Prescription of oral antidiabetic drugs in K/DIGO chronic kidney disease stage 3 and 4: a single centre report.

AIM: Evaluation of chronic kidney disease (CKD) is essential in order to prescribe properly oral antidiabetic drugs (OADs). The aim of our study was to report hypoglycemic drugs prescription to CKD in a cohort of type 2 diabetes mellitus (DM) outpatients. METHODS: This survey included 1686 outpatients with type 2 DM treated with OADs who were not taking insulin evaluated by a team of diabetologists. Glomerular filtration rate (GFR) was calculated by the CKD-EPI formula and subjects were classified in the K/DIGO stages. Main clinical parameters were also evaluated. RESULTS: Patients were aged 68±10 years, 57.1% were males, Body Mass Index was 30±5 kg/m2, glycated hemoglobin 8±1%, systolic and diastolic blood pressure values were 138±15/80±9 mmHg. Serum creatinine was 1.03±0.35 mg/dL and GFR 71±21 mL/min/1.73 m2. In 504 patients (30%) GFR was lower than 60 mL/min/1.73 m2. The different treatment groups had different GFR and hypoglycaemic drugs were prescribed differently in the different K/DIGO stages. The majority of subjects in stage 3A and 3B were treated with repaglinide, however a significant percentage of them were treated with metformin and sulfonylureas. Nearly half of subjects with CKD stage 4 were treated with metformin and sulfonylureas. CONCLUSION: In this report we found that nearly one third of patients with type DM 2 had CKD and in a significant percentage of them OADs were prescribed even if they were in K/DIGO CKD stage 3 and 4.

Sleep-time ambulatory blood pressure as a novel therapeutic target for cardiovascular risk reduction.

Diagnosis of hypertension and clinical decisions regarding its treatment are typically based upon daytime clinic blood pressure (BP) measurements, occasionally supplemented by wake-time patient self-assessment. Yet, correlation between BP level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is higher for ambulatory BP monitoring (ABPM) measurements. Numerous studies consistently reveal CVD events are better predicted by the asleep than awake or 24 h BP means. In addition, when the asleep BP mean is adjusted by the awake mean, only the former is a significant independent predictor of outcome. Endogenous circadian rhythms explain statistically and clinically significant ingestion time differences in efficacy, duration of action, safety and/or effects on the daily BP pattern of most hypertension medications and their combinations. Bedtime versus morning-time ingestion of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, independent of drug terminal half-life, both better reduces asleep BP and normalizes the daily BP profile into a more normal dipper pattern. The recently completed prospective outcome MAPEC Study verifies therapeutic restoration of the normal sleep-time BP decline, a novel therapeutic goal most effectively achieved by ingestion of the entire daily dose of ⩾ 1 conventional hypertension medications at bedtime, best decreases CVD morbidity and mortality. Our findings indicate around-the-clock ABPM is a clinical necessity to accurately detect abnormal sleep-time BP and assess CVD risk, and that hypertension ought to be managed by a bedtime therapeutic strategy, preferably one including medication that antagonizes the activities and actions of the renin-angiotensin-aldosterone system.

The estimation of glomerular filtration rate in type 2 diabetic patients may depend on the equation used.

BACKGROUND: The aim of this study was to compare the estimation of glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) outpatients. PATIENTS AND METHODS: The study included 1686 subjects, aged 68±10 years. GFR was evaluated with five different equations: GFRMDRD186, GFRMDRD175, GFRCKD-EPI, GFRMAYO, GFRC-G. RESULTS: GFR was lower than 60 ml min-1 kg-1 in 456 patients (27%) by GFRMDRD186, in 531 (31.5%) by GFRMDRD175, in 504 (30%) by GFRCKD-EPI, in 433 (26%) by GFRC-G, and in 255 (15%) by GFRMAYO. The mean differences in measuring GFR with the different formulae ranged from 1.03±6.20 to -14.5±11.9 ml min-1 1.73 m2-1. CONCLUSIONS: The evaluation of GFR with different formulae in type 2 DM patients may identify different chronic kidney disease (CKD) stages. Physicians could take advantage by the knowledge of the formula used for evaluation of renal function, for a better interpretation of values and a more appropriate use in the everyday clinical practice.

