60 results on '"PICCIOTTO D"'
Search Results
2. ACTIVATION OF THE NLRP3 INFLAMMASOME PROMOTES INFLAMMATION IN SKELETAL MUSCLE OF PATIENTS WITH CKD
- Author
-
Milanesi, (Milanesi, S, 1 ), Samantha), Verzola, Daniela, (Verzola, D, 1 ), Daniela), Barisione, (Barisione, C, 1 ), Chiara), Garibaldi, (Garibaldi, S, 1 ), Silvano), Saio, Michela, (Saio, M, 1 ), Michela), Picciotto, (Picciotto, D, Murugavel, Abitha, (Murugavel, A, 1 ), Abitha), Costigliolo, (Costigliolo, F, 1 ), Francesca), Gianetta, Ezio, (Gianetta, E, Ezio)(, 2, Brunori, 3, (Brunori, G, 4 ), Giuliano), Venturelli, (Venturelli, C, 4 ), Chiara), Garibotto, (Garibotto, G, and Giacomo
- Published
- 2018
3. INDOXYL SULFATE INDUCES FIBROSIS AND INFLAMMATION BY UPREGULATING HEAT SHOCK PROTEIN 90 (HSP 90) IN RENAL FIBROBLASTS
- Author
-
Saio, Michela, Verzola, Daniela, (Verzola, D, Daniela), Milanesi, Samantha, Barisione, (Barisione, C, 1 ), Chiara), Garibaldi, (Garibaldi, S, 1 ), Silvano), Carta, Annalisa, (Carta, A, 1 ), Annalisa), Picciotto, (Picciotto, D, 1 ), Daniela), Costigliolo, Costigliolo, Francesca, 1 ), Francesca), Viazzi, (Viazzi, F, 2 ), Francesca), Garibotto, Giacomo, (Garibotto, G, and Giacomo)
- Published
- 2018
4. THE REGULATION OF ADIPONECTIN AND ITS RECEPTOR IN SKELETAL MUSCLE AND VISCERAL FAT IN PATIENTS WITH CKD: A ROLE IN MAINTAINING THE ANTI-INFLAMMATORY HOMEOSTASIS
- Author
-
Milanesi, Samantha), Saio, (Saio, M, 1 ), Michela), Picciotto, (Picciotto, D, 1 ), Daniela), Gianetta, Ezio, (Gianetta, E, 2 ), Ezio), Brunori, Andrea, (Brunori, G, 3 ), Giuliano), Venturelli, (Venturelli, C, 3 ), Chiara), Garibotto, Giacomo, (Garibotto, G, 1 ), Giacomo), Verzola, Daniela, and (Verzola, D
- Published
- 2018
5. Analysis of seroprevalence against Coxiella burnetii in a sample of farm workers in Western Sicily.
- Author
-
Verso, M. G., Vesco, G., Villari, S., Galluzzo, P., Gargano, V., Matranga, D., De Marchis, P., and Picciotto, D.
- Abstract
Introduction and objective. Little is known about the development of chronic Q fever caused by Coxiella burnetii in occupational risk groups and in the general population in Italy, as well as in many countries in the world. The aim of this study was to highlight the presence of the infection in a sample of workers operating outdoors (but not directly in contact with animals), in three provinces of western Sicily, in order to detect the human seroprevalence and compare the obtained data with those found in animals raised in the same territory. Materials and methods. The study included 126 generic seasonal agricultural workers (labourers), 84 male and 42 female; none of whom were aware of any previous contact with Coxiella burnetii. Their immunologic status against Coxiella burnetii was tested through research and titration of both phases I and II specific antibodies (IgG) with an indirect immunofluorescence assay, using anti-antibodies labeled with fluorescein isothiocyanate. All data were statistically analyzed, comparing all positive results from the three provinces through variance analysis, and then comparing human results with those obtained from animals raised in the considered areas, specifically, 1,511 cows, 46 of which were found positive (3.04%), and 3,391 sheep, 548 of which were found positive (16.16%). Results. Anti-Coxiella antibodies were found in nine of 42 females sampled (21.4%; 95%CI=[9.0-33.8]) and 21 of 84 males sampled (25.0%; 95%CI=[15.7-34.3]). 60% (18 of 30; 95%CI=[42.5-77.5]) of seropositive samples were positive either for Phase I antigen or for both Phase I and II antigens, representing cases of chronic infection. Applying Spearman's rank correlation, the percentage of seropositive humans was significantly correlated with that observed for sheep (r=1.00; p<0.001), but not for cows (r=-0.5; p=0.667). Conclusions. The results obtained, although based on a small sample, suggest that the disease is present in the territory of Western Sicily, both in animals and in humans. A closer collaboration between doctors and veterinarians is therefore necessary to fight against the spread of the infection. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
6. Ten-Year Efficacy and Safety of Once-Daily Tacrolimus in Kidney Transplant: A Prospective Cohort Study.
- Author
-
Parodi, E.L., La Porta, E., Russo, R., Marsano, L., Bellino, D., Paoletti, E., Massarino, F., Sofia, A., Garibotto, G., Esposito, P., Murugavel, A., Cappadona, F., Fontana, I., Viazzi, F., and Picciotto, D.
- Subjects
- *
TACROLIMUS , *KIDNEY transplantation , *IMMUNOSUPPRESSIVE agents , *PATIENT compliance , *GLOMERULAR filtration rate - Abstract
Tacrolimus is a cornerstone in the immunosuppressive therapy of kidney transplantation. The once-daily formulation of tacrolimus has been shown to improve adherence of patients without affecting short-term efficacy. However, long-term proof of once-daily tacrolimus efficacy and safety is still lacking. From January 2009 to November 2013, 170 clinically stable kidney transplant patients were offered to change from the ongoing twice-daily tacrolimus (TDT) formulation to a once-daily tacrolimus (ODT) regimen. Kidney transplant recipients agreeing to the change to be treated with an ODT regimen (n = 105, estimated glomerular filtration rate [eGFR] 57.1 ± 1.6 mL/min/1.73 m2) and patients continuing on a TDT formulation (n = 65, eGFR 52.0 ± 2.2 mL/min/1.73 m2) were prospectively followed (median follow-up time 10.4 and 12.6 years in the ODT and TDT groups, respectively, P = not significant). At the end of the follow-up, patients in both groups experienced similar eGFR (50.4 ± 2.2 vs 48.0 ± 2.7 mL/min/1.73 m2 in the ODT and TDT groups, respectively, P = not significant). No differences were observed in biopsy-proven acute rejection, overall graft survival, doubling of serum creatinine, and new onset of proteinuria. The 2 groups also had a comparable rate of death, sepsis, and neoplasia. In conclusion, ODT appears safe and effective in stable kidney graft recipients even 10 years after transplantation. These findings support the use of ODT as a primary tacrolimus formulation in patients with kidney transplantation. • Once-daily tacrolimus may overcome noncompliance and rejection risks. • Over the long term, once-daily tacrolimus is as safe as the twice-daily formulation. • Tacrolimus demonstrates equivalence in the rate of acute rejections, graft survival, and renal function. • Treatment with tacrolimus results in the same rate of death, sepsis, and neoplasia even 10 years after transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
7. Suspected cutaneous leishmaniasis in a sample of Western Sicily residents: what correlation with occupation?
- Author
-
VERSO, Maria Gabriella, Vitale, F., Castelli, G., Bruno, F., Migliazzo, A., BONGIORNO, Maria Rita, Santi, F., PISTONE, Giuseppe, Amodio, E., PICCIOTTO, Diego, Verso, M., Vitale, F., Castelli, G., Bruno, F., Migliazzo, A., Bongiorno, M., Santi, F., Pistone, G., Amodio, E., and Picciotto, D.
- Subjects
Cutaneous leishmaniasis ,Leishmania infantum ,work-related leishmaniasis ,climate change ,Settore MED/44 - Medicina Del Lavoro ,Cutaneous leishmaniasi ,work-related leishmaniasi - Abstract
Background: Leishmaniasis is a widespread infectious disease, but there is not much information about its prevalence in high risk occupational categories. Objectives: Te aim of this study is to assess the prevalence of Leishmania immunological positivity in human skin tissues collected from subjects living in Western Sicily, with suspected cutaneous Leishmania infection, in order to explore the risk possibly related to occupation. Methods: 318 consecutive subjects (M/F ratio=1.0, mean age=40±25.4 years), attending the Dermatology Department of the University of Palermo Hospital from 2013 to 2015, without any previous history of Leishmania infection and performing various occupations, were included. Parasite isolation and PCR-RT test on skin scrapings were performed to evaluate the immunological status; all data were analyzed by the chi square test, comparing all positive results from the different provinces. Results: 81 (50.9%) out of 159 females and 79 (49.7%) out of 159 males were found PCR-RT positive to Leishmania infantum, with a higher risk in the Agrigento district (p
- Published
- 2017
8. Screening for Latent Tuberculosis Infection among Students of Healthcare Professions and Postgraduates of the Faculty of Medicine of the University of Palermo
- Author
-
Maria Gabriella Verso, Noto Laddeca E, Emanuele Amodio, Diego Picciotto, Lo Cascio N, Verso, M., Picciotto, D., Lo Cascio, N., Noto Laddeca, E., and Amodio, E.
