Giorgio Gentile

Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function and gene modulation effects. The metabolism of vitamin E depends on hepatic binding proteins that selectively retain food alpha-tocopherol for incorporation into nascent VLDL and tissue distribution together with esterified cholesterol and triglycerides. Chronic kidney disease (CKD) is a condition of oxidative stress and increased lipid peroxidation, that are associated with alterations of alpha-tocopherol metabolism and function. Specific changes have been reported for the levels of its enzymatic metabolites, including both short-chain and long-chain metabolites, the latter being endowed with regulatory functions on enzymatic and gene expression processes important for the metabolism of lipids and xenobiotics detoxification, as well as for the control of immune and infla...

Hypertension affects over a billion people worldwide and is the leading cause of cardiovascular disease and premature death worldwide, as well as one of the key determinants of chronic kidney disease worldwide. People with chronic kidney disease and hypertension are at very high risk of renal outcomes, including progression to end-stage renal disease, and, even more importantly, cardiovascular outcomes. Hence, blood pressure control is crucial in reducing the human and socio-economic burden of renal and cardiovascular outcomes in those patients. However, current guidelines from hypertension and renal societies have issued different and sometimes conflicting recommendations, which risk confusing clinicians and potentially contributing to a less effective prevention of renal and cardiovascular outcomes. In this review, we critically appraise existing evidence and key international guidelines, and we finally formulate our own opinion that clinicians should aim for a blood pressure targ...

Hypertension is a key risk factor for chronic kidney disease (CKD), but can also be a detrimental consequence of established CKD. Unsurprisingly, the majority of subjects with abnormal creatinine in the general population are also hypertensive, with a huge toll on national health care systems worldwide due to a staggering increase in the risk of cardiovascular complications and end-stage renal disease requiring renal replacement therapy. In this setting, a comprehensive and careful assessment of the whole 24-h blood pressure (BP) profile could be of paramount importance in ensuring a timely diagnosis of hypertension and an optimal therapeutic control. Hence, ambulatory BP monitoring (ABPM) has the potential to become the preferred method for optimal clinical management of CKD patients. ABPM might better define the relationship between BP, target organ damage (TOD), and clinical outcomes. Current evidence suggests that specific day–night BP components, along with average BP values, may have clinical relevance in such patients, despite the suboptimal statistical power of available studies and inconsistencies on the prognostic value of individual BP components. The main aim of our review is to scrutinize the evidence for the usage of ABPM in CKD patients, including the relationship between ambulatory BP recordings and cardiovascular events, and the distinctive features of ABPM in these subjects.

Several randomized trials compared a more versus less intensive blood pressure–lowering strategy on the risk of major cardiovascular events and death. Cumulative meta-analyses and trial sequential analyses can establish whether and when firm evidence favoring a specific intervention has been reached from accrued literature. Therefore, we conducted a cumulative trial sequential analysis of 18 trials that randomly allocated 53 405 patients to a more or less intensive blood pressure–lowering strategy. We sought to ascertain the extent to which trial evidence added to previously accrued data. Outcome measures were stroke, myocardial infarction, heart failure, cardiovascular death, and all-cause death. Achieved blood pressure was 7.6/4.5 mm Hg lower with the more intensive than the less intensive blood pressure–lowering strategy. For stroke and myocardial infarction, the cumulative Z curve crossed the efficacy monitoring boundary solely after the SPRINT (Systolic Blood Pressure Intervent...

Recent years have witnessed the unprecedented development and integration of genomics, epigenetics, transcriptomics, proteomics, and metabolomics, as well as a growing interest in novel single biomarkers and process-specific biomarker panels in human renal diseases. In a scenario currently dominated by kidney biopsy and established biomarkers such as serum creatinine, albuminuria, and proteinuria, novel biomarkers could potentially provide vital diagnostic and prognostic information and help to predict response to treatment in several clinical settings, including acute kidney injury, renal transplant, autosomal dominant polycystic kidney disease, and glomerulopathies. However, it is still uncertain whether and to what extent novel biomarkers will succeed in this difficult task. To date, they have generally failed to provide relevant information over and above what is already granted by established, cheap, and easily available biomarkers such as proteinuria, while the complexity and ...

