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Background: Ef cacy of chlorthalidone (CT) and thiazides is considered low in low kidney function (LKF). Methods: A parallel-arm,non-inferiority study was done on CT effects in hypertensives with LKF and hypertensives without LKF (Italian Drug Agency Registry ID#671).Study design included:screening visit,baseline visit, 8-week CT treatment with visits at week 1,2,4,6 and 8.The screening visit selected patients on antihypertensive treatment with uncontrolled hypertension (SBP140 or DBP90),ages 25-74,complete diagnostic workup. Eligible patients were prescribed lab evaluations and re-examined after 1-2 week (baseline).Exclusion criteria were treatment with diuretics,CT contraindications,refused consent,SBP180 or DBP110, severe co-morbidities.At baseline, 25 mg CT was prescribed on the top of ongoing treatments to 60 patients with LKF (eGFR by CKD-Epi equation stably 0.17). Week 8 changes were signi cant for eGFR (LKF and Control, mL/min= -2 and -5; -4/-1 and -7/-3), serum potassium (mmol/L= -0.2 and -0.2; -0.3/-0.1 and -0.3/-1), serum uric acid (mg/dL= +0.8 and +0.9; +0.5/+1.1 and +0.7/+1.1). Adverse events incidence was 13.3% in both groups. The commonest events were serum sodium

Background: Exposure to microgravity results in alterations of renal function, uid redistribution and bone loss which contributes to the potential risk of renal stone formation. Hypercalciuria is recognized as a condition predisposing to calcium nephrolitiasis and long-term space ights cause bone loss coupled to a rise of urinary calcium excretion. Methods: AQP2 excretion was measured by ELISA in urines collected from healthy volunteers participating at the studies. Results: We recently demonstrated that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2) mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration and reducing calcium saturation. To analyze alteration of renal water handling during microgravity, we evaluated two ground-based analog of space ight, thermoneutral water immersion and bed rest. AQP2 excretion and diuresis were measured in two separated studies mimicking acute adaptation (6 hours water immersion) or chronic adaptation (35 days bed rest) to microgravity. Water immersion resulted in a signi cant increase in urinary output apparently not related to AQP2 alteration and manly due to reduced vasopressin secretion. On the other hand 35 days bed rest resulted in an increase in urinary calcium, which coincided with a signi cant decrease in AQP2 excretion (645±7.4 fmol/ml to 569±10.3 fmol/ml), which is expected to result in urine dilution reducing the risk of calcium saturation. Conclusions: Our data indicate that calciuria and water balance have to be strictly controlled during microgravity and long-term bed rest as key elements for the risk of kidney stone formation.

BACKGROUND: Relative survival, a methodology previously used in epidemiologic studies of cancer, compares the observed survival of a patient cohort with expected survival derived from general population life tables. We examined relative survival in patients treated by long-term dialysis in the Italian Dialysis and Transplantation Registry in order to determine the prognosis of dialysis patients. STUDY DESIGN: Cohort study drawn from a registry. SETTING & PARTICIPANTS: Patients enrolled in the Italian Dialysis and Transplantation Registry. FACTORS: Sex, age, primary kidney disease, renal replacement therapy modality, and main comorbid conditions. OUTCOMES: Death from any cause. MEASUREMENTS: Relative survival ratio (the ratio of observed survival in the population of interest to the survival expected given the age- and period-specific mortality of the general population) and excess mortality rate (difference between observed and expected mortality rates). RESULTS: In January 2000 to December 2008, a total of 27,642 patients were included. The 5-year relative survival estimate was 55.6% (95% CI, 54.7%-56.5%). The excess mortality rate showed a peak at 3 months (21 deaths/100 patient-years), then decreased, becoming constant from the end of year 1 to year 8, with leveling off at about 10 deaths/100 patient-years. Older age, systemic diseases, and diabetes showed the strongest association with excess mortality. Peritoneal dialysis was associated with a lower relative excess risk in only the first year of treatment. LIMITATIONS: The patient cohort comprises about half the Italian patients beginning dialysis therapy in the period. CONCLUSIONS: This study highlights the applicability of relative survival methods in dialysis patients. This measure allows estimation of disease prognosis and severity comparisons among chronic diseases. The excess mortality rate appears to be a more sensitive and informative measure than the simple proportion of survivors.

The authors describe a Retroperitoneal De Differentiated LipoSarcomas (DDLs), that for its clinical behavior shows peculiar characteristics and original aspects: typical is the recurrence due to local invasiveness, but absolutely original seems to be the surviving time, maybe correlated to its histological evolution (dedifferentiation from leiomyosarcoma to liposarcoma) and an interesting correlation from the tumor recurrence and the glycemic curve first and after the surgical treatments.

