Age dependency of myocardial structure: a quantitative two-dimensional echocardiographic study in a normal population.

Histological changes of the myocardium occur with aging due to an increase in collagen content, hypertrophy of fibers, and patchy fibrosis. Quantitative analysis of conventional echocardiographic images provides an in vivo assessment of myocardial structure by the evaluation of the gray level distribution; with this technique, a relation between myocardial fibrosis and pathological ultrasonic response has been documented. The aim of this study was to evaluate the relation between ultrasonically assessed myocardial structure and age in a normal population. Seventy-eight subjects (47 men; mean age, 51 years; age range, 23-87 years) without apparent cardiovascular and systemic disease underwent conventional two-dimensional echocardiographic examinations. Still frames at end-diastole from apical four-chamber view were digitized and converted in matrices of 256 x 256 pixels. First-order statistical analysis was performed to describe a region of interest in the interventricular septum. The following parameters were studied: mean (gray level amplitude), standard deviation (overall contrast), uniformity (tonal organization), and entropy (tendency of gray levels to be spread). Myocardial structure was assessed in 75 of 78 subjects, divided into three groups: I, age 23-40 years; II, age 41-65 years; and III, > 65 years. Significant differences for all the parameters were found between the age groups. Age correlated directly with mean and entropy (r = 0.77 and 0.69, respectively) and inversely with uniformity (r = 0.70). Our results suggest that quantitative echocardiography can reveal age-related changes in myocardial structure that are characterized by a greater echogenicity and loss in tonal organization, possibly due to increased collagen content within the fibers.

Double-chamber on-line hemodiafiltration: a novel technique with intra-treatment monitoring of dialysate ultrafilter integrity.

On-line hemodiafiltration is a technique that relies on the re-injection of pyrogen-free substitution fluid obtained by cold filtration of dialysate. Therefore, safety of this treatment modality depends on the quality of dialysate and, mainly, on the integrity of the ultrafilter(s) employed. Double-chamber on-line hemodiafiltration is a new technique where re-infusion takes place inside the dialyser by means of dialysate backfiltration. The peculiar geometry of the dialyser allows intra-treatment assessment of its fibre integrity. In this paper, we tested feasibility and safety of this new modality of on-line treatment. The extracorporeal blood and infusate pressure values resulted well inside the safety range. Blood urea clearances and beta(2) removal were consistent with the figures usually found in standard hemodiafiltration. Whole blood production of cytokines was similar when blood was exposed to saline or infusate, both values being comparable to the spontaneous whole blood cytokine release. The on-line dialyser fibre integrity check showed a great sensitivity even for minimal dialyser damage. We conclude that double-chamber on-line hemodiafiltration is a feasible and safe procedure. Our preliminary results encourage the undertaking of multicentre, prospective, randomised studies.

Cardiovascular stability during haemodialysis, haemofiltration and haemodiafiltration.

Several comparative studies have claimed that procedures based substantially or exclusively on pressure-driven water-solute transport, such as haemodiafiltration or haemofiltration, afford better protection of the cardiovascular tolerance to fluid removal than conventional haemodialysis. During each depurative modality, several factors are set in motion that might impact, each in its own right, upon the haemodynamic response to fluid withdrawal. To explore the haemodynamic effect of each of them singularly, one needs to keep all other components unvaried. However, this is very difficult to accomplish. For instance, to confirm the alleged greater protection of cardiovascular stability by pure convection vs diffusion, one needs to keep unvaried all the other factors potentially affecting haemodynamic tolerance, i.e. the rate of body fluid removal, the membrane, the buffer, the blood temperature in the extracorporeal circuit, depuration efficiency, the sodium balance, the fluid sterility and so on. Such studies are still awaited. However, clinical trials published to date have not resolved the question of whether haemofiltration and haemodiafiltration provide a better haemodynamic tolerance to fluid removal. If we limit our consideration to controlled trials only, most prospective studies have adopted a cross-over design implemented on very small patient samples and for very short periods. Such an approach is liable to generate misleading results because the incidence of dialysis hypotension often fluctuates from time to time. Owing to such fluctuations, results can be strongly affected by the 'order effect' of the cross-over from one technique to the other. The negative results provided by parallel comparisons of procedures should be taken with caution because patients samples did not include a suitable proportion of unstable patients.