The effect of mammalian target of rapamycin (mTOR) inhibitors has never been tested in patients with autosomal dominant polycystic kidney disease (ADPKD) and severe renal insufficiency. In this academic, prospective, randomized, open label, blinded end point, parallel group trial (ClinicalTrials.gov no. NCT01223755), 41 adults with ADPKD, CKD stage 3b or 4, and proteinuria ≤0.5 g/24 h were randomized between September of 2010 and March of 2012 to sirolimus (3 mg/d; serum target levels of 5-10 ng/ml) added on to conventional therapy (n=21) or conventional treatment alone (n=20). Primary outcome was GFR (iohexol plasma clearance) change at 1 and 3 years versus baseline. At the 1-year preplanned interim analysis, GFR fell from 26.7±5.8 to 21.3±6.3 ml/min per 1.73 m(2) (P<0.001) and from 29.6±5.6 to 24.9±6.2 ml/min per 1.73 m(2) (P<0.001) in the sirolimus and conventional treatment groups, respectively. Albuminuria (73.8±81.8 versus 154.9±152.9 μg/min; P=0.02) and proteinuria (0.3...

Angiotensin-converting enzyme (ACE) inhibitors have been available for more than a decade for clinical use to treat hypertension and congestive heart failure (CHI). An intravenous agent, enalaprilat, has been approved by the Food and Drug Administration (FDA) for use in hypertension, and ten oral agents—benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril—are approved and available in the United States. Spirapril has also been approved by the FDA for the treatment of hypertension; however, this agent has not been marketed by the pharmaceutical industry at press time. All ACE Inhibitors are similar in their effects, differing principally in their pharmacokinetics and approved indications.

Blood pressure (BP) targets in diabetic patients stills represent the object of a major debate, fueled by the recent publication of post hoc observational analyses of the INVEST and the ONTARGET trials, suggesting an increased risk of cardiovascular events with tighter control, the J-curve effect, and by the results of the ACCORD trial, showing no improvements in the composite primary outcome of nonfatal myocardial infarction, stroke, or cardiovascular death in the intensive BP-lowering arm (<120/80 mmHg). In the present review, we focus on existing evidence about different BP targets in diabetic subjects and we present the results of our recent meta-analysis, showing that tight BP control may significantly reduce the risk of stroke in these patients without increasing the risk of myocardial infarction. Therapeutic inertia (leaving diabetic patients with BP values of 140/90 mmHg or higher) should be avoided at all costs, as this would lead to an unacceptable toll in terms of human lives, suffering, and socioeconomic costs.

We investigated the relationship between the day-night blood pressure (BP) dip and the early morning BP surge in an cohort of 3012 initially untreated subjects with essential hypertension. The day-night reduction in systolic BP showed a direct association with the sleep trough ( r =0.564; P <0.0001) and the preawakening ( r =0.554; P <0.0001) systolic BP surge. Over a mean follow-up period of 8.44 years, 268 subjects developed a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and heart failure requiring hospitalization) and 220 subjects died. In a Cox model, after adjustment for predictive covariates, including age, sex, diabetes mellitus, cigarette smoking, total cholesterol, left ventricular hypertrophy on ECG, estimated glomerular filtration rate, and average 24-hour systolic BP, a blunted sleep trough (≤19.5 mm Hg; quartile 1) and preawakening (≤9.5 mm Hg; quartile 1) BP surge was associated with an excess ris...

... Auteur(s) / Author(s). PARATI Gianfranco ; OMBONI Stefano ; BILO Grzegorz ; VERDECCHIA Paolo ; ANGELI Fabio ; MAZZOTTA Giovanni ; GENTILE Giorgio ; REBOLDI Gianpaolo ; Revue / Journal Title. Hypertension ISSN 0194-911X CODEN HPRTDN Source / Source. ...