Left kidney: an unusual site of cocaine-related renal infarction. A case report.

Acute renal infarction is a well known, although relatively unfrequent, cause of flank pain resistant to administration of spasmolytic and nonsteroidal anti-inflammatory drugs. We present an original case of a 41-year-old man, complaining of acute severe left flank pain, resistant to common analgesic therapy, who was diagnosed of segmental renal infarction of a branch of left renal artery. Pathophysiology of renal damage in cocaine users is multifactorial, and it has been postulated that the right kidney was more prone to ischaemia. Left kidney represents an extremely unusual site of cocaine-related renal infarction.

Cocaine and acute vascular diseases.

Cocaine is one of the most widely used drugs of abuse. Chest pain is the most common side effect requiring emergency visits after cocaine use. Vasoconstriction and platelet activation are the main effects of cocaine in the vasculature. In this brief review, we consider the most important clinical effects of cocaine abuse on the heart, brain and kidney. Symptoms related to cocaine toxicity such as myocardial infarction, congestive heart failure, arrhythmias, aortic dissection, stroke, renal failure, are similar to the clinical picture of atherosclerotic vascular damage, even if the age of cocaine abusers is usually in the second and third decades. Clinicians (especially emergency department physicians) should consider substance abuse among the differential diagnosis of chest pain in young people.

Clinical features of cardio-renal syndrome in a cohort of consecutive patients admitted to an internal medicine ward.

INTRODUCTION: Cardiorenal syndrome (CRS) is a disorder of the heart and kidney whereby interactions between the 2 organs can occur. We recorded the clinical features of CRS in patients consecutively admitted to an Internal Medicine ward. PATIENTS AND METHODS: We retrospectively analyzed the anthropometric, history, clinical, biochemical and treatment characteristics in 438 out of 2,998 subjects (14.6%) admitted to our unit (from June 2007 to December 2009), diagnosed with CRS, according to Acute Dialysis Quality Initiative (ADQI) recommendations. Estimated glomerular filtration (eGFR) was calculated using several equations: MDRD (Modification of Diet in Renal Disease; 2 variations GFR(MDRD186), GFR(MDRD175)), Mayo, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockroft-Gault. RESULTS: Mean age was 80±8 years, 222 (50.6%) were males, 321 (73.2%) were smokers, 229 (52.2%) were diabetic, 207 (47.2%) had a history of acute myocardial infarction, 167 (38.1%) had angina, 135 (30.8%) were affected by cerebrovascular disease, 339 (77.3%) had peripheral arterial disease. CRS was type 1 in 211 cases (48.2%), type 2 in 96 (21.9%), type 3 in 88 (20.1%), type 4 in 29 (6.6%) and type 5 in 14 (3.2%). eGFR, calculated by different formulae, ranged between 31 and 36 ml/min/1.73 m(2). GFR was lower in CRS type 3 than in the other types, and the values ranged between 24 and 27 ml/min/1.73 m(2). Mean hospital length-of-stay (LOS) was 9.8±6.3 days. Diuretics were the most prescribed medication (78.7%); only 5 patients underwent haemodialysis. CONCLUSIONS: CRS is common, especially in the elderly. CRS Type 1 was the prevalent subset and patients had stage 3-4 renal insufficiency. Results obtained from the GFR equations were similar although the Mayo equation tended to overestimate the eGFR.

The dilemma of diagnosing fever of unknown origin: large arteries vasculitis revealed by 18F-FDG PET/CT imaging. A case report.