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.

Impaired sympathetic response before intradialytic hypotension: a study based on spectral analysis of heart rate and pressure variability.

The purpose of this study was to evaluate the autonomic response to standard haemodialysis and the changes associated with the onset of intradialytic hypotension in 12 normotensive patients with uraemia. Power spectra of R-R interval and of blood pressure fluctuations were obtained during a standard dialysis session and estimated in the low-frequency (LF, 30-150 mHz) and high-frequency (HF, 150-400 mHz) range. The absolute power of the LF component of blood pressure variations and the LF/HF ratio of R-R interval were assumed as indexes of sympathetic activity. Standard haemodialysis induced hypotension in six patients (unstable) while a minor pressure decline was present in the other six (stable). Normalized blood volume before dialysis and percentage volume reduction were similar in the two groups. Tachycardia in response to pressure and volume decrease was more pronounced in stable than in unstable patients, as evidenced by a higher slope of the relation between R-R interval and systolic blood pressure (7.9 versus 0.9 ms/mmHg, P<0.01). Sympathetic tone was enhanced during early dialysis in all patients (+2+/-1 for R-R LF/HF ratio, +2.4+/-0.6 mmHg2 and +7.2+/-2 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05), compared with baseline predialysis values. During late dialysis, unstable patients showed an impairment of sympathetic activation which preceded hypotension and was maximal during the crisis (-2.9+/-1.4 for R-R LF/HF ratio, -2.7+/-1.4 mmHg2 and -8.6+/-4.0 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05). On the contrary, stable patients showed constantly elevated indexes (+3.7+/-1.4 for R-R LF/HF ratio, +5.9+/-2.7 mmHg2 and +13.3+/-6.2 mmHg2 for LF of diastolic and of systolic blood pressure, P<0.05). Values returned to predialysis levels after the end of the dialysis session in all patients. We conclude that standard haemodialysis activates a marked and reversible sympathetic response in both stable and unstable uraemic patients. However, in unstable patients, such activation is impaired in late dialysis, therefore contributing to the onset of the hypotensive crisis.

Signal-averaged ECG abnormalities in haemodialysis patients. Role of dialysis.

BACKGROUND: Late potentials (LP) on the signal-averaged electrocardiogram (SAECG) are predictive of malignant ventricular arrhythmias and sudden cardiac death in patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction, both regional and global, as well as supraventricular and ventricular arrhythmias are reported in a high percentage of patients with end-stage renal failure (ESRF). The aim of the study was to assess the prevalence of LP and the effects of haemodialysis on the SAECG of ESRF patients. METHODS: SAECG was recorded immediately before and within 30 min after the end of dialysis in 48 patients in sinus rhythm, free of conduction disturbances on ECG and of signs of congestive heart failure. Serum electrolytes were sampled together with the SAECG recordings. An echo-Doppler exam was performed within 2 weeks of the study. SAECGs were adequate for analysis in 45/48 patients. LP were present when at least two of the following criteria were fulfilled: QRS duration < or = 115 ms, LAS40 < or = 38 ms, RMS40 > or = 38 microV at 40 Hz high pass bidirectional filter, and noise <0.7 microV. RESULTS: LP were detected in 12/45 patients (25%) on the SAECG before dialysis; of these 12 patients, seven had a history of a previous myocardial infarction and two had documented coronary artery disease (CAD). A significant greater wall motion score index--calculated on a 16 segment model--was reported in patients with LP (1.20+/-0.20 vs 1.01+/-0.03, P<0.01), while left ventricular mass was comparable in the two groups of patients. At the end of dialysis, a significant prolongation of fQRS duration was found both at 25 and 40 Hz filters (from 98+/-11 to 106+/-16 ms and from 97+/-12 s to 102+/-13 ms, respectively, P<0.001). A significant inverse relationship was seen between the percentage of dialysis-induced serum potassium reduction and fQRS changes at 40 Hz (r=-0.68, P<0.001). CONCLUSIONS: LP were detected in a significant proportion of dialysis patients, probably related to underlying CAD with left ventricular dysfunction. Prolongation of fQRS after dialysis could be explained by the acute reduction in serum potassium levels.

