Publications by authors named "Sandro Mazzaferro"

88 Publications

Focus on the Possible Role of Dietary Sodium, Potassium, Phosphate, Magnesium, and Calcium on CKD Progression.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Nephrology Unit Policlinico Umberto I Hospital, 00185 Rome, Italy.

The impressive estimated number of chronic kidney disease (CKD) patients in the world justifies any possible effort at implementing preventive measures of disease progression. Renal insufficiency is associated with significant changes in the electrolyte handling and body balance of sodium, potassium, phosphate, magnesium, and calcium, all of which are biologically vital molecules. Dietary habits could contribute significantly to the optimal management of possible derangements. In this review, we examined the available evidence recommending dietary prescriptions for these five elements aiming at reducing CKD progression. Clear evidence that specific dietary prescriptions may halt or reduce CKD progression is lacking. However, some practical recommendations are possible to prescribe the best possible therapy to the individual CKD patient.
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http://dx.doi.org/10.3390/jcm10050958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957473PMC
March 2021

Oxygen extraction ratio to identify patients at increased risk of intradialytic hypotension.

Sci Rep 2021 Feb 26;11(1):4801. Epub 2021 Feb 26.

Department of Translational and Precision Medicine, Nephrology Unit at Policlinico Umberto I Hospital, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Intradialytic hypotension (IDH) is a hemodynamic phenomenon recently associated with decreased blood oxygen saturation (SO). The ratio between peripheral oxygen saturation (SpO) and central venous SO (ScvO) or Oxygen Extraction Ratio (OER), which represents a roughly estimate of the amount of oxygen claimed by peripheral tissues, might be used to estimate haemodialysis (HD) related hypoxic stress. Aim of this pilot study was to evaluate the relationship between OER increments during dialysis sessions (ΔOER) and episodes of IDH. We enrolled chronic HD patients with permanent central venous catheter (CVC) and no fistula, in whom ScvO measurement is at hand. OER ([(SpO - ScvO)/SpO] × 100) was measured in three consecutive HD sessions (HD OER sessions) before HD, after 15', 30' and 60' min and at the end of HD. Then, a one-year follow-up was planned to record the number of IDH episodes. In the 28 enrolled patients (age 74 ± 2.6 years), during 12 ± 1.2 months of follow up, incidence of IDH was 3.6%. We divided patients into two groups, above or below the median value of ΔOER at the end of HD, which was 36%. In these groups, the average incidence of IDH was 7% and 2% respectively (p < 0.01), while OER values before HD were not different. Notably, in the high ΔOER group the OER increment was evident since after 15' and was significantly higher than in the low ∆OER group (∆OER-15' = 19 ± 3.0% vs. 9.0 ± 3.0%; p < 0.05). By comparison, blood volume changes overlapped in the two groups (average change - 9 ± 0.8%). Values of ∆OER > 19% after only 15' of HD treatment or > 36% at the end of the session characterize patients with higher rates of hypotension. Intradialytic ∆OER, a parameter of tissue hypoxic stress, identifies more fragile patients at greater risk of IDH.
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http://dx.doi.org/10.1038/s41598-021-84375-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910620PMC
February 2021

Waves of infection and waves of communication: the importance of sharing in the era of Covid-19.

J Nephrol 2021 Feb 3. Epub 2021 Feb 3.

Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.1007/s40620-021-00974-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856453PMC
February 2021

Inflammation, Oxidative Stress, and Bone in Chronic Kidney Disease in the Osteoimmunology Era.

Calcif Tissue Int 2021 Apr 2;108(4):452-460. Epub 2021 Jan 2.

Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Bone is not only a mineralized and apparently non-vital structure that provides support for locomotion and protection to inner organs. An increasing number of studies are unveiling new biologic functions and connections to other systems, giving the rise to new fields of research, such as osteoimmunology. The bone marrow niche, a new entity in bone physiology, seems to represent the site where a complex crosstalk between bone and immune/inflammatory responses takes place. An impressive interplay with the immune system is realized in bone marrow, with reciprocal influences between bone cells and haematopoietic cells. In this way, systemic chronic inflammatory diseases realize a crosstalk with bone, resulting in bone disease. Thus, pathogenetic links between chronic kidney disease-mineral bone disorders and osteoporosis, cardiovascular disease, and ageing are common. The aim of this narrative review is to provide a general view of the progresses in the field of bone research and their potential clinical implications, with emphasis on the links with inflammation and the connections to osteoimmunology and chemokines.
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http://dx.doi.org/10.1007/s00223-020-00794-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778498PMC
April 2021

Association between Multidimensional Prognostic Index and Hospitalization and Mortality among Older Adults with Chronic Kidney Disease on Conservative or on Replacement Therapy.

