study investigating the association between CKD prevalence and air pollutant levels utilizing a Fuzzy Logic Interference model. Despite the study's limitations, the results correlate with the previous meta-analysis and observational studies. Higher fine particular matter (PM2.5) levels are associated with the increased global burden of CKD and may also influence the unequal distribution of burden in low-to-middle income countries. Despite growing evidence of the association of air pollution with CKD risk, the underlying pathophysiology has yet to be fully understood. Future studies investigating the pathophysiology and efficiency of the potential therapeutic and preventive measures against air pollution-related kidney injury are required to reduce the CKD burden., NA

Background: the coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multiorgan failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis.Methods: the main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. Discussion: this study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options., Ministry of Research and Innovation; CNCS-UEFISCDI

Kidney disease is one of the most important factors affecting the prognosis of patients with coronavirus disease 2019 (COVID-19). Patients on kidney replacement therapy (KRT; dialysis and kidney transplant recipients) are vulnerable to severe complications of COVID-19. As the pandemic evolves and preventive strategies, availability of healthcare facilities, treatment approaches and vaccination strategies change, studies are needed on COVID-19 epidemiology and outcomes in KRT patients that contribute to vaccination regimens, treatment protocols and immunosuppressive therapies of KRT patients with COVID-19. In their registry-based study, Quiroga et al. analyzed COVID-19 KRT patients in Spain across six pandemic waves in order to evaluate dynamic treatment approaches and outcomes as well as the efficacy of vaccination., NA

During the coronavirus disease 2019 (COVID-19) pandemic, hemodialysis patients constitute one of the most vulnerable patient populations as they have more significant comorbidities and need to visit healthcare settings frequently even under pandemic conditions. It was also largely demonstrated that hemodialysis patients have high mortality rates with severe to fatal disease due to COVID-19 during their initial hospitalization. Even though the functional decline and fatigue after severe infections are not a novel entity, some long-term effects of COVID-19 have drawn attention with their prolonged effects even after discharge. A recent prospective, observational study by Carriazo et al. provided the first evidence to compare long-term mortality rates of hemodialysis patients with and without COVID-19. Carriazo et al. stated a hazard ratio of 3.00 for the mortality rates of hemodialysis patients over a 1-year follow-up period after their COVID-19 diagnosis. They emphasized that the high mortality rates of hemodialysis patients with COVID-19 are not limited to the initial hospitalization period but also continue after discharge, especially in the first 3 months. In light of this study, it can be recommended that hemodialysis patients with COVID-19 should be monitored closely and continuously, and hemodialysis patients should be prioritized for vaccination against COVID-19 with close follow-up for their antibody levels., NA

COVID-19, a disease caused by a novel coronavirus (SARS-CoV-2), is a major global threat that has turned into a pandemic. Despite the emergence of multiple vaccination alternatives and developing therapeutic options, dramatic short- and long-term clinical outcomes have been recorded with more than 250 million infected people and over 5 million deaths as of November 2021. COVID-19 presents various respiratory, cardiovascular, neuropsychiatric, musculoskeletal and kidney features during the acute phase; nevertheless, renal involvement in the post-infection period has recently been emphasized. The present review aims to evaluate the growing literature on kidney involvement in the SARS-CoV-2 infection along with clinical features reported both in the acute phase of the infection and in the post-acute COVID-19 period by assessing potential pathophysiological frameworks explaining such conditions. Chronic kidney disease and development of acute kidney injury (AKI) in the course of initial hospitalization are associated with high mortality and morbidity rates. Moreover, growing evidence suggests a decline in renal function in the 6-to-12-month follow-up period even in patients without any signs of AKI during the acute phase. Despite such concerns there are no guidelines regulating the follow-up period or therapeutic alternatives for such patient population. In conclusion, the burden of COVID-19 on the kidney is yet to be determined. Future prospective large scale studies are needed with long follow-up periods assessing kidney involvement via multiple parameters such as biopsy studies, urinalysis, measurement of serum creatinine and cystatin C, directly measured glomerular filtration rate, and assessment of tubular function via urinary beta(2)-microglobulin measurements., NA

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease. Recent evidence suggests that the pathogenesis of ADPKD is a complex web of abnormal cellular processes including altered cell signaling, disordered cell metabolism, impaired autophagy, increased apoptosis, mitochondrial dysfunction and chronic inflammation. Sodium-glucose cotransporter (SGLT) inhibitors (SGLTi) reduce body weight, blood pressure and blood glucose levels, have kidney and cardiovascular protective activity, and have been reported to decrease inflammation, increase autophagy and improve mitochondrial dysfunction. We now review results from preclinical studies on SGLTi for ADPKD identified through a systematic search of the MEDLINE, Cochrane Library, Embase and PubMed databases. Potential underlying mechanisms for the conflicting results reported as well as implications for clinical translation are discussed, as ADPKD patients were excluded from clinical trials exploring kidney protection by SGLT2 inhibitors (SGLT2i). However, they were not excluded from cardiovascular safety trials or trials for cardiovascular conditions. A post-hoc analysis of the kidney function trajectories and safety of SGLT2i in ADPKD patients enrolled in such trials may provide additional information. In conclusion, SGLT2i are cardio- and nephroprotective in diverse clinical situations. Currently, it is unclear whether ADPKD patients may benefit from SGLT2i in terms of kidney function preservation, and their safety in this population remains unexplored. We propose a roadmap to address this unmet clinical need., NA