Convective treatments with on-line production of replacement fluid: a clinical experience lasting 6 years.

BACKGROUND: The introduction of techniques with on-line (OL) production of replacement fluid by filtration of dialysis fluid raises concerns about exposure of dialysis patients to pyrogenic substances. This work was undertaken to evaluate safety and feasibility of OL preparation of replacement fluid for haemodiafiltration (HDF). METHODS: OL HDF was carried out with commercially available monitors without any adjustment in the operational organization of our Centre. Bicarbonate dialysis fluid was filtered twice before being reinjected into the patients. The effects of acute load of OL fluid were assessed by very sensitive in vitro and in vivo tests; the chronic effects were assessed by monitoring the patients for the appearance of any untoward clinical manifestations and by measuring their cytokine response. RESULTS: In a pilot study the membrane filter culture technique of replacement fluid yielded no bacteria or mycetes growth, while LAL test was < 0.01 EU/ml. The normal human monocyte production of TNF alpha, IL-1 beta and IL-1Ra was not significantly different when cells were incubated with OL or commercial replacement fluid. The patients' body temperature profile (continuous recording during treatments and the following 24 h) overlapped with that of the control procedure. Over 6 years we performed 4284 OL treatments (total amount reinjected fluid 102,900 litres) on 13 patients treated for 26 +/- 9 months. In none of these treatments did we observe pyrogenic reactions. In comparison with the previous period on standard bicarbonate haemodialysis, OL HDF afforded significantly better cardiovascular tolerance to fluid removal and higher Kt/V values. The nutritional status did not deteriorate, while the acute-phase reactants and serum beta 2M levels did not increase. Moreover, no translucent cysts or destructive arthropathy were observed on bone X-rays. The patients' plasma cytokine levels and monocytes cytokines production, measured either before or after a single OL HDF, were comparable with the values obtained in controls treated with standard HDF. CONCLUSIONS: We conclude that OL-prepared replacement fluid is as safe as that of the commercial bags with regard to sterility and non-pyrogenicity. OL HDF can be readily implemented in any dialysis centre without bringing any further burden on the staff.

Nutritional and prognostic correlates of bioimpedance indexes in hemodialysis patients.

We carried out a cross sectional and longitudinal study to assess whether bioimpedance indexes (resistance, Rz; reactance, Xc; phase angle, PA) reflect the nutritional status of hemodialysis (HD) patients, and bear a significant association with their long-term survival. The bioimpedance data of 131 patients on chronic HD treatment were compared with those of 272 healthy controls matched for age and sex. Nutritional status was assessed by anthropometric variables, serum albumin (SA), normalized protein catabolic rate (nPCR), and subjective global assessment (SGA). All three bioimpedance indexes varied significantly with HD treatment, however, with the exception of Xc in post-HD, they were on average significantly (P < 0.016) different from controls either pre- and post-HD. Post-HD PA appeared to be the best index of nutritional status, being significantly correlated with SA, age, mid arm muscle circumference (MAMC), SGA, and nPCR (R2 = 0.44; P < 0.01). However, depending on the cut-off levels, PA failed to detect clinically overt malnutrition in one to two thirds of the patients with the worst SGA score. During the follow-up the changes in bioimpedance indexes reflected poorly the changes in dry blood weight, only delta Rz bore a significant correlation (r = 0.29; P < 0.01) with delta body wt. Patients having baseline phase angle values within the lower quartile had a significantly lower two-year survival rate than patients having higher values (59.3% vs. 91.3%; P < 0.01). Cox's analysis (proportional hazard model) showed that phase angle as a predictor of death outweighed all other parameters included in the model (age, SA, nPCR, MAMC, SGA), with a relative risk of 2.6 (95% CI = 1.6 to 4.2). Bioimpedance indexes do not appear to be reliable in detecting clinically overt depletion of lean body mass. However, the strong association of PA with patient survival suggests that this bioimpedance index reflects some dimension of the illness, which is not fully identifiable with the deranged nutritional status.