J Clin Med 2020 Dec 7;9(12). Epub 2020 Dec 7.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

The prevalence of renal disease is constantly increasing in older adults and a prognostic evaluation by a valid tool may play a key role in treatment management. We aimed to assess the association(s) between the multidimensional prognostic index (MPI) and both the hospitalization and mortality among older adults with renal disease. Patients with chronic kidney disease (CKD) (stage 3-5 KDOQI) and on dialysis were considered. Clinical parameters were registered at baseline and after 2 years. In all the patients, the MPI was calculated and divided into grade 0 (low risk), 1 (moderate risk), and 2 (severe risk). Hospitalizations and mortality were recorded during the follow-up and analyzed according to MPI grade. A total of 173 patients, with a median age of 76 years, on conservative ( = 105) and replacement therapy (32 patients on hemodialysis, 36 patients on peritoneal dialysis) were enrolled. Of them, 60 patients were in MPI grade 0, 102 in grade 1, and 11 in grade 2. The median duration of all the hospitalizations was 6 days and the number of deaths was 33. MPI significantly correlated with days of hospitalization ( = 0.801, < 0.00001) and number of hospitalizations per year ( = 0.808, < 0.00001), which was higher in MPI grade 2 compared to grade 1 ( < 0.001) and to grade 0 ( < 0.001). We found a significant association between MPI grades and mortality ( < 0.001). Our results indicate that MPI was associated with outcomes in patients with renal disease, suggesting that a multidimensional evaluation should be implemented in this clinical setting.
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http://dx.doi.org/10.3390/jcm9123965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762388PMC
December 2020

Bone biopsy in chronic kidney disease: still neglected and in need of revitalization.

Nephrol Dial Transplant 2021 01;36(2):202-204

Department of Internal Medicine and Medical Specialties, UOC Nefrologia Azienda Ospedaliero Universitaria Policlinico Umberto, Rome, Italy.

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http://dx.doi.org/10.1093/ndt/gfaa269DOI Listing
January 2021

Renal resistive index in IgA nephropathy and renal scleroderma vasculopathy.

Microvasc Res 2021 01 7;133:104095. Epub 2020 Oct 7.

Department of Translational and Precision Medicine, "Sapienza", University of Rome, Italy. Electronic address:

Background: Renal Ultra-Sound (US) and Doppler US provide measurements which reflect changes in renal and systemic haemodynamic. The renal resistive index (RRI), obtained through the Doppler spectrum analysis of renal small arteries, is altered in several pathologic conditions. Glomerulonephritis cause minor RRI changes, while renal scleroderma vasculopathy (RSV) leads to significant RRI modifications. The aim of our study was to assess RRI in IgA nephropathy (IgAN) and RSV in a retrospective observational study and to investigate determinants of the RRI in these groups of patients.

Methods: We enrolled 61 IgAN patients [23 female, median age 41 (33-58) years] and 80 SSc patients [71 female, median age 52 (43-60) years]. RRI was evaluated in all patients at the time of enrolment. Laboratory tests and clinical assessment were evaluated in all patients.

Results: IgAN patients showed lower RRI values than RSV patients [0.70 (0.65-0.73) vs 0.66 (0.62-0.72), p < 0.01], while no significant difference in longitudinal length was observed. Median age was significantly lower in IgAN patients than in RSV patients [41 (33-58) vs 52 (43-60), p < 0.05] while IgAN patients showed a higher prevalence of high blood pressure than RSV patients (39.3% vs 13.8%, p < 0.01). The multiple regression analysis, weighted for age, showed that RRI inversely correlates with estimated glomerular filtration rate (β coefficient = -0.524, p < 0.0001).

Conclusion: Higher RRI were found in RSV patients than IgAN patients. IgAN is characterized mainly by glomerular injury, not leading to major RRI changes.
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http://dx.doi.org/10.1016/j.mvr.2020.104095DOI Listing
January 2021

Cardiovascular risk and quality of life in autosomal dominant polycystic kidney disease patients in therapy with tolvaptan: A pilot study.

Curr Vasc Pharmacol 2020 Sep 17. Epub 2020 Sep 17.

Department of Translational and Precision Medicine, Nephrology Unit, Sapienza University of Rome, Rome. Italy.

Introduction: Cardiovascular (CV) complications are the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients. In 2017, the Italian Medicines Agency authorised tolvaptan, a vasopressin V2 receptor antagonist, for the treatment of ADPKD, based on the Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO 3: 4), TEMPO 4: 4 and Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) studies.

Aim Of The Study: To assess the impact of tolvaptan on CV risk and quality of life, evaluated by nutritional, inflammatory, metabolic, instrumental parameters and psychocognitive tests in ADPKD patients.

Methods And Materials: We evaluated 36 patients with ADPKD; 10 patients (7 males, mean age 42.5±7.0 years) treated with tolvaptan and 26 controls (11 males, mean age 36.7±9.1 years). They underwent, at T0, monthly, and at T1 (1 year) clinical, laboratory and instrumental evaluation, in addition to psychocognitive tests.