Sleeping disorders are very common in patients with chronic kidney disease on dialysis (CKD5D) and are an emerging risk factor able to predict mortality. Parathyroid hormone (PTH) although considered a pivotal uremic toxin has rarely been associated with sleep disorders in uremia. In a study from our laboratory PTH concentrations failed to distinguish patients with sleep disorders from those without. In a study performed by Chou et al a 97% prevalence of insomnia was found in patients undergoing hemodialysis requiring parathyroidectomy. Surgery reduced PTH and increased sleeping hours within 3 months. The aim of this study was to study the effects of parathyroidectomy on the sleep disorders of insomniacs on maintenance hemodialysis. The study was performed in 16 insomniac patients on maintenance hemodialysis who successfully underwent surgery with autotransplantation of autologous parathyroid tissue (40 mg) under the skin of the forearm. Patients (5 F and 11 M) were studied from 1 month before surgery to 1 year after. Sleep disorders were assessed by means of a 27-item questionnaire--Sleep Disorder questionnaire (SDQ)--that identified sleeping disorders according to Diagnostic and Statistical Manual of Mental Disorders - IV Edition (DSM-IV) criteria. The Charlson Comorbidity Index (CCI) was also measured along with systolic and diastolic blood pressure, Hb, PTH, Ca, P. A 95.5% prevalence of sleep disorders was found pre operatively. Patients slept 4.90+/-1.2 hours, Ca averaged 10.09+/-0.54 mg/dL, Phosphate 5.5+/-1.93, CCI 9.8+/-1.1, PTH 1498+/-498 ng/mL. After 1 year follow-up 2 out 16 patients had normal sleep, 6 out 16 patients had subclinical sleep disorders and 8 remained insomniacs (p=0.008, Mc Nemar Test for paired data, insomniacs vs. no disturbance + subclinical disorders). Sleeping hours increased up to 6.0+/-1.24 (p

We need a new health care system that is based on patients' needs. The present cadre of health managers who acquired power by cutting expenditures must be removed from office. We need to educate a new cadre of health managers who are 1) convinced that safeguarding health does not use up the resources of the next generations; 2) capable of switching the system from curative to preventive medicine; and 3) able to reinforce clinical research. Such principles have been recently adopted by the French President Sarkozy in devising the national health care program.

CKD is utilized as a paradigm, a chronic disease which allows decades of life conquered with great effort through a machine, a life with many losses and many dependencies. We must understand the patient's needs, which are not related to availability of drugs and machines and hospitals. We cannot provide good medical care with the limited amount of national product devoted to health care. Society is much older than ever before. We need a new cadre of economists working on health care with vision and ability, keeping in mind that there are no resources and there are no expenses which can be cut in medical care nowadays. We have to switch from curative medicine towards prevention, by implementing clinical research, bearing in mind that in the Western world, democracy was granted through the correct allocation of resources. The search for happiness and good quality of life are old concepts born in the Mediterranean area over the centuries, starting with Hesiod and Homer, and sleep and dreams were being investigated centuries before Freud was born. © Società Italiana di Nefrologia.

BACKGROUND: The classification, diagnostic recognition and surgical treatment of breast lesions at risk of neoplastic transformation represent some of the most important objectives in breast research. Attention has been focused on lesions at risk of neoplastic transformation in breast pathology, such as: atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), multiple intraductal papilloma and sclerosing adenosis. METHODS: Our experience regards activity carried out from 1996 to 2001; the diagnostic approach included routine performance of echotomographic examination, mammography screening indicated in women >40 and, in selected cases, in women 40 and, in selected cases, in women

FOLIA MEDICA

The paper deals with the use of estimated glomerular filtration rate (eGFR) as marker of low kidney function in the population. Data were collected on serum creatinine, other laboratory indices, blood pressure, and medical history in a population sample of 2083 men and 2491 women aged between 18-95 years. Estimated GFR was calculated by the equation of Modification Diet in Renal Disease study. Disorders included in the analysis were hypertension, cardiovascular disease, high serum uric acid, high serum phosphorus/low serum calcium, anemia, and high serum potassium. Prevalence of low eGFR (eGFR60 mL/min per 1.73 m2) increased with age: from1% for ages 18-24 to30% for agesor =75, P0.001. On the basis of these data, prevalence of low eGFR in the adult Italian population was 5.7% for men (n=1.3 million, 95%CI = 1.1/1.5) and 6.2% for women (n=1.5 million, 95%CI = 1.3/1.8). Disorders associated with kidney dysfunction were two or more in the majority of persons with low eGFR and were more frequent with lower eGFR (p0.001). Previous diagnosis of kidney disease was reported by less than 5% in people with low eGFR and was progressively higher with higher serum creatinine or with number of associated disorders (p0.03). Hypertension tended to be more frequently treated but not more frequently controlled in people with low eGFR. Data support the use of eGFR to identify people with or at risk of low kidney function. Awareness of kidney disease is low in people with low eGFR unless serum creatinine is very high or they have many associated disorders.