Background and aims: beverages are an important aspect of diet, and their quality can possibly affect health. The Healthy Beverage Index (HBI) has been developed to take into account these effects. This study aimed to highlight the relationships between health and beverage quality by assessing the association of the HBI and its components with kidney and cardiometabolic (CM) outcomes in an initially healthy population-based familial cohort. Methods: this study included 1,271 participants from the STANISLAS cohort. The HBI, which includes 10 components of habitual beverage consumption, was calculated. Associations of the HBI and its components with estimated glomerular filtration rate (eGFR), albuminuria, hypertriglyceridemic waist (HTG waist), metabolic syndrome (MetS), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LV mass) were analyzed using multivariable linear or logistic regression models. Results: the median HBI score was 89.7 (78.6–95) out of 100 points. While the overall HBI score was not significantly associated with any of the studied outcomes, individual HBI components were found differently associated with the outcomes. cfPWV and cIMT were lower in participants who did not meet the full-fat milk criteria (p = 0.03 and 0.001, respectively). In men, higher cfPWV was observed for the “low Fat milk” (p = 0.06) and “alcohol” (p = 0.03) non-adherence criteria. Odds of HTG waist were higher with the non-adherence to sugar-sweetened beverages criteria (p < 0.001). eGFR was marginally higher with non-adherence to the coffee/tea criteria (p = 0.047). Conclusions: In this initially healthy population, HBI components were differently associated with kidney and cardiometabolic outcomes, despite a good overall HBI score. Our results highlight specific impacts of different beverage types and suggest that beverages could have an impact on kidney and cardiometabolic health., Centre Hospitalier Regional Universitaire of Nancy (CHRU); French Ministry of Health (Programme Hospitalier de Recherche Clinique Inter-regional 2013); Fonds Europeen de Developpement Regional (FEDER Lorraine); French National Research Agency (ANR); European Union (EU); Horizon 2020; 6th EU Research Framework Programme Network of Excellence Ingenious HyperCare; 7th Research Framework Programme Europeen Cooperation-Theme Health/FP7HEALTH-2010-single-stage; Heart OMics in AGEing (HOMEGA); FOCUS-MR; FIBROTARGETS; ERA-CVD EXPERT; Contrat de Plan Etat-Lorraine IT2MP

Chronic kidney disease (CKD) is associated with cognitive functional impairment or dementia in addition to cardiovascular diseases. Aging of the population and the increasing prevalence of CKD in elderly patients are making dementia more prevalent. Blood pressure (BP) variability is an important risk factor for dementia. Although ample data link high BP variability with the risk of dementia in the general population, data on CKD patients are scarce. An observational cohort study conducted by Park et al., including 103 139 patients, demonstrated a strong association between higher visit-to-visit BP variability and increased risk of dementia in CKD patients. Both higher systolic and diastolic BP variabilities were associated with any type of dementia, including Alzheimer's and vascular dementia. Physicians must be aware of BP variability when evaluating CKD patients with hypertension., NA

Background: Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome-wide association study on SUA levels, and (3) investigate the association between certain single-nucleotide polymorphisms and target organ damage. Methods and results: the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Sante des Lorrains Assures Sociaux) study cohort is a single-center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed approximate to 20 years apart. Serum lipid profile, SUA, urinary albumin/creatinine ratio, estimated glomerular filtration rate, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiography, pulse wave velocity, and genotyping for each participant were assessed at V4. A total of 1573 participants were included at V4, among whom 1417 had available SUA data at visit 1. Genome-wide association study results highlighted multiple single-nucleotide polymorphisms on the SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele (rs16890979) had significantly lower SUA levels. Although SUA level at V4 was highly associated with diabetes, prediabetes, higher body mass index, CRP (C-reactive protein) levels, estimated glomerular filtration rate variation (visit 1-V4), carotid intima-media thickness, and pulse wave velocity, rs16890979 was only associated with higher carotid intima-media thickness. Conclusions: our findings demonstrate that rs16890979, a genetic determinant of SUA levels located on the SLC2A9 gene, is associated with carotid intima-media thickness despite significant associations between SUA levels and several clinical outcomes, thereby lending support to the hypothesis of a link between SUA and cardiovascular disease., Nancy Centre Hospitalier Regional Universitaire; French Ministry of Health; French National Research Agency (ANR); Contrat de Plan Etat?Lorraine and Fonds Européen de Développement Régional Lorraine; Programme Hospitalier de Recherche Clinique Inter regional 2013; Investissements d’Avenir; FIGHT?heart failure; French Plan d'Investissement d'Avenir project “Lorraine Université d’Excellence; European Union (EU); European Fibro?Targets Project; European HOMAGE project; 7th Framework Program; MEDIA project; FOCUS?MR; ERA?CVD EXPERT; Fondation de Recherche en Hypertension Artérielle

Patients with chronic kidney disease, chronic heart failure and hypertension have an increased risk of coronavirus disease 2019 (COVID-19)-related death. Renin-angiotensin-aldosterone system (RAS) blockers are commonly prescribed to decrease morbidity and mortality in these conditions. Following the pre-clinical demonstration of COVID-19 viral entry into cells via angiotensin-converting enzyme-2, the use of RAS blockers was questioned in infected individuals. Theodorakopoulou et al. extensively review the pathophysiology behind that hypothesis and observational or clinical trials on RAS blockers and COVID-19. Despite being a scientific hot spot of an ongoing debate, discontinuation of RAS blockers is not associated with improved clinical outcomes in COVID-19 and may have potential harmful effects, including exacerbation of the underlying disease., NA