Results: In ADPKD patients treated with tolvaptan we found at T1 a decrease in carotid intima media thickness (p=0.048), epicardial adipose tissue thickness (p=0.002), C-reactive protein (p=0.026), sympathovagal balance during the night (p=0.045) and increases flow mediated dilation (p=0.023) with a reduction in depression (Hamilton and Beck tests, p=0.008 and p=0.002, respectively) compared with controls.

Conclusions: These preliminary results suggest that treatment with tolvaptan could improve early atherosclerosis and endothelial dysfunction markers and improve the mood in ADPKD patients (probably by the acting on endothelial cell and adipocyte V2 receptors).
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http://dx.doi.org/10.2174/1570161118999200918094809DOI Listing
September 2020

Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

Toxins (Basel) 2020 06 9;12(6). Epub 2020 Jun 9.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus ( ≤ 0.01) and serum uric acid ( ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, ≤ 0.01; base excess, ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin ( = 0.008) and fasting glucose levels ( = 0.022), HOMA-IR ( = 0.004), as well as lower total serum cholesterol ( = 0.012), triglycerides ( = 0.016), C-reactive protein ( = 0.044) and homocysteine ( = 0.044) and higher HDL ( < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.
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http://dx.doi.org/10.3390/toxins12060381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354587PMC
June 2020

Dialysate calcium concentration during calcimimetic treatment: a neglected issue.

J Nephrol 2021 02;34(1):19-22

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1007/s40620-020-00741-0DOI Listing
February 2021

A new technique for measuring fistula flow using venous blood gas oxygen saturation in patients with a central venous catheter.

Clin Kidney J 2020 Apr 1;13(2):184-187. Epub 2019 Jun 1.

Nephrology and Dialysis Unit, ICOT Hospital, Polo Pontino Sapienza University of Rome, Italy.

Background: Doppler ultrasound (DU) monitoring early after arteriovenous fistula (AVF) creation allows the identification of low blood flow (Qa) requiring prompt revision, but it is costly (needs skilled operators and technical instruments) and is not available in all dialysis units. Therefore alternative first-line methods to measure Qa would be welcomed. We reasoned that once an AVF is created, an increment in central venous oxygen saturation (ScvO) is predictable and proportional to Qa.

Methods: Accordingly, in patients receiving dialysis through a central venous catheter (CVC) in whom an AVF was created, we measured, by means of blood gas analysis, the ScvO increment before and after manual compression of the arteriovenous shunt and verified its correlation with DU-measured Qa.

Results: We sampled blood gas in 18 patients with CVC and AVF before and after 30 s manual compression of the AVF. ScvO averaged 70.5 ± 3% before and 65.2 ± 3% after AVF closure, with an average drop of 5.1 ± 3% (range 1-12). AVF Qa, which was measured within 24 h by means of DU, averaged 635 ± 349 mL/min (range 50-1300) and was strictly and positively correlated with ΔScvO ( 0.954, P < 0.0001).

Conclusions: Therefore we suggest that in patients with CVC and a newly created AVF, it is possible to monitor AVF Qa without DU by simply measuring blood gas and ΔScvO. This technique is simple, cheap, repeatable, non-invasive and operator independent and represents a new useful screening test to detect delayed AVF access maturation deserving prompt DU measurement and surgical revision. It helps to quickly identify patients in urgent need of DU verification and possible surgical revision. Regrettably, it is applicable only in patients with CVC.
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http://dx.doi.org/10.1093/ckj/sfz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147307PMC
April 2020

Bone, inflammation and chronic kidney disease.

Clin Chim Acta 2020 Jul 8;506:236-240. Epub 2020 Apr 8.

Azienda Ospedaliero-Universitaria Policlinico Umberto I, Roma, Italy. Electronic address:

Increasing knowledge on inflammatory mediators and bone metabolism highlights the relationship between inflammation and bone disease. During acute illness, inflammatory cells and cytokines modulate bone cells activity so as to mobilize calcium seemingly to supply the metabolic requirements for immune response. In case of long lasting, chronic inflammatory states a condition of maladaptive, smouldering inflammation is realized and negatively affects calcium bone balance. Aging, now nicknamed inflammaging, is regarded as a chronic inflammatory condition, characterized by increased circulating inflammatory cytokines, that contributes to the development of osteoporosis, cardiovascular diseases and chronic kidney disease. In patients with renal insufficiency, the development of bone and mineral disorders (so called CKD-MBD "syndrome") is now a recognized pathogenic factor for the seemingly accelerated process of aging and for the increased risk of cardiovascular death in these patients. The adaptive changes in mineral and bone metabolism developing in the early stages of chronic kidney disease could represent a hypothetical model of accelerated aging, osteoporosis and cardiovascular disease.
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http://dx.doi.org/10.1016/j.cca.2020.03.040DOI Listing
July 2020

Effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular risk indices in renal cell carcinoma.

Cancer Med 2020 06 9;9(11):3752-3757. Epub 2020 Apr 9.

