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1.
J Nephrol ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193834

RESUMO

To add new molecular and pathogenetic insights into the biological machinery associated to kidney allograft fibrosis is a major research target in nephrology and organ transplant translational medicine. Interstitial fibrosis associated to tubular atrophy (IF/TA) is, in fact, an inevitable and progressive process that occurs in almost every type of chronic allograft injury (particularly in grafts from expanded criteria donors) characterized by profound remodeling and excessive production/deposition of fibrillar extracellular matrix (ECM) with a great clinical impact. IF/TA is detectable in more than 50% of kidney allografts at 2 years. However, although well studied, the complete cellular/biological network associated with IF/TA is only partially evaluated. In the last few years, then, thanks to the introduction of new biomolecular technologies, inflammation in scarred/fibrotic parenchyma areas (recently acknowledged by the BANFF classification) has been recognized as a pivotal element able to accelerate the onset and development of the allograft chronic damage. Therefore, in this review, we focused on some new pathogenetic elements involved in graft fibrosis (including epithelial/endothelial to mesenchymal transition, oxidative stress, activation of Wnt and Hedgehog signaling pathways, fatty acids oxidation and cellular senescence) that, in our opinion, could become in future good candidates as potential biomarkers and therapeutic targets.

2.
Nutrients ; 12(3)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32183500

RESUMO

Nephrolithiasis is a common medical condition influenced by multiple environmental factors, including diet. Since nutritional habits play a relevant role in the genesis and recurrence of kidney stones disease, dietary manipulation has become a fundamental tool for the medical management of nephrolithiasis. Dietary advice aims to reduce the majority of lithogenic risk factors, reducing the supersaturation of urine, mainly for calcium oxalate, calcium phosphate, and uric acid. For this purpose, current guidelines recommend increasing fluid intake, maintaining a balanced calcium intake, reducing dietary intake of sodium and animal proteins, and increasing intake of fruits and fibers. In this review, we analyzed the effects of each dietary factor on nephrolithiasis incidence and recurrence rate. Available scientific evidence agrees on the harmful effects of high meat/animal protein intake and low calcium diets, whereas high content of fruits and vegetables associated with a balanced intake of low-fat dairy products carries the lowest risk for incident kidney stones. Furthermore, a balanced vegetarian diet with dairy products seems to be the most protective diet for kidney stone patients. Since no study prospectively examined the effects of vegan diets on nephrolithiasis risk factors, more scientific work should be made to define the best diet for different kidney stone phenotypes.

3.
Urolithiasis ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980850

RESUMO

Due to the difficulty of collecting 24-h urines in the stone-forming patient, some authors have suggested other types of urine collection, but their usefulness is not yet well studied. The objective of this study is to evaluate the variation of urinary supersaturation (SS) throughout the day and to analyze whether timed urine collections offer accurate information. 48 urine samples were collected from 12 young adults. Each 24-h urine was collected on 7 2-h urine fractions and a 10-h overnight sample. Solute concentrations and SS for calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA) were determined. Linear regression and relative importance of predictors were used to determine the percentage of R2 attributed to each timed collection (individual SS). 43 24-h urine samples were included in the study. The highest SS values were: for CaOx, night period and first morning urine; for CaP, between 2 and 6 pm and at night; for UA, between 8 am and 12 pm. For CaOx, the SS from the samples between 8 pm and 8 am accounted for more than 40% of the R2; for CaP, the results were more equally distributed throughout the day, and for UA, the SS values from 12 to 4 pm accounted for more than 45% of the observed variability. In conclusion, urinary SS varies throughout the day, being higher for CaOx and CaP at night, and in the early morning for UA. For CaOx and UA, the overnight and 12-4 pm urine samples, respectively, contribute most to the variability observed in the SS of 24-h urine.