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Tuberculosis ,education ,030106 microbiology ,Population ,Mantoux skin test ,QuantiFERON ,Occupational biohazard ,03 medical and health sciences ,0302 clinical medicine ,Medical and nursing students ,Quantiferon ,Latent tuberculosis ,Medical and nursing student ,Health care ,Epidemiology ,medicine ,030212 general & internal medicine ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Settore MED/44 - Medicina Del Lavoro ,Mantoux test ,Latent tuberculosi ,medicine.disease ,Family medicine ,Observational study ,business - Abstract
Introduction and objective: Italy is a country with a low incidence of tuberculosis and in the last fifty years the annual number of TB cases decreased from 12,247 to 4,418, showing a reduction of approximately 64% in the number of cases and 71% in incidence. Despite of this encouraging trend, in the last years the epidemiology of tuberculosis changed and today it is a re-emerging infectious. The aim of this study is to measure the prevalence of positivity to tuberculosis infection (latent TB) in students, without any obvious manifestation of disease, attending degree courses of the health care professions and postgraduate medical courses of the School of Medicine of the University of Palermo, Italy. Materials and methods: A cross-sectional observational study in students of nursing, midwifery, dentistry degree courses and in resident physicians of postgraduate medical schools was carried out from January 2012 to July 2016. Mantoux test was performed and all positive cases were tested with Interferon-Gamma Release Assay (IGRA). Results: Of the 1,351 subjects evaluated, 25 (1.8%) resulted positive to Mantoux test; in 17 students (1.2%) the diagnosis was confirmed with IGRA. Positive cases were significantly more frequent among students attending Postgraduated Medical School Courses (p
- Published
- 2017
9. Analysis of seroprevalence against Coxiella burnetii in a sample of farm workers in Western Sicily
- Author
-
M G, Verso, G, Vesco, S, Villari, P, Galluzzo, V, Gargano, D, Matranga, P, De Marchis, D, Picciotto, Verso, M., Vesco, G., Villari, S., Galluzzo, P., Gargano, V., Matranga, D., De Marchis, P., and Picciotto, D.
- Subjects
Adult ,Male ,Farmers ,Sheep ,Settore MED/44 - Medicina Del Lavoro ,Cattle Diseases ,Sheep Diseases ,Middle Aged ,Young Adult ,Coxiella burnetii ,Seroepidemiologic Studies ,Prevalence ,Q fever, environmental exposure, Coxiella burnetii ,Animals ,Humans ,Cattle ,Female ,Fluorescent Antibody Technique, Indirect ,Q Fever ,Sicily - Abstract
Introduction and objective. Little is known about the development of chronic Q fever caused by Coxiella burnetii in occupational risk groups and in the general population in Italy, as well as in many countries in the world. The aim of this study was to highlight the presence of the infection in a sample of workers operating outdoors (but not directly in contact with animals), in three provinces of western Sicily, in order to detect the human seroprevalence and compare the obtained data with those found in animals raised in the same territory. Materials and methods. The study included 126 generic seasonal agricultural workers (labourers), 84 male and 42 female; none of whom were aware of any previous contact with Coxiella burnetii. Their immunologic status against Coxiella burnetii was tested through research and titration of both phases I and II specific antibodies (IgG) with an indirect immunofluorescence assay, using anti-antibodies labeled with fluorescein isothiocyanate. All data were statistically analyzed, comparing all positive results from the three provinces through variance analysis, and then comparing human results with those obtained from animals raised in the considered areas, specifically, 1,511 cows, 46 of which were found positive (3.04%), and 3,391 sheep, 548 of which were found positive (16.16%). Results. Anti-Coxiella antibodies were found in nine of 42 females sampled (21.4%; 95%CI=[9.0–33.8]) and 21 of 84 males sampled (25.0%; 95%CI=[15.7–34.3]). 60% (18 of 30; 95%CI=[42.5–77.5]) of seropositive samples were positive either for Phase I antigen or for both Phase I and II antigens, representing cases of chronic infection. Applying Spearman’s rank correlation, the percentage of seropositive humans was significantly correlated with that observed for sheep (r=1.00; p
- Published
- 2016
10. Female age at first pregnancy and work task: finding correlation and evolution over the past two decades in a Sicilian province
- Author
-
VERSO, Maria Gabriella, MATRANGA, Domenica, PICCIOTTO, Diego, Palumbo, R., Giannola, A., Verso, M., Palumbo, R., Giannola, A., Matranga, D., and Picciotto, D.
- Subjects
Settore MED/44 - Medicina Del Lavoro ,aging, first pregnancy, infant, occupation, unemployed - Abstract
Background: the entrance of women in the workforce, due to a their growing cultural and, accordingly, social commitment, changed many aspects of their lives; the research or the maintenance of a job, especially during periods of severe economic crisis, leads to a delay of many physiological stage, maternity at first. The aim of this study is to verify and, if it really happened, to quantify an increasing age of first-time mothers in a sample of mothers in the province of Agrigento in the last 20 years, correlating any positive response to the work task performed. Material and Methods: we have enrolled all primiparous women who gave birth in a hospital in the province of Agrigento, from January 1993 to December 2012; through retrospective analysis of medical records, prepared during hospitalization, we have assessed the following parameters: a history (family, physiological, pathological remote and proximate, pharmacological and work), nationality, age at first birth, the task being performed, mode of delivery, days of hospitalization and possible fetal pathologies occuring in newborns. Then we have processed statistically data calculating mean, median, range and standard deviation. To assess statistical significance of the difference in the average age of the first pregnancy by professional category and decade, it was used the two-way anova test. Results: the results show an overall increase in age of first-time mothers, especially in women workers with high profile professional tasks. Discussion: the increase in the age at first pregnancy can’t be considered a positive event, because of the increasing risk of complications and maternal-fetal pathologies that is directly proportional to aging.
- Published
- 2015
11. Laryngopathies by vocal abuse: clinical multidisciplinary evaluation in workers at risk
- Author
-
VERSO, Maria Gabriella, PICCIOTTO, Diego, Iovino L, Pastorello, T, Giammanco, V, Provenzani, A, Verso MG, Iovino L, Pastorello, T, Giammanco, V, Provenzani, A, and Picciotto D
- Subjects
Settore MED/44 - Medicina Del Lavoro ,laryngopathies, vocal abuse, singers, teachers - Abstract
Background: Attention to vocal pathologies in occupational categories that provide for a continuous use and often abuse of phonation has grown in recent decades. Objectives: Aim of this study was to evaluate presence of laryngopathies by vocal abuse in subjects occupationally exposed, namely teachers and singers, compared with non-exercising jobs at risk, also checking if self-assessment tests and spectrographic signals could be predictive of disease observed with endoscopy. Methods: We therefore proceeded to enroll on a voluntary basis, after information campaign, subjects, which in addition to an ananmnestic framework, underwent a multidisciplinary evaluation, which included, besides a fiber optic laryngoscopic examination, the preventive administration of self report test on perception the quality of their voice, or the voice Handicap Index for professional speaking voice and not exposed to risk, and the Singing Handicap Index for the singers, and also the spectrographic analysis of voice output (spoken or sung). Results: The results, in addition to confirming the guessed higher prevalence of disease in voice professionals, provide the opportunity to integrate the common medical diagnostic investigations, such as fiber optic laryngoscopy, with self report test and spectrographic survey, which showed a significant relationship with endoscopic data. In fact, the results confirmed that the VHI and the MSHI, integrated with the spectrographic test can be a valuable tool to assess the implications of bio-psycho-social aspects of professional and non-voice disorders, contributing significantly to validate the provisional diagnosis of diseas. Conclusions: This study recommends not only the implementation of vocal education during the training of teacher to prepare the vocal professional user, but also a multidisciplinary approach to voice disorders in occupational exposure population.
