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Biomedical subjects

C Zoccali

Publications and source records attributed to C Zoccali.

At least 55 records · Page 3Linked to original sources

Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria.

BACKGROUND: Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h. METHODS: In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (> or =53 g/24 h). Median follow-up was 31 months. FINDINGS: The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05] mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2. INTERPRETATION: In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.

Adult↗

Prediction of left ventricular geometry by clinic, pre-dialysis and 24-h ambulatory BP monitoring in hemodialysis patients: CREED investigators.

OBJECTIVE: Arterial hypertension is an established risk factor for left ventricular hypertrophy (LVH) in the uremic population. However, whether 24-h monitoring is a better predictor of LVH than clinic blood pressure and routine pre-dialysis measurements in these patients is still undefined. METHODS: This problem was studied in 64 nondiabetic hemodialysis patients without heart failure. The echocardiographic study as well as the clinic and 24-h ambulatory blood pressure (BP) measurements were performed during the day off-dialysis. Pre-dialysis arterial pressure was calculated as the average value of the 12 routine recordings taken during the month preceding the study. RESULTS: In multivariate models, including also sex, body mass index, hematocrit and serum cholesterol, pre-dialysis systolic, diastolic and pulse pressures were the only independent BP determinants of heart geometry. Twenty-four hour ambulatory BP monitoring (ABPM) did add significant (but weak) information to the prediction of left ventricular internal dimension, i.e. it increased by 9% (P = 0.01) the variance already explained by pre-dialysis diastolic BP and other significant covariates. However, 24-h ABPM did not add any significant and independent explanatory information to the corresponding pre-dialysis measurements for the posterior wall and interventricular septum measurements, and for left ventricular mass (-0.6 to +3.9%; average +1.1%). CONCLUSIONS: In dialysis patients, pre-dialysis BP is at least as strong a predictor of left ventricular mass as 24-h ambulatory monitoring. Thus, the average of 12 routine pre-dialysis measurements may be used to predict heart geometry in dialysis patients without any loss of information in comparison with 24-h ambulatory monitoring.

Adult↗

In chronic nephropathies prolonged ACE inhibition can induce remission: dynamics of time-dependent changes in GFR. Investigators of the GISEN Group. Gruppo Italiano Studi Epidemiologici in Nefrologia.

The Ramipril Efficacy in Nephropathy Core and Follow-Up Study found that > or =36 mo of continued ramipril therapy decreased substantially the risk of end-stage renal failure (ESRF) in patients with chronic nephropathies and a urinary protein excretion rate > or =3 g/24 h. This study investigates the time-dependent changes in GFR in these patients and in control subjects who were randomized to conventional therapy during the Core period and switched to ramipril during the Follow-Up study. Analyses included 150 patients (continued ramipril: n = 74; switched to ramipril: n = 76) who had at least three GFR measurements (including baseline) during the whole observation period and a subgroup of 43 patients (continued ramipril: n = 26; switched to ramipril: n = 17) who had at least six GFR measurements, including at least three on the Core and at least three on the Follow-Up study. Ramipril (1.25 to 5 mg/d) and conventional therapy were targeted at achieving a diastolic BP below 90 mm Hg. The main efficacy variables were GFR and ESRF (need for dialysis). Analysis was by intention to treat. Throughout the study, the mean +/- SEM rate of GFR decline (deltaGFR) was significantly lower in patients continued on ramipril compared to those switched to ramipril (0.51+/-0.09 versus 0.76+/-0.10 ml/min per 1.73 m2 per mo, P<0.03). In patients on continued ramipril who had at least six GFR measured--but not in control subjects--deltaGFR progressively improved with time and, in the cohort with the longest follow-up, decreased from (in ml/min per 1.73 m2 per mo): 0.16+/-0.12 (at 18 mo) to 0.10+/-0.05 (at 60 mo). This rate was about 10-fold slower compared to patients on conventional therapy during the REIN Core study. Analyses of the individual slopes found that at the end of the follow-up, 10 of 26 patients on continued ramipril therapy had a positive deltaGFR and another 10 patients had an improvement of deltaGFR while on ramipril therapy. DeltaGFR significantly improved in parallel with a significant reduction in proteinuria. Changes in deltaGFR (P = 0.0001) and proteinuria (P = 0.04) were significantly different in the two groups. Baseline characteristics and changes in systolic and diastolic BP and 24-h urine urea and sodium excretion were comparable. The present results offer evidence that in chronic nephropathies, the tendency of GFR to decline with time can be effectively halted, even in patients with remarkably severe disease.

Adult↗

Calcium channel blockers in diabetic subjects: innocent at last?

