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The aim of renal replacement therapy is to obtain blood purification from metabolic waste products sufficient to achieve patient rehabilitation, the control of dry body weight, and the correction of acid base and electrolyte imbalances (1–3). Among these, the correction of the hormonal imbalances as a result of renal disease would also be required (4). However, this is difficult to achieve, and the majority of substitute therapies such as hemodialysis and peritoneal dialysis focus on blood purification and fluid and electrolyte homeostasis. For this reason the search for the optimal dialytic therapy has been limited to the possibility of achieving a treatment that could at least be adequate in terms of blood purification and patient rehabilitation. Therefore, dialysis adequacy has been selected as a term to indicate successful renal replacement therapy, one that could overcome most of the uremic symptoms and allow the patient to reach a sufficient degree of rehabilitation, even though the treatment is far from the complete and optimal substitution of the lost kidney function in its whole. In recent years the concept of dialysis adequacy has been studied by several authors, and a continuous evolution of this concept has been observed. From the original description of the square-meter-hour hypothesis of Babb and Scribner in 1971 (5), a series of new studies led to the clinical application of various indices devoted to describing the level of efficiency achieved by dialysis treatment (6,7). Finally, after the American National Cooperative Dialysis Study was analyzed, and the KTN index was selected as a marker for dialysis adequacy, the majority of authors now rely on this index and are proposing various formulas for its calculation (8–11).

Vascular access is the essential step in performing hemodialysis in uremic patients. In the absence of a permanent and utilizable native arterio-venous fistula, the use of a tunnelled catheter makes dialysis therapy possible. The Ash Split Cath, a recently introduced chronic hemodialysis catheter, was inserted in five patients (7.1 % of our prevalent dialysis population) because of repeated venous thrombosis in three patients and a poor venous tree in two. The mean age of patients was 78 years ± 7. The average blood flow rate was 250 ± 50 ml/minute and the mean venous pressure 140mm Hg ± 35. Recirculation determined by low flux technique was less than 2 %. KT/V calculated 3 months after the catheter placement was 1.2 ± 0.02. During the follow-up we did not document any infection of the exit site or related to the catheter. This device is simple to place, gives adequate dialysis treatment and is useful in geriatric dialyzed patients in whom the arterio-venous fistula can no longer be used.

While reports of venous calcifications are scarce, vascular calcifications frequently occur in the arteries of uraemic patients. Venous calcification of an aged arterious-venous (a-v) fistula in a young patient with a long-standing history of hyperparathyroidism was detected on a forearm X-ray. Risk factors for vascular calcifications are still under debate, but calcium-phosphate product appears to be involved in its pathogenesis. We suggest that a-v fistula of patients with hyperparathyroidism history should be monitored as calcifications could be a risk factor for access thrombosis.

Several strategies have been proposed to increase dialysis efficiency in order to reduce dialysis treatment time. Paired filtration dialysis (two-chamber technique) is a new technique combining the advantages of highly permeable membranes and convective transport with the high depurative efficacy of diffusion. The system operates with two units in series (hemofilter + dialyzer) with membranes of polysulfone and hemophan, respectively. A detailed analysis of the hydraulic properties of the system and its possible optimization in terms of depurative efficiency is reported in this paper. In vitro and in vivo tests provided data sufficient to draw some hypotheses on a new utilization of the system. The system appears to be adequate for operating under conditions of high blood flows, however, some limitations were evidenced during our evaluation: the convective component may be insufficient and further increases are impossible because of the limiting effect of the low surface area of the hemofilter; the configuration in which the weight loss is achieved in the hemofilter exposes to the risk of backfiltration in the dialyzer, reducing the benefits of a highly biocompatible system, and the use of acetate in the dialysate and/or lactate in the substitution fluid may interfere with a satisfactory correction of metabolic acidosis. On the basis of our evaluations, some changes can be proposed such as: (1) increased surface area of the hemofilter; (2) use of blood flows higher than 300 ml/min; (3) use of bicarbonate in the dialysate and in the replacement solution; (4) increased convective component with ultrafiltration rates of 50-60 ml/min and full replacement with substitution fluid in between the two filters, and (5) weight loss achieved in the dialyzer with a constantly positive transmembrane pressure. With such a modification of the operative conditions, paired filtration dialysis can be probably applied as a highly efficient dialysis technique in a large number of patients with a significant reduction of dialysis treatment time.