- Published
- 2014
12. Survey of condition of light and humidity microclimate in some work and/or study areas
- Author
-
LACCA, Guido, FIORDISPINA, Morena, PICCIOTTO, Diego, Lacca, G, Fiordispina, M, and Picciotto, D
- Subjects
light and humidity microclimate and occupational health ,Settore MED/44 - Medicina Del Lavoro - Published
- 2012
13. Occupational exposure to environmental pollutants: evaluation of long-term effects on a group of newsagents in the city of Palermo
- Author
-
VERSO, Maria Gabriella, PROVENZANI, Ambra, LACCA, Guido, PICCIOTTO, Diego, Verso, MG, Provenzani, A, Lacca, G, and Picciotto, D
- Subjects
occupational exposure, newsagent, carotid's damage ,Settore MED/44 - Medicina Del Lavoro - Abstract
Environmental pollution constantly threatens the health of urban populations. This problem of environmental hygiene takes a particular interest in Occupational Medicine, whereas some tasks take place mostly outdoors, so the airborne pollutants and noise can be considered as occupational hazards. The subject of this study is to evaluate the health of a group of newsagents in the city of Palermo, in relation to the level of urban pollution and noise monitored in ten years (2000-2010). It was assessed lung function, hearing, kidney, liver and cardiovascular systems, with particular reference to endothelial structures. Analysis of the results show the high prevalence of damage to the carotid district, for which we can not exclude a role simultaneously, contribute to various airborne pollutants.
- Published
- 2012
14. Asbestos: decontamination works and use of individual protection devices. Some remarks on the right use of IPD, considering the cost-benefit relation
- Author
-
TRANCHINA, Giuseppe, VEGNA, Francesco, E. NOTO LADDECA, AUGELLO, Claudia, M. DI GIOVANNI, E, PISCIONE, F. GULLO, S. ILARDO, PALERMO PATERA, Giovanni, E. TERMINI, TRANCHINA, Ernesto, VEGNA, Valerio, P. IMBURGIA, LACCA, Guido, FARINELLA, Vito, PICCIOTTO, Diego, G TRANCHINA, F VEGNA, E NOTO LADDECA, C AUGELLO, M DI GIOVANNI, PISCIONE, F GULLO, S ILARDO, G PALERMO PATERA, E TERMINI, E TRANCHINA, VEGNA, P IMBURGIA, LACCA G, V FARINELLA, and Picciotto, D.
- Subjects
Asbestos, Decontamination works, Exposure limit, IPD - Published
- 2004
15. Observational study on a group of people exposed to chemical agents in a research laboratory
- Author
-
TRANCHINA, Giuseppe, LACCA, Guido, MANGIONE, G, DI VENTI, E, GULLO, F, PISCIONE, E, SAITO, R, D'AMICO, M, SCELSA, D, IMBURGIA, P, DI GIOVANNI, M, TRANCHINA, Ernesto, FARINELLA, Vito, PALERMO PATERA, Giovanni, TERMINI, E, VEGNA, Valerio, PICCIOTTO, Diego, TRANCHINA, G, LACCA, G, MANGIONE, G, DI VENTI, E, GULLO, F, PISCIONE, E, SAITO, R, D'AMICO, M, SCELSA, D, IMBURGIA, P, DI GIOVANNI, M, TRANCHINA, E, FARINELLA, V, PALERMO PATERA, G, TERMINI, E, VEGNA, V, and Picciotto, D.
- Subjects
D.Lgs 25/2002 , chemical risks, Occupational Health, Occupational Medicine - Abstract
The law D.Lgs 25/2002 provides the lowest qualifications for the protection of workers exposed to chemical risks. Our research aim at investigating acute and chronic pathologies related to the exposure to chemical pollutants used. With this purpose we have examined 42 subjects assigned to the laboratory of the Department of Chemistry of Palermo, exposed to chemical substances. We have also examined a control group of 10 people non exposed, belonging to the same Department. Our study has shown that, previous a correct information and training of workers, the right use of techniques, working methods and the use of personal protection devices reduce chemical risks.
- Published
- 2004
16. Visit-to-Visit Systolic Blood Pressure Variability Independently Predicts Cardiovascular Events in a Kidney Transplant Recipients' Cohort.
- Author
-
Bussalino E, Picciotto D, Macciò L, Parodi A, Gandolfo MT, and Viazzi F
- Subjects
- Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Risk Factors, Risk Assessment methods, Transplant Recipients statistics & numerical data, Systole, Time Factors, Blood Pressure Determination methods, Predictive Value of Tests, Kidney Transplantation, Blood Pressure physiology, Cardiovascular Diseases physiopathology, Cardiovascular Diseases mortality, Cardiovascular Diseases epidemiology, Cardiovascular Diseases diagnosis, Cardiovascular Diseases etiology
- Abstract
Background: The predictive role of blood pressure variability for all-cause mortality and fatal and nonfatal cardiovascular events has been described in the general population and in patients with diabetes, independently of mean BP. Although systolic blood pressure variability has been proposed as an informative measure for predicting clinical outcomes in patients with chronic kidney disease, its role in kidney transplant recipients is still debatable., Methods and Results: We performed a retrospective, observational, monocentric analysis of all kidney transplant recipients in follow-up at the outpatient Nephrology Clinic of San Martino Hospital from January 1, 2016 to December 31, 2016, who underwent kidney transplantation >12 months. The primary outcome was a fatal or nonfatal cardiovascular event (myocardial infarction, unstable angina, stroke, and hospitalization for heart failure). Visit-to-visit systolic blood pressure variability was expressed as the SD of systolic blood pressure values recorded at baseline and 3 months up to 18 months. Among the 272 patients (mean age, 64±13; 63% men) included in the present analyses, for each increase of 2.7 mm Hg in systolic blood pressure SD, the risk for events increased 3-fold (hazard ratio [HR], 3.1 [95% CI, 1.19-7.88]; P =0.02), and patients in the highest tertile of systolic blood pressure SD showed a 4-fold increased risk (HR, 4.1 [95% CI, 1.34-12.43]; P =0.01). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, and prior cardiovascular event (HR, 3.2 [95% CI, 1.1-10.0]; P =0.04)., Conclusions: Long-term blood pressure variability represents a risk factor for cardiovascular events in kidney transplant recipients, even independently by several confounding factors including blood pressure load.
- Published
- 2024
- Full Text
- View/download PDF
17. Cognitive Disorders in Chronic Kidney Disease: We Are What We Eat.
- Author
-
Garneata L, Garibotto G, Picciotto D, and Moore LW
- Subjects
- Humans, Cognition Disorders, Diet methods, Renal Insufficiency, Chronic complications
- Published
- 2024
- Full Text
- View/download PDF
18. Altered adiponectin regulation in skeletal muscle of patients with chronic kidney disease.
- Author
-
Verzola D, Saio M, Milanesi S, Picciotto D, Frascio M, Brunori G, Laudon A, La Porta E, Rumeo N, Zanetti V, Russo E, Garibotto G, Viazzi F, and Esposito P
- Subjects
- Humans, Adiponectin metabolism, Muscle, Skeletal metabolism, Renal Insufficiency, Chronic metabolism, Renal Insufficiency, Chronic complications
- Published
- 2024
- Full Text
- View/download PDF
19. Pathophysiology of Physical Exercise in Kidney Patients: Unveiling New Players- The Role of Myokines.
- Author
-
Picciotto D, Macciò L, Verzola D, Baciga F, Momentè C, Russo E, Viazzi F, Battaglia Y, and Esposito P
- Abstract
Background Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle physiology, such as sarcopenia, are particularly significant, as they are associated with poor outcomes and reduced quality of life. Summary Various interventions, including pharmacological approaches and lifestyle modifications have been investigated to slow CKD progression and prevent or treat its complications. Physical exercise, in particular, has emerged as a promising intervention with multiple beneficial effects. These include improvements in physical functioning, increased muscle mass, modulation of metabolic abnormalities, and reduced cardiovascular risk. However, the pathophysiology of physical exercise in patients with kidney disease is complex and remains only partially understood. A crucial advancement in understanding this phenomenon has been the identification of myokines-molecules expressed and released by skeletal muscle in response to physical activity. These myokines can exert both paracrine and systemic effects, influencing not only skeletal muscle physiology but also other processes such as energy metabolism and lipid regulation. Key Messages The interplay among skeletal muscle, physical activity, and myokines may act as a pivotal regulator in various physiological processes, including aging, as well as in pathological conditions like cachexia and sarcopenia, frequently observed in CKD patients at different stages, including patients on dialysis. Despite the potential importance of this relationship, only a limited number of studies have explored the relationship between exercise and myokine, and the effect of this interaction on experimental models or individuals with kidney disease. In the following sections, we review and discuss this topic., (The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2024
- Full Text
- View/download PDF
20. SA-β-Gal in Kidney Tubules as a Predictor of Renal Outcome in Patients with Chronic Kidney Disease.
- Author
-
Esposito P, Picciotto D, Verzola D, Garibotto G, Parodi EL, Sofia A, Costigliolo F, Gaggero G, Zanetti V, Saio M, and Viazzi F
- Abstract
Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology; however, the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-β-Gal in kidney biopsies obtained in a cohort [ n = 22] of incident patients who were followed up for 3 years as standard of care. SA-β-Gal staining was approximately fourfold higher in the tubular compartment of patients with CKD vs. controls [26.0 ± 9 vs. 7.4 ± 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-β-Gal, but not proteinuria, at the time of biopsy correlated with eGFR loss at the follow up; moreover, SA-β-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In conclusion, our study shows that SA-β-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD and suggests that tubular SA-β-Gal is associated with accelerated loss of renal function.