Blood pressure (BP) decreases by 10% to 20% from day to night. However, in 25% to 35% of hypertensive subjects there is some reduction in the day-night BP decline. In 3% to 5% of uncomplicated hypertensive subjects there is actually an increase, not a decrease, in BP from day to night. Many studies from independent centers showed that not only left ventricular hypertrophy, but also ventricular arrhythmias, silent cerebrovascular disease, microalbuminuria and progression of renal damage are more advanced in subjects with blunted or abolished fall in BP from day to night than in those with normal day-night BP difference. There is also evidence from longitudinal studies that a blunted, abolished or even reversed BP drop from day to night is associated with an increase in the risk of serious cardiovascular complications. However, if the quantity or quality of sleep is poor during overnight BP monitoring, night-time BP rises and its prognostic significance is no longer reliable. Studies which compared the prognostic value of daytime BP with that of night-time BP inevitably found the superiority of the latter for predicting prognosis. The exciting potential therapeutic implication that the control of night-time BP could be more rewarding, in terms of prevention of cardiovascular disease, than that of daytime BP has yet to be addressed in appropriately designed intervention trials. Of note, 24-hour ABP monitoring is the only practical way to assess the day-night rhythm of BP.

L'attuale situazione economica, politica e sociale richiede a tutti coloro che operano nella Sanità parti-colari sforzi per cercare di ideare e mettere in atto nuovi modelli organizzativi e gestionali, sperimentando nuove forme di interazione tra chi ha idee e chi ha le capacità di realizzarle. L'interazione tra i ricer-catori e le aziende, tuttavia, non è sempre agevole per una mancanza di una lingua comune. " L'Accademia delle Idee " è un nuovo progetto della Società Italiana di Nefrologia (SIN) per rispondere a questa proble-matica. Il fine di questo progetto è quello di consentire ai giovani ricercatori (età inferiore a 40 anni) di poter interagire in modo proficuo con le aziende e di fornire il supporto tecnico necessario per la realiz-zazione di uno studio di fattibilità (business plan) che possa attirare eventuali investimenti di aziende ope-ranti nell'ambito sanitario. In questo articolo saranno presentati i principi, la metodologia e le tempistiche de " L'Accademia delle Idee ".

Guidelines for the management of hypertension almost invariably include sections where the evidence
for or against treatment or for certain types of treatment in certain types of patients is inconclusive.
This is especially the case of older patients with hypertension. As a consequence, although a large
number of randomized trials including hypertensive patients aged ≥60 years showed that antihypertensive
drugs reduce cardiovascular morbidity and mortality, health care professionals who take care
of older adults have been often reluctant to provide adequate antihypertensive therapy. In a recent
meta-analysis, the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) compared the
effects of different drugs for reducing blood pressure (BP) in older and younger adults; the reduction
in BP levels and the relative risk reduction of a cardiovascular event with various antihypertensive
drugs occurred independently of the patients’ ages, and the benefits of antihypertensive regimens
based on different drug classes were widely comparable across age groups. The BPLTTC analysis
strongly suggests an early and aggressive management of hypertension irrespectively of age; more
myocardial infarctions, strokes, heart failures and deaths will be prevented by treating hypertensive
patients aged ≥65 years than by treating patients ≤50 years with the same BP levels. Antihypertensive
treatment should be embedded within the management of global cardiovascular risk, with the
use of charts for stratifying risk based on additional risk factors, target organ damage or additional
clinical conditions.

