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Many studies have demonstrated that left ventricular hypertrophy is the most frequent cardiac alteration in patients on chronic hemodialysis. Autopsy studies have shown that hypertrophic hearts of uremic patients have peculiar characteristics, namely deposition of calcium salts, intermyocytic fibrosis, sometimes amyloid. None of the parameters obtainable from conventional echocardiografic images provides information on myocardial tissue structure. Analysis of "texture" originated as analysis of images sent by satellites for military or agricultural purposes and subsequently was applied to medicine for studying various organs like mainly and widely heart. Videodensitometry is a method for in vivo analysis of myocardial structure using computer-assisted quantitative assessment of grey levels of conventional echocardiographic images. In dialysis patients quantitative ultrasonic analysis of myocardial texture appears a promising technique for an observer-independent assessment of myocardial tissue characteristics. Although it may be hampered by many potentially confounding factors, quantitative echocardiography may offer useful parameters for the follow-up of myocardial structural changes in chronic uremia. Further studies are ongoing to completely understand the prognostic significance of myocardial ultrasonic textural alterations in dialysis population.

Background: Many reports note that the use of cool dialysate has a protective effect on blood pressure during hemodialysis (HD) treatments. However, formal clinical trials in which dialysate temperature is tailored to the body temperature of appropriately selected hypotension-prone patients are lacking., Methods: We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients selected from 27 centers in nine European countries. Patients were eligible for the study if they had symptomatic hypotensive episodes in 25% or more of their HD sessions, assessed during a prospective screening phase over 1 month. The study is designed as a randomized crossover trial with two phases and two treatment arms, each phase lasting 4 weeks. We used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), by which we compared a procedure aimed at preventing any transfer of thermal energy between dialysate and extracorporeal blood (thermoneutral dialysis) with a procedure aimed at keeping body temperature unchanged (isothermic dialysis)., Results: One hundred sixteen HD patients were enrolled, and 95 patients completed the study. During thermoneutral dialysis (energy flow rate: DeltaE = -0.22 +/- 0.29 kJ/kg x h), 6 of 12 treatments (median) were complicated by hypotension, whereas during isothermic dialysis (energy flow rate: DeltaE = -0.90 +/- 0.35 kJ/kg x h), the median decreased to 3 of 12 treatments (P < 0.001). Systolic and diastolic blood pressures and heart rate were more stable during the latter procedure. Isothermic dialysis was well tolerated by patients., Conclusion: Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients., (Copyright 2002 by the National Kidney Foundation, Inc.)

Standard hemodialysis (dialysate temperature >or=37 degrees C) induces an increase in body temperature capable of eliciting circulatory adjustments dictated by the maintenance of thermal homeostasis. These adjustments oppose, and can overcome, those elicited by the hypovolemia caused by the ultrafiltration process, and thus predispose patients to develop hypotensive crises during the treatment. Hemodynamic studies in hypotension-prone patients treated with standard hemodialysis showed that during the hypotensive crisis the peripheral vascular resistances decrease, while the stroke volume decreases proportionally more than the blood volume, suggesting cardiac underfilling due to blood volume redistribution. On the other hand, removal of the body heat surplus by cool dialysis helped the same patients to sustain their peripheral vasoconstriction and cardiac filling. To prevent the increase in body temperature, dialysate temperature should be regulated in such a way as to remove through the dialyzer the heat surplus accumulated in the body as a result of the ultrafiltration process. The amount of heat removal should be tailored to each patient because there are wide interindividual and intraindividual variations in baseline body temperature and ultrafiltration requirements. This can be accomplished by the use of a device that can adjust the dialysate temperature automatically in order to keep the body temperature of the patient unchanged (isothermic hemodialysis). Isothermic hemodialysis reduced from 50% to 25% the incidence of treatments complicated by episodes of symptomatic hypotension in a large randomized clinical trial involving 95 high-risk patients. The thermoregulated treatment results in better patient tolerance because the cold stress inherent in this procedure is lower than that inflicted by the use of a fixed low temperature as was done in the past. Overall, the available evidence supports the Gotch hypothesis that the increase in body temperature during hemodialysis is due to the ultrafiltration process eliciting peripheral vasoconstriction and heat accumulation in the body. Heat accumulation brings into play the thermal homeostatic mechanisms endangering cardiovascular tolerance to ultrafiltration.

