[Health-related quality of life in patients with chronic kidney disease]. / Qualita' della vita nei nefropatici.

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

[A contrast with good intentions]. / Un contrasto a fin di bene.

A seventy-five-year-old woman with moderate chronic renal failure was admitted to evaluate a complex renal cyst in the frame of acquired cystic kidney disease. Computed tomography (CT) was performed without contrast media due to the risk of radiocontrast-induced nephrotoxicity. Sonographic investigation at our ultrasound unit revealed a hypoechoic lesion measuring 20x20 mm in size by conventional B-mode sonography, confirmed by NTHI. The Hypoechoic lesion was consistent with complex renal cyst or renal tumour. This finding triggered investigation with CEUS.A sulphur hexafluoride-filled microbubble contrast medium was injected intravenously. The focal lesion CES pattern was characterized by intralesional enhancement in the arterial phase. Further diagnostic imaging including CT with contrast media confirmed a lesion consistent with renal tumour. The patient underwent right-sided nephrectomy; histopathological work-up revealed a renal cell carcinoma. Contrast-enhanced sonography could be clinically useful for the differential diagnosis of kidney lesions in patients with chronic renal failure.

Reduction of mononuclear cytokine production in hemodialysis patients treated with steam-sterilized low-flux polysulphone membranes.

An increased cytokine production, correlated with long term complications of uremic disease, has been described during hemodialysis. To identify possible differences in the cytokine release of differently sterilized membranes, we enrolled six uremic patients on chronic hemodialysis. The patients underwent dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG) for at least three months (A1), they were then switched to steam-sterilized polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one (B1) and two months (B2) were carried out. A final evaluation (A2) was made one month after switching back to F6 dialyzers. At each time period, samples were drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover, dialysate samples were collected to test endotoxin levels. C3a and C5a levels were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1; falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2: 284, p<0.01. Post-dialysis levels followed the same pattern. No correlation between the dialysate endotoxin level and cytokine release was found. Complement activation did not change and in all the phases of the study no anti-ETO IgE was detected in any of the subjects. Our data suggest that the steam sterilized polysulphone membrane induces a lower cytokine release than the ETO sterilized membrane, although the mechanism by which it does so remains to be clarified.

Is steam sterilization really making any difference in dialysis-induced cytokine release?

Ethylene oxide (ETO) is presently the most commonly used sterilization method for medical devices. Although alternative sterilization modes such as steam sterilization have been suggested, the effect of steam on dialysis-induced cytokine release is unknown. We enrolled 9 patients on chronic hemodialysis and evaluated at different intervals IL-1beta production while treated with ETO (NC 1785-Bellco) and steam sterilized NC 1785S-Bellco) Synthetically Modified Cellulose (SMC). A basal test during treatment with NC 1785 was performed (A); the same test was set up 4 weeks after treatment with NC 1785S (B) and, lastly, 4 weeks after returning to NC 1785 (C). Peripheral blood mononuclear cells (PBMC) were purified before and after the dialysis session, were isolated on a Ficoll/Hypaque gradient and incubated for 24 h. Spontaneous IL-1beta release was evaluated in the supernatant and in the lysate. In A, IL-1beta levels were (in pg/ml/10(6) cells, in supematant and lysate, respectively): 5.8 +/- 4.8 and 7.6+/-5.2 in pre-HD and 4.68 +/- 3.6 and 9.7 +/- 6.65 in post-HD. These levels showed a clear reduction in B: 2.5 +/- 2.2 and 4.4 +/- 3.1 in pre-HD, and 4.35+/- 6.6 and 7.52 +/- 7.22 in post-HD. In the C test, 4 weeks after the return to the ETO membrane, IL-1beta levels remained unchanged: 2.9 +/- 1.8 and 4.5 +/- 3.1 in pre-HD; and 2.6 +/- 3 and 5.7 +/- 6.6 in post-HD. Statistical analysis showed significant changes in the pre-HD levels both in supematant (p < 0.04) and in lysate (p < 0.04). Steam sterilization of SMC induced a lower spontaneous IL-1beta release, but this effect was not statistically significant due to the large inter-individual variation. Hence, contrary to claims of better biocompatibility, steam sterilization does not result in a reduced production of pro-inflammatory IL-1beta.