4.
BMC Nephrol ; 21(1): 23, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992222

RESUMO

BACKGROUND: Estimating CKD prevalence is difficult. Information on CKD prevalence is rather scanty in Italy and available figures come from surveys in selected geographical areas. Administrative data have been already demonstrated to be an effective tool in estimating the epidemiological burden of diseases, however there is limited experience in literature as far as CKD is concerned. METHODS: The aim of this study is to develop an algorithm based on regional Health Administrative Databases to identify individuals with CKD and provide estimates of disease prevalence in Lazio Region (Italy); about 5.500.000 inhabitants in 2017. A population-level analysis based on a record-linkage strategy using data from Health Administrative Databases has been applied in Lazio Region. CKD cases were identified between January 1, 2012 and December 31, 2017 using Outpatient Specialist Service Information System, Hospital Discharge Registry, Ticket Exemption Registry and Drug Dispensing Registry. Age-specific and standardized prevalence rates were calculated by gender. CKD cases were classified as higher and lower severity. RESULTS: The algorithm identified 99,457 individuals with CKD (mean age 71 years, 55.8% males). The exclusive contributions of each regional source used were: 35,047 (35.2%) from Outpatient Specialist Service Information System, 27,778 (27.9%) from Hospital Discharge Registry, 4143 (4.2%) from Ticket Exemption Registry and 463 (0.5%) from Drug Dispensing Registry; 5.1% of cases were found in all databases. The standardized prevalence rate at December 31, 2017 was 1.76, 2.06% for males and 1.50% for females. The prevalence increased with age, rising from 0.33% (age 0-18) up to 14.18% (age 85+) among males and from 0.25% up to 8.18% among females. The proportion of CKD individuals with lower severity disease was 78.7% in both genders. CONCLUSIONS: The proposed algorithm represents a novel tool to monitor the burden of CKD disease, that can be used by the regional government to guide the development and implementation of evidence-based pathways of care for CKD patients. The high prevalence of people with CKD of lower severity should be carefully considered in order to promote diagnosis and optimal management at early stages.

5.
J Nephrol ; 33(1): 167-176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31471818

RESUMO

BACKGROUND: Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist's expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys. METHODS: 46 discarded kidneys were identified with their corresponding biopsies. The biopsies were reviewed by three general and two specialist pathologists, blinded to the original report, according to Remuzzi score. The intraclass correlation coefficient (ICC) was calculated for both groups. Discarded kidneys were scored according to Remuzzi score by a single specialist pathologist. Biopsies and organs were compared by Wilcoxon signed rank test. Weighted κ coefficients between biopsy and organ scores were also calculated. RESULTS: Specialist pathologists achieved higher values of ICC, reaching excellent or good agreement in most of the parameters, while general pathologists values were mainly fair or good. On whole organs, scores were consistently lower than biopsies, with a significant difference in most of the parameters. Weighted κ coefficient was slight or fair for most of the parameters. CONCLUSIONS: Our data suggests that the creation of a pool of specialist pathologists would improve organ utilization. Moreover, biopsies are not representative of the whole organ. As the Remuzzi score on biopsy is a major reasons for discard, a quota of transplantable kidneys may be erroneously discarded. Refinement in Remuzzi cut-offs based on expert reporting and recognition of sampling error of biopsies in correlation with clinical outcome data should be undertaken.