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

Background: Sunitinib is a standard treatment for metastatic renal cell carcinoma (RCC). Currently, the data available on the effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular (CV) risk factors are limited, and we aimed to evaluate these aspects in patients with RCC after a short period of treatment.

Methods: Patients affected by metastatic RCC were enrolled and evaluated before starting sunitinib (T0) and after 40 days of treatment (T1) by the flow-mediated dilation (FMD), carotid intima media thickness (IMT), ankle-brachial pressure index (ABI), and 24-hour proteinuria. We also assessed serum metabolic and nutritional parameters at T0 and T1.

Results: Twenty patients (7 female), with a mean age of 61.4 ± 12.0 years, were studied. Overtime, we observed a reduction in estimated glomerular filtration rate (P = .002), FMD (P = .001) and in fasting plasma glucose levels (P = .04), as well as an increase in plasma insulin (P < .001), HOMA-IR (P < .01), and serum total cholesterol levels (P = .01). Moreover at T1 we found a significant increase in systolic and diastolic blood pressure (P ≤ .001) and 24-hour proteinuria (P < .001) compared to baseline, whereas no changes in IMT and ABI were detected.

Conclusion: The changes observed overtime after sunitinib treatment in terms of markers of early endothelial dysfunction, blood pressure, as well as in glucose/insulin metabolism and proteinuria may contribute to increase CV risk in RCC patients and suggest a strict follow-up in this setting. Larger evidences are mandatory to confirm our observations.
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http://dx.doi.org/10.1002/cam4.2910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286450PMC
June 2020

[Peritoneal dialysis in the Lazio region: results from 2017 regional audit].

G Ital Nefrol 2020 Feb 12;37(1). Epub 2020 Feb 12.

Ospedale San Lazzaro Alba-Cuneo, Italy.

In 2011, a first peritoneal dialysis audit was held in the Lazio region to analyze the problems hindering the spread of this method and to improve the quality of care through the sharing of best practices across Centers. A scientific board was therefore set up, representing all the Centers offering PD, in order to assess clinical effectiveness using KPIs (Key Performance Indicators) and to quantify the objectives to be achieved. The analysis made it possible to identify the main problems and take action, all the while monitoring progress through KPIs. A second audit was carried out in 2017 and the collected data was analyzed and compared with the findings of the previous study. Overall, data showed an increase in prevalence, although the incidence showed a slight decrease. Indicators on the change of dialysis treatment, the dropout from domiciliary treatment and the incidence of late referral appeared stable over time. A slight improvement was observed in clinical data on peritonitis and on the length of hospitalization. All participants in the audit declared that sharing and discussing clinical practices had been really useful. In addition, through the drafting of practical documents (guides for patients, guidance on informed consent, protocols of clinical follow-up), a number of tools have been provided to ensure a uniformly high level of care across the different regional Centers.
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February 2020

On the role of skin biopsy in the diagnosis of calcific uremic arteriolopathy: a case-based discussion.

J Nephrol 2020 Aug 2;33(4):859-865. Epub 2019 Dec 2.

Dialysis Unit at ICOT Hospital, Latina, Italy.

Calciphylaxis is a rare disease characterized by ectopic calcification of skin arterioles resulting in ischemia, thrombosis and necrosis. Since end stage renal disease patients are those mainly affected, the term calcific uremic arteriolopathy (CUA) is also suggested. Early clinical manifestations are subtle, while overt necrotic ulcers may quickly spread and become infected so as to result in ominous outcome. Diagnosis might not be easy due to the number of other ischemic and non-ischemic skin lesions observed in uraemia. Skin biopsy, has been proposed as the diagnostic test and is often considered, but not systematically performed due to the hypothetical risk of further spreading of the lesions. Such ambiguity could be responsible for misdiagnosis or underdiagnosis. We review here five consecutive cases recorded in our Unit, all submitted to skin biopsy but with inconsistent results which generated some clinical frustration. Thus, we decided to carefully re-evaluate all of them together with pathologists and dermatologists. However, even after this ex-post discussion, we could not reach a complete agreement on the final diagnosis. In the meanwhile, papers were published in the literature that started to shed some light on the role of skin biopsy in the diagnosis of CUA.
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http://dx.doi.org/10.1007/s40620-019-00678-zDOI Listing
August 2020

α-lipoic acid in patients with autosomal dominant polycystic kidney disease.

Nutrition 2020 03 27;71:110594. Epub 2019 Sep 27.

Department of Translational and Precision Medicine, Secondary Hypertension Unit, Sapienza University of Rome, Italy.

Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls.

Methods: This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2).

Results: Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P <0.001; respectively) and significantly higher values of base excess (P < 0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P <0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1β, and tumor necrosis factor-α concentrations in either group.

Conclusions: We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.
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http://dx.doi.org/10.1016/j.nut.2019.110594DOI Listing
March 2020

Renal involvement and metabolic alterations in adults patients affected by cystic fibrosis.

