Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial.

BACKGROUND AND AIMS: In patients with chronic kidney disease (CKD), alterations in gut microbiome are posited to be responsible for gastrointestinal symptoms and generation of p-cresol, a uremic toxin that has been associated with CKD progression and cardiovascular mortality. This pilot study investigated whether Probinul-neutro®, a synbiotic that normalizes intestinal microflora, may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients. METHODS AND RESULTS: This was a double-blind, randomized placebo-controlled trial. Thirty patients on 3-4 CKD stages were randomized to receive either Probinul neutro® or placebo for 4 weeks. Total plasma p-cresol concentration was assessed at baseline, and 15 and 30 days after treatment start. At the same study times, ease and frequency of defecation, upper and lower abdominal pain, stool shape, borborygmi, and flatus were quantified by subjective assessment questionnaires. Compared to baseline total plasma p-cresol median concentrations on 15th and 30th day were significantly lower in patients receiving Probinul-neutro® (2.31 and 0.78 vs. 3.05 µg/ml, p < 0.05; n = 18); no changes of plasma p-cresol concentrations were recorded in placebo-treated patients. No significant changes in gastrointestinal symptoms were observed during the study both in Probinul-neutro®-treated and placebo-treated patients. CONCLUSION: Probinul-neutro® lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients. Because high plasma concentrations of p-cresol in early phases of CKD are predictive of progression to end-stage renal disease, the results of our study suggest that synbiotics deserve attention as possible tools to delay CKD progression towards end-stage renal disease (ESRD). CLINICALTRIALSGOV IDENTIFIER: NCT02008331.

Dietary phosphate restriction in dialysis patients: a new approach for the treatment of hyperphosphataemia.

BACKGROUND AND AIM: Elevated serum phosphate and calcium-phosphate levels play an important role in the pathogenesis of vascular calcifications in uraemic patients and appear to be associated with increased cardiovascular mortality. We aimed to evaluate the effects of a partial replacement of food protein with a low-phosphorus and low-potassium whey protein concentrate on phosphate levels of dialysis patients with hyperphosphataemia. METHODS AND RESULTS: Twenty-seven patients undergoing chronic haemodialysis were studied for a 3-month period. In the intervention group (n = 15), food protein were replaced by 30 or 40 g of low-phosphorus and low-potassium protein concentrate aimed at limiting the phosphate intake. In the control group (n = 12) no changes were made to their usual diet. Anthropometric measurements, biochemical markers and dietary interviews were registered at baseline and during the follow-up period. From baseline to the end of the study, in the intervention group, serum phosphate and circulating intact parathyroid hormone levels lessened significantly (8.3 ± 1.2 mg/dL vs 5.7 ± 1.4 mg/dL and 488 ± 205 pg/ml vs 177 ± 100 pg/ml respectively; p < 0.05) with decreasing of phosphate and potassium intake. No significant differences were found in the control group. No significant changes were observed in serum albumin, calcium, potassium, Kt/V, body weight and body composition in both the intervention and control groups. CONCLUSION: Dietary intake of phosphate mainly comes from protein sources, so dietary phosphorus restriction may lead to a protein/energy malnutrition in a dialysis patient. A phosphorus-controlled diet plan including a nutritional substitute resulted in serum phosphate and intact parathyroid hormone decrease without nutritional status modifications in dialysis patients.

Intrarenal determinants of sodium retention in mild heart failure: effects of angiotensin-converting enzyme inhibition.