Fever of unknown origin (FUO) is an uncommon disease, and its underlying etiology may include a number causes, i.e., infections, malignancies, autoimmune conditions. Diagnosis is often a difficult task, and usually physician spend time and money in order to define the etiology of FUO. We report a case of patient who presented with FUO and headache, and positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) allowed to reveal the presence of a large vessel vasculitis. 18F-FDG PET may represent an useful tool in patients with FUO, since it can early depict an hypermetabolic activity due to inflammation and so help to achieve a final diagnosis in some cases of FUO.

Relationship between major adverse cardiac events and angiographic findings in dialysis patients.

BACKGROUND: In dialysis patients, coronary angiography (CA) predicts major adverse coronary events (MACE) better than non-invasive tests. The aim of this study was to investigate in such patients the relationship between coronary atherosclerotic damage shown by angiography and MACE, during an average follow-up period of more than 5 years. PATIENTS AND METHODS: Coronary angiography was performed in 63 dialysis patients (mean age 56 ± 12 years, 49 men); 37 subjects awaiting kidney transplantation had no history of cardiac disease, whereas the remaining 26 patients had clinical evidence of coronary artery disease (CAD). During a follow-up period of 62 ± 20 months (range 12-109), all the MACE were recorded. Statistical analysis was carried out by dividing the patients into two groups, those who had MACE (MACE group) and those who were free of cardiac events (FCE group). Severe CAD on CA was defined as luminal stenosis ≥ 75% in at least one vessel. Logistic regression analysis and Cox regression analysis were carried out in order to evaluate which variable was associated with MACE. RESULTS: At the end of follow-up, 17 subjects had MACE and severe CAD was shown in the epicardial arteries of 31 patients (49%). Compared to the FCE group, the MACE group had older age (65 ± 10 vs 53 ± 11 years, P = 0.002), lower diastolic blood pressure (79 ± 7 vs 85 ± 7 mmHg, P = 0.0037), higher prevalence of CAD (82 vs 30%, P = 0.0002) and cerebrovascular disease (41 vs 15%, P = 0.0278). Coronary artery damage was higher in the MACE group than in the FCE group. Logistic and Cox regression analyses showed that age was the only variable independently associated with MACE (OR 1.109 95% CI 1.022-1.204, P = 0.0133, hazard ratio 1.066 95% CI 1.010-1.125, P = 0.02, respectively). After removal of age from the model, MACE were independently associated with haemodynamic stenosis of coronary arteries (OR 7.429 95% CI 1.829-30.173, P = 0.005, hazard ratio 5.992 95% CI 1.655-21.698, P = 0.006, respectively). Event-free survival was much better in the 37 renal transplant candidates with no history of CAD than in the 26 patients who had clinical evidence of CAD. CONCLUSIONS: This observational study confirms that in dialysis patients coronary atherosclerotic damage shown by angiography is strongly related to MACE and that age and severe CAD are major risk factors for MACE.

Detection of urinary abnormalities in a community from northern Italy based on the World Kidney Day screening program.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide health problem, and promotion of the World Kidney Day has improved general population education and awareness of renal illnesses aimed at ameliorating disease prevention. The Kidney Day was also an opportunity for us to investigate risk factors for CKD in an Italian population. PATIENTS AND METHODS: A total of 1,341 subjects from the general population living in the area of Ferrara, a town in the northeast of Italy, aged 50-70 years, were investigated. From each participant age, sex, smoking status, current antihypertensive medications, hypercholesterolemic and diabetic status, body mass index (BMI), waist circumference and blood pressure (BP) were obtained. All subjects underwent dipstick urinalysis for the evaluation of proteinuria, hematuria and leukocyturia. RESULTS: Fifteen percent of patients were diabetics, and 20% were smokers. Mean BMI was 26.9 ± 4.3 kg/m(2), mean systolic BP was 133.7 ± 18.7 mmHg and mean diastolic BP 78.1 ± 9.9 mmHg. A total of 828 participants were not taking any antihypertensive drugs. In 24% of subjects, we found proteinuria, in 18% hematuria and in 16% leukocyturia. Proteinuria was significantly associated with age and diabetes, hematuria was associated with age, female sex and smoking status, and leukocyturia was associated with age and female sex. CONCLUSIONS: Urinary abnormalities are common in general population, and in many cases, various abnormalities overlap. These abnormalities could be associated with cardiovascular risk factors. We believe that our initiative, based on the experience of the World Kidney Day, could increase the awareness of general practitioners and general population of the risks of renal conditions.