6.
Cytokine ; 125: 154823, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31541903

RESUMO

BACKGROUND: Little is known about the underlying aetiology of fatigue in haemodialysis (HD) patients apart from a significant association and overlapping symptomatology with depressive symptoms. Growing evidence exists for the involvement of the immune system, by pro-inflammatory cytokines, in the development of fatigue in other inflammatory diseases. In HD patients, increased exposure to bacterial endotoxins may contribute to an inflammatory response and may potentially lead to fatigue. We therefore aimed (i) to assess the interrelationship between serum endotoxin (EA) levels, interleukin-6 (IL-6) levels and fatigue in HD patients; (ii) to evaluate whether there is a relationship between depressive symptoms and inflammation as well and (iii) to what extent depressive symptoms and fatigue are related to each other. METHODS: Fatigue and depressive symptoms in daily life were assessed in 59 individuals using the SF-36 vitality subscale and the Geriatric Depression Scale. Blood samples were collected on a mid-week dialysis session to determine EA levels, through the Endotoxin Activity Assay (EAA™), and IL-6 concentrations, through the commercially available Abcam ELISA (Enzyme-Linked Immunosorbent Assay) kit. RESULTS: EA, IL-6 levels and depressive symptoms were significantly correlated with fatigue. EA levels and depressive symptoms were significant predictors of fatigue, explaining 31% of its variance. However, EA and IL-6 were not significantly associated with depression. CONCLUSIONS: Fatigue in HD patients may be related to endotoxemia and inflammation through IL-6. Furthermore, fatigue is significantly associated with depressive symptoms. Future research into the causal interrelationship of inflammation, fatigue and depression in HD patients might lead to potential targets for therapeutic strategies.

7.
Int J Mol Sci ; 20(21)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694344

RESUMO

Medullary sponge kidney (MSK) disease is a rare and neglected kidney condition often associated with nephrocalcinosis/nephrolithiasis and cystic anomalies in the precalyceal ducts. Little is known about the pathogenesis of this disease, so we addressed the knowledge gap using a proteomics approach. The protein content of microvesicles/exosomes isolated from urine of 15 MSK and 15 idiopathic calcium nephrolithiasis (ICN) patients was investigated by mass spectrometry, followed by weighted gene coexpression network analysis, support vector machine (SVM) learning, and partial least squares discriminant analysis (PLS-DA) to select the most discriminative proteins. Proteomic data were verified by ELISA. We identified 2998 proteins in total, 1764 (58.9%) of which were present in both vesicle types in both diseases. Among the MSK samples, only 65 (2.2%) and 137 (4.6%) proteins were exclusively found in the microvesicles and exosomes, respectively. Similarly, among the ICN samples, only 75 (2.5%) and 94 (3.1%) proteins were exclusively found in the microvesicles and exosomes, respectively. SVM learning and PLS-DA revealed a core panel of 20 proteins that distinguished extracellular vesicles representing each clinical condition with an accuracy of 100%. Among them, three exosome proteins involved in the lectin complement pathway maximized the discrimination between MSK and ICN: Ficolin 1, Mannan-binding lectin serine protease 2, and Complement component 4-binding protein ß. ELISA confirmed the proteomic results. Our data show that the complement pathway is involved in the MSK, revealing a new range of potential therapeutic targets and early diagnostic biomarkers.

9.
Kidney Blood Press Res ; 44(5): 1306-1312, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597132

RESUMO

INTRODUCTION: Dent's disease is a rare X-linked recessive disorder that manifests in childhood or early adulthood and can lead to end-stage renal disease (ESRD). It occurs in males, who are hemizygous. In patients who develop ESRD, a deceased donor kidney transplant cures the disease. Females are obligate carriers of the mutated gene, and some show a mild Dent's disease phenotype. There may be reason for concern when considering a female obligate carrier (i.e., the mother) for kidney donation because of the risk of kidney function deterioration. CASE PRESENTATION: We describe the first successful kidney transplantation involving a patient with type 1 Dent's disease and ESRD given a kidney by an obligate carrier of the gene mutation, his mother. CONCLUSIONS: After careful assessment of the female obligate carriers, intrafamilial kidney donation in Dent's disease type 1 is feasible. No deteriorating renal function in the donor was observed.

10.
J Am Soc Nephrol ; 30(10): 1785-1805, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31506289

RESUMO

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.

