Publications by authors named "Alberto Ortiz"

595 Publications

Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients: the SENCOVAC study.

Nephrol Dial Transplant 2021 Nov 12. Epub 2021 Nov 12.

Nephrology Department, Infanta Leonor University Hospital, Madrid, Spain.

Background: Chronic kidney disease (CKD) patients are at high-risk for severe Covid-19. The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of SARS-CoV-2 vaccines in CKD patients. Safety and immediate humoral response results are reported here.

Methods: Four cohorts of patients were included: kidney transplant (KT) recipients, haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analyzed.

Results: 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (p<0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated to KT (OR 20.56, p = 0.001) and to BNT162b2 vaccine (OR 6.03, p = 0.023).

Conclusion: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%; suggesting that KT patients require persistent isolation measures and booster doses of a Covid-19 vaccine. Potential differences between Covid-19 vaccines should be explored in prospective controlled studies.
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http://dx.doi.org/10.1093/ndt/gfab313DOI Listing
November 2021

Aguascalientes: one of the hottest chronic kidney disease (CKD) hotspots in Mexico and a CKD of unknown aetiology mystery to be solved.

Clin Kidney J 2021 Nov 15;14(11):2285-2294. Epub 2021 Jul 15.

IIS-Fundacion Jimenez Diaz UAM and School of Medicine, UAM, Madrid, Spain.

In a recent issue of (), Gutierrez-Peña reported a high incidence and prevalence of advanced chronic kidney disease (CKD) in Aguascalientes, Mexico. This contradicts Global Burden of Disease estimates, which should be updated. A key component of this high burden of CKD relates to young people ages 20-40 years in whom the cause of CKD was unknown [CKD of unknown aetiology (CKDu)]. The incidence of kidney replacement therapy in this age group in Aguascalientes is among the highest in the world, second only to Taiwan. However, high-altitude Aguascalientes, with a year-round average temperature of 19°C, does not fit the geography of other CKDu hotspots. Furthermore, kidney biopsies in young people showed a high prevalence of focal segmental glomerulosclerosis. Potential causes of CKDu in Aguascalientes include the genetic background (no evidence, although podocytopathy genes should be explored) and environmental factors. The highest prevalence of CKD was found in Calvillo, known for guava farming. Thus guava itself, known to contain bioactive, potentially nephrotoxic molecules and pesticides, should be explored. Additionally, there are reports of water sources in Aguascalientes contaminated with heavy metals and/or pesticides. These include fluoride (increased levels found in Calvillo drinking water) as well as naturally occurring arsenic, among others. Fluoride may accumulate in bone and cause kidney disease years later, and maternal exposure to excess fluoride may cause kidney disease in offspring. We propose a research agenda to clarify the cause of CKDu in Aguascalientes that should involve international funders. The need for urgent action to identify and stem the cause of the high incidence of CKD extends to other CKD hotspots in Mexico, including Tierra Blanca in Veracruz and Poncitlan in Jalisco.
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http://dx.doi.org/10.1093/ckj/sfab136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573004PMC
November 2021

Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in CKD: translational opportunities and challenges.

Nephrol Dial Transplant 2021 Nov 1. Epub 2021 Nov 1.

Nephrology and Transplantation Unit, Grande Ospedale Metropolitano and CNR-IFC, Reggio Cal, Italy.

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and the immune function. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of the gut-brain cross-talk. A progressive rise in circulating NPY accompanies the progression of CKD toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in the accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, Interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost as well as the complexity of diseases potentially addressable by NPY/NPY antagonists have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now a renewed research interest on the NPY system in psycho pharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health by drugs interfering with this system.
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http://dx.doi.org/10.1093/ndt/gfab284DOI Listing
November 2021

Acidosis, cognitive dysfunction and motor impairments in patients with kidney disease.

Nephrol Dial Transplant 2021 Oct 31. Epub 2021 Oct 31.

Institute of Physiology, University of Zurich, Zürich, Switzerland.

Metabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10-30% of patients with advanced stages of CKD. Likewise, in patients with a kidney transplant, prevalence rates of metabolic acidosis range from 20% to 50%. CKD has recently been associated with cognitive dysfunction, including mild cognitive impairment with memory and attention deficits, reduced executive functions and morphological damage detectable with imaging. Also, impaired motor functions and loss of muscle strength are often found in patients with advanced CKD, which in part may be attributed to altered central nervous system (CNS) functions. While the exact mechanisms of how CKD may cause cognitive dysfunction and reduced motor functions are still debated, recent data point towards the possibility that acidosis is one modifiable contributor to cognitive dysfunction. This review summarizes recent evidence for an association between acidosis and cognitive dysfunction in patients with CKD and discusses potential mechanisms by which acidosis may impact CNS functions. The review also identifies important open questions to be answered to improve prevention and therapy of cognitive dysfunction in the setting of metabolic acidosis in patients with CKD.
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http://dx.doi.org/10.1093/ndt/gfab216DOI Listing
October 2021

Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?

