Assessment of occlusion of the vascular access in patients on chronic hemodialysis: comparison of physical examination with continuous-wave Doppler ultrasound. STOP Investigators. Shunt Thrombotic Occlusion Prevention with Picotamide.

BACKGROUND: Dialysis access occlusion is the most common cause of hospitalization and a frequent indirect cause of mortality in patients on chronic hemodialysis. The clinical assessment of an arteriovenous shunt is presently the most widely adopted method for the diagnosis of vascular access occlusion in hemodialysis patients, but no studies have yet investigated objectively its sensitivity and positive predictive value (PPV). Continuous-wave (CW) Doppler ultrasound is a simple, inexpensive, and noninvasive technique for the assessment of arterial blood flow. We have carried out a prospective evaluation of the PPV of CW Doppler for the diagnosis of vascular access occlusion in hemodialysis patients and compared it with clinical investigation. METHODS: Fourty-one hemodialysis patients with clinical diagnosis of occlusion of their fistula were studied, and in 23 of them the diagnosis of occlusion was objectively validated. RESULTS: CW Doppler in the patients in whom occlusion was objectively validated showed PPV of 86 and 83% under basal conditions and after fistula compression, respectively, with sensitivities of 95 and 100%, respectively. Clinical diagnosis, under the same conditions, showed a PPV of 83% and a sensitivity of 100%. CONCLUSIONS: CW Doppler and clinical examination have a similar high sensitivity for the diagnosis of occlusion of the dialysis access; thus, there is no need to use routinely Doppler CW examination, unless objective documentation is required.

Acute renal failure of medical type in an elderly population.

One hundred and nine unselected patients with Acute Renal Failure (ARF) of medical aetiology were hospitalized at the Nephrological Unit of Policlinico University Hospital (Modena) during a 30-month period. ARF was considered as a rapid increase of serum creatinine > 2mg/dl over the baseline level or the doubling of pre-existing value in chronic renal failure. Mean age of patients was 67+/-17 years and median age was 72; 64.2% needing dialytic treatment. Four main causes of ARF were identified: 33 patients had reduced renal perfusion by dehydration, hypotension etc.; 20 multifactorial aetiology; 14 biopsy-investigated renal parenchymal diseases and 39 had drug-related acute renal failure (D-ARF). The clinical outcome was significantly worse in elderly patients as regard mortality (P < 0.02), chronic dialytic treatment (P < 0.04) and complete recovery (P < 0.004). The mean age of D-ARF patients was significantly greater than remaining ARF patients (72.6+/-12.8 vs 63.2+/-18.5: P < 0.004. Nonsteroidal antiinflammatory drugs (NSAIDs) and ACE-inhibitors (Ace-i) caused ARF in 24 and 8 patients respectively. Elderly age, vascular disease and monoclonal gammopathy represented the main risk factors and were significantly more frequent in D-ARF patients (P<001, <0.01, <0.04 respectively). Our data confirm the high susceptibility of ageing kidneys to nephrotoxic damage caused by drugs affecting glomerular autoregulation by microvascular mechanisms. Greater attention to renal changes in ageing and an increased dissemination of preventative measures among nephrologists, could reduce the incidence of these serious and potentially lethal diseases.

Which level of cytokine production is critical in haemodialysis?

Monocyte activation with cytokine production is a well known event in the course of dialysis treatment but its relation to symptoms of haemodialysis or long-term pathological changes in chronic dialysis patients is still under discussion. Cytokine production depends on the balance between inducers and inhibitors while effects rely on the peculiar uraemic environment and cell metabolism. 'Foot-prints' for monocyte activation have been found, but no marker for clinical symptoms has been demonstrated clearly. In this scenario it is almost impossible to link a specific symptom to a definite stimulus such as dialysate microbial contamination or membrane complement generation. The topics discussed in this paper include cytokines synthesis modulation factors, levels in haemodialysis patients, and results of finding markers of clinical relevance. Special attention is paid to microbial contamination of dialysis fluid with analysis of cytokine inducing substances in commercial sterile solutions. Data on cytokine synthesis and activity in the aged are also discussed, with special regard to the haemodialysis setting.