Caffeine intake induces an alteration in human neutrophil A2A adenosine receptors.

Caffeine is the most widely used drug in the world and acts mainly through antagonism of the effects mediated by the adenosine receptor subtypes A1, A2A, A2B and A3. We determined whether repeated caffeine administration at different doses and for different periods of time (400 or 600 mg/day for 1 week and 400 mg/day for 2 weeks) alters human neutrophil A2A adenosine receptor density and function. Saturation binding assays showed an increase in affinity (K(D)) and density (B(max)) of A2A adenosine receptors after caffeine intake. These changes were accompanied by increases in cAMP accumulation and decreases in superoxide anion production after stimulation of the A2A receptor subtype using the agonist 5'-N-ethylcarboxamidoadenosine (NECA). Binding and functional changes of A2A receptors returned to baseline after 48 h of caffeine withdrawal. The findings are consistent with a potential anti-inflammatory effect of caffeine mediated by neutrophil A2A receptors.

Oxidative stress in essential hypertension.

A major cause for endothelial dysfunction in essential hypertension is decreased availability of nitric oxide (NO). Impairment in NO bioavailability is likely to be the consequence of multiple mechanisms affecting NO synthesis as well as NO breakdown. An alteration in the redox balance in endothelial cells leads to increased superoxide anion production and oxidative stress. This in turn not only exerts negative effects on vascular tone, but is also able to activate important mechanisms (such as platelet activity, leukocyte adhesion, vascular smooth muscle cell proliferation and expression of adhesion molecules) with an established central role in the pathogenesis of hypertensive target organ damage. As a consequence, a drug therapy able to restore NO availability in essential hypertensive patients would probably exert additional benefits, as compared to blood pressure lowering per se, in terms of prevention of target organ damage and improved prognosis of these patients. Unfortunately, as of today only the antagonists of the renin-angiotensin system and the calcium-channel blockers have shown some ability in this respect, whereas no longitudinal intervention study has been undertaken, so far, to prove that the restoration of NO bioavailability through an antihypertensive treatment may confer additional prognostic advantage to essential hypertensive patients.

Circadian variation in onset of acute cardiogenic pulmonary edema is independent of patients' features and underlying pathophysiological causes.

BACKGROUND: The present study aimed to confirm the existence of a circadian pattern in the onset of acute pulmonary edema (APE) and to verify whether sex, age, preexisting diseases, and clinical causes determining the event may influence it. SUBJECTS AND METHODS: The study considered all consecutive cases of APE observed at the St. Anna General Hospital of Ferrara, Italy, during a 7-year period from January 1, 1992, to December 31, 1998. The sample population was divided into subgroups by sex, age (<75 and > or =75 years), presence or absence of diabetes and hypertension, clinical causes determining the event (i.e., acute myocardial infarction (AMI), pulmonary embolism, arrhythmias). The most important associated or concomitant diseases were also considered (i.e., coronary heart disease and angina, previous myocardial infarction, chronic cardiac failure, dilatative cardiopathy, chronic atrial fibrillation, valvular disease, chronic obstructive pulmonary disease, chronic cor pulmonale, malignancy, chronic renal failure). Time of symptom onset of each event was recorded accurately, then tabulated into 24 increments of 1h (e.g., 06:00 to 06:59 was reported as 6 A.M.). For statistical chronobiological analysis, partial Fourier series were used. RESULTS: During the 7-year period, 1321 consecutive cases of APE in 1014 different subjects were observed. The majority of events occurred at night, and statistical analysis showed a 24h rhythmicity both in the total sample population and in all considered subgroups, with the only exception being patients with pulmonary embolism and arrhythmias, for which the small number of cases made the study of rhythms in APE impossible. CONCLUSIONS: The nighttime preference in the occurrence of APE appears to be quite independent of all demographic features or underlying pathophysiological causes.