Calcium antagonists are indicted as a potential trigger of a variety of complications spanning from myocardial infarction to bleeding and cancer. Three randomised controlled trials, the MIDAS, the FACET and the ABCD trial, seem to suggest that the risk for myocardial infarction is increased in diabetics on calcium antagonists. These trials in aggregate totalled only 92 cardiovascular events and it is possible that the observed differences were due to random errors. Most of the patients of the ABCD trial discontinued the medication to which they were initially randomised before the end of the study, which raised the possibility of systematic bias. In both the MIDAS and ABCD studies cardiovascular events were secondary end-points and the apparent adverse effects were identified only by subgroup analyses. Furthermore, in both studies, patients in the control groups were being treated with ACE inhibitors. The lack of a placebo group makes it impossible to establish whether the observed effects were due to the harmful influence of calcium antagonism or to the favourable effects of ACE inhibition. New data abstracted from the PIUMA database show that the rate of total cardiovascular and cardiac events did not differ between diabetics on calcium antagonists and diabetics not using these drugs. These new data are in keeping with findings in the HOT study where an impressive degree of cardiac protection was observed in diabetic patients on felodipine.

Angiotensin-Converting Enzyme Inhibitors↗

Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients.

BACKGROUND: Adrenomedullin, is a potent vasorelaxant that is highly expressed in the adrenal medulla, kidney, heart and lung. Since there is indirect evidence that hypervolemia enhances the release of this peptide, we measured plasma adrenomedullin in 9 uremic patients on chronic dialysis treatment and in 10 healthy subjects matched for age and gender. METHODS: Measurements were performed in baseline conditions, after isotonic fluid subtraction (by isolated ultrafiltration) and during a 70 degrees tilt. Tilt was performed in volume-depleted state, that is, after isolated ultrafiltration (UF). In the control experiment patients underwent sham UF (UF = 0) followed by a period of supine resting identical to the one they had spent in tilted position in the active experiment. Adrenomedullin was measured on pre-extracted plasma samples (Sep-Pak C-18 cartridges) by a specific RIA for human adrenomedullin 1-52. RESULTS: The average plasma adrenomedullin was 2.6 times higher (P < 0.01) in uremic patients (103 +/- 8 pg/ml) than in healthy subjects (39 +/- 7 pg/ml). After fluid subtraction (-2.6 +/- 0.2 liter) adrenomedullin fell to 79. +/- 8 pg/ml (P = 0.02) but remained well above the upper limit of the 95% CI in normal subjects (52 pg/ml). There was no relationship between adrenomedullin and ANF changes. In the control experiment sham UF did not modify plasma adrenomedullin. Tilt did not significantly change plasma adrenomedullin either in dialysis patients or healthy subjects. CONCLUSIONS: Plasma adrenomedullin is markedly raised in uremic patients on dialysis, which confirms that the kidney has a major role in the clearance of this peptide. However, the fall in plasma adrenomedullin after isolated UF indicates that the plasma concentration of this peptide is influenced by the body fluid volume status. Whether or not adrenomedullin participates in the counter-regulatory response to fluid subtraction in uremic patients remains to be explored by specific antagonists of this substance.

Adrenomedullin↗

Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular geometry in dialysis patients.

It is well established that nocturnal hypoxemia in sleep apnea causes an inversion of the circadian arterial pressure rhythm and triggers nocturnal hypertension. Since sleep apnea is very frequent in dialysis patients, we hypothesized that nocturnal hypoxemia may be a factor that contributes to alter the 24-hour arterial pressure profile in these patients. To test the hypothesis 32 dialysis patients underwent 24-hour blood pressure (BP) monitoring and continuous monitoring of arterial O2 saturation during the night-time. Hemodialysis patients were studied during the non-dialysis day. All patients underwent an echocardiographic study. Thirteen patients had no episode of nocturnal hypoxemia (group I), 7 had at least one episode overnight but less than 2 episodes/hr (group II) and 12 had > or = 2 episodes/hr (group III). The average daytime systolic pressure was similar in the three groups. However, the average nocturnal systolic pressure fell in the first group (-2.5 +/- 4.2%) and rose in the second (+2.0 +/- 3.6%) and in the third (+3.9 +/- 2.2%) group (one way ANOVA, P < 0.005). The relative wall thickness of the left ventricle (RWT) was significantly (P < 0.05) higher in group III than in group I, and in the aggregate (N = 32) there was an inverse relationship between average nocturnal SaO2 and RWT (r = -0.43, P = 0.015). The proportion of patients with concentric remodeling or concentric hypertrophy was higher (P = 0.05) in the group with a more severe degree of nocturnal hypoxemia (group III, 8 of 12) than in the other two groups (group I, 3 of 13; group II, 2 of 7). Nocturnal hypoxemia is associated with the "non-dipping" arterial pressure profile in dialysis patients. Disturbed respiratory control during the night may represent an important cardiovascular risk factor in dialysis patients.

Adolescent↗

Medical knowledge, quality of life and accreditation of quality in health care. The perspective of the clinical nephrologist.