FOLIA MEDICA

Water was a prominent substance with Pythagoras, Xenophanes, Heraclitus and Parmenides, who flourished in the years 530-490 BC. The basic Pythagorean elements were earth and fire, and between them there were 2 intermediate entities (water and air), which were instrumental and indispensable components of specific solids. All things are a blend of different elements. For Xenophanes, "All things that come into being and grow are earth and water," "We all originated from earth and water" and "And in certain caves water drips down." For Heraclitus water is an ambivalent substance: " One cannot bathe in the same river on two occasions." "The sea is the safest and the most polluted water, for fish it is healthy and gives life, for men it is unhealthy and causes death." "Fire experiences the death of earth, air experiences that of fire, water experiences the death of air and the earth that of water." Parmenides was a man who sought the truth through reasoning and was, according to Hegel, the founder of Western philosophy. He built a dualist theory of the cosmos based on heat and cold, fire and earth - the former as a cause, the latter as substrate. The former unified, the latter separated. According to Aristotle, Parmenides considered air and water as mixtures of earth and fire.

Background and aim: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. Methods and results: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-1.47) and CV mortality (HR:1.31, 95%CI:1.03-1.66), than those with SUA

Bone is an important tissue for space specialists since it undergoes significant changes under microgravity conditions and its healing is slow. Bone has been considered a special tissue since the very inception of medical theories. In Akragas, Empedocles' (493-432 BC) hypothesis regarding bone was that it was made of two parts earth, two parts water and four parts fire, thus marking the beginning of quantitative chemistry.

BackgroundThe relationships of sodium intake to kidney function within the population have been poorly investigated and are the objective of the study.MethodsThis observational, population-based, cross-sectional and longitudinal study targeted 4595 adult participants of the Gubbio study with complete data at baseline exam. Of these participants, 3016 participated in the 15-year follow-up (mortality-corrected response rate 78.4%). Baseline measures included sodium:creatinine ratio in timed overnight urine collection, used as an index of sodium intake, together with serum creatinine, sex, age and other variables. Follow-up measures included serum creatinine and other variables. Estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) was calculated using serum creatinine, sex and age and was taken as an index of kidney function.ResultsThe study cohort was stratified in sex- and age-controlled quintiles of baseline urine sodium:creatinine ratio. A higher quintile associated with higher baseline eGFR (P ConclusionsWithin the general population, an index of higher sodium intake associated cross-sectionally with higher kidney function but longitudinally with greater kidney function decline.

Background/Aims: Basal cell carcinoma (BCC) is a frequent type of nonmelanoma skin cancer, which shows a greater prevalence in kidney-transplanted (KT) patients than in the general population. The study of this tumor in KT patients may allow us to understand the influence of the tumor inflammatory microenvironment on cancer behavior, and to design new image analysis methods to determine prognosis and apply personalized medicine. The major hypothesis of the present work is that antirejection drugs, by modifying the B-cell/T-cell balance, induce measurable differences in tumoral cell microarchitecture and in the inflammatory microenvironment in KT patients compared to nontransplanted controls. Methods: In this retrospective study in an Italian cohort including 15 KT patients and 15 control subjects from the general population who developed BCC, we analyzed tissue microarchitecture and inflammatory infiltrates of BCC using state-of-the-art nonlinear image analysis techniques such as fractal dimension and sample entropy of internuclear distances. Results: KT patients showed a nonsignificant trend to a greater number of nuclei in the basal cell layer compared to non-KT controls and subtle changes in the intact skin compared to controls. Similarly, the number of mitoses per unit length was almost doubled in the patients with KT compared to controls. However, when the number of mitotic cells was normalized by the total number of cells in the basal layer (mitotic index), these differences were not significant, although a clear trend was still present. Finally, KT patients showed a nonsignificant trend to an increased ­density of inflammatory cells close to the tumoral cell layer. When considering the intact skin, this difference was significant, with a 70% increase in the density of inflammatory cells. Conclusion: Data comparing the microarchitecture of BCC in normal subjects and KT patients are scanty, and the present study is the first to use nonlinear image analysis techniques to this aim. The observed differences underscore the relevance of T-cell suppression in cancer behavior. These data suggest that BCC develops in treated patients with specific biological characteristics which should be further analyzed in terms of therapeutic response.