Alpha 1-Antichymotrypsin (alpha 1-AK) and alpha-1-antitrypsin (alpha 1-AT) represent a defense mechanism to protect the tissues from proteolytic enzyme activity. We studied the implication of alpha 1-AK and alpha 1-AT in glomeruli of patients with different nephropathies based on the analysis of 52 paraffin-embedded renal biopsies with alpha 1-AK and alpha 1-AT antisera. The results demonstrate an intense alpha 1-AK glomerular staining in renal biopsies from patients with minimal-change disease, while a minor staining of this protein was found in the other nephropathies. No significant evidence of alpha 1-AT deposits was observed in our cases. Our findings suggest that when alpha 1-AK is lacking in glomeruli the defense mechanisms against proteolytic enzymes may not be efficient enough to protect the glomerular structures and limit the damage. Since alpha 1-AK is a reactant of the acute phase of inflammation, it may be considered as a marker of activity for monocyte-macrophages in glomerular damage.

The temporary vascular access is the essential condition required to perfrom hemodialysis in uremic patients in the absence of a permanent and utilizable vascular access. The cannulation of a central vein with a dual lumen catheter may be useful when a few weeks are required for the maturation of AVF. Longer times for AVF maturation (such as in diabetic patients and in aged patients) impose the use of a tunnelled catheter such as Tesio Catheter or Hickman Catheter which lead to minor complications and more efficient dialysis treatment. The Ash Split Cath®, a recently introduced chronic hemodialysis catheter, provides dialysis via a transcutaneous portion containing a 14 French cylindrical shaped catheter with D-shaped lumens and a dacron cuff. Due to the slow maturing of AVF, in our Department the Ash Split Cath has been used in 7 uremic patients (3 males and 4 females) who required hemodialysis. The cannulation of the internal jugular vein was performed by an ultrasound assisted technique and the correct catheter position was verified by standard chest X-rays. The average blood flowrates were 250 ml/min, and the mean KT/V calculated in all patients one month after the beginning of the dialytic therapy was 1.09 ± 0.02. In six patients the catheter was utilized for at least 4 months, in one patient for 8 months. The devices were easily removed when the patient's AVF was functional and usable. We found that the use of the Ash Split Cath as a temporary, prolonged vascular access in uremic patients was optimal allowing for flexibility in organizing the dialysis treatment schedule and in yielding a good performance in the initial dialysis therapy. Moreover, this device allows, in these patients, a satisfactory dialysis efficiency.

A 77-year-old woman was admitted due to AV graft thrombosis; given the technical impossibility of performing other native AV fistulas, we chose to insert a tunnelled central venous catheter. Considering the vascular history of the patient, the central venous catheter could not be placed into the internal jugular vein; it was therefore put into the left femoral vein. Following a 3-month-period of the catheter working properly, the patient was hospitalized due to sudden acute pain in the left thigh. In a few days the patient developed an important haematoma with serious anemization in the left lower limb. Ultrasonography showed the presence of a fistula between the left common femoral artery and the femoral vein, leading to the subsequent successful positioning of a stent into the common femoral artery through right trans-femoral access. Angiography examination showed the femoral vein patency along the proximal stretch with respect to the function of the tunnelled venous catheter.