11.
Am J Kidney Dis ; 74(6): 736-741, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31543288

RESUMO

RATIONALE & OBJECTIVE: The intestinal microbiome may affect urinary stone disease by modulating the amount of oxalate absorbed from the intestine and subsequently excreted in urine. This study sought to explore the association between antibiotics, which alter the intestinal microbiota, and risk for urinary stone disease. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 5,010 women in the Nurses' Health Study (NHS) I and II who had collected 24-hour urine samples. EXPOSURES: Use of antibiotics during the age range of 40 to 49 (NHS II), 40 to 59 (NHS I), and 20 to 39 years (both cohorts). OUTCOMES: Incident symptomatic urinary stone disease; urine composition. ANALYTICAL APPROACH: Cause-specific hazards regression adjusted for age, body mass index, comorbid conditions, thiazide use, and dietary factors. Follow-up was censored at the time of asymptomatic kidney stones, cancer, or death. RESULTS: Cumulative use of antibiotics for a total of 2 or more months during the age range of 40 to 49 years (NHS II) and 40 to 59 years (NHS II) was associated with significantly higher risk for developing incident stones compared with no use (pooled HR, 1.48; 95% CI, 1.12-1.96). Similar results were found for the period of 20 to 39 years (pooled HR, 1.36; 95% CI, 1.00-1.84). Results were unchanged after excluding participants who reported urinary tract infection with their stone event or as the most common reason for antibiotic use. Urine composition was generally similar across antibiotic groups except for marginally lower urine pH and citrate values among those taking antibiotics for 2 or more months. LIMITATIONS: Observational design; lack of information for type of antibiotic used; relatively large span of time between antibiotic use and urine collection. CONCLUSIONS: Use of antibiotics for more than 2 months in early adulthood and middle age is associated with higher risk for urinary stone disease in later life.

12.
Ann Ist Super Sanita ; 55(3): 205-208, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553311

RESUMO

BACKGROUND: The combination of infrared spectroscopy and morphological analysis significantly improves the urinary stone analysis. In addition to common urinary stones, it is not unusual to encounter spurious or factitious stones that, if not appropriately identified, can lead to errors in the diagnosis. In this study, we show the importance of Infrared Spectroscopy and the morphological analysis, for determining the presence of drugs crystals or atypical components in the calculi. METHODS: 1041 urinary stones were analyzed by morphocostitutional analysis, in addition the rare stones were analyzed by chemical spot test analysis. RESULTS: Among 1041 calculi analyzed, 1018 had a known composition, 23 samples were stones with rare composition or fake urinary stones. CONCLUSIONS: Infrared spectroscopy (FT-IR), allows to identify, theoretically, any substance, including drug-containing calculi or calculi with unusual composition and identify false stones. This is mandatory to treat patients affected by urolithiasis with a personalized clinical approach.


Assuntos
Cálculos Urinários/química , Cálculos Urinários/ultraestrutura , Cristalização , Humanos , Microscopia , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Adv Ther ; 36(11): 3253-3264, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31489572

RESUMO

INTRODUCTION: Patients with chronic kidney disease on hemodialysis (HD) are at high risk of developing both iron deficiency and iron deficiency anemia (IDA). The administration of intravenous iron therefore represents the standard of care for the management of anemia in this patient setting. METHODS: A retrospective cohort of 38 HD patients in Italy was analyzed to assess the clinical and economic implications of switching from intravenous ferric gluconate (FG) to ferric carboxymaltose (FCM) on achievement of adequate hemoglobin (Hb) values and iron balance. The total observational period for each patient was 12 months, 6 months before and 6 months after switching to iron FCM. The pharmacoeconomic analysis considered the hospital perspective and the consumption of iron, blood transfusions and erythropoiesis-stimulating agents (ESAs), including healthcare personnel time. RESULTS: Switching from FG to FCM in dialysis adult patients with IDA allows a cost reduction per patient/month in the range €14-46, considering the use of biosimilar ESA or originator ESA, respectively. The percentage of patients with Hb target values increased from 63% to 82%, considering the entire observation period. In addition, other clinical parameters (ferritin, transferrin saturation, erythropoietin resistance index) improved after switching from FG to FCM. CONCLUSION: FCM in HD patients was shown to provide a favorable efficacy profile over FG, with a lower cost per patient, mainly driven by a consistent reduction of ESA consumption. FUNDING: Vifor Pharma Italia Srl.