Data are conflicting about the effects of alcohol intake on kidney function. This population-based study investigated associations of alcohol intake with kidney function and mortality. The study cohort included adult participants in Exam-1, Exam-2 (6-year follow-up), and Exam-3 (20-year follow-up) of the Gubbio study. Kidney function was evaluated as estimated glomerular filtration rate (eGFR, CKD-Epi equation, mL/min × 1.73 m2). Daily habitual alcohol intake was assessed by questionnaires. Wine intake accounted for >94% of total alcohol intake at all exams. Alcohol intake significantly tracked over time (R > 0.66, p < 0.001). Alcohol intake distribution was skewed at all exams (skewness > 2) and was divided into four strata for analyses (g/day = 0, 1–24, 25–48, and >48). Strata of alcohol intake differed substantially for lab markers of alcohol intake (p < 0.001). In multivariable regression, strata of alcohol intake related cross-sectionally to eGFR at all exams (Exam-1: B = 1.70, p < 0.001; Exam-2: B = 1.03, p < 0.001; Exam-3: B = 0.55, p = 0.010) and related longitudinally to less negative eGFR change from Exam-1 to Exam-2 (B = 0.133, p = 0.002) and from Exam-2 to Exam-3 (B = 0.065, p = 0.004). In multivariable Cox models, compared to no intake, intakes > 24 g/day were not associated with different mortality while an intake of 1–24 g/day was associated with lower mortality in the whole cohort (HR = 0.77, p = 0.003) and in the subgroup with eGFR < 60 mL/min × 1.73 m2 (HR = 0.69, p = 0.033). These data indicate a positive independent association of alcohol intake with kidney function not due to a mortality-related selection.

The prevalence, determinants, and clinical significance of vitamin D deficiency in the population are debated. The population-based study investigated the cross-sectional associations of several variables with serum 25-hydroxyvitamin D (calcidiol) measured using standardized calibrators. The study cohort consisted of 979 persons of the Moli-sani study, both sexes, ages ≥35 years. The correlates in the analyses were sex, age, education, local solar irradiance in the month preceding the visit, physical activity, anthropometry, diabetes, kidney function, albuminuria, blood pressure, serum cholesterol, smoking, alcohol intake, calorie intake, dietary vitamin D intake, and vitamin D supplement. The serum calcidiol was log transformed for linear regression because it was positively skewed (skewness = 1.16). The prevalence of calcidiol deficiency defined as serum calcidiol ≤12 ng/mL was 24.5%. In multi-variable regression, older age, lower solar irradiance, lower leisure physical activity, higher waist/hip ratio, higher systolic pressure, higher serum cholesterol, smoking, lower alcohol intake, and no vitamin D supplement were independent correlates of lower serum calcidiol (95% confidence interval of standardized regression coefficient ≠ 0) and of calcidiol deficiency (95% confidence interval of odds ratio > 1). The data indicate that low serum calcidiol in the population could reflect not only sun exposure, age, and vitamin D supplementation but also leisure physical activity, abdominal obesity, systolic hypertension, hypercholesterolemia, smoking, and alcohol intake.

Background—Some data suggest favorable effects of a high potassium intake on kidney function. The present population-based study investigated cross-sectional and longitudinal relations of urinary potassium with kidney function. Methods—Study cohort included 2027 Gubbio Study examinees (56.9% women) with age ≥ 18 years at exam-1 and with complete data on selected variables at exam-1 (1983–1985), exam-2 (1989–1992), and exam-3 (2001–2007). Urinary potassium as urinary potassium/creatinine ratio was measured in daytime spot samples at exam-1 and in overnight timed collections at exam-2. Estimated glomerular filtration rate (eGFR) was measured at all exams. Covariates in analyses included demographics, anthropometry, blood pressure, drug treatments, diabetes, smoking, alcohol intake, and urinary markers of dietary sodium and protein. Results—In multivariable regression, urinary potassium/creatinine ratio cross-sectionally related to eGFR neither at exam-1 (standardized coefficient and 95%CI = 0.020 and −0.059/0.019) nor at exam-2 (0.024 and −0.013/0.056). Exam-1 urinary potassium/creatinine ratio related to eGFR change from exam-1 to exam-2 (0.051 and 0.018/0.084). Exam-2 urinary potassium/creatinine ratio related to eGFR change from exam-2 to exam-3 (0.048 and 0.005/0.091). Mean of urinary potassium/creatinine ratio at exam-1 and exam-2 related to eGFR change from exam-1 to exam-3 (0.056 and 0.027/0.087) and to incidence of eGFR &lt, 60 mL/min per 1.73 m2 from exam-1 to exam-3 (odds ratio and 95%CI = 0.78 and 0.61/0.98). Conclusion—In the population, urinary potassium did not relate cross-sectionally to eGFR but related to eGFR decline over time. Data support the existence of favorable effects of potassium intake on ageing-associated decline in kidney function.

Background/aim Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step. Patients and methods We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC. Results KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria. Conclusion KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.