Dose and time effects of caffeine intake on human platelet adenosine A(2A) receptors : functional and biochemical aspects.

BACKGROUND-We determined whether repeated caffeine administration at different dosages and for different periods of time (400 or 600 mg/d for 1 week or 400 mg/d for 2 weeks) upregulates human platelet adenosine A(2A) receptors and is accompanied by increases in cAMP accumulation and decreases in aggregation and calcium levels after stimulation of A(2A) receptors by the selective agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA). METHODS AND RESULTS-Platelets were obtained from peripheral venous blood of 45 healthy human volunteers at the end of 2 weeks of caffeine abstinence and at 12, 60, and 108 hours after the last dose of caffeine. The lowest dose of caffeine, when given for only 7 days, had no effect. Increasing the total dose, either by giving 400 mg/d for 14 days or giving 600 mg/d, resulted in binding assays performed with the adenosine A(2A) receptor radioligand [(3)H]SCH 58261 [5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1, 5-c]pyrimidine], in the upregulation of A(2A) receptors. Moreover, the potency of HE-NECA to produce antiaggregatory effects, a rise in cAMP accumulation, and a decrease in calcium levels was significantly increased. CONCLUSIONS-Chronic caffeine intake can lead to upregulation of adenosine A(2A) receptors, which is accompanied by sensitization, in a time- and dose-dependent manner, to the actions of the agonist HE-NECA.

Platelet alpha2-adrenoceptor alterations in patients with essential hypertension are normalized after treatment with doxazosin but not propranolol.

OBJECTIVE: Marked alterations have been demonstrated to occur in the platelet alpha2-adrenoceptors of patients with essential hypertension. The purpose of this study was to determine whether antihypertensive treatment with alpha-adrenergic blocker doxazosin or beta-adrenergic blocker propranolol can affect the affinity and the density of platelet alpha2-adrenoceptors in such patients. SUBJECTS AND METHODS: In two groups of 22 previously untreated, essential hypertensive patients, the mean affinity (Kd) and density (B(max)) of platelet alpha2-adrenoceptors were studied by [3H]-UK 14304 binding assays; the first assays were performed before any medication was begun, the second were performed after treatment for up to 13 weeks with doxazosin or propranolol. A third group of 22 healthy normotensive volunteers matched by age, sex and body mass index was used as control. RESULTS: Blood pressure did not differ significantly in the two hypertensive groups, and treatment with the two drugs resulted in closely similar, normal blood pressure levels. Kd and B(max) values were significantly higher in the two hypertensive groups than in controls. After treatment with propranolol the binding parameters did not change significantly, whereas after treatment with doxazosin Kd and B(max) returned to normotensive values. CONCLUSIONS: In previously untreated, essential hypertensive patients platelet alpha2-adrenoceptors have a lower affinity but a higher density than in normotensive subjects. Despite similar effects on blood pressure, the treatment with the alpha-adrenergic blocker doxazosin is followed by restoration of normal findings in the binding assays of platelet alpha2-adrenoceptors whereas the treatment with the beta-adrenergic blocker propranolol does not alter the Kd and B(max) values.

Seasonal variation in the occurrence of nontraumatic rupture of thoracic aorta.

Research has identified circadian and seasonal patterns for several acute cardiovascular diseases. In order to investigate the possible existence of a seasonal variation in the onset of acute nontraumatic ruptures of thoracic aorta, this study considered all patients referred to the emergency department of St Anna Hospital of Ferrara, Italy, from January 1985 to December 1996. In the considered period, 85 patients (52 males, 33 females) of nontraumatic ruptures of thoracic aorta were observed. Cosinor analysis and partial Fourier series with up to 4 harmonics were applied to monthly data, and the best-fitting curves for circannual rhythmicity were calculated. A higher winter occurrence with a significant peak in January was found for the total population and the male subgroup. Although the underlying factors are not fully known, such patterns strictly resemble that of arterial blood pressure. Emergency doctors can put to practical use the recognition of a clearly identified chronorisk for aortic rupture, increasing alertness, and providing the most effective antihypertensive protection at the specific vulnerable periods.