Hemolysis, elevated liver enzymes, and low platelet count syndrome(HELLP) is a severe pregnancy complication since it is life-threatening for both mother and fetus. When HELLP syndrome associates with disseminated intravascular coagulation (DIC) or with other complications it is necessary to terminate the pregnancy; however, due to fetal prematurity, it may be advisable to wait for the effectiveness of the corticosteroid prophylaxis of neonatal respiratory distress syndrome when such complications are not present. This article reports an initially mild HELLP syndrome case, with onset at week 26 and two days of pregnancy, where it was necessary to wait for the effectiveness of respiratory distress prophylaxis and, consequently, to carry out a close monitoring of the onset and worsening of DIC. Tests for blood cell distribution width, D-dimer, plasmatic electrolytes and urinary sediment, which undergo precocious and rapid variations in DIC, are quickly processed, and useful for the conservative management of HELLP

In recent years, evidence-based medicine (EBM) has acquired its own dignity and cultural identity, and increasing importance. EBM helps doctors understand that the uncertainties of medicine must be analyzed quantitatively in order to rationalize and systematize the information gathered from clinical observation; on the other hand, it provides them with suitable instruments to estimate the performance of diagnostic tests and the efficacy of drugs. One of the main merits of EBM has been the progressive spread of randomized controlled trials as the gold standard for evaluating the effectiveness of treatments. EBM's primary objectives can be summarized by the following points: 1) To transform the physicians' need for information into questions that may be answered (ie, formulate the questions); 2) To find in an as efficient way as possible the best evidence to answer these questions; 3) To critically evaluate the evidence obtained (ie, assign a weight to it) in order to determine its validity (ie, its approximation to the truth) and its usefulness (ie, its concrete clinical applicability); 4) To introduce into clinical practice the conclusions drawn from the results; 5) To estimate individual physicians' performance (ie, one's own conduct and efficiency). EBM's advantages are not only that physicians have acquired a method to search for the right evidence and to apply diagnostic and therapeutic procedures, but, more importantly, that it has provided them with the only tool for true quality improvement, namely the critical appraisal of their own work. Unfortunately, the latter is too often based on a different type of EBM: Evidence-Based Medicine.

An elevateci urinary albumin excretion (UAE) below
the proteinuric level, Le. microalbuminuria
(MAU), has long been recognized as a marker
of kidney disease and increased cardiovascular
risk in both types of diabetes meiiitus.
Subsequent ciinical evidence documented an
association between MAU and other cardiovascular
risk factors, target organ damage and risk
of cardiovascular disease in the genera1 population
and in specific clinical contexts including
essential hypertension. This article reviews the
available evidence on the clinical value of MAU
in subjects with essential hypertension. In these
subjects, the reported prevalence of MAU ranges
from about 4% to 46% across different studies
and these differences may be explained by the
huge intraindividual variability in UAE, age and
ethnicity, discrepancies in the technique of
measurement and different definitions of MAU.
A direct and continuous association between
UAE and blood pressure (BP) and left ventricular
mass has been found in most studies. In contrast,
it is not yet clear whether the association
between UAE and other factors including age,
gender, smoking, ethnicity, insulin resistance,
lipids and obesity is independent or due to confounders,
particularly BP. Severa1 prospettive
studies disclosed an association between MAU
and the risk of future cardiovascular disease.
Of particular note, in some of these studies the
incidence of major cardiovascular events progressively
increased with UAE starting below
the conventional MAU thresholds. Thus, besides
being a direct risk factor for progressive
renal damage, MAU can be considered a marker
which integrates and reflects the long-term
level of activity of severd other detrirnental factors
on cardiovascular system Antihypertensive
treatment reduces UAE and such effect may be
detected after just a few days of treatment.
Among available antihypertensive drugs, angiotensin
converting enzyme (ACE) inhibitors
and the angiotensin I1 receptor antagonists
seem to be superior to other antihypertensive
drugs in reducing UAE. The dual blockade of
the renin angiotensin system with an ACE inhibitor
and an angiotensin I1 receptor antagonist
is a new and promising approach to contro1
UAE in hypertensive patients. Determination
of MAU is recommended in the initial work-up
of subjects with essential hypertension as suggested
in the most recent European hypertension
guidelines, even though, as upcoming evidence
suggest, the periodic evaluation of this
simple, inexpensive and predictive marker
might be valuable and cost-effective.