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.

[Calcitriol increases burst forming unit-erythroid (BFU-E) in vitro proliferation in chronic uremia. Synergic effect with DNA recombinant erythropoietin (rHu-Epo)]. / Aumentata proliferazione dei precursori eritroidi burst forming unit-erythroid (BFU-E) indotta in vitro dal calcitriolo nell'uremia cronica. Effetto sinergico con l'eritropoietina da DNA ricombinante (rHu-Epo).

BACKGROUND: It has been suggested that calcitriol (C) could improve anemia in chronic renal failure. However it remains debatable whether vitamin D has a specific effect on erythropoiesis, or it acts via suppression of hyperparathyroidism. METHODS: We enrolled 29 patients with chronic renal failure, free from malignancies, iron deficiency or other chronic or hematological diseases. Aluminium accumulation was also excluded by DFO test. 22 were on hemodialysis and 7 on conservative management, creatinine clearance ranging 22-48 ml/min. Their mean age was 62+/-28 years and duration of renal disease was 98+/-51 months. No patient under-went rHu-Epo or Vitamin D treatment. 4 subjects were enrolled as controls. Samples of peripheral blood were drawn for the Burst Forming Unit-Erythroid (BFU-E) assay. After isolation of mononuclear cells by density gradient centrifugation with Fycoll-Hypaque, a 15-day incubation was set up with four different conditions: a) adding standard dose, 3 U/ml, of r-HuEpo (Dompè Biotec), standard colture; b) combined doses of r-HuEpo, 3 U/ml, and C (Abbott), 30 pg; c) standard dose, 3 U/ml, of r-HuEpo and high dose, 300 pg, of C; and lastly d) combined high doses of r-HuEpo, 30 U/ml, and C, 300 pg. RESULTS: In the b colture (combined low doses) a higher BFU-E proliferation was found vs standard (a) colture (33.2+/-15.5 vs 17.1+/-9.2, p<0.02); interestingly, either in the c and d studies BFU-E showed an even higher proliferation (52.3+/-24 and 86.3+/-37.8 respectively, p<0.01 vs a). No difference was found when evaluating separately preterminal and hemodialysis patients. In control subjects only colture d showed an increased BFU-E proliferation. CONCLUSIONS: C has a direct effect on erythroid precursors proliferation in vitro, acting in a sinergystic manner with rHuEpo. C may be useful as adjuvant therapy for renal anemia.

[A genetic viewpoint of focal glomerular sclerosis: fom genes to glomerular pathophysiology [corrected]]. / La genetica della glomerulosclerosi focale: dai geni alla fisiopatologia del glomerulo.

Recent studies of Mendelian disease have begun to clarify the clinical spectrum of the group of disorders that make up familial, focal segmental glomerulosclerosis (FSGS) and nephrotic syndromes. In familial forms of focal segmental glomerulosclerosis (FSGS), both autosomal recessive and dominant inheritance patterns have been reported. At least three genes have been identified which, when defective, cause familial FSGS or nephrosis: the NPHS1 gene, encoding nephrin; the NPHS2 gene, encoding podocin; and the ACTN4 gene, encoding a-actinin-4. Because the majority of FSGS cases occur as sporadic disease, the recently described mutations in the NPHS2 gene "in approximately 25 percent of cases of apparently sporadic, steroid-resistant FSGS in children" have claimed great interest. The applicability of these observations to adults, including the possible importance of the nephrin and alpha-actinin-4 genes in the sporadic disease, remain to be determined. Finally, the mechanisms of podocyte damage and the molecular basis of glomerulosclerosis are reviewed.