The onset and the mechanisms leading to Na+ retention in incipient congestive heart failure (CHF) have not been systematically investigated. To investigate renal Na+ handling in the early or mild stages of CHF, Na+ balance and renal clearances were assessed in 10 asymptomatic patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (HF) off treatment (left ventricular ejection fraction, 29.7+/-2%) and in 10 matched normal subjects during a diet containing 100 mmol/d of NaCl and after 8 days of high salt intake (250 mmol/d). Six patients were studied again after 6 weeks of treatment with enalapril (5 mg/d P.O.). At the end of the high salt diet, in patients with mild HF the cumulative Na+ balance exceeded by 110 mmol that of normal subjects (F=3.86, P<.001). During high salt intake, renal plasma flow and glomerular filtration rate were similarly increased in both normal subjects and mild HF patients. In spite of comparable increases of filtered Na+ in the two groups, fractional excretion of Na+, fractional clearance of free water, and fractional excretion of K+ (indexes of distal delivery of Na+) increased in normal subjects and were reduced in patients with mild HF. During enalapril treatment, in the mild HF patients the cumulative Na+ balance was restored to normal; furthermore, enalapril significantly attenuated the abnormalities in the distal delivery of Na+. Our results indicate that a defective adaptation of Na+ reabsorption in the proximal nephron is associated with Na+ retention in response to increased salt intake in the early or mild stages of HF. These abnormalities of renal Na+ handling are largely reversed by enalapril.

Low-dose dopamine induces early recovery of recombinant interleukin-2--impaired renal function.

Recombinant interleukin-2 (rIL-2) can produce impairment of renal function with hypotension, fluid retention, elevated blood urea nitrogen, oliguria and low fractional sodium excretion; these side-effects are a common cause of reduction or interruption of rIL-2 infusion. The aim of this study was to investigate the control and treatment of renal toxicity induced by rIL-2 therapy. Here we show that dopamine, at a low dose of 2 micrograms/kg/min, completely prevented renal toxicity induced by rIL-2. While continuing rIL-2 therapy, 24-h continuous infusion of low-dose dopamine produced a rapid normalisation of urine output and a significant decrease in serum creatinine levels and body weight (P < 0.01), with an early and complete recovery of the rIL-2--impaired renal function: mean recovery time of renal function in patients treated with dopamine was significantly lower (P < 0.05) than in nontreated patients (4.8 days vs. 10 days, respectively).

Stop-flow technique for loco-regional delivery of high dose chemotherapy in the treatment of advanced pelvic cancers.

AIM: To verify the rationale of a pelvic stop-flow technique for the perfusion of high-doses of mitomycin C and anthacyclines in patients with inoperable, recurrent pelvic cancer. METHODS: The stop-flow technique was realized by using percutaneous double-balloon arterial-venous catheters that selectively isolate the pelvic vascular section and a perfusion provided by an extracorporeal pump for 20 min. Ten patients (pts) with unresectable pelvic recurrence from colon-rectal cancer were treated with a combination of Mitomycin C (MMC, 20 mg/sqm) plus doxorubicin (DOXO, 75 mg/sqm; 8pts) or epirubicin (EPI, 75 mg/sqm; 2pts) infused into the isolated pelvic compartment. Blood samples were collected from the extracorporeal vascular flow and from peripheral plasma, and analysed for drug quantitation. RESULTS: During the procedure, there were no technical or hemodynamic complications, and no deaths occurred during surgery or in the postoperative period. MMC and DOXO peak levels measured in the extracorporeal system which irrotates the tumor area, were on average 21.6 (range: 4.3-44.3, MMC) and 17.2 (range: 1.8-48.4, DOXO) times higher than those observed in the peripheral blood. Similarly; the area under concentration (AUC) versus time curves measured in the pelvic compartment during stop-flow perfusion were 19.9 (range: 3.8-45.0, MMC) and 13.4 (range: 1.2-26.6, DOXO) times higher than the corresponding value in peripheral circulation. The drug percentage eliminated in the ultra filtrate was only 7.7% (MMC) and 0.9% (DOXO), and the plasmatic AUC(0-24) were similar to those observed with iv bolus of equivalent drug doses. Minimal systemic and local toxicities were observed. One complete pathological and 2 partial responses were observed; pain remission in 8/10 patients. median survival was 12 months (8-31). CONCLUSION: The endo-arterial administration into the local vasculature produces high pelvic-systemic concentration gradients during the stop-flow perfusion with limited local and systemic toxicity. The encouraging clinical results suggest further evaluation.

Nutritional intervention in a hemodialysis pregnant woman: a case report.