Convective and adsorptive removal of β2-microglobulin during predilutional and postdilutional hemofiltration. Background Beta 2 -microglobulin (β2-m) removal in patients with end-stage renal disease (ESRD) is maximal with convective techniques, such as hemofiltration (HF) or hemodiafiltration (HDF). Although the infusion mode of the replacement solution (predilution or postdilution) is expected to influence the efficiency of HF, experimental data in this respect are scanty. We therefore investigated the impact of the fluid reinfusion mode on the efficiency of HF in 11 ESRD patients who underwent both treatments. Methods The dialyzer (AK 200 ULTRA) was equipped with a 3-layer polyamide membrane (Poliflux 21 S, surface 2.1m 2 ) and blood flow was kept between 300 and 400mL/min. β2-m concentrations were measured in plasma water and ultrafiltrate at appropriate times during a 240-minute treatment. The following dialytic parameters were calculated: total amount of β2-m removed (A tot ), β2-m removed by convection (A con ) and by adsorption (A ads ), percent reduction in β2-m plasma water concentration (% Cpw in ), total plasma water clearance (CLpw tot ), convective plasma water clearance (CLpw con ), adsorptive plasma water clearance (CLpw ads ), and sieving coefficient (SC). Results CLpw tot , CLpw ads , and% Cpw in were similar in pre- and postdilutional conditions, whereas CLpw con and SC were higher and CLpw ads was lower in postdilution than in predilution HF. Since a significant inverse correlation was found between A ads and SC, predilution probably determines greater protein fouling than postdilution. Conclusion The 2 techniques appear to be equivalent in terms of total β2-m removal, although this final result is obtained by different contributions of convective and adsorptive elimination.

Organic anion transporters (OATs), which are expressed in proximal tubule cells, mediate diuretic secretion into tubular fluid. Increased plasma levels of organic anions and urate and metabolic acidosis, i.e. two characteristic features of chronic renal insufficiency, could be factors contributing to diuretic resistance. These limitations demand increasing doses of diuretics up to a maximum level, or the use of a loop diuretic with non-renal metabolism. Diuretic responsiveness in nephrotic syndrome is limited by strong Na+ reabsorption in the distal nephron. Strategies to improve loop diuretic responsiveness include diuretic dosage and the combination of a loop diuretic with a distal acting diuretic. Strategies to limit protein excretion include the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and appropriate salt intake limitation.

Although hemodiafiltration (HDF) offers the advantage of increased convective clearance for middle molecules, there is still controversy as to whether reinfusion should occur pre- or post-filter. Mid-dilution hemodiafiltration (MD HDF) is a new HDF technique that uses a special dialyzer, MD190, which allows both pre- and post-reinfusion. While externally the dialyzer looks similar to conventional hemodialyzers, the internal fibers are divided into two bundles by a special annular header that first lets the blood pass through the peripheral bundle in post-dilution, mix with the reinfusion fluid at the opposite end of the dialyzer and then proceed (after pre-dilution) to the dialyzer blood exit. The dialyzer is able to support substantially higher reinfusion rates (10-12 l/h). We have compared the removal characteristics of several small solutes and larger middle-molecular-weight toxins by examining instantaneous clearance at 45 min, the dialysis reduction ratio and total mass removal (by spilling) in a three-center prospective cross-over study. Twenty patients were randomized to a treatment sequence of one-week high-flux bicarbonate hemodialysis (HD) followed by MD HDF, or vice versa. The parameters evaluated included urea, creatinine, beta2-microglobulin, angiogenin, leptin, retinol-binding protein, and the effects on sodium, potassium, bicarbonate and calcium. Blood flow rates ranged between 300-450 ml/min (mean 359 +/- 44 HD, 367 +/- 35 MD HDF). The mean reinfusion for MD HDF was 166 +/-17 ml/min. MD HDF had a significantly better instantaneous clearance for urea (328 +/- 28 vs 277 +/- 40); creatinine (292 +/- 32 vs. 212 +/- 66); phosphate (324 +/- 38 vs. 242 +/- 63); beta2-microglobulin (249 +/- 27 vs. 100 +/- 24); angiogenin (173 +/- 27 vs. 28 +/- 32); and leptin (202 +/- 29 vs. 63 +/- 43). Treatments were well tolerated with no adverse reactions occurring during any of the treatments. The MD HDF filter's unique configuration is designed to deliver high-efficiency HDF with a significant improvement in small and middle molecule removal. MD HDF supports substantially higher ultrafiltration rates, and as such, results in a higher removal of middle-molecular-weight toxins.