Nephrol Dial Transplant 2021 Oct 31. Epub 2021 Oct 31.

Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Villejuif, France.

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care.
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http://dx.doi.org/10.1093/ndt/gfab223DOI Listing
October 2021

Substitution of Sugar-Sweetened Beverages for Other Beverages: Can It Be the Next Step Towards Healthy Aging?

Curr Nutr Rep 2021 Sep 30. Epub 2021 Sep 30.

Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.

Purpose Of Review: With the prolongation of life expectancy, the gap between lifespan and "health span," the disease-free lifespan, has been widening due to the massive burden of age-related chronic diseases and research on healthy aging has been gaining momentum. A growing body of evidence suggests that diet is a strong determinant of healthy aging and consumption of sugar-sweetened beverages (SSB), a major source of added sugars, predicts poor health outcomes in the aging population, including cardiovascular disease, diabetes, and cancer. Evidence further supports a link between sugar-sweetened beverages-triggered pathological processes and biologic factors of aging, including inflammaging, oxidative stress, and alterations in intestinal microbiota. At present, substitution of sugar-sweetened beverages with healthier alternative beverage remains the most robust strategy to limit the deleterious effects of sugar-sweetened beverages on health worldwide and may help achieve healthy longevity. The purpose of this review is to provide an overview of mechanisms by which sugar-sweetened beverages consumption may impact the physiological aging process and how a simple intervention of beverage replacement may promote healthy aging.

Recent Findings: Recent findings indicate that SSB are associated with accelerated aging phenotype and activate various adverse biological processes such as chronic inflammation, oxidative stress, insulin resistance, and gut dysbiosis. Replacing SSB with healthier beverages may be a reasonable option to reduce the burden of chronic disease in the aging population and even prolong life and healthspan.
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http://dx.doi.org/10.1007/s13668-021-00372-2DOI Listing
September 2021

Obesity and metabolic syndrome induce hyperfiltration, glomerulomegaly, and albuminuria in obese ovariectomized female mice and obese male mice.

Menopause 2021 Sep 27;28(11):1296-1306. Epub 2021 Sep 27.

Research Unit, Hospital Universitario de Canarias, University of La Laguna, Faculty of Medicine, Tenerife, Spain.

Objective: Obese patients with metabolic syndrome have a high risk of chronic kidney disease. The prevalence of obesity, metabolic syndrome, and insulin resistance increase in women after menopause, as does the risk of chronic kidney disease. This may indicate an interaction between obesity, metabolic syndrome, and menopause in the induction of renal damage. However, the pathogenesis of kidney disease in postmenopausal obese women is poorly understood.

Methods: We investigated the interaction of an obesogenic diet and menopause on renal dysfunction in ovariectomized and non-ovariectomized lean (n = 8 and 17) and obese (n = 12 and 20) female mice. Obese (n = 12) and lean (n = 10) male mice were also studied. Glucose metabolism, insulin resistance, and kidney function were evaluated with gold standards procedures. Changes in kidney histology and lipid deposition were analyzed. Females had a lower number of glomeruli than males at baseline.

Results: Only female ovariectomized obese animals developed insulin resistance, hyperglycemia, and kidney damage, evidenced as glomerulomegaly, glomerular hyperfiltration, and increased urinary albumin excretion, despite a similar increase in weight than obese non-ovariectomized female mice. Male obese mice developed hyperglycemia, insulin resistance, and hyperfiltration without major renal histological changes. Males on high fat diet showed higher renal lipid content and females on high fat diet (ovariectomized or non-ovariectomized) showed higher total cholesterol content than males.

Conclusions: In mice, there is a clear interplay between obesity, metabolic syndrome, and menopause in the induction of kidney damage.
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http://dx.doi.org/10.1097/GME.0000000000001842DOI Listing
September 2021

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease.

Kidney Int Rep 2021 Sep 12;6(9):2392-2403. Epub 2021 Jun 12.

University of La Laguna, Faculty of Medicine, Tenerife, Spain.

Introduction: The clinical-histologic correlation in diabetic nephropathy is not completely known.

Methods: We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR).

Results: Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%;  = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III.

Conclusions: Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes.
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http://dx.doi.org/10.1016/j.ekir.2021.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419124PMC
September 2021

A primer on metabolic memory: why existing diabesity treatments fail.