Kidney transplantation (KT) is an increasingly utilized treatment for end-stage kidney disease. Hypertension either as a cause of kidney disease or as a complication of chronic kidney disease is the most frequently encountered comorbidity of KT patients. Hence, the management of hypertension in KT patients is crucial to prolong patient and graft survival. Ambulatory blood pressure monitoring (ABPM) appeared as a promising technique that has superiority over office and home blood pressure (BP) monitoring to correctly diagnose and manage hypertension. A recent meta-analysis by Pisano et al. including 42 studies with 4115 participants provided strong data for the comparison of ABPM with office BP monitoring in KT patients. In addition to the current literature knowledge, the findings of Pisano et al. filled the long-awaited evidence gap to suggest ABPM as a first-line BP monitoring technique for KT patients. Despite its disadvantages, such as patient discomfort, cost-effectiveness and limited availability, ABPM has crucial advantages in the management of hypertension including the detection of abnormal circadian BP patterns, the assessment of effects of physical activity and short-term variability of BP, and the exclusion of masked and white-coat hypertension., NA

Background: the consumption of sweetened beverages is associated with increased risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus. Objective: we hypothesized that the metabolic effects of fructose in sugary beverages might be modulated by the speed of ingestion in addition to the overall amount. Design: thirty healthy subjects free of any disease and medication were recruited into two groups. After overnight fasting, subjects in group 1 drank 500 mL of apple juice over an hour by drinking 125 mL every 15 min, while subjects in group 2 drank 500 mL of apple juice over 5 min. Blood samples were collected at time zero and 15, 30, 60, and 120 min after ingestion to be analyzed for serum glucose, insulin, homeostatic model assessment (HOMA-IR) score, fibroblast growth factor 21, copeptin, osmolarity, sodium, blood urea nitrogen (BUN), lactate, uric acid, and phosphate levels. Results: serum glucose, insulin, HOMA-IR, fibroblast growth factor 21, copeptin, osmolarity, sodium, BUN, and lactate levels increased following apple juice ingestion. The increases were greater in the fast-drinking group, which were more significant after 15 min and 30 min compared to baseline. The changes in uric acid were not statistically different between the groups. Phosphate levels significantly increased only in the fast-drinking group. Conclusion: fast ingestion of 100% apple juice causes a significantly greater metabolic response, which may be associated with negative long-term outcomes. Our findings suggest that the rate of ingestion must be considered when evaluating the metabolic impacts of sweetened beverage consumption.

Background: to investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. Methods: four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. Results: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). Conclusion: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

Subjects with obesity frequently have elevated serum vasopressin levels, noted by measuring the stable analog, copeptin. Vasopressin acts primarily to reabsorb water via urinary concentration. However, fat is also a source of metabolic water, raising the possibility that vasopressin might have a role in fat accumulation. Fructose has also been reported to stimulate vasopressin. Here, we tested the hypothesis that fructose-induced metabolic syndrome is mediated by vasopressin. Orally administered fructose, glucose, or high-fructose corn syrup increased vasopressin (copeptin) concentrations and was mediated by fructokinase, an enzyme specific for fructose metabolism. Suppressing vasopressin with hydration both prevented and ameliorated fructose-induced metabolic syndrome. The vasopressin effects were mediated by the vasopressin 1b receptor (V1bR), as V1bR-KO mice were completely protected, whereas V1a-KO mice paradoxically showed worse metabolic syndrome. The mechanism is likely mediated in part by de novo expression of V1bR in the liver that amplifies fructokinase expression in response to fructose. Thus, our studies document a role for vasopressin in water conservation via the accumulation of fat as a source of metabolic water. Clinically, they also suggest that increased water intake may be a beneficial way to both prevent or treat metabolic syndrome.

The prevalence of both cancer and end-stage renal disease is increasing. In addition, medical advances have meant increased survival rates for both diseases. Many chemotherapeutics are renally excreted, and conversely, renal insufficiency promotes a pro-neoplastic state, including genitourinary and other cancers. Dialysis prolongs life while increasing cancer risk. Proposed oncogenic mechanisms include immune dysfunction, chronic inflammation, changes in gut microbiota and stimulation of the renin-angiotensin system. This review summarizes current concepts in the relationship between cancer and renal insufficiency., NA

Kidney transplant recipients and dialysis patients constitute a risk group for severe COVID-19. They are highly advised to get vaccinated according to the current guidelines. However, data on antibody response, cell responses and protection from events, and factors that might alter this response after a rou-tine full series of vaccination remain incomplete for these populations. The aim of this article was to analyze the antibody responses after a full series of mRNA-based SARS-CoV-2 vaccination in kidney transplantation and dialysis patients and to define the factors that alter seroconver-sion status in these populations. In this systematic review, 18 studies investigating the antibody response to full vaccination with two doses of COVID-19 mRNA vaccines in hemodialysis, peritoneal dialysis, and kidney transplant patients were included. Kidney transplant and dialysis patients have a lower seroconversion rate after mRNA-based SARS-CoV-2 vaccination than the healthy population: 27.2% for kidney transplantation, 88.5% for dialysis patients while all healthy control in these studies seroconverted. Moreover, anti-S antibody titers were lower in seroconverted kidney transplantation or dialysis patients than in healthy control in all studies that assessed this variable. Older age and dialysis vintage, immunosuppressive or chemotherapy treatment, and lower serum albumin, white blood cell, lymphocyte and hemoglobin counts were associated with lower/no antibody response to vaccination. Dialysis patients and kidney transplant recipients have lower seroconversion rates after a full series of mRNA-based SARS-CoV-2 vaccination than the general population. Several factors are associated with an altered antibody response. A third dose could be considered in this patient group / Böbrek nakilli ve diyaliz hastaları COVID-19 enfeksiyonu açısından yüksek riskli gruptadırlar. Güncel klavuzlar bu nedenle bu hastaların öncelikli aşılanması gereken grupta olduğunu belirtmişlerdir. Bununla, NA