Although hemodiafiltration (HDF) offers the advantage of increased convective clearance for middle molecules, there is still controversy as to whether reinfusion should occur pre- or postfilter. Mid-dilution hemodiafiltration (MD HDF) is a new HDF technique that uses a special dialyzer, MD190, which allows both pre- and postreinfusion. While externally the dialyzer looks similar to conventional hemodialyzers, the internal fibers are divided into two bundles by a special annular header that first lets the blood pass through the peripheral bundle in ‘postdilution’, mix with the reinfusion fluid at the opposite end of the dialyzer and then proceed (after ‘predilution’) to the dialyzer blood exit. The dialyzer is able to support substantially higher reinfusion rates (10-12 l/h). We have compared the removal characteristics of several small solutes and larger middle-molecular-weight toxins by examining instantaneous clearance at 45 min, the dialysis reduction ratio and total mass removal (by spilling) in a three-center prospective cross-over study. Twenty patients were randomized to a treatment sequence of one-week high-flux bicarbonate hemodialysis (HD) followed by MD HDF, or vice versa. The parameters evaluated included urea, creatinine, Β2-microglobulin, angiogenin, leptin, retinol-binding protein, and the effects on sodium, potassium, bicarbonate and calcium. Blood flow rates ranged between 300-450 ml/min (mean 359 ± 44 HD, 367 ± 35 MD HDF). The mean reinfusion for MD HDF was 166 ±17 ml/min. MD HDF had a significantly better instantaneous clearance for urea (328 ± 28 vs 277 ± 40); creatinine (292 ± 32 vs. 212 ± 66); phosphate (324 ± 38 vs. 242 ± 63); Β2-microglobulin (249 ± 27 vs. 100 ± 24); angiogenin (173 ± 27 vs. 28 ± 32); and leptin (202 ± 29 vs. 63 ± 43). Treatments were well tolerated with no adverse reactions occurring during any of the treatments. The MD HDF filter’s unique configuration is designed to deliver high-efficiency HDF with a significant improvement in small and middle molecule removal. MD HDF supports substantially higher ultrafiltration rates, and as such, results in a higher removal of middle-molecular-weight toxins.

In absence of a permanent and useful native arterio-venous fistula, the use of a tunnelled catheter allows dialysis therapy to be carried out. The Ash Split Cath is a recently introduced chronic hemodialysis catheter. An ASC was inserted in nine patients (7.1% of our prevalent dialysis population), for repeated venous thrombosis in seven patients and a poor venous tree in two. The average blood flow rate was 250 +/- 50 mL/minute and the mean venous pressure measured was 140mm Hg +/- 35. Recirculation determined by low flow technique was less than 5% and 4 months after the catheter placement, calculated Kt/V, was 1.2 +/- 0.02. During the follow up we did not document any infection of the exit site or related to the catheter.

Pre-eclampsia is a pregnancy-specific disorder that presents major health problems for both mothers and babies. It is a major cause of maternal mortality, especially in developing countries, where it may account for 80% of maternal deaths. In this review we have discussed the putative pathogenetic mechanisms of this severe illness.Review of the international literature on pre-eclampsia.Pre-eclampsia occurs predominantly in primigravidas and is associated with increased foetal and maternal risk. Generally speaking, one could hypothesise that during pre-eclampsia the oxidative, coagulative and vasomotor balance is altered by increased sensitivity to angiotensin II associated with reduced synthesis of vasodilator prostaglandins, sympathetic nervous system hyperactivity, hyperlipidaemia associated with raised lipoperoxide synthesis and incomplete implant of cytotrophoblast in maternal spiral arteries. General vasoconstriction could then be a consequence with related utero-placental ischaemia and endothelial damage. These features are clinically characterised by arterial hypertension, proteinuria and sodium retention. The predisposition to develop pre-eclampsia seems to be at least partially hereditary and the risk seems to be transmissible through male sons. To explain the susceptibility of some women to develop pre-eclampsia, specific genetic polymorphisms have been associated to increased risk.Many factors are involved in the pathogenesis of pre-eclampsia. Occasionally these factors seem to act together, sometimes they do not and, consequently, it might be difficult to postulate a common pathogenesis for the disorder. Good obstetrical practice will identify known risk factors but will not enable physicians to determine the risk value for a particular pregnancy. Moreover, we are far from understanding the exact mechanisms involved, let alone acting upon them. The achievement of these objectives constitute a remarkable challenge for research.