Clin Kidney J 2021 Mar 2;14(3):756-767. Epub 2020 Sep 2.

Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey.

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.
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http://dx.doi.org/10.1093/ckj/sfaa143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422888PMC
March 2021

Near-Infrared Spectroscopy (NIRS) as a Tool for Classification of Pre-Sliced Iberian Modified Atmosphere Packaged (MAP) According to the Official Commercial Categories of Raw Meat.

Foods 2021 Aug 12;10(8). Epub 2021 Aug 12.

Meat Quality Area, Center of Scientific and Technological Research of Extremadura (CICYTEX-La Orden), Junta de Extremadura, Ctra, A-V, Km372, 06187 Guadajira, Spain.

This study evaluates near-infrared spectroscopy (NIRS) feasibility in combination with various pre-treatments and chemometric approaches for pre-sliced Iberian under modified atmosphere (MAP) classification according to the official commercial category (defined by the combination of genotype and feeding regime) of the raw material used for its manufacturing ( and purebred Iberian and Iberian × Duroc crossed (50%) pigs, respectively, reared outdoors in a system and Iberian × Duroc crossed (50%) pigs with feed based on commercial fodder) without opening the package. In parallel, NIRS feasibility in combination with partial least squares regression (PLSR) to predict main quality traits was assessed. The best-fitting models developed by means of partial least squares discriminant analysis (PLS-DA) and linear discriminant analysis (LDA) yielded high discriminant ability and thus offered a tool to support the assignment of pre-sliced MAP Iberian according to the commercial category of the raw material. In addition, good predictive ability for C18:3 n-3 was obtained, which may help to support quality control.
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http://dx.doi.org/10.3390/foods10081865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393770PMC
August 2021

Assessment of Stress by Serum Biomarkers in Calves and Their Relationship to Ultimate pH as an Indicator of Meat Quality.

Animals (Basel) 2021 Aug 3;11(8). Epub 2021 Aug 3.

Servicio Regional de Investigación y Desarrollo Agroalimentario (SERIDA), Ctra AS-267 PK19, 33300 Villaviciosa, Asturias, Spain.

Seventy-eight calves from Asturiana de los Valles, Retinta, and Rubia Gallega breeds, under extensive and intensive farm systems and animal mixing and non-mixing conditions, and during the transport and lairage in slaughterhouses, were studied. This research aimed to study the effect of breed, farm system and mixing conditions on serum biomarkers (cortisol, lactate, glucose, serum amyloid A, haptoglobin, and C-reactive protein) and their relationship with pH at slaughter time, and to evaluate the response of the serum biomarkers of calves throughout fattening period. Moreover, this study aims to evaluate the response of the biomarkers in each breed during the fattening period. At slaughter time, cortisol and lactate were affected by BreedxFarm; Retinta showed the opposite pattern to the others and revealed the highest glucose in extensive farm systems. Rubia Gallega in mixing revealed the highest Amyloid A and haptoglobin. Extensive calves in mixing conditions showed the highest glucose. There was a relationship among the variables cortisol, lactate, Amyloid A, and pH. Slaughter time was a major stressor, and the stress response was mainly affected by breed. At slaughter, several biomarkers should be considered.
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http://dx.doi.org/10.3390/ani11082291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388433PMC
August 2021

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals.

Cell Rep 2021 08 4;36(8):109570. Epub 2021 Aug 4.

Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169547, Singapore.

The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination. Our results demonstrate that, while the second dose increases both the humoral and cellular immunity in naive individuals, COVID-19 recovered individuals reach their peak of immunity after the first dose. These results suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.
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http://dx.doi.org/10.1016/j.celrep.2021.109570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8332924PMC
August 2021

Effect of Animal Age at Slaughter on the Muscle Fibres of and Meat Quality of Fresh Loin from Iberian × Duroc Crossbred Pig under Two Production Systems.

Animals (Basel) 2021 Jul 20;11(7). Epub 2021 Jul 20.

Department of Animal Medicine, Faculty of Veterinary, University of Extremadura, Av. Universidad s/n, 10071 Cáceres, Spain.