[The hemodiafiltration with endogenous reinfusion reduces the erythroid progenitor inhibition by uremic serum]. / L'emodiafiltrazione con reinfusione endogena (HFR) riduce l'inibizione dei precursori eritroidi (BFU-E) da siero uremico.

PURPOSE: Anemia in end-stage renal disease (ESRD) patients shows a lower proliferation of erythroid progenitor cells such as burst forming unit-erythroid (BFU-E) than in normal subjects. As on-line hemodiafiltration with endogenous reinfusion(HFR) is thought to have a better biocompatibility and a wide range of uremic toxin removal, we compared the effect of serum obtained pre- and post-standard hemodialysis (HD) and HFR dialysis performed in four ESRD patients with proliferation in normal subject) (controls) bone marrow BFU-E. METHODS: Mononuclear fraction was obtained by Ficoll-Hypaque density centrifugation and studies were performed in three different conditions: standard culture, adding serum from controls, adding serum from ESRD patients pre- and post HD and HFR dialysis. BFU-E were counted after 14 days with an inverted microscope and expressed as average scores from two dishes. Standardization between experiments was checked with a control culture for each experimental culture. RESULTS: The BFU-E proliferation rate was clearly reduced by adding serum from ESRD patients either pre-HD or pre-HFR. However, while this inhibition was exacerbated by post-HD serum, it showed a significant reduction with post-HFR serum. CONCLUSIONS: This effect could be due to the removal of uremic toxins or to a lower dialysis-induced cytokine release, both mechanisms involved in erythropoiesis inhibition in ESRD.

[Thalassaemia minor: national survey of uraemic patients under substitutive treatment]. / Talassemia minor: indagine nazionale dei pazienti uremici in trattamento sostitutivo.

BACKGROUND: The incidence of thalassaemia minor in end-stage renal disease patients is similar to that of the general population. Both these conditions are characterized by anaemia, but the underlying pathophysiology is quite different. Current literature lacks an adequate clinical survey of haemodialysis patients with thalassaemia minor. METHODS: The prevalence of thalassaemia minor (thal-m) in haemodialysis patients was assessed by a national survey collecting general information as well as clinical and haematological parameters. Data were also collected on the use of recombinant erythropoietin in these subjects. A dedicated questionnaire was sent to all Italian dialysis units. RESULTS: Only 116/705 dialysis units returned the questionnaire (16.4%): 33 units did not have any patients affected by thalassaemia minor. No response was obtained from six Italian regions whereas ten regions returned only partial answers. The response from four regions was satisfactory (20%) while the completed questionnaire was returned by all units in only two small regions. A total of 7731 ESRD patients were collected, 240 (3.1%) were also affected by thal-m, 142 males and 98 females. In the four regions with the highest response rates, Calabria 45%, Puglia 65%, Basilicata and Molise 100%, the prevalence of thal-m were 3.68%, 4.56%, 3.3% and 1%, respectively. A total of 3623 uraemic patients (47% of all enrolled subjects) were collected from these four regions. Here is the patient geographic distribution: northern Italy 2.16% (response rate of 9.44%); central Italy 1.69% (response rate of 7.64%), southern Italy 3.77% (response rate of 29.46%). The age range of thal-m patients was 17 to 90 years, the time spent on dialysis was between 3 and 384 months, the body weight was between 35 and 93 kg, the Hb value was between 6.2 and 13.6 g/dl, and the Htc value was between 19 and 44%. A total of 230 thal-m patients were on haemodialysis while 10 patients were on peritoneal dialysis (4.2%). The mean haemoglobin level for the thal-m group was 9.8+/-1.4 g/dl and for the control group the value was 11.4+/-1.4 g/dl (p < 0.0001). The use of rhEPO was on the average 7659+/-6256 u/wk for the thal-m and 4378+/-4435 u/wk for the control group (p < 0.0001). The bodyweight was 129+/-105 u/kg/wk (range 0-370). Finally, 17.9% of the thal-m patient did not use rhEPO, their Hb value was 10.66+/-1.67 g/dl (range 8.2-13). No patient went over 30 thousand units and only 4 had such dosage in therapy. The 12.1% thal-m patients with Hb < 10 g/dl did not use rhEPO. The need for rhEPO per gram of Hb was 796+/-722 u/wk in thal-m patients and 416+/-449 U/wk in control patients (p < 0.0001). Uraemic anaemia was corrected with 4.8 million red blood cells in the control group and with about 7.7 million red blood cells in the thal-m group. CONCLUSIONS: Data from this national survey, although incomplete, show that rHuEpo is less effective in these patients and its use does not seems to be correct. It is important to emphasise that recent Guidelines do not recommend neither a specific treatment for these patients nor the use of r-HuEpo. However, it should also be underscored that most thal-m patients do not reach the target Hb level suggested by the National Guidelines for the general population in chronic dialysis.