Natural history of nutrition in chronic renal failure.

Dietetic manipulation significantly influences the progression of renal failure in laboratory animals. Clinical results in humans are contradictory. The aim of the study was epidemiological research on a large sample of kidney disease patients to verify whether renal failure influences nutrient intake before dietetic manipulation. Four hundred and forty-one consecutive, non-selected adult patients with renal insufficiency (creatinine 133-963 mumol, mean 301 +/- 178 mumol in male, 288 +/- 156 mumol/l in female) and 43 kidney disease patients without renal failure were enrolled in the prospective study in the period 1988-1995. Interview at the time of the first nephrological check was performed by only one dietician; the record by recall of intake over 7 days with quantitative assessment was collected with the assistance of nutritional dossier and photographic measures. The patients with renal failure consume energy, proteins, lipids and carbohydrates in lesser quantities than the national population of the same geographical area, but the total lipid and monounsaturated fatty acid intake is higher compared with Italian dietary reference values. In patients with renal failure mean protein intake was 1.02 +/- 0.2 g/kg/day in males and 0.96 +/- 0.2 g/kg/day in females; mean lipid intake was 1.10 +/- 0.2 g/kg/day in males and 1.17 +/- 0.3 g/kg/day in females; mean carbohydrate intake was 3.7 +/- 1.1 g/kg/day in males and 3.49 +/- 1 g/kg/day in females. The nutrition alterations observed in chronic renal failure may be a biological adaptation due to neurological changes affecting the sense of taste.

Haemodialysis therapy in the elderly.

Haemodialysis therapy in the elderly has become a recognized reality only in the last decade Information collected from restricted statistics often leads to conflicting conclusions. Length of survival may be a useful indicator of the appropriateness of initiating treatment. Survival and important determinants of survival, such as cardiovascular problems, nutritional status and adequacy of dialysis, are addressed in this study and evaluated in 365 elderly patients, treated at a single institution over a 20 year period.

No direct evidence of increased lipid peroxidation in hemodialysis patients.

Lipid peroxidation, as measured by the thiobarbituric acid test, has been reported to have increased in hemodialysis (HD) patients, even though the test has low specificity in vivo. Conjugated diene fatty acid (CDFA) hydroperoxides are formed during lipid peroxidation, but not all conjugated dienes (CD) detected in humans originate from lipid peroxidation: octadeca-9,11-dienoic acid, a nonhydroperoxide CD derivative of linoleic acid (CDLA), has a dietary origin. We evaluated CDFA hydroperoxides, CDLA and linoleic acid, using high-performance liquid chromatography, in lipids extracted from plasma, adipose tissue and RBC membranes obtained from 25 patients treated with HD, 16 patients treated with hemodiafiltration (HDF) and 29 controls. No differences in the levels of CDFA hydroperoxides and linoleic acid were seen in any of the groups. Concentrations of CDLA were found to be significantly high in the adipose tissue and low in the RBC membranes of HD patients. HDF-treated patients showed the same results as HD patients. No direct evidence of increased lipid peroxidation was found in HD patients. This does not exclude the possibility that lipid peroxidation is increased and escapes direct detection due to the body's homeostatic control eliminating the increased production of hydroperoxides. Both HD- and HDF-treated patients showed a significant change in CDLA concentrations, either in the adipose tissue, or in the RBC membranes. These dietary CD may be mistaken for markers of lipid peroxidation by conventional methodologies.

Leaching and corrosion of polyvinyl chloride (PVC) tubes in a dialysis water distribution system.

PVC tubes, from the dialysis water distribution system of a 14 and a 7 year old plant, were analysed by scanner electron microscopy (SEM) and X-ray microanalysis (EDAX). Results showed that the leaching of material occurs depending on time of use. The phenomenon does not modify the chemical composition of the material. Results suggest that PVC alterations, induced by time, could support bacterial proliferation thus reducing the quality of dialysate.

Beta 1 and beta 3 integrin upregulation in rapidly progressive glomerulonephritis.