Characterization of myocardial tissue in patients undergoing maintenance hemodialysis by quantitative echocardiography.

The uremic state affects myocardial structure, bringing about, among other things, interstitial calcium deposition. Abnormalities of myocardial structure can be assessed quantitatively and noninvasively during life by the analysis of the gray-level distribution of conventional two-dimensional echocardiograms. The aim of this study was to evaluate the role of quantitative echocardiography in providing information on myocardial structure in patients under maintenance hemodialysis and to relate the ultrasonic findings with abnormalities in calcium-phosphate metabolism. Forty patients undergoing dialysis without abnormalities in left ventricular regional and global function and 17 hypertensive patients with comparable left ventricular hypertrophy were studied. The distribution of the gray levels within a region of interest in the interventricular septum was analyzed off-line by an array processor-based computer. Compared with hypertensive patients, patients undergoing dialysis showed a greater myocardial echogenicity (mean 92 +/- 20 versus 72 +/- 15; p = 0.004) and a reduced homogeneity of distribution of gray levels (entropy 4.5 +/- 0.2 versus 4.2 +/- 0.2, p < 0.01; uniformity 0.010 +/- 0.003 versus 0.020 +/- 0.004, p < 0.005). In the same patients, a significant negative linear relation was found between entropy and calcium-phosphate product (r = -0.66; p = 0.001). Quantitative analysis of conventional two-dimensional echocardiograms allows the detection of a pathologic myocardial structure in patients under maintenance hemodialysis with normal left ventricular function. These abnormalities are related to disorders of calcium-phosphate metabolism and bear no relationship to the degree of left ventricular hypertrophy.

[Early diagnosis of rapidly progressive glomerulonephritis]. / Diagnosi precoce delle glomerulonefriti rapidamente progressive.

The term rapidly progressive glomerulonephritis (RPGN) designates a group of glomerular diseases with different pathogenetic and clinical features, rapidly leading to renal or patient death in about 90% of the untreated cases. Histopathologically, it is characterized by glomerular crescents in at least 50-75% of the glomeruli (necrotizing crescentic glomerulonephritis), and very often, glomerular necrosis. The situation is, however, potentially reversible if adequately treated, and a favourable outcome depends largely on early diagnosis and treatment. Early diagnosis can be achieved if due importance is given to even seemingly unspecific manifestations such as "flu like syndrome" associated with "glomerular" hematuria. These manifestations are detectable before the down-hill course of renal functional derangement becomes evident and should lead the physician to consider RPGN among the diagnostic possibilities. Final diagnosis rests on serological tests and kidney biopsy. The battery of diagnostic serological tests (anti-GBM, anti-DNA antibodies, cryoglobulins, etc.) has recently been enriched by the assay of anti-neutrophil cytoplasmic antibodies (ANCA). These antibodies are detectable in over 90% of cases of Wegener's granulomatosis and primary necrotizing crescentic glomerulonephritis with or without lung involvement. ANCA-associated glomerulonephritis is the commonest form of RPGN, and the new serological assay provides an important tool for its early recognition. Renal biopsy is necessary to evaluate the severity of the nephritic process and modulate treatment accordingly. Timely diagnosis is one of the most important factors contributing to successful treatment outcome over both the short and the long term.

Non-invasive monitoring of hemodynamic parameters during hemodialysis.

We studied in 13 hemodialysis patients intradialytic variations of blood volume (BV) and cardiac output, by means of non-invasive methods. We found a weak correlation, r 0.2 or less, between BV variations and intradialysis blood pressure variations. The sensitivity of the former in describing the variations of the latter was only 32%. During the 30 min preceeding the hypothensive crisis the percent BV variations did not show any predictive trend. On the contrary, refilling increased as blood pressure dropped and a weak inverse relation (r -0.35) was found between these two parameters. Unstable patients had predialytic blood volume values significantly lower than stable ones and comparable to healthy subjects. On the contrary, the correlation between percent variations of cardiac output index and MAP was 0.68 with a sensitivity and specificity of 90% and 59%, respectively. Unfortunately these promising results were obtained only with an estimate of cardiac output obtained by echocardiography and not by transthoracic impedance cardiography, which is much more feasible than the former as on-line monitoring of cardiac output. On-line monitoring of hemodynamic parameters is an appealing but still unsolved task.