Two production systems and several ages at slaughter were used: 12, 14 and 16 months for outdoor rearing (with the final finishing phase in the system, in which fed was based on natural resources, mainly acorns and grass) and 8, 10 and 12 months for animals reared indoors (intensive system: with feed based on commercial fodder) to evaluate their effect on the muscle fibre population and size of the , (LT) muscle, as well as fresh loin quality traits. Animals that were older at slaughter revealed increased fibre sizes of the LT muscles in the pigs reared in the system. The LT muscles of the animals reared in intensive systems had a lower percentage of type I fibres and higher size of type IIB than those reared in the system. The approximate composition and instrumental colour of fresh loins were affected by the animal slaughter age. In the case of the intensive system, the effect of animal slaughter age had an impact on the approximate composition, instrumental colour, water loss and textural properties. Therefore, different ages at slaughter of Iberian pigs showed variations in some quality parameters in the fresh loins in both the and Intensive systems, thus proving to be a factor of variability and homogeneity of the Iberian products. The meat from Iberian pigs reared in an intensive system and slaughtered at a younger age proved to be more tender. The production system affected all the above quality traits, with the exception of water loss.
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http://dx.doi.org/10.3390/ani11072143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300732PMC
July 2021

Genetic kidney diseases as an underrecognized cause of chronic kidney disease: the key role of international registry reports.

Clin Kidney J 2021 Aug 12;14(8):1879-1885. Epub 2021 Mar 12.

Molecular Biology Laboratory, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Universitat Autónoma de Barcelona, REDinREN, Instituto de Investigación Carlos III, Barcelona, Spain.

Inherited kidney diseases (IKDs) are among the leading causes of early-onset chronic kidney disease (CKD) and are responsible for at least 10-15% of cases of kidney replacement therapy (KRT) in adults. Paediatric nephrologists are very aware of the high prevalence of IKDs among their patients, but this is not the case for adult nephrologists. Recent publications have demonstrated that monogenic diseases account for a significant percentage of adult cases of CKD. A substantial number of these patients have received a non-specific/incorrect diagnosis or a diagnosis of CKD of unknown aetiology, which precludes correct treatment, follow-up and genetic counselling. There are a number of reasons why genetic kidney diseases are difficult to diagnose in adulthood: (i) adult nephrologists, in general, are not knowledgeable about IKDs; (ii) existence of atypical phenotypes; (iii) genetic testing is not universally available; (iv) family history is not always available or may be negative; (v) lack of knowledge of various genotype-phenotype relationships and (vi) conflicting interpretation of the pathogenicity of many sequence variants. Registries can contribute to visualize the burden of IKDs by regularly grouping all IKDs in their annual reports, as is done for glomerulonephritis or interstitial diseases, rather than reporting only cystic disease and hiding other IKDs under labels such as 'miscellaneous' or 'other'. Any effort to reduce the percentage of patients needing KRT with a diagnosis of 'nephropathy of unknown etiology' or an unspecific/incorrect diagnosis should be encouraged as a step towards precision nephrology. Genetic testing may be of value in this context but should not be used indiscriminately, but rather on the basis of a deep knowledge of IKDs.
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http://dx.doi.org/10.1093/ckj/sfab056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323147PMC
August 2021

Milestones of Precision Medicine: An Innovative, Multidisciplinary Overview.

Mol Diagn Ther 2021 09 30;25(5):563-576. Epub 2021 Jul 30.

Department of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz-UAM, Madrid, Spain.

Although the concept of precision medicine, in which healthcare is tailored to the molecular and clinical characteristics of each individual, is not new, its implementation in clinical practice has been heterogenous. In some medical specialties, precision medicine has gone from being just a promise to a reality that achieves better patient outcomes. This is a fact if we consider, for example, the great advances made in the genetic diagnosis and subsequent treatment of countless hereditary diseases, such as cystic fibrosis, which have improved the life expectancy of many of the affected children. In the field of oncology, the development of targeted therapies has prolonged the survival of patients with breast, lung, colorectal, melanoma, and hematological malignancies. In other disciplines, clinical milestones are perhaps less well known, but no less important. The current challenge is to expand and generalize the use of technologies that are central to precision medicine, such as massively parallel sequencing, to improve the management (prevention and treatment) of complex conditions such as cardiovascular, kidney, or autoimmune diseases. This process requires investment in specialized expertise, multidisciplinary collaboration, and the nationwide organization of genetic laboratories for diagnosis of specific diseases.
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http://dx.doi.org/10.1007/s40291-021-00544-4DOI Listing
September 2021

Hyperkalemia in Chronic Kidney Disease in the New Era of Kidney Protection Therapies.

Drugs 2021 Sep 27;81(13):1467-1489. Epub 2021 Jul 27.

School of Medicine, IIS-Fundacion Jimenez Diaz, University Autonoma of Madrid, FRIAT and REDINREN, Madrid, Spain.