[Medullary sponge kidney (MSK) in association with glomerulonephritis (GNP)]. / Glomerulonefrite mesangiale in paziente con rene a spugna midollare: descrizione di un caso clinico.

BACKGROUND: Medullary sponge kidney (MSK) is a congenital, non-hereditary anomaly characterized by dilation of the precalix ducts. It is often associated with other diseases, and its symptoms are linked to frequent complications, such as sepsis of the urinary system and the renal colic of nephrolithiasis. However, MSK is rare in association with glomerulonephritis (GNP), as can be seen from medical literature data that shows only one case (reported in 1974) in which MSK with a concomitant focal sclerosing glomerulonephritis was noted. In this report, we describe a case of MSK that was found after a routine renal echograph and biopsy of a mesangial GNP previously diagnosed at another center. The echographic results showing typical MSK was confirmed by means of RX urography and renal TC. The MSK-glomerulonephritis combination appears to be completely random, because the involved structures (the collecting duct and the glomerule) have different embryologic origin. Therefore, a pathogenic hypothesis common to the two anomalies seems rather unlikely. CONCLUSIONS: Although MSK is a usually benign disease, because a compromise of glomerular filtration that occurs in approximately 10% of cases, proper diagnosis is important to allow prophylactic intervention aimed at the reduction of complications that could reduce overall renal function when associated with other nephropathies. Renal echography is an important diagnostic tool that may reveal more cases of MSK than previously reported.

[Increased in vitro and ex vivo proliferation of erythroid precursors induced by calcitriol in chronic renal failure. Synergistic effect with rHuEPO]. / Aumentata proliferazione dei precursori eritroidi indotta in vitro ed ex vivo dal calcitriolo in corso di uremia cronica.Effetto sinergico con rHuEPO.