Pregnancy in dialysis patients is a rare occurrence. When pregnancy does occur, the risk of spontaneous abortion, stillbirth and neonatal complications, such as prematurity and growth retardation, are fairly high. The authors describe their experience in the follow-up of a patient with chronic renal failure who became pregnant during regular dialysis treatment and followed nutritional care. The outcomes were successful and she gave birth to a healthy baby. It is emphasized that special dedication to the nutritional control enabled a good outcome of the pregnancy. The importance of the nutritionist intervention in the follow-up of dialysis patients with the integration of a multidisciplinary staff is stressed.

The place of loop diuretics in the treatment of acute and chronic renal failure.

Loop diuretics (furosemide, bumetanide, muzolimine, piretamide, torasemide) are powerful drugs capable of increasing sodium excretion and urine output even when renal function is markedly impaired. In patients with chronic renal failure (CRF), loop diuretics may be given to control extracellular volume (ECV) expansion responsible for hypertension. But the use of loop diuretics in chronic uremia is mostly helpful when impaired renal function co-exists with nephrotic syndrome or chronic heart failure. Due to their powerful natriuretic activity, loop diuretics have been administered also to patients on maintenance dialysis to reduce the frequency of and/or to curtail dialysis time. In this condition, however, the increase of sodium and water excretion is very limited; whereas the use of diuretics in high dosage is not devoid of risky side effects such as neurologic lesions, cramps, deafness, weakness, muscle pain. In some patients with oliguric form of acute renal failure (ARF), loop diuretics increase sodium excretion and urine output. They do not affect the mortality rate for ARF but may facilitate the treatment of patients by reverting an oliguric form to a non-oliguric form of ARF.

Twice versus thrice weekly administration of intravenous calcitriol in dialysis patients: a randomized prospective trial. Gruppo Italiano di Studio dell'Osteodistrofia Renale.

BACKGROUND: Administration of intravenous (i.v.) calcitriol three times weekly effectively controls the synthesis and secretion of PTH in most uremic patients. Administration of a single dose of 1.25(OH)2D3 reduces synthesis of PTH-mRNA for 6 days in rats. Moreover, it can lower PTH levels for up to 4 days in chronic hemodialysis patients. Therefore, a good response to the administration of i.v. calcitriol two times weekly can be expected. We studied - in a multicenter randomized study in patients with moderate to severe secondary hyperparathyroidism - the effects of the same doses of intravenous calcitriol, administered two or three times weekly. METHODS: Twenty-two hemodialysis patients were randomized into two frequencies of treatment groups: two times (G-2/w) and three times weekly (G-3/w). Both groups were treated with increasing doses of intravenous calcitriol for 3 months (first month 3 microg, second month 4 microg, third month 6 microg weekly). RESULTS: After 12 weeks of therapy with intravenous calcitriol the G-2/w group showed a significant reduction in serum PTH levels (from 821 +/- 392 to 350 +/- 246 pg/ml; mean reduction = 57.4%) comparable to the decrease observed in the G-3/w group (from 632 +/- 116 to 246 +/- 190 pg/ml; mean reduction = 61.2%). Ionized calcium (G-2/w from 1.13 +/-0.10 to 1.14 +/- 0.08 and G-3/w 1.21 +/- 0.13 to 1.26 +/- 0.18 mmol/l) and phosphate levels (G-2/w from 4.99 +/- 1.01 to 5.99 +/- 1.78 and G-3/w 5.31 +/- 0.73 to 5.81 +/- 1.18 mg/dl) did not change significantly and phosphate binders were not modified during the study. CONCLUSION: This study confirms that intravenous calcitriol is an effective therapy for moderate to severe secondary hyperparathyroidism. The administration of two doses per week of intravenous calcitriol is as efficacious as three doses per week in suppressing PTH secretion.

Atrial natriuretic factor in amniotic fluid and in maternal venous blood of pregnancies with fetal cardiac malformations and chromosomal abnormalities.