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.

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., (Copyright 2000 S. Karger AG, Basel)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

We carried out a retrospective survey to assess prevalence and type of diabetes in three Italian Renal Units located respectively in the North (Tradate, Varese), in the Middle (Latina) and in the South (Reggio Calabria) of Italy. The prevalence of diabetes among patients accepted for RRT was 10.5% (60/659). 40 patients (66.7%) were non-insulin dependent and only 6 patients were insulin-dependent. A similar pattern was observed among the 289 patients referred to the Renal Unit of Reggio Calabria during 1972-1987 for evaluation of Chronic Renal Failure. Our data suggest that among the Italian diabetic patients treated by dialysis and transplantation insulin-dependent diabetes is uncommon. This finding could be explained by the low incidence of insulin-dependent diabetes in Italy.

We tested in vivo the effect of methyl-prednisolone (MP) on C5a release and granulocytopenia occurring early in the course of extracorporeal blood circulation through a Cuprophan dialyzer. MP boluses (30 mg/kg) were given to 10 consenting patients suffering from acute renal failure, immediately before blood started to circulate through a hollow-fiber Cuprophan dialyzer. To avoid drug loss through the dialyzer membrane, dialysate flow was withheld during the first hour of treatment and ultrafiltration was kept near zero (sham dialysis). Control procedures were carried out in a similar way, without MP. MP concentration, differential WBC count and anaphylotoxin C5a were serially measured during the procedures. MP pharmacokinetics was evaluated in six other uremic patients off dialysis. As shown by similar C5a levels in dialyzer effluent blood, complement cascade was activated by Cuprophan to a comparable degree whether or not patients received MP. Neutrophil count dropped 68% during the control procedure and 54% during sham dialysis preceded by MP (95% confidence interval of the difference, 1.97-27.2). Sham dialysis did not apparently influence serum MP levels, as shown by similar peak values in patients undergoing sham dialysis (203 micrograms/ml +/- SEM 33) and in patients off dialysis (177 micrograms/ml +/- 42). In vitro aggregometry showed that the uremic milieu does not interfere with the antiaggregating effect of MP. Our results show that MP at the dosage of 30 mg/kg does not affect complement-mediated granulocytopenia in any important way.

A number of reports on dialysis and transplantation for diabetic patients in the UK and USA are available. The aim of the present survey was to assess the prevalence, main characteristics and complications of diabetic patients treated by dialysis and transplantation in Italy. On 31 December 1987 in Italy, 1605 diabetic patients were being treated by dialysis or transplantation. The prevalence was 28 per million compared with the UK and the USA where the corresponding figures were 17 and 78 per million respectively. The annual incidence in 1987 was 9 per million (UK: 4 per million; USA: 33 per million). The mean age of the Italian diabetic patients was 59 years whereas that for British diabetic patients similarly evaluated was 48 years. Of the Italian diabetic patients 67% had NIDDM (UK: 22%; USA: 50%). Haemodialysis was used in 81% of the Italian patients, peritoneal dialysis in 14%, and only 5% were transplanted. This is in contrast to the UK where only 18% of the patients were treated by haemodialysis and 39% were transplanted. Amongst Italian patients who started RRT in 1987, 9% died within the year, and of the remainder 38% had severe bilateral visual impairment (UK 35%), 3% had had amputations (UK 6%), 7% had suffered from disabling strokes (UK 6%) and 7% had had a myocardial infarction (UK 17%). Before 31 December 1987 another 2.2% developed severe bilateral visual impairment, 0.6% underwent amputations, 1.0% had a disabling stroke and 0.6% suffered from a myocardial infarction. The proportion of diabetic patients treated by RRT in Italy is twice that of the UK but only half that of the USA.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the effect of long-term propranolol therapy on uremic osteodystrophy, we evaluated retrospectively the biochemical, X-ray, and bone histological changes in 9 dialysed hypertensives who had been on propranolol treatment for periods ranging from 1 to 8 years. The control group included 9 well-matched dialysed uremics never treated with beta-blockers. The two groups did not differ in serum ionized calcium or iPTH levels. The incidence of bone resorption evaluated on X-ray findings and on bone biopsy specimens was of a comparable degree in the two groups. Our data show that propranolol even if started early in the course of renal failure, is of no benefit in preventing uremic bone disease.