Despite massive government and private sector investments into prevention of cardiovascular disease, diabetes mellitus and obesity, efforts have largely failed, and the burden of cost remains in the treatment of downstream morbidity and mortality, with overall stagnating outcomes. A new paradigm shift in the approach to these patients may explain why existing treatment strategies fail, and offer new treatment targets. This review aims to provide a clinician-centred primer on metabolic memory, defined as the sum of irreversible genetic, epigenetic, cellular and tissue-level alterations that occur with long-time exposure to metabolic derangements., NA

Backgroud: metabolic syndrome affects 35% of the adult population in developed countries associated with non-alcoholic steatohepatitis, insulin resistance, and cardiovascular events. Fatty infiltration of the pancreas, or pancreatic steatosis, is a risk factor for acute pancreatitis, pancreatic malignancies, and diabetes mellitus, yet its relationship with metabolic syndrome is not well defined. Methods: we performed a single-centered retrospective observational study of 322 healthy subjects (subjects volunteering to be kidney transplant donors, mean age=46.3±13.5, 163 men and 159 women) in the last 2 years (July 2018-February 2020) from our institution. Pancreatic steatosis and hepatosteatosis were confirmed by computed tomography. Results: pancreatic steatosis was present in 26.3% (85/322) of the subjects, and this finding correlated with age, body mass index (BMI), male sex, a family history of diabetes, creatinine, cystatin C, uric acid, low-density lipoprotein (LDL) cholesterol, triglycerides, glycemia, hemoglobin, transverse body diameter, and subcutaneous fat thickness levels by univariable logistic regression. On multiple linear regression only age (95% CI 1.01, 1.06), BMI (95% CI 1.01, 1.19), male sex (95% CI 1.49-5.99), uric acid (95% CI 1.01, 1.76), and subcutaneous fat thickness levels (95% CI 1.21-2.36) remained independently associated with pancreatic steatosis. Conclusion: pancreatic steatosis is common and associated with obesity, elevated serum uric acid, subcutaneous fat thickness, and male sex. Future studies are needed to evaluate if there are specific clinical consequences to the presence of pancreatic steatosis., NA

NA

Left atrial strain (LASr) represents a relatively new but promising technique for left atrial and left ventricle function evaluation. LASr was strongly linked to myocardial fibrosis and endocardial thickness, suggesting the utility of LASr in subclinical cardiac dysfunction detection. As CKD negatively impacts cardiovascular risk and mortality, underlying structural and functional abnormalities of cardiac remodeling are widely investigated. LASr could be used in LV diastolic dysfunction grading with an excellent discriminatory power. Our objectives were to assess the impact and existing correlations between LASr and cardiovascular outcomes, as reported in clinical trials, including patients with CKD. We searched PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials for full-text papers. As reported in clinical studies, LASr was associated with adverse cardiovascular outcomes, including cardiovascular death and major adverse cardiovascular events (HR 0.89, 95% CI, 0.84-0.93, p < 0.01), paroxysmal atrial fibrillation (OR 0.847, 95% CI, 0.760-0.944, p = 0.003), reduced exercise capacity (AUC 0.83, 95% CI, 0.78-0.88, p < 0.01), diastolic dysfunction (p < 0.05), and estimated pulmonary capillary wedge pressure (p < 0.001). Despite limitations attributed to LA deformation imaging (image quality, inter-observer variability, software necessity, learning curve), LASr constitutes a promising marker for cardiovascular events prediction and risk evaluation in patients with CKD., NA

Diabetic kidney disease (DKD) represents a growing public health burden and is the leading cause of end-stage kidney diseases. In recent years, host-gut microbiota interactions have emerged as an integral part for host homeostasis. In the context of nephropathies, mounting evidence supports a bidirectional microbiota-kidney crosstalk, which becomes particularly manifest during progressive kidney dysfunction. Indeed, in chronic kidney disease (CKD), the “healthy” microbiota structure is disrupted and intestinal microbes produce large quantities of uremic solutes responsible for renal damage; on the other hand, the uremic state, fueled by reduced renal clearance, causes shifts in microbial metabolism and composition, hence creating a vicious cycle in which dysbiosis and renal dysfunction are progressively worsened. In this review, we will summarize the evidence from clinical/experimental studies concerning the occurrence of gut dysbiosis in diabetic and non-diabetic CKD, discuss the functional consequences of dysbiosis for CKD progression and debate putative therapeutic interventions targeting the intestinal microbiome., Top Consortia for Knowledge and Innovation (TKI-PPP) Grant; Health-Holland, 2020