Despite recent therapeutic advances, chronic kidney disease (CKD) is one of the fastest growing global causes of death. This illustrates limitations of current therapeutic approaches and, potentially, unidentified knowledge gaps. For decades, renin-angiotensin-aldosterone system (RAAS) blockers have been the mainstay of therapy for CKD. However, they favor the development of hyperkalemia, which is already common in CKD patients due to the CKD-associated decrease in urinary potassium (K) excretion and metabolic acidosis. Hyperkalemia may itself be life-threatening as it may trigger potentially lethal arrhythmia, and additionally may limit the prescription of RAAS blockers and lead to low-K diets associated to low dietary fiber intake. Indeed, hyperkalemia is associated with adverse kidney, cardiovascular, and survival outcomes. Recently, novel kidney protective therapies, ranging from sodium/glucose cotransporter 2 (SGLT2) inhibitors to new mineralocorticoid receptor antagonists have shown efficacy in clinical trials. Herein, we review K pathophysiology and the clinical impact and management of hyperkalemia considering these developments and the availability of the novel K binders patiromer and sodium zirconium cyclosilicate, recent results from clinical trials targeting metabolic acidosis (sodium bicarbonate, veverimer), and an increasing understanding of the role of the gut microbiota in health and disease.
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http://dx.doi.org/10.1007/s40265-021-01555-5DOI Listing
September 2021

Role of Macrophages and Related Cytokines in Kidney Disease.

Front Med (Lausanne) 2021 8;8:688060. Epub 2021 Jul 8.

Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain.

Inflammation is a key characteristic of kidney disease, but this immune response is two-faced. In the acute phase of kidney injury, there is an activation of the immune cells to fight against the insult, contributing to kidney repair and regeneration. However, in chronic kidney diseases (CKD), immune cells that infiltrate the kidney play a deleterious role, actively participating in disease progression, and contributing to nephron loss and fibrosis. Importantly, CKD is a chronic inflammatory disease. In early CKD stages, patients present sub-clinical inflammation, activation of immune circulating cells and therefore, anti-inflammatory strategies have been proposed as a common therapeutic target for renal diseases. Recent studies have highlighted the plasticity of immune cells and the complexity of their functions. Among immune cells, monocytes/macrophages play an important role in all steps of kidney injury. However, the phenotype characterization between human and mice immune cells showed different markers; therefore the extrapolation of experimental studies in mice could not reflect human renal diseases. Here we will review the current information about the characteristics of different macrophage phenotypes, mainly focused on macrophage-related cytokines, with special attention to the chemokine CCL18, and its murine functional homolog CCL8, and the macrophage marker CD163, and their role in kidney pathology.
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http://dx.doi.org/10.3389/fmed.2021.688060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295566PMC
July 2021

Non-targeted analysis by DLLME-GC-MS for the monitoring of pollutants in the Mar Menor lagoon.

Chemosphere 2022 Jan 17;286(Pt 1):131588. Epub 2021 Jul 17.

Department of Analytical Chemistry, Faculty of Chemistry, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, E-30100, Murcia, Spain. Electronic address:

Non-targeted analysis for the monitoring of organic pollutants resulting from agricultural and industrial practices, plastics and pharmaceutical products of seawater from the Mar Menor lagoon (SE Spain) is proposed using dispersive liquid-liquid microextraction (DLLME) and gas chromatography-mass spectrometry (GC-MS). Initially, a home-made MS database including 118 environmental organic pollutants, whose presence in different ecosystems has already been reported, was created. The analytical method was applied for the analysis of 42 samples and a total of 18 pollutants were detected and identified. Samples were obtained from different sites around the Mar Menor in three sampling campaigns, enabling the assessment of impact of rain on the input of the detected chemicals and their distribution. In addition, this methodology was validated using a standard mixture containing 54 of the environmental pollutants included in the database, allowing the quantification of the 9 of the identified compounds (dibutyl phthalate, diisobutyl phthalate, diethyl phthalate, bis(2-ethylhexyl) phthalate, anthracene, 2-methylnaphthalene, hexachlorocyclopentadiene, bis(2-ethylhexyl) adipate and oleamide) with concentration between 3 and 271 μg L.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131588DOI Listing
January 2022

The need for a cardionephrology subspecialty.

Clin Kidney J 2021 Jun 10;14(6):1491-1494. Epub 2021 Mar 10.

Red de Investigación Renal, Madrid, Spain.