BACKGROUND: Calcitriol (C) improves anemia in chronic renal failure. This improvement may be related to the suppression of iPTH release, but also to a direct effect on erythropoiesis. MATERIALS AND METHODS: In order to verify this hypothesis, 33 patients with chronic renal failure were enrolled: 24 were undergoing hemodialysis, 9 managed conservatively. All patients were free from other chronic or hematological disease, had a negative DFO test and aluminum levels below 20 mcg/l. iPTH range was 250-480 pg/l. None had yet been treated with C. In vitro study- Samples were drawn for a basal erythroid precursors (Burst Forming Unit-Erythroid BFU-E) study. After mononuclear cells were isolated by centrifugation with Ficoll-Hypaque, they were incubated for 15 days with rHuEPO 3U/ml (A), rHuEPO 3U/l + C 30 pg (B), rHuEPO 3U/ml + C 300 pg (C), rHuEPO 30 U/ml + C 300 pg (D) was performed. Ex vivo study- After the basal evaluation, 10 pts on dialysis were treated with C (Calcijex-Abbott) 1 g three times a week. BFU-E studies were performed after 1,2 and 4 months. RESULTS: In vitro, culture B showed an increased BFU-E proliferation vs A (41+/- 23 vs 27+/-15, p less than 0.02); in C and D cultures proliferation was 61+/-31 and 78+/- 42 respectively, p less than 0.01 vs A. There was no difference among pts with renal failure and pts treated conservatively. During the in vivo study all cultures showed a progressive proliferation increase, without a plateau level (basal, after 1, 2, 4 months respectively): in A: 17+/-8, 22+/-13, 30.9+/-14.9, 41.4+/-20; in B: 27.3+/-15, 35.6+/-20, 45.5+/-21, 57+/-26; in C: 48.2+/-20.6, 63.7+/-32, 75.7+/-37, 83+/-40; in D: 72+/-24, 91+/-42, 106+/-42, 110+/-42.3 (always p less than 0.001). The hematocrit and hemoglobin increase was constant but not significant. The iPTH decrease was not related to BFU-E proliferation. CONCLUSIONS: In chronic uremia C has a direct effect on erythroid precursor proliferation, both in vitro and ex vivo, with a sinergystic effect with rHuEPO. This effect is not related to iPTH suppression. C may be a useful adjuvant therapy for rHuEPO treatment.

[Macrohaematuria post-partum: an unusual case of acquired haemophilia after pregnancy]. / Macroematuria post-partum: un insolito caso di emofilia acquisita del peurperio.

BACKGROUND: Acquired hemophilia is a rare disorder due to spontaneous development of antibodies directed against the factor VIII molecule in patients with previously normal levels of factor VIII. In this paper we report an unusual case of acquired hemophilia admitted to our department of nephrology due to persisting gross hematuria. CASE REPORT: A 38-year-old primigravida woman, previously fit and well, had an uncomplicated pregnancy, labor and a caesarean delivery at 38 weeks of gestation. Two weeks after delivery she developed gross hematuria with anemia. She was therefore admitted to a department of urology where urinary system and hematological investigation did not reveal important anomalies. Due to persisting gross hematuria and suspected kidney disease, the patient was admitted to our department of nephrology where serious anemia and prolongation of aPTT were noted; factor VIII procoagulant activity was low with a Bethesda assay confirming the presence of anti human f VIII antibody. Diagnosis of acquired hemophilia was confirmed and treated with corticosteroid therapy, intravenous immunoglobulins and recombinant factor VIII. After 10 days, gross hematuria stopped with improvement of aPTT and level of factor VIII. DISCUSSIONS: It is postulated that pregnancy leads to an altered immune status whereby the F VIII from the embryo, through transplacental leakage, may be considered as a foreign antigen by the mother, leading to the formation of antibodies. Bleeding symptoms usually became apparent within 3 months of delivery but could be as late as 12 months post-delivery and sometimes coagulation investigation results are normal at the beginning. It is therefore very important to estimate many times the activated partial thromboplastin time in macrohematuria post-partum. Mortality due to hemorrhage varies between 14 and 22 % in previous series. In the vast majority complete remission is achieved spontaneously within a few months. The diagnosis of acquired hemophilia is of fundamental importance for an adequate treatment preventing serious complications and high mortality.

[Acute biocompatibility of hemodiafiltration with endogenous reinfusion (HFR)]. / Emodiafiltrazione con reinfusione endogena (HFR): profilo di biocompatibilità in acuto.

PURPOSE: In order to reduce the hemodialysis (HD)-induced pro-inflammatory activity we need to use a biocompatible dialysis membrane, avoid backfiltration and possibly use adsorbents. Hemodiafiltration reinfusion (HFR) is a new on-line hemodiafiltration (HDF) technique combining these aspects. This study aimed to evaluate the biocompatibility of the single dialysis session comparing standard HD and HFR. METHODS: Eighteen patients on chronic HD were enrolled in five Centers. Patients underwent one standard and two HFR study sessions; in each session we evaluated leukocyte activation at 0, 5, 15, 60 and 240 min; and interleukin-6 (IL-6), C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1Ra) levels at 0, 60 and 240 min. RESULTS: Leukocyte activation was similar in HD and HFR, while the post-dialysis IL-6 increase was lower with HFR; CRP levels were stable during HFR, but increased after HD, and IL-1Ra did not demonstrate any difference. CONCLUSIONS: These preliminary data show that HFR still has a better biocompatibility in the single dialysis session.