The problem of Quality has three dimensions: the dimension of quality of life (the patients, perspective), the dimension of quality of medical knowledge and of the appropriate use of medical technology (i.e. the "evidence based" medical approach to clinical decision making) and the dimension of accreditation of health care providers. The problem of keeping clinicians well updated is a difficult one but there are solutions. The medical literature can be selectively but thoroughly analysed and on the basis of high quality studies specific recommendations (i.e. guidelines) can be produced. Scientific societies are now making major efforts to produce high quality guidelines for the treatment of patients with chronic renal failure and for those on chronic dialysis. The DOQI and the Standards Document by the Renal Association offer first class examples of how scientific knowledge can be translated into clear practice guidelines. As far as the dimension of quality of medical knowledge is concerned, there is now increasing evidence that the taking into full account of quality of life issues such as those regarding the physical, psychic and social dimensions of health improves substantially patient's satisfaction and the patient-doctor relationship. Quality of life considerations are now fully considered when evaluating the efficacy erythropoietin in the treatment of uraemic anemia. If we accept the perspective that health care organisations should aim at excellence, the performance of a given provider can be evaluated on the basis of various indicators and its performance made transparent to the potential users. The internet has become the most accessible source of such kind of information and it can be easily forecasted that the performances of all major hospitals and health care organisations will soon be in the public domain.

Accreditation↗

The heart rate response pattern to dialysis hypotension in haemodialysis patients.

BACKGROUND: Hypotension during haemodialysis may be caused by the activation of a cardiovascular reflex causing abrupt sympathetic withdrawal, vasodilatation and bradycardia (bradycardic hypotension). However, the frequency of this type of hypotension is undefined and it is unclear whether or not it underlies a peculiar predisposition to vasodepressor syncope. OBJECTIVE: To assess the prevalence of bradycardic hypotension and to test the hypothesis that dialysis patients are predisposed to vasodepressor syncope. RESULTS: Sixty hypotensive episodes were recorded in 20 patients (> or = 2 episodes in 15 patients). Heart rate increased in 35 episodes, did not change in 19 episodes and decreased in six episodes. The HR response pattern to hypotension was reproducible in 10 patients (always tachycardia, 6; always unchanged heart rate 4). Patients developing bradycardic hypotension (n = 5) all had an erratic HR response to hypotension (i.e. bradycardia preceded or followed by tachycardia or by no HR change) and were characterized either by the typical haemodynamic pattern of hypovolaemia (predialysis hypotension, tachycardia and low TBW) or by being treated with a very high UF rate (> 0.3 ml/kg/min). Post-dialysis echocardiography showed that the LVEDD was less (one-tailed P = 0.055) in patients with bradycardic hypotension than in those with tachycardic responses or with unchanged HR. On tilt testing (after dialysis) three of 11 (27%) dialysis hypotensive patients developed bradycardic hypotension. This proportion was identical to that expected in healthy subjects and in control patients without syncope. CONCLUSIONS: Tachycardia is the more frequent heart rate response to dialysis hypotension in uraemic patients. Bradycardic hypotension in dialysis patients is associated with a haemodynamic profile indicating a more severe degree of cardiovascular underfilling. Bradycardic hypotension probably represents a physiological response to hypovolaemia rather than the expression of a peculiar predisposition to vasodepressor syncope.

Adult↗

The influence of volume depletion and central hypovolemia on the plasma concentration of parathyroid hormone in dialysis patients.

Because changes in extracellular volume during dialysis cause reflex neurohonnonal changes that may influence parathyroid hormone (PTH) release independently of calcium, the influence of isotonic volume depletion (by isolated ultrafiltration) and central hypovolemia (70 degrees tilt) on serum PTH1-84 was studied in 16 hemodialysis patients. Tilting was performed in volume depleted state, i.e., immediately after hemodialysis. In the control study, patients underwent sham ultrafiltration (UF = 0) and after dialysis maintained the supine position for the same length of time they remained in the tilt position in the active experiment. Isolated ultrafiltration (-2.3 +/- SEM 0.3 L) caused a 21% fall in mean arterial pressure (from 101 +/- 6 to 80 +/- 6 mmHg, P < 0.01), a fall that was accompanied by a marked increase in plasma catecholamine levels (norepinephrine P < 0.001, epinephrine P < 0.025), in plasma renin activity (P < 0.001) and in plasma arginine vasopressin (P < O.001). Atrial natriuretic factor showed a slight reduction, whereas the plasma endothelin-1 level did not change. Serum Ca showed the expected, hemoconcentration-dependent rise (from 4.1 +/- 0.1 to 4.4 +/- 0.1 meq/L, P < 0.01). Interestingly, UF caused a marked rise in plasma PTH1-84 concentration (from 252 +/- 62 to 335 +/- 72 pg/ml, P < 0.01). UF-induced changes in serum PTH1-84 were related to norepinephrine changes (r = 0.57) as well as to plasma renin activity (r = 0.50). After hemodialysis, tilting induced a pronounced rise in serum PTH1-84 (from 102 +/- 29 to 200 +/- 55 pg/ml), and these changes were slightly related to plasma epinephrine (r = 0.49) but independent of other parameters. In the control experiment, neither sham UF nor recumbency modified serum PTH. In hemodialysis patients, serum PTH is sensitive to changes in extracellular and central blood volume of magnitude sufficient to decrease arterial pressure. Avoiding marked volume stimuli might help to refine the interpretation of the Ca/PTH curves during hemodialysis in these patients.

Adult↗