Chronic kidney disease (CKD) has structural and functional repercussions for the cardiovascular system that facilitate the development of cardiovascular disease (CVD). In fact, cardiovascular complications are frequent in the CKD population and thus cause a great clinical, public health and economic burden. Despite this challenge, the prevention and management of cardiovascular complications is one among several aspects of CKD that meets the criteria of an unmet medical need. This probably has to do with the misperception by the nephrologist of the global relevance of CVD in the CKD patient which, in turn, may be due to insufficient cardiovascular training during nephrology specialization. Therefore a change in approach is necessary to understand CKD as a disease in which the manifestations and complications related to CVD become so frequent and important that they require dedicated multidisciplinary clinical management. From this perspective, it makes sense to consider training in the subspecialty of cardionephrology to provide adequate cardiovascular care for CKD patients by the nephrologist. In addition, the cardionephrology subspecialist would be better able to interact with other specialists in multidisciplinary care settings created to achieve a deeper understanding and more effective clinical handling of the interactions between CKD and CVD.
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http://dx.doi.org/10.1093/ckj/sfab054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280941PMC
June 2021

Sodium-glucose cotransporter 2 inhibitors for diabetes mellitus control after kidney transplantation: Review of the current evidence.

Nephrology (Carlton) 2021 Dec 27;26(12):1007-1017. Epub 2021 Jul 27.

Steno Diabetes Center Copenhagen, Copenhagen Denmark and University of Copenhagen, Copenhagen, Denmark.

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are promising drugs to treat chronic kidney disease patients with or without diabetes mellitus (DM). Besides improving glycemic control, SGLT2i are cardioprotective and kidney protective and decrease bodyweight, serum uric acid, blood pressure, albuminuria and glomerular hyperfiltration. These effects may benefit graft function and survival in kidney transplant (KT) patients. In this review, we evaluate data on the efficacy and safety of SGLT2i for KT patients with DM. Eleven studies with 214 diabetic KT patients treated with SGLT2i have been reported. SGLT2i lowered haemoglobin A1c and bodyweight. While glomerular filtration rate may be reduced in the short-term, it remained similar to baseline after 3-12 months. In two studies, blood pressure decreased and remained unchanged in the others. There were no significant changes in urine protein to creatinine ratio. Regarding safety, 23 patients had urinary tract infections, 2 patients had a genital yeast infection, one had acute kidney injury, and one had mild hypoglycaemia. No cases of ketoacidosis or acute rejection were reported. In conclusion, the limited experience so far suggests that SGLT2i are safe in KT patients with DM, decrease bodyweight and improve glycemic control. However, some of the benefits observed in larger studies in the non-KT population have yet to be demonstrated in KT recipients, including preservation of kidney function, reduction in blood pressure and decreased proteinuria.
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http://dx.doi.org/10.1111/nep.13941DOI Listing
December 2021

Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes.

Front Pharmacol 2021 22;12:662020. Epub 2021 Jun 22.

Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma Madrid, Madrid, Spain.

Acute kidney injury (AKI) is more frequent in elderly patients. Mechanisms contributing to AKI (tubular cell death, inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest) have been linked to cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular and pathological basis of the age-related increase in AKI incidence is not completely understood. To explore these mechanisms, experimental AKI was induced by folic acid (FA) administration in young (3-months-old) and old (1-year-old) mice, and kidneys were evaluated in the early phase of AKI, at 48 h. Tubular damage score, KIM-1 expression, the recruitment of infiltrating immune cells (mainly neutrophils and macrophages) and proinflammatory gene expression were higher in AKI kidneys of old than of young mice. Tubular cell death in FA-AKI involves several pathways, such as regulated necrosis and apoptosis. Ferroptosis and necroptosis cell-death pathways were upregulated in old AKI kidneys. In contrast, caspase-3 activation was only found in young but not in old mice. Moreover, the antiapoptotic factor BCL-xL was significantly overexpressed in old, injured kidneys, suggesting an age-related apoptosis suppression. AKI kidneys displayed evidence of cellular senescence, such as increased levels of cyclin dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA damage response marker γH2AX. Furthermore, p21cip1 mRNA expression and nuclear staining for p21cip1 and γH2AX were higher in old than in young FA-AKI mice, as well as the expression of senescence-associated secretory phenotype (SASP) components (, and ). Interestingly, some infiltrating immune cells were p21 or γH2AX positive, suggesting that molecular senescence in the immune cells ("immunosenescence") are involved in the increased severity of AKI in old mice. In contrast, expression of renal protective factors was dramatically downregulated in old AKI mice, including the antiaging factor Klotho and the mitochondrial biogenesis driver PGC-1α. In conclusion, aging resulted in more severe AKI after the exposure to toxic compounds. This increased toxicity may be related to magnification of proinflammatory-related pathways in older mice, including a switch to a proinflammatory cell death (necroptosis) instead of apoptosis, and overactivation of cellular senescence of resident renal cells and infiltrating inflammatory cells.
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http://dx.doi.org/10.3389/fphar.2021.662020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258347PMC
June 2021

Quality Traits of Iberian Dry-Cured as Affected by Pre-Cure Freezing Practice.