- Published
- 2024
- Full Text
- View/download PDF
21. Multifaceted relationship between diabetes and kidney diseases: Beyond diabetes.
- Author
-
Esposito P, Picciotto D, Cappadona F, Costigliolo F, Russo E, Macciò L, and Viazzi F
- Abstract
Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
22. Daratumumab in the treatment of C3 glomerulopathy with monoclonal gammopathy: a case report and literature review.
- Author
-
Esposito P, Picciotto D, Costigliolo F, Russo E, Macciò L, Cenacchi G, Cagnetta A, Cea M, Lemoli RM, and Viazzi F
- Abstract
Although rare, C3 glomerulopathy (C3G) is increasingly recognized thanks to the currently available diagnostic skills. C3G is not a single disease but a group of disorders with distinct pathogenesis and progression. Thus, an essential step for its management remains an in-depth characterization of the specific form and the identification of underlying conditions, which may also impact treatment choices as well. Among these entities, an emerging condition is the association of C3G with monoclonal gammopathy, which confers poor outcomes. Overall, diagnosis of C3G remains challenging, and determining the appropriate treatment remains unclear. Conventional immunosuppressive therapy has proven ineffective in such cases, while clone-directed therapies have shown promising results in small interventional studies and case series. Here, we report a case of a patient affected by C3G with monoclonal gammopathy of renal significance who experienced rapid deterioration of kidney function requiring replacement therapy. After the failure of first-line treatment, a switch to the anti-CD38 therapy with daratumumab resulted in the progressive improvement of the patient's kidney function, leading to the discontinuation of hemodialysis after approximately 10 months. Serial renal biopsies were also performed to study the disease's evolution in response to the treatment. Based on the description of this single case, we have comprehensively reviewed available studies on daratumumab use in patients with C3G associated with monoclonal gammopathy to provide insights for the design of prospective studies which aim to enhance the management of such poor prognosis disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Esposito, Picciotto, Costigliolo, Russo, Macciò, Cenacchi, Cagnetta, Cea, Lemoli and Viazzi.)
- Published
- 2023
- Full Text
- View/download PDF
23. Histology for nephrology, from pre-implantation to post-transplant kidney biopsy. Lesson learned from ReBIrth (Renal BIopsy for Kidney Transplantation Therapy).
- Author
-
Caliò A, Barreca A, Marletta S, Achenza MIS, Alessi M, Angelico R, Apicella L, Argiolas D, Bossini N, Carrano R, Carriero C, Castellano G, Comai G, Di Bella C, D'Ignoto F, Gallico A, Gastaldon F, Merlotti G, Paloschi V, Panarese A, Parodi A, Perna F, Picciotto D, Regalia A, Rossini M, Russo E, Salerno MP, Toti L, Tulissi P, Vischini G, Zaza G, and Eccher A
- Subjects
- Humans, Kidney surgery, Kidney pathology, Immunosuppression Therapy, Biopsy, Kidney Transplantation adverse effects, Kidney Transplantation methods, Nephrology
- Abstract
A meeting entitled Renal BIopsy for Kidney Transplantation Therapy (ReBIrth) took place on May 31
st , 2022 in Bologna, Italy. The meeting drew together nephrologists, surgeons, and pathologists and recognized as experts in the field of kidney transplantation in Italy. In this paper, we present our experience working with kidney transplants in the current era of immunosuppression therapy. The primary aim is to report the histopathological characteristics of failed kidney allografts after a consensus of experts reviewed the cases on a wholeslide imaging digital platform. Regardless of the cases discussed, digital pathology was reliable in identifying all the morphological and immunohistochemical features required to improve the correct use of immunosuppressive therapy to prevent graft failure and optimize patient management., (Copyright © 2023 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)- Published
- 2023
- Full Text
- View/download PDF
24. The Contribution of Muscle Innate Immunity to Uremic Cachexia.
- Author
-
Esposito P, Verzola D, Saio M, Picciotto D, Frascio M, Laudon A, Zanetti V, Brunori G, Garibotto G, and Viazzi F
- Subjects
- Humans, Cachexia complications, Toll-Like Receptor 4 metabolism, Immunity, Innate, Inflammation complications, Muscles metabolism, Renal Insufficiency, Chronic therapy, Uremia complications
- Abstract
Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, "sterile" muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering "sterile" tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.
- Published
- 2023
- Full Text
- View/download PDF
25. Homocysteine exchange across skeletal muscle in patients with chronic kidney disease.
- Author
-
Garibotto G, Picciotto D, Verzola D, Valli A, Sofia A, Costigliolo F, Saio M, Viazzi F, and Esposito P
- Subjects
- Humans, Renal Dialysis, Folic Acid, Vitamin B 12, Muscle, Skeletal, Homocysteine, Renal Insufficiency, Chronic therapy
- Abstract
Sites and mechanisms regulating the supply of homocysteine (Hcy) to the circulation are unexplored in humans. We studied the exchange of Hcy across the forearm in CKD patients (n = 17, eGFR 20 ± 2 ml/min), in hemodialysis (HD)-treated patients (n = 14) and controls (n = 9). Arterial Hcy was ~ 2.5 folds increased in CKD and HD patients (p < 0.05-0.03 vs. controls). Both in controls and in patients Hcy levels in the deep forearm vein were consistently greater (+~7%, p < 0.05-0.01) than the corresponding arterial levels, indicating the occurrence of Hcy release from muscle. The release of Hcy from the forearm was similar among groups. In all groups arterial Hcy varied with its release from muscle (p < 0.03-0.02), suggesting that muscle plays an important role on plasma Hcy levels. Forearm Hcy release was inversely related to folate plasma level in all study groups but neither to vitamin B12 and IL-6 levels nor to muscle protein net balance. These data indicate that the release of Hcy from peripheral tissue metabolism plays a major role in influencing its Hcy plasma levels in humans and patients with CKD, and that folate is a major determinant of Hcy release., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
- Published
- 2023
- Full Text
- View/download PDF
26. Role of Uric Acid in Vascular Remodeling: Cytoskeleton Changes and Migration in VSMCs.
- Author
-
Russo E, Bertolotto M, Zanetti V, Picciotto D, Esposito P, Carbone F, Montecucco F, Pontremoli R, Garibotto G, Viazzi F, and Verzola D
- Subjects
- Mice, Animals, Vascular Remodeling, Angiotensin Receptor Antagonists pharmacology, Proteasome Endopeptidase Complex metabolism, Angiotensin-Converting Enzyme Inhibitors pharmacology, Cytoskeleton metabolism, Cell Movement, Myocytes, Smooth Muscle metabolism, Cells, Cultured, Cell Proliferation, Muscle, Smooth, Vascular metabolism, Uric Acid pharmacology, Uric Acid metabolism
- Abstract
The mechanisms by which hyperuricemia induces vascular dysfunction and contributes to cardiovascular disease are still debated. Phenotypic transition is a property of vascular smooth muscle cells (VSMCs) involved in organ damage. The aim of this study was to investigate the effects of uric acid (UA) on changes in the VSMC cytoskeleton, cell migration and the signals involved in these processes. MOVAS, a mouse VSMC line, was incubated with 6, 9 and 12 mg/dL of UA, angiotensin receptor blockers (ARBs), proteasome and MEK-inhibitors. Migration property was assessed in a micro-chemotaxis chamber and by phalloidin staining. Changes in cytoskeleton proteins (Smoothelin B (SMTB), alpha-Smooth Muscle Actin (αSMA), Smooth Muscle 22 Alpha (SM22α)), Atrogin-1 and MAPK activation were determined by Western blot, immunostaining and quantitative reverse transcription PCR. UA exposition modified SMT, αSMA and SM22α levels ( p < 0.05) and significantly upregulated Atrogin-1 and MAPK activation. UA-treated VSMCs showed an increased migratory rate as compared to control cells ( p < 0.001) and a re-arrangement of F-actin. Probenecid, proteasome inhibition and ARBs prevented the development of dysfunctional VSMC. This study shows, for the first time, that UA-induced cytoskeleton changes determine an increase in VSMC migratory rate, suggesting UA as a key player in vascular remodeling.