Background. A recent clinical trial showed harmful renal effects with the combined use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) in people with diabetes or vascular disease. We examined the benefits and risks of these agents in people with albuminuria and one or more cardiovascular risk factors. Methods. MEDLINE, EMBASE and Renal Health Library were searched for trials comparing ACEI, ARB or their combination with placebo or with one another in people with albuminuria and one or more cardiovascular risk factor. Results. Eighty-five trials (21 708 patients) were included. There was no significant reduction in the risk of all-cause mortality or fatal cardiac–cerebrovascular outcomes with ACEI versus placebo, ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI 1 ARB versus monotherapy. There was a significant reduction in the risk of nonfatal cardiovascular events with ACEI versus placebo but not with ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI 1 ARB versus monotherapy. Development of end-stage kidney disease and progression of microalbuminuria to macroalbuminuria were reduced significantly with ACEI versus placebo and ARB versus placebo but not with combined therapy with ACEI 1 ARB versus monotherapy. Conclusions. ACEI and ARB exert independent renal and nonfatal cardiovascular benefits while their effects on mortality and fatal cardiovascular disease are uncertain. There is a lack of evidence to support the use of combination therapy. A comparative clinical trial with ACE, ARB and its combination in people with albuminuria and a cardio-vascular risk factor is warranted.

Abstract: For patients with hypertension, effective control of blood pressure (BP) reduces
cardiovascular (CV), and renal risk. Antihypertensive agents that offer benefits that extend
beyond those associated with BP reduction alone, to include tissue protective effects and
effects on the vasculature, may be of benefit for many patients with increased CV risk due
to comorbidities or prior history of CV events. Renin–angiotensin system (RAS) blockers
[angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)]
are guideline-recognized, highly effective antihypertensive agents that exert their BP-lowering
action through different mechanisms at different levels of the RAS. Large-scale clinical studies
suggest that small, between-treatment differences in BP lowering do not account for observed
outcome differences between RAS blockers and other antihypertensive agents. Analysis of
data from seminal clinical studies and meta-analyses identify that, controlling for effects
on BP control, RAS blockers may be more effective than calcium channel blockers (CCBs)
in reducing risk of myocardial infarction and congestive heart failure; ARBs may be more
effective than either ACEIs or β blockers in stroke prevention; CCBs may be more effective
than RAS blockers in stroke prevention; and ARBs may be more effective than β blockers in
reducing left ventricular hypertrophy. This review considers the rationale and evidence for
benefits of RAS blockade beyond BP lowering, and highlights the differences between ARBs
and ACEIs, and between agents within these drug classes.

Abstract
Background. Factors associated with erectile dysfunction
in men on haemodialysis are incompletely identified due to
suboptimal existing studies. We determined the prevalence
and correlates of erectile dysfunction and identified combinations
of clinical characteristics associated with a higher
risk of erectile dysfunction using recursive partitioning and
amalgamation (REPCAM) analysis.
Methods. We conducted a multinational cross-sectional
study in men on haemodialysis within a collaborative network.
Erectile dysfunction and depressive symptoms were
evaluated using the erectile function domain of the International
Index of Erectile Function questionnaire and
the Center for Epidemiological Studies-Depression Scale,
respectively.
Results. Nine hundred and forty-six (59%) of 1611 eligible
men provided complete data for erectile dysfunction.
Eighty-three per cent reported erectile dysfunction and
47% reported severe erectile dysfunction. Four per cent of
those with erectile dysfunction were receiving pharmacological
treatment. Depressive symptoms were the strongest
correlate of erectile dysfunction [adjusted odds ratio 2.41
(95% confidence interval (CI) 1.57–3.71)]. Erectile dysfunction
was also associated with age (1.06, 1.05–1.08),
being unemployed (1.80, 1.17–2.79) or receiving a pension
(2.05, 1.14–3.69) and interdialytic weight gain (1.9–2.87 kg,
1.92 [CI 1.19–3.09]; >2.87 kg, 1.57 [CI 1.00–2.45]).
Married men had a lower risk of erectile dysfunction
(0.49, 0.31–0.76). The prevalence of erectile dysfunction
was highest (94%) in unmarried and unemployed or retired
men who have depressive symptoms.
Conclusions. Most men on haemodialysis experience erectile
dysfunction and are untreated. Given the prevalence of
this condition and the relative lack of efficacy data for
pharmacological agents, we suggest that large trials of
pharmacological and non-pharmacological interventions
for erectile dysfunction and depression are needed.