J Transl Med 2019 11 25;17(1):388. Epub 2019 Nov 25.

Department of Public Health and Infectious Diseases, Special Unit of Cystic Fibrosis, "Sapienza" University of Rome, Rome, Italy.

Background: Cystic fibrosis (CF) is one of the most frequent genetic diseases and the median survival of these patients has improved in the last few decades, therefore it becomes necessary to evaluate the long-term complications as renal and cardiovascular risk factors.

Aim Of The Study: To evaluate the incidence, the manifestations of renal disease and the possible association with metabolic and endothelial dysfunction markers in the CF population.

Materials And Methods: We performed a cross-sectional, observational study on 226 CF patients. Clinical and laboratory instrumental parameters (metabolic, inflammatory and endothelial dysfunction markers) were evaluated.

Results: We showed 65 patients with chronic kidney disease (CKD) and 158 patients with a reduced value of forced expiratory volume in 1 s (FEV1), of which 58 patients with a severe reduction of FEV1. Moreover 28 patients had undergone lung transplantation and them had a significant lower estimated Glomerular Filtration Rate (eGFR) with respect to the non-transplanted patients (p < 0.001). We reported also a significant association between lower eGFR value and serum triglycerides, total cholesterol and low-density lipoproteins (LDL) (p = 0.005, p < 0.001, p = 0.040; respectively), with a significant negative correlation between eGFR and serum triglycerides (r = - 0.28; p < 0.01). Moreover we found a significant association between lower eGFR value and serum uric acid (SUA) (p = 0.005), while we did not found an association with 25-hydroxy-vitamin-D value, serum glucose and hemoglobin A1c levels.

Conclusions: Our study showed a high prevalence of CKD in CF patients. Moreover we showed an increase of endothelial dysfunction and metabolic indexes in patients with reduced renal function, as SUA, serum triglycerides and LDL, suggesting the need for an early and complete screening of the main metabolic indexes to reduce cardiovascular risk and progression of renal damage, in particular in patients with lung transplant.
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http://dx.doi.org/10.1186/s12967-019-02139-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878680PMC
November 2019

Calciphylaxis: a conundrum for patients and nephrologists?

J Nephrol 2019 Oct 30;32(5):677-680. Epub 2019 Aug 30.

Policlinico Umberto 1 Hospital, Rome, Italy.

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http://dx.doi.org/10.1007/s40620-019-00639-6DOI Listing
October 2019

Valvular heart disease and calcification in CKD: more common than appreciated.

Nephrol Dial Transplant 2020 12;35(12):2046-2053

Fundació Puigvert, Department of Nephrology and Cardiology, IIB Sant Pau, RedinRen, Barcelona, Catalonia, Spain.

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10-20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.
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http://dx.doi.org/10.1093/ndt/gfz133DOI Listing
December 2020

Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial.

Am J Kidney Dis 2019 09 23;74(3):338-350. Epub 2019 Apr 23.

Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, UT.

Rationale & Objective: Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD.

Study Design: Phase 2, randomized, controlled, open-label, crossover trial.

Setting & Participants: Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs)>15mL/min/1.73m and residual proteinuria with protein excretion≥0.5g/24h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy.

Intervention: After stratification by serum phosphate level, ≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period.

Outcomes: The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness.

Results: Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer.

Limitations: Short treatment duration, lower pretreatment proteinuria than expected.

Conclusions: 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria.

Funding: Sanofi (Milan, Italy).

Trial Registration: Registered at ClinicalTrials.gov with study number NCT01968759.
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http://dx.doi.org/10.1053/j.ajkd.2019.01.029DOI Listing
September 2019

Direct bone effects of calcimimetics in chronic kidney disease?

Kidney Int 2019 05;95(5):1012-1014

Ospedale Universitario Policlinico Umberto I, Rome, Italy.

Calcimimetics are widely used in patients on dialysis to treat secondary hyperparathyroidism. Our current view is that bone effects are only indirect through parathyroid hormone suppression. However, because bone cells express the calcium-sensing receptor, direct calcium-sensing receptor-mediated effects are also possible. New experimental data demonstrate direct anabolic bone actions of calcimimetics, independent of parathyroid hormone suppression. Because these effects could be clinically useful, further studies are necessary to confirm the validity of this observation.
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http://dx.doi.org/10.1016/j.kint.2019.01.045DOI Listing
May 2019

Novel insights into parathyroid hormone: report of The Parathyroid Day in Chronic Kidney Disease.

Clin Kidney J 2019 Apr 20;12(2):269-280. Epub 2018 Jul 20.

Division of Nephrology, Ambroise Paré University Medical Center, APHP, University of Paris Ouest (UVSQ), Boulogne Billancourt/Paris, France.