The expression and distribution pattern of beta 1 (alpha 1-alpha 6) and alpha v beta 3 integrins and ICAM-1 and VCAM-1 counter receptors were evaluated by an immunohistochemical technique on eight renal samples from patients affected by rapidly progressive glomerulonephritis (RPGN) of different aetiologies. In all cases integrins and counterreceptors displayed similar patterns. On tubular cells of renal cortex, a marked upregulation of alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3 integrins and VCAM-1 was observed with as many as 60-90% of tubular cross-sections labelled, while a strong ICAM-1 reactivity was limited to the luminal surface. The same adhesion molecules were also uniformly expressed on crescentic cells. In glomeruli, integrin upregulation occurred only on apparently preserved capillary tufts, i.e. in an early stage of lesion, while collapsed and sclerotic tufts showed a reduced integrin expression. In addition a morphometric study of extracellular matrix (EM) proteins cellular fibronectin and tenascin showed a 9.56 +/- 1.9-fold and 3.35 +/- 0.6-fold increase respectively in these proteins, as compared to normal kidney (P < 0.001). The upregulation of alpha v beta 3 on podocytes might play a role in the adhesion of crescentic cells. An increased production of cytokines, in particular transforming growth factor-beta, might induce augmented deposition of EM proteins and upregulation of beta 1 and beta 3 integrins in RPGN.

On line filtration of dialysate: structural and functional features of an asymmetric polysulfone hollow fiber ultrafilter (Diaclean).

The endotoxin transfer across dialysis membranes has been investigated using specific in vitro circuits. Backdiffusion and backfiltration have been analyzed and most dialysis membranes have shown to be permeable to LAL positive substances. Synthetic membranes however display the better capacity of retention of these products despite their higher porosity and permeability. For such reason synthetic polysulfone ultrafilters are used as pyrogen filters to obtain ultrapure dialysate. We have investigated the characteristics of a polysulfone ultrafilter named Diaclean and manufactured by Amicon Ireland. The capacity of endotoxin retention has been investigated both in filtration and backfiltration modes on new and used ultrafilters. The capacity of endotoxin adsorption was investigated as well. Used ultrafilters appeared to maintain the retention capacity and the adsorption capacity up to 4 months of use. Only slight differences were noted from the baseline values (p = n.s.). The best adsorption capacity is always displayed by the outer layer of the membrane suggesting its best utilization in back filtration mode with tangential flow. No morphological changes were observed in the used membrane analyzed by scanning electron microscopy.

Beta-1 integrins in the normal human glomerular capillary wall: an immunoelectron microscopy study.

The localization of the alpha 2, alpha 3 and alpha 6 subunits of the beta 1 integrin family on different cells of the glomerular capillary wall and on juxta-capillary mesangium was investigated using an immunoelectron microscopic technique on freshly harvested normal human glomeruli. Alpha 2 beta 1, alpha 3 beta 1 and alpha 6 beta 1 were weakly expressed on both luminal and abluminal surfaces of glomerular endothelial cells; alpha 2 beta 1 and alpha 3 beta 1 were also found on the mesangium of the juxta-capillary areas. Alpha 3 beta 1 was regularly present in great density on the basal and lateral surface of podocyte foot processes, confirming alpha 3 beta 1 as the unique beta 1 integrin on glomerular epithelial cells. None of these integrins was strictly polarized along the glomerular basement membrane, thus suggesting, in agreement with recent literature, that these molecules perform other biological functions in addition to adhesivity.

[Myopathies associated with tubular aggregates]. / Miopatias associadas a agregados tubulares.

The authors report the case of a 58-year-old male patient with clinical and electromyographic features of myasthenia. Muscle biopsy with histochemistry and electronic microscopy made it possible to diagnose a myopathy associated with tubular aggregates. Attention is called to the fact that the anatomical pathologic alterations which were found may be present in a heterogenous group of patients showing a great variety of symptoms. Thus, there is no reason to consider the existence of a myopathy associated with tubular aggregates, since the anatomical and pathologic findings are inespecific and do not characterize any specific disease.

A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome.