Thermal balance and dialysis hypotension.

Many studies have confirmed our original observation that dialysate T set at about 35 degrees C affords a better hemodynamic protection than the standard dialysate T of 37-38 degrees C. In this review we present some new data on the hemodynamic mechanism of the protective effect of cold dialysis on blood pressure. The study was based on serial assessment of the percent changes occurring during dialysis treatment in estimated stroke volume (aortic blood flow determined by Doppler echocardiography), blood volume (hemoglobinometry), arterial pressure (Dynamap), and heart rate (ECG), from which cardiac output (CO) indexes and total peripheral vascular resistances (TPVR) were derived. Of the 14 pts studied, 7 showed a drop in mean arterial pressure (MAP) of 25% or greater during standard dialysis (unstable patients). Compared with the 7 patients having more stable intradialysis MAP, unstable pts showed greater reduction in CO which was disproportionately greater than the reduction in blood volume, and a paradoxical decrease in TPVR, the difference being highly significant (p < 0.01 for both changes). When crossed-over to cold dialysis, along with a significantly lower reduction in MAP (p < 0.01) the unstable pts showed a lower decrease in CO which paralleled the reduction in blood volume, and an increase in TPVR. These changes were highly significant (p < 0.01). Data suggest that dialysis hypotension is characterized by an impaired venous return, probably due to the peripheral blood pooling (increased ratio between the 'unstressed' and 'stressed' blood volume) associated with the decrease in TPVR. Exposure of extracorporeal blood to cold dialysate favours the venous return to the heart by increasing TPVR and the 'stressed' blood volume.

Effects of low-dose captopril on renal hemodynamics and function in patients with cirrhosis of the liver.

BACKGROUND: In cirrhotic patients with ascites, captopril has deleterious effects on renal function, which have been referred to as captopril-induced arterial hypotension. The effects of this drug on renal function in cirrhosis were evaluated using low-dose captopril, thereby avoiding any change in arterial pressure. METHODS: In a randomized, double-blind, placebo controlled, cross-over trial, the effects of 12.5 mg captopril on renal plasma flow, glomerular filtration rate (measured by radioisotopic techniques), and sodium excretion in healthy controls and cirrhotic patients with and without ascites were determined. RESULTS: In healthy subjects, captopril only induced a significant, 18% increase in renal plasma flow. In contrast, glomerular filtration rate significantly decreased in patients with (from 108 +/- 7 to 78 +/- 9 mL/min) and without ascites (from 102 +/- 4 to 88 +/- 3 mL/min), whereas renal plasma flow did not change. Urinary sodium excretion also significantly decreased in ascitic patients (from 43.8 +/- 4.4 to 30.6 +/- 3.8 mumol/min). CONCLUSIONS: These data suggest that angiotensin II contributes to maintain renal hemodynamics in cirrhosis with and without ascites.

Parathyroidectomy and blood pressure in hemodialysis patients.

To assess whether parathyroidectomy (PTx) affects blood pressure (BP) in hemodialysis (HD) patients, we studied 11 uremics on HD treatment for 8.2 +/- 0.9 years who underwent successful PTx. As the control group, we selected 11 HD patients not submitted to PTx, matched with the study group for sex, age, years on HD, dialysis procedure and BP values. In the controls, BP and body weight did not change during the 2 years of observation. In the patients, BP remained stable in the year before PTx. PTx caused a progressive reduction in BP in 7 of the 11 patients. The fall was significant from the 3rd quarter onward (mean BP values before PTx: 139/82 mm Hg, 1 year after PTx: 122/75 mm Hg). The magnitude of the hypotensive effect of PTx was related to the pre-PTx systolic BP value (r = -0.70, p = 0.016). PTx also caused a significant progressive increase in body weight (1.56 +/- 0.57 kg 1 year after PTx). In conclusion, PTx causes BP fall in HD patients regardless of whether their preintervention values are normal or increased. The BP reduction occurs in concomitance with a consistent increase in body weight. BP variations are clinically relevant and may be related to the post-PTx calcium efflux from the vessel wall.