Caffeine alters A2A adenosine receptors and their function in human platelets.

BACKGROUND: Caffeine acts mainly via blockade of adenosine receptors, which have been classified into A1, A2A, A2B, and A3 subtypes. We determined whether repeated caffeine administration (750 mg/d for 1 week) upregulates the human platelet A2A adenosine receptor and is accompanied by sensitization of platelet responses (increase in cAMP accumulation and decrease in platelet aggregation) to selective stimulation of the A2A receptors. METHODS AND RESULTS: Platelets were obtained from peripheral venous blood of 9 human volunteers at the end of 1 week of caffeine abstinence (control) and at 12 and 60 hours after the last dose of caffeine (withdrawal). The A2A receptor radioligand [3H]SCH 58261 (5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1, 5-c]-pyrimidine) bound to a single affinity class of sites in platelet membranes from controls with a Bmax of 98+/-2 fmol/mg protein and a KD of 1.29+/-0.05 nmol/L. At 12 and 60 hours after caffeine withdrawal, the radioligand bound with similar affinity (KD=1.36+/-0.06 and 1.21+/-0.05 nmol/L, respectively), but the Bmax was increased (P<0.01) to 128+/-3 and 132+/-2 fmol/mg protein. The A2A receptor agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA) increased cAMP accumulation (EC50=59+/-3 nmol/L) and inhibited (IC50=90+/-6 nmol/L) aggregation of control platelets. The EC50 values for HE-NECA to increase cAMP accumulation of platelets were reduced (P<0.01) at 12 and 60 hours after caffeine withdrawal (31+/-3 and 21+/-2 nmol/L, respectively). The IC50 values for HE-NECA to inhibit ADP-induced platelet aggregation were 50+/-5 and 30+/-2 nmol/L at 12 and 60 hours after caffeine withdrawal, respectively. CONCLUSIONS: Chronic caffeine intake leads to upregulation of A2A receptors and is accompanied by sensitization to the actions of the agonist HE-NECA.

Platelet alpha2-adrenoceptor alterations in patients with essential hypertension.

AIMS: The purpose of this study was to determine whether human platelet alpha2-adrenoceptors were altered in essential hypertension. A systematic analysis was carried out on 165 normotensives and 124 untreated primary hypertensives. METHODS: The study was performed at different levels: i) density and affinity of platelet alpha2-adrenoceptors were determined by receptor binding assays using the full alpha2-adrenoceptor agonist [3H]-UK 14304 and a thermodynamic analysis of data was carried out to evaluate if binding mechanisms at the molecular level were altered during hypertension; ii) the functionality of Gi proteins coupled to alpha2-adrenoceptors and iii) forskolin-stimulated cAMP levels were measured. RESULTS: Platelet alpha2-adrenoceptors mean density (Bmax) and affinity (Kd) (+/-s.e.mean) were significantly lower and higher, respectively, in normotensive than in hypertensive subjects [Bmax=327+/-4 vs 435+/-5 fmol mg(-1) of protein (P<0.01) and Kd=3.76+/-10.05 vs 6.50+/-0.15 nM (P<0.01), respectively]. The 50% stimulating concentration of adrenaline on [35S]-GTPgammaS binding to Gi proteins was significantly (P<0.01) lower in normotensives (12+/-2 nM) than in hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on forskolin-stimulated cAMP levels was significantly (P<0.01) lower in normotensive (22+/-2 nM) than in hypertensive subjects (200+/-25 nM). CONCLUSIONS: Present analysis, including receptorial and functional data, provides evidence that marked alterations occur in platelet alpha2-adrenoceptors of hypertensive subjects.