[Epidemiology of hepatitis C virus infection in hemodialysis. A study of the Gargano area]. / Epidemiologia dell'infezione da virus dell'epatite C in emodialisi. Studio dell'area garganica.

In order to evaluate epidemiological features of hepatitis C virus infection in patients with chronic renal failure, we enrolled 80 haemodialyzed subjects in four centers of Gargano area (Southern Italy). In a 28 months follow-up we checked antiHCV antibodies by EIA II and viraemia by polymerase chain reaction. Seroprevalence of HCV infection was 35%, while incidence was 2.4%/year; viraemia was detected in 62.5% of antiHCV+ and in only one of antiHCV-. In our opinion there is a definitive need of special precautions (or isolation of antiHCV+) in haemodialysis units to avoid community-acquired HCV infection.

Systematic monitor disinfection is effective in limiting HCV spread in hemodialysis.

BACKGROUND: Patients on chronic hemodialysis are at high risk of HCV infection due to nosocomial transmission. The strict adhesion to universal precautions is the first step in prevention, but other simple tools such as systematic monitor disinfection and the use of separate machines for anti-HCV-positive patients need to be evaluated. METHODS: A 5-year prospective study was carried out in 4 dialysis centers enrolling 135 patients. General precautions were adopted, but anti-HCV-positive patients were not isolated. In period A, lasting 24 months, monitor disinfection was performed after each dialysis session with sodium hypochlorite; peracetic acid was also used 3 times a week. In period B, lasting 36 months, 3 dialysis units (77 patients) prolonged the same preventive protocol of period A, while another unit (58 patients) also adopted the use of separate machines for anti-HCV-positive subjects. A third-generation ELISA anti-HCV test was performed every 2 months throughout the study. RESULTS: Anti-HCV antibodies were initially detected in 43 patients (31.8%), prevalence rate ranging from 25 to 39.4%. One seroconversion occurred in period A, with an overall seroconversion rate of 0.54%/year. Also in period B one seroconversion occurred (unit 2), seroconversion rate of 0.36%/year. Therefore the mean seroconversion rate throughout the 5 years was 0.43%/year. CONCLUSION: Systematic monitor disinfection may be a simple and quite effective tool to avoid nosocomial transmission of HCV infection in the hemodialysis setting. In our opinion its use is mandatory. The use of separate machines for anti-HCV-positive patients seems unnecessary.

Long-term comparison between captopril and nifedipine in the progression of renal insufficiency.

To verify the hypothesis that angiotensin-converting enzyme (ACE) inhibitors possess a unique renoprotective effect in progressive chronic renal disease, we decided to compare the effects of an ACE inhibitor and a calcium antagonist on both hypertension and the progression of non-diabetic renal insufficiency in a long-term study. A four-year, multicenter, prospective, randomized trial was conducted on 142 hypertensive patients (pts) with established chronic renal failure from six Italian nephrology departments. They were on standard antihypertensive therapy with a low-protein diet and underwent twice-monthly surveillance for a one year pre-randomization period. After that year, 121 pts were randomly allocated to captopril or slow-release nifedipine therapies for a three-year study period. The progression of renal insufficiency was monitored every two months. Blood pressure control was significantly better after randomization than during the year of standard antihypertensive therapy. The progression rate before randomization (BR) was definitely higher before than after randomization (AR): Creatinine clearance (CCr) change BR = -0.46 +/- 0.45 ml/min/month, creatinine clearance change AR = -0.23 +/- 0.43 ml/min/month (P less than 0.01). After randomization, the mean blood pressure values were virtually the same throughout the three year period of the study in the two groups treated by captopril (group I), or nifedipine (group II).(ABSTRACT TRUNCATED AT 250 WORDS)

Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in haemodialysis patients.