Conglomerates of food and mucus or phytobezoars composed of vegetable matter are sometimes found in the stomach in the general population. Reports of phytobezoars in uremic patients are, however, scarce. Here we describe 2 uremic patients in which esophagogastroduodenoscopy was performed due to dyspepsia associated with weight loss and in which stomach phytobezoars were discovered. Theoretically, uremic patients should be at risk for producing bezoars. In fact, these patients frequently present predisposing conditions such as autonomic neuropathy, diabetes mellitus and delayed gastric emptying. Gastric bezoars cause anorexia. Anorexia is a frequent symptom in dialysis patients and is associated with malnutrition. In these patients, malnutrition is strongly associated with mortality and is quite difficult to reverse. Similarly, phytobezoars cause chronic anorexia. We suggest that clinicians working in dialysis units should consider the possibility of a gastric bezoar when evaluating anorexic uremic patients.

Vascular access is the essential step in performing hemodialysis in uremic patients. In the absence of a permanent and utilizable native arterio-venous fistula, the use of a tunnelled catheter makes dialysis therapy possible. The Ash Split Cath, a recently introduced chronic hemodialysis catheter, was inserted in five patients (7.1% of our prevalent dialysis population) because of repeated venous thrombosis in three patients and a poor venous tree in two. The mean age of patients was 78 years +/- 7. The average blood flow rate was 250+/-50 ml/minute and the mean venous pressure 140mm Hg +/- 35. Recirculation determined by low flux technique was less than 2%. KT/V calculated 3 months after the catheter placement was 1.2+/-0.02. During the follow-up we did not document any infection of the exit site or related to the catheter. This device is simple to place, gives adequate dialysis treatment and is useful in geriatric dialyzed patients in whom the arterio-venous fistula can no longer be used.

The TINU syndrome (tubulointerstitial nephritis and uveitis) was first described by Dobrin et al. in 1975. Since then, more than 50 cases have been documented each with diverse immunopathogenetic and genetic characteristics. The aim of this report is to describe a case of TINU associated with reduced complement levels. We profile a 48-year-old white female with persistently reduced C4 complement levels during the acute phase of the pathology and with an unaltered immunologic profile. Renal biopsy evidenced a significant lymphocytic interstitial infiltration. Immunohistochemical studies of the interstitium infiltrates was positive for the presence of the T (CD3) markers (CD4 > CD8). Steroid therapy yielded a complete regression of the symptomatology with normalization of the complement levels. We suggest that it is possible to hypothesize that the various immunologic alterations associated with TINU, including the transient reduction complement levels, may be secondary to multiple inflammatory mechanisms which express themselves throughout the pathology.

Central venous catheterization allows immediate and easy vascular access for hemodialysis. Accidental arterial puncture is the most frequent complication of central vein cannulation and may occur in up to 8% of cases with the classic Seldinger procedure. We compared the Seldinger technique which implies manual localization of the vascular access, and an ultrasound guided technique, to assess whether the latter is an improvement on the Seldinger procedure.