Chronic kidney disease (CKD) is often associated with a mineral and bone disorder globally described as CKD-Mineral and Bone Disease (MBD), including renal osteodystrophy, the latter ranging from high bone turnover, as in case of secondary hyperparathyroidism (SHPT), to low bone turnover. The present article summarizes the important subjects that were covered during 'The Parathyroid Day in Chronic Kidney Disease' CME course organized in Paris in September 2017. It includes the latest insights on parathyroid gland growth, parathyroid hormone (PTH) synthesis, secretion and regulation by the calcium-sensing receptor, vitamin D receptor and fibroblast growth factor 23 (FGF23)-Klotho axis, as well as on parathyroid glands imaging. The skeletal action of PTH in early CKD stages to the steadily increasing activation of the often downregulated PTH receptor type 1 has been critically reviewed, emphasizing that therapeutic strategies to decrease PTH levels at these stages might not be recommended. The effects of PTH on the central nervous system, in particular cognitive functions, and on the cardiovascular system are revised, and the reliability and exchangeability of second- and third-generation PTH immunoassays discussed. The article also reviews the different circulating biomarkers used for the diagnosis and monitoring of CKD-MBD, including PTH and alkaline phosphatases isoforms. Moreover, it presents an update on the control of SHPT by vitamin D compounds, old and new calcimimetics, and parathyroidectomy. Finally, it covers the latest insights on the persistence and occurrence of SHPT in renal transplant recipients.
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http://dx.doi.org/10.1093/ckj/sfy061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452197PMC
April 2019

Sarcopenia and cardiovascular risk indices in patients with chronic kidney disease on conservative and replacement therapy.

Nutrition 2019 06 11;62:108-114. Epub 2018 Dec 11.

Department of Translational and Precision Medicine, Sapienza University of Rome, Italy.

Objective: Chronic kidney disease (CKD) is a condition with high cardiovascular mortality associated with emerging risk factors, including sarcopenia. Several mechanisms can affect muscle mass, such as vitamin D deficiency, low protein intake, physical inactivity, metabolic acidosis, and inflammation leading to a worsening of cardiovascular outcomes and cognitive function. We aimed to evaluate the prevalence of sarcopenia in CKD patients on conservative and replacement therapy and the associations between sarcopenia and markers of atherosclerosis, endothelial dysfunction, psychological and cognitive function.

Methods: We enrolled CKD patients (stage 3/5 KDIGO [Kidney Disease: Improving Global Outcomes]) and hemodialysis, peritoneal dialysis, and post-kidney transplant patients. Clinical, laboratory and instrumental assessments, including bioimpedance analysis, hand-grip strength, intima media thickness, flow-mediated dilation, and epicardial adipose tissue, were performed in addition to analysis of psychological and cognitive status by the Montreal Cognitive Assessment, Mini-Mental State Examination, and Geriatric Depression Scale.

Results: A total of 77 patients (43 male) with a mean age of 69.6 ± 9.85 y were studied. According to validated criteria (using bioimpedance analysis and hand-grip strength), the prevalence of sarcopenia was 49.4%. Sarcopenic patients had higher values of intima media thickness (P = 0.032) and epicardial adipose tissue (P = 0.012) and lower flow-mediated dilation (P = 0.002), total cholesterol (P = 0.005), and high-density lipoprotein cholesterol (P = 0.008) with respect to non-sarcopenic patients. We found higher Geriatric Depression Scale scores (P = 0.04) in sarcopenic patients, whereas we did not find differences between the two groups in Mini-Mental State Examination and Montreal Cognitive Assessment score.

Conclusion: Sarcopenia is highly prevalent in CKD/end stage renal disease patients and is associated with changes in early systemic indices of atherosclerosis and endothelial dysfunction, known as markers of worse prognosis.
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http://dx.doi.org/10.1016/j.nut.2018.12.005DOI Listing
June 2019

Clinical impact of vitamin D hydroxylation efficiency.

Minerva Med 2019 Jun 22;110(3):259-262. Epub 2019 Feb 22.

Unit of Nephrology, Umberto I Polyclinic Hospital, Rome, Italy.

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http://dx.doi.org/10.23736/S0026-4806.19.06029-4DOI Listing
June 2019

[Hyperphosphatemia in dialysis: which binder?]

G Ital Nefrol 2018 Sep;35(5)

Presidio Ospedaliero San Paolo, ASST Santi Paolo e Carlo, Milano, Università degli Studi di Milano.

Several studies have evidenced the association between high serum phosphorus concentrations and adverse events especially in patients on dialysis. Recent K-DIGO guidelines suggest lowering elevated phosphate levels toward the normal range. This goal should be achieved by combining dietary counseling, optimizing dialysis procedures and prescribing phosphate binders. Despite the availability of several binders, the "ideal" phosphate binder that combines high efficacy, low pills burden, minimal side effects and low cost is still not available. In clinical practice it is crucial to reach a high patient's compliance to therapy. The pill burden is the most relevant factor contributing to low compliance. This is the case of phosphate binder therapy that represents almost 50% of total pills prescribed to patients on dialysis. It has been evidenced an association between pills of phosphate binder and poor control of phosphorus and PTH. In recent years sucroferric oxyhydroxide is available as a new phosphate binder. Its peculiarity is an high phosphate binding capability that requires prescription of low number of pills per day. This characteristic has been confirmed by several randomized controlled trials. These trials have also evidenced that sucroferric oxyhydroxide may cause some gastrointestinal side effects. There is an ongoing study to confirm in "the real world" the incidence of side effects reported by controlled trials.
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September 2018

Multicenter study on parathyroidectomy (PTX) in Italy: preliminary results.