Background. Oral disease may be increased in people with
chronic kidney disease (CKD) and, due to associations with
inflammation and malnutrition, represents a potential modifi-
able risk factor for cardiovascular disease and mortality. We
summarized the prevalence of oral disease in adults with
CKD and explored any association between oral disease and
mortality.
Methods. We used systematic review of observational studies
evaluating oral health in adults with CKD identified in
MEDLINE (through September 2012) without language restriction.
We summarized prevalence and associations with
all-cause and cardiovascular mortality using random-effects
ORIGINAL ARTICLE
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behalf of ERA-EDTA. All rights reserved.
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meta-analysis. We explored for sources of heterogeneity
between studies using meta-regression.
Results. Eighty-eight studies in 125 populations comprising
11 340 adults were eligible. Edentulism affected one in five
adults with CKD Stage 5D (dialysis) {20.6% [95% confidence
interval (CI), 16.4–25.6]}. Periodontitis was more common in
CKD Stage 5D [56.8% (CI, 39.3–72.8)] than less severe CKD
[31.6% (CI, 19.0–47.6)], although data linking periodontitis
with premature death were scant. One-quarter of patients
with CKD Stage 5D reported never brushing their teeth
[25.6% (CI, 10.2–51.1)] and a minority used dental floss
[11.4% (CI, 6.2–19.8)]; oral pain was reported by one-sixth
[18.7% (CI, 8.8–35.4)], while half of patients experienced a dry
mouth [48.4% (CI, 37.5–59.5)]. Data for kidney transplant
recipients and CKD Stages 1–5 were limited.
Conclusions. Oral disease is common in adults with CKD,
potentially reflects low use of preventative dental services, and
may be an important determinant of health in this clinical setting

The global population is progressively aging, to the extent that over 1.5 billion people worldwide will be aged 65 years or more by 2050, and the prevalence of end-stage renal disease in the elderly will remain high in forthcoming years. Since older patients typically suffer from several comorbidities, the above issue poses a hefty financial burden on healthcare systems. Although current guidelines might be useful for older individuals with fewer comorbidities and no significant disability, a tailored therapeutic approach is often essential in individuals with severe comorbidities, short life expectancy or poor treatment compliance. In such patients, rather than aggressively pursuing different therapeutic targets, physicians should strive to enhance quality of life by treating comorbidity-related symptoms and addressing common geriatric syndromes, including cognitive impairment, depression, incontinence, falls and polypharmacy, and the decision about starting dialysis should be guided not only by medical reasons, but also by patients‘ personal beliefs and preferences.

Introduction: Diabetes mellitus is increasingly common worldwide and is
expected to affect 592 million people by 2035. The kidney is often involved.
A key goal in treating diabetes is to reduce the risk of development of kidney
disease and, if kidney disease is already present, to delay the progression to
end-stage renal disease (ESRD). This represents a social and ethical issue, as a
significant proportion of patients reaching ESRD in developing countries do
not have access to renal replacement therapy.
Areas covered: The present review focuses on novel therapeutic approaches
for diabetic nephropathy (DN), implemented on the basis of recent insights
on its pathophysiology, which might complement the effects of single inhibition
of the renin-angiotensin-aldosterone system (RAAS), the cornerstone of
renoprotective interventions in diabetes, along with glycemic and blood
pressure control.
Expert opinion: Although a plethora of new treatment options has arisen
from experimental studies, the number of novel renoprotective molecules
successfully implemented in clinical practice over the last two decades is
disappointingly low. Thus, new investigational strategies and diagnostic
tools -- including the appropriate choice of relevant renal end points and
the study of urinary proteome of patients -- will be as important as new
therapeutic interventions to fight DN. Finally, in spite of huge financial interests
in replacing the less expensive ACE inhibitors and angiotensin II receptor
blockers with newer drugs, any future therapeutic approach has to be tested
on top of -- rather than instead of -- optimal RAAS blockade.