Acute Kidney Injury (AKI) is an often neglected but crucial element of clinical nephrology. The aim of the Nephrology Public Policy Committee (NPPC) of the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) is to promote several key aspects of European nephrology. One of the targets proposed by NPPC was to advance European nephrology involvement in AKI. We undertook literature analyses to define the current position of European nephrology in the field of AKI compared to other regions, and about how different European countries compare to each other. It appeared that vis-à-vis countries with a comparable socio-economic status (the US, Australia, New Zealand, Canada), the European contribution was almost 50% lower. Within Europe, Central/Eastern Europe and countries with a lower gross domestic product (GDP) showed lower scientific output. Nephrologists contributed to less than half of the output. There was no trend for a change over the last decade. It is concluded that there is room to improve the contribution of European nephrology in the field of AKI. We propose a model on how to promote clinical collaboration on AKI across Europe, the creation of a pan-European nephrology network of interested units is proposed, to improve clinical outcomes, increase nephrologist involvement and awareness outside nephrology, and stimulate research on AKI in Europe. Accordingly, we also propose a list of research priorities and stress the need for more European funding of AKI research., Secarna; Previpharma; Novartis; Bayer; GlaxoSmithKline; Boehringer; AstraZeneca; AM-Pharma; FAST Biomedical and Renibus Therapeutics; Servier; Sanofi; Mundipharma; Amgen; Otsuka; Kyowa; Alexion Pharmaceuticals

Sodium-glucose co-transporter-2 (SGLT2) inhibitors decreased cardiovascular (CV) events and improved renal outcomes in CV safety studies in type 2 diabetes melitus (T2DM) patients at high CV risk. Canagliflozin also improved kidney outcomes in diabetic kidney disease in the Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluationtrial. More recently, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial showed that dapagliflozin improved CV outcomes in patients with HF with or without diabetes. Protection from HF in nondiabetics was confirmed for empagliflozin in the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. A meta-analysis of DAPA-HF and EMPEROR-Reduced confirmed reductions in all-cause and CV death and the combined risk of CV death or worsening HF, as well as in the composite renal endpoint fhazard ratio [HR] 0.62 [95% confidence interval (CI) 0.43-0.90] g without differences based on the presence of diabetes or baseline estimated glomerular filtration rate (eGFR). Moreover, the Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) showed that dapagliflozin as an add-on over renin-angiotensin system blockade in patients with chronic kidney disease (CKD; with or without T2DM) reduced the HR for the primary endpoint (time to the first occurrence of >= 50% eGFR decline, end-stage kidney disease or renal or CV death) to 0.61 (95% CI 0.51-0.72) and for the secondary endpoints of worsening renal function or death from kidney failure [HR 0.56 (95% CI 0.45-0.68)], hospitalization for HF or CV death [HR 0.71 (95% CI 0.55-0.92)] and all-cause mortality [HR 0.69 (95% CI 0.53-0.88)]. These beneficial effects were consistent in patients with and without T2DM. In conclusion, SGLT2 inhibitors offer CV and kidney protection in both diabetic and non-diabetic C, European Union (European Union); FIS/Fondos FEDER; ERAPerMed-JTC2018; Comunidad de Madrid en Biomedicina; Sociedad Espanola de Nefrologia; FRIAT

The clinical course of viral infections in patients under immunosuppression can be atypical and/or fatal if not diagnosed and treated appropriately. The coronavirus disease 2019 (COVID-19) may also have an atypical presentation. Contrary to the general opinion, transplant patients may be asymptomatic or oligosymptomatic, which could be a risk factor for underdiagnosis and the dissemination of this viral disease. This study presents the clinical features of 2 oligosymptomatic kidney transplant patients diagnosed with COVID-19. We suggest that new screening algorithms for COVID-19 should be reconsidered for the transplant patient population., NA

Melatonin is the main biochronologic molecular mediator of circadian rhythm and sleep. It is also a powerful antioxidant and has roles in other physiologic pathways. Melatonin deficiency is associated with metabolic derangements including glucose and cholesterol dysregulation, hypertension, disordered sleep and even cancer, likely due to altered immunity. Diabetic nephropathy (DN) is a key microvascular complication of both type 1 and 2 diabetes. DN is the end result of a complex combination of metabolic, haemodynamic, oxidative and inflammatory factors. Interestingly, these same factors have been linked to melatonin deficiency. This report will collate in a clinician-oriented fashion the mechanistic link between melatonin deficiency and factors contributing to DN., FAPESP Funding

Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure., European Union (European Union); FIS/Fondos FEDER; Comunidad de Madrid en Biomedicina; Sociedad Espanola de Nefrologia; FRIAT