J Nephrol 2018 Oct 28;31(5):767-773. Epub 2018 Aug 28.

Nephrology Unit, Azienda Policlinico Umberto I, Rome, Italy.

Background: When medical therapy is unable to achieve biochemical control of secondary hyperparathyroidism, parathyroidectomy (PTX) is indicated, fortunately in a minority of patients. Thus, data on PTX prevalence and biochemical control are limited and, in particular in Italy, date back to 1999.

Methods: We designed a prospective, observational and multicenter study to collect data from dialysis units distributed throughout the Italian regions. Clinical data were collected with a dedicated data sheet.

Results: From January to December 2010, 149 Centers serving a total of 12,515 patients provided data on 528 living PTX cases (PTX prevalence = 4.2%). Prevalence was higher in hemo- than in peritoneal dialysis (4.5 vs. 1.9%, X = 21.52; p < 0.001), with non-significant regional differences (range 0.8-7.4%). PTX patients were younger (57.6 ± 12.5 vs. 67.1 ± 14.5 years; p < 0.001), more frequently female (56 vs. 38%, X = 68.05, p < 0.001) and had been on dialysis for a longer time (14.63 ± 8.37 vs. 4.8 ± 6.0 years, p < 0.001) compared to the 11,987 who did not undergo neck surgery. Median time since surgery was 6.0 years (3.0-9.0; 50%, IQR). The most frequent type of surgery was subtotal PTX (sPTX = 55.0%), significantly higher than total PTX (tPTX = 38.7%) or total PTX plus auto-transplantation (aPTX = 6.3%) (X = 5.18; Bonferroni post-hoc test, sPTX vs. tPTX + aPTX = p < 0.05). As for parathyroid hormone (PTH), calcium and phosphate control, cases targeting the KDOQI ranges were 18, 50.1 and 54.4%, respectively. The most prevalent biochemical condition was low PTH (62.7%).

Conclusion: PTX prevalence in Italy is stable compared to previous observations, is higher in hemodialysis than in peritoneal dialysis and results in a suboptimal biochemical control.
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http://dx.doi.org/10.1007/s40620-018-0527-xDOI Listing
October 2018

Obesity and kidney stone disease: a systematic review.

Minerva Urol Nefrol 2018 Aug 31;70(4):393-400. Epub 2018 May 31.

Unit of Urology, Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy -

Introduction: Currently, abdominal obesity has reached an epidemic stage and obesity represents an important challenge for worldwide health authorities. Epidemiologic studies have demonstrated that the stone risk incidence increases with Body Mass Index, through multiple pathways. Metabolic syndrome and diabetes are associated with an increased renal stones disease incidence. The aim of this systematic review was to investigate the prevalence, morbidity, risk factors involved in the association between obesity and urolithiasis.

Evidence Acquisition: The search involved finding relevant studies from MEDLINE, EMBASE, Ovid, the Cochrane Central Register of Controlled Trials, CINAHL, Google Scholar, and individual urological journals between January 2001 and May 2017. The inclusion criteria were for studies written in the English language, reporting on the association between obesity and urinary stones.

Evidence Synthesis: The underlying pathophysiology of stone formation in obese patients is thought to be related to insulin resistance, dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium oxalate stones are observed frequently in these patients. Insulin resistance is thought to alter the renal acid-base metabolism, resulting in a lower urine pH, and increasing the risk of uric acid stone disease. Obesity is also associated with excess nutritional intake of lithogenic substances and with an increase in urinary tract infection incidence. Recent studies highlighted that renal stone disease increases the risk of myocardial infarction, progression of chronic kidney disease, and diabetes. Contemporary, bariatric surgery has been shown to be associated with hyperoxaluria and oxalate nephropathy. Certainly, the many health risks of obesity, including nephrolithiasis, will add more burden on urologists and nephrologists.

Conclusions: Obesity related nephrolithiasis seems to necessitate weight loss as primary treatment, but the recognition of the associated complications is necessary to prevent induction of new and equally severe medical problems. The optimal approach to obesity control that minimizes stone risk needs to be determined in order to manage obesity-induced renal stones disease.
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http://dx.doi.org/10.23736/S0393-2249.18.03113-2DOI Listing
August 2018

Bone, inflammation and the bone marrow niche in chronic kidney disease: what do we know?

Nephrol Dial Transplant 2018 12;33(12):2092-2100

Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St Orsola Hospital, University of Bologna, Bologna, Italy.

Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase). Further, in recent years the close link between bone and inflammation has been better appreciated and a wide range of chronic inflammatory states (from rheumatoid arthritis to ageing) are being explored to discover the biochemical changes that ultimately lead to bone loss and OP. Also, it has been acknowledged that the concept of the bone-vascular axis may explain, for example, the relationship between bone metabolism and vessel wall diseases like atherosclerosis and arteriosclerosis, with potential involvement of a number of cytokines and metabolic pathways. A very important discovery in bone physiology is the bone marrow (BM) niche, the functional unit where stem cells interact, exchanging signals that impact on their fate as bone-forming cells or immune-competent haematopoietic elements. This new element of bone physiology has been recognized to be dysfunctional in diabetes (so-called diabetic mobilopathy), with possible clinical implications. In our opinion, ROD, the metabolic bone disease of renal patients, will in the future probably be identified as a cause of BM niche dysfunction. An integrated view of bone, which includes the BM niche, now seems necessary in order to understand the complex clinical entity of chronic kidney disease-mineral and bone disorders and its cardiovascular burden. Bone is thus becoming a recurrently considered paradigm for different inter-organ communications that needs to be considered in patients with complex diseases.
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http://dx.doi.org/10.1093/ndt/gfy115DOI Listing
December 2018

Oxygen Extraction Ratio (OER) as a Measurement of Hemodialysis (HD) Induced Tissue Hypoxia: A Pilot Study.

Sci Rep 2018 04 4;8(1):5655. Epub 2018 Apr 4.

Nephrology and Dialysis Unit, ICOT Hospital, Polo Pontino Sapienza University of Rome, Rome, Italy.

HD tissue hypoxia associates with organ dysfunctions. OER, the ratio between SaO and central-venous-oxygen-saturation, could estimate oxygen requirements during sessions, but no data are available. We evaluated OER behavior in 20 HD patients with permanent central venous catheter (CVC) as vascular access. Pre-HD OER (33.6 ± 1.4%; M ± SE) was higher than normal (range 20-30%). HD sessions increased OER to 39.2 ± 1.5% (M ± SE; p < 0.05) by 30' and to 47.4 ± 1.5% (M ± SE; p < 0.001) by end of treatment (delta 40%). During HD sessions of the long and short interdialytic intervals, OER values overlapped, suggesting no influence of patient's hydration status shifts. OER increased (p < 0.05) after 30' of isolated HD (zero ultrafiltration), but not during isolated ultrafiltration (zero dialysate flow), suggesting a role for blood-membrane-dialysate interaction, independent of volume reduction. In ten patients, individual variability of pre-HD OER was low and repeatable (maximum calculated difference over time 6.6%), and negatively correlated with HD-induced OER increments (r = 0.860; p < 0.005), suggesting a decline in the adaptive response along with resting OER increments. In 30 prevalent patients, adjusted multivariate analysis showed that pre-HD OER (HR = 0.88, CI 0.79-0.99, p = 0.028) and percent HD-induced OER (HR = 1.04, CI 1.01-1.08, p = 0.015) were both associated with mortality, with threshold values respectively <32% and >40%. In HD patients with CVC as vascular access, OER is a cheap, easily measurable and repeatable parameter useful to assess intradialytic hypoxia, and a potential biomarker of HD related stress and morbidity, helpful to recognize patients at increased risk of mortality.
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http://dx.doi.org/10.1038/s41598-018-24024-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884820PMC
April 2018

[Day of Prevention of Renal Diseases in Amatrice, Italy].

G Ital Nefrol 2018 Mar;35(2)

Presidente A.N.Di.P. Associazione Nazionale Dialisi Peritoneale Onlus "Enzo Siciliano".

Chronic kidney disease (CKD) is a very common condition and its prevalence is increasing worldwide. The CARHES study in Italy showed a prevalence of 6.5% in women and 7.5% in men. As a matter of fact, an early diagnosis is essential to slow down the progression and improve the renal and cardiovascular prognosis. For this purpose the A.N.Di.P. association (National Association of Peritoneal Dialysis-Onlus "Enzo Siciliano ") organized the DAY OF PREVENTION OF RENAL DISEASES which was held in AMATRICE the 15th of July 2017 called "WE START A NEW PATH OF LIFE TOGETHER". The goal of this initiative was to highlight and spread the importance of prevention and early diagnosis of renal disease in Amatrice and its surroundings. During this day, medical history, blood pressure measurements, urinalysis, serum creatinine and serum uric acid were carried out and we suggested to patients how to proceed, if necessary, in a further diagnostic and therapeutic process. We also recommended a correct lifestyle, based on healthy eating and regular physical activity. The choice to dedicate particular attention to the population tragically affected by the earthquake occurred to identify renal diseases, since they are a possible consequence of the earthquake, to draw attention to the importance of renal function and to demonstrate that simple routine checks may lead to an early diagnosis of unrecognized kidney diseases, also reducing cardiovascular risk.
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March 2018