BACKGROUND: In chronic renal failure, desferrioxamine (DFO) may improve erythropoiesis independent from its aluminium (Al) chelating effect. The mechanism of this action is still unknown. METHODS: To verify whether DFO influences proliferation of erythropoietic precursors, we studied 10 patients on chronic haemodialysis, free from malignancies or other haematological diseases, iron deficiency, bone marrow fibrosis, and Al toxicity. Al accumulation was excluded by the DFO test. Peripheral blood samples were drawn for basal burst-forming unit erythroid (BFU E) assay. Mononuclear cells were isolated by density gradient centrifugation with Ficoll Hypaque, and incubated for 15 days with three different experimental conditions: (a) low-dose recombinant human erythropoietin (rHuEpo) (3 U/ml); (b) high dose rHuEpo, (30 U/ml); (c) both DFO (167 microg/ml) and rHuEpo (3 U/ml). We determined TIBC, transferrin, ferritin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor (sTR), haemoglobin (Hb), and haematocrit (Hct) at baseline and then every 14 days. Patients received 5 mg/kg DFO infused during the last hour of each dialysis session for 6 weeks; six patients remained in the study for an additional 6 more weeks. BFU E assays were set up after 6 and 12 weeks of DFO therapy. RESULTS: At baseline DFO had small effect on BFU E proliferation (33.9+/-25 vs 30.4+/-25.9) and high-dose rHuEpo had a significant effect (45.15+/-27 vs 30.4+/-25.9, P<0.01). After 6 weeks of DFO therapy a significant increase in BFU E proliferation was observed in all culture conditions (78.25+/-32 vs 30.45+/-25.9 standard culture, P<0.01; 110.9+/-30 vs 45.15+/-27 high dose rHuEpo, P<0.01; 98.75+/-32 vs 45.15+/-27 DFO culture, P<0.01). Moreover, the increase in BFU E proliferation was significant greater with DFO culture than standard culture (P<0.01). The same trend was found at the third BFU E assay, performed in only six patients, when all culture conditions showed a further increase of erythroid precursor proliferation. However, the DFO culture was not significantly greater than the standard culture, while the high-dose rHuEpo was significantly greater than the DFO culture. Patients in group I (n=10), had a significant increase in reticulocytes (1.5+/-0.6 vs 1.72+/-0.3, P<0.01) and of hypochromic erythrocytes (HE) (5.6+/-5.1 vs 14.4+/-12.7, P<0.01), while sTR, Epo, Hb, and Hct were only minimally increased. Ferritin decreased significantly (448+/-224 vs 196+/-215, P<0.01) and TIBC and transferrin were unchanged. CONCLUSIONS: Thus DFO increases erythroid activity by BFU E proliferation and increases reticulocytes in haemodialysis patients. Such an effect may be related to increased iron utilization. DFO may be a useful tool for anaemic patients with good iron stores and without Al overload.

Synergistic effect of desferrioxamine and recombinant erythropoietin on erythroid precursor proliferation in chronic renal failure.