Foods 2021 Jun 30;10(7). Epub 2021 Jun 30.

Meat Quality Area, Center of Scientific and Technological Research of Extremadura (CICYTEX-La Orden), Junta de Extremadura, Ctra, A-V, Km372, 06187 Guadajira, Spain.

The seasonality to which dry-cured products from Iberian breed pigs finished in (free-range rearing system with feed based exclusively on ad libitum consumption of natural resources; acorns and grass) are subjected could be overcome by pre-cure freezing. Three sets of Iberian ( muscle)( = 15) were established to assess the impact of frozen storage -0, or non-frozen, 3 and 6 months-previous to the technological process of curing-on the quality traits of the dry-cured product Iberian dry-cured . Similar seasoning and curing processing conditions were applied to all sets. Lower productive performance due to higher weight loss during curing, and lower colour intensity were observed in pre-frozen dry-cured . The fatty acid profile was more saturated, and the oxidative status increased as a result of pre-cure freezing. On the matter of texture, all parameters were modified, highlighting the higher values of hardness and shear force of pre-frozen dry-cured . The time that raw material was frozen exerted a slight, thus helping manufacturers to better address the gap between industry and consumer demand with minimal effect on quality traits.
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http://dx.doi.org/10.3390/foods10071511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306522PMC
June 2021

Intravenous iron therapy and the cardiovascular system: risks and benefits.

Clin Kidney J 2021 Apr 26;14(4):1067-1076. Epub 2020 Nov 26.

CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Calabria, Italy.

Anaemia is a common complication of chronic kidney disease (CKD). In this setting, iron deficiency is frequent because of the combination of increased iron needs to sustain erythropoiesis with increased iron losses. Over the years, evidence has accumulated on the involvement of iron in influencing pulmonary vascular resistance, endothelial function, atherosclerosis progression and infection risk. For decades, iron therapy has been the mainstay of therapy for renal anaemia together with erythropoiesis-stimulating agents (ESAs). Despite its long-standing use, grey areas still surround the use of iron therapy in CKD. In particular, the right balance between either iron repletion with adequate therapy and the avoidance of iron overload and its possible negative effects is still a matter of debate. This is particularly true in patients having functional iron deficiency. The recent Proactive IV Iron Therapy in Haemodialysis Patients trial supports the use of intravenous (IV) iron therapy until a ferritin upper limit of 700 ng/mL is reached in haemodialysis patients on ESA therapy, with short dialysis vintage and minimal signs of inflammation. IV iron therapy has also been proven to be effective in the setting of heart failure (HF), where it improves exercise capacity and quality of life and possibly reduces the risk of HF hospitalizations and cardiovascular deaths. In this review we discuss the risks of functional iron deficiency and the possible benefits and risks of iron therapy for the cardiovascular system in the light of old and new evidence.
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http://dx.doi.org/10.1093/ckj/sfaa212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223589PMC
April 2021

TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

J Am Soc Nephrol 2021 08 21;32(8):1913-1932. Epub 2021 Jun 21.

Group of Genetics and Developmental Biology of Renal Diseases, Nephrology Laboratory (N°11), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela Clinical Hospital Complex (CHUS), Santiago de Compostela, Spain.

Background: In autosomal dominant polycystic kidney disease (ADPKD), cyst development and enlargement lead to ESKD. Macrophage recruitment and interstitial inflammation promote cyst growth. TWEAK is a TNF superfamily (TNFSF) cytokine that regulates inflammatory responses, cell proliferation, and cell death, and its receptor Fn14 (TNFRSF12a) is expressed in macrophage and nephron epithelia.

Methods: To evaluate the role of the TWEAK signaling pathway in cystic disease, we evaluated Fn14 expression in human and in an orthologous murine model of ADPKD. We also explored the cystic response to TWEAK signaling pathway activation and inhibition by peritoneal injection.

Results: Meta-analysis of published animal-model data of cystic disease reveals mRNA upregulation of several components of the TWEAK signaling pathway. We also observed that TWEAK and Fn14 were overexpressed in mouse ADPKD kidney cysts, and TWEAK was significantly high in urine and cystic fluid from patients with ADPKD. TWEAK administration induced cystogenesis and increased cystic growth, worsening the phenotype in a murine ADPKD model. Anti-TWEAK antibodies significantly slowed the progression of ADPKD, preserved renal function, and improved survival. Furthermore, the anti-TWEAK cystogenesis reduction is related to decreased cell proliferation-related MAPK signaling, decreased NF-B pathway activation, a slight reduction of fibrosis and apoptosis, and an indirect decrease in macrophage recruitment.