Chronic kidney disease (CKD) affects approximately 500 million people worldwide and is increasingly common in both industrialized and emerging countries. Although the mechanisms underlying the inexorable progression of CKD are incompletely defined, recent discoveries may pave the way to a more comprehensive understanding of the pathophysiology of CKD progression and the development of new therapeutic strategies. In particular, there is accumulating evidence indicating a key role for the complex and yet incompletely understood system of divalent cation regulation, which includes phosphate metabolism and the recently discovered fibroblast growth factor 23 (FGF-23)/klotho system, which seems inextricably associated with vitamin D deficiency. The aim of this review is to discuss the links between high blood pressure, proteinuria, phosphate levels, and CKD progression and explore new therapeutic strategies to win the fight against CKD. Am J Kidney Dis. 62(5):984-992.

In experimental diabetic and non-diabetic chronic kidney disease (CKD), angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) combination therapy reduces proteinuria and prevents structural lesions more effectively than either drug alone. Consistently, in humans, a multidrug individually tailored antiproteinuric treatment based on combination therapy with maximum tolerated doses of ACEi and ARB (Remission Clinic protocol) reduced proteinuria and prevented end-stage renal disease (ESRD) more effectively than ACEi/ARB monotherapy, in particular in subjects with non-diabetic CKD. Fixed doses of an ACEi or renin inhibitor added to losartan failed to exert any additional renoprotective effect as compared with losartan monotherapy in patients at increased cardiovascular risk (ONTARGET study) or with type 2 diabetes and overt nephropathy (ALTITUDE study). The VA NEPHRON D study found that losartan and lisinopril combination therapy reduced by 34% the risk of predefined reductions in estimated glomerular filtration rate, ESRD or death as compared to losartan in 1,448 type 2 diabetes patients with overt nephropathy. Unfortunately, the treatment effect failed to achieve the nominal significance (p = 0.07) because of premature trial interruption. Thus, the Remission Clinic protocol is the most powerful tool to prevent progression to ESRD in non-diabetic proteinuric CKD. Results of the ongoing VALID trial will show whether this approach can be safely extended to type 2 diabetes patients.

Introduction. To compare the effects of angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) on the risk of myocardial infarction (MI), stroke, cardiovascular mortality and total mortality. Methods. We conducted a meta-analysis of randomised comparative trials between ARBs and ACEIs. Inclusion criteria were publication in peer-reviewed journals indexed in Medline, randomised comparison ARBs vs. ACEIs, or ARBs+ACEIs vs. ACEIs, report of major complications including MI, stroke, cardiovascular mortality or all-cause mortality; average follow-up of at least 1 year in at least 200 patients. Results. Six trials fulfilled the inclusion criteria, for a total of 49924 patients. In the pooled estimate, there were no significant differences between ARBs and ACEIs on the risk of MI (OR 1.01; 95% CI 0.95-1.07; p=0.75), cardiovascular mortality (OR 1.03; 95% CI 0.98-1.08; p=0.23) and total mortality (OR 1.03; 95% CI 0.97-1.10; p=0.20). This was the case also when the analysis involved only the comparison between ACEIs and ARBs. Overall, the risk of stroke was slightly lower with ARBs than ACEIs (OR 0.92; 95% CI 0.85-0.99; p=0.037),the direct ACEIs and ARBs comparison showing a non-significant trend in a similar direction. Statistical heterogeneity among trials was not significant, with a low to null inconsistency statistic, for stroke (p=0.67), MI (p=0.86), cardiovascular mortality (p=0.1 4) and total mortality (p=.12). Conclusions. This overview suggests that ARBs are as effective as ACEIs on the risk of MI, cardiovascular mortality and total mortality. ARBs may be slightly more protective than ACEIs on the risk of stroke.