Intradialytic hypotension (IDH) is a frequent and serious complication of chronic haemodialysis, linked to adverse longterm outcomes including increased cardiovascular and all-cause mortality. IDH is the end result of the interaction between ultrafiltration rate (UFR), cardiac output and arteriolar tone. Thus excessive ultrafiltration may decrease the cardiac output, especially when compensatory mechanisms (heart rate, myocardial contractility, vascular tone and splanchnic flow shifts) fail to be optimally recruited. The repeated disruption of end-organ perfusion in IDH may lead to various adverse clinical outcomes affecting the heart, central nervous system, kidney and gastrointestinal system. Potential interventions to decrease the incidence or severity of IDH include optimization of the dialysis prescription (cool dialysate, UFR, sodium profiling and high-flux haemofiltration), interventions during the dialysis session (midodrine, mannitol, food intake, intradialytic exercise and intermittent pneumatic compression of the lower limbs) and interventions in the interdialysis period (lower interdialytic weight gain and blood pressure-lowering drugs). However, the evidence base for many of these interventions is thin and optimal prevention and management of IDH awaits further clinical investigation. Developing a consensus definition of IDH will facilitate clinical research. We review the most recent findings on risk factors, pathophysiology and management of IDH and, based on this, we call for a new consensus definition of IDH based on clinical outcomes and define a roadmap for IDH research., Ministry of Research and Innovation; CNCS-UEFISCDI; PNCDI III; European Union (EU); Horizon 2020; ERA-PerMed-JTC2018; PERSTIGAN; ISCIII-RETIC REDinREN FEDER Funds; Comunidad de Madrid; Fundacion Renal Inigo Alvarez de Toledo (FRIAT)

The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) started in December 2019 and has affected millions of lives worldwide, while many aspects of the illness are still unknown. Current data show that many hospitalized COVID-19 patients suffer from kidney damage, in the form of proteinuria, hematuria or acute kidney injury (AKI). AKI is especially prevalent among severe and critically ill COVID-19 patients and is a predictor of mortality. The pathophysiology of AKI in COVID-19 is unclear. Early reports of histopathologic examination from autopsied kidney tissue show SARS-CoV-2 viral particles in renal tubular cells and podocytes, suggesting direct viral infection, as well as findings of acute tubular necrosis, while rhabdomyolysis-associated AKI and glomerulopathies may also occur. As of today, only remdesivir has been authorized to treat COVID-19. Ongoing research investigates potential of anti-viral and anti-inflammatory agents along with safety and efficacy of commonly prescribed drugs such as renin-angiotensin-aldosterone system blockers. This review discusses the prevalence of AKI and its association with outcome, while highlighting possible mechanisms of AKI and suggesting organ protective measures to prevent the development of kidney damage., British Heart Foundation; Dunhill Medical Trust; Welcome Trust; EPSRC; Community Jameel Imperial College COVID-19 Excellence Fund; UK MRC

The clinical course of viral infections in patients under immunosuppression can be atypical and/or fatal if not diagnosed and treated appropriately. The coronavirus disease 2019 (COVID-19) may also have an atypical presentation. Contrary to the general opinion, transplant patients may be asymptomatic or oligosymptomatic, which could be a risk factor for underdiagnosis and the dissemination of this viral disease. This study presents the clinical features of 2 oligosymptomatic kidney transplant patients diagnosed with COVID-19. We suggest that new screening algorithms for COVID-19 should be reconsidered for the transplant patient population., NA

Hyperuricaemia is frequent in chronic kidney disease (CKD). Observational studies have shown an association with adverse outcomes and acquired hyperuricaemia (meaning serum urate levels as low as 1.0 mg/dL) in animal models induces kidney injury. This evidence does not justify the widespread use of urate-lowering drugs for asymptomatic hyperuricaemia in CKD. However, promising results from small, open-label studies led some physicians to prescribe urate-lowering drugs to slow CKD progression. Two recent, large, placebo-controlled trials (CKD-FIX and PERL) showed no benefit from urate lowering with allopurinol on the primary endpoint of CKD progression, confirming prior negative results. Despite these negative findings, it was still argued that the study population could be optimized by enrolling younger non-proteinuric CKD patients with better preserved glomerular filtration rate (GFR). However, in these low-risk patients, GFR may be stable under placebo conditions. Additionally, the increased mortality trends already identified in gout trials of urate-lowering therapy were also observed in CKD-FIX and PERL, sending a strong safety signal: 21/449 (4.7%) and 10/444 (2.2%) patients died in the combined allopurinol and placebo groups, respectively [chi-squared P-value 0.048; relative risk 2.07 (95% CI 0.98-4.34); P = 0.06]. Given the absent evidence of benefit in multiple clinical trials and the potentially serious safety issues, the clear message should be that urate-lowering therapy should not be prescribed for the indication of slowing CKD progression. Additionally, regulatory agencies should urgently reassess the safety of chronic prescription of urate-lowering drugs for any indication., FIS/Fondos FEDER; ERAPerMed-JTC2018; European Commission; European Union (EU); Horizon 2020; Comunidad de Madrid en Biomedicina; Sociedad Espanola de Nefrologia; FRIAT

The potential contribution of serum osmolarity in the modulation of blood pressure has not been evaluated. This study was done to examine the relationship between hyperosmolarity and hypertension in a five-year longitudinal design. We enrolled 10,157 normotensive subjects without diabetes who developed hypertension subsequently as determined by annual medical examination in St. Luke’s International Hospital, Tokyo, between 2004 and 2009. High salt intake was defined as >12 g/day by a self-answered questionnaire and hyperosmolarity was defined as >293 mOsm/L serum osmolarity, calculated using serum sodium, fasting blood glucose, and blood urea nitrogen. Statistical analyses included adjustments for age, gender, body mass index, smoking, drinking alcohol, dyslipidemia, hyperuricemia, and chronic kidney disease. In the patients with normal osmolarity, the group with high salt intake had a higher cumulative incidence of hypertension than the group with normal salt intake (8.4% versus 6.7%, p = 0.023). In contrast, in the patients with high osmolarity, the cumulative incidence of hypertension was similar in the group with high salt intake and in the group with normal salt intake (13.1% versus 12.9%, p = 0.84). The patients with hyperosmolarity had a higher incidence of hypertension over five years compared to that of the normal osmolarity group (p < 0.001). After multiple adjustments, elevated osmolarity was an independent risk for developing hypertension (OR (odds ratio), 1.025; 95% CI (confidence interval), 1.006–1.044), regardless of the amount of salt intake. When analyzed in relation to each element of calculated osmolarity, serum sodium and fasting blood glucose were independent risks for developing hypertension. Our results suggest that hyperosmolarity is a risk for developing hypertension regardless of salt intake., NA