OBJECTIVE: We evaluated the levels of atrial natriuretic factor (ANF) in amniotic fluid and in maternal venous blood in pregnancies with fetal cardiac malformations and chromosomal abnormalities. METHOD: Between the 16th and 18th week of pregnancy, 151 women were divided into three groups. Group A included patients at lowest risk, carrying a fetus with a normally developing heart and normal karyotype (control group). Group B included women with a fetus suffering from cardiac malformations, with or without associated chromosomal abnormalities. Group C included women carrying a fetus affected with chromosomal abnormalities without congenital cardiopathies. ANF was evaluated by radioimmunoassay. RESULTS: In maternal venous blood, the mean levels of ANF were 42.1, 53.1 and 38.7 pg/ml in groups A, B and C, respectively. In amniotic fluid, the mean levels of ANF were 34.2, 101.8 and 35.8 pg/ml in groups A, B and C, respectively. In group A (control group) there was no statistical difference in ANF levels across the gestational age range of 16-18 weeks, either in amniotic fluid or in maternal venous blood. A significant difference of ANF content in maternal venous blood was revealed in comparing group A with group B (p < 0.01), and group C with group B (p < 0.01). A statistically significant difference in ANF levels was also found in amniotic fluid between group A and group B (p < 0.01), and between group C and group B (p < 0.01). No statistically significant differences were found between group C and group A in comparing ANF levels in maternal venous blood and amniotic fluid. CONCLUSION: ANF levels in amniotic fluid and in maternal venous blood are increased early in the case of fetuses with cardiac malformations, with or without associated karyotype alteration. Chromosomally abnormal fetuses without heart malformations have normal ANF levels. These results could be useful for elucidating fetal pathophysiology mechanisms.

Hemodialysis related interleukin-2 receptor release by peripheral blood mononuclear cells.

To evaluate the effects of hemodialysis treatment on the spontaneous cell release of interleukin-2 receptor (IL-2R), we studied 19 hemodialyzed patients (HD), 9 non hemodialyzed patients with chronic uremia (UR, glomerular filtration rate: 8.4 +/- 1.8 ml/min), and 8 healthy control subjects (C). We measured the release of IL-2R in the supernatant of peripheral blood mononuclear cells (PBMC) cultured for 24 hrs in Iscove's medium as well as the plasma levels of IL-2R. A significant increase of IL-2R release was detected in the supernatant of PBMC harvested from HD patients (32.4 +/- 2.4 and 34.2 +/- 5.6 U/3 x 10(6) PBMC daily before and after HD, respectively) as compared with UR (16.6 +/- 5.2 U/3 x 10(6) PBMC daily) and C (21.4 +/- 3.8 U/3 x 10(6) PBMC daily). Similarly, IL-2R plasma levels were significantly higher in HD (378.5 +/- 164.6 U/ml) than in UR (189.5 +/- 89.3 U/ml) and C (11.2 +/- 2.68 U/ml). To summarize, the current study demonstrates: a) an enhancement of spontaneous IL-2R cell release in HD patients; b) an increase of sIL-2R plasma levels in UR patients possibly related to reduced metabolism and/or urinary excretion, because it was not associated with high IL-2R cell release; and c) a further increment of IL-2R systemic levels in HD likely secondary to the high cell release of IL-2R. Therefore, a chronic T cell activation with increased release of IL-2R secondary to the dialysis procedure is suggested.

Membrane distillation of human plasma ultrafiltrate and its theoretical applications to haemodialysis techniques.

Membrane Distillation (MD) is a technique that allows the extraction of water from aqueous solutions. The basic principle is that vapour, but not liquid water, can pass through hydrophobic micro-porous membranes, along a temperature gradient, with consequent separation of water from solutes. In this study we evaluated the possibility to utilise MD to extract water from Plasma Ultrafiltrate (PU) of patients with Chronic Renal Failure (CRF). The experiments were carried out in vitro by a hydro-phobic polypropylene hollow-fibre distillation module; PU was obtained by a CRF patient utilising a high permeability polisulphone membrane. The results show that water can be extracted by MD from PU of CRF subjects at a constant rate and that none of the substances analysed in PU was able to pass through the polypropilene membrane. In the future MD could integrate extra-corporeal blood purification techniques allowing the re-utilisation of plasmatic water thus ameliorating the treatment of uraemia.