Conclusions: This study identifies the TWEAK signaling pathway as a new disease mechanism involved in cystogenesis and cystic growth and may lead to a new therapeutic approach in ADPKD.
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http://dx.doi.org/10.1681/ASN.2020071094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455272PMC
August 2021

Verinurad/Febuxostat and Nephrotoxicity.

Am J Kidney Dis 2021 09 11;78(3):468. Epub 2021 Jun 11.

Fundacion Jimenez Diaz Hospital, Madrid, Spain.

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http://dx.doi.org/10.1053/j.ajkd.2021.03.029DOI Listing
September 2021

The renal patient seen by non-renal physicians: the kidney embedded in the 'milieu intérieur'.

Clin Kidney J 2021 Apr 11;14(4):1077-1087. Epub 2020 Dec 11.

RD-Néphrologie, Montpellier, France.

Chronic kidney disease is defined as a decrease in renal function or evidence of kidney injury for >3 months. This represents an oversimplification that may confuse physicians. Thus kidney function is equated to glomerular filtration rate, which represents one of multiple kidney functions. Some potentially more important renal functions are lost earlier, such as the production for the anti-ageing factor Klotho. Overall, these changes modify the emergent properties of the body, altering the relationships between different organs and systems, in a manner that is difficult to predict the response to interventions based on normal physiology concepts, as there is a novel steady state of interorgan relations. In this regard we now discuss the impact of CKD on heart failure; osteomuscular and joint pain and bone fragility and fractures; and osteosarcopaenia as seen by a cardiologist, a rheumatologist and a geriatrician.
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http://dx.doi.org/10.1093/ckj/sfaa234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173597PMC
April 2021

Renin-Angiotensin System Blockers and the Risk of COVID-19-Related Mortality in Patients with Kidney Failure.

Clin J Am Soc Nephrol 2021 07 4;16(7):1061-1072. Epub 2021 Jun 4.

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background And Objectives: There is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Patients with kidney failure, who often use ACEis/ARBs, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population.

Design, Setting, Participants, & Measurements: From the European Renal Association COVID-19 database (ERACODA), we retrieved data on kidney transplant recipients and patients on dialysis who were affected by COVID-19, between February 1 and October 1, 2020, and had information on 28-day mortality. We used Cox proportional-hazards regression to calculate hazard ratios for the association between ACEi/ARB use and 28-day mortality risk. Additionally, we studied the association of discontinuation of these agents with 28-day mortality.

Results: We evaluated 1511 patients: 459 kidney transplant recipients and 1052 patients on dialysis. At diagnosis of COVID-19, 189 (41%) of the transplant recipients and 288 (27%) of the patients on dialysis were on ACEis/ARBs. A total of 88 (19%) transplant recipients and 244 (23%) patients on dialysis died within 28 days of initial presentation. In both groups of patients, there was no association between ACEi/ARB use and 28-day mortality in both crude and adjusted models (in transplant recipients, adjusted hazard ratio, 1.12; 95% confidence interval [95% CI], 0.69 to 1.83; in patients on dialysis, adjusted hazard ratio, 1.04; 95% CI, 0.73 to 1.47). Among transplant recipients, ACEi/ARB discontinuation was associated with a higher mortality risk after adjustment for demographics and comorbidities, but the association was no longer statistically significant after adjustment for severity of COVID-19 (adjusted hazard ratio, 1.36; 95% CI, 0.40 to 4.58). Among patients on dialysis, ACEi/ARB discontinuation was not associated with mortality in any model. We obtained similar results across subgroups when ACEis and ARBs were studied separately, and when other outcomes for severity of COVID-19 were studied, , hospital admission, admission to the intensive care unit, or need for ventilator support.

Conclusions: Among kidney transplant recipients and patients on dialysis with COVID-19, there was no significant association of ACEi/ARB use or discontinuation with mortality.
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http://dx.doi.org/10.2215/CJN.18961220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425613PMC
July 2021

Hypertension in kidney transplantation: a consensus statement of the 'hypertension and the kidney' working group of the European Society of Hypertension.

J Hypertens 2021 08;39(8):1513-1521

Associazione Ipertensione, Nefrologia e Trapianto Renal (IPNET) C/O CNR-IFC, Ospedali Riuniti, Reggio Calabria, Italy.

Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.
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http://dx.doi.org/10.1097/HJH.0000000000002879DOI Listing
August 2021
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