To compare the efficacy (induction of remission) and safety of cyclosporine (CsA) with those of supportive therapy in patients with steroid-resistant idiopathic nephrotic syndrome (INS), we organized an open, prospective, randomized, multicentric, controlled study for parallel groups, stratified for adults and children. Forty-five patients with steroid-resistant INS were randomly assigned to supportive therapy or CsA (5 mg/kg/day for adults, 6 mg/kg/day for children) for six months, then tapered off by 25% every two months until complete discontinuation. Four patients were lost to follow-up. During the first year 13/22 CsA-treated patients versus three of 19 controls attained remission of the nephrotic syndrome (P < 0.001). A symptom score was assessed at time 0 and at six months. The mean score significantly decreased in the CsA group (P < 0.001), but remained unchanged in the controls. At month 6 the mean urinary protein excretion, the mean serum proteins and plasma cholesterol had significantly improved in the CsA group but were not changed in the controls. There were no significant differences in serum creatinine and creatinine clearance between treatments (interaction time* treatments, P = 0.089 and P = 0.935, respectively) at month 6 versus basal. The CsA-related side-effects were mild; no significant difference in blood pressure between the two groups was seen at any time. This study shows that CsA can bring about remission in some 60% of patients with steroid-resistant INS. In patients with normal renal function and without severe hypertension, CsA at the therapeutic scheme adopted did not produce severe renal or extrarenal toxicity.

Ultrafiltration and endotoxin removal from dialysis fluids.

Biocompatibility in hemodialysis is now regarded as a multifactorial problem and dialysate represents a main risk. Pyrogenic fractions mostly coming from gram-negative bacteria easily pass through dialysis membrane, either by backdiffusion or by backfiltration, and induce blood cell activation. To demonstrate the long-term efficiency of a 2 m2 polyamide ultrafilter in producing a pyrogen free solution, we used an experimental circuit ultrafiltering for 240 hours (500 ml/min) a bicarbonate dialysate contaminated (5 to 48 EU/ml) by a Pseudomonas aeruginosa filtrate. The efficiency was monitored by LAL-test and IL-1 PBMC so to detect not only lipid A containing endotoxins but also other cytokines inducing bacterial fractions. At the post-ultrafilter sampling port the LAL-test was < 0.005 to 0.034 EU/ml; IL-1 PBMC was below the detection limit (20 pg/ml) being 27 to 63 pg/ml at the pre-ultrafilter level. Polyamide ultrafiltration represents an efficient system to obtain an endotoxin-free dialysate and a single filter works up to 240 hours.

Removal of limulus reactivity and cytokine-inducing capacity from bicarbonate dialysis fluids by ultrafiltration.

Bicarbonate-based dialysate solutions support the rapid growth of bacteria. The long-term (360-h) efficacy of ultrafiltration by two polysulphone ultrafilters in removing not only endotoxin but also the cytokine(IL-1, TNF)-inducing capacity was evaluated using an experimental circuit contaminated with Pseudomonas aeruginosa filtrates. One of the polysulphone ultrafilters was submitted to a standard sanitization procedure every 12 h (hypochlorite 1.2% solution for 5 min and rinsing for 20 min). Endotoxin was detected by the kinetic quantitative chromogenic limulus amoebocyte lysate (LAL) assay. Immunoreactive IL-1 and TNF were evaluated in the lysates of peripheral blood mononuclear cells containing 5 x 10(5) human monocytes. The results of the present studies show that although LAL-reactive bacterial products were significantly removed in post-ultrafilter samples, they remained detectable, albeit below the upper limit accepted by the present European pharmacopeias (< 0.125 EU/ml). The removal of cytokine-inducing capacity was time-dependent and correlated with time of use in the case of the sanitized ultrafilter. Beyond the time of use, two other factors emerged as possibly capable of reducing the efficacy of the ultrafilter in removing LAL-reactive bacterial components, namely the pressure and the cytokine-inducing activity in pre-ultrafilter samples. Preincubation with polymyxin B, an agent that irreversibly binds lipid A and blocks lipid A-induced biological activities, did not abrogate the cytokine-inducing capacity in all post-ultrafilter samples; this suggests that either low-molecular-weight endotoxin subunits or lipid A-unrelated components may be responsible for the residual biological activity in post-ultrafilter samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Conjugated diene fatty acids in patients with chronic renal failure: evidence of increased lipid peroxidation?