Concentration polarization phenomenon in new and re-used RP610 hemofilters during post-dilutional hemofiltration.

RP610 hemofilters have been used up to five times in post-dilutional hemofiltration. Clearance studies were performed "in vivo" (creatinine and phosphate) and "in vitro" (Cr51 EDTA, I131 Hypaque, Co57 vitamin B12, H3 Inulin, C14 Dextran, I125 Albumin,) in new hemofilters and in those re-used once and five times. Hydraulic permeability and rejection coefficients, for the six markers different molecular weight, were also measured. Our preliminary results show that repeated cleansing with Amuchina does not alter the characteristics of RP610 hemofilters. A scintigraphic method is suggested for visualizing possible changes in polarized areas between new and re-used hemofilters.

Is 3000 S Hospal a suitable dialyzer to shorten dialysis time schedule? A cooperative study on biofiltration.

The Biofilter 3000 S Hospal may combine higher convective clearance rates (Cc) with usual diffusive clearance rates (Cd) (i.e. similar to Cuprophan dialyzers), giving a higher total clearance rate (Ct) of small and middle molecules. Use of the Biofilter has been suggested to shorten dialysis time schedules. This study was carried out in 8 patients on RDT 3 times weekly, by cuprophan filter and acetate dialysis. The patients were shifted to dialysis with 3000 S guided by two principles: to shorten dialysis time by 1 hour per session, and to reinfuse 6 liters of bicarbonate-saline solution (40 mEq/l) per single dialysis. Besides the usual clinical and laboratory controls, in three patients clearance studies were carried out during four different dialysis sessions: Ct, Cc and Cd of urea K+, creatinine, uric acid and phosphate were measured. No change was observed in the main clinical and laboratory parameters after 3-5 months (average 3.9) of treatment with Biofilter 3000 S; in addition, serum alkaline phosphatase concentration decreased progressively. Clearance results, however, indicate that the expected high values of Ct do not occur, because Cd decreases as Cc is increased. A primary goal of research in hemodialysis is to reduce the average time of treatment while ensuring simultaneously "physiological" dialysis. A possible approach to this problem is to use dialyzers with highly permeable and biocompatible membranes such as the "biofilter" 3000 S Hospal.(ABSTRACT TRUNCATED AT 250 WORDS)

[The IL-6 soluble receptors in hemodialyzed patients]. / Il ruolo dei recettori solubili dell'interleuchina-6 nei pazienti in trattamento dialitico.

Pro-inflammatory cytokines, in addition to their role in host defence, can be considered a disease mediator; therefore, a reduction in cytokine synthesis or its effects is becoming a target of many diseases. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that could play a role in several clinical problems related to dialysis treatment. Biological activities of IL-6 could be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R can enhance the inflammatory effects of IL-6 and; therefore, is an "agonistically" acting molecule. On the contrary, sgp130 efficiently binds the IL-6/sIL-6R complex with "antagonistic" effects. In this study we evaluated sgp130 release by peripheral blood mononuclear cells (PBMC) harvested from 10 healthy controls (CON) and 11 end-stage renal disease (ESRD) patients undergoing renal dialysis therapy RDT) with cellulosic hemophan membrane (HD). We also evaluated gp130 gene expression by reverse transcriptase polymerase chain reaction (RT-PCR). gp130 is the membrane bound receptor of IL-6 that could be proteolytically cleaved to generate soluble sgp130. Our results demonstrated that HD. at basal conditions, showed a higher release of sgp130 as compared with CON. We also demonstrated by RT-PCR at basal conditions a higher gene expression of gp130 in HD, as compared with CON. These results took place in the absence of any mitogenic stimulation and suggest that in HD patients an inflammatory subclinical status increases sgp130 release. The results obtained after lipopolysaccharide (LPS) stimulation confirm the role of inflammation on the increased release of sgp130 in HD patients.