14.
Intern Emerg Med ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388894

RESUMO

The aim of this observational retrospective cohort study was to analyze the association between hyperchloremia and serum chloride variation with in-hospital acute kidney injury (AKI) and mortality in a general, no-ICU hospitalized population. We performed a retrospective study on inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 2010 and December 2014 with inclusion of adult patients with at least two values available for chloride, sodium and creatinine. Hyperchloremia was defined as serum chloride concentration ≥ 108 mmol/L (moderate hyperchloremia: chloremia between 108-110 mmol/L, severe hyperchloremia: chloremia > 110 mmol/L). According to the time of onset of the electrolyte disturbance, hyperchloremia was then classified as hospital acquired (HA) and community acquired (CA). In patients with HA-hyperchloremia, chloride variation (ΔCl) was calculated. In-hospital AKI was defined according to creatinine kinetics criteria occurring 48 h after hospital admission. Logistic regression analysis was used to evaluate the association between the exposures of interest and in-hospital AKI and mortality. A total of 24,912 hospital admissions met the inclusion criteria. Regression analyses showed that only severe HA-hyperchloremia was associated with increased risk of in-hospital AKI [odds ratio (OR) 2.60, 95% confidence interval (CI) 1.58, 4.30, p value < 0.001] and death (OR 3.89, 95% CI 2.11, 7.18, p value < 0.001). With increasing ΔCl, the OR of in-hospital AKI increased progressively (p value for trend = 0.005). In conclusion, severe hyperchloremia is an independent predictor for in-hospital AKI and mortality; HA-hyperchloremia is more detrimental for patient outcome; higher ΔCl from hospital admission is associated with increased risk of AKI.

15.
Kidney Blood Press Res ; 44(4): 604-614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31330509

RESUMO

BACKGROUND/AIMS: Aim of our study was to describe the association between natremia (Na) fluctuation and hospital mortality in a general population admitted to a tertiary medical center. METHODS: We performed a retrospective observational cohort study on the patient population admitted to the Fondazione Policlinico A. Gemelli IRCCS Hospital between January 2010 and December 2014 with inclusion of adult patients with at least 2 Na values available and with a normonatremic condition at hospital admission. Patients were categorized according to all Na values recorded during hospital stay in the following groups: normonatremia, hyponatremia, hypernatremia, and mixed dysnatremia. The difference between the highest or the lowest Na value reached during hospital stay and the Na value read at hospital admission was used to identify the maximum Na fluctuation. Cox proportional hazards models were used to estimate hazard ratios (HRs) for in-hospital death in the groups with dysnatremias and across quartiles of Na fluctuation. Covariates assessed were age, sex, highest and lowest Na level, Charlson/Deyo score, cardiovascular diseases, cerebrovascular diseases, dementia, congestive heart failure, severe kidney disease, estimated glomerular filtration rate, and number of Na measurements during hospital stay. RESULTS: 46,634 admissions matched inclusion criteria. Incident dysnatremia was independently associated with in-hospital mortality (hyponatremia: HR 3.11, 95% CI 2.53, 3.84, p < 0.001; hypernatremia: HR 5.12, 95% CI 3.94, 6.65, p < 0.001; mixed-dysnatremia: HR 4.94, 95% CI 3.08, 7.92, p < 0.001). We found a higher risk of in-hospital death by linear increase of quartile of Na fluctuation (p trend <0.001) irrespective of severity of dysnatremia (HR 2.34, 95% CI 1.55, 3.54, p < 0.001, for the highest quartile of Na fluctuation compared with the lowest). CONCLUSIONS: Incident dysnatremia is associated with higher hospital mortality. Fluctuation of Na during hospital stay is a prognostic marker for hospital death independent of dysnatremia severity.