Professionalità e qualità potrebbero sembrare sinonimi , ma così non è, sono totalmente diverse, sia come significato che come background di esperienze, atteggiamenti e soprattutto in termini di risultato. La professionalità attiene alla formazione e alla cultura, la qualità agli atteggiamenti. Purtroppo gran parte della preparazione che ci viene impartita si basa solo sulla preparazione professionale inculcandoci, come è giusto che sia, nozioni specifiche attinenti alla nostra professione. Pensiamo alla preparazione di tipo universitario che oramai accomuna diverse figure sanitarie. Si passa da nozioni di base, a nozioni specifiche del campo di applicazione prescelto fino, nei casi fortunati, alla esplicazione pratica di quanto imparato. Veniamo considerati professionisti quando, superata la laurea, siamo in grado di entrare nel mondo del lavoro. In realtà è da questo momento che dobbiamo dimostrare di essere professionisti e soprattutto di continuare ad esserlo! Il nostro compito è quello di mettere in pratica ciò che abbiamo imparato negli anni precedenti, con l'illusione, che per un comportamento corretto si verifichi il riscontro di un risultato altrettanto corretto. Questo però non è sempre vero, frequentemente infatti, i risultati sono esaltanti in alcuni casi che peraltro (e forse purtroppo), sono quelli di cui ci ricordiamo meglio e che siamo soliti citare come esempi di grande professionalità, ma che in verità dimostrano solo la eventuale presenza di professionalità. Il nostro compito istituzionale è invece quello di agire continuamente (e non sporadicamente) in maniera qualitativamente corretta. In altre parole, per fare un grande pilota non basta vincere ogni tanto una gara di formula uno, bensì è necessario vincere il campionato, così come non basta segnare un gol magnifico, quanto segnarne diversi, magari brutti ma decisivi. Questo significa fare qualità. La qualità attiene quindi non solo alla professionalità (che è alla base) ma al sistema organizzativo sia del singolo che della organizzazione in cui lavora 1. Tornando all'esempio del calciatore, per fare un campione ,è necessario che questi agisca in modo corretto anche quando è lontano dal campo di gioco, che si limiti con l'alimentazione, con l'acool, con il fumo etc. Ma ciò non è sufficiente: è indispensabile che la squadra dove gioca gli procuri un buon medico sportivo, un massaggiatore, scarpe di ottimo livello, trasporti adeguati, tranquillità nell'ambito dello spazio contrattuale etc. E ancora non basta: necessita che la squadra gli fornisca anche un ottimo allenatore perchè deve integrarsi con gli altri per formare la squadra! Solo la squadra otterrà i risultati voluti, il singolo sarebbe solo un oggetto prezioso ma senza scopo. Nel nostro ambiente si ha spesso la sensazione che si consideri il lavoro finito quando si assume un professionista saltando, o peggio non considerando, le fasi successive che sono però le sole ad assicurare un risultato di qualità. Partiamo da una semplice attività che pratichiamo ogni giorno: la dialisi. Domandiamoci cosa ci stiamo a fare in sala dialisi. Le risposte potrebbero essere tante, sempre più articolate e con implicazioni sempre più complesse: A fare la dialisi A fare la dialisi nel modo migliore possibile A fare la dialisi e a rispondere alle chiamate del paziente A fare la dialisi e a rispondere alle chiamate del paziente e ad assisterlo se sta male A fare la dialisi e a rispondere alle chiamate del paziente e ad assisterlo se sta male e ad educarlo al trattamento.