- Published
- 2023
- Full Text
- View/download PDF
27. Kidney Transplantation in a Patient Affected by Sickle Cell Trait: A Case Report and State-of-the-Art Review.
- Author
-
Picciotto D, Bussalino E, Viazzi F, Paoletti E, and Esposito P
- Abstract
Chronic kidney disease (CKD) is a common feature of sickle cell disease (SCD). The awareness of the clinical presentation and renal involvement in patients affected by hemoglobinopathies is greatly needed. Patient management is particularly complex, especially with kidney transplantation. We, therefore, report the case of a 56-year-old patient affected by sickle cell trait who underwent kidney transplantation. This case will underline all the various challenges the nephrologist must face in this clinical setting and their management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Picciotto et al.)
- Published
- 2023
- Full Text
- View/download PDF
28. Kidney transplantation from deceased donors with vaccine-induced thrombosis and thrombocytopenia (VITT): Definitely feasible and safe?
- Author
-
Picciotto D, Bussalino E, and Paoletti E
- Subjects
- Humans, Vaccines, Tissue and Organ Procurement, COVID-19 Vaccines adverse effects, Kidney Transplantation adverse effects, Thrombocytopenia chemically induced, Tissue Donors
- Published
- 2022
- Full Text
- View/download PDF
29. Treatment of Chronic Kidney Disease: Moving Forward.
- Author
-
Garibotto G, Picciotto D, and Esposito P
- Abstract
Chronic kidney disease (CKD) affects ~10% of the adult population [...].
- Published
- 2022
- Full Text
- View/download PDF
30. The Evolving Scenario of COVID-19 in Hemodialysis Patients.
- Author
-
Esposito P, Picciotto D, Cappadona F, Russo E, Falqui V, Conti NE, Parodi A, Mallia L, Cavagnaro S, Battaglia Y, and Viazzi F
- Subjects
- Hospitalization, Humans, Pandemics prevention & control, Renal Dialysis, Retrospective Studies, COVID-19 epidemiology
- Abstract
Coronavirus disease 2019 (COVID-19) is a rapidly changing disease. Therefore, in this study, to evaluate the evolution of COVID-19 in hemodialysis patients, we retrospectively compared patients affected by COVID-19 during the first pandemic waves of 2020 (from March to December 2020-Group 1) with patients with COVID-19 from September 2021 to February 2022 (Group 2) after the full completion of vaccination. Group 1 was constituted of 44 patients (69.3 ± 14.6 years), and Group 2 of 55 patients (67.4 ± 15.3 years). Among Group 2, 52 patients (95%) were vaccinated. Patients of Group 2, compared with Group 1, were more often asymptomatic (38 vs. 10%, p = 0.002) and reported less frequent fever and pulmonary involvement. At diagnosis, Group 2 showed a significantly higher number of lymphocytes and lower levels of circulating IL-6 (16 ± 13.3 vs. 41 ± 39.4 pg/mL, p = 0.002). Moreover, in Group 2, inflammatory parameters significantly improved after a few days from diagnosis. Patients of Group 2 presented a lower hospitalization rate (12.7 vs. 38%, p = 0.004), illness duration (18.8 ± 7.7 vs. 29.2 ± 19.5 days, p = 0.005), and mortality rate (5.4 vs. 25%, p = 0.008). Finally, responders to the vaccination (80% of vaccinated patients) compared with nonresponders showed a reduction in infection duration and hospitalization (5 vs. 40%, p = 0.018). In conclusion, we found that COVID-19 presentation and course in hemodialysis patients have improved over time after the implementation of vaccine campaigns. However, due to the evolving nature of the disease, active surveillance is necessary.
- Published
- 2022
- Full Text
- View/download PDF
31. Changes of Acute Kidney Injury Epidemiology during the COVID-19 Pandemic: A Retrospective Cohort Study.
- Author
-
Esposito P, Russo E, Picciotto D, Cappadona F, Battaglia Y, Traverso GB, and Viazzi F
- Abstract
To evaluate the impact of the Coronavirus Disease-19 (COVID-19) pandemic on the epidemiology of acute kidney injury (AKI) in hospitalized patients, we performed a retrospective cohort study comparing data of patients hospitalized from January 2016 to December 2019 (pre-COVID-19 period) and from January to December 2020 (COVID-19 period, including both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative and positive patients). AKI was classified by evaluating the kinetics of creatinine levels. A total of 51,681 patients during the pre-COVID-19 period and 10,062 during the COVID-19 period (9026 SARS-CoV-2-negative and 1036 SARS-CoV-2-positive) were analyzed. Patients admitted in the COVID-19 period were significantly older, with a higher prevalence of males. In-hospital AKI incidence was 31.7% during the COVID-19 period (30.5% in SARS-CoV-2-negative patients and 42.2% in SARS-CoV-2-positive ones) as compared to 25.9% during the pre-COVID-19 period (p < 0.0001). In the multivariate analysis, AKI development was independently associated with both SARS-CoV-2 infection and admission period. Moreover, evaluating the pre-admission estimated glomerular filtration rate (eGFR) we found that during the COVID-19 period, there was an increase in AKI stage 2−3 incidence both in patients with pre-admission eGFR < 60 mL/min/1.73 m2 and in those with eGFR ≥ 60 mL/min/1.73 m2 (“de novo” AKI). Similarly, clinical outcomes evaluated as intensive care unit admission, length of hospital stay, and mortality were significantly worse in patients admitted in the COVID-19 period. Additionally, in this case, the mortality was independently correlated with the admission during the COVID-19 period and SARS-CoV-2 infection. In conclusion, we found that during the COVID-19 pandemic, in-hospital AKI epidemiology has changed, not only for patients affected by COVID-19. These modifications underline the necessity to rethink AKI management during health emergencies.
- Published
- 2022
- Full Text
- View/download PDF
32. Myostatin: Basic biology to clinical application.
- Author
-
Esposito P, Picciotto D, Battaglia Y, Costigliolo F, Viazzi F, and Verzola D
- Subjects
- Animals, Biology, Cachexia, Humans, Muscle, Skeletal metabolism, Epigenesis, Genetic, Myostatin genetics, Myostatin metabolism
- Abstract
Myostatin is a member of the transforming growth factor (TGF)-β superfamily. It is expressed by animal and human skeletal muscle cells where it limits muscle growth and promotes protein breakdown. Its effects are influenced by complex mechanisms including transcriptional and epigenetic regulation and modulation by extracellular binding proteins. Due to its actions in promoting muscle atrophy and cachexia, myostatin has been investigated as a promising therapeutic target to counteract muscle mass loss in experimental models and patients affected by different muscle-wasting conditions. Moreover, growing evidence indicates that myostatin, beyond to regulate skeletal muscle growth, may have a role in many physiologic and pathologic processes, such as obesity, insulin resistance, cardiovascular and chronic kidney disease. In this chapter, we review myostatin biology, including intracellular and extracellular regulatory pathways, and the role of myostatin in modulating physiologic processes, such as muscle growth and aging. Moreover, we discuss the most relevant experimental and clinical evidence supporting the extra-muscle effects of myostatin. Finally, we consider the main strategies developed and tested to inhibit myostatin in clinical trials and discuss the limits and future perspectives of the research on myostatin., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
33. Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification.
- Author
-
Esposito P, Verzola D, Picciotto D, Cipriani L, Viazzi F, and Garibotto G
- Subjects
- Animals, Atherosclerosis metabolism, Atherosclerosis pathology, Humans, Renal Insufficiency, Chronic metabolism, Renal Insufficiency, Chronic pathology, Signal Transduction, Vascular Calcification metabolism, Vascular Remodeling, Activins metabolism, Blood Vessels metabolism, Myostatin metabolism, Vascular Calcification pathology
- Abstract
A current hypothesis is that transforming growth factor-β signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally leading to modulation of gene expression. Myostatin and activin-A are expressed by different cell types and tissues, including muscle, kidney, reproductive system, immune cells, heart, and vessels, where they exert pleiotropic effects. In arterial vessels, experimental evidence indicates that myostatin may mostly promote vascular inflammation and premature aging, while activin-A is involved in the pathogenesis of vascular calcification and CKD-related mineral bone disorders. In this review, we discuss novel insights into the biology and physiology of the role played by myostatin and activin in the vascular wall, focusing on the experimental and clinical data, which suggest the involvement of these molecules in vascular remodeling and calcification processes. Moreover, we describe the strategies that have been used to modulate the activin downward signal. Understanding the role of myostatin/activin signaling in vascular disease and bone metabolism may provide novel therapeutic opportunities to improve the treatment of conditions still associated with high morbidity and mortality.