[Guidelines for dialysis. Replacement therapy for acute renal failure in critically ill patients]. / Linee Guida sulla Dialisi. Il trattamento sostitutivo della Insufficienza Renale Acuta nel paziente critico.

Acute renal failure (ARF) in patients admitted to the intensive care unit (ICU) is mostly caused by ischemic or toxic injury, with a higher incidence in the latest years due to the growing number of interventions in cardiac and vascular surgery and to the general enhancement of reanimation techniques, which allow a better outcome among ICU patients. In critically ill patients, the ARF incidence reported in the literature ranges between 1 and 25%. Among ICU patients with ARF the mortality is between 40 and 65%, much more than in patients without this complication. Higher mortality rates, longer hospitalisation times and higher therapy costs demand from us an early diagnosis and treatment of ARF. Due to the lack of controlled and randomized proofs, recommended criteria for starting renal replacement therapy (RRT) in critical ARF patients might overlap with those for ESRD therapy. Moreover, randomised and controlled trials, confirming the actual efficacy of early onset of RRT on the mortality rate, are not yet available. As for stable ESRD patients, a direct relationship between dialytic doses and mortality and morbidity has been established for ARF patients. For ARF patients, as well as for ESRD patients, a minimum Kt/V of 1.2 three times a week should be ensured, although higher doses for critical ARF patients may achieve better results. The choice between intermittent (IRRT) and continuous renal replacement therapy (CRRT) in these patients is still a controversial issue. In spite of the fact that most studies report a better outcome in patients treated with CRRT, a recent meta-analysis failed to demonstrate any difference on the relative risk (RR) of mortality and on the rate of renal recovery between patients treated with either IRRT or CRRT. Furthermore, the use of peritoneal dialysis for the treatment of ARF patients in ICU has not been dismissed yet; so far this is indeed considered to be the technique of choice in some specific clinical situations. The intrinsic urgency of dialysis in ARF patients entails the use of temporary central venous catheters. The internal right jugular vein is usually preferred for these catheters because of the easier insertion and the lower risk of stenosis and thrombosis. The anticoagulant procedure should be chosen on the basis of patient characteristics, treatment typology and the likelihood of effectively monitoring its action. The choice of buffers in the dialysate, mostly lactate or bicarbonate, should depend on patient characteristics; so far, however, controlled but not randomized studies do not show any significant difference in the correction of metabolic acidosis between lactate and bicarbonate.

[Predictive and diagnostic factors of malnutrition in hemodialysis patients]. / Fattori predittivi e diagnostici della malnutrizione nel paziente in trattamento emodialitico.

The relationship between malnutrition and inflammation is by now well established. IL-6 and, probably, other proinflammatory cytokines (mainly IL-1 and TNF) may represent the link between these two entities since these interleukins may promote loss of appetite, muscle protein breakdown and reduced hepatic synthesis of "negative" acute phase proteins like albumin, prealbumin and transferrin. IL-6 also stimulates up to 1000 fold the hepatic synthesis of "positive" acute phase proteins, mainly C-reactive Protein (CRP) and Serum Amyloid A. The association between CRP and cardiovascular mortality in the general population, as well as in haemodialysed uraemic patients, is well established. These crucial interrelationships have modified the interpretation of serum albumin concentration in the diagnosis of malnutrition; a reduced serum albumin concentration, in fact, in the presence of high CRP values should point towards a diagnosis of inflammation, though the inflammation may often induce weight loss or a condition of malnutrition. After switching most patients to a more biocompatible dialysis membrane and improvement of the quality of the dialysis fluid (by adopting hydrophobic filters at the water entry of dialysis devices and bicarbonate powder cartridges) nephrologists have focused their attention on other sources of inflammation (e.g. artificial vascular protheses, presence of infected thrombi, Clamidiae, Helicobacter Pilori, dental granulomas etc.). Starting from these assumptions the diagnosis of malnutrition, once focused mainly on serum albumin reduction, must be based on other parameters (clinical history of body mass wasting, dietary and anthropometric assessment, subjective global assessment, bioimpedance analysis etc.). All these investigations, however, must be examined together to obtain suitable information on the risk of malnutrition in dialysis patients. A comprehensive approach to malnutrition-inflammation in dialysis patients is the object of the present nephrology conference.

