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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. [ABSTRACT FROM PUBLISHER]

Key words:cytokines; endotoxins; infusion fluid; on-line haemodiafiltration; safety [ABSTRACT FROM PUBLISHER]

Background: Late potential (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. [ABSTRACT FROM PUBLISHER]

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). [ABSTRACT FROM PUBLISHER]

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 bilaterial 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. The patients are on average 10 years older compared to the UK and are treated mostly by haemodialysis. In spite of this the proportion of patients with complications seems to be no greater than that reported for the younger UK population. [ABSTRACT FROM PUBLISHER]

The application of a new statistical method (‘breakpoint’ test) to the study of the progression of chronic renal failure is described. This test establishes whether the best fit of a series of GFR measurements is linear or broken. Such an approach avoids the analytical constraint of the time of intervention assumed by other methods. Re-analysis by this test of previous studies of low-protein diet suggests that in some cases the effect of the dietary regimen has been overemphasised. [ABSTRACT FROM PUBLISHER]

We have investigated the influence of body fluid volume status on plasma levels of immunoreactive atrial natriuretic peptide (irANP) in eight uraemic patients on chronic haemodialysis, including two diabetics with severely impaired reflex control of the heart. IrANP was significantly higher in volume-expanded uraemic patients (36±16 pg/ml) than in a group of seven age and sex-matched normal subjects (14±2 pg/ml), and fell consistently, approaching the normal range after the removal of 2.0–4.3 litres of isotonic plasma ultrafiltrate (by isolated ultrafiltration). Plasma levels of the hormone were strictly related to right atrial pressure. The irANP response to ultrafiltration in the two diabetics was similar to that of the other uraemic patients. The results suggest that the elevated irANP levels found in volume-expanded uraemic patients depend largely on fluid overload per Se. The preserved irANP response to ultrafiltration of the two diabetics with severe autonomic neuropathy indicates that in chronic renal failure irANP secretion may be regulated independently from autonomic influences. [ABSTRACT FROM PUBLISHER]

Plasma met-enkephalin and leu-enkephalin has been measured in a group of 28 patients with chronic renal failure, to discover whether these opioids are affected by standard haemodialysis and haemofiltration. Met-enkephalin was markedly higher (<0.001) in uraemic patients than in a group of 13 normal subjects, and was directly related to plasma creatinine (=0.60; <0.01) and to plasma urea (=0.36; =0.06). In contrast, leuenkephalin was suppressed in uraemic patients (<0.001). Met-enkephalin fell slightly but significantly (<0.02) after both haemodialysis and haemofiltration; however, on average it remained at concentrations four times higher than normal. No changes in plasma leu-enkephalin were observed after haemodialysis and haemofiltration. The cause(s) of the altered plasma concentrations of these opioid substances remains to be clarified. [ABSTRACT FROM PUBLISHER]

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.

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.

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.