- Published
- 2021
- Full Text
- View/download PDF
34. How to Overcome Anabolic Resistance in Dialysis-Treated Patients?
- Author
-
Garibotto G, Saio M, Aimasso F, Russo E, Picciotto D, Viazzi F, Verzola D, Laudon A, Esposito P, and Brunori G
- Abstract
A current hypothesis is that dialysis-treated patients are "anabolic resistant" i. e., their muscle protein synthesis (MPS) response to anabolic stimuli is blunted, an effect which leads to muscle wasting and poor physical performance in aging and in several chronic diseases. The importance of maintaining muscle mass and MPS is often neglected in dialysis-treated patients; better than to describe mechanisms leading to energy-protein wasting, the aim of this narrative review is to suggest possible strategies to overcome anabolic resistance in this patient's category. Food intake, in particular dietary protein, and physical activity, are the two major anabolic stimuli. Unfortunately, dialysis patients are often aged and have a sedentary behavior, all conditions which per se may induce a state of "anabolic resistance." In addition, patients on dialysis are exposed to amino acid or protein deprivation during the dialysis sessions. Unfortunately, the optimal amount and formula of protein/amino acid composition in supplements to maximixe MPS is still unknown in dialysis patients. In young healthy subjects, 20 g whey protein maximally stimulate MPS. However, recent observations suggest that dialysis patients need greater amounts of proteins than healthy subjects to maximally stimulate MPS. Since unneccesary amounts of amino acids could stimulate ureagenesis, toxins and acid production, it is urgent to obtain information on the optimal dose of proteins or amino acids/ketoacids to maximize MPS in this patients' population. In the meantime, the issue of maintaining muscle mass and function in dialysis-treated CKD patients needs not to be overlooked by the kidney community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garibotto, Saio, Aimasso, Russo, Picciotto, Viazzi, Verzola, Laudon, Esposito and Brunori.)
- Published
- 2021
- Full Text
- View/download PDF
35. Hyperkalemia-induced acute flaccid paralysis: a case report.
- Author
-
D'Ercole M, Cipriani L, Picciotto D, Bianzina S, Russo E, Viazzi F, and Esposito P
- Subjects
- Aged, Central Nervous System Viral Diseases, Creatinine, Electrocardiography, Female, Humans, Myelitis, Neuromuscular Diseases, Renal Dialysis, Hyperkalemia etiology
- Abstract
Acute flaccid paralysis is a medical emergency that may be caused by primary neuro-muscular disorders, metabolic alterations, and iatrogenic effects. Severe hyperkalemia is also a potential cause, especially in elderly patients with impaired renal function. Early diagnosis is essential for appropriate management. Here, we report the case of a 78-year-old woman with hypertension and diabetes presenting to the emergency department because of pronounced asthenia, rapidly evolving in quadriparesis. Laboratory examinations showed severe hyperkalemia of 9.9 mmol/L, metabolic acidosis, kidney failure (creatinine 1.6 mg/dl), and hyperglycemia (501 mg/dl). The electrocardiography showed absent P-wave, widening QRS, and tall T-waves. The patient was immediately treated with medical therapy and a hemodialysis session, presenting a rapid resolution of electrocardiographic and neurological abnormalities. This case offers the opportunity to discuss the pathogenesis, the clinical presentation, and the management of hyperkalemia-induced acute flaccid paralysis., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)
- Published
- 2021
36. Central line-associated bloodstream infections in hemodialysis patients in the COVID-19 era.
- Author
-
Esposito P, Civati A, Picciotto D, Falqui V, Conti N, Russo E, and Viazzi F
- Published
- 2021
- Full Text
- View/download PDF
37. Testosterone Disorders and Male Hypogonadism in Kidney Disease.
- Author
-
Garibotto G, Esposito P, Picciotto D, and Verzola D
- Subjects
- Child, Humans, Libido, Male, Testosterone, Erectile Dysfunction etiology, Hypogonadism complications, Renal Insufficiency, Chronic complications
- Abstract
Chronic kidney disease (CKD) causes substantial alterations in the male endocrine system, which affect puberty, libido, and sexual function. A major effect of CKD is a reduction in testosterone levels because of both primary and hypogonadotrophic hypogonadism. In addition to impairment of pubertal growth and sexual maturation in children with CKD, clinical evidence suggests that uremic hypogonadism strongly contributes to several CKD complications, including erectile dysfunction, muscle wasting and frailty, anemia, decreased bone mineralization, depression, and cognitive impairment. This review focuses on a reappraisal of the physiologic role of testosterone, with an emphasis on the hypogonadal condition linked to CKD and its complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
38. Low Protein Diets and Plant-Based Low Protein Diets: Do They Meet Protein Requirements of Patients with Chronic Kidney Disease?
- Author
-
Verzola D, Picciotto D, Saio M, Aimasso F, Bruzzone F, Sukkar SG, Massarino F, Esposito P, Viazzi F, and Garibotto G
- Subjects
- Aging, Amino Acids, Animals, Chronic Disease, Diet, High-Protein, Disease Progression, Humans, Muscle, Skeletal, Nitrogen, Plant Proteins genetics, Sarcopenia, Animal Proteins, Dietary, Diet, Protein-Restricted, Plant Proteins, Dietary, Renal Insufficiency, Chronic diet therapy
- Abstract
A low protein diet (LPD) has historically been used to delay uremic symptoms and decrease nitrogen ( N )-derived catabolic products in patients with chronic kidney disease (CKD). In recent years it has become evident that nutritional intervention is a necessary approach to prevent wasting and reduce CKD complications and disease progression. While a 0.6 g/kg, high biological value protein-based LPD has been used for years, recent observational studies suggest that plant-derived LPDs are a better approach to nutritional treatment of CKD. However, plant proteins are less anabolic than animal proteins and amino acids contained in plant proteins may be in part oxidized; thus, they may not completely be used for protein synthesis. In this review, we evaluate the role of LPDs and plant-based LPDs on maintaining skeletal muscle mass in patients with CKD and examine different nutritional approaches for improving the anabolic properties of plant proteins when used in protein-restricted diets.
- Published
- 2020
- Full Text
- View/download PDF
39. Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation.
- Author
-
Tinel C, Vermorel A, Picciotto D, Morin L, Devresse A, Sauvaget V, Lebreton X, Aouni L, Prié D, Brabant S, Avettand-Fenoel V, Scemla A, Timsit MO, Snanoudj R, Legendre C, Terzi F, Rabant M, and Anglicheau D
- Subjects
- Adult, Biomarkers urine, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Middle Aged, Polyomavirus Infections urine, Polyomavirus Infections virology, Predictive Value of Tests, Retrospective Studies, Time Factors, Treatment Outcome, Tumor Virus Infections urine, Tumor Virus Infections virology, Urinalysis, Viral Load, BK Virus pathogenicity, Chemokine CXCL10 urine, Kidney Transplantation adverse effects, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Virus Activation
- Abstract
BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline [HR = 1.65, 95% CI (1.08-2.51), P = 0.02], irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Tinel, Vermorel, Picciotto, Morin, Devresse, Sauvaget, Lebreton, Aouni, Prié, Brabant, Avettand-Fenoel, Scemla, Timsit, Snanoudj, Legendre, Terzi, Rabant and Anglicheau.)
- Published
- 2020
- Full Text
- View/download PDF
40. New Treatment Options for Hyperkalemia in Patients with Chronic Kidney Disease.
- Author
-
Esposito P, Conti NE, Falqui V, Cipriani L, Picciotto D, Costigliolo F, Garibotto G, Saio M, and Viazzi F
- Abstract
Hyperkalemia may cause life-threatening cardiac and neuromuscular alterations, and it is associated with high mortality rates. Its treatment includes a multifaceted approach, guided by potassium levels and clinical presentation. In general, treatment of hyperkalemia may be directed towards stabilizing cell membrane potential, promoting transcellular potassium shift and lowering total K
+ body content. The latter can be obtained by dialysis, or by increasing potassium elimination by urine or the gastrointestinal tract. Until recently, the only therapeutic option for increasing fecal K+ excretion was represented by the cation-exchanging resin sodium polystyrene sulfonate. However, despite its common use, the efficacy of this drug has been poorly studied in controlled studies, and concerns about its safety have been reported. Interestingly, new drugs, namely patiromer and sodium zirconium cyclosilicate, have been developed to treat hyperkalemia by increasing gastrointestinal potassium elimination. These medications have proved their efficacy and safety in large clinical trials, involving subjects at high risk of hyperkalemia, such as patients with heart failure and chronic kidney disease. In this review, we discuss the mechanisms of action and the updated data of patiromer and sodium zirconium cyclosilicate, considering that the availability of these new treatment options offers the possibility of improving the management of both acute and chronic hyperkalemia.- Published
- 2020
- Full Text
- View/download PDF
41. Long-term blood pressure behavior and progression to end-stage renal disease in patients with immunoglobulin A nephropathy: a single-center observational study in Italy.