[Guideline for the hemodialytic treatment of chronic uremia]. / Le linee-guida per il trattamento emodialitico dell'uremia cronica.

In this review we have summarized the guidelines on hemodialysis prescription and dose in order to attempt of simplify an issue often difficult to understand for the majority of physicians. In brief, we start from the results of National Cooperative Dialysis Study and then we describe the Urea Kinetic Model, the KT/V and the Protein Catabolic Rate (PCR). Simplified formulas to obtain KT/V and PCR are also reported. At the end, the modalities related to postdialytic blood samples and connected problems are described.

Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin.

OBJECTIVE: Erythropoietin has been shown to have a protective effect in certain models of ischaemia-reperfusion, and in some cases the protection has been correlated with activation of signalling pathways known to play a role in cell survival and proliferation. We have studied whether erythropoietin would overcome direct toxic effects of hydrogen peroxide (H(2)O(2)) treatment to human renal proximal tubular (HK-2) cells. MATERIALS AND METHODS: HK-2 cells were incubated with H(2)O(2) (2 mm) for 2 h with or without erythropoietin at concentrations of 100 and 400 U/ml, and cell viability/proliferation was assessed by chemical reduction of MTT. Changes in phosphorylation state of the kinases Akt, glycogen synthase kinase-3beta (GSK-3beta), mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2) were also analysed. RESULTS: Cells incubated with H(2)O(2) alone showed a significant decrease in viability, which did not significantly change by addition of erythropoietin at concentration of 100 U/ml, but was further reduced when concentration of erythropoietin was increased to 400 U/ml. Phosphorylation state of the kinases Akt, GSK-3beta, mTOR and ERK1/ERK2 of H(2)O(2)-treated HK-2 cells was slightly altered in the presence of erythropoietin at concentration of 100 U/ml, but was significantly less in the presence of erythropoietin at a concentration of 400 U/ml. Phosphorylation of forkhead transcription factor FKHRL1 was diminished in cells incubated with H(2)O(2) and erythropoietin at a concentration of 400 U/ml. CONCLUSIONS: Erythropoietin, at high concentrations, may significantly increase cellular damage in HK-2 cells subjected to oxidative stress, which may be due in part to decrease in activation of important signalling pathways involved in cell survival and/or cell proliferation.

Cytokine production in haemodialysis.

Many aspects regarding morbidity and mortality of dialysis patients are related to the production of cytokines by peripheral blood mononuclear cells. Clinical alterations resulting from cytokine production and release may include dialysis amyloidosis, malnutrition and atherogenesis. Cytokine release may also play a relevant role in immunodeficiency of dialysis patients by inducing alterations in immune and host-defense system. Interleukin-1, interleukin-6 and tumor necrosis factor are three pro-inflammatory cytokines, mainly produced by monocytes, and involved in pathogenetic aspects of hemodialysis-related diseases. In this review we analyse the mechanisms underlying monocyte activation and describe the different modalities for studying cytokine production and release. Clinical implications of cytokine production are also discussed.

Loop diuretics and renal vasodilators in acute renal failure.

Loop diuretics are powerful drugs able to increase urinary sodium and water excretion even in conditions of marked impairment of renal function. Loop diuretics are useful in preventing or ameliorating the course of acute renal failure. This effect may be obtained when they are used within 18 h after the ischaemic and/or toxic event. Loop diuretics reduce tubular work, providing resistance to cellular ischaemia. Other important beneficial effects include tubular wash-out of cellular debris and inhibition of tubuloglomerular feedback. Among vasodilators, dopamine, when used at 'dopaminergic dosage' is useful in preventing acute renal failure. Its efficacy is demonstrated in several situations of renal hypoperfusion, i.e. salt depletion, cyclosporin administration, and therapy with recombinant interleukin 2 in cancer patients. According to our studies it appears that dopamine should be used in the early phases of acute renal failure to improve renal perfusion, re-establish glomerular filtration rate, and increase tubular flow.