BACKGROUND: Desferrioxamine (DFO) has been suggested to improve erythropoiesis in end-stage renal failure independently of its aluminium (Al)-chelating effect. A possible synergistic effect of DFO and recombinant human erythropoietin (r-HuEpo) could be very useful in treating anaemia of chronic renal failure. METHODS: In order to verify whether a synergistic action of DFO and r-HuEpo exists, we enrolled 11 patients undergoing chronic haemodialysis and r-HuEpo treatment. All had a negative DFO test, very low serum Al levels (< 20 microg/l), ferritin > 100 ng% and iPTH < 200 pg/l. Samples were drawn for a basal erythroid precursor (burst-forming unit-Erythroid, BFU-E) evaluation. After isolation by Ficoll Hypaque, a 14 day incubation was carried out with: (i) r-HuEpo 3 U/ml; (ii) r-HuEpo 30 U/ml; and (iii) r-HuEpo 30 U/ml + DFO 167 microg/ml. Patients then received 5 mg/kg DFO infused during the last hour of each dialysis session for 12 weeks. New BFU-E evaluations were performed after 2, 6 and 12 weeks of treatment. BFU-E colonies were counted in duplicate with an inverted microscope after 14 days. Haemoglobin (Hb), ferritin, transferrin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor and serum erythropoietin were also evaluated at the same time. RESULTS: High dose r-HuEpo achieved greater proliferation than low dose r-HuEpo cultures during all phases of the study. At baseline, r-HuEpo and DFO culture had a greater number of colony units than high dose r-HuEpo culture ( 103.7 +/- 50.2 vs 95.1 +/- 50.5, NS). This increase became significant after 2 weeks (145 +/- 59.3 vs 122.9 +/- 59.6, P < 0.02), and remained so at 6 (167.4 +/- 60.3 vs 149 +/- 55.6, P < 0.01) and 12 weeks (191 +/- 64.5 vs 155.1 +/- 56.3, P < 0.01). An increased proliferation was observed after DFO therapy in all culture studies: low dose r-HuEpo culture increased from 69.4 +/- 38.2 to 86.6 +/- 48.5, 115 +/- 39 and 123 +/- 46; high dose r-HuEpo culture increased from 95.1 +/- 50.5 to 122.9 +/- 59, 149 +/- 55.6 and 155.1 +/- 56.3 and r-HuEpo plus DFO culture from 103.7 +/- 50.2 to 145 +/- 59.3, 167 +/- 60.3 and 191 +/- 64.5 at 2, 6 and 12 weeks, respectively (all P < 0.01 by ANOVA). Haemoglobin, reticulocytes and soluble transferrin receptor were slightly increased, while ferritin decreased. Hypochromic erytrocytes were variable. CONCLUSIONS: DFO increases erythroid precursor proliferation and has a synergistic in vivo effect with r-HuEpo in patients with chronic renal failure. Further investigations are needed to evaluate whether such an effect may have clinical application.

Hepatitis C virus infection in four haemodialysis units of southern Italy: epidemiological report.

UNLABELLED: The haemodialysis patients are an high risk population for hepatitis viral infections. While the incidence of HBV has decreased worldwide, HCV is now the major cause of viral infection in these patients. The aim of our study was to define a complete map of patients undergoing routine replacement therapy by haemodialysis in the province of Foggia, Southern Italy, who were HCV Ab positive, the presence of viraemia and their genotypes; moreover, we investigated the probable factors involved in determining the infection as well as the means of prevention. MATERIALS AND METHODS: We enrolled 330 patients treated in four haemodialysis centres (DC) and six secondary units; mean age was 57 years and mean duration of dialysis 76 months. Samples were drawn to determine cytolysis indexes and the HCV Ab status; in HCV positive patients, we also looked for viraemia and HCV genotypes. Data were analysed by a transversal cross-section study. RESULTS AND CONCLUSIONS: Prevalence of HCV infection was 0.43 (males 0.45, females 0.42). The risk of contracting the infection was shown to be significantly different in the various DCs and did not seem to be related to the severity of the preventive measures. There was no significant difference between the various DCs in the comparison between the odds of HCV-RNA+ and HCV-RNA- patients. No significant prevalence of a given genotype emerged from a cross-sectional study related to the comparison between different genotypes. Moreover, transfusions of blood products seemed to have no significant relation to HCV infection. Finally, patients treated with haemodialysis for more than 36 months run a seven time greater risk of contracting HCV infection.