- Author
-
Russo E, Verzola D, Salvidio G, Bonino B, Picciotto D, Drovandi S, Pozzi C, Ferrario F, Pontremoli R, Garibotto G, and Viazzi F
- Subjects
- Adult, Aged, Disease Progression, Female, Glomerulonephritis, IGA pathology, Humans, Italy, Kidney pathology, Kidney Failure, Chronic pathology, Male, Middle Aged, Proteinuria pathology, Proteinuria physiopathology, Retrospective Studies, Blood Pressure physiology, Glomerular Filtration Rate physiology, Glomerulonephritis, IGA physiopathology, Kidney physiopathology, Kidney Failure, Chronic physiopathology
- Abstract
Background: Antihypertensive treatment by the use of RAAS inhibitors (RAAS-is) is of paramount importance in the management of slowly progressive IgA nephropathy (IgAN). With the aim of better understanding the relationship between BP behavior and progression, we looked at time-averaged SBP and time-averaged proteinuria and renal outcome in a single-center cohort of IgAN patients., Methods: Among 248 consecutive patients referred to the Clinic of Nephrology of San Martino Hospital from 1996 to 2018 for native renal biopsy with a diagnosis of IgAN, we retrospectively analyzed 145 with available data at baseline and during follow-up. All patients received Supportive Care, 39% were on RAAS-is alone, 45% plus steroids, and 16% plus steroids and immunosuppressors. Renal replacing treatment (RRT) was the primary endpoint., Results: During a mean follow-up of 67 ± 6 months, 23% of study patients (n = 33) progressed to RRT and 6% (n = 9) died. Patients who reached the renal endpoint, had lower baseline eGFR and higher proteinuria and proteinuria indexed at baseline. Moreover, they had higher TA-SBP (139 ± 17 vs. 130 ± 13, P = 0.0016). The incidence of RRT was higher in IgAN patients in the highest time-averaged SBP tertile as compared with the others (32 vs. 23 vs. 9%, χ 6.8, P = 0.033). After adjusting for baseline SBP, baseline and time-averaged proteinuria indexed, MEST-C score, and treatment, the association between TA-SBP and RRT persisted., Conclusion: Time-averaged low BP values were independently associated to a decreased risk of renal progression in IgAN with no evidence of a J-curve relationship even at SBP levels below 125 mmHg.
- Published
- 2020
- Full Text
- View/download PDF
42. Muscle protein turnover and low-protein diets in patients with chronic kidney disease.
- Author
-
Garibotto G, Picciotto D, Saio M, Esposito P, and Verzola D
- Subjects
- Humans, Nutritional Status, Proteolysis, Renal Insufficiency, Chronic metabolism, Diet, Protein-Restricted methods, Dietary Supplements, Muscle Proteins metabolism, Renal Insufficiency, Chronic diet therapy
- Abstract
Adaptation to a low-protein diet (LPD) involves a reduction in the rate of amino acid (AA) flux and oxidation, leading to more efficient use of dietary AA and reduced ureagenesis. Of note, the concept of 'adaptation' to low-protein intakes has been separated from the concept of 'accommodation', the latter term implying a decrease in protein synthesis, with development of wasting, when dietary protein intake becomes inadequate, i.e. beyond the limits of the adaptive mechanisms. Acidosis, insulin resistance and inflammation are recognized mechanisms that can increase protein degradation and can impair the ability to activate an adaptive response when an LPD is prescribed in a chronic kidney disease (CKD) patient. Current evidence shows that, in the short term, clinically stable patients with CKD Stages 3-5 can efficiently adapt their muscle protein turnover to an LPD containing 0.55-0.6 g protein/kg or a supplemented very-low-protein diet (VLPD) by decreasing muscle protein degradation and increasing the efficiency of muscle protein turnover. Recent long-term randomized clinical trials on supplemented VLPDs in patients with CKD have shown a very good safety profile, suggesting that observations shown by short-term studies on muscle protein turnover can be extrapolated to the long-term period., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
43. Enhanced myostatin expression and signalling promote tubulointerstitial inflammation in diabetic nephropathy.
- Author
-
Verzola D, Milanesi S, Viazzi F, Ansaldo F, Saio M, Garibaldi S, Carta A, Costigliolo F, Salvidio G, Barisione C, Esposito P, Garibotto G, and Picciotto D
- Subjects
- Cell Line, Cell Proliferation genetics, Diabetic Nephropathies metabolism, Diabetic Nephropathies pathology, Epithelial Cells metabolism, Epithelial Cells pathology, Gene Expression Regulation genetics, Glucose metabolism, Humans, Inflammation metabolism, Inflammation pathology, Kidney metabolism, Kidney pathology, Kidney Tubules pathology, Leukocyte Common Antigens genetics, RNA, Messenger genetics, Signal Transduction genetics, Transforming Growth Factor beta genetics, Diabetic Nephropathies genetics, Inflammation genetics, Kidney Tubules metabolism, Myostatin genetics
- Abstract
Myostatin (MSTN), a family member of the transforming growth factor (TGF)-β super family, has been detected in the tubuli of pig kidney, but its role in the human kidney is not known. In this study we observed upregulation of MSTN mRNA (~8 to 10-fold increase) both in the glomeruli and tubulointerstitium in diabetic nephropathy (DN). In DN, immunoreactive MSTN was mainly localized in the tubuli and interstitium (∼4-8 fold increase), where it colocalized in CD45
+ cells. MSTN was also upregulated in the glomeruli and the arterial vessels. Tubulointerstitial MSTN expression was directly related to interstitial fibrosis (r = 0.54, p < 0.01). In HK-2 tubular epithelial cells, both high (30 mmol) glucose and glycated albumin upregulated MSTN mRNA and its protein (p < 0.05-0.01). MSTN-treated HK-2 cells underwent decreased proliferation, together with NF-kB activation and CCL-2 and SMAD 2,3 overexpression. In addition, MSTN induced intracellular ROS release and upregulated NADPH oxidase, effects which were mediated by ERK activation. In conclusion, our data show that MSTN is expressed in the human kidney and overexpressed in DN, mainly in the tubulointerstitial compartment. Our results also show that MSTN is a strong inducer of proximal tubule activation and suggest that MSTN overexpression contributes to kidney interstitial fibrosis in DN.- Published
- 2020
- Full Text
- View/download PDF
44. Nutritional Challenges in Pregnant Women with Renal Diseases: Relevance to Fetal Outcomes.
- Author
-
Esposito P, Garibotto G, Picciotto D, Costigliolo F, Viazzi F, and Conti NE
- Subjects
- Female, Humans, Kidney Diseases diagnosis, Kidney Diseases etiology, Kidney Diseases therapy, Kidney Transplantation, Pregnancy, Pregnancy Outcome, Prenatal Care, Prenatal Nutritional Physiological Phenomena, Renal Dialysis, Renal Insufficiency, Chronic epidemiology, Kidney Diseases epidemiology, Nutrition Assessment, Pregnancy Complications epidemiology
- Abstract
Pregnancy in women affected by chronic kidney disease (CKD) has become more common in recent years, probably as a consequence of increased CKD prevalence and improvements in the care provided to these patients. Management of this condition requires careful attention since many clinical aspects have to be taken into consideration, including the reciprocal influence of the renal disease and pregnancy, the need for adjustment of the medical treatments and the high risk of maternal and obstetric complications. Nutrition assessment and management is a crucial step in this process, since nutritional status may affect both maternal and fetal health, with potential effects also on the future development of adult diseases in the offspring. Nevertheless, few data are available on the nutritional management of pregnant women with CKD and the main clinical indications are based on small case series or are extrapolated from the general recommendations for non-pregnant CKD patients. In this review, we discuss the main issues regarding the nutritional management of pregnant women with renal diseases, including CKD patients on conservative treatment, patients on dialysis and kidney transplant patients, focusing on their relevance on fetal outcomes and considering the peculiarities of this population and the approaches that could be implemented into clinical practice.