The rationale for using sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) has evolved over the last decade. Due to the effects on glucosuria and body weight loss, SGLT2 inhibitors were originally approved for glycemic control in T2D. Since glucosuria is attenuated in chronic kidney disease (CKD) Stages 3-5, initial regulatory approval for SGLT2 inhibitor use was limited to patients with T2D and preserved estimated glomerular filtration rate. Over time, however, it has become increasingly apparent that these therapies have a variety of important pharmacodynamic and clinical effects beyond glycemic lowering, including antihypertensive and antialbuminuric properties, and the ability to reduce glomerular hypertension. Importantly, these sodium-related effects are preserved across CKD stages, despite attenuated glycemic effects, which are lost at CKD Stage 4. With the completion of cardiovascular (CV) outcome safety trials-EMPA-REG OUTCOME, CANVAS Program and DECLARE TIMI-58-in addition to reductions in CV events, SGLT2 inhibition consistently reduces hard renal endpoints. Importantly, these CV and renal effects are independent of glycemic control. Subsequent data from the recent CREDENCE trial-the first dedicated renal protection trial with SGLT-2 inhibition-demonstrated renal and CV benefits in albuminuric T2D patients, pivotal results that have expanded the clinical importance of these therapies. Ongoing trials will ultimately determine whether SGLT2 inhibition will have a role in renal protection in other clinical settings, including nondiabetic CKD and type 1 diabetes., University of Toronto Merit Award; Canadian Institutes of Health Research; Diabetes Canada; Heart and Stroke/Richard Lewar Centre of Excellence; Heart and Stroke Foundation of Canada

Coronaviruses are a major pathogen for adults, causing up to one-third of community-acquired respiratory tract infections in adults during epidemics. Although the pandemic outbreak of coronavirus disease-2019 (COVID-19) targets preferentially patient’s lungs, recent data have documented that COVID-19 causes myocarditis, acute myocardial infarction, exacerbation of heart failure and acute kidney injury. Studies show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to its predecessor SARS-CoV, engages angiotensin-converting enzyme 2 (ACE2) as the entry receptor. ACE2 is also expressed in the heart, providing a link between coronaviruses and the cardiovascular system., NA

The optimal range of serum uric acid (urate) associated with the lowest risk for developing cardiometabolic diseases is unknown in a generally healthy population. This 5-year cohort study is designed to identify the optimal range of serum urate. The data were collected from 13,070 Japanese between ages 30 and 85 at the baseline (2004) from the Center for Preventive Medicine, St. Luke's International Hospital, Tokyo. We evaluated the number of subjects (and prevalence) of those free of the following conditions: hypertension, diabetes, dyslipidemia, and chronic kidney disease (CKD) over 5 years for each 1 mg/dL of serum urate stratified by sex. Furthermore, the odds ratios (ORs) for remaining free of these conditions were calculated with multiple adjustments. Except for truly hypouricemic subjects, having lower serum urate was an independent factor for predicting the absence of hypertension, dyslipidemia, and CKD, but not diabetes. The OR of each 1 mg/dL serum urate decrease as a protective factor for hypertension, dyslipidemia, and CKD was 1.153 (95% confidence interval, 1.068-1.245), 1.164 (1.077-1.258), and 1.226 (1.152-1.306) in men; 1.306 (1.169-1.459), 1.121 (1.022-1.230), and 1.424 (1.311-1.547) in women, respectively. Moreover, comparing serum urate of 3-5 mg/dL in men and 2-4 mg/dL in women, hypouricemia could be a higher risk for developing hypertension (OR: 4.532; 0.943-21.78) and CKD (OR: 4.052; 1.181-13.90) in women, but not in men. The optimal serum urate range associated with the lowest development of cardiometabolic diseases was less than 5 mg/dL for men and 2-4 mg/dL for women, respectively., National Endowment for the Humanities; National Science Foundation; Netherlands Organization for Scientific Research (NWO); Institute for Aegean Prehistory; Loeb Classical Library Foundation; Merops Foundation; Boston University Vecchiotti Archaeology Fund; Catharine van Tussenbroek/Anneke Clason Zooarchaeology Grant

COVID-19 is a global pandemic fuelled in some countries by government actions. The current issue of Clinical Kidney Journal presents 15 articles on COVID-19 and kidney disease from three continents, providing a global perspective of the impact of severe acute respiratory syndrome coronavirus 2 on electrolytes and different kidney compartments (glomeruli, tubules and vascular compartments) and presenting clinically as a syndrome of inappropriate antidiuretic hormone secretion, acute kidney injury, acute kidney disease, collapsing glomerulopathy and thrombotic microangiopathy, among others, in the context of a brand-new cardiorenal syndrome. Kidney injury may need acute dialysis that may overwhelm haemodialysis (HD) and haemofiltration capabilities. In this regard, acute peritoneal dialysis (PD) may be lifesaving. Additionally, pre-existent chronic kidney disease increases the risk of more severe COVID-19 complications. The impact of COVID-19 on PD and HD patients is also discussed, with emphasis on preventive measures. Finally, current therapeutic approaches and potential future therapeutic approaches undergoing clinical trials, such as complement targeting by eculizumab, are also presented., FIS/Fondos FEDER; ERA-PerMed-JTC2018; European Commission; European Union (European Union); Comunidad de Madrid en Biomedicina; Sociedad Espanola de Nefrologia; FRIAT

Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic., FIS; ERA-PerMed-JTC2018; National Institute of Health; ISCIII-RETIC REDinREN Fondos FEDER; FRIAT; Sociedad Española de Nefrología, Comunidad de Madrid; Miguel Servet; IIS-Fundacion Jimenez Diaz Biobank, part of the Spanish Biobanks Platform

National Institute of Health; Toranomon Hospital; Okinaka Memorial Institute for Medical Research; Gout Research Foundation in Japan

Chronic non-communicable diseases have become a pandemic public problem in the 21st century, causing enormous burden on the economy, health and quality of life of societies. The role of a chronic inflammatory state in the pathogenesis of chronic disease has been more comprehensively recognized by recent findings. The new paradigm 'metaflammation' focuses on metabolism-induced (high fat or fructose-based diet or excessive calorie intake) chronic inflammation. There is a close correlation between the increased incidence of chronic kidney disease (CKD) and chronic heart failure with both increased inflammatory marker levels and western-type diet. In this review we describe the concept of metaflammation, its role in the development of CKD and chronic heart disease, the molecular and signalling pathways involved and the therapeutic consequences., FIS ISCIII FEDER Funds; ISCIII-RETIC REDinREN; Comunidad de Madrid en Biomedicina; EUTOX; Fundacio´n Renal Inigo Alvarez de Toledo

The endothelium is the largest organ in the body and recent studies have shown that the endothelial glycocalyx (eGCX) plays a major role in health and disease states. The integrity of eGCX is vital for homoeostasis and disruption of its structure and function plays a major role in several pathologic conditions. An increased understanding of the numerous pathophysiological roles of eGCX may lead to the development of potential surrogate markers for endothelial injury or novel therapeutic targets. This review provides a state-of-the-art update on the structure and function of the eGCX, emphasizing the current understanding of interorgan crosstalk between the eGCX and other organs that might also contribute to the pathogenesis of kidney diseases., NA

Three major guidelines deal with blood pressure thresholds and targets for antihypertensive drug therapy in chronic kidney disease (CKD) patients: The 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease; the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults; and the 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension. However, a careful reading of the three guidelines leaves the practicing physician confused about the definition of CKD, how hypertension and secondary hypertension should be diagnosed in CKD patients and what the blood pressure thresholds, targets and compelling indications of antihypertensive drug therapy should be for this population. Current guidelines refer to different CKD populations and propose different definitions of hypertension, different thresholds to initiate antihypertensive therapy in CKD patients and different BP targets compelling antihypertensive drug use. The different bodies producing guidelines should work together towards a unified definition of CKD, a unified concept of hypertension and unified BP thresholds and targets for hypertensive drug therapy for CKD patients. Otherwise they risk promoting confusion and therapeutic nihilism among physicians and patients., FIS; ERA-PerMed-JTC2018; ISCIII-RETIC REDinREN; Sociedad Española de Nefrología, Comunidad de Madrid; Fondos FEDER; FRIAT

Researchers related to micobiota have claimed that intestinal microbiome exerts an effect on development of disease in many organ systems. Fat tissue, kidneys, heart and vasculature, intestines and even brain tissue are affected by dysbiosis of gut flora. With the increasing number, and quality of the studies, the topics investigated have demonstrated variations from being focused solely on microbiome itself to metabolites of this flora penetrating into serum and immune response of the body to these metabolites. Metabolites released by intestinal flora trigger chronic inflammation in the body and lead to the development of metabolic syndrome, chronic renal disease or cardiovascular diseases. With such a vast gamut of diseases and pathologic conditions related to intestinal microbiome, it should come as no surprise that there have been attempts at treatment of dysbiosis with methods including flora transfer from healthy individuals. This review will focus on these disease states and how they are affected by dysbiosis of flora. The roles played by specific metabolites that increase during intestinal dysbiosis such as indoxyl sulfate, p-cresyl sulfate or trimethylamine N-oxide in chronic kidney disease and atherosclerosis will be discussed. Besides, increase in the permeability of intestinal barriers due to the evolvement of uremia as a result of chronic renal disease, ensuing development of dysbiosis, and the effects of these diseases on dysbiosis will be also dealt with. / Mikrobiyota hakkındaki araştırmalar bir çok sistemdeki hastalık gelişiminde bağırsak mikrobiyomunun etkisi olduğunu iddia ediyor. Bunlardan birkaçı; yağ doku, kalp, dolaşım sistemi, sindirim sistemi ve hatta santral sinir sistemidir. Bu konudaki araştırmaların sayısının ve kalitesinin artmasıyla birlikte üzerinde araştırılan konular; bağırsak mikrobiyomunun saf oluşumundan, bu floranın kana geçiş yapan metabolitleri ve vucüdun buna verdiği tepkiye kadar çeşitlilik göstermeye başladı. Bağırsak flora, NA