Cryoglobulins were removed from the plasma of two patients with mixed cryoglobulinaemia (IgM(k)-IgG type) associated with severe membrano-proliferative glomerulonephritis and angiitis. The removal of about half the circulating cryo-Igs ('cryo-Igpheresis') was followed by a brisk rebound in cryo-Igs due to the rapid synthesis rate of monoclonal IgM(k) with anti-IgG activity. 'Cryo-Igpheresis' + cyclophosphamide treatment suppressed the rebound of cryo-IgGs, but not that of the cryo-IgMs. This differential effect was due to decrease of the antibody activity of cryo-IgMs. The clinical implications of such changes need further evaluation.

We studied the effect of the opiate antagonist naloxone on the response to Valsalva manoeuvre in nine dialysis patients, in six diabetics with normal renal function whose response to Valsalva manoeuvre was similar to that of dialysis patients and in eight healthy subjects. Naloxone caused a progressive increase in the subnormal Valsalva ratio in dialysis patients but it did not cause any change in diabetics nor in healthy subjects. The increase in Valsalva ratio observed in dialysis patients was due to restoration of the parasympathetically mediated reflex bradycardia of the release phase of the manoeuvre. Endogenous opioids may be responsible for the baroreflex dysfunction of dialysis patients.

We tested the hypothesis that differing temperature (T) changes in extracorporeal blood circuit might partly account for the difference in vascular stability (VS) between isolated ultrafiltration (UF) and simultaneous UF-hemodialysis (HD). The study was carried out in 6 patients who presented frequent episodes of symptomatic hypotension during the routine dialytic sessions. During simultaneous UF-HD with dialysate T set at 37.5 degrees C (standard HD), blood reentered the patients with a T of about 2 degrees C higher, whereas during isolated UF (standard UF) 2 degrees C lower, than at its exit. These extracorporeal blood T changes were reciprocated by warming the venous line in isolated UF (warm UF) and by setting the dialysate at 34.5 degrees C in simultaneous UF-HD (cold HD). During warm UF mean arterial pressure (MAP) fell and heart rate (HR) increased nearly as much as during standard HD. Vice versa, during cold HD MAP and HR remained nearly as stable as during standard UF. It is concluded that the T changes in blood flowing through the extracorporeal circuit largely account for the differing VS between isolated UF and simultaneous UF-HD.

Paraneoplastic syndromes are often associated with renal parenchymal tumours. This report describes a case of renal-cell carcinoma with kappa-chain nephropathy. The patient, a 60-year-old man, had renal tubular dysfunction, shown by low serum concentrations of urate and phosphate. Kappa-chains were found in both serum and urine, but no lambda-chains were found. Investigations showed a clear-cell carcinoma, and the patient underwent a radical nephrectomy. Two years after operation serum phosphate and urate concentrations had returned to normal, and kappa-chains were undetectable in serum or urine. The absence of lambda-chains indicates that the light-chain proteinuria was due to overproduction of the M component, and the disappearance of kappa-chains after the operation suggests a causal relation between the renal tumour and the overproduction of the M component.

Skin biopsy specimens from 2 patients with dermatitis herpetiformis were examined by means of direct immunofluorescence with fluoresceinated aggregated human IgG (FAIgG) for the presence of tissue antiglobulin activity. Positive FAIgG staining was seen in both skin biopsy specimens yielding a fluorescence pattern similar to that of immunoglobulin and complement deposits. Tissue antiglobulin activity was no more detectable in a second skin biopsy obtained from one patient whose rash was controlled by Dapsone. These findings suggest an involvement of tissue antiglobulin activity in the pathogenesis of dermatitis herpetiformis. In fact, tissue antiglobulin activity is capable of acting as an immunoabsorbent and binding immunocomplexes from the circulation.

The effect of oxolinic acid, administered at the rate of 750 mg twice/day, has been studied on 31 patients with urinary tract infections. Many of them had a marked impairment of renal function due to nephropathies of various origin. Favourable results, with sterile urine and complete remission of symptoms, were obtained in 73.3%. Patients who were resistant to previous different therapies, were successfully treated. Oxolinic acid was on the whole well tolerated and proved to be effective also in patients with impaired renal function. In some of the latter an improvement in renal function occurred as a result of the effective urinary infection care. The tolerability of oxolinic acid was good: only one patient interrupted the treatment because of insomnia; other 4 had transient and mild side-effects.

We investigated whether cooling of the extracorporeal blood during hemodialysis could prevent anaphylatoxin generation and leukopenia caused by blood-cuprophan contact. After preliminary in vitro studies confirming the temperature dependence of C5a generation, we carried out hypothermic dialysis on nine patients by manipulating blood and dialysate temperature in such a way that blood temperature within the dialyzer averaged 25 degrees C. In comparison with the control procedure (blood temperature within the dialyzer 35 degrees C) hypothermic dialysis reduced peak C5a generation from 41.7 +/- 17 ng/ml to 9.7 +/- 3.4 ng/ml (P less than 0.01), and white blood cell fall from 72 +/- 15 to 25 +/- 20% (P less than 0.01). Arterial PO2 decreased less in hypothermic dialysis (-19 +/- 9% of pre-HD value) than in the control procedure (-30 +/- 11%) (P less than 0.05). We conclude that blood cooling attenuates cuprophan-induced anaphylatoxin generation and leukopenia.

To evaluate the role of the hepatitis B virus infection in the pathogenesis of glomerulonephritis, we screened 136 consecutive patients with various types of glomerular lesions for the presence of HBsAg either in serum or in kidney biopsy specimens by means of radioimmunoassay and direct immunofluorescence technique, respectively. In selected patients, we carried out the search for antiglobulin activity (AA) factor(s) within the renal tissue with a fluoresceinated aggregated human IgG preparation (FITC-IgGagg). Eleven HbsAg seropositive patients were found, none of whom showed HBsAg deposits within their kidney biopsy specimen. Five of the remaining 125 seronegative patients, 3 with mixed cryoglobulinemia and 2 with lupus nephritis, showed glomerular-positive staining with a rabbit fluoresceinated anti-HBs serum and deposits of IgM endowed with AA, along with IgG and complement factors. The presence of HBsAg within the glomeruli was not confirmed, however, when a fluoresceinated anti-HBs Fab' preparation was used instead of the fluoresceinated anti-HBs serum. The pretreatment of the tissue sections with unconjugated anti-IgM serum blocked the direct staining for HBsAg and FITC-IgGagg, but not that of the other immunoreactants. Conclusion. The IgM AA deposits may interfere with the direct immunofluorescence testing for HBsAg, leading to erroneous interpretation.

Temperature (T) changes in the blood flowing through the extracorporeal circuit markedly affect cardiovascular tolerance to fluid removal during either hemodialysis (HD) and isolated ultrafiltration. In this study we investigated the effect of blood T changes during postdilutional hemofiltration (HF). To this purpose we compared the changes in mean arterial pressure (MAP) and heart rate (HR) during HF and HD carried out at equivalent T of blood in the venous segment of the extracorporeal circuit. Results show that HF entails some heat loss from blood flowing in the extracorporeal circuit; if heat loss is made similar, HD affords nearly as much blood pressure protection as HF does. On the other hand at equivalent heat gain, HF causes nearly as much hypotension as HD does. We conclude that blood T changes in the extracorporeal circuit affect vascular stability (VS) even in HF. The marginal benefit of HF over HD, still observed at equalized T changes, remains to be elucidated.

One hundred and forty-four kidney biopsy specimens with various forms of glomerulonephritis were studied to assess the presence of Rheumatoid Factor (RF) deposits. RF deposits were found in 21 specimens: six with acute post-streptococcal glomerulonephritis, two with crescentic glomerulonephritis, four with lupus nephritis, eight with essential mixed cryoglobulinaemia glomerulonephritis, and one with end-stage kidney disease. Blocking and elution studies carried out on specimens with essential mixed cryoglobulinaemia provided evidence that the RF deposits derive from circulating monoclonal RF. This data suggests that RF participates in the formation of glomerular immune deposits in several forms of immune complex mediated glomerulonephritis.