Adequacy of peritoneal dialysis has been less well studied than that of hemodialysis. Fractional urea removal, total creatinine removal, and various indices have been proposed to reflect or predict patient morbidity and mortality. No prospective study has been published in this regard. To evaluate this area further, in addition to reviewing selected literature, 45 continuous ambulatory peritoneal dialysis (CAPD) patients were recruited in two dialysis centers for a prospective study on treatment adequacy. Patients were well rehabilitated and had no peritonitis or hospitalization in the 6 months before the study. Urea and creatinine kinetics were analyzed, as were dietary intake and fluid balance. The weekly Kt/V, calculated to include peritoneal and residual renal clearance (KprT/V), averaged 1.77 with a Kt/V hemodialysis equivalent of 0.59. Patients with residual renal function (58% of the studied population) had an average residual renal clearance of 3.42 mL/min, and had lower steady-state concentrations of urea nitrogen and creatinine in the plasma than patients with no residual renal function. As a consequence, a lower percent excretion of urea and creatinine in the peritoneal fluid was observed in the former patients compared with the latter, where the peritoneal route was the only one for solute excretion. The concentration profiles in blood appear to be the critical factor in achieving the final target of the treatment, ie, the excretion of the overall amount of waste products derived from protein and other metabolic pathways. The constant blood levels in CAPD explain why such a low Kt/V can be adequate whereas, in hemodialysis, a higher Kt/V is required.(ABSTRACT TRUNCATED AT 250 WORDS)

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Eight samples of human peritoneal tissue were obtained from patients undergoing hemicholectomy for cancer. An artery and a vein were cannulated and perfused with blood in vitro with a special circuit able to provide different perfusion pressures. Ultrafiltration and clearance studies were performed in these samples. Both ultrafiltration and small-solute clearances linearly correlated with the blood flow, demonstrating a strong dependence on this parameter. The peritoneal capillary showed a typical filtration pressure equilibrium with a constant filtration fraction at different blood flows. The results suggest that the blood flow may be a factor limiting the efficiency of peritoneal dialysis both in terms of mass transfer coefficients and maximal ultrafiltration rates.

Reactive oxygen species have been implicated in the pathogenesis of tissue injury. It is generally accepted that selenium-glutathione peroxidases form an integrated system defending the living organism against oxidative damage. Phospholipid hydroperoxide glutathione peroxidase (PHGPX) is thought to play a prominent role in preventing lipid peroxidation. Indeed, the function of PHGPX is to reduce the lipophilic substrates in membranes. In the present study, we evaluated the expression of PHGPX in normal human kidney by immunohistochemistry. The enzyme in glomeruli is mainly expressed in podocytes and parietal epithelial cells. In addition, PHGPX antigen was detected in tubule epithelial cells. Therefore, these results suggest that renal epithelial cells possess an important antioxidizing activity related to the presence of PHGPX.

Chronic gastritis in patients with chronic renal failure may have different causes and mechanisms. Recent observations suggest that severe gastritis often found in uraemic patients might be related to Helicobacter pylori (HP) infection. In chronic gastritis HP has been found in the mucus and on the epithelial cell surface of gastric foveolas. Significant infiltration of the subepithelial gastric layer by polymorphonuclear leucocytes has been described. Moreover, beta-2-microglobulin deposits have been found by immunohistochemical methods in the subepithelial layer of gastric mucosa of uraemic dialysed patients with active chronic gastritis and HP infection. Similar findings have also been demonstrated in gastric biopsies from patients with HP positive active chronic gastritis and normal renal function. Since HP infection is associated with significant leucocyte infiltration, it is hypothesized that the inflammatory process causes the release of beta-2-M from the surface of the leucocytes and its subsequent deposition at gastric level.

Pathophysiology of peritoneal ultrafiltration is analyzed in the present study. Peritoneal equilibration test is the easiest procedure to study in detail the possible causes of failure to control the ultrafiltration rate in patients undergoing peritoneal dialysis. Membrane failure, reduction in peritoneal blood flow, excessive lymphatic reabsorption catheter malposition, and fluid sequestration are the most common causes of ultrafiltration loss. Pharmacologic manipulation of peritoneal membrane, correction of mechanical inconvenients, reduction in peritonitis rate and in the level of immunostimulation of the mesotelial macrophages, together with a careful policy in terms of glucose concentration in the dialysate and dwell times may contribute not only to treat different forms of ultrafiltration loss but also to prevent their incidence.