- Published
- 2020
- Full Text
- View/download PDF
45. Cellular Senescence Is Associated with Faster Progression of Focal Segmental Glomerulosclerosis.
- Author
-
Verzola D, Saio M, Picciotto D, Viazzi F, Russo E, Cipriani L, Carta A, Costigliolo F, Gaggero G, Salvidio G, Esposito P, Garibotto G, and Poggi L
- Subjects
- Adult, Aged, Disease Progression, Female, Glomerulosclerosis, Focal Segmental pathology, Glomerulosclerosis, Focal Segmental physiopathology, Humans, Male, Middle Aged, Time Factors, Cellular Senescence, Glomerulosclerosis, Focal Segmental complications, Kidney Failure, Chronic etiology
- Abstract
Background: A current, albeit unproven, hypothesis is that an acceleration of cellular senescence is involved in impaired renal repair and progression of glomerular diseases. Focal segmental glomerulosclerosis (FSGS) is a glomerular disease with a substantial risk for progression to ESRD. However, if and to what extent cell senescence predicts a negative outcome in FSGS is still unknown., Methods: The hypothesis that cell senescence represents a proximate mechanism by which the kidney is damaged in FSGS (NOS phenotype) was investigated in 26 consecutive kidney biopsies from adult FSGS cases (eGFR 72 ± 4 mL/min, proteinuria 2.3 ± 0.6 g/day) who were incident for 2 years in a Northern Italian nephrology center and had a 6-year clinical follow-up., Results: Cell senescence (p16INK4A, SA-β-galactosidase [SA-β-Gal]) was upregulated by ∼3- to 4-fold in both glomerular and tubular cells in kidney biopsies of FSGS as compared to age-matched controls (p < 0.05-0.01). Tubular SA-β-Gal correlated with proteinuria and glomerulosclerosis, while only as a trend, tubular p16INK4A was directly associated with interstitial fibrosis. At univariate analysis, basal eGFR, proteinuria, and tubular expression of SA-β-Gal and p16INK4A were significantly directly related to the annual loss of eGFR. No correlation was observed between glomerular p16INK4A and eGFR loss. However, at multivariate analysis, eGFR, proteinuria, and tubular p16INK4A, but not SA-β-Gal, contributed significantly to the prediction of eGFR loss., Conclusions: The results indicate that an elevated cell senescence rate, expressed by an upregulation of p16INK4A in tubules at the time of initial biopsy, represents an independent predictor of progression to ESRD in adult patients with FSGS., (© 2021 S. Karger AG, Basel.)
- Published
- 2020
- Full Text
- View/download PDF
46. Activin/myostatin receptor signaling and vascular calcifications in chronic kidney disease: A "liaison dangereuse"?
- Author
-
Garibotto G, Esposito P, Picciotto D, and Verzola D
- Published
- 2019
- Full Text
- View/download PDF
47. Testosterone deficiency, frailty and muscle wasting in CKD: a converging paradigm?
- Author
-
Garibotto G, Picciotto D, and Verzola D
- Subjects
- Humans, Male, Muscular Atrophy, Renal Dialysis, Testosterone, Frailty, Renal Insufficiency, Chronic
- Published
- 2019
- Full Text
- View/download PDF
48. Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway.
- Author
-
Milanesi S, Garibaldi S, Saio M, Ghigliotti G, Picciotto D, Ameri P, Garibotto G, Barisione C, and Verzola D
- Subjects
- Animals, Disease Models, Animal, Humans, Mice, Rats, Fibroblasts metabolism, HSP90 Heat-Shock Proteins metabolism, Indican metabolism, Kidney pathology
- Abstract
Indoxyl sulfate (IS) accumulation occurs early during chronic kidney disease (CKD) progression and contributes to renal dysfunction by inducing fibrosis, inflammation, oxidative stress, and tissue remodeling. Renal toxicity of high IS concentrations (250 μ M) has been widely explored, particularly in resident tubular and glomerular cells, while the effect of a moderate IS increase on kidneys is still mostly unknown. To define the effects of IS accumulation on renal fibroblasts, we first analyzed kidneys of C57BL/6 mice receiving IS (0.1%) in drinking water for 12 weeks. As a next step, we treated renal fibroblasts (NRK-49F) with IS (20 μ M) with or without the HSP90 inhibitor 17-AAG (1 μ M). In mouse kidneys, IS increased the collagen deposition and HSP90 and α -SMA expression (immunohistochemistry) in interstitial fibroblasts and caused tubular necrosis (histological H&E and picrosirius red staining). In NRK-49F cells, IS induced MCP1, TGF- β , collagen I, α -SMA, and HSP90 gene/protein expression and Smad2/3 pathway activation. IS had no effects on fibroblast proliferation and ROS production. 17-AAG counteracted IS-induced MCP1, TGF- β , collagen I, and α -SMA expression and Smad2/3 phosphorylation. Our study demonstrates that the IS increase promotes renal fibroblast activation by a HSP90-dependent pathway and indicates HSP90 inhibition as a potential strategy to restrain IS-induced kidney inflammation and fibrosis in CKD.
- Published
- 2019
- Full Text
- View/download PDF
49. Emerging role of myostatin and its inhibition in the setting of chronic kidney disease.
- Author
-
Verzola D, Barisione C, Picciotto D, Garibotto G, and Koppe L
- Subjects
- Activin Receptors, Type II antagonists & inhibitors, Activin Receptors, Type II metabolism, Anabolic Agents therapeutic use, Animals, Clinical Trials as Topic, Disease Models, Animal, Exercise Therapy, Feeding Behavior physiology, Humans, Muscle, Skeletal pathology, Myostatin antagonists & inhibitors, Proteolysis drug effects, Renal Insufficiency, Chronic rehabilitation, Sarcopenia etiology, Sarcopenia prevention & control, Signal Transduction drug effects, Treatment Outcome, Activins metabolism, Anabolic Agents pharmacology, Myostatin metabolism, Renal Insufficiency, Chronic complications, Sarcopenia pathology
- Abstract
The past two decades have witnessed tremendous progress in our understanding of the mechanisms underlying wasting and cachexia in chronic kidney disease (CKD) and in other chronic illnesses, such as cancer and heart failure. In all these conditions wasting is an effect of the activation of protein degradation in muscle, a response that increases the risk of morbidity and mortality. Major recent advances in our knowledge on how CKD and inflammation affect cellular signaling include the identification of the myostatin (MSTN)/activin system, and its related transcriptional program that promotes protein degradation. In addition, the identification of the role of MSTN/activin in the vascular wall shows premise that its inhibition can better control or prevent some effects of CKD on vessels, such as accelerated atherosclerosis and vascular calcifications. In this review, we summarize the expanding role of MSTN activation in promoting muscle atrophy and the recent clinical studies that investigated the efficacy of MSTN/activin pathway antagonism in sarcopenic patients. Moreover, we also review the utility of MSTN inhibition in the experimental models of CKD and its potential advantages in CKD patients. Lessons learned from clinical studies on MSTN antagonism in sarcopenic patients tell us that the anabolic intervention is likely better if we use a block of the two ActRII receptors. At the same time, however, it is becoming clear that MSTN-targeted therapies should not be seen as a substitute for physical activity and nutritional supplementation which are mandatory to successfully manage patients with wasting., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
50. The Organ Handling of Soluble Klotho in Humans.
- Author
-
Picciotto D, Murugavel A, Ansaldo F, Rosa GM, Sofia A, Milanesi S, Viazzi F, Saio M, Balbi M, Garibotto G, and Verzola D
- Subjects
- Aged, Female, Glucuronidase blood, Humans, Kidney blood supply, Klotho Proteins, Male, Oxygen blood, Sodium, Solubility, Splanchnic Circulation, Uric Acid, Glucuronidase metabolism, Kidney metabolism, Oxygen metabolism
- Abstract
Background: Chronic kidney disease (CKD) reduces both Klotho expression and its shedding into circulation, an effect that accelerates progression and cardiovascular complications. However, the mechanisms that regulate Klotho release by the human kidney are still unknown., Methods: We measured plasma Klotho across the kidney, splanchnic organs and lung in 22 patients (71 ± 2 years, estimated glomerular filtration rate [eGFR] 60 ± 5.4 mL/min 1.73 m2) during elective diagnostic cardiac catheterizations., Results: Although the Klotho average renal vein concentrations were remarkably higher (by ∼9%) than arterial values, the kidney removed Klotho (or was at zero balance) in 7 subjects, indicating that the kidney contribution to systemic Klotho is not constant. Klotho fractional enrichment across the kidney was inversely related to plasma sodium (r = 0.43, p = 0.045) and acid uric acid levels (r = 0.38, p = 0.084) and directly, to renal oxygen extraction (r = 0.56, p = 0.006). In multivariate analysis, renal oxygen extraction was the only predictor of the enrichment of Klotho across the kidney, suggesting the dependence of renal Klotho release on tubular hypoxia or oxidative metabolism. Klotho balance was neutral across the lung. In patients with eGFR <60 mL/min, Klotho was also removed by splanchnic organs (single pass fractional extraction ∼11%)., Conclusions: The present study identifies kidney oxygen uptake as a predictor of Klotho release, and splanchnic organs as a site for Klotho removal. This study provides new understanding of kidney Klotho release and suggests that modulating kidney oxygen metabolism could increase Klotho delivery, as an option to slow disease progression and blunt organ damage., (© 2019 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.