Assuntos
Mortalidade Hospitalar , Sódio/metabolismo , Adulto , Idoso , Estudos de Coortes , Feminino , Hospitalização , Humanos , Hipernatremia , Hiponatremia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais
16.
Semin Cancer Biol ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31348993

RESUMO

Heparanase (HPSE) is an endoglycosidase that catalyses the cutting of the side chains of heparan-sulphate proteoglycans (HS), thus determining the remodelling of the extracellular matrix and basement membranes, as well as promoting the release of different HS-related molecules as growth factors, cytokines and enzymes. Ever since the HPSE was identified in the late 1980s, several experimental studies have shown that its overexpression was instrumental in increasing tumor growth, metastatic dissemination, angiogenesis and inflammation. More recently, HPSE involvment has also been demonstrated in mediating tumor-host crosstalk, in inducing gene transcription, in the activation of signaling pathways and in the formation of exosomes and in autophagy. All of these activities (enzymatic and non-enzymatic) together make heparanase a multifunctional molecule that increases the aggressiveness and chemo-resistance of tumor cells. Conversely, heparanase gene-silencing or tumor treatment with compounds that inhibit heparanase activity have been shown to significantly attenuate tumor progression in different animal models of tumorigenesis, further emphasizing the therapeutic potential of anti-heparanase therapy for several types of neoplasms. This review focuses on present knowledge and recent development in the study of heparanase in cancer progression as well as on novel mechanisms by which heparanase regulates tumor metastasis and chemo-resistance. Moreover, recent advances in strategies for its inhibition as a potential therapeutic option will be discussed.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31204242

RESUMO

PURPOSE: Little is known on the impact of contrast-induced acute kidney injury (CI-AKI) on mid- and long-term renal function after percutaneous coronary procedure. The aim of the study was to investigate the incidence of persistent renal damage (PRD) after CI-AKI in a cohort of patients undergoing coronary angiography and/or intervention. Moreover, we sought to assess the predictive value of small creatinine change at 12-24 h (SCrΔ%12-24 h) from contrast exposure in predicting CI-AKI and PRD. METHODS: Complete clinical and biochemical data of 731 patients were retrospectively analyzed at sequential time intervals at baseline, 12-24 h and 48-72 h from the procedure. Data at 30 ±â€¯10 days and 12-24 months were available in 59% and 49% of the cases respectively. Logistic regression was used to assess variables associated with CI-AKI and PRD. ROC analysis was used to test the diagnostic accuracy of SCrΔ%12-24 h in predicting CI-AKI and PRD. RESULTS: CI-AKI occurred in 130/731 patients (17.8%). At 30 ±â€¯10 days PRD occurred in 54.8% patients who developed CI-AKI. A SCrΔ%12-24 h >5% demonstrated independent predictive value (OR = 1.05, CI = 1.04-1.06, p < 0.001) and fair accuracy (AUC = 0.80, CI = 0.77-0.84) for CI-AKI. CONCLUSION: CI-AKI was associated with PRD in >50% of the cases in this single centre cohort. A small and early SCrΔ%12-24 h demonstrated high predictive value for CI-AKI and may be used as a useful tool to unmask a group of patients at risk for PRD after percutaneous coronary procedures.

18.
Eur J Pharmacol ; 859: 172494, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31238062

RESUMO

To better define the biological impact of immunosuppression on peripheral blood mononuclear cells (PBMC), we employed RNASeq analysis to compare the whole transcriptomic profile of a group of renal transplant recipients undergoing maintenance treatment with Everolimus (EVE) with those treated with Tacrolimus (TAC). Then, obtained results were validated by classical biomolecular methodologies. The statistical analysis allowed the identification of four genes discriminating the 2 study groups: Sushi Domain Containing 4 (SUSD4, P = 0.02), T Cell Leukemia/Lymphoma 1A (TCL1A, P = 0.02), adhesion G protein-coupled receptor E3 (ADGRE3, P = 0.01), Immunoglobulin Heavy Constant Gamma 3 (IGHG3, P = 0.03). All of them were significantly down-regulated in patients treated with EVE compared to TAC. The Area under Receiver Operating Characteristic (AUROC) of the final model based on these 4 genes was 73.1% demonstrating its good discriminative power. RT-PCR and ELISA validated transcriptomic results. Additionally, an in vitro model confirmed that EVE significantly down-regulates (P<0.001) TCL1A, SUSD4, ADGRE3 and IgHG3 in PBMCs as well as in T cells and monocytes isolated from healthy subjects. Taken together, our data, revealed, for the first time, a new four gene-based transcriptomic fingerprint down-regulated by EVE in PBMCs of renal transplant patients that could improve the available knowledge regarding some of the biological/cellular effects of the mTOR-Is (including their antineoplastic and immune-regulatory properties).


Assuntos
Everolimo/farmacologia , Perfilação da Expressão Gênica , Imunossupressores/farmacologia , Transplante de Rim/efeitos adversos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Tacrolimo/farmacologia , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade
19.
J Nephrol ; 32(4): 589-594, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165423

RESUMO

Kidney stone disease is associated with cardiovascular outcomes; it is unclear whether stone composition is associated with differential cardiovascular risk. To analyze such association, we performed a cross-sectional study in which data were collected for patients who underwent at least one stone composition analysis from January 01 2015 to May 30 2018. The original dataset was linked with the imaging database to identify those patients with at least one abdominal CT scan examination during the period of interest. In total, 180 patients were included. The outcome of interest was the presence of any abdominal aortic calcifications (AAC) computed from CT scans. There were 108 (60.0%) patients with AAC. Calcium phosphate content was associated directly with eGFR, inversely with age, and was higher among females. Uric acid content was associated directly with age and inversely with eGFR, was higher among males, patients with diabetes and high blood pressure. After adjustment for age and gender, there was a significant association between calcium phosphate content and AAC (OR 1.25, 95% CI 1.00, 1.56, p = 0.045). No interaction by gender was found between calcium phosphate content and AAC (p = 0.84). In conclusion, we demonstrated a significant direct association of AAC and the amount of calcium phosphate was found, suggesting an increased cardiovascular risk. Our study suggests that some subtypes of kidney stone disease deserve a closer cardiovascular risk assessment.

20.
Nutrients ; 11(5)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137803

RESUMO

Kidney stone disease should be viewed as a systemic disorder, associated with or predictive of hypertension, insulin resistance, chronic kidney disease and cardiovascular damage. Dietary and lifestyle changes represent an important strategy for the prevention of kidney stone recurrences and cardiovascular damage. A full screening of risk factors for kidney stones and for cardiovascular damage should be recommended in all cases of calcium kidney stone disease, yet it is rarely performed outside of stone specialist clinics. Many patients have a history of kidney stone disease while lacking a satisfactory metabolic profile. Nonetheless, in a real-world clinical practice a rational management of kidney stone patients is still possible. Different scenarios, with different types of dietary approaches based on diagnosis accuracy level can be envisaged. The aim of this review is to give patient-tailored dietary suggestions whatever the level of clinical and biochemistry evaluation. This can help to deliver a useful recommendation, while avoiding excessive dietary restrictions especially when they are not based on a specific diagnosis, and therefore potentially useless or even harmful. We focused our attention on calcium stones and the different scenarios we may find in the daily clinical practice, including the case of patients who reported renal colic episodes and/or passed stones with no information on stone composition, urinary risk factors or metabolic cardiovascular risk factors; or the case of patients with partial and incomplete information; or the case of patients with full information on stone composition, urinary risk factors and metabolic cardiovascular profile.


Assuntos
Bebidas , Cálcio na Dieta/administração & dosagem , Ingestão de Líquidos , Exercício , Cálculos Renais/prevenção & controle , Comportamento de Redução do Risco , Bebidas/efeitos adversos , Cálcio na Dieta/efeitos adversos , Cálcio na Dieta/metabolismo , Humanos , Cálculos Renais/epidemiologia , Cálculos Renais/metabolismo , Fatores de Proteção , Medição de Risco , Fatores de Risco
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