Conjugated diene fatty acids (CDFA) were evaluated by second derivative spectrophotometry in the plasma and adipose tissue of 42 chronic renal failure (CFR) patients in conservative treatment, 40 patients treated by hemodialysis (HD) with cuprophane, cellulose acetate or hemophan, 29 treated by hemodiafiltration (HDF) with polysulfone, polyacrylonitrile or polyamide, and 28 healthy controls. Plasma CDFA were also evaluated at the beginning, at 30 min and at the end of the dialytic session. CDFA were unchanged in CRF patients with creatinine clearance (Ccr) > 10 ml/min respect to the controls, CRF patients with Ccr < 10 ml/min showed a higher level of CDFA both in plasma and adipose tissue (p < 0.02). HD patients showed values similar to those of the control group. The lowest level of CDFA was found in HDF patients (p < 0.01 for plasma, p < 0.05 for adipose tissue versus both control and any other group). A significant relationship between plasma and adipose tissue CDFA was found in all groups. In the group of CRF patients with Ccr < 10 ml/min, females exhibited a higher level of CDFA both in plasma and adipose tissue. No significant change was found during dialytic session, independently from the membrane used. CDFA are not only primary products of lipid peroxidation, but also have a dietary origin, primarily from dairy products. Taking into account the reduced dietary intake, the increase in end-stage CRF may be due to an enhanced oxidative stress and/or to abnormalities in CDFA metabolism. Uremic patients, particularly in the predialytic stage, should be considered at risk for increased oxidative stress. HDF treatment better corrects the abnormality compared to conventional HD.

Prevalence of hepatitis C virus (HCV) antibodies in haemodialysis patients.

The prevalence of antibodies to HCV and the course of hepatitis have been determined in 357 haemodialysed patients treated at a single institution. The prevalence of HCV infection increases with the duration of haemodialysis and with the use of blood transfusions, yet there is high frequency of HCV seropositivity even without blood transfusions. Evolution of HCV hepatitis to chronicity is frequent and biological signs of chronic hepatopathy can coexist with absence of alanine aminotransferase (ALT) abnormalities.

Very late activation-3 integrin is the dominant beta 1-integrin on the glomerular capillary wall: an immunofluorescence study in nephrotic syndrome.

The expression of alpha 2; alpha 3; alpha 5; alpha 6-subunits of the beta 1 [very late activation (VLA)] integrin family was studied in kidney specimens using an immunofluorescent technique. 6 specimens from normal kidney were compared with 10 specimens from patients affected by various glomerulopathies [minimal change nephropathy (MCN), membranous nephropathy (MN) and systemic lupus erythematosus nephritis (SLEN)]. On normal glomeruli, alpha 3 was the dominant integrin, being mainly present on podocytes and showing a linear fluorescent pattern codistributed with laminin. In MCN and SLEN, alpha 3 presented a normal pattern. In MN, alpha 3 revealed a trabecular picture on thickened glomerular basement membranes. Moreover, in stage-III MN, a segmental loss of alpha 3-integrin was detected. In our opinion, VLA-3 may offer an interesting approach to the study of the relationships between podocytes and their substrate.

Behavior of antibody profile against hepatitis C virus in patients on maintenance hemodialysis.

The prevalence of anti-hepatitis C virus (HCV) in dialysis setting is still a nonstandard datum. In particular, it is not known of the phenomenon is stable or increasing or decreasing, even in a given geographical area. We studied the behavior of anti-HCV prevalence during a 12-month follow-up in 415 hemodialysis patients treated at a single institution and belonging to a limited geographical area with standard HCV endemic. Point prevalence of anti-HCV has shown a tendency to growth linked in part of the incidence of infection, in part to new positivities in patients already on dialysis treatment. More than 50% of the new HCV-positive patients, had no history of classical parenteral transmission of the virus. These findings suggest that HCV infection is a phenomenon on the increase in dialysis units and that dialysis treatment emerges